MSAC Assessment Report Template
MSAC application no 1190Magnetic Resonance Imaging (MRI) for small bowel Crohn’s disease and fistulising perianal Crohn’s diseaseDecember 2013Assessment 1190 - Magnetic Resonance Imaging (MRI) for small bowel Crohn’s disease and fistulising perianal Crohn’s diseaseISBN (Online)978-1-74186-140-2ISSN (Online1443-7139Publication approval number10783Internet site ? Commonwealth of Australia 2013This work is copyright. You may download, display, print and reproduce the whole or part of this work in unaltered form for your own personal use or, if you are part of an organisation, for internal use within your organisation, but only if you or your organisation do not use the reproduction for any commercial purpose and retain this copyright notice and all disclaimer notices as part of that reproduction. Apart from rights to use as permitted by the Copyright Act 1968 or allowed by this copyright notice, all other rights are reserved and you are not allowed to reproduce the whole or any part of this work in any way (electronic or otherwise) without first being given the specific written permission from the Commonwealth to do so. Requests and inquiries concerning reproduction and rights are to be sent to the Online, Services and External Relations Branch, Department of Health, GPO Box 9848, Canberra ACT 2601, or via e-mail to copyright@.au. Electronic copies of the report can be obtained from the Medical Service Advisory Committee’s Internet site at about the content of the report should be directed to the above address.This report is a contracted technical report for use by the Medical Services Advisory Committee (MSAC) to inform its deliberations. MSAC is an independent committee which has been established to provide advice to the Minister for Health and Ageing on the strength of evidence available on new and existing medical technologies and procedures in terms of their safety, effectiveness and cost effectiveness. This advice will help to inform government decisions about which medical services should attract funding under Medicare.MSAC’s advice does not necessarily reflect the views of all individuals who participated in the MSAC evaluation.This report was prepared for MSAC by L Gordon, T Comans and P Scuffham from Griffith University Assessment Group with the assistance of Health Expert Standing Panel members (Assoc Prof Damien Stella, Prof Richard Mendelson). The report was commissioned by the Department of Health on behalf of MSAC.This report should be referenced as follows: Gordon L, Comans T, Scuffham P. (2013). MRI for small bowel Crohn’s disease and fistulising perianal Crohn’s disease. MSAC Application 1190, Assessment Report. Commonwealth of Australia, Canberra, ACT.Template Version updated 21 October 2013Contents TOC \o "1-3" \h \z \u Contents PAGEREF _Toc374513810 \h iiiList of Tables PAGEREF _Toc374513811 \h vList of Figures PAGEREF _Toc374513812 \h viExecutive summary PAGEREF _Toc374513813 \h 7The procedure PAGEREF _Toc374513814 \h 7Medical Services Advisory Committee – role and approach PAGEREF _Toc374513815 \h 7Assessment of MRI PAGEREF _Toc374513816 \h 8Introduction PAGEREF _Toc374513817 \h 14Background PAGEREF _Toc374513818 \h 15Crohn’s disease PAGEREF _Toc374513819 \h 15Magnetic resonance imaging (MRI) PAGEREF _Toc374513820 \h 15Intended purpose PAGEREF _Toc374513821 \h 16Clinical need PAGEREF _Toc374513822 \h 16Existing tests PAGEREF _Toc374513823 \h 17Current guidelines PAGEREF _Toc374513824 \h 18Marketing status of technology PAGEREF _Toc374513825 \h 19Current reimbursement arrangements PAGEREF _Toc374513826 \h 19Approach to assessment PAGEREF _Toc374513827 \h 20Objective PAGEREF _Toc374513828 \h 20Clinical decision pathway PAGEREF _Toc374513829 \h 20Comparators PAGEREF _Toc374513830 \h 20The reference standard PAGEREF _Toc374513831 \h 20Research questions PAGEREF _Toc374513832 \h 21Review of literature PAGEREF _Toc374513833 \h 22Appraisal of the evidence PAGEREF _Toc374513834 \h 27Assessment of the body of evidence PAGEREF _Toc374513835 \h 31Expert advice PAGEREF _Toc374513836 \h 32Results of assessment PAGEREF _Toc374513837 \h 33Relevant studies for assessment PAGEREF _Toc374513838 \h 33Is it safe? PAGEREF _Toc374513839 \h 33Is it effective? PAGEREF _Toc374513840 \h 36Direct evidence PAGEREF _Toc374513841 \h 38Indirect evidence PAGEREF _Toc374513842 \h 38Other relevant considerations PAGEREF _Toc374513843 \h 43Ongoing trials PAGEREF _Toc374513844 \h 43Expert opinion PAGEREF _Toc374513845 \h 43Consumer implications and other considerations PAGEREF _Toc374513846 \h 43What are the economic considerations? PAGEREF _Toc374513847 \h 45Summary of the evidence PAGEREF _Toc374513848 \h 45Overview of the economic considerations PAGEREF _Toc374513849 \h 45Published economic literature PAGEREF _Toc374513850 \h 46Economic evaluation PAGEREF _Toc374513851 \h 47Costing PAGEREF _Toc374513852 \h 51Discussion PAGEREF _Toc374513853 \h 57Is it safe? PAGEREF _Toc374513854 \h 57Is it effective? PAGEREF _Toc374513855 \h 57What are the economic considerations? PAGEREF _Toc374513856 \h 59Conclusions PAGEREF _Toc374513857 \h 60Safety PAGEREF _Toc374513858 \h 60Effectiveness PAGEREF _Toc374513859 \h 60Economic considerations PAGEREF _Toc374513860 \h 60Appendix A Treatment algorithms for six proposed indications PAGEREF _Toc374513861 \h 61Appendix B Health Expert Standing Panel Members and Evaluators PAGEREF _Toc374513862 \h 67Health Expert Standing Panel Members PAGEREF _Toc374513863 \h 67Evaluators PAGEREF _Toc374513864 \h 67Appendix C Search strategies PAGEREF _Toc374513865 \h 68Appendix D Studies included in the review PAGEREF _Toc374513866 \h 70Study profiles of included systematic reviews PAGEREF _Toc374513867 \h 70Study profiles of included clinical studies on diagnostic accuracy and change in management PAGEREF _Toc374513868 \h 73Appendix E Excluded studies PAGEREF _Toc374513869 \h 81Incorrect comparator PAGEREF _Toc374513870 \h 81Data duplicated in another study PAGEREF _Toc374513871 \h 83Incorrect intervention PAGEREF _Toc374513872 \h 84Did not meet inclusion criteria regarding population PAGEREF _Toc374513873 \h 85Incorrect purpose PAGEREF _Toc374513874 \h 86Incorrect study type PAGEREF _Toc374513875 \h 86Insufficient outcomes data PAGEREF _Toc374513876 \h 87Incorrect disease PAGEREF _Toc374513877 \h 87Appendix F Assessment of economic evaluation PAGEREF _Toc374513878 \h 89Glossary and abbreviations PAGEREF _Toc374513879 \h 91References PAGEREF _Toc374513880 \h 92List of TablesPageTable SEQ Table \* ARABIC 1: Proposed MBS item descriptor for MRI for small bowel Crohn’s disease with andwithout contrast agent9Table SEQ Table \* ARABIC 2: Proposed MBS item descriptor for MRI for fistulising perianal Crohn’s disease9Table 3: Proposed indications of MRI and clinical place in therapy10Table 4: Summary of indications for MRI application and replacement tests21Table 5: PPICO criteria22Table 6: Electronic databases searched23Table 7: Selection criteria for included studies24Table 8: Evidence dimensions28Table 9: Designations of levels of evidence according to type of research question ADDIN EN.CITE <EndNote><Cite><Author>NHMRC</Author><Year>2008</Year><RecNum>132</RecNum><DisplayText>(NHMRC, 2008a)</DisplayText><record><rec-number>132</rec-number><ref-type name="Electronic Source">12</ref-type><contributors><authors><author>NHMRC</author></authors></contributors><titles><title>NHMRC additional levels of evidence and grades for recommendations for developers of guidelines. Stage 2 consultation.</title></titles><number>11/03/08</number><dates><year>2008</year></dates><publisher>National Health and Medical Research Council, Australian Government</publisher><work-type>Internet</work-type><urls><related-urls><url>.au/consult/index.htm</url></related-urls></urls></record></Cite></EndNote>(NHMRC, 2008a)29Table 10: Grading system used to rank included studies29Table 11: Criteria used to assess the quality of diagnostic accuracy studies – the QUADAStool30Table 12: Criteria used to assess the quality of systematic review studies30Table 13: Body of evidence assessment matrix31Table 14: Relevant studies included in the assessment33Table 15: Annual radiation dose among patients with Crohn’s disease receiving imagingtests35Table 16: Characteristics and appraisal of included systematic reviews38Table 17: Characteristics and appraisal of 6 included accuracy studies41Table 18: Summary of key results from diagnostic studies and systematic reviews42Table 19: Patient-relevant differences in MRI or CT scans in Australia46Table 20: Summary of evidence for MRI versus Comparator(s)47Table 21: Parameters used in the decision-analytic model for pelvic MRI versus CTfor detection of fistulas/abscesses in fistulising perianal Crohn’s disease50Table 22: Results of the cost-utility analysis of MRI and endoanal ultrasound fordetecting perianal fistulas in Crohn’s disease (12 months)52Table 23: Australian epidemiological studies on inflammatory bowel disease (IBD)54Table 24: Estimates and sources to calculate eligible population55Table 25: Cost estimates used in the financial estimates56Table 26: Results of the financial estimates (2014-2018)57Table 27: Sensitivity analyses of financial estimates (selected)57Table 28: Completed body of evidence assessment matrix60List of FiguresPageFigure SEQ Figure \* ARABIC 1: Simplified clinical decision tree21Figure 2: Summary of the process used to identify and select studies for the review25Figure 3: Two-by-two table of data used to determine test accuracy26Figure 4: Diagram of decision-analytic model for pelvic MRI versus CT for detection of fistulas/abscesses in fistulising perianal Crohn’s disease51Figure 5: Incremental cost effectiveness scatterplot of MRI vs CT in perianal Crohn’sdisease53Figure A.1: Evaluation of disease extent at time of initial diagnosis of Crohn’s diagnosis63Figure A. SEQ Figure \* ARABIC 2: Evaluation of exacerbation/suspected complications of known Crohn’sdisease64Figure A. SEQ Figure \* ARABIC 3: Evaluation of suspected Crohn’s disease in pregnancy65Figure A. SEQ Figure \* ARABIC 4: Assessment of change to therapy in patients with Crohn’s disease66Figure A. SEQ Figure \* ARABIC 5: Evaluation of pelvic sepsis and fistulas associated with established orsuspected Crohn’s disease67Figure A. SEQ Figure \* ARABIC 6: Assessment of change to therapy in patients with pelvis sepsis and fistulasfrom Crohn’s disease68Executive summary The procedure Magnetic Resonance Imaging (MRI) for the evaluation of small bowel Crohn’s disease and fistulising perianal Crohn’s disease. MRI allows accurate visualisation of the entire gastrointestinal tract through the acquisition of multi-planar images with high-contrast resolution of the tissue. Bowel distension is needed to obtain optimal visualisation and is achieved through the use of an enteric contrast material. MRI is believed to be beneficial over other modalities that emit ionising radiation which may be contraindicated in children and pregnant women or when patients are at risk of multiple diagnostic procedures.Medical Services Advisory Committee – role and approach The Medical Services Advisory Committee (MSAC) was established by the Australian Government to strengthen the role of evidence in health financing decisions in Australia. MSAC advises the Minister for Health on the evidence relating to the safety, effectiveness and cost-effectiveness of new and existing medical technologies and procedures and under what circumstances public funding should be supported.A rigorous assessment of evidence is thus the basis of decision making when funding is sought under Medicare. A team from Griffith University was engaged to conduct a systematic review of the literature and an economic evaluation of MRI in Crohn’s disease for the indications proposed. Research questions: Six focused research questions were outlined in the Decision Analytic Protocol (DAP) to help inform the decision as to whether public funding should be supported:What is the safety, effectiveness and cost-effectiveness of MRI small bowel compared with:Computer tomography (CT) or small bowel follow-through (SBFT) for the evaluation of disease extent in patients initially diagnosed with Crohn’s disease with suspected small bowel involvement?CT and SBFT for the evaluation of patients with exacerbation/suspected complications of known Crohn’s disease?Ultrasound (US) in pregnant women with suspected small bowel Crohn’s disease?CT, SBFT or endoscopic assessment in the assessment of change to therapy in patients with small bowel Crohn’s disease?What is the safety, effectiveness and cost-effectiveness of MRI pelvis compared with:surgical assessment or endoanal ultrasound in patients with pelvic sepsis and fistulas associated with established or suspected Crohn’s disease?surgical assessment or endoanal ultrasound in assessment of change to therapy in patients with pelvis sepsis and fistulas from Crohn’s disease?Assessment of MRIPurpose of applicationAn application requesting MBS listing of MRI for patients with Crohn’s disease was received from the Gastroenterology Society of Australia by the Department of Health and Ageing in July 2011. The application requests three new MBS Items including MRI for small bowel, pelvis and associated enteroclysis.The application specifically looks at two populations: 1) MRI small bowel in patients with small bowel Crohn’s disease, 2) MRI pelvis for patients with fistulising perianal Crohn’s disease. The application is somewhat complex in that there are six specific indications involving a target group with mainly established Crohn’s disease but also suspected Crohn’s disease in pregnancy or patients with suspected perianal fistulas. In addition there are several comparators involved depending on the separate indications for MRI.Small bowel and pelvis MRI is used in conjunction with enteric contrast material to achieve bowel distention (the exception to this is in pregnant women where the use of the contrast agent may not be used). As such small bowel MRI may involve preparatory drinking or enteral tube intubation about one hour before the test as well as insertion of an intravenous cannula for intravenous contrast. Similarly an MRI of the pelvis generally requires insertion of intravenous cannula and intravenous contrast. The actual MRI takes around 30 to 40 minutes depending on whether it is for the small bowel or pelvis.BackgroundMRI for Crohn’s disease is not currently funded under the MBS. An application requesting MBS listing of capsule endoscopy for the diagnosis of suspected small bowel Crohn’s disease was not supported by MSAC (Application #1146, 27/07/2011). The application was re-submitted in July 2013 and is awaiting an outcome.Prerequisites to implementation of any funding adviceTo perform a MRI in patients with Crohn’s disease, a specialist radiologist with expertise in interpreting MRI scanning and familiarity with Crohn’s disease would be needed. The scan, in order to attract a rebate, must also be requested by a specialist medical practitioner or consultant physician and be performed on a Medicare-eligible MRI unit by a Medicare-eligible provider, and be an MRI service listed in the MBS.MRI is currently available in public and private facilities in major centres in each state and territory. There are 339 Medicare-eligible MRI units across Australia. This comprises 170 units with full Medicare-eligibility and 169 units with partial Medicare-eligibilityProposal for public fundingTables 1 and 2 present the proposed MBS item descriptors for the six indications of this application.Table 1: Proposed MBS item descriptor for MRI for small bowel Crohn’s disease with and without contrast agentCategory 5 – Diagnostic Imaging ServicesMRI to evaluate small bowel Crohn’s disease. Medicare benefits are only payable for this item if the service is provided to patients for : Evaluation of disease extent at time of initial diagnosis of Crohn’s disease Evaluation of exacerbation/suspected complications of known Crohn’s diseaseEvaluation of known or suspected Crohn’s disease in pregnancyAssessment of change to therapy in patients with small bowel Crohn’s diseaseNOTE 1: Assessment of change to therapy can only be claimed once in a 12 month period.Fee: $627.50 Benefit:?75% = $470.63 85% = $533.38 MRI enteroclysis for Crohn’s disease. Medicare benefits are only payable for this item if the service is related to item XXXX : Fee: $265.25 Benefit:?75% = $198.94 85% = $225.46Table 2: Proposed MBS item descriptor for MRI for fistulising perianal Crohn’s diseaseCategory 5 – Diagnostic Imaging ServicesMRI for fistulising perianal Crohn’s disease. Medicare benefits are only payable for this item if the service is provided to patients for: Evaluation of pelvic sepsis and fistulas associated with established or suspected Crohn’s diseaseAssessment of change to therapy of pelvis sepsis and fistulas from Crohn’s diseaseNOTE 1: Assessment of change to therapy can only be claimed once in a 12 month period.Fee: $403.20 75% = $302.40 85% = $342.72The Royal Australian and New Zealand College of Radiologists suggest separate descriptors and fees would be needed to distinguish between MR enterography and MR enteroclysis.The item descriptors may need amending following MSAC discussions of this report.The proposed fee for MRI small bowel is based on being similar in procedural complexity to MBS item 63473 for staging cervical cancer. For MRI pelvis, the proposed fee is based on being similar in complexity to MBS #63482 (MRI for pancreas and biliary tree). For MRI enteroclysis in small bowel, the fee is based on the cost of a nasojejunal tube $130 + procedure $135.25. The fees proposed seem appropriate.5.Consumer Impact StatementConsumers are likely to view a decision of public access to the proposed indications of MRI favourably. Patients currently have out-of-pocket expenses for MRI that may or may not be reimbursed through private insurers. Although a MRI procedure takes longer than the comparators, the procedure is non-invasive and may be substantially less embarrassing for patients with fistulising perianal disease requiring endoanal ultrasound ADDIN EN.CITE <EndNote><Cite><Author>Siddiqui</Author><Year>2012</Year><RecNum>25</RecNum><DisplayText>(Siddiqui et al., 2012)</DisplayText><record><rec-number>25</rec-number><foreign-keys><key app="EN" db-id="5ww0vavvyz92p9ewfdqptwwwrrxxzfvdadas" timestamp="0">25</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Siddiqui, M. R.</author><author>Ashrafian, H.</author><author>Tozer, P.</author><author>Daulatzai, N.</author><author>Burling, D.</author><author>Hart, A.</author><author>Athanasiou, T.</author><author>Phillips, R. K.</author></authors></contributors><auth-address>St. Mark's Institute, Harrow, United Kingdom. md0u812a@</auth-address><titles><title>A diagnostic accuracy meta-analysis of endoanal ultrasound and MRI for perianal fistula assessment</title><secondary-title>Dis Colon Rectum</secondary-title><alt-title>Diseases of the colon and rectum</alt-title></titles><periodical><full-title>Dis Colon Rectum</full-title><abbr-1>Diseases of the colon and rectum</abbr-1></periodical><alt-periodical><full-title>Dis Colon Rectum</full-title><abbr-1>Diseases of the colon and rectum</abbr-1></alt-periodical><pages>576-85</pages><volume>55</volume><number>5</number><edition>2012/04/20</edition><keywords><keyword>Anal Canal/pathology/ultrasonography</keyword><keyword>Crohn Disease/complications/diagnosis</keyword><keyword>Diagnosis, Differential</keyword><keyword>Endosonography/*standards</keyword><keyword>Humans</keyword><keyword>Magnetic Resonance Imaging, Interventional/*standards</keyword><keyword>Rectal Fistula/*diagnosis/etiology</keyword><keyword>Reproducibility of Results</keyword><keyword>Sensitivity and Specificity</keyword></keywords><dates><year>2012</year><pub-dates><date>May</date></pub-dates></dates><isbn>0012-3706</isbn><accession-num>22513437</accession-num><urls></urls><electronic-resource-num>10.1097/DCR.0b013e318249d26c</electronic-resource-num><remote-database-provider>Nlm</remote-database-provider><language>eng</language></record></Cite></EndNote>(Siddiqui et al., 2012). Consumer feedback confirms that only some patients experience claustrophobia with MRI. Further, they suggest that funding faecal calprotectin, as a non-invasive marker of gut inflammation, needs to be considered to complement MRI for small bowel Crohn’s disease. Increased access for rural and remote patients has recently occurred due to the MRI Expansion Initiative which increased the number of machines in rural areas. 6. Proposed intervention’s place in clinical managementIt is proposed that MRI will be indicated in six specific situations when evaluating patients with Crohn’s disease and there are several proposed changes to current practice. These separate places in the clinical management algorithm are summarised in Table 3. Separate illustrations of the clinical algorithms are provided in Appendix A. In this assessment, the clinical evidence addressed the requirements of the agreed Protocol.Table 3: Proposed indications of MRI and clinical place in therapyProposed Indication MRI is intended to:Evaluation of extent of disease at time of diagnosis for suspected or known Crohn’s disease Replace CT or SBFTEvaluation of suspected complications in known Crohn’s disease Replace CT or SBFTEvaluation of suspected Crohn’s disease in pregnancyReplace Ultrasound Assessment of change to therapy in known Crohn’s disease Complement CT or SBFT or endoscopyEvaluation of pelvic sepsis and fistulas suspected or known fistulising perianal Crohn’s disease Replace surgical examination or endoanal ultrasoundAssessment of change to therapy in patients with pelvic sepsis and fistulas in known fistulising perianal Crohn’s disease Complement surgical examination or endoanal ultrasoundCT = computer tomography, MRI = magnetic resonance imaging, SBFT = small bowel follow through. 7.Other options for MSAC considerationThe wording of the proposed MBS item descriptor does not fully reflect the intended use of patients with small bowel Crohn’s disease. With the exceptions of women who are pregnant or those with suspected perianal disease, the evaluation of Crohn’s disease with MRI is after initial assessment and diagnosis using other tests (i.e., ileocolonoscopy or endoscopy and histopathology tests). The MRI is designed for second-line testing in patients with established Crohn’s disease and ongoing management. The proposed wording of the descriptor may require the addition of these prior tests or what the applicant defines as known Crohn’s disease. This issue is important because the diagnosis of Crohn’s disease can be achieved through many tests, usually ileocolonoscopy, but there is no ‘gold standard’. However, a definitive diagnosis is crucial in Crohn’s disease in Australia because it allows for certain PBS medications and biological therapies to be administered.Furthermore, the proposed MRI service is required to be undertaken by a specialist radiologist with expertise in interpreting MRI scanning and familiarity with Crohn’s disease. The scan must also be requested by a specialist medical practitioner or consultant physician. MSAC may also wish to consider if there are limits to the number of MRIs that a patient can receive in a given time period for all six indications. Currently, once per 12 month period is stated in the descriptor for the two ‘change in therapy’ indications.parator to the proposed interventionThe nominated comparators are; computer tomography (CT), small bowel follow through (SBFT) and ultrasound for the small bowel indications and endoanal ultrasound and surgical examination for the fistulising perianal Crohn’s disease indications. The MBS item numbers are 56507 for CT with or without enterography, 58915 for SBFT, 55700 ultrasound and 55014 for abdominal/endoanal ultrasound. Other MBS items for CT and ultrasound may also be relevant. HESP advises that the vast majority of patients with Crohn’s disease currently receive CT in Australia. These comparators are appropriate. Comparative safetyNo studies were identified that report the safety outcomes of MRI compared with the nominated comparators. However, there are few perceived clinical issues around patient safety when performing MRI. On its own, MRI is non-invasive, does not emit ionizing-radiation and presents no chemical or bodily harm to the patient. The main safety issues of MRI relate to: the procedure being in a confined space and potentially uncomfortable for patients with claustrophobic tendencies or anxiety disorders, the exclusion of patients with allergies to the contrast enteric material necessary to distend the bowel in preparation for the MRI and the exclusion of individuals with internal metal or magnetic devices that may malfunction.Clinical management using MRI is widely viewed as being safer than CT, SBFT and surgical examination. MRI and ultrasound do not emit ionizing radiation and do not have the attendant risks of adverse events in surgery. Evidence suggests that CT results in small annual effective radiation doses but, in a small proportion of patients (7-15%) with Crohn’s disease, the cumulative dose is considered excessive PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5EZXNtb25kPC9BdXRob3I+PFllYXI+MjAwODwvWWVhcj48
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ADDIN EN.CITE.DATA (Desmond et al., 2008, Kroeker et al., 2011). Higher susceptibility to cumulative radiation occurs in younger age and in abdominal structures. There is no direct evidence that radiation from imaging procedures in Crohn’s disease results in increased cancer mortality. Some evidence suggests that cancer incidence is elevated in patients with Crohn’s disease but this has not been linked to imaging procedures in the study populations PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5KZXNzPC9BdXRob3I+PFllYXI+MjAwNTwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA (Jensen et al., 2011, Schmidt et al., 2010) demonstrated good (NHMRC Level II) evidence for diagnostic studies. Diagnostic performance of MRI small bowel is equivalent to the comparators for sensitivity and specificity. Across the studies, the sensitivity of MRI was high and consistent with the results from the systematic reviews (range 74% to 100%). Similarly, CT also produced high sensitivity across the studies (range 83% to 100%). The specificity of MRI was also high for the studies reporting this outcome (range 80% to 100%) but similar compared with CT (range 67% to 100%).The high-quality study by Jensen et al. (2011) found sensitivity and specificity results at the lower end of the overall range across all the studies. Statistical analysis showed that the sensitivity and specificity of MR enterography was not statistically significant from CT enterography ADDIN EN.CITE <EndNote><Cite><Author>Jensen</Author><Year>2011</Year><RecNum>33</RecNum><DisplayText>(Jensen et al., 2011)</DisplayText><record><rec-number>33</rec-number><foreign-keys><key app="EN" db-id="5ww0vavvyz92p9ewfdqptwwwrrxxzfvdadas" timestamp="0">33</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Jensen, M. D.</author><author>Kjeldsen, J.</author><author>Rafaelsen, S. R.</author><author>Nathan, T.</author></authors></contributors><auth-address>Department of Internal Medicine, Section of Gastroenterology, Lillebaelt Hospital Vejle, Kabbeltoft 25, Vejle, Denmark. michael.dam.jensen@slb.regionsyddanmark.dk</auth-address><titles><title>Diagnostic accuracies of MR enterography and CT enterography in symptomatic Crohn's disease</title><secondary-title>Scand J Gastroenterol</secondary-title><alt-title>Scandinavian journal of gastroenterology</alt-title></titles><pages>1449-57</pages><volume>46</volume><number>12</number><edition>2011/09/13</edition><keywords><keyword>Adolescent</keyword><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Constriction, Pathologic/etiology/radiography</keyword><keyword>Crohn Disease/complications/*diagnosis/radiography</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Intestine, Small/*radiography</keyword><keyword>Logistic Models</keyword><keyword>*Magnetic Resonance Imaging</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Predictive Value of Tests</keyword><keyword>Prospective Studies</keyword><keyword>Single-Blind Method</keyword><keyword>*Tomography, X-Ray Computed</keyword><keyword>Young Adult</keyword></keywords><dates><year>2011</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>0036-5521</isbn><accession-num>21905974</accession-num><urls></urls><electronic-resource-num>10.3109/00365521.2011.613947</electronic-resource-num><remote-database-provider>Nlm</remote-database-provider><language>eng</language></record></Cite></EndNote>(Jensen et al., 2011). In a meta-analysis for MRI pelvis in fistulising perianal Crohn’s disease for identifying fistulas, the pooled sensitivity of MRI was 87% (95%CI: 63%-96%) and specificity 69% (95%CI: 51%-82%). For endoanal ultrasound, pooled sensitivity was identical to MRI at 87% (95%CI: 70%-95%) but lower for specificity 43% (95%CI: 21%-69%) ADDIN EN.CITE <EndNote><Cite><Author>Siddiqui</Author><Year>2012</Year><RecNum>25</RecNum><DisplayText>(Siddiqui et al., 2012)</DisplayText><record><rec-number>25</rec-number><foreign-keys><key app="EN" db-id="5ww0vavvyz92p9ewfdqptwwwrrxxzfvdadas" timestamp="0">25</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Siddiqui, M. R.</author><author>Ashrafian, H.</author><author>Tozer, P.</author><author>Daulatzai, N.</author><author>Burling, D.</author><author>Hart, A.</author><author>Athanasiou, T.</author><author>Phillips, R. K.</author></authors></contributors><auth-address>St. Mark's Institute, Harrow, United Kingdom. md0u812a@</auth-address><titles><title>A diagnostic accuracy meta-analysis of endoanal ultrasound and MRI for perianal fistula assessment</title><secondary-title>Dis Colon Rectum</secondary-title><alt-title>Diseases of the colon and rectum</alt-title></titles><periodical><full-title>Dis Colon Rectum</full-title><abbr-1>Diseases of the colon and rectum</abbr-1></periodical><alt-periodical><full-title>Dis Colon Rectum</full-title><abbr-1>Diseases of the colon and rectum</abbr-1></alt-periodical><pages>576-85</pages><volume>55</volume><number>5</number><edition>2012/04/20</edition><keywords><keyword>Anal Canal/pathology/ultrasonography</keyword><keyword>Crohn Disease/complications/diagnosis</keyword><keyword>Diagnosis, Differential</keyword><keyword>Endosonography/*standards</keyword><keyword>Humans</keyword><keyword>Magnetic Resonance Imaging, Interventional/*standards</keyword><keyword>Rectal Fistula/*diagnosis/etiology</keyword><keyword>Reproducibility of Results</keyword><keyword>Sensitivity and Specificity</keyword></keywords><dates><year>2012</year><pub-dates><date>May</date></pub-dates></dates><isbn>0012-3706</isbn><accession-num>22513437</accession-num><urls></urls><electronic-resource-num>10.1097/DCR.0b013e318249d26c</electronic-resource-num><remote-database-provider>Nlm</remote-database-provider><language>eng</language></record></Cite></EndNote>(Siddiqui et al., 2012). No studies were found comparing the extent of Crohn’s disease or complications of disease using SBFT as the comparator, all used CT for small bowel Crohn’s disease. No studies reported outcomes for MRI in pregnant women most likely because the studies included CT and CT is contraindicated in pregnancy. It is unclear if there is any direct or indirect impact on clinical or patient outcomes based from the evidence in this assessment. 11.Economic evaluationA cost-utility analysis was performed for one of the six proposed indications; pelvis MRI for extent of Crohn’s disease in fistulising perianal Crohn’s disease. This was the only indication where a cost-utility analysis was justified based on the superior specificity of MRI to endoanal ultrasound ADDIN EN.CITE <EndNote><Cite><Author>Siddiqui</Author><Year>2012</Year><RecNum>25</RecNum><DisplayText>(Siddiqui et al., 2012)</DisplayText><record><rec-number>25</rec-number><foreign-keys><key app="EN" db-id="5ww0vavvyz92p9ewfdqptwwwrrxxzfvdadas" timestamp="0">25</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Siddiqui, M. R.</author><author>Ashrafian, H.</author><author>Tozer, P.</author><author>Daulatzai, N.</author><author>Burling, D.</author><author>Hart, A.</author><author>Athanasiou, T.</author><author>Phillips, R. K.</author></authors></contributors><auth-address>St. Mark's Institute, Harrow, United Kingdom. md0u812a@</auth-address><titles><title>A diagnostic accuracy meta-analysis of endoanal ultrasound and MRI for perianal fistula assessment</title><secondary-title>Dis Colon Rectum</secondary-title><alt-title>Diseases of the colon and rectum</alt-title></titles><periodical><full-title>Dis Colon Rectum</full-title><abbr-1>Diseases of the colon and rectum</abbr-1></periodical><alt-periodical><full-title>Dis Colon Rectum</full-title><abbr-1>Diseases of the colon and rectum</abbr-1></alt-periodical><pages>576-85</pages><volume>55</volume><number>5</number><edition>2012/04/20</edition><keywords><keyword>Anal Canal/pathology/ultrasonography</keyword><keyword>Crohn Disease/complications/diagnosis</keyword><keyword>Diagnosis, Differential</keyword><keyword>Endosonography/*standards</keyword><keyword>Humans</keyword><keyword>Magnetic Resonance Imaging, Interventional/*standards</keyword><keyword>Rectal Fistula/*diagnosis/etiology</keyword><keyword>Reproducibility of Results</keyword><keyword>Sensitivity and Specificity</keyword></keywords><dates><year>2012</year><pub-dates><date>May</date></pub-dates></dates><isbn>0012-3706</isbn><accession-num>22513437</accession-num><urls></urls><electronic-resource-num>10.1097/DCR.0b013e318249d26c</electronic-resource-num><remote-database-provider>Nlm</remote-database-provider><language>eng</language></record></Cite></EndNote>(Siddiqui et al., 2012). The evaluation was a simple decision-analytic model with a 12 month time horizon. The analysis should be viewed as exploratory due to the absence of key estimates from an evidence base.The main inputs to the economic model were the sensitivity and specificity estimates from the main supporting meta-analysis ADDIN EN.CITE <EndNote><Cite><Author>Siddiqui</Author><Year>2012</Year><RecNum>25</RecNum><DisplayText>(Siddiqui et al., 2012)</DisplayText><record><rec-number>25</rec-number><foreign-keys><key app="EN" db-id="5ww0vavvyz92p9ewfdqptwwwrrxxzfvdadas" timestamp="0">25</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Siddiqui, M. R.</author><author>Ashrafian, H.</author><author>Tozer, P.</author><author>Daulatzai, N.</author><author>Burling, D.</author><author>Hart, A.</author><author>Athanasiou, T.</author><author>Phillips, R. K.</author></authors></contributors><auth-address>St. Mark's Institute, Harrow, United Kingdom. md0u812a@</auth-address><titles><title>A diagnostic accuracy meta-analysis of endoanal ultrasound and MRI for perianal fistula assessment</title><secondary-title>Dis Colon Rectum</secondary-title><alt-title>Diseases of the colon and rectum</alt-title></titles><periodical><full-title>Dis Colon Rectum</full-title><abbr-1>Diseases of the colon and rectum</abbr-1></periodical><alt-periodical><full-title>Dis Colon Rectum</full-title><abbr-1>Diseases of the colon and rectum</abbr-1></alt-periodical><pages>576-85</pages><volume>55</volume><number>5</number><edition>2012/04/20</edition><keywords><keyword>Anal Canal/pathology/ultrasonography</keyword><keyword>Crohn Disease/complications/diagnosis</keyword><keyword>Diagnosis, Differential</keyword><keyword>Endosonography/*standards</keyword><keyword>Humans</keyword><keyword>Magnetic Resonance Imaging, Interventional/*standards</keyword><keyword>Rectal Fistula/*diagnosis/etiology</keyword><keyword>Reproducibility of Results</keyword><keyword>Sensitivity and Specificity</keyword></keywords><dates><year>2012</year><pub-dates><date>May</date></pub-dates></dates><isbn>0012-3706</isbn><accession-num>22513437</accession-num><urls></urls><electronic-resource-num>10.1097/DCR.0b013e318249d26c</electronic-resource-num><remote-database-provider>Nlm</remote-database-provider><language>eng</language></record></Cite></EndNote>(Siddiqui et al., 2012), costs for MRI pelvis, costs for surgical procedures and endoanal ultrasound and utilities for patients with Crohn’s disease. In the base case, the mean costs of a MRI strategy were lower over 12 months than a strategy of endoanal ultrasound (by $806), while the corresponding quality-adjusted life years (QALYs) were slightly higher (0.05). MRI pelvis therefore dominated endoanal ultrasound. Probabilistic sensitivity analyses showed a high likelihood of MRI being cost-effective for this indication and may be cost-saving in most cases, subject to the assumptions of the model.Financial/budgetary impactsLikely volume of use of the proposed imaging test per year: 13597Frequency of use per patient per year over 5 years: 1 per yearPatient numbers per year (prevalence/ incidence mix over time): 13597Total cost of the proposed imaging test to the MBS per year: $8,718,243Total cost of the service to the public: unknownNet financial cost/year to the MBS (without safety net impacts): $6,256,00613.Other significant factorsNil14.ConclusionsThe key clinical issues that remain a source of uncertainty for this assessment include:The proposed patient population is predominantly for established Crohn’s disease but the current proposed MBS item descriptors could target this population more definitively by defining the duration of disease or prior tests that must have been undertaken;The diagnostic accuracy is based on satisfactory evidence for detecting extent and complications of disease. However the studies included in this assessment have limitations relating to study heterogeneity, small sample sizes, and potential unblinding across the tests and reference standards. Furthermore, all studies are European-based and details of patient characteristics were minimally reported. Therefore, the applicability to an Australian population is unclear.MRI test accuracy has an unknown impact on management decisions and in turn, patient outcomes. It is therefore unclear what benefits patients receive from MRI in addition to the comparators. The claim that the reduction in exposure to ionizing radiation is the central argument but there is unclear evidence of how harmful CT and SBFT are likely to be.There were no comparative safety or effectiveness outcomes for pregnant patients suspected of Crohn’s disease therefore conclusions cannot be drawn about the safety or effectiveness in this subgroup.The key economic considerations include:The lack of evidence on the epidemiology, actual utilisation of imaging modalities and clinical management patterns of Australian’s with Crohn’s disease. This hinders accurate estimates for the financial estimates and economic evaluation.The main driver of the costs to the MBS and Australian health system for the proposed use of MRI here is the frequency of tests per person required for a disease that is incurable and chronic. The likelihood of MRI uptake is high and potentially rapid considering the high proportions of patients with Crohn’s disease experiencing complications, complex disease and abscesses/fistulas.The cost-utility model within this assessment is largely hypothetical and several assumptions were necessary during construction due to the absence of data. In this light, the analysis should be seen as exploratory until more robust estimates are available.The likely repercussions of a rejection are likely to fall heavier on patients with suspected or known fistulising perianal Crohn’s disease. This subgroup will be disadvantaged due to the uncomfortable and invasive alternatives in current use. However, relatively fewer consequences will be felt for those with small bowel Crohn’s disease due to the alternative imaging options readily available and their equivalent diagnostic performance.IntroductionThe Medical Services Advisory Committee (MSAC) has reviewed the use of magnetic resonance imaging (MRI), which is a diagnostic test for the management of Crohn’s disease. MSAC evaluates new and existing health technologies and procedures for which funding is sought under the Medicare Benefits Scheme in terms of their safety, effectiveness and cost-effectiveness, while taking into account other issues such as access and equity. MSAC adopts an evidence-based approach to its assessments, based on reviews of the scientific literature and other information sources, including clinical expertise.MSAC is a multidisciplinary expert body, comprising members drawn from such disciplines as diagnostic imaging, pathology, surgery, internal medicine and general practice, clinical epidemiology, health economics, consumer health and health administration.This report summarises the assessment of current evidence for MRI small bowel and pelvis in the evaluation of small bowel Crohn’s disease and fistulising perianal Crohn’s disease.BackgroundCrohn’s diseaseCrohn’s disease is most common in adolescents and young adults, but can occur at any age.?Diagnosis is based on a composite of endoscopy, radiography and pathological findings. Crohn’s disease is a lifelong condition which often requires repeat diagnostic investigations to evaluate and assess disease; patients may undergo imaging as frequently as several times a year or not at all depending on their progress and disease severity. As many as 50-60% of patients require surgery at some point, to manage their disease. Many require repeat surgery for recurrent disease despite treatment with pharmacotherapy. Management depends on the disease location, disease severity, and disease-associated complications ADDIN EN.CITE <EndNote><Cite><Author>Zimmermann</Author><Year>2011</Year><RecNum>160</RecNum><DisplayText>(Zimmermann and Al-Hawary, 2011)</DisplayText><record><rec-number>160</rec-number><foreign-keys><key app="EN" db-id="5ww0vavvyz92p9ewfdqptwwwrrxxzfvdadas" timestamp="1386650216">160</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Zimmermann, E. M.</author><author>Al-Hawary, M. M.</author></authors></contributors><auth-address>Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 49109, USA. ezimmer@umich.edu</auth-address><titles><title>MRI of the small bowel in patients with Crohn's disease</title><secondary-title>Curr Opin Gastroenterol</secondary-title><alt-title>Current opinion in gastroenterology</alt-title></titles><periodical><full-title>Curr Opin Gastroenterol</full-title><abbr-1>Current opinion in gastroenterology</abbr-1></periodical><alt-periodical><full-title>Curr Opin Gastroenterol</full-title><abbr-1>Current opinion in gastroenterology</abbr-1></alt-periodical><pages>132-8</pages><volume>27</volume><number>2</number><edition>2011/02/08</edition><keywords><keyword>Crohn Disease/*diagnosis/radiography</keyword><keyword>Humans</keyword><keyword>Intestine, Small/*pathology/radiography</keyword><keyword>Magnetic Resonance Imaging/*methods</keyword><keyword>Tomography, X-Ray Computed</keyword></keywords><dates><year>2011</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0267-1379</isbn><accession-num>21297471</accession-num><urls></urls><custom2>Pmc3433225</custom2><custom6>Nihms337012</custom6><electronic-resource-num>10.1097/MOG.0b013e3283438e5d</electronic-resource-num><remote-database-provider>Nlm</remote-database-provider><language>eng</language></record></Cite></EndNote>(Zimmermann and Al-Hawary, 2011). Magnetic resonance imaging (MRI)MRI is not a new technology and it has been used in medical imaging since the 1980s. It involves the production of a magnetic field that causes hydrogen atoms in the body to align in a certain direction. When the field is switched off, the atoms return to their normal alignment sending off a signal that can be interpreted by a computer to produce images. There is no ionising radiation from an MRI scan as it uses magnetic and radio waves. Therefore there is no increased risk of cancer and it is theoretically safe in pregnancy. MRI is not suitable for people with metal implants as the magnetic field can dislodge metal parts, depending on their size and location. Also, MRI scans can cause pacemakers or defibrillators to malfunction.MRI allows accurate visualisation of the entire gastrointestinal tract through the acquisition of multi-planar images with high-contrast resolution of the tissue. Bowel distension is needed to obtain optimal visualisation and is achieved through the use of an enteric contrast material. This may be administered orally (MR enterography) or through an nasojejunal tube (MR enteroclysis). Small bowel MRI is used in conjunction with enteric contrast material to achieve bowel distension (the exception to this is in pregnant women where the use of the contrast agent may not be used). As such small bowel MRI may involve preparatory drinking or enteral tube intubation about one hour before the test as well as insertion of an intravenous cannula for intravenous contrast. Similarly an MRI of the pelvis generally requires insertion of intravenous cannula and intravenous contrast. The actual MRI takes around 30 to 40 minutes depending on whether it is for the small bowel or for pelvis. The individual is required to stay very still in a dark space for this time. Ear plugs are offered due to the loud knocking noise of the machine. This noise is not loud enough to cause pain or hearing damage to the individual.Improvements in MRI technology such as fast scanning techniques and the use of bowel anti-peristaltic agents have permitted more accurate diagnosis of complications of Crohn’s disease, including abscess, fistula and stenosis. MRI is widely believed to be useful when ionising radiation is contraindicated such as in children and pregnant women and where multiple diagnostic procedures are needed, as may occur in chronic, remitting and relapsing conditions such as Crohn’s disease.To perform a MRI in patients with Crohn’s disease, a specialist radiologist with expertise in interpreting MRI scans and familiarity with Crohn’s disease is needed. The scan, in order to attract a rebate, must also be requested by a specialist medical practitioner or consultant physician and be performed on a Medicare-eligible MRI unit by a Medicare-eligible provider, and be an MRI service listed in the MBS. All radiologists providing MRI services must demonstrate that they meet minimum?MRI training requirements. The Department of Human Services (DHS) uses 'participation in the Royal Australian and New Zealand College of Radiologists (RANZCR) Quality and Accreditation Program' as one of the eligibility criteria under MRI Eligible Provider regulations. All eligible providers for MRI declare that they are participants in the Quality and Accreditation Program in their MRI Statutory Declarations to DHS, which means they are declaring that they are complying with MRI-specific requirements in the RANZCR Standards of Practice and the MRI Quality ProgramIntended purpose This report assesses MRI in patients with Crohn’s disease. Collectively, the intended purpose of this application is for MRI to be used in patients who have previously been diagnosed with Crohn’s and where the imaging is designed to investigate known disease to direct further treatment. Patients with suspected Crohn’s disease are usually diagnosed with ileocolonoscopy and histopathology. The spectrum of uses in this application therefore goes beyond initial diagnosis of Crohn’s disease. It focusses on patients with small bowel or pelvic Crohn’s disease and the purposes of evaluating disease extent, complications, in pregnancy and informs any change of therapy required. Patients with suspected fistulising perianal Crohn’s disease or are pregnant with suspected Crohn’s disease are the exceptions.Clinical need Epidemiology of Crohn’s disease Quantifying the burden of Crohn’s disease in Australia is difficult since there are few epidemiological studies on this topic and those that exist combine Crohn’s disease with ulcerative colitis, known collectively as inflammatory bowel disease. However, in a recent prospective, population-based study of inflammatory bowel disease incidence, the Asia-Pacific Crohn’s and Colitis Epidemiology Study, the crude annual overall incidence of Crohn’s disease in Australia during 2011-2012 was 14.00 (95%CI: 10.09-18.92) per 100,000 persons (n=49) PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5OZzwvQXV0aG9yPjxZZWFyPjIwMTM8L1llYXI+PFJlY051
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ADDIN EN.CITE.DATA (Ng et al., 2013). This equates to approximately 3,220 new cases each year in Australia. In this study, there were slightly more females (51%) than males (49%) and all incident cases were Caucasians with a mean age of 40 years. The peak age of diagnosis was 20-24 years with a second smaller peak at 40-44 years. The ratio of Crohn’s disease to ulcerative colitis in Australia was 2:1. Median time from the onset of symptoms to diagnosis was 5? months (interquartile range 1.4 – 15 months) and 25% of patients were diagnosed as an inpatient. Complications of Crohn’s disease by way of structuring, penetrating or perianal disease were found in 24% of patients and a family history was found in 17% of cases PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5OZzwvQXV0aG9yPjxZZWFyPjIwMTM8L1llYXI+PFJlY051
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ADDIN EN.CITE.DATA (Ng et al., 2013). A report in March 2013 has estimated updated prevalence figures of inflammatory bowel disease for Australia ADDIN EN.CITE <EndNote><Cite><Author>PricewaterhouseCoopers Australia</Author><Year>2013</Year><RecNum>168</RecNum><DisplayText>(PricewaterhouseCoopers Australia, 2013)</DisplayText><record><rec-number>168</rec-number><foreign-keys><key app="EN" db-id="5ww0vavvyz92p9ewfdqptwwwrrxxzfvdadas" timestamp="1386651311">168</key></foreign-keys><ref-type name="Report">27</ref-type><contributors><authors><author>PricewaterhouseCoopers Australia,</author></authors></contributors><titles><title>Improving Inflammatory Bowel Disease care across Australia</title></titles><volume>March 2013</volume><dates><year>2013</year></dates><pub-location>.au</pub-location><publisher>PricewaterhouseCoopers</publisher><urls></urls></record></Cite></EndNote>(PricewaterhouseCoopers Australia, 2013). They report the disease affects approximately 75,000 Australians each year. Impact on patient quality of lifeCrohn’s disease exerts a significant burden to individuals since it is an incurable chronic condition that manifests most commonly in adolescents and young adults. It substantially impairs quality of life due to the experience of symptoms such as abdominal pain and diarrhoea. Factors that concern patients include the uncertainty of the disease, adverse effects of medication, incontinence, having to use an ostomy bag, low energy levels and the possible need for surgery. These experiences can severely interrupt normal role activities and good quality of life. Aspects specifically related to fistulising perianal disease include: discharge, pain, restriction of sexual activity and time with the disease ADDIN EN.CITE <EndNote><Cite><Author>Taxonera</Author><Year>2009</Year><RecNum>161</RecNum><DisplayText>(Taxonera et al., 2009)</DisplayText><record><rec-number>161</rec-number><foreign-keys><key app="EN" db-id="5ww0vavvyz92p9ewfdqptwwwrrxxzfvdadas" timestamp="1386650354">161</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Taxonera, C.</author><author>Schwartz, D. A.</author><author>Garcia-Olmo, D.</author></authors></contributors><auth-address>Inflammatory Bowel Disease Unit, Department of Gastroenterology, Hospital Clinico, Madrid 28040, Spain. ctaxonera.hcsc@salud.</auth-address><titles><title>Emerging treatments for complex perianal fistula in Crohn's disease</title><secondary-title>World J Gastroenterol</secondary-title><alt-title>World journal of gastroenterology : WJG</alt-title></titles><periodical><full-title>World J Gastroenterol</full-title><abbr-1>World journal of gastroenterology : WJG</abbr-1></periodical><alt-periodical><full-title>World J Gastroenterol</full-title><abbr-1>World journal of gastroenterology : WJG</abbr-1></alt-periodical><pages>4263-72</pages><volume>15</volume><number>34</number><edition>2009/09/15</edition><keywords><keyword>6-Mercaptopurine/therapeutic use</keyword><keyword>Anti-Bacterial Agents/therapeutic use</keyword><keyword>Azathioprine/therapeutic use</keyword><keyword>Crohn Disease/*complications</keyword><keyword>Humans</keyword><keyword>Immunologic Factors/therapeutic use</keyword><keyword>Rectal Fistula/diagnosis/etiology/*therapy</keyword><keyword>Tumor Necrosis Factor-alpha/therapeutic use</keyword></keywords><dates><year>2009</year><pub-dates><date>Sep 14</date></pub-dates></dates><isbn>1007-9327 (Print)
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ADDIN EN.CITE.DATA (Duricova et al., 2010). The higher number of deaths relative to population norms was explained by increased deaths from gastrointestinal diseases (including Crohn’s disease) as well as other diseases (COPD, lung disease and genitourinary disease). In a second study by Canavan et al. (2007) including 13 published studies from 1970, a meta-analysis found an elevated risk of mortality for individuals with Crohn’s disease (standardized mortality ration 1.52 (95%CI: 1.32-1.74), p<0.001 ADDIN EN.CITE <EndNote><Cite><Author>Canavan</Author><Year>2007</Year><RecNum>165</RecNum><DisplayText>(Canavan et al., 2007)</DisplayText><record><rec-number>165</rec-number><foreign-keys><key app="EN" db-id="5ww0vavvyz92p9ewfdqptwwwrrxxzfvdadas" timestamp="1386650566">165</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Canavan, C.</author><author>Abrams, K. R.</author><author>Mayberry, J. F.</author></authors></contributors><auth-address>Digestive Diseases Centre, University Hospitals of Leicester, Leicester General Hospital, Gwendolen Road, Leicester. cc71@le.ac.uk</auth-address><titles><title>Meta-analysis: mortality in Crohn's disease</title><secondary-title>Aliment Pharmacol Ther</secondary-title><alt-title>Alimentary pharmacology & therapeutics</alt-title></titles><periodical><full-title>Aliment Pharmacol Ther</full-title><abbr-1>Alimentary pharmacology & therapeutics</abbr-1></periodical><alt-periodical><full-title>Aliment Pharmacol Ther</full-title><abbr-1>Alimentary pharmacology & therapeutics</abbr-1></alt-periodical><pages>861-70</pages><volume>25</volume><number>8</number><edition>2007/04/04</edition><keywords><keyword>Age Factors</keyword><keyword>Crohn Disease/diagnosis/*mortality</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Randomized Controlled Trials as Topic</keyword><keyword>Risk Factors</keyword></keywords><dates><year>2007</year><pub-dates><date>Apr 15</date></pub-dates></dates><isbn>0269-2813 (Print)
0269-2813</isbn><accession-num>17402989</accession-num><urls></urls><electronic-resource-num>10.1111/j.1365-2036.2007.03276.x</electronic-resource-num><remote-database-provider>Nlm</remote-database-provider><language>eng</language></record></Cite></EndNote>(Canavan et al., 2007). However, many of the studies in the review do not reflect current clinical practice and improved therapies.Hospital separationsIn 2009-10, there were 16,756 hospital separations with the principal diagnosis of Crohn’s disease (ICD code K50) ADDIN EN.CITE <EndNote><Cite><Author>AIHW</Author><Year>2011</Year><RecNum>169</RecNum><DisplayText>(AIHW, 2011)</DisplayText><record><rec-number>169</rec-number><foreign-keys><key app="EN" db-id="5ww0vavvyz92p9ewfdqptwwwrrxxzfvdadas" timestamp="1386651695">169</key></foreign-keys><ref-type name="Online Database">45</ref-type><contributors><authors><author>AIHW,</author></authors></contributors><titles><title>AIHW National Hospital Morbidity Datatase (Internet)</title></titles><dates><year>2011</year></dates><pub-location>Canberra</pub-location><publisher>Australian Institute of Health and Welfare</publisher><urls><related-urls><url>;(AIHW, 2011). Of these, 2,785 (16.6%) separations were for small bowel Crohn’s disease (K50.1). Between 1998-99 and 2008-09, hospital separations for Crohn’s disease (K50) increased 2.5-fold, increasing from 6,485 to 16,756 ADDIN EN.CITE <EndNote><Cite><Author>AIHW</Author><Year>2011</Year><RecNum>169</RecNum><DisplayText>(AIHW, 2011)</DisplayText><record><rec-number>169</rec-number><foreign-keys><key app="EN" db-id="5ww0vavvyz92p9ewfdqptwwwrrxxzfvdadas" timestamp="1386651695">169</key></foreign-keys><ref-type name="Online Database">45</ref-type><contributors><authors><author>AIHW,</author></authors></contributors><titles><title>AIHW National Hospital Morbidity Datatase (Internet)</title></titles><dates><year>2011</year></dates><pub-location>Canberra</pub-location><publisher>Australian Institute of Health and Welfare</publisher><urls><related-urls><url>;(AIHW, 2011). This is consistent with reported global increases in the prevalence of Crohn’s disease; however it could also represent an increased rate of admissions per patient PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5XaWxzb248L0F1dGhvcj48WWVhcj4yMDEwPC9ZZWFyPjxS
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ADDIN EN.CITE.DATA (Wilson et al., 2010, Zimmermann and Al-Hawary, 2011). Existing testsDiagnosis of Crohn’s disease can be difficult as the symptoms for Crohn’s disease mimic those of ulcerative colitis and other gastrointestinal conditions. Currently, there are no clinical, endoscopic or pathological markers for a definitive diagnosis of Crohn’s disease. In the absence of an agreed ‘gold standard’ test, diagnosis of Crohn’s disease is based on a combination of; clinical judgement on the basis of patient history, physical examination, radiographic and endoscopic evidence and histological and laboratory findings. Ileocolonoscopy is commonly used to diagnose Crohn’s disease as first-line testing. In most cases, a definitive diagnosis of Crohn’s can be made but sometimes results of ileocolonoscopy are indeterminate. Sometimes, this is due to ileocolonoscopy not allowing view the entire bowel. In this case, second-line imaging if often undertaken to confirm a diagnosis of Crohn’s disease. For assessing known Crohn’s disease in the small bowel or pelvis, there are four existing imaging tests:Abdominal computer tomography (CT)Abdominal CT is a radiological technique used to examine the extent or complications of small bowel Crohn’s disease. This test provides multiplanar images of the lumen, wall and mesentery of the small bowel. These images have a high degree of spatial resolution and are generated via the use of multidetector CT technology following intravenous contrast and the ingestion of a contrast agent by the patient either orally (CT enterography) or via a naso-jejunal tube (CT enteroclysis). Abdominal CT is funded under MBS item 56507 with a fee $480.05. A range of other MBS items for CT also exist.Small bowel follow through (SBFT)SBFT is a radiological technique for imaging the small bowel. Barium is either ingested by the patient or administered by enteroclysis and then x-ray images are taken of the abdomen. In some Australia settings, SBFT has been superseded by abdomen CT/CT enteroclysis however clinical practice varies across settings. Moreover, its use is limited by high radiation exposure. SBFT is funded under MBS item 58915 with a fee $78.95.Endoanal UltrasoundTo perform endoanal ultrasound, a dedicated probe is required which can be attached to some standard ultrasound machines. Endoanal ultrasound is only used for perianal disease, as opposed to standard ultrasound which is used for gynaecological evaluation of the pelvis, renal tract or hepatobiliary-pancreatic tree. Expertise in Australia with endoanal ultrasound is limited as there is no formal training and the investigation is usually carried out by interested clinicians who may not have specific radiological training in ultrasound ADDIN EN.CITE <EndNote><Cite><Author>Rieger</Author><Year>2004</Year><RecNum>159</RecNum><DisplayText>(Rieger et al., 2004)</DisplayText><record><rec-number>159</rec-number><foreign-keys><key app="EN" db-id="5ww0vavvyz92p9ewfdqptwwwrrxxzfvdadas" timestamp="1386650177">159</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Rieger, N.</author><author>Tjandra, J.</author><author>Solomon, M.</author></authors></contributors><auth-address>University of Adelaide Department of Surgery, The Queen Elizabeth Hospital, Woodville Road, Woodville, SA 5011, South Australia. nrieger@medicine.adelaide.edu.au</auth-address><titles><title>Endoanal and endorectal ultrasound: applications in colorectal surgery</title><secondary-title>ANZ J Surg</secondary-title><alt-title>ANZ journal of surgery</alt-title></titles><periodical><full-title>ANZ J Surg</full-title><abbr-1>ANZ journal of surgery</abbr-1></periodical><alt-periodical><full-title>ANZ J Surg</full-title><abbr-1>ANZ journal of surgery</abbr-1></alt-periodical><pages>671-5</pages><volume>74</volume><number>8</number><edition>2004/08/19</edition><keywords><keyword>*Endosonography</keyword><keyword>Fecal Incontinence/surgery/*ultrasonography</keyword><keyword>Humans</keyword><keyword>Inflammatory Bowel Diseases/surgery/*ultrasonography</keyword><keyword>Rectal Neoplasms/surgery/*ultrasonography</keyword></keywords><dates><year>2004</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1445-1433 (Print)
1445-1433</isbn><accession-num>15315569</accession-num><urls></urls><electronic-resource-num>10.1111/j.1445-1433.2004.02884.x</electronic-resource-num><remote-database-provider>Nlm</remote-database-provider><language>eng</language></record></Cite></EndNote>(Rieger et al., 2004) ADDIN REFMGR.CITE <Refman><Cite><Author>Rieger</Author><Year>2004</Year><RecNum>40</RecNum><IDText>Endoanal and endorectal ultrasound: applications in colorectal surgery</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>40</Ref_ID><Title_Primary>Endoanal and endorectal ultrasound: applications in colorectal surgery</Title_Primary><Authors_Primary>Rieger,N</Authors_Primary><Authors_Primary>Tjandra,J</Authors_Primary><Authors_Primary>Solomon,M</Authors_Primary><Date_Primary>2004</Date_Primary><Reprint>In File</Reprint><Start_Page>671</Start_Page><End_Page>675</End_Page><Periodical>ANJ Surgery</Periodical><Volume>74</Volume><ZZ_JournalFull><f name="System">ANJ Surgery</f></ZZ_JournalFull><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>.The main advantage with endoanal ultrasound is its ability to assess deep, complex fistulas accurately.Surgical ExaminationIn practice, surgical examination (under anaesthesia) and exploration is undertaken to evaluate fistulising Crohn’s disease. This consists of visual inspection, palpation and the passage of metal probes into fistula tracks under general anaesthesia. Surgical examination under anaesthesia is the gold standard in the evaluation and classification of acute deterioration of perianal sepsis in Crohn’s disease. It is expensive however and carries the risk of damage to the anal sphincter during the procedure leading to incontinence. Current guidelinesUpdated Australian guidelines for inflammatory bowel disease have been available from the Gastroenterological Society of Australia in May 2013. These provide general practitioners and clinicians with specific diagnosis and treatment options and, where applicable, reference the current PBS and MBS reimbursed services and products. With respect to MRI and this application specifically, the guidelines state: ‘Cross-sectional imaging (CT, ultrasonogragphy, MRI including CT enterography and MRI enterography). To determine disease extent and severity and to assess for perforating complications. Ultrasound and MRI are preferred as the patients are often young and are likely to require repeat imaging over time’ page 11 ADDIN EN.CITE <EndNote><Cite><Author>Gastroenterological Society of Australia</Author><Year>2013</Year><RecNum>156</RecNum><DisplayText>(Gastroenterological Society of Australia, 2013)</DisplayText><record><rec-number>156</rec-number><foreign-keys><key app="EN" db-id="5ww0vavvyz92p9ewfdqptwwwrrxxzfvdadas" timestamp="1386649920">156</key></foreign-keys><ref-type name="Report">27</ref-type><contributors><authors><author>Gastroenterological Society of Australia,</author></authors></contributors><titles><title>Inflammatory Bowel Disease: Australian Guidelines for General Practitioners and Physicians</title><secondary-title>3rd Edition</secondary-title></titles><dates><year>2013</year></dates><publisher>Digestive Health Foundation</publisher><urls></urls></record></Cite></EndNote>(Gastroenterological Society of Australia, 2013).Marketing status of technology MRI is currently available in public and private facilities in major centres in each state and territory. There are 339 Medicare-eligible MRI units across Australia. This comprises 170 units with full Medicare-eligibility and 169 units with partial Medicare-eligibility. MRI is subject to the capital sensitivity measure for all diagnostic imaging equipment. Most diagnostic imaging services (except for PET) have two different schedule items: schedule K items and schedule NK items. Schedule NK items have a fee approximately half the corresponding K item. Whether a service is a schedule K or a schedule NK service depends on the age of the equipment, whether the equipment has been upgraded or whether a location based exemption of the age requirements has been granted (see?).In Australia, the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) uses Diagnostic Reference Levels on specified imaging protocols to help avoid excessive radiation doses to patients. This quality assurance tool is part of the ARPANSA Code of Practice (RPS 14) that must be complied with by accredited RANZCR radiologists. ARPANSA and other stakeholders are currently establishing a national survey program for the development of national Diagnostic Reference Levels with the first being applied to multidetector computer tomography ADDIN EN.CITE <EndNote><Cite><Author>ARPANSA</Author><Year>2013</Year><RecNum>180</RecNum><DisplayText>(ARPANSA, 2013)</DisplayText><record><rec-number>180</rec-number><foreign-keys><key app="EN" db-id="5ww0vavvyz92p9ewfdqptwwwrrxxzfvdadas" timestamp="1386736106">180</key></foreign-keys><ref-type name="Government Document">46</ref-type><contributors><authors><author>ARPANSA</author></authors><secondary-authors><author>Australian Radiation Protection and Nuclear Safety Agency</author></secondary-authors></contributors><titles><title>National Diagnostic Reference Level Fact Sheet </title></titles><pages>10</pages><dates><year>2013</year></dates><pub-location>Melbourne</pub-location><publisher>Australian Government</publisher><urls></urls></record></Cite></EndNote>(ARPANSA, 2013). Current reimbursement arrangementsMRI is currently not listed for the diagnosis or ongoing assessment of known small bowel or pelvis Crohn’s disease. For the proposed indications, MRI is currently funded by patients.Approach to assessment ObjectiveThe objective of this assessment is to undertake a structured evaluation of the clinical need, safety, effectiveness and cost-effectiveness of MRI for patients with small bowel or fistulising perianal Crohn’s disease.Clinical decision pathwayFor the six indications proposed in the application, there are six corresponding clinical decision flow charts for MRI for patients as provided in the final DAP. These flow charts are provided in Appendix A. Figure 1 provides a simplified clinical pathway to summarise the clinical place of the six MRI indications (shown in red numerals) proposed in this application. Table 4 provides the details of the corresponding relevant comparators for each paratorsFor the specific indications proposed in the application, there are six relevant comparators for MRI for patients with small bowel or perianal fistulising Crohn’s disease:Small bowel:CT Ultrasound (in pregnancy)SBFTEndoscopyFistulising perianal:Surgical examination Endoanal ultrasoundThe reference standard This application primarily targets patients initially diagnosed with Crohn’s disease and the potential uses during the monitoring or management of the condition. MRI is intended for use in patients with established Crohn’s disease, except for pregnant women who may have suspected Crohn’s disease and are ineligible for prior tests and a small subgroup of patients with suspected perianal Crohn’s disease.Small bowel: There is no agreement as to the optimal gold standard and due to the advantages of MRI over the most common comparator CT, MRI may become the new gold standard. For small bowel Crohn’s disease, the reference standard is a panel of tests (excluding the index or comparator tests). Fistulising perianal: Surgical examination is considered the reference standard for fistulising Crohn’s disease. Figure 1: Simplified clinical decision tree Table 4: Summary of indications for MRI application and replacement testsProposed Indication (numbers refer to Figure 1)MRI to replace:Evaluation of extent of disease at time of diagnosis for suspected or known Crohn’s disease CT or SBFTEvaluation of suspected complications in known Crohn’s disease CT or SBFTEvaluation of suspected Crohn’s disease in pregnancyUltrasound Assessment of change to therapy in known Crohn’s disease CT or SBFT or endoscopyEvaluation of pelvic sepsis and fistulas suspected or known fistulising perianal Crohn’s disease Surgical examination or endoanal ultrasoundAssessment of change to therapy in patients with pelvic sepsis and fistulas in known fistulising perianal Crohn’s disease Surgical examination or endoanal ultrasoundCT = computer tomography, MRI = magnetic resonance imaging, SBFT = small bowel follow through. Research questionsWhat is the safety, effectiveness and cost-effectiveness of MRI small bowel compared with:CT and SBFT for the evaluation of disease extent in patients initially diagnosed with Crohn’s disease with suspected small bowel involvement?CT and SBFT for the evaluation of patients with exacerbation/suspected complications of known Crohn’s disease?US in pregnant women with suspected small bowel Crohn’s disease?CT, SBFT or endoscopic assessment in the assessment of change to therapy in patients with small bowel Crohn’s disease?What are the safety and effectiveness and cost-effectiveness of MRI pelvis compared with:surgical assessment and endoanal ultrasound in patients with pelvic sepsis and fistulas associated with established or suspected Crohn’s disease?surgical assessment and endoanal ultrasound in assessment of change to therapy in patients with pelvis sepsis and fistulas from Crohn’s disease?Table 5 provides details of the PPICO criteria for assessment of diagnostic tests.Table 5: PPICO criteriaPatientsPrior testsInterventionComparatorOutcomes to be assessedPatients with initial diagnosis of Crohn’s disease with symptoms of small bowel involvement or patients with suspected Crohn’s disease and are pregnant.Clinical examination involving patient history, assessment of symptoms, blood tests. First line endoscopy, ileocolonoscopy and histopathology.MRI small bowel including MR enterography or MR enteroclysisCT enterography or CT enteroclysisSBFTEndoscopyUltrasound (in pregnancy)Diagnostic performanceSensitivitySpecificityAdditional TP and FPDiagnostic yieldTherapeutic impact% change in management plans (for example from medical to surgery)Patient outcomesImpact of treatment on symptomsActivity of diseaseDevelopment of complicationsCrohn’s disease progressionTreatment morbidityQuality of lifePatients with suspected or established fistulising perianal Crohn’s diseaseClinical examination involving patient history, assessment of symptoms, blood tests.MRI pelvisEndoanal ultrasoundSurgical examinationCT = computer tomography, MRI = magnetic resonance imaging, SBFT = small bowel follow through, TP = true positives, FP = false positives. Review of literature Literature sources and search strategiesThe medical literature was searched to identify relevant studies and reviews for the period up to November 2013. Searches were conducted via MEDLINE, The Cochrane Library (including Cochrane Reviews, NHS-EED, DARE and HTA), clinical registers and HTA sites (Table 6). Reference lists of the selected studies were manually searched.Table 6: Electronic databases searchedDatabasePeriod coveredMEDLINE via OVID MEDLINEUp to 11 November 2013The Cochrane LibraryNHS-EEDCochrane ReviewsDAREHTAUp to 15 November 2013Clinical RegistersCurrent Controlled Trials controlled- Australian New Zealand Clinical Trials Registry .auWHO International Clinical Trials Registry Platform websitesInternational Network of Agencies for Health Technology Assessment (INAHTA) NHS Centre for Reviews and Dissemination databases The search terms used included ‘Crohn’ ‘Crohn’s’ ‘enteritis’‘enterocolitis’ ‘small bowel’ ‘pelvic sepsis’ ‘fistula’‘magnetic resonance’ ‘MRI’ ‘MRE’ ‘fistulising’ and ‘perianal’. Search terms were confined to the title, abstract or keywords fields. Full details of the search strategies are provided in Appendix B.Title and abstracts were screened by two evaluators for potential relevance and omitted where appropriate. Of those remaining, full text articles were retrieved and examined in more depth. Table 7 provides full details of the a priori inclusion and exclusion criteria used for the studies included for this assessment.Table 7: Selection criteria for included studiesSelection criteria IncludedExcludedPublication typeComparative clinical studies and systematic reviews of comparative studies. Diagnostic accuracy studies and test agreement studiesNon-systematic reviews, letters, editorials, animal, in-vitro, laboratory studies, conference abstracts, pilot studies and technical reports excluded. Clinical studies or systematic reviews that have been superseded. Clinical studies that are within a systematic review selected for this review.Change in patient management studies excluded if reported outcomes are a subjective rating of physician’s perceived usefulness of the test without actual changes in management planPatients Studies with patients with known Crohn’s disease:including patients who are pregnantincluding patients with pelvic sepsis or perianal fistulaeStudies with patients with suspected Crohn’s disease AND are pregnant.Studies with patients with suspected perianal Crohn’s diseaseStudies that have selected patients with both known and suspected Crohn’s disease.Studies with <20 patients undergoing MR for the indication of interest (unless there are none).Studies that reported combined results for inflammatory bowel disease (they did not separate patients with ulcerative colitis and Crohn’s disease).Intervention/testMagnetic resonance MR+/– enterography or MR+/– enteroclysisStudies that did not have the primary purpose of comparing MRI with the nominated comparators for the six specified parators As per the nominated indications, comparators had to be either:Abdomen CT +/– enterographyCT Ultrasound (in pregnancy)Small bowel follow-through (SBFT) EndoscopyEndoanal ultrasound Surgical examinationStudies comparing MR enterography vs MR enteroclysis onlyStudies assessing inter-rater agreement only Studies with the following comparators:Capsule endoscopyConventional enteroclysisOutcomeStudies included if at least one of the following outcomes were reported:diagnostic accuracy: sensitivity and specificity (or data enabling calculation); diagnostic odds ratio or ROC curves; Q*, additional TP and FP, diagnosticyield impact of MRI results on clinical management: definitive treatment avoided, investigations avoided, definitive treatment instigated, overall change, type of change occurring in ≥10% patients)patient outcomes: Crohn’s disease progression, treatment morbidity, adverse events, quality of life prognostic value of MRI results (patient outcomes following specific therapy selected with MR versus without MR; patient outcomes in MR+ or MR– undergoing same treatment, no change of original treatment plan of patients was altered based on a MR result)LanguageEnglish language articlesNon-English language articles Search resultsQuorum FlowchartFigure 2: Summary of the process used to identify and select studies for the reviewData extraction and analysisData were extracted using a standardised instrument designed for this review. Items extracted included characteristics of the study, objective and design, study population, type of diagnostic test, reference standard, comparator, study quality and relevant endpoints. Data were extracted by one reviewer and checked by a second reviewer. Any discrepancies were resolved by discussion and by the involvement of a third reviewer if necessary. The data extraction tables are provided in Appendix D. Where possible, measures of diagnostic accuracy (sensitivity, specificity, positive predictive value, negative predictive value and likelihood ratios) and associated 95% CIs for each test were extracted. Measurement of test accuracyThe accuracy of a test is determined by its ability to identify the target condition compared with a reference standard test that is used as a proxy for true disease status. Subjects who test positive using the reference standard are classified as having the disease; those who test negative are classified as disease-free.Results of the index test and reference standard for a group of tested subjects were summarised in a two-by-two table where appropriate (see REF _Ref202174689 \h \* MERGEFORMAT Figure 3).Figure 3: Two-by-two table of data used to determine test accuracyAs shown, subjects who test positive for the disease of interest by both the index test and the reference standard were recorded as true-positive (TP). Subjects without the target condition who test negative by both tests were recorded as true-negative (TN). The index test result was recorded as a false-positive (FP) if it detected the target condition and the reference standard did not. A false-negative (FN) was recorded if the reference standard confirmed the target condition and the index test did not.Sensitivity and specificityThe sensitivity of a test is the probability of a positive test in subjects with the disease of interest. The specificity of a test is the probability of a negative result in subjects without the disease. The sensitivity and specificity of a test are always considered together and vary according to the threshold used to define a positive test. Sensitivity and specificity vary according to the spectrum of disease (eg variation in disease severity) in the patient group tested. High sensitivity is particularly important if the penalty for missing a disease is high. However, high specificity is particularly important if a false-positive result can harm the patient.CalculationSensitivity = TP/(TP + FN)Specificity = TN/(TN + FP)Positive and negative predictive valuesIn studies reporting the additional value of a test, only patients testing positive may receive follow-up with the reference standard. In this case the proportion of positive test results that were correct (positive predictive value (PPV)) was calculated. Where patients with discordant negative results also receive the reference standard, the proportion of negative test results that were correct (negative predictive value (NPV)) was calculated. PPV and NPV vary according to the prevalence of disease in the population.CalculationPositive predictive value = TP/(TP + FP)Negative predictive value = TN/(TN + FN)Likelihood ratio (LR)The LR measures the probability of the test result in patients with the disease compared with those without the disease.CalculationPositive LR (LR+): the odds that a positive test result would be found in a patient with, versus without, a disease.LR(+) = [TP / (TP + FN)] / [FP / (FP + TN)]Negative LR (LR–): the odds that a negative test result would be found in a patient with, versus without, a disease.LR(–) = [FN / (TP + FN)] / [TN / (FP + TN)]InterpretationAn LR of 1 indicates that the test does not provide any useful diagnostic information.Positive LRs >10 and negative LRs <0.1 can provide convincing evidence of diagnostic effectiveness.Positive LRs >5 and LRs <0.2 can provide strong evidence of diagnostic effectiveness.However, the interpretation depends on the context in which the test is used.Diagnostic yieldThe diagnostic yield measures the proportion of MRI tests in which an (apparent) positive result or diagnosis occurred. The number of positive results and negative results are not compared against a reference standard and hence the extent of false-positives and false-negatives is unknown. Calculation Diagnostic yield = Number of diagnoses/Number of tests performed.Appraisal of the evidenceAppraisal of the evidence was conducted at 3 stages:Stage 1: Appraisal of the applicability and quality of individual studies included in the review.Stage 2: Appraisal of the precision, size and clinical importance of the primary outcomes used to determine the safety and effectiveness of the intervention. Stage 3: Integration of this evidence for conclusions about the net clinical benefit of the intervention in the context of Australian clinical practice. Validity assessment of individual studiesThe evidence presented in the selected studies was assessed and classified using the dimensions of evidence defined by the National Health and Medical Research Council ADDIN EN.CITE <EndNote><Cite><Author>NHMRC</Author><Year>2000a</Year><RecNum>182</RecNum><DisplayText>(NHMRC, 2000a)</DisplayText><record><rec-number>182</rec-number><foreign-keys><key app="EN" db-id="5ww0vavvyz92p9ewfdqptwwwrrxxzfvdadas" timestamp="1386736450">182</key></foreign-keys><ref-type name="Government Document">46</ref-type><contributors><authors><author>NHMRC,</author></authors><secondary-authors><author>National Health and Medical Research Council</author></secondary-authors></contributors><titles><title>How to review the evidence: systematic identification and review of the scientific literature</title></titles><dates><year>2000a</year></dates><pub-location>Canberra</pub-location><publisher>Commonwealth of Australia</publisher><urls></urls></record></Cite></EndNote>(NHMRC, 2000a). These dimensions ( REF _Ref206478845 \h \* MERGEFORMAT Table 8) consider important aspects of the evidence supporting a particular intervention and include three main domains: strength of the evidence, size of the effect and relevance of the evidence. The first domain is derived directly from the literature identified as informing a particular intervention. The last two require expert clinical input as part of its determination.Table 8: Evidence dimensionsType of evidenceDefinitionStrength of the evidenceLevelQualityStatistical precisionThe study design used, as an indicator of the degree to which bias has been eliminated by design.The methods used by investigators to minimise bias within a study design.The p-value or, alternatively, the precision of the estimate of the effect. It reflects the degree of certainty about the existence of a true effect.Size of effectThe distance of the study estimate from the “null” value and the inclusion of only clinically important effects in the confidence interval.Relevance of evidenceThe usefulness of the evidence in clinical practice, particularly the appropriateness of the outcome measures used.Strength of the evidenceThe three sub-domains (level, quality and statistical precision) are collectively a measure of the strength of the evidence. LevelThe “level of evidence” reflects the effectiveness of a study design to answer a particular research question. Effectiveness is based on the probability that the design of the study has reduced or eliminated the impact of bias on the results. The NHMRC evidence hierarchy provides a ranking of various study designs (‘levels of evidence’) by the type of research question being addressed (see Table 9).Table 9: Designations of levels of evidence according to type of research question ADDIN EN.CITE <EndNote><Cite><Author>NHMRC</Author><Year>2008</Year><RecNum>132</RecNum><DisplayText>(NHMRC, 2008a)</DisplayText><record><rec-number>132</rec-number><ref-type name="Electronic Source">12</ref-type><contributors><authors><author>NHMRC</author></authors></contributors><titles><title>NHMRC additional levels of evidence and grades for recommendations for developers of guidelines. Stage 2 consultation.</title></titles><number>11/03/08</number><dates><year>2008</year></dates><publisher>National Health and Medical Research Council, Australian Government</publisher><work-type>Internet</work-type><urls><related-urls><url>.au/consult/index.htm</url></related-urls></urls></record></Cite></EndNote>(NHMRC, 2008a).LevelDiagnostic accuracy 2I 4A systematic review of level II studiesIIA study of test accuracy with: an independent, blinded comparison with a valid reference standard,5 among consecutive persons with a defined clinical presentation6III-1A study of test accuracy with: an independent, blinded comparison with a valid reference standard,5 among non-consecutive persons with a defined clinical presentation6III-2A comparison with reference standard that does not meet the criteria required for Level II and III-1 evidenceIII-3Diagnostic case-control study6IVStudy of diagnostic yield (no reference standard)11Table notes can be found in NHMRC (2008: 2009) ADDIN EN.CITE <EndNote><Cite><Author>NHMRC</Author><Year>2008</Year><RecNum>183</RecNum><DisplayText>(NHMRC, 2008b)</DisplayText><record><rec-number>183</rec-number><foreign-keys><key app="EN" db-id="5ww0vavvyz92p9ewfdqptwwwrrxxzfvdadas" timestamp="1386736513">183</key></foreign-keys><ref-type name="Government Document">46</ref-type><contributors><authors><author>NHMRC,</author></authors><secondary-authors><author>National Health and Medical Research Council</author></secondary-authors></contributors><titles><title>NHMRC additional levels of evidence and grades for recommendations for developers of guidelines: stage 2 consultation</title></titles><dates><year>2008</year></dates><pub-location>Canberra</pub-location><publisher>Commonwealth of Australia</publisher><urls></urls></record></Cite></EndNote>(NHMRC, 2008b)Individual studies assessing diagnostic effectiveness were graded according to pre-specified quality and applicability criteria ADDIN EN.CITE <EndNote><Cite><Author>MSAC</Author><Year>2005</Year><RecNum>181</RecNum><DisplayText>(MSAC, 2005)</DisplayText><record><rec-number>181</rec-number><foreign-keys><key app="EN" db-id="5ww0vavvyz92p9ewfdqptwwwrrxxzfvdadas" timestamp="1386736398">181</key></foreign-keys><ref-type name="Government Document">46</ref-type><contributors><authors><author>MSAC,</author></authors><secondary-authors><author>Department of Health</author></secondary-authors></contributors><titles><title>Guidelines for the assessment of diagnostic technologies.</title></titles><dates><year>2005</year></dates><pub-location>Canberra</pub-location><publisher>Commonwealth of Australia</publisher><urls></urls></record></Cite></EndNote>(MSAC, 2005), as shown in REF _Ref206477516 \h \* MERGEFORMAT Table 10.Table 10: Grading system used to rank included studiesValidity criteriaDescriptionGrading SystemAppropriate comparisonDid the study evaluate a direct comparison of the index test strategy versus the comparator test strategy?C1 direct comparison CX other comparisonApplicable populationDid the study evaluate the index test in a population that is representative of the subject characteristics (age and sex) and clinical setting (disease prevalence, disease severity, referral filter and sequence of tests) for the clinical indication of interest?P1 applicableP2 limited P3 different populationQuality of studyWas the study designed to avoid bias?High quality = no potential for bias based on pre-defined key quality criteria Medium quality = some potential for bias in areas other than those pre-specified as key criteriaPoor quality = poor reference standard and/or potential for bias based on key pre-specified criteriaQ1 high quality Q2 medium Q3 poor reference standardpoor qualityor insufficient informationQualityA structured appraisal was performed to assess the quality of all included studies. The quality of studies of diagnostic accuracy was assessed against a checklist of 11 items adapted from the QUADAS (Quality Assessment of Studies of Diagnostic Accuracy Included in Meta-Analyses) tool ADDIN EN.CITE <EndNote><Cite><Author>Whiting</Author><Year>2003</Year><RecNum>178</RecNum><DisplayText>(Whiting et al., 2003)</DisplayText><record><rec-number>178</rec-number><foreign-keys><key app="EN" db-id="5ww0vavvyz92p9ewfdqptwwwrrxxzfvdadas" timestamp="1386656053">178</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Whiting, P.</author><author>Rutjes, A. W.</author><author>Reitsma, J. B.</author><author>Bossuyt, P. M.</author><author>Kleijnen, J.</author></authors></contributors><auth-address>Centre for Reviews and Dissemination, University of York, England, UK. pfw2@york.ac.uk</auth-address><titles><title>The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews</title><secondary-title>BMC Med Res Methodol</secondary-title><alt-title>BMC medical research methodology</alt-title></titles><periodical><full-title>BMC Med Res Methodol</full-title><abbr-1>BMC medical research methodology</abbr-1></periodical><alt-periodical><full-title>BMC Med Res Methodol</full-title><abbr-1>BMC medical research methodology</abbr-1></alt-periodical><pages>25</pages><volume>3</volume><edition>2003/11/11</edition><keywords><keyword>Bias (Epidemiology)</keyword><keyword>*Diagnosis</keyword><keyword>Evidence-Based Medicine</keyword><keyword>Humans</keyword><keyword>Quality Control</keyword><keyword>*Questionnaires</keyword><keyword>Reference Standards</keyword><keyword>Reproducibility of Results</keyword><keyword>*Review Literature as Topic</keyword></keywords><dates><year>2003</year><pub-dates><date>Nov 10</date></pub-dates></dates><isbn>1471-2288</isbn><accession-num>14606960</accession-num><urls></urls><custom2>Pmc305345</custom2><electronic-resource-num>10.1186/1471-2288-3-25</electronic-resource-num><remote-database-provider>Nlm</remote-database-provider><language>eng</language></record></Cite></EndNote>(Whiting et al., 2003)(see REF _Ref161566552 \h \* MERGEFORMAT Table 11). This tool was developed by experts in the field following a systematic review of the evidence relating to sources of bias and variation relevant to studies of diagnostic test accuracy. Studies were required to meet all 11 criteria to be assessed as high quality (see details in footnote to REF _Ref161566552 \h \* MERGEFORMAT Table 11). Only prospective diagnostic test accuracy studies were assessed as high quality. Studies that did not use a valid reference standard in all patients were classified as low quality. Table 11: Criteria used to assess the quality of diagnostic accuracy studies – the QUADAS tool (Adapted from Whiting et al 2003).ItemCriteria1Were patients prospectively recruited? 2Were patients consecutively recruited (ie a consecutive group of patients presenting with a defined clinical presentation)? 3Were selection criteria explicitly described (ie in enough detail to clearly define eligibility of patients and to be reproducible)?4Is the reference standard likely to correctly classify the target condition (valid/invalid/optimal)?5Did all patients receive verification using a reference standard? 6Is the time period between reference standard, comparator and index test short enough to be reasonably sure that the target condition did not change between the tests?7Were MR/comparator results interpreted blind to reference standard?8Were reference standard results interpreted blind to MR/comparator results?9Were the same clinical data, including conventional imaging, available when test results were interpreted as would be available when the test is used in practice?10Were uninterpretable/intermediate test results reported?11Were withdrawals from the study explained?MR = magnetic resonanceHigh quality: Yes to 1, 3, 4, 5, 9, 10; other items required to be either Yes or Unclear.Poor quality: No/Unclear for 4, 5 or 6.Other studies are assessed as fair quality.Seven criteria were used to assess the quality of systematic reviews, as outlined in REF _Ref278534842 \h \* MERGEFORMAT Table 12. For the criterion addressing heterogeneity, systematic reviews that did not undertake a meta-analysis were rated ‘not applicable’ (N/A), unless heterogeneity was specifically mentioned. Studies were required to meet all seven criteria to be assessed as high quality. A study with four or fewer ‘Yes’ or ‘N/A’ ratings was considered to be of low quality. Seven criteria were used to assess the quality of case series, as outlined in REF _Ref278534842 \h \* MERGEFORMAT Table 12.Table 12: Criteria used to assess the quality of systematic review studies (adapted from ADDIN EN.CITE <EndNote><Cite><Author>NHMRC</Author><Year>2000a</Year><RecNum>182</RecNum><DisplayText>(NHMRC, 2000a)</DisplayText><record><rec-number>182</rec-number><foreign-keys><key app="EN" db-id="5ww0vavvyz92p9ewfdqptwwwrrxxzfvdadas" timestamp="1386736450">182</key></foreign-keys><ref-type name="Government Document">46</ref-type><contributors><authors><author>NHMRC,</author></authors><secondary-authors><author>National Health and Medical Research Council</author></secondary-authors></contributors><titles><title>How to review the evidence: systematic identification and review of the scientific literature</title></titles><dates><year>2000a</year></dates><pub-location>Canberra</pub-location><publisher>Commonwealth of Australia</publisher><urls></urls></record></Cite></EndNote>(NHMRC, 2000a) and ADDIN EN.CITE <EndNote><Cite><Author>CRD</Author><Year>2009</Year><RecNum>186</RecNum><DisplayText>(CRD, 2009)</DisplayText><record><rec-number>186</rec-number><foreign-keys><key app="EN" db-id="5ww0vavvyz92p9ewfdqptwwwrrxxzfvdadas" timestamp="1386736992">186</key></foreign-keys><ref-type name="Report">27</ref-type><contributors><authors><author>CRD, </author></authors><secondary-authors><author>(Centre for Reviews and Dissemination)</author></secondary-authors></contributors><titles><title>Systematic reviews: CRD's guidance for undertaking reviews in health care</title></titles><dates><year>2009</year></dates><pub-location>York UK</pub-location><publisher>University of York</publisher><urls><related-urls><url> </url></related-urls></urls></record></Cite></EndNote>(CRD, 2009))Study designQuality checklist Systematic reviewWas the research question specified?Was the search strategy explicit and comprehensive?Were the eligibility criteria explicit and appropriate?Was a quality assessment of included studies undertaken?Were the methods of the study appraisal reproducible?Were sources of heterogeneity explored?Was a summary of the main results clear and appropriate?Statistical precisionStatistical precision was determined using statistical principles. Small confidence intervals and p-values give an indication as to the probability that the reported effect is real and not attributable to chance ADDIN EN.CITE <EndNote><Cite><Author>NHMRC</Author><Year>2000</Year><RecNum>25</RecNum><DisplayText>(NHMRC, 2000)</DisplayText><record><rec-number>25</rec-number><ref-type name="Report">27</ref-type><contributors><authors><author>NHMRC,</author></authors></contributors><titles><title>How to use the evidence: assessment and application of scientific evidence</title></titles><pages>84</pages><keywords><keyword>Practice guidelines</keyword><keyword>Review literature</keyword><keyword>Australia</keyword><keyword>Evidence-Based Medicine</keyword></keywords><dates><year>2000</year><pub-dates><date>February 2000</date></pub-dates></dates><pub-location>Canberra</pub-location><publisher>National Health and Medical Research Council</publisher><call-num>SHELF 7</call-num><label>evidence ; treatment path ; clinical decisions ; guidelines; methodology; health technology;</label><work-type>Handbook series on preparing clinical practice guidelines</work-type><urls></urls></record></Cite></EndNote>(NHMRC, 2000). Studies need to be appropriate to ensure that a real difference between groups will be detected in the statistical analysis.Size of effectThe size of the effect needed to be determined, as well as whether the 95% confidence interval included only clinically important effects. Relevance of evidenceThe outcomes being measured in this report should be appropriate and clinically relevant. Inadequately validated (predictive) surrogate measures of a clinically relevant outcome should be avoided ADDIN EN.CITE <EndNote><Cite><Author>NHMRC</Author><Year>2000</Year><RecNum>25</RecNum><DisplayText>(NHMRC, 2000)</DisplayText><record><rec-number>25</rec-number><ref-type name="Report">27</ref-type><contributors><authors><author>NHMRC,</author></authors></contributors><titles><title>How to use the evidence: assessment and application of scientific evidence</title></titles><pages>84</pages><keywords><keyword>Practice guidelines</keyword><keyword>Review literature</keyword><keyword>Australia</keyword><keyword>Evidence-Based Medicine</keyword></keywords><dates><year>2000</year><pub-dates><date>February 2000</date></pub-dates></dates><pub-location>Canberra</pub-location><publisher>National Health and Medical Research Council</publisher><call-num>SHELF 7</call-num><label>evidence ; treatment path ; clinical decisions ; guidelines; methodology; health technology;</label><work-type>Handbook series on preparing clinical practice guidelines</work-type><urls></urls></record></Cite></EndNote>(NHMRC, 2000). Assessment of the body of evidenceAppraisal of the body of evidence was conducted along the lines suggested by the NHMRC in their guidance on clinical practice guideline development ADDIN EN.CITE <EndNote><Cite><Author>NHMRC</Author><Year>2008</Year><RecNum>132</RecNum><DisplayText>(NHMRC, 2008a)</DisplayText><record><rec-number>132</rec-number><ref-type name="Electronic Source">12</ref-type><contributors><authors><author>NHMRC</author></authors></contributors><titles><title>NHMRC additional levels of evidence and grades for recommendations for developers of guidelines. Stage 2 consultation.</title></titles><number>11/03/08</number><dates><year>2008</year></dates><publisher>National Health and Medical Research Council, Australian Government</publisher><work-type>Internet</work-type><urls><related-urls><url>.au/consult/index.htm</url></related-urls></urls></record></Cite></EndNote>(NHMRC, 2008a). Five components are considered essential by the NHMRC when judging the body of evidence: The evidence base – which includes the number of studies sorted by their methodological quality and relevance to patients;The consistency of the study results – whether the better quality studies had results of a similar magnitude and in the same direction ie homogenous or heterogenous findings;The potential clinical impact - appraisal of the precision, size and clinical importance or relevance of the primary outcomes used to determine the safety and effectiveness of the test;The generalisability of the evidence to the target population; andThe applicability of the evidence - integration of this evidence for conclusions about the net clinical benefit of the intervention in the context of Australian clinical practice.A matrix for assessing the body of evidence for each research question, according to the components above, was used for this assessment (see Table 13). ADDIN EN.CITE <EndNote><Cite><Author>NHMRC</Author><Year>2008</Year><RecNum>132</RecNum><DisplayText>(NHMRC, 2008a)</DisplayText><record><rec-number>132</rec-number><ref-type name="Electronic Source">12</ref-type><contributors><authors><author>NHMRC</author></authors></contributors><titles><title>NHMRC additional levels of evidence and grades for recommendations for developers of guidelines. Stage 2 consultation.</title></titles><number>11/03/08</number><dates><year>2008</year></dates><publisher>National Health and Medical Research Council, Australian Government</publisher><work-type>Internet</work-type><urls><related-urls><url>.au/consult/index.htm</url></related-urls></urls></record></Cite></EndNote>(NHMRC, 2008a).Table 13: Body of evidence assessment matrixComponentABCDExcellentGoodSatisfactoryPoorEvidence base1One or more level I studies with a low risk of bias or several level II studies with a low risk of biasOne or two level II studies with a low risk of bias or a SR/several level III studies with a low risk of bias One or two level III studies with a low risk of bias, or level I or II studies with a moderate risk of biasLevel IV studies, or level I to III studies/SRs with a high risk of biasConsistency2All studies consistentMost studies consistent and inconsistency may be explainedSome inconsistency reflecting genuine uncertainty around clinical questionEvidence is inconsistentClinical impactVery largeSubstantial ModerateSlight or restrictedGeneralisabilityPopulation/s studied in body of evidence are the same as the target population for the guidelinePopulation/s studied in the body of evidence are similar to the target population for the guidelinePopulation/s studied in body of evidence differ to target population for guideline but it is clinically sensible to apply this evidence to target population3 Population/s studied in body of evidence differ to target population and hard to judge whether it is sensible to generalise to target populationApplicabilityDirectly applicable to Australian healthcare contextApplicable to Australian healthcare context with few caveats Probably applicable to Australian healthcare context with some caveatsNot applicable to Australian healthcare contextSR = systematic review; several = more than two studiesLevel of evidence determined from the NHMRC evidence hierarchy – Table 6If there is only one study, rank this component as ‘not applicable’.3 For example, results in adults that are clinically sensible to apply to children OR psychosocial outcomes for one cancer that may be applicable to patients with another cancer.Source: ADDIN EN.CITE <EndNote><Cite><Author>NHMRC</Author><Year>2009</Year><RecNum>185</RecNum><DisplayText>(NHMRC, 2009)</DisplayText><record><rec-number>185</rec-number><foreign-keys><key app="EN" db-id="5ww0vavvyz92p9ewfdqptwwwrrxxzfvdadas" timestamp="1386736648">185</key></foreign-keys><ref-type name="Government Document">46</ref-type><contributors><authors><author>NHMRC,</author></authors><secondary-authors><author>National Health and Medical Research Council</author></secondary-authors></contributors><titles><title>NHMRC additional levels of evidence and grades for recommendations for developers of guidelines</title></titles><dates><year>2009</year></dates><pub-location>Canberra</pub-location><publisher>Commonwealth of Australia</publisher><urls></urls></record></Cite></EndNote>(NHMRC, 2009)Expert advice An advisory panel was established to provide guidance to the health technology assessors to ensure that the assessment is clinically relevant and takes into account consumer interests. Membership of the advisory panel is provided at Appendix B.Results of assessment Relevant studies for assessmentThe outcome of the systematic review yielded a total of 12 studies that were relevant for this assessment. A summary of these studies in provided in Table 14.Table 14: Relevant studies included in the assessmentReviewed for assessment of:StudyStudy designChange of managementEfficacy(accuracy)Efficacy(yield)Economic EvaluationWu et al. 2013Systematic review (17 studies) Cheriyan et al. 2013Retrospective, n=57Siddqui et al. 2012Systematic review, (4 studies) Cipriano et al. 2012Economic study, Markov modelSanka et al. 2012Retrospective, n=34Malgras et al. 2012Retrospective, n=52Panes et al. 2011Systematic review (68 studies)Jensen et al. 2011Prospective, n=50Ippolito et al. 2010Prospective, consecutive, n=29Schmidt et al. 2010Prospective, consecutive, n=57Schreyer et al. 2010Retrospective, consecutive, n=53Schwartz et al. 2001Prospective, n=34Is it safe? No studies were identified that looked at the comparative safety of MRI for small bowel or pelvis with that of CT, SBFT or any other comparator. The safety impact of MRI in pregnancy is unknown.There appears to be few clinical issues around patient safety with performing MRI. On its own, the test is non-invasive, does not emit ionizing-radiation and presents no chemical or bodily harm to the patient. The patient is required to lie very still on a table that is slid into a cylinder where the imaging is performed. A loud knocking sound is produced by the machine but this is not damaging to hearing and ear plugs or earphones may be used. In preparation for the MRI, the bowel must be distended with contrast enteric material, taken either orally or through a nasojejunal tube. This can be a source of discomfort to patients and their cooperation to keep immobile is needed by the radiologist to obtain a clear image. In addition, some patients can have allergic reactions to the dye although these patients have been excluded from clinical studies on MRI. Due to being enclosed in a space for the duration of the test (approximately 30 minutes) an MRI may not be appropriate for patients experiencing claustrophobia or anxiety disorders (such as panic attacks). These patients were excluded from many of the clinical studies in this assessment. Other contraindications for MRI relate to patients with internal metal devices or other electrically, magnetically or mechanically activated devices because they may dislodge or malfunction.In summary, for safety reasons individuals should not have an MRI if they have a:Brain aneurysm or haemostatic clip Cardiac pacemaker or cardiac defibrillator Cochlear implant Insulin pump Metal splinter in the eye Condition of claustrophobia or panic attackIonizing radiation of CT and SBFTThe main argument of choosing MRI over the other imaging modalities within this assessment is the advantage in not exposing patients, particularly children, to ionizing radiation. This is seen among radiologists as an important benefit in Crohn’s disease, a chronic, non-curable condition that involves inflammatory relapses and therefore requires repeated testing and surveillance during the course of the patient’s life. Small doses of ionizing radiation received frequently over time can lead to increased risk of cancer. Ultrasound and MRI do not emit ionizing radiation.The effective radiation dose is a product of the radiation dose and the biological sensitivity of tissue, measured in millisieverts (mSv). Abdominal structures are more biologically active and imaging results in higher effective doses than other body parts. Susceptibility to higher effective doses is also found in younger age groups. High cumulative dose is considered >50 mSv over a 5-year period ADDIN EN.CITE <EndNote><Cite><Author>Kroeker</Author><Year>2011</Year><RecNum>167</RecNum><DisplayText>(Kroeker et al., 2011)</DisplayText><record><rec-number>167</rec-number><foreign-keys><key app="EN" db-id="5ww0vavvyz92p9ewfdqptwwwrrxxzfvdadas" timestamp="1386650713">167</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kroeker, K. I.</author><author>Lam, S.</author><author>Birchall, I.</author><author>Fedorak, R. N.</author></authors></contributors><auth-address>Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.</auth-address><titles><title>Patients with IBD are exposed to high levels of ionizing radiation through CT scan diagnostic imaging: a five-year study</title><secondary-title>J Clin Gastroenterol</secondary-title><alt-title>Journal of clinical gastroenterology</alt-title></titles><periodical><full-title>J Clin Gastroenterol</full-title><abbr-1>Journal of clinical gastroenterology</abbr-1></periodical><alt-periodical><full-title>J Clin Gastroenterol</full-title><abbr-1>Journal of clinical gastroenterology</abbr-1></alt-periodical><pages>34-9</pages><volume>45</volume><number>1</number><edition>2010/08/04</edition><keywords><keyword>Adult</keyword><keyword>Colitis, Ulcerative/*radiography</keyword><keyword>Crohn Disease/*radiography</keyword><keyword>Female</keyword><keyword>Follow-Up Studies</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>*Radiation Dosage</keyword><keyword>Radiation, Ionizing</keyword><keyword>Retrospective Studies</keyword><keyword>Tomography, X-Ray Computed/methods</keyword><keyword>Young Adult</keyword></keywords><dates><year>2011</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>0192-0790</isbn><accession-num>20679907</accession-num><urls></urls><electronic-resource-num>10.1097/MCG.0b013e3181e5d1c5</electronic-resource-num><remote-database-provider>Nlm</remote-database-provider><language>eng</language></record></Cite></EndNote>(Kroeker et al., 2011) and cumulative effective dose of >75 mSv is associated with an increased cancer risk of 7.3%. A small proportion of patients with Crohn’s disease have been reported to have exceeded these benchmarks (7-15%) PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5EZXNtb25kPC9BdXRob3I+PFllYXI+MjAwODwvWWVhcj48
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ADDIN EN.CITE.DATA (Desmond et al., 2008, Kroeker et al., 2011).The ARPANSA state that total radiation exposure should take into account background radiation exposure received from natural sources ADDIN EN.CITE <EndNote><Cite><Author>ARPANSA</Author><Year>2011</Year><RecNum>170</RecNum><DisplayText>(ARPANSA, 2011)</DisplayText><record><rec-number>170</rec-number><foreign-keys><key app="EN" db-id="5ww0vavvyz92p9ewfdqptwwwrrxxzfvdadas" timestamp="1386652349">170</key></foreign-keys><ref-type name="Government Document">46</ref-type><contributors><authors><author>ARPANSA</author></authors><secondary-authors><author>Australian Radiation Protection and Nuclear Safety Agency</author></secondary-authors></contributors><titles><title>Ionising Radiation and Health Fact Sheet 17</title></titles><pages>3</pages><dates><year>2011</year></dates><pub-location>Melbourne</pub-location><publisher>Australian Government</publisher><urls></urls></record></Cite></EndNote>(ARPANSA, 2011). In Australia, this is reported to be 1.5mSv per year. The risk of cancer of 1 mSv of radiation is 1 in 17,000 (against the age-standardised incidence rate of 57 in 17,000) or the equivalent risk of getting cancer from smoking 100 cigarettes ADDIN EN.CITE <EndNote><Cite><Author>ARPANSA</Author><Year>2011</Year><RecNum>170</RecNum><DisplayText>(ARPANSA, 2011)</DisplayText><record><rec-number>170</rec-number><foreign-keys><key app="EN" db-id="5ww0vavvyz92p9ewfdqptwwwrrxxzfvdadas" timestamp="1386652349">170</key></foreign-keys><ref-type name="Government Document">46</ref-type><contributors><authors><author>ARPANSA</author></authors><secondary-authors><author>Australian Radiation Protection and Nuclear Safety Agency</author></secondary-authors></contributors><titles><title>Ionising Radiation and Health Fact Sheet 17</title></titles><pages>3</pages><dates><year>2011</year></dates><pub-location>Melbourne</pub-location><publisher>Australian Government</publisher><urls></urls></record></Cite></EndNote>(ARPANSA, 2011). The relative exposures of ionizing radiation by imaging modality are: abdominal x-ray 0.7 mSv; SBFT 5.0 mSv and abdominal/pelvic CT 10 mSv. However, the effective radiation dose for each person is highly variable due to different machine settings, the amount of radioactive material used and patient metabolism. Table 15 shows the findings of several studies that have followed patients with Crohn’s disease over time and measured their radiation doses. These studies were not identified within a systematic review and therefore are not an exhaustive list of studies on this topic PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5EZXNtb25kPC9BdXRob3I+PFllYXI+MjAwODwvWWVhcj48
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ADDIN EN.CITE.DATA (Desmond et al., 2008, Kroeker et al., 2011, Peloquin et al., 2008, Sauer, 2012).Factors found to be associated with higher radiation exposure were children (<17 years) (hazards ratio 2.1, 95%CI: 1.1 – 4.1) and those who had multiple surgeries (hazards ratio 2.7, 95%CI: 1.4 – 5.4), among others PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5EZXNtb25kPC9BdXRob3I+PFllYXI+MjAwODwvWWVhcj48
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ADDIN EN.CITE.DATA (Desmond et al., 2008).Table 15: Annual radiation dose among patients with Crohn’s disease receiving imaging testsStudyAnnual effective radiation dose (mSv)nFollow up time% from CT enterographySauer et al. 20123.0 to 5.0 (3 studies)3183.5 to 5.2 years-Kroeker et al. 20112.83925 years75%Peloquin et al. 20083.1103Mean 8.9 years51%Desmond et al. 20085.3409Mean 6.7 years77.2% Risk of cancer in Crohn’s diseaseThe risk of intestinal cancer in Crohn’s disease has been studied by Jess et al. (2005) in a meta-analysis of population-based studies. Six papers were included in the pooled analyses and the standardized incidence ratio for colorectal cancer was significantly increased in patients with Crohn’s disease (1.9 (95%CI: 1.4-2.5). The authors’ called for caution when interpreting this finding because the six studies included in the review were old and did not reflect current treatments or practises PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5KZXNzPC9BdXRob3I+PFllYXI+MjAwNTwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA (Jess et al., 2005). There has since been a shift towards ‘low-dose’ CT techniques.The risk of extra-intestinal cancer in inflammatory bowel disease was also been reported in a meta-analysis by Pedersen et al. (2010). Six population-based studies reporting on Crohn’s disease were identified and involved mainly European cohorts. Overall, patients with Crohn’s disease had a slightly elevated risk of extra-intestinal cancer but it was not significant; standardized incidence ratio 1.13 (95%CI: 0.89-1.40). However, patients with Crohn’s disease were found to have significantly increased risks for specific site cancers: upper gastrointestinal cancer, lung, urinary bladder, and squamous cell cancer, compared with the background population PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5QZWRlcnNlbjwvQXV0aG9yPjxZZWFyPjIwMTA8L1llYXI+
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ADDIN EN.CITE.DATA (Pedersen et al., 2010). In these two meta-analyses, the authors discussed the possible causal factors for the increased risks. Explanations provided included the nature of the disease (inflammatory), the immunosuppressive agents given to patients and the extent of cigarette smoking. They did not mention the increase risk of imaging tests as a potential source of cancer risk PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5KZXNzPC9BdXRob3I+PFllYXI+MjAwNTwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA (Jess et al., 2005, Pedersen et al., 2010). Is it effective? With the exception of the economic evaluation study identified in the review, 11 studies were included in the effectiveness assessment. Effectiveness data were reported for eight primary clinical studies and three systematic reviews. Relevant data has been extracted from these studies and are provided in tables in Appendix D.Existing systematic reviews and HTA reportsThe review yielded three relevant systematic reviews and no HTA reports. Table 16 provides the characteristics and quality assessment summaries for the three systematic reviews PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5QYW5lczwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+PFJl
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ADDIN EN.CITE.DATA (Panes et al., 2011, Siddiqui et al., 2012, Wu et al., 2013).Technically, Wu et al. 2013 did not meet the inclusion criteria of this assessment because it does not include studies that involve within-study direct comparisons for different imaging modalities. Rather it includes diagnostic accuracy studies of MRI compared with a common reference standard (but no other imaging comparisons). However, Wu et al. 2013 is a high quality, recent systematic review that provides clear evidence of diagnostic performance of MRI in pooled meta-analyses of 17 studies. It also presents results of a meta-regression to assess what factors influence diagnostic performance. For these reasons, the study by Wu et al. 2013 was retained for assessment. As reported by Wu et al. (2013), the pooled sensitivity of MRI was 87% (95%CI: 77%-93%) indicating a high ability for MRI to detect disease when it actually exists. Similarly, specificity was also high 91% (81%-96%) indicating MRI can accurately rule out Crohn’s disease when it does not exist. The overall area under the receiver operator curve was 95% (95%CI: 93% -97%) ADDIN EN.CITE <EndNote><Cite><Author>Wu</Author><Year>2013</Year><RecNum>3</RecNum><DisplayText>(Wu et al., 2013)</DisplayText><record><rec-number>3</rec-number><foreign-keys><key app="EN" db-id="5ww0vavvyz92p9ewfdqptwwwrrxxzfvdadas" timestamp="0">3</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Wu, Lian-Ming</author><author>Xu, Jian-Rong</author><author>Gu, Hai-Yan</author><author>Hua, Jia</author><author>Hu, Jiani</author></authors></contributors><titles><title>Is Magnetic Resonance Imaging a Reliable Diagnostic Tool in the Evaluation of Active Crohn’s Disease in the Small Bowel?</title><secondary-title>Journal of Clinical Gastroenterology</secondary-title></titles><periodical><full-title>J Clin Gastroenterol</full-title><abbr-1>Journal of clinical gastroenterology</abbr-1></periodical><pages>328-338 10.1097/MCG.0b013e31825d5034</pages><volume>47</volume><number>4</number><keywords><keyword>Crohn's disease</keyword><keyword>magnetic resonance imaging</keyword><keyword>small bowel</keyword><keyword>meta-analysis</keyword><keyword>00004836-201304000-00010</keyword></keywords><dates><year>2013</year></dates><isbn>0192-0790</isbn><urls><related-urls><url>;(Wu et al., 2013). The review provided strong evidence of between-study heterogeneity. The most important factors associated with test accuracy were magnet strength and experience of the radiologist (in years). The applicability to the Australian population is unclear because the details of the sample profiles were minimal. The key strengths of the study include: study selection based on quality reporting, common referent test (ileocolonoscopy and histopathology) and publications were relatively recent (post 2000) and indication there was no publication bias. The main weaknesses of the evidence included whether the interpretation of pathology was blinded to the MRI introducing possible bias and overestimation of MRI accuracy.In Siddiqui et al. (2012), this review specifically targeted studies assessing Crohn’s perianal fistulas and compared diagnostic accuracy of MRI with endoanal ultrasound. The four studies included in the review must have compared these imaging techniques as their primary objective. The quality of the review was high and QUADAS assessment of each study was transparently reported. Meta-analysis showed that for identifying fistulas, the pooled sensitivity of MRI was 87% (95%CI: 63%-96%) and specificity 69% (95%CI: 51%-82%). For endoanal ultrasound, pooled sensitivity was identical to MRI at 87% (95%CI: 70%-95%) but lower for specificity 43% (95%CI: 21%-69%). Studies were found to be highly heterogeneous. The main weaknesses of the evidence were whether blinding occurred at the time of endoanal ultrasound and the different use of a referent (although most used surgical examination under anaesthesia) ADDIN EN.CITE <EndNote><Cite><Author>Siddiqui</Author><Year>2012</Year><RecNum>25</RecNum><DisplayText>(Siddiqui et al., 2012)</DisplayText><record><rec-number>25</rec-number><foreign-keys><key app="EN" db-id="5ww0vavvyz92p9ewfdqptwwwrrxxzfvdadas" timestamp="0">25</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Siddiqui, M. R.</author><author>Ashrafian, H.</author><author>Tozer, P.</author><author>Daulatzai, N.</author><author>Burling, D.</author><author>Hart, A.</author><author>Athanasiou, T.</author><author>Phillips, R. K.</author></authors></contributors><auth-address>St. Mark's Institute, Harrow, United Kingdom. md0u812a@</auth-address><titles><title>A diagnostic accuracy meta-analysis of endoanal ultrasound and MRI for perianal fistula assessment</title><secondary-title>Dis Colon Rectum</secondary-title><alt-title>Diseases of the colon and rectum</alt-title></titles><periodical><full-title>Dis Colon Rectum</full-title><abbr-1>Diseases of the colon and rectum</abbr-1></periodical><alt-periodical><full-title>Dis Colon Rectum</full-title><abbr-1>Diseases of the colon and rectum</abbr-1></alt-periodical><pages>576-85</pages><volume>55</volume><number>5</number><edition>2012/04/20</edition><keywords><keyword>Anal Canal/pathology/ultrasonography</keyword><keyword>Crohn Disease/complications/diagnosis</keyword><keyword>Diagnosis, Differential</keyword><keyword>Endosonography/*standards</keyword><keyword>Humans</keyword><keyword>Magnetic Resonance Imaging, Interventional/*standards</keyword><keyword>Rectal Fistula/*diagnosis/etiology</keyword><keyword>Reproducibility of Results</keyword><keyword>Sensitivity and Specificity</keyword></keywords><dates><year>2012</year><pub-dates><date>May</date></pub-dates></dates><isbn>0012-3706</isbn><accession-num>22513437</accession-num><urls></urls><electronic-resource-num>10.1097/DCR.0b013e318249d26c</electronic-resource-num><remote-database-provider>Nlm</remote-database-provider><language>eng</language></record></Cite></EndNote>(Siddiqui et al., 2012).Table 16: Characteristics and appraisal of included systematic reviewsAuthor (year) Objective and methodsIncluded studiesQuality assessment of reviewWu et al (2010)Objective: To evaluate the overall diagnostic accuracy of MRI in assessing the activity of Crohn’s disease in the small bowel Method: Meta-analysis and meta-regressionTime period: until Sept 2011Inclusion criteria: studies with patients if MRI was assessed to assess active CD, studies meeting 9/14 QUADAS criteria for quality, studies applied histopathologic and ileocolonoscopy assessment as the referent standard Outcomes: Sensitivity, specificity, area under receiver operator curveSuspected and established Crohn’s disease:17 retrospective and prospective studies.Studies did not provide direct comparisons (in same sample) of the different modalities, comparison with referent standard only.Test: MRComparator: NoneReferent: Ileocolonoscopy and histopathologic assessment.Quality: HIGHWas the research question specified? YesWas the search strategy explicit and comprehensive? YesWere the eligibility criteria explicit and appropriate? YesWas a quality assessment of included studies undertaken? YesWere the methods of the study appraisal reproducible? YesWere sources of heterogeneity explored? YesWas a summary of the main results clear and appropriate? YesSiddqui et al. (2012)Objective: To undertake a systematic review to compare endoanal ultrasound with MRI for perianal fistulas in Crohn’s disease.Method: Meta-analysisTime period:Jan1970-Oct 2010 Inclusion criteria: Studies that compared MR with endoanal ultrasound for patients with suspected perianal fistulas. Exclusion criteria: if the surgical standard was not applied.Outcomes: Sensitivity, specificity,Established Crohn’s disease4 studiesTest: MRComparator: Endoanal ultrasoundReferent: Examination under anaestheticQuality: HIGHWas the research question specified? YesWas the search strategy explicit and comprehensive? YesWere the eligibility criteria explicit and appropriate? YesWas a quality assessment of included studies undertaken? Yes (QUADAS used and reported)Were the methods of the study appraisal reproducible? YesWere sources of heterogeneity explored? YesWas a summary of the main results clear and appropriate? YesPanes et al. 2011Objective: To undertake a systematic review to compare ultrasound, CT and MRI for diagnosis, assessment of activity and complications of Crohn’s disease.Methods: No meta-analysisTime period: Jan 1994 to Dec 2010Inclusion criteria: Studies that compared MR ± ultrasound ± CT, had an adequate reference standard, prospective design, data allowed for calculation of sensitivity / specificity / yieldOutcomes: Sensitivity, specificitySuspected and established Crohn’s disease68 studiesTest: MR, CT, ultrasoundComparator: Not clear (Few studies included direct comparisons of imaging tests, most were single test with a referent) Referent: Either ileocolonoscopy, capsule endoscopy, enteroscopy, surgery, pathology.No additional formal quality assessment was performed.Quality: LOWWas the research question specified? YesWas the search strategy explicit and comprehensive? YesWere the eligibility criteria explicit and appropriate? YesWas a quality assessment of included studies undertaken? NoWere the methods of the study appraisal reproducible? UnclearWere sources of heterogeneity explored? N/AWas a summary of the main results clear and appropriate? NoCT = computerised tomography, MR = magnetic resonance The systematic review by Panes et al. (2011) was extensive (68 studies) and included different purposes of MRI within Crohn’s disease (i.e., extent of disease, severity of disease, detection of abscesses and fistulas). The review was relatively non-selective in the inclusion of studies compared with Siddiqui (2012) and Wu (2013) reviews. Few studies included comparative assessments across different imaging modalities. Quality assessment of the included studies and pooled analyses were not undertaken by the authors. Appendix D provides full details of the different outcomes by MRI purpose. For the detection of Crohn’s disease activity in four studies, the range of sensitivity estimates for MRI were 80-91% and specificity 67-100% compared with CT sensitivity 60-95% and specificity 80-100% PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5QYW5lczwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+PFJl
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ADDIN EN.CITE.DATA (Panes et al., 2011). The review was assessed as low quality due to the unclear methods used, the lack of quality assessment of the included studies, heterogeneity of the studies and lack of summary of main results. Importantly, the studies included a range of referent standards in which to measure accuracy making comparisons difficult.Direct evidenceThe current review did not identify any studies comparing the health outcomes of patients evaluated with MRI for small bowel and perianal fistulising suspected or known Crohn’s disease. In the absence of direct evidence for the effectiveness of MRI, the evidence of diagnostic accuracy, change in management and the expected benefits of changes in treatment on health outcomes are presented using a linked evidence approach on the value of MRI in these indications.Indirect evidenceA total of eight primary clinical studies met the inclusion criteria for this review PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DaGVyaXlhbjwvQXV0aG9yPjxZZWFyPjIwMTM8L1llYXI+
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ADDIN EN.CITE.DATA (Panes et al., 2011, Siddiqui et al., 2012, Wu et al., 2013). As shown in Table 17, all studies were conducted in Europe and there were no Australian studies meeting the eligibility criteria. All studies involved patients with established Crohn’s disease with similar mean age (34-42 years) and range (18-70 years) but different gender proportions with the proportion of males ranging from 26% to 69%. Four studies compared MR enterography with CT enterography PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5JcHBvbGl0bzwvQXV0aG9yPjxZZWFyPjIwMTA8L1llYXI+
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ZT5=
ADDIN EN.CITE.DATA (Ippolito et al., 2010, Jensen et al., 2011, Schmidt et al., 2010, Schreyer et al., 2010), one compared MR enterography with CT enterocylsis PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NYWxncmFzPC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48
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ADDIN EN.CITE.DATA (Schwartz et al., 2001).Only one high quality study was included ADDIN EN.CITE <EndNote><Cite><Author>Jensen</Author><Year>2011</Year><RecNum>33</RecNum><DisplayText>(Jensen et al., 2011)</DisplayText><record><rec-number>33</rec-number><foreign-keys><key app="EN" db-id="5ww0vavvyz92p9ewfdqptwwwrrxxzfvdadas" timestamp="0">33</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Jensen, M. D.</author><author>Kjeldsen, J.</author><author>Rafaelsen, S. R.</author><author>Nathan, T.</author></authors></contributors><auth-address>Department of Internal Medicine, Section of Gastroenterology, Lillebaelt Hospital Vejle, Kabbeltoft 25, Vejle, Denmark. michael.dam.jensen@slb.regionsyddanmark.dk</auth-address><titles><title>Diagnostic accuracies of MR enterography and CT enterography in symptomatic Crohn's disease</title><secondary-title>Scand J Gastroenterol</secondary-title><alt-title>Scandinavian journal of gastroenterology</alt-title></titles><pages>1449-57</pages><volume>46</volume><number>12</number><edition>2011/09/13</edition><keywords><keyword>Adolescent</keyword><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Constriction, Pathologic/etiology/radiography</keyword><keyword>Crohn Disease/complications/*diagnosis/radiography</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Intestine, Small/*radiography</keyword><keyword>Logistic Models</keyword><keyword>*Magnetic Resonance Imaging</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Predictive Value of Tests</keyword><keyword>Prospective Studies</keyword><keyword>Single-Blind Method</keyword><keyword>*Tomography, X-Ray Computed</keyword><keyword>Young Adult</keyword></keywords><dates><year>2011</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>0036-5521</isbn><accession-num>21905974</accession-num><urls></urls><electronic-resource-num>10.3109/00365521.2011.613947</electronic-resource-num><remote-database-provider>Nlm</remote-database-provider><language>eng</language></record></Cite></EndNote>(Jensen et al., 2011) and one further study was judged as medium quality ADDIN EN.CITE <EndNote><Cite><Author>Schmidt</Author><Year>2010</Year><RecNum>48</RecNum><DisplayText>(Schmidt et al., 2010)</DisplayText><record><rec-number>48</rec-number><foreign-keys><key app="EN" db-id="5ww0vavvyz92p9ewfdqptwwwrrxxzfvdadas" timestamp="0">48</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Schmidt, S.</author><author>Guibal, A.</author><author>Meuwly, J. Y.</author><author>Michetti, P.</author><author>Felley, C.</author><author>Meuli, R.</author><author>Schnyder, P.</author><author>Denys, A.</author></authors></contributors><auth-address>Department of Radiology, University Hospital, CHUV, Lausanne, Switzerland. sabine.schmidt@chuv.ch</auth-address><titles><title>Acute complications of Crohn's disease: comparison of multidetector-row computed tomographic enterography with magnetic resonance enterography</title><secondary-title>Digestion</secondary-title><alt-title>Digestion</alt-title></titles><pages>229-38</pages><volume>82</volume><number>4</number><edition>2010/07/01</edition><keywords><keyword>Acute Disease</keyword><keyword>Adolescent</keyword><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Crohn Disease/*complications</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Image Interpretation, Computer-Assisted</keyword><keyword>Magnetic Resonance Imaging/*methods</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Prospective Studies</keyword><keyword>Sensitivity and Specificity</keyword><keyword>Statistics, Nonparametric</keyword><keyword>Tomography, X-Ray Computed/*methods</keyword></keywords><dates><year>2010</year></dates><isbn>0012-2823</isbn><accession-num>20588038</accession-num><urls></urls><electronic-resource-num>10.1159/000288521</electronic-resource-num><remote-database-provider>Nlm</remote-database-provider><language>eng</language></record></Cite></EndNote>(Schmidt et al., 2010). Two studies represented NHMRC Level II evidence PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5KZW5zZW48L0F1dGhvcj48WWVhcj4yMDExPC9ZZWFyPjxS
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ADDIN EN.CITE.DATA (Malgras et al., 2012, Schwartz et al., 2001) but specificity was not reported or calculable from the available results.As shown in Table 18, the sensitivity of MRI was high and consistent with the results from the systematic reviews (range 74% to 100%). Similarly, CT also produced high sensitivity across the studies (range 83% to 100%). With the low and high confidence intervals of these estimates overlapping, the diagnostic accuracy of MRI and CT is considered equal for sensitivity in assessing extent of disease, complications and perianal disease.The specificity of MRI was also high for the studies reporting this outcome (range 80% to 100%) but similar compared with CT (range 67% to 100%).The study by Jensen et al. (2011) assessed as high quality, and having the least chance of biased outcomes, found sensitivity and specificity results at the lower end of the overall range across the studies. Statistical analysis showed that the sensitivity and specificity of MR enterography was not significantly different from CT enterography. Of concern is the specificity of MRI 80% (95% CI: 44%, 98%) with a negative predictive value of 47% (95%CI: 23%, 72%) and slightly lower than for CT for detection of disease extent ADDIN EN.CITE <EndNote><Cite><Author>Jensen</Author><Year>2011</Year><RecNum>33</RecNum><DisplayText>(Jensen et al., 2011)</DisplayText><record><rec-number>33</rec-number><foreign-keys><key app="EN" db-id="5ww0vavvyz92p9ewfdqptwwwrrxxzfvdadas" timestamp="0">33</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Jensen, M. D.</author><author>Kjeldsen, J.</author><author>Rafaelsen, S. R.</author><author>Nathan, T.</author></authors></contributors><auth-address>Department of Internal Medicine, Section of Gastroenterology, Lillebaelt Hospital Vejle, Kabbeltoft 25, Vejle, Denmark. michael.dam.jensen@slb.regionsyddanmark.dk</auth-address><titles><title>Diagnostic accuracies of MR enterography and CT enterography in symptomatic Crohn's disease</title><secondary-title>Scand J Gastroenterol</secondary-title><alt-title>Scandinavian journal of gastroenterology</alt-title></titles><pages>1449-57</pages><volume>46</volume><number>12</number><edition>2011/09/13</edition><keywords><keyword>Adolescent</keyword><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Constriction, Pathologic/etiology/radiography</keyword><keyword>Crohn Disease/complications/*diagnosis/radiography</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Intestine, Small/*radiography</keyword><keyword>Logistic Models</keyword><keyword>*Magnetic Resonance Imaging</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Predictive Value of Tests</keyword><keyword>Prospective Studies</keyword><keyword>Single-Blind Method</keyword><keyword>*Tomography, X-Ray Computed</keyword><keyword>Young Adult</keyword></keywords><dates><year>2011</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>0036-5521</isbn><accession-num>21905974</accession-num><urls></urls><electronic-resource-num>10.3109/00365521.2011.613947</electronic-resource-num><remote-database-provider>Nlm</remote-database-provider><language>eng</language></record></Cite></EndNote>(Jensen et al., 2011). MRI and CT therefore do not discriminate negative test findings well in those without disease. The implications in terms of patient management mean that treatments may not be offered in those patients with disease but who received a negative MR test.No studies were found specifically assessing MRI in pregnancy. Studies that reported exclusion criteria excluded women who were pregnant or lactating due to the comparisons involving MRI with CT. CT is contraindicated for women who are pregnant.No studies were found comparing extent of disease or complications of disease using the comparator small bowel follow through.Table 17: Characteristics and appraisal of 6 included accuracy studiesAuthor (year)SettingTime periodNTest comparisonPopulationStudy designQuality and applicabilityMalgras (2012)FranceSingle centre 52MR enterography vs CT enteroclysisPatients with known CD referred for surgeryMean age 37 years, 56% malePrior tests: videocolonoscopyStudy design: RetrospectiveReference standard: Surgical exam + pathologyOutcomes: Accuracy, diagnostic yield NHMRC level of evidence: IVComparison: CXApplicability: P1Quality: PoorJensen (2011)DenmarkMulti centre 50MR enterography vs CT enterographyPatients with known CDMedian age 39 years, 26% malePrior tests: endoscopy, radiology, surgeryStudy design: Prospective Reference standard: Surgical exam, ileoscopy or endoscopyOutcomes: Accuracy, diagnostic yield NHMRC level of evidence: IIComparison: C1Applicability: P1Quality: HighIppolito (2010)ItalySingle centre 29MR enterography vs CT enterography Patients with known CDAge range 14-70 years, 69% malePrior tests: biopsy confirmed CDStudy design: Prospective, consecutive Reference standard: noneOutcomes: Diagnostic yield, NHMRC level of evidence: IVComparison: C1Applicability: P1Quality: PoorSchmidt (2010)ItalySingle centre 57MR enterography vs CT enterographyPatients with known CDMean age 33.5 years, range 17-69 years Prior tests: NSStudy design: ProspectiveReference standard: Composite of surgery, endoscopy, long-term follow up Outcomes: Accuracy, diagnostic yield NHMRC level of evidence: IVComparison: CXApplicability: P1Quality: MediumSchreyer (2010)GermanySingle centre 53MR enterography vs CT contrast enhancedPatients with known CD presenting to emergency departmentMedian age 37 years, range 18-73 years Prior tests: NSStudy design: Retrospective Reference standard: noneOutcomes: Diagnostic yield NHMRC level of evidence: IVComparison: C1Applicability: P2Quality: PoorSchwartz (2001)USASingle centre 34Endoanal ultrasound vs MRI pelvis vs surgical examPatients with known CD and suspected perianal fistulasMean age 36 years, range 18-70 years Prior tests: No other pre-operative imagingStudy design: Retrospective Reference standard: Combined endoanal ultrasound, MRI pelvis, surgical examOutcomes: Accuracy, diagnostic yield NHMRC level of evidence: IIComparison: C1Applicability: P1Quality: PoorAbbreviations: AU = abdominal ultrasound, CD = Crohn’s disease, CT = computed tomography, MRE = magnetic resonance imaging with enterography, MRI = magnetic resonance imaging, SBFT = small bowel follow-throughTable 18: Summary of key results from diagnostic studies and systematic reviewsStudyNDiagnostic YieldSensitivity % (95%CI)Specificity % (95%CI)MREComparatorMREComparatorMREComparatorWu (2013)725--87% (95%CI: 77%, 93%)n/a91%(95%CI: 81%, 96%)n/aSiddiqui (2012)113--MRI 87%(95%CI: 63%, 96%)Endoanal US87% (95%CI: 70%, 95%) MRI 69% (95%CI: 51%, 82%) Endoanal US43% (95%CI: 21%, 69%) Panes (2011)4 studies1--Range 80-91%CT Range 60-95%Range 67-100%CT Range 80-100%Malgras (2012)52--100% (95%CI: 92%, 100%)CT enteroclysis93% (95%CI: 82%, 99%)Not calculableNot calculableJensen (2011)250--74% (CI: 57%-88%)CT enterography 83% (CI: 66%-93%)80% (CI: 44%-98%)CT enterography 70% (CI: 35%-93%)Ippolito (2010)29--100%CT enterography100%100%CT enterography100%Schmidt (2010)57--84%CT enterography93%91%CT enterography67%Schreyer (2010)5349/53 (92%)3CT enterography49/53 (92%)----Schwartz4(2001)3426/30 (87%) (CI 69%-96%)Endoanal US 29/32 91% (CI 75%-98%) Surgical exam 29/32 91% (CI 75%-98%)Not calculableNot calculableCD= Crohn’s disease, MRE= magnetic resonance enterography, US= ultrasound, SBFT=small bowel follow-throughResults are presented for 4 studies for detection of activity in CD (Fiorino 2011, Lee 2009, Siddiki 2009, Low 2000)Results are for detection of activity in CD PPV MR: 93% (CI: 77%-99%) CT 91% (CI: 75%-98%) NPV MR: 47% (CI: 23%-72%) CT NPV: 54% (CI: 25%-81%)Terminal ileum disease activity MRI pelvisDoes it change patient management?Two studies were identified with the primary purpose of investigating the change in patient management using MRI for patients with known Crohn’s disease PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DaGVyaXlhbjwvQXV0aG9yPjxZZWFyPjIwMTM8L1llYXI+
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ADDIN EN.CITE.DATA (Cheriyan et al., 2013, Sanka et al., 2012).The study by Cheriyan (2012) involved 57 patients with small bowel Crohn’s disease and mean disease duration of 9.5 years. There was no referent for the MRI and a description of current management options for the participants was not provided. A total of 50/57 patients had abnormal MR enterography (i.e., 5 stricturing, 17 active, 14 both active and structuring) and most of these 42/50 had a change in management, 22 (53%) had medical intervention and 20 (47%) underwent surgery. The authors concluded that MRI had a substantial clinical impact on patient management ADDIN EN.CITE <EndNote><Cite><Author>Cheriyan</Author><Year>2013</Year><RecNum>151</RecNum><DisplayText>(Cheriyan et al., 2013)</DisplayText><record><rec-number>151</rec-number><foreign-keys><key app="EN" db-id="5ww0vavvyz92p9ewfdqptwwwrrxxzfvdadas" timestamp="0">151</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Cheriyan, D. G.</author><author>Slattery, E.</author><author>McDermott, S.</author><author>Kilcoyne, A.</author><author>Kingston, C.</author><author>Keegan, D.</author><author>Mulcahy, H. E.</author><author>Doherty, G. A.</author><author>Malone, D. E.</author><author>Murphy, S. J.</author></authors></contributors><auth-address>Department of Gastroenterology Hospital, St Vincent's University Hospital, Centre for Colorectal Disease, Dublin, Ireland. dgcheriyan@</auth-address><titles><title>Impact of magnetic resonance enterography in the management of small bowel Crohn's disease</title><secondary-title>Eur J Gastroenterol Hepatol</secondary-title><alt-title>European journal of gastroenterology & hepatology</alt-title></titles><pages>550-5</pages><volume>25</volume><number>5</number><edition>2013/01/18</edition><keywords><keyword>Adolescent</keyword><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Crohn Disease/complications/*diagnosis/drug therapy/surgery</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Intestinal Obstruction/diagnosis/etiology/surgery</keyword><keyword>Intestine, Small/*pathology/surgery</keyword><keyword>Magnetic Resonance Imaging/*methods</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Prospective Studies</keyword><keyword>Young Adult</keyword></keywords><dates><year>2013</year><pub-dates><date>May</date></pub-dates></dates><isbn>0954-691x</isbn><accession-num>23325284</accession-num><urls></urls><electronic-resource-num>10.1097/MEG.0b013e32835d4e9c</electronic-resource-num><remote-database-provider>Nlm</remote-database-provider><language>eng</language></record></Cite></EndNote>(Cheriyan et al., 2013). The results should be viewed with caution due to the descriptive nature of the study and poor overall quality (see Appendix D)In a retrospective paediatric study by Sanka (2012), 34 children were evaluated for change in management for small bowel Crohn’s disease. Nine children had normal MR enteroclysis and were either discharged (n=8) or management did not change (n=1). After MR enteroclysis, 13 patients commenced azathioprine, methotrexate, adalimumab or infliximab and five patients underwent surgery PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TYW5rYTwvQXV0aG9yPjxZZWFyPjIwMTI8L1llYXI+PFJl
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ADDIN EN.CITE.DATA (Sanka et al., 2012). As for Cheriyan (2012), the results were descriptive and had a number of limitations including reporting the medical management at baseline (Appendix D). A notable limitation of the two studies above is that the current management of Crohn’s disease before MRI was undertaken was not stated and therefore the transitions between pharmacological or other treatments are not clear. The claim that earlier or more appropriate treatment, or the avoidance of surgery, or the cessation of expensive drug therapy, is not supported by these two studies.No studies were identified involving patients with perianal fistulising Crohn’s disease that addressed change or response in therapy.Does change in management improve patient outcomes?No comparative studies were identified in the systematic review that reported on improvements to patient outcomes as a response to MRI in Crohn’s disease.Other relevant considerationsOngoing trialsA number of trials are currently underway which are related to this application but not directly. These include:NCT01881490 ImageKids Study: Developing the Pediatric?Crohn's?Disease Intestinal Damage Score NCT00204165 (PECDID) & the Pediatric MRE-Based Activity Index (P-MECAI)Comparison of MR Enteroclysis and MRI With Per Oral Contrast Using a 6 % Mannitol Solution.NCT01183403 CE-U and MRE to Predict the Efficacy of Anti-TNF Therapy in Crohn’s Disease (CREOLE)NCT01593462 Comparative Effectiveness of MR Enterography (children, currently recruiting)NCT01671579 Comparison of Bowel Ultrasound & MR Enterography in the Follow-up of Previously Diagnosed Pediatric Small Bowel?Crohn’s Disease (currently recruiting)NTR2201 Evaluation of dynamic MRI with T1-maps correlated with histopathology in patients with crohn’s disease. (Netherlands, recruiting)Expert opinionDuring this assessment a number of issues were raised by HESP experts. One relates to the age of the MRI machines currently in existence in Australian hospitals. Some of these machines are ageing and new advances in fast scanning techniques etc have improved imaging quality. Experts have expressed the view that MRI would be used more widely if it were available in all hospitals and patients did not have to pay out-of-pocket expenses. Furthermore, they suggested that SBFT is virtually superseded by CT enterography; the current use of SBFT is very low. Clinicians would be more likely to refer their patients to a location where MRI or CT was available than to use SBFT.Consumer implications and other considerationsConsumer survey responses for this item were positive and supportive and note that potential disadvantages are few (only that some patients experience claustrophobia with MRI).?In addition, in order to complement the introduction of MRI to diagnose small bowel Crohns disease, survey responses also feel that funding faecal calprotectin as a non-invasive marker of gut inflammation needs to be considered.? From a patient perspective the main differences between MRI and CT scans are summarised in Table 19. These relate to greater cost for MRI, lower comparative access to MRI, time burden of MRI and reduction in ionizing radiation. This kind of information is readily available to consumers via imaging company websites.Table 19: Patient-relevant differences in MRI or CT scans in AustraliaCT - Computed TomographyMRI - Magnetic Resonance ImagingIonising radiationNo ionising radiationUnsafe in pregnancyNo known risk but avoided in pregnancyScans takes around 5-10 minutesScans take 30 minutes or longerCheaper:Part rebate from MedicareSome practices bulk billingExpensive:Few rebates from MedicareFew practices bulk billingHundreds of locations in AustraliaDozens of locations in AustraliaMetal implants OKMetal implants potentially dangerousCardiac devices mostly OKCardiac devices may malfunctionCochlear implants usually OKCochlear implants may be affectedInsulin pumps usually OKInsulin pumps may malfunctionSource: are the economic considerations? Summary of the evidenceA summary of the evidence for assessing the diagnostic accuracy, safety and subsequent patient consequences of MRI compared to various comparators in this application are provided in Table 20.Table 20: Summary of evidence for MRI versus Comparator(s)Diagnostic AccuracyProposed indication of MRIComparatorSensitivitySpecificityPatient BenefitsSafety outcomesSmall Bowel Extent of CD SBFT, CTEquivalent to CTEquivalent to CTNo evidenceNo evidence Complications in CDSBFT, CTEquivalent to CTEquivalent to CTNo evidenceNo evidence PregnancyUltrasoundNo evidenceNo evidenceNo evidenceNo evidence Change in therapySBFT, CTNo evidenceNo evidenceNo evidenceNo evidencePerianal/Fistulising Pelvic sepsis and fistulasSurgical exam or endoanal ultrasoundEquivalentEquivalent/ superiorNo evidenceNo evidence Change in therapyEndoanal ultrasoundNo evidenceNo evidenceNo evidenceNo evidenceCD= Crohn’s disease, CT = Computed Tomography, MRE= magnetic resonance enterography, US= ultrasound, SBFT=small bowel follow-throughSmall bowel CD: The evidence suggests that MRI is equivalent to CT for detecting the extent or complications in patients with known Crohn’s disease in the small bowel. There were no comparative studies to provide evidence of MRI for diagnostic accuracy in pregnancy or for assessing change in therapy. No comparative studies were found for assessing use of MRI and linking this to patient benefits or patient safety outcomes. On the basis of the overall evidence base for the proposed MR indications for small bowel in this application a full cost-utility analysis is not warranted.Perianal fistulising CD: For evaluating the presence of pelvic sepsis and fistulas, MRI was assessed as being equivalent to endoanal ultrasound for sensitivity and superior for specificity. However, the improvement in specificity for MRI was not tested statistically and the specificity for both CT and MRI was considered low. No comparative studies provided evidence of MRI for assessing change in therapy. No comparative studies were found for assessing use of MRI and linking this to patient benefits or patient safety outcomes. On the basis of the evidence for MRI for perianal fistulising CD, a cost-effectiveness analysis is appropriate for assessing pelvic sepsis and fistulas.Overview of the economic considerationsThe economic considerations appropriate to this application include:An assessment of the cost-effectiveness analysis of MRI for pelvic sepsis and fistulas; andAn assessment of the financial implications of the proposed reimbursement of MRI for all the proposed indications.Published economic literatureIn order to inform the cost-effectiveness study, a review of the literature for relevant economic studies was undertaken at the time of the clinical effectiveness data search. Figure 2 and Table 7 provide full details of the literature search.One published economic evaluation was identified as relevant to this application (Cipriano et al. 2012) and more specifically to MRI small bowel Crohn’s disease. 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ADDIN EN.CITE.DATA (Pedersen et al., 2010). The Markov model was validated and checked according to the increased risk of cancer across various sites (e.g., kidney, colon, stomach, lung etc). Two important issues relating to the analysis included:The model assumed equivalent diagnostic accuracy and consequently equivalent patient management across the CT and MRI options; andThe authors found no prospective studies specifically linking CT-radiation exposure to cancer mortality and concluded that randomized controlled trials on this topic were probably not feasible.Using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist ADDIN EN.CITE <EndNote><Cite><Author>Husereau</Author><Year>2013</Year><RecNum>174</RecNum><DisplayText>(Husereau et al., 2013)</DisplayText><record><rec-number>174</rec-number><foreign-keys><key app="EN" db-id="5ww0vavvyz92p9ewfdqptwwwrrxxzfvdadas" timestamp="1386654199">174</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Husereau, D.</author><author>Drummond, M.</author><author>Petrou, S.</author><author>Carswell, C.</author><author>Moher, D.</author><author>Greenberg, D.</author><author>Augustovski, F.</author><author>Briggs, A. H.</author><author>Mauskopf, J.</author><author>Loder, E.</author></authors></contributors><auth-address>Institute of Health Economics, Edmonton, Canada. donh@</auth-address><titles><title>Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement</title><secondary-title>Int J Technol Assess Health Care</secondary-title><alt-title>International journal of technology assessment in health care</alt-title></titles><periodical><full-title>Int J Technol Assess Health Care</full-title><abbr-1>International journal of technology assessment in health care</abbr-1></periodical><alt-periodical><full-title>Int J Technol Assess Health Care</full-title><abbr-1>International journal of technology assessment in health care</abbr-1></alt-periodical><pages>117-22</pages><volume>29</volume><number>2</number><edition>2013/04/17</edition><dates><year>2013</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0266-4623</isbn><accession-num>23587340</accession-num><urls></urls><electronic-resource-num>10.1017/s0266462313000160</electronic-resource-num><remote-database-provider>Nlm</remote-database-provider><language>eng</language></record></Cite></EndNote>(Husereau et al., 2013), the transparency and comprehensiveness of the reported model was assessed. These findings are reported in Appendix F. Overall, the study methods and reported results were of high quality, subject to some caveats and necessary assumptions in the absence of evidence. Full details of the synthesized evidence base and analytical decisions were provided in an online supplementary file. The economic model found that the incremental cost effectiveness ratios for an annual MRI scan to replace CT scans were; (USD 2009) $54,345 per QALY until age 30, $65,494 per QALY until age 40 and $124,217 per QALY until age 60. The incremental QALYs were marginal from MR until age 30 and ranged from 0.14 to MR until 40 years and 0.23 to MR until age 60 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DaXByaWFubzwvQXV0aG9yPjxZZWFyPjIwMTI8L1llYXI+
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ADDIN EN.CITE.DATA (Cipriano et al., 2012). Unit costs for each MR enterography were US$2155 and US$1304 for CT enterography. These prices are 3-fold higher than Australian prices. In sensitivity analyses, if the difference between MR enterography and CT enterography was more than $600 per scan, the cost effectiveness ratio was greater than US$100,000 per QALY. The cost of MR is a key driver of cost-effectiveness in this long-term model. Using the same model with Australian costs, where the cost of the comparable MRI is $627.50 and CT, $480.05 and a price differential of $147, would result in a greatly improved cost-effectiveness ratio.However, the applicability of the findings of Cipriano et al. (2012) to the Australian setting are unclear and may not be especially relevant given the differences in cancer epidemiology health care systems and resource use between Australia and the US. Nonetheless, this study provides a useful contribution to the potential downstream consequences of MR as a replacement for CT in a careful and comprehensive health economic report.Economic evaluationAn economic evaluation was undertaken to model the costs and effects of superior specificity of pelvic MRI for detection of fistulas/abscesses in fistulising Crohn’s disease.OverviewA linked approach was taken whereby a higher specificity of MRI compared with endoanal ultrasound lead to fewer false negatives and potentially more appropriate management. The evidence supporting this link for an altered clinical course of disease is not firmly supported by the evidence and therefore this analysis should be viewed with caution and is considered hypothetical. The key parameters of the model are provided in Table 21 together with the sources. The structure of the model is provided in Figure 4.Justification of model parameters and assumptionsA decision-analytic model was constructed and all analyses were performed in TreeAge Pro 2013 software. The model was a simple representation comparing the two test strategies and draws on evidence from the literature. In the absence of long-term clinical data, the model duration was 12 months. Although Crohn’s disease is incurable and chronic in nature, the flare-ups and complications that arise need to be attended to quickly and in acute care settings. We therefore made assumptions regarding only the potential short-term consequences of testing performance on early healthcare resource use and patient quality of life (utility values). The main outcomes of the model are costs and QALYs over 12 months. Due to the short duration, discounting costs or QALYs was not necessary.Schwartz et al. (2004) referenced several studies that have shown when abscesses and fistulas are not detected, it can result in recurrent fistulas or convert simple fistulas to complex ones with significantly reduced healing rates PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TY2h3YXJ0ejwvQXV0aG9yPjxZZWFyPjIwMDQ8L1llYXI+
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ADDIN EN.CITE.DATA (Schwartz and Herdman, 2004). An assessment of these individual studies did not provide clear figures on the extent of recurrence in failed imaging studies. Others state that repeated surgeries and higher medical costs are accrued for patients with more severe Crohn’s disease ADDIN EN.CITE <EndNote><Cite><Author>Yu</Author><Year>2008</Year><RecNum>175</RecNum><DisplayText>(Yu et al., 2008)</DisplayText><record><rec-number>175</rec-number><foreign-keys><key app="EN" db-id="5ww0vavvyz92p9ewfdqptwwwrrxxzfvdadas" timestamp="1386654963">175</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Yu, A. P.</author><author>Cabanilla, L. A.</author><author>Wu, E. Q.</author><author>Mulani, P. M.</author><author>Chao, J.</author></authors></contributors><auth-address>Analysis Group, Inc., Boston, MA 02199, USA. ayu@</auth-address><titles><title>The costs of Crohn's disease in the United States and other Western countries: a systematic review</title><secondary-title>Curr Med Res Opin</secondary-title><alt-title>Current medical research and opinion</alt-title></titles><periodical><full-title>Curr Med Res Opin</full-title><abbr-1>Current medical research and opinion</abbr-1></periodical><alt-periodical><full-title>Curr Med Res Opin</full-title><abbr-1>Current medical research and opinion</abbr-1></alt-periodical><pages>319-28</pages><volume>24</volume><number>2</number><edition>2007/12/11</edition><keywords><keyword>Crohn Disease/*economics/epidemiology</keyword><keyword>Europe/epidemiology</keyword><keyword>Health Care Costs/*statistics & numerical data</keyword><keyword>Health Resources/economics</keyword><keyword>Hospitalization/economics</keyword><keyword>Humans</keyword><keyword>Prevalence</keyword><keyword>United States/epidemiology</keyword></keywords><dates><year>2008</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>0300-7995</isbn><accession-num>18067689</accession-num><urls></urls><electronic-resource-num>10.1185/030079908x260790</electronic-resource-num><remote-database-provider>Nlm</remote-database-provider><language>eng</language></record></Cite></EndNote>(Yu et al., 2008). It is possible that simple fistulas that go undetected during imaging will cause a delay in appropriate treatment (usually surgery combined with medical treatment), ongoing patient discomfort and increased testing and resources for symptom relief PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TY2h3YXJ0ejwvQXV0aG9yPjxZZWFyPjIwMDQ8L1llYXI+
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ADDIN EN.CITE.DATA (Schwartz and Herdman, 2004). Therefore, it was assumed that a false negative finding on either MR or endoanal ultrasound would result in a proportion of these patients (30%) accruing higher costs for additional tests and examinations and possibly repeat surgical procedures for complex or recurrent disease. This proportion was tested between 20% and 50%. We also tested the scenario of $0 additional cost for false negatives. Recurrence is especially high for complex perianal fistulas and has been reported at 53% at 14 months ADDIN EN.CITE <EndNote><Cite><Author>Makowiec</Author><Year>1997</Year><RecNum>176</RecNum><DisplayText>(Makowiec et al., 1997)</DisplayText><record><rec-number>176</rec-number><foreign-keys><key app="EN" db-id="5ww0vavvyz92p9ewfdqptwwwrrxxzfvdadas" timestamp="1386655089">176</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Makowiec, F.</author><author>Jehle, E. C.</author><author>Becker, H. D.</author><author>Starlinger, M.</author></authors></contributors><auth-address>Department of Surgery, Eberhard-Karls-University, Tubingen, Germany.</auth-address><titles><title>Perianal abscess in Crohn's disease</title><secondary-title>Dis Colon Rectum</secondary-title><alt-title>Diseases of the colon and rectum</alt-title></titles><periodical><full-title>Dis Colon Rectum</full-title><abbr-1>Diseases of the colon and rectum</abbr-1></periodical><alt-periodical><full-title>Dis Colon Rectum</full-title><abbr-1>Diseases of the colon and rectum</abbr-1></alt-periodical><pages>443-50</pages><volume>40</volume><number>4</number><edition>1997/04/01</edition><keywords><keyword>Abscess/*etiology/surgery</keyword><keyword>Adult</keyword><keyword>Anus Diseases/*etiology/surgery</keyword><keyword>Crohn Disease/*complications</keyword><keyword>Drainage/methods</keyword><keyword>Enterostomy</keyword><keyword>Female</keyword><keyword>Follow-Up Studies</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Prospective Studies</keyword><keyword>Rectal Fistula/*etiology</keyword><keyword>Recurrence</keyword><keyword>Risk Factors</keyword></keywords><dates><year>1997</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0012-3706 (Print)
0012-3706</isbn><accession-num>9106694</accession-num><urls></urls><remote-database-provider>Nlm</remote-database-provider><language>eng</language></record></Cite></EndNote>(Makowiec et al., 1997). Table 21: Parameters used in the decision-analytic model for pelvic MRI versus CT for detection of fistulas/abscesses in fistulising perianal Crohn’s disease DescriptionBaseLowHighDistributionSourceModel duration12 months---Discountingn/a---ProbabilitiesMRI specificity0.690.510.82Beta α=22.90 β=10.29Siddiqui 2012MRI sensitivity0.870.630.96Beta α=13.01 β=1.94Siddiqui 2012EUS specificity0.430.210.69Beta α=6.60 β=8.76Siddiqui 2012EUS sensitivity0.870.700.95Beta α=21.51 β=3.21Siddiqui 2012Probability of perianal fistula in one year0.120.090.25Beta α=5.87 β=43.02Ng 2013Proportion of surgery requiring repeat surgery for recurrence0.30.200.50Beta α=18.67 β=43.56AssumptionCostsCost of pelvic MRI$403.20$342.72$463.68Normal ?=403.20 σ=60.48Proposed, ±15%Cost of endoanal ultrasound$55.65$0$55.65Normal ?=55.65 σ=8.35MBS item #55014Cost of surgery$3878$3296$4460Normal ?=3878 σ=581.40AR-DRG item #J09ZCost of surgery if false negativec_surgery*(1+p_repeat_surg)$0$7756-AssumptionUtilitiesUtility of CD in person with true positive0.8150.7250.955Beta α=22.90 β=10.29Cipriano 2012Utility of CD when false negative or false positive occurs0.7250.6250.825Beta α=1.83 β=0.70Cipriano 2012Utility of CD in person with true negative0.9550.8151.000Beta α=12.16 β=0.57Cipriano 2012CD= Crohn’s disease, CT = computer tomography, EUS = endoanal ultrasound, MRI= magnetic resonance imagingFigure 4: Diagram of decision-analytic model for pelvic MRI versus CT for detection of fistulas/abscesses in fistulising perianal Crohn’s diseaseCosts were assigned to perianal surgery, ultrasound and MRI using MBS scheduled fees, the proposed MBS fee for MRI and the latest AR-DRG public hospital cost weights for perianal procedures. Utility values were derived from Cipriano 2012 which sourced EQ-5D utility values (for patients with Crohn’s disease) from the Medical Expenditure P Survey in the US. A range of values were reported around the mean 0.81 (95%CI: 0.725, 0.955) PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DaXByaWFubzwvQXV0aG9yPjxZZWFyPjIwMTI8L1llYXI+
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ADDIN EN.CITE.DATA (Cipriano et al., 2012). An assumption was made to use 0.81 for positive tests with accompanying prompt and effective treatment, 0.725 for false negative or false positive tests and 0.955 for true negatives where patient quality of life may be relatively high. These values were tested generously in sensitivity analyses.It is assumed that medical therapies and other resources already used by individuals will be equal across the imaging strategies and these were omitted from the model. It is also assumed that individuals will be those of a demographic and clinical description of those from the meta-analysis of Siddiqui et al. (2012) on where the key sensitivity and specificity MRI data are derived.Base case and sensitivity analysesA mean expected value analysis was performed. The costs and QALYs were aggregated across the branches to produce mean outcomes. Sensitivity analyses were undertaken as warranted by the high level of assumptions made in the data parameters. One-way sensitivity analyses were undertaken for all variables using the 95% confidence intervals for the high and low values, where available, or estimates were assigned to reflect wide variation in the base value (Table 21). Probability sensitivity analyses were undertaken to vary all variables simultaneously and 1000 Monte Carlo simulations were produced. Beta distributions were assigned for probabilities and utilities and normal distributions were used for costs (due to expected stability in the cost estimates). Results of the cost-utility analysis The results of the cost-utility analyses are presented in Table 22.Table 22: Results of the cost-utility analysis of MRI and endoanal ultrasound for detecting perianal fistulas in Crohn’s disease (12 months)BaseMean CostsMean QALYsICERMRI$22430.87Endoanal ultrasound$30490.82Incremental outcomes-$8060.05DominantOne-way sensitivity analyses (selected)Incremental CostsIncremental QALYsICERCost of surgery if false negativeLow $0High $7756$348-$14270.050.05$6,604DominantUtility of CD in person with true negativeLow 0.815High 1.00$806$8060.020.06DominantDominantEndoanal ultrasound specificityLow 0.21High 0.69-$1782$3480.100.00Dominant$3,476MRI specificityLow 0.51High 0.82-$7-$13830.020.08DominantDominantUtility of CD when false negative or false positive occursLow 0.625High 0.825$806$8060.080.03DominantDominantProbability sensitivity analysisIncremental outcomes-$7950.05Dominant (95% CrI: dominant, $508,192)CD = Crohn’s disease, CrI = Credible Interval (interpreted like a Confidence Interval but based on a ranking order and excluding the top and bottom 2.5% of simulations), MRI = Magnetic resonance imagingIn the base case analysis, the mean cost of MRI was lower than endoanal ultrasound (by $806) meaning MRI could potentially produce cost-savings over 12 months. The corresponding QALYs were slightly higher in the MRI strategy compared with endoanal ultrasound (by 0.05). Therefore, MRI could be considered superior to endoanal ultrasound as it is less costly and more effective, based on the model assumptions. The results of the model were most influenced by the cost of surgery if there was false negative finding, the utility score with true negative, the specificities of endoanal ultrasound and MRI and the utility scores of false negatives or false positives. However, even when using wide variation to these values in the sensitivity analyses (e.g. $0 for resource impact of a false negative result), they did not change the finding that MRI would be a cost-effective choice.In the probabilistic sensitivity analysis, the incremental cost and incremental QALY pairings from 1000 simulations are illustrated in (Figure 5). The figure illustrates that 78.6% of simulations would be cost-effective at $50,000 per QALY and in the vast majority, (74%) MRI would be cost-saving compared with endoanal ultrasound. However, this favourable outcome for MRI is volatile to the choice of costs for perianal surgery) for patients with false negative results from MRI. The model is also highly dependent on the quality of life impact of the various test results and immediate consequences on clinical treatment. These appear to be the main drivers of the model as per the one-way sensitivity analyses.Figure 5: Incremental cost effectiveness scatterplot of MRI vs CT in perianal Crohn’s diseaseInterpretation of diagram: the dots in the top right quadrant below the diagonal willingness to pay (WTP) line and the dots in the bottom right quadrant – together are considered cost-effective outcomes. The proportion of these dots to all dots is 78.6%. Conclusion: MRI for fistulsing perianal Crohn’s disease for the extent of abscesses and fistulas is cost-effective compared with CT. The likelihood of MRI being cost effective relative to CT is 78.6%, subject to the parameters and assumptions made in the model.CostingIn order to provide financial estimates of MRI for the proposed indications in this application, an assessment of the epidemiology and the natural history of Crohn’s disease is required. The financial estimates presented here take an epidemiological approach.Australian epidemiological studiesNatural history studies of Crohn’s disease in Australian populations are important information for the economic assessments in this application. A brief literature search uncovered only two studies reporting epidemiological information for Australians with Crohn’s disease within larger cohorts of inflammatory bowel disease PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5OZzwvQXV0aG9yPjxZZWFyPjIwMTM8L1llYXI+PFJlY051
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ADDIN EN.CITE.DATA (Ng et al., 2013, Wilson et al., 2010). A summary comparing these key outcomes are provided in Table 23. Figures for Ng et al. (2013) apply to the Australian cohort (as a subset of the entire sample) unless otherwise stated.Table 23: Australian epidemiological studies on inflammatory bowel disease (IBD)Wilson et al. 2010Ng et al. 2013Time of case ascertainment2007/2008 (12 months)2011/2012 (12 months)N (IBD)7671 (Australia only)Crude annual incidence Crohn’s disease (95%CI)17.4 per 100,000(95%CI: 13.0-23.2)14.0 per 100,000(95%CI: 10.1-18.9)Crude annual incidence ulcerative colitis (95%CI)11.2 per 100,000(95%CI: 7.8-16.1)7.3 per 100,000(95%CI: 4.6-11.1)% of Crohn’s to IBD45/76 (59.2%)59.1%1% of Crohn’s to ulcerative colitis 45/29 (155.2%)191.0%1Median age34 years34 years2Age range9-76 years5-812% females (IBD)43/76 (56.6%)52.4%Crohn’s disease phenotype22% terminal ileum or small bowel27% isolated colon24% colon and small bowel31% small bowel24% colonic45% ileocolonic5% upper gastrointestinalDisease behaviour93% Inflammatory4.5% Stricturing1.5% Penetrating88% Inflammatory10% Stricturing2% Penetrating12% Perianal12% Stricturing and perianalBased on crude annual incidence ratesApplies to the whole sample of study n=419 new IBD casesBoth studies involved detailed and validated case ascertainment in the Geelong region of Victoria, Australia with a population of 300,000. Geelong has well-defined boundaries and is relatively geographically isolated. It has one central pathology and endoscopy centre. It is also representative of the wider Australian population according to many socio-demographic variables. The study by Ng et al. 2013 was undertaken 4 years after Wilson and show similar incidence rates albeit slightly lower.Prevalence estimates in Crohn’s disease are difficult to assess because they require knowledge of historical incidence data. However, two separate reports have estimated the prevalence of inflammatory bowel disease at 75,000 ADDIN EN.CITE <EndNote><Cite><Author>PricewaterhouseCoopers Australia</Author><Year>2013</Year><RecNum>168</RecNum><DisplayText>(PricewaterhouseCoopers Australia, 2013)</DisplayText><record><rec-number>168</rec-number><foreign-keys><key app="EN" db-id="5ww0vavvyz92p9ewfdqptwwwrrxxzfvdadas" timestamp="1386651311">168</key></foreign-keys><ref-type name="Report">27</ref-type><contributors><authors><author>PricewaterhouseCoopers Australia,</author></authors></contributors><titles><title>Improving Inflammatory Bowel Disease care across Australia</title></titles><volume>March 2013</volume><dates><year>2013</year></dates><pub-location>.au</pub-location><publisher>PricewaterhouseCoopers</publisher><urls></urls></record></Cite></EndNote>(PricewaterhouseCoopers Australia, 2013) and 65,000 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5XaWxzb248L0F1dGhvcj48WWVhcj4yMDEwPC9ZZWFyPjxS
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ADDIN EN.CITE.DATA (Wilson et al., 2010).Eligible populationTable 24 provides a list of values and their sources considered in the financial analysis relating to the number of patients in Australia potentially eligible for the proposed MRI indications.Table 24: Estimates and sources to calculate eligible populationBaseSensitivity Source (s)Annual estimatesEstimateLowHighEstimated Australian population23,301,991--ABS #3101.0 Australian Demographic StatisticsGrowth rate in population per year1%--ABS #3222.0 Population projectionsIncidence rate of Crohn's disease - crude per 100,000 individuals14.010.123.2Ng 2013, Wilson 2010Prevalence of IBD (cases)75,00065,00085,000Price Waterhouse 2013, Wilson 2010% of IBD diagnosed as Crohns59%--Wilson 2010 based on incidence figuresEstimated growth rate in Crohn's disease (annual)2%0%5%Assumption, rapid growth reported in many international studies% of small bowel Crohn's disease46%31%65%Wilson 2010, Ng 2013% of perianal fistulising Crohn's disease12%8%16%Ng 2013, DAP estimates during first year, 1% thereafter% pts with CD presenting for extent of CD small bowel100%80%-Of all incident cases, diagnose and assess extent, Assumption% pts with CD presenting with complications small bowel20%15%25%Of all prevalent cases, Gollop 1988 (19%)% pts who are pregnant and suspected CD0.2%--Assumption, known to be a very small number% pts with CD for assessment of therapy small bowel20%15%25%Of all prevalent cases, trials indicate this difference in response rate to therapy% pts with CD for suspected perianal CD100%80%Of all perianal CD cases% pts with CD for assessment of therapy perianal fistulising50%40%60%Of all perianal CD casesCD= Crohn’s disease, IBD = inflammatory bowel disease, pts = patients The current use of various imaging techniques for MRI is not documented or readily available. The Department of Health has no information on CT or MRI for inflammatory bowel disease. HESP advises the vast majority of patients in Australia with Crohn’s disease are receiving CT, while another proportion is receiving MR and a very small (next to nil) proportion would receive SBFT as CT is becoming phased out. For these estimates, the relative existing usage of imaging was therefore assumed to be 70% CT/CT enterography, 25% MR small bowel and 5% SBFT. It was further assumed that the proportion currently using MRI pelvis was 20%, 50% were using endoanal ultrasound and 30% received surgical examination. These proportions were altered in sensitivity analyses due to their high inherent uncertainty.Further assumptions were necessary for the proportions of eligible patients that are expected to present with each of the six indications. It was assumed 100% of all new cases would require a small bowel MRI for assessing extent of disease, 20% of prevalent cases would require a small bowel MRI for complications, 0.2% with pregnancy and 20% for assessment of therapy in small bowel Crohn’s disease. It was assumed 100% of patients with suspected perianal disease would require MRI pelvis and 50% would require a MRI for assessment of therapy. In the base case, the number of small bowel or pelvis MRIs per person was 1 per year for any indication. This is intended as an overall average with a small proportion of patients likely to require multiple MRIs within a 12 month period and others zero. This frequency was tested at 0.75, 1.5 and 2.0 in sensitivity analyses.Table 25 provides the costs used in the financial estimates and their sources. The full MBS calculations are provided in Table 26. However, the estimates in the calculations were based on 85% of the proposed fees because this is what the Government normally reimburses for outpatient services. We included radiologist and surgical consultation fees with the respective procedures. Contrast was also added to MRI procedures as this is not described as being included in the proposed MBS item descriptors.Table 25: Cost estimates used in the financial estimatesDescriptionCostSourceMRI small bowel per image$ 627.50 Proposed by applicant and similar in complexity to MBS #63473 (staging cervical cancer)MRI pelvis per image$403.20 Proposed by applicant and similar in complexity to MBS #63482 (MRI for pancreas and biliary tree) MRI enterocylsis$265.25 Proposed by applicant (nasojejunal tube $130 + procedure $135.25) used with MRI small bowelContrast$44.80 MBS item #63491CT/CTE$480.05 MBS item #56507 Abdominal ultrasound (for endoanal)$55.65 MBS item #55014Abdominal ultrasound in pregnancy$ 60.00 MBS item #55700SBFT$78.95 MBS item #58915Surgical examination (perianal)$3,878.00 AR-DRG item #J09Z perianal procedureSurgical consultation$85.55 MBS item #104Radiologist consultation$ 85.55 MBS item #104CD= Crohn’s disease, CT = Computed Tomography, CTE = Computed Tomography enterography, MRI= magnetic resonance imaging, US= ultrasound, SBFT=small bowel follow-throughOther health resources will be used by patients being managed for Crohn’s disease such as medical therapies (e.g., immunosuppression, antibiotics, biologicals, corticosteroids etc), other monitoring visits and potential hospitalisations. However, these resources were omitted from the analyses in order to focus on the imaging-related costs alone and potential cost-offsets proposed by the client. In effect, therefore, all other health costs are held constant in these financial estimates. All calculations were performed on an Excel? spreadsheet. The results of these calculations are provided in Table 26.Table 26: Results of the financial estimates (2014-2018) (with patient co-payment)20142015201620172018New cases of CD33613462356736753786Prevalent cases of CD4772451186547535842862213Total cases of Small bowel CD2349925138268272856730359Total cases of Perianal CD61306558699874527920Estimated MRI procedures byindicationMRI small bowel - extent of CD15461593164116901741MRI small bowel - complx of CD43914709503753755724MRI small bowel - pregnancy33333MRI small bowel - change in therapy43914709503753755724MRI pelvis –extent of CD403415428441454MRI pelvis - change in therapy28633071328535063733Total number of small bowel MRI tests1033011014117191244413192Total number of pelvis MRI tests32673487371339474187Total MBS costs for small bowel MRI$7,236,726 $7,715,785 $8,209,311 $8,717,742 $9,241,528 Total MBS costs for pelvis MRI$1,481,516 $1,581,253 $1,684,001 $1,789,853 $1,898,901 MBS cost offsets small bowel MRI1 $2,147,426 $2,279,532 $2,415,627 $2,555,832 $2,700,272 MBS cost offsets pelvis MRI2$314,810 $336,003 $357,836 $380,329 $403,501 Reduction in surgical costs pelvis MRI$3,800,507 $4,056,358 $4,319,937 $4,591,475 $4,871,214 Total net MBS costs$6,256,006 $6,681,503 $7,119,849 $7,571,434 $8,036,656 Overall Net Government costs$2,455,500 $2,625,144 $2,799,912 $2,979,958 $3,165,442 CD= Crohn’s disease, complx = complications; MRI= magnetic resonance imagingReductions in consultations, CT, ultrasounds, small bowel follow throughReductions in consultations and endoanal ultrasounds. Sensitivity analyses were performed on virtually all estimates used in the model. Table 27 presents the key results for the first year and only for a selection of these analyses. The analyses presented are those with the most variation to the base results.Table 27: Sensitivity analyses of financial estimates (selected)Sensitivity AnalysesNet MBS costsNet All costsBase case $6,256,006 $2,455,500 % small bowel - low 31%$4,596,452 $795,945 % small bowel - high 65%$8,358,109 $4,557,602 % of pts requiring for small bowel CD assess low 15%$5,487,063 $1,686,556 % of pts requiring for small bowel CD assess high 25%$7,024,950 $ 3,224,444 Lower cost of MRI small bowel (by 20%)$5,154,028 $1,353,522 Number of tests per person per year: 0.75$4,613,302 $812,796 Number of tests per person per year: 1.5$9,541,415 $5,740,908 Number of tests per person per year: 2.0$12,826,823 $9,026,316 CD= Crohn’s disease, MRI = magnetic resonance imaging, pts=patientsAs shown in Table 27, the financial costs are highly driven by the number of tests expected per person per year. Variation in the proportions of patients using alternative imaging tests or the proportions of patients with Crohn’s disease presenting for the six indications did not materially change the base results, that is, costs varied within approximately ± $1 million. Similarly, most epidemiological indicators also did not change the results notably, with the exception of the proportion of patients with Crohn’s disease with small bowel disease (Table 27).Costs to the Medical Benefits Scheme (MBS) The proposed fee for MRI small bowel is $627.50 based on being similar in procedural complexity to MBS item 63473 for staging cervical cancer. For MRI pelvis, the proposed fee is $403.20 based on being similar in complexity to MBS #63482 (MRI for pancreas and biliary tree). For MRI enteroclysis in small bowel, the applicant proposes the fee $265.25 which is based on the cost of a nasojejunal tube $130 + procedure $135.25. The fees proposed seem appropriate.As shown in Table 26, the estimated net cost to the MBS for MRI for the proposed indications is $6.3 million in the first year and rising to $8.0 million by 2018. This includes cost savings for replaced MBS costs for CT, CTE, abdominal ultrasound and SBFT services. Costs to the Australian healthcare system overallTotal costs to the Australian health system, including MBS and hospital costs, resulted in net costs of $2.5 million in the first year to $3.2 million in 2018.Costs to the private health insurer and/or patientOur financial estimates have assumed that 15% of the Medicare scheduled fees for MRI will be made by the patient and/or their private health insurer. In reality, what the patient pays will depend on whether the radiologist decides to bulk bill, charge the scheduled fee or charge above the scheduled fee. Currently, some private health insurers cover MRI in their products but many do not. In MSAC application #1146.1, the average patient co-payment was $25.32 for each CT scan.Discussion Is it safe? MRI small bowel and pelvis for Crohn’s disease appears to be relatively safe compared with CT, SBFT, endoscopy, ultrasound and surgical examination. There were no studies reporting on the comparative safety of these alternatives however MRI is non-invasive, has clear contraindications in small number of patients and does not emit ionizing-radiation. Table 15 provides the annual effective ionizing radiation doses from studies that have followed patients with Crohn’s disease over long periods. The radiation received was largely attributable to CT radiation exposure. The effective radiation ranges were from 2.8 to 5.3 mSv (mean annually). Background exposure in Australia is 1.5 mSv per person per year. 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ADDIN EN.CITE.DATA (Desmond et al., 2008).In conclusion, imaging modalities of SBFT and CT emit ionizing radiation at low levels however the combined factors of Crohn’s disease requiring repeated tests, young adults and abdominal tissue, make the cumulative exposure potentially high over a lifelong disease course and may be harmful to health.Is it effective? The body of evidence included in this assessment was appraised using the NHMRC guidelines (NHMRC 2008). A summary of the body of evidence for the diagnostic accuracy of MRI small bowel or pelvis is presented in Table 28. It is important to note that Table 28 does not cover all six indications proposed in this application. There were no studies identified for the subgroup of pregnant women with suspected Crohn’s disease. There was poor quality evidence to assess change in management of disease following MRI for both small bowel and fistulising perianal Crohn’s disease.The evidence base was small but with two Level II accuracy studies, was considered satisfactory to address some of the research questions. Collectively, the studies reported consistent results showing high sensitivity and high specificity. Most authors concluded that MR enterography was equivalent to CT enterography at detecting extent and complications of Crohn’s disease. The factors that appear to be important in accurately detecting the many features of Crohn’s disease and its manifestations are the experience of the radiologist and magnet strength ADDIN EN.CITE <EndNote><Cite><Author>Wu</Author><Year>2013</Year><RecNum>3</RecNum><DisplayText>(Wu et al., 2013)</DisplayText><record><rec-number>3</rec-number><foreign-keys><key app="EN" db-id="5ww0vavvyz92p9ewfdqptwwwrrxxzfvdadas" timestamp="0">3</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Wu, Lian-Ming</author><author>Xu, Jian-Rong</author><author>Gu, Hai-Yan</author><author>Hua, Jia</author><author>Hu, Jiani</author></authors></contributors><titles><title>Is Magnetic Resonance Imaging a Reliable Diagnostic Tool in the Evaluation of Active Crohn’s Disease in the Small Bowel?</title><secondary-title>Journal of Clinical Gastroenterology</secondary-title></titles><periodical><full-title>J Clin Gastroenterol</full-title><abbr-1>Journal of clinical gastroenterology</abbr-1></periodical><pages>328-338 10.1097/MCG.0b013e31825d5034</pages><volume>47</volume><number>4</number><keywords><keyword>Crohn's disease</keyword><keyword>magnetic resonance imaging</keyword><keyword>small bowel</keyword><keyword>meta-analysis</keyword><keyword>00004836-201304000-00010</keyword></keywords><dates><year>2013</year></dates><isbn>0192-0790</isbn><urls><related-urls><url>;(Wu et al., 2013). Although, we cannot rule out a degree of selection bias in some Level III studies and the high level of study heterogeneity within the systematic reviews, the findings for sensitivity and specificity remained consistent. Table 28: Completed body of evidence assessment matrix Body of evidence (X axis)ABCDComponent (Y axis)ExcellentGoodSatisfactoryPoorEvidence baseOne or two level II studies with low risk of bias or a SR/multiple level III studies with low risk of bias ConsistencyMost studies consistent and inconsistency may be explainedClinical impactUnknown1GeneralisabilityPopulation/s studied in body of evidence different to target population for guideline but it is clinically sensible to apply this evidence to target population ApplicabilityProbably applicable to Australian healthcare context with some caveatsAdapted from ADDIN EN.CITE <EndNote><Cite><Author>NHMRC</Author><Year>2008</Year><RecNum>132</RecNum><DisplayText>(NHMRC, 2008a)</DisplayText><record><rec-number>132</rec-number><ref-type name="Electronic Source">12</ref-type><contributors><authors><author>NHMRC</author></authors></contributors><titles><title>NHMRC additional levels of evidence and grades for recommendations for developers of guidelines. Stage 2 consultation.</title></titles><number>11/03/08</number><dates><year>2008</year></dates><publisher>National Health and Medical Research Council, Australian Government</publisher><work-type>Internet</work-type><urls><related-urls><url>.au/consult/index.htm</url></related-urls></urls></record></Cite></EndNote>(NHMRC, 2008a)Relates to the impact of MRI small bowel and pelvis on patient outcomesThe diagnostic studies in this review did not examine any patient or clinical outcomes beyond test performance indicators. Therefore no links can be made to infer changes in management following MRI. Further research is required to determine the decisions of management in a well-designed study that improves upon the two studies assessing management patterns in this assessment PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DaGVyaXlhbjwvQXV0aG9yPjxZZWFyPjIwMTM8L1llYXI+
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ADDIN EN.CITE.DATA (Cheriyan et al., 2013, Sanka et al., 2012). We are unable to drawn clear conclusions about these results because they were largely descriptive studies only. Generalisability to the target population in this application is difficult to judge. This is because there were very few details provided on the study samples, for example, few studies reported the duration the patients had had Crohn’s disease, concomitant medication use or prior tests or other health indicators. On the few demographics (age and gender) that were reported across the studies, these appear to be close to those in two recent Australian studies PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5OZzwvQXV0aG9yPjxZZWFyPjIwMTM8L1llYXI+PFJlY051
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ADDIN EN.CITE.DATA (Ng et al., 2013, Wilson et al., 2010). Hampering the generalizability across populations are the small samples involved in all studies (less than 80 patients in all studies) and the high likelihood of patient heterogeneity. However, the scarcity of Australian research in Crohn’s disease may mean it is clinically sensible to apply this evidence to the target population.The applicability of the studies to the Australian healthcare context is unclear but may be acceptable. This is due to the US and European populations studied, the developed health care systems and high experience of radiologists involved in the studies. It is unknown if the MRI machines used in the study centres within the clinical studies are the same as those in use in Australia. The studies were all published within the last ten years, with the exception of Schwartz et al. 2001, and therefore it adds weight to the more advanced fast-scanning MRI machines now available.What are the economic considerations?Due to the superior performance of MRI pelvis found in a meta-analysis comparing it to endoanal ultrasound, one cost-utility analysis was performed on one of the six proposed indications in this application. However, the analysis is simple, short-term and relies heavily on a number of assumptions relating to the clinical impact of a false negative test.Subject to these simplifications and caveats, MRI pelvis was found to be a cost-effective strategy due to the potential for avoided surgical examination, which is relatively expensive, and may leave patients vulnerable to adverse surgical events. The financial impact of public funding for MRI small bowel and pelvis was estimated as the potential incremental costs to the MBS and wider health care system and included all the intended uses of MRI within this application. These analyses should be interpreted cautiously given the limited epidemiological data of Crohn’s disease and scarce utilisation data on the respective imaging strategies. The analyses drew on HESP advice, published evidence and two Australian epidemiological studies.The sensitivity analyses show that the strongest factor influencing the financial estimates to the MBS and wider health system is the mean number of MRIs that would be required by the eligible patients for the proposed indications. In the base case, the mean was one MRI per person annually. If surveillance of Crohn’s disease is the general intention of the MRI for small bowel and perianal disease, the number of times MRI is used will be the most important driver of costs to the MBS and wider health system. To a lesser degree, the estimated number of patients with Crohn’s in the small bowel was also a notable factor. Depending on the accuracy of this proportion, the base financial estimates could vary by ±$2 million in the first year.Conclusions Safety MRI appears to be a safe procedure and may be safer than CT, SBFT, endoscopy and surgical examination. This is because MRI is non-invasive, does not emit ionizing-radiation and presents no chemical or bodily harm to the patient. There are no studies to firmly establish the widely perceived comparative safety of MRI over the nominated comparators. The safety of MRI is unknown for pregnant women.Effectiveness Diagnostic accuracyMR enterography appears to have equivalent sensitivity and specificity compared with CT enterography for evaluation of established Crohn’s disease in the small bowel. For suspected or known fistulising perianal Crohn’s disease, MRI appears to have similar sensitivity and superior specificity compared with endoanal ultrasound or surgical examination.Impact on patient managementThe poor quality of evidence precludes firm conclusions about whether patients receive earlier or more appropriately targeted surgical or medical intervention following MRI. Further research is required on this specific topic.Impact on health outcomesNo evidence was identified to inform the direct or indirect links of MRI testing and patient health outcomes.Economic considerationsA cost-utility analysis was performed only for MRI pelvis for detecting fistulas and abscesses in fistulising perianal Crohn’s disease. The findings are exploratory and rely on some assumptions but in general suggest that MRI pelvis is cost-effective compared with endoanal ultrasound over a 12 month period.CostingThe expected uptake of MRI small bowel and pelvis is estimated at 13597 procedures for 13597 patients annually.The total cost to the Medical Benefits Scheme for MRI small bowel and pelvis is estimated to be $6.256 million annually.Total cost to the Australian healthcare system including MBS for MRI small bowel and pelvis is estimated to be $2.456 million annually.Appendix A Treatment algorithms for six proposed indicationsFigure A.1: Evaluation of disease extent at time of initial diagnosis of Crohn’s diagnosisFigure A.2: Evaluation of exacerbation/suspected complications of known Crohn’s diseaseFigure A.3: Evaluation of suspected Crohn’s disease in pregnancyFigure A.4: Assessment of change to therapy in patients with Crohn’s diseaseFigure A.5: Evaluation of pelvic sepsis and fistulas associated with established or suspected Crohn’s diseaseFigure A.6: Assessment of change to therapy in patients with pelvis sepsis and fistulas from Crohn’s diseaseAppendix BHealth Expert Standing Panel Members and EvaluatorsHealth Expert Standing Panel MembersMemberNomination / Expertise or AffiliationProfessor Richard MendelsonConsultant Radiologist, Royal Perth HospitalAssociate Professor Damien StellaDirector of CT, Dept of Radiology, Royal Melbourne Hospital, University of MelbourneEvaluatorsNameOrganisationLouisa GordonGriffith UniversityTracy ComansGriffith UniversityAppendix CSearch strategiesMEDLINE Ovid MEDLINE (1946 to present with Daily Update) Search Date: 7/11/13No.Search termResults1Crohn*389112enteritis125313enterocolitis134154small bowel248915pelvic sepsis3316fistula*8411571 or 2 or 36247384 or 5 or 610808097 and 8593910magnetic resonance50403811MRI13150512MRE10451310 or 11 or 12524321149 and 1346715Limit 14 to (English language and humans and (clinical trial, all or comparative study or controlled clinical trial or evaluation studies or randomized controlled trial or systematic reviews)11416fistulising80177 and 166818perianal46471918 and 171220Limit 19 to (English language and humans and (clinical trial, all or comparative study or controlled clinical trial or evaluation studies or randomized controlled trial or systematic reviews)1115 citations exported into Word files for further filtering. Titles & abstracts read for relevance (1st screen).Excluded: 73ResultsDuplicates5Included in systematic reviews4Wrong or no comparator29Wrong disease6Wrong intervention20Wrong purpose2Wrong study type742 articles downloaded for relevance (PDFs retrieved)Excluded: 30ResultsLess than 20 patients with CD3All IBD, CD not differentiated 2Included in systematic reviews3Wrong comparator11Wrong intervention2Wrong purpose or outcome5Wrong study type1Insufficient outcome data2Study superseded by later study1Final numbers: 12 studies - 3 systematic reviews, 9 clinical studies.The Cochrane LibrarySearch Date: 15/11/13No.Search termResults1Crohn* ti: ab,kw in Cochrane Reviews (Reviews only), Trials, Technology Assessments and Economic Evaluations12212enteritis3133enterocolitis8324small bowel20575pelvic sepsis1566fistula*152771 or 2 or 3231784 or 5 or 6351397 and 8555810magnetic resonance759511MRI375312MRE181310 or 11 or 128461149 and 13 in Cochrane Reviews (Reviews only), Trials, Technology Assessments and Economic Evaluations1471514 and 11916fistulising10177 and 16418perianal2821918 and 17121 retrieved for filtering, 9 duplicates (from MEDLINE search), 12 new hitsExcluded: 9Wrong comparator3Wrong intervention6Included: 33 for further full text filtering – all includedGrand 2012, Cipriano 2012 ec econ, Levesque 2012 ec econClinical trials registers:# hitsRelevantCurrent Controlled Trialscontrolled- 131 (duplicate)Australian New Zealand Clinical Trials Registry .au 00WHO International Clinical Trials Registry Platform 60HTA Agencies:#hitsRelevantCentres for Reviews and Dissemination Network of Agencies for Health Technology Assessment (INAHTA) DStudies included in the review Study profiles of included systematic reviewsAuthor/YearObjective of reportNumber and publication datesPopulation considered in included studies, Test comparison Conclusions/recommendationQuality assessmentWu et al (2013)To evaluate the overall diagnostic accuracy of MRI is assessing the activity of CD in the small bowel.17 studies (n=725 patients)Search methods: Publications from Jan 2001 to Sept 2011 were selected from MEDLINE, EMBASE and other electronic databases.Studies were included if MRI was used to assess active CD in the small bowel, 9/14 QUADAS criteria were fulfilled for methodological quality, sufficient raw data were reported, studies applied histopathologic and ileocolonoscopy assessment as referent standard, >10 patients.Mean age range 8 to 77 yearsPatients in which MR can be used to evaluate active CD.Test: MRComparator: NoneReferent: Ileocolonoscopy and histopathologic assessment.MRI has high sensitivity and specificity for diagnosis of active CD in the small bowel and is a suitable modality for imaging and surveillance of active CD.HIGH QUALITYWas the research question specified? YesWas the search strategy explicit and comprehensive? YesWere the eligibility criteria explicit and appropriate? YesWas a quality assessment of included studies undertaken? YesWere the methods of the study appraisal reproducible? YesWere sources of heterogeneity explored? YesWas a summary of the main results clear and appropriate? YesMeta-analysis pooled results: Sensitivity 0.87 (95%CI: 0.77, 0.93) I2 = 0.98 (strong evidence of significant heterogeneity)Specificity 0.91 (95%CI: 0.81, 0.96) Overall AUC(ROC) 0.95 (95%CI: 0.93, 0.97)Authors conclusions: Results showed MRI had good diagnostic accuracy and good clinical utilityUsing meta-regression analyses, magnet strength and experience of the radiologist were the most important variables influencing mon weaknesses in the included studies were whether interpretation of pathology was blinded from MRI. Funnel plot asymmetry tests showed no major publication bias.Author/YearObjective of reportNumber and publication datesPopulation considered in included studies, Test comparison Conclusions/recommendationQuality assessmentSiddiqui et al (2012)To undertake a systematic review to compare endoanal ultrasound or MRI for perianal fistulas in Crohn’s disease.4 studies (n=113 patients)Search methods: Publications from Jan 1970 to Oct 2010 were selected from MEDLINE, EMBASE and other electronic databases.Studies were included if they compared MRI with endoanal ultrasound for patients with suspected perianal fistulas. Excluded if the surgical standard was not applied.Mean age range 17 to 76 yearsTest: MRComparator: Endoanal ultrasoundReferent: Examination under anaesthetic MRI has similar sensitivity to endoanal ultrasound but may have better specificity for identifying the presence of perianal fistulas in CD. Small number of studies and high heterogeneity between studies precludes any firm conclusions.HIGH QUALITYWas the research question specified? YesWas the search strategy explicit and comprehensive? YesWere the eligibility criteria explicit and appropriate? YesWas a quality assessment of included studies undertaken? Yes (QUADAS used and reported)Were the methods of the study appraisal reproducible? YesWere sources of heterogeneity explored? YesWas a summary of the main results clear and appropriate? YesMeta-analysis pooled results for fistula detection: MRISensitivity 0.87 (95%CI: 0.63, 0.96) I2 = 0.93 (strong evidence of significant heterogeneity)Specificity 0.69 (95%CI: 0.51, 0.82) Endoanal ultrasoundSensitivity 0.87 (95%CI: 0.70, 0.95) I2 = 0.92 (strong evidence of significant heterogeneity)Specificity 0.43 (95%CI: 0.21, 0.69) Authors conclusions: Results showed MRI had comparable sensitivity and possibly better specificity for identifying fistulas. Findings are important because when clinicians can understand the fistula, it can assist with sphincter preservation and adequate mon weaknesses in the included studies were whether blinding occurred at the time of endoanal ultrasound and the different use of standard tests (most were examination under anaesthetic) but one included the index test into the overall outcomes (incorporation bias). Some time delay may be problematic in some studies. Overall quality of QUADAS assessments were ‘good’.Author/YearObjective of reportNumber and publication datesPopulation considered in included studies, Test comparison Conclusions/recommendationQuality assessmentPanes et al (2011)To undertake a systematic review to compare ultrasound, CT and MRI for diagnosis, assessment of activity and complications of Crohn’s disease.68 studiesSearch methods: Publications from Jan 1994 to Dec 2010 were selected from MEDLINE, EMBASE.Studies were included if they compared MR ± ultrasound ± CT, had an adequate reference standard, prospective design, data allowed for calculation of sensitivity / specificity etc. No additional formal quality assessment was performed.Mean age range – not clearTest: MR, CT, ultrasoundComparator: Not clear (Few studies included direct comparisons of imaging tests, most were single test with a referent) Referent: Either ileocolonoscopy, capsule endoscopy, enteroscopy, surgery, pathology. Cross sectional imaging techniques have high accuracy for evaluation of CD, reliably measure complications and disease severity. Lack of established reference standard and small sample sizes in the included studies precludes any firm conclusions.Many studies use different definitions of disease parameters.LOW QUALITYWas the research question specified? YesWas the search strategy explicit and comprehensive? YesWere the eligibility criteria explicit and appropriate? YesWas a quality assessment of included studies undertaken? NoWere the methods of the study appraisal reproducible? UnclearWere sources of heterogeneity explored? N/AWas a summary of the main results clear and appropriate? NoDirect comparison of different imaging techniques for assessment of location and extent of inflammatory lesions in CD (one relevant study Fiorino et al. 2011)MRI: Sensitivity 0.88 Specificity 0.88 CT: Sensitivity 0.88 Specificity 0.88 Direct comparison of different imaging techniques for detection of activity in CD (4 relevant studies: Fiorino 2011, Lee 2009, Siddiki 2009, Low 2000)(Ranges presented – unpooled) MRI: Sensitivity 0.80-0.91 Specificity 0.67-1.00 CT: Sensitivity 0.60-0.95 Specificity 0.80-1.00 Direct comparison of different imaging techniques for assessment of severity in CD (1 relevant study: Pascu 2004)MRI no luminal contrast vs ultrasound: ultrasound showed better correlation with endoscopic findings (r>0.80) than MRI (r>0.50)Direct comparison of different imaging techniques for assessment of stenosis in CD (1 relevant study Fiorino et al. 2011)MRI: Sensitivity 0.92 Specificity 0.90 CT: Sensitivity 0.85 Specificity 1.00 Direct comparison of different imaging techniques for assessment of fistulas and abscesses in CD (1 relevant study Lee et al. 2011)MRI: Sensitivity 1.00 Specificity 1.00 CT: Sensitivity 1.00 Specificity 1.00 Study profiles of included clinical studies on diagnostic accuracy and change in managementAuthor/Year/Country Setting/ NStudy objective and designStudy populationResults Quality assessmentCheriyan et al (2012)Ireland, single centreN=57Objective: To determine whether MR enterography influenced the medical an surgical management of patients with small bowel CDStudy design:Retrospective, consecutiveTiming: 01/2007-12/2010Index test: MR enterographyComparator test: n/aTiming interval: n/aReference test: n/aTest interpretation: MR enterography evaluated by one radiologist with expertise in gastrointestinal imaging.Inclusion/exclusion criteriaInclusion: histologically confirmed CD, underwent MR enterography for symptom and disease assessment Exclusion: Management options not clearly stated after MR enterography, or occurred after 1 month of MR enterographyPatient characteristics:Age/Gender: 47% male, median age 36 years (range 16-68), prior surgery 39 (68%)Length of time with Crohn’s disease: 9.5 years (range 1 – 35)Prior tests: Not statedClinical characteristics:Symptoms not stated68% had previous surgeryChange in management7 patients had normal MR enterography50 patients had abnormal MR enterography (5 stricturing, 17 active, 14 both active and structuring)6/7 patients with normal MR enterography had no change in management42 patients had a change in management, 22 (53%) had medical intervention and 20 (47%) underwent surgery.Conclusion: High clinical impact on patient management. Patients with abnormal imaging had significantly more changes in management both surgical and medical.NHMRC level of evidence: IVQuality: Q3 POOR Comparison: C1: other comparison (no comparison)Applicability: P2 limited (unclear)QUADASProspective: noConsecutive: unclear/yesExplicit selection criteria: yesReference standard: n/aTest interval in days/weeks: n/aTests and ref std well described/reproducible: yesTests assessed and independent of ref std: n/aRef std assessed and blinded to other tests: n/aRoutine clinical data available: yesUninterpretable/intermed results reported: noStudy withdrawals explained: n/aSufficient data for 2x2 table: n/aRelevant population: yesApplicable comparator: n/aApplicable intervention: yesSanka et al (2012)England, single centreN=34Objective: To report on the outcomes of performing magnetic resonance enteroclysis in the diagnosis and management of children with inflammatory bowel disease. Study design:RetrospectiveTiming: 09/2008-11/2010Index test: MR enteroclysis. Previous afternoon upper endoscopy to place naso-jejunal parator test: n/aTiming interval: n/aReference test: n/aTest interpretation: MR enteroclysis evaluated by one radiologist with expertise in gastrointestinal imaging.Inclusion/exclusion criteriaInclusion: confirmed or suspected CD or ulcerative colitisExclusion: not statedPatient characteristics:Age/Gender: 45% male, mean age 15.3 years, CD confirmed in 19 patientsLength of time with Crohn’s disease: not statedPrior tests: Not statedClinical characteristics:Symptoms not statedConfirming a diagnosis8 normal MRE – patients discharged1 normal MRE – no changesChanges in management2 patients commenced azathioprine7 patients commenced infliximab, 4 had ileo-caecal resection, adalimumab in 3 patients, 1 patient referred to psychological support, 6 patients for complx, 5 normal and continued current management, 1 significant complx, Other – one underwent surgery, one patient commenced methotrexateLimitations in use of MR enterocylsis2 patients did not complete MR enterogclysis (1 extreme discomfort from stricture, 1 claustrophobia)NHMRC level of evidence: IVQuality: Q3 POOR Comparison: C1: other comparison (no comparison)Applicability: P2 limited (unclear)QUADASProspective: noConsecutive: unclear/yesExplicit selection criteria: yesReference standard: n/aTest interval in days/weeks: n/aTests and ref std well described/reproducible: yesTests assessed and independent of ref std: n/aRef std assessed and blinded to other tests: n/aRoutine clinical data available: yesUninterpretable/intermed results reported: noStudy withdrawals explained: yesSufficient data for 2x2 table: n/aRelevant population: yesApplicable comparator: n/aApplicable intervention: yesMalgras et al (2012)France, single centreN=52Objective: To determine and compare the diagnostic accuracy of MR enterography and CT enterocylsis for detecting extent of disease and predicting operative approach.Study design:RetrospectiveTiming: 01/2006 - 11/2010Index test: MR enterographyComparator test: CT enteroclysis(Patients received either the index or comparator test)Timing interval: immediately after each other in alternating orderReference test: surgical exam and pathology Test interpretation: One radiologist and one abdominal surgeon in consensus. Separate assessment of reference standard blinded to index and comparator tests.Inclusion/exclusion criteriaInclusion: patients with established CD recommended for surgeryExclusion: Imaging tests undergone within 3 months of operation, not presented with CD (e.g. peritonitis, gastrointestinal bleeding).Patient characteristics:Age/Gender: 56% male, mean age 37, range 18-69 years. Length of time with Crohn’s disease: Mean duration of medical treatment for CD 9.5 yearsPrior tests: videocolonoscopyClinical characteristics:33% patients already had surgery for CDAll patients received medications for CD.Test AccuracyLesions presentMR - Sensitivity 1.00 (95%CI: 0.92, 1.00)CT - Sensitivity 0.93 (95%CI: 0.82, 0.99)No significant difference between sensitivity between two imaging tests (p=0.242).Joint sensitivity of imaging for stenosis, abscesses and fistulas reported only.Impact on operative approachImaging allowed correct estimation of disease in 49/52 patients 94% (95%CI: 84%-99%). Discrepancy in 3/52 patients in pre-op imaging and actual operative approach.Open laparotomy 34 (65%) and laparoscopic approach in 18 (35%) NHMRC level of evidence: IVQuality: Q3 POOR Comparison: CX: other comparisonApplicability: P1 applicableQUADASProspective: noConsecutive: unclearExplicit selection criteria: noReference standard: surgical exam and pathologyValid: yesApplied to all patients: YesTest interval in days/weeks: Comparator: n/a patients received either index or comparator testRef std: not statedTests and ref std well described/reproducible: yesTests assessed and independent of ref std: yesRef std assessed and blinded to other tests: noRoutine clinical data available: yesUninterpretable/intermed results reported: unclearStudy withdrawals explained: n/aSufficient data for 2x2 table: noRelevant population: yesApplicable comparator: yesApplicable intervention: yesJensen et al (2011)Denmark, multicentreN=50Objective: To determine and compare the diagnostic accuracy of MR enterography and CT enterography for detection of small bowel lesions with emphasis on stenosesStudy design:ProspectiveTiming: 10/2007-08/2009Index test: MR enterographyComparator test: CT enterographyTiming interval: immediately after each other in alternating orderReference test: surgical exam ± enteroscopy or ileoscopyTest interpretation: Endoscopists blinded to results of MR enterography and CT enterography. Separate radiologists (>10 yrs experience) were randomly assigned to assess MR enterography or CT enterography,blinded to other imaging.Inclusion/exclusion criteriaInclusion: >=15 years, established CD based upon endoscopic, histological, radiological and surgical findings, symptomatic patients requiring assessment to change treatment strategyExclusion: acute bowel obstruction, elevated serum-creatinine, severe claustrophobia, cardiac pacemaker, implanted magnetic foreign bodies, pregnancy, lactation.Patient characteristics:Age/Gender: 26% male, median age 39 Length of time with Crohn’s disease: Median 10 yearsPrior tests: As aboveClinical characteristics:Abdominal pain n=48Diarrhea n= 32Weight loss >3 kg n=14Fever n=3Test AccuracyDetection of disease activity:MR enterographySensitivity: 74% (CI: 57%-88%) Specificity: 80% (CI: 44%-98%) PPV: 93% (CI: 77%-99%) NPV: 47% (CI: 23%-72%)CT enterographySensitivity: 83% (CI: 66%-93%) Specificity: 70% (CI: 35%-93%) PPV: 91% (CI: 75%-98%) NPV: 54% (CI: 25%-81%)Prevalence of CD: 78%Detection of small bowel stenosis:MR enterographySensitivity: 55% (CI: 32%-77%) Specificity: 92% (CI: 74%-99%) PPV: 85% (CI: 55%-98%) NPV: 72% (CI: 53%-86%)CT enterographySensitivity: 70% (CI: 46%-88%) Specificity: 92% (CI: 74%-99%) PPV: 88% (CI: 62%-98%) NPV: 79% (CI: 60%-92%)Prevalence of stenosis: 44%NHMRC level of evidence: IIQuality: Q1 HIGH Comparison: C1: direct comparisonApplicability: P1 applicableQUADASProspective: yesConsecutive: unclearExplicit selection criteria: yesReference standard: surgical exam or ileoscopyValid: yesApplied to all patients: No (5 did not receive it)Test interval in days/weeks: Comparator: 51 minutes (range 34-91)Ref std: surgical exam or ileoscopy performed mean 51 days (range 3-211)Tests and ref std well described/reproducible: yesTests assessed and independent of ref std: yesRef std assessed and blinded to other tests: yesRoutine clinical data available: yesUninterpretable/intermed results reported: noStudy withdrawals explained: yes (2 because interval between tests were too long ,75-84 days)Sufficient data for 2x2 table: yesRelevant population: yesApplicable comparator: yesApplicable intervention: yesIppolito et al (2010)Italy, single centreN=29Objective: To assess the agreement between MR enterography and CT enterography in assessing extent of small bowel CD in patients Study design:ProspectiveTiming: Not statedIndex test: MR enterographyComparator test: CT enterographyTiming interval: immediately after each other Reference test: noneTest interpretation: 1 radiologist all with >10 yrs experience. Inclusion/exclusion criteriaInclusion: known CD biopsyproven with clinical suspicion of relapse, CD Activity Index >150, and at least one elevated acute phase reactant(erythrocyte sedimentation rate or C-reactiveprotein active > 5 mg/dL). Exclusion:contraindications for MRI (electrically, magnetically,or mechanically activated devices; central nervoussystem hemostasia clips, or the inability to administer agadolinium contrast agent because of known allergicproblems), pregnancy, renal insufficiency, and documented adverse reaction to iodinated contrast materialPatient characteristics:Age/Gender: 69% male, CD confirmed, age 14-70 yearsLength of time with Crohn’s disease: Median 10 yearsPrior tests: Not stated.Clinical characteristics:Not statedTest Agreement study (no referent)Detection of disease activity:100% agreement 19 MR enterography and CT enterography positive, 100% agreement 10 MR enterography and CT enterography negative Cohen’s kappa =1.0Detection of fistulasMR enterography and CT enterography both positive=2, MR enterography positive, CT enterography negative = 3MR enterography negative, CT enterography positive = 0MR enterography and CT enterography both negative = 24Cohens kappa = 0.52 (CI 0.08-0.97)No patient was found to have abscesses.MR enterography and CT enterography have a similar accuracy in the identification of active CD in small bowel. These findings show MR enterography is more accurate in detection of enteric fistulas and sinus tracts than CT enterography.NHMRC level of evidence: IVQuality: Q3 POOR Comparison: C1: direct comparisonApplicability: P1 applicableQUADAS n/aProspective: yesConsecutive: yesExplicit selection criteria: yesReference standard: noTest interval in days/weeks: not statedTests and ref std well described/reproducible: yesTests assessed and independent of ref std: n/aRef std assessed and blinded to other tests: n/aRoutine clinical data available: yesUninterpretable/intermed results reported: noStudy withdrawals explained: yes (2 because interval between tests were too long ,75-84 days)Sufficient data for 2x2 table: no (no referent)Relevant population: yesApplicable comparator: yesApplicable intervention: yesSchmidt et al (2010)Switzerland, single centreN=57Objective: To assess the agreement between MR enterography and CT enterography in assessing extent of small bowel CD in patients Study design:ProspectiveTiming: Not statedIndex test: MR enterographyComparator test: CT enterographyTiming interval: < 24 hoursReference test: Composite of surgery, endoscopy and long-term follow-upTest interpretation: 3 radiologists, independent and blind assessmentsInclusion/exclusion criteriaInclusion: histologically proven CD, emergency presentation for acute exacerbation Exclusion:contraindications for MRI acute or chronic renal failure, lack of proof of CDPatient characteristics:Age/Gender: 69% male, CD confirmed, mean age 33.5 range (17-69 years)Length of time with Crohn’s disease: Median 10 yearsPrior tests: Not stated.Clinical characteristics:Not statedTest AccuracyBowel wall thickeningMR enterographySensitivity: 84% Specificity: 91% CT enterographySensitivity: 93% Specificity: 67% FistulaMR enterographySensitivity: 86% Specificity: 93% CT enterographySensitivity: 89% Specificity: 98% AbscessMR enterographySensitivity: 79% Specificity: 99% CT enterographySensitivity: 83% Specificity: 97%NHMRC level of evidence: IVQuality: Q2 MEDIUM Comparison: CX: other comparisonApplicability: P1 applicableQUADASProspective: yesConsecutive: yesExplicit selection criteria: yesReference standard: compositeValid: yesApplied to all patients: yesTest interval in days/weeks: Comparator: same dayRef std: not statedTests and ref std well described/reproducible: yesTests assessed and independent of ref std: noRef std assessed and blinded to other tests: noRoutine clinical data available: yesUninterpretable/intermed results reported: noStudy withdrawals explained: noneSufficient data for 2x2 table: yesRelevant population: yesApplicable comparator: yesApplicable intervention: yesSchreyer et al (2010)Germany, single centreN=53Objective: To assess the diagnostic value CT (contrast-enhanced) and MR enterography in evaluation of small bowel Crohn’s disease in an emergency setting. Study design:Retrospective, consecutiveTiming: 01/2006 – 05/2008Index test: Multi-detector CT(contrast orally and rectally and intravenously)Comparator test: MRI enterographyTiming interval: CT and MR within 2 days. CT performed first in all patients.Reference test: noneTest interpretation: 2 radiologists with 3 and 7 years experience, consensus readingInclusion/exclusion criteriaInclusion: known CD, patients presenting to the emergency department with acute abdominal pain Exclusion: Not statedPatient characteristics:Age/Gender: 57% Male, age range 18-73 years, median 37 years, most patients were ill with advanced CDLength of time with Crohn’s disease: Not statedPrior tests: Not stated.Clinical characteristics:Not statedTest Agreement study (no referent)MRIDetection of disease activity:Jejunum 32/53 (60%)Ileum 47/53 (89%)Terminal Ileum 49/53 (92%)Detection of complicationsFistulas 27/53 (51%)Abscess 32/53 (60%)Enlarged lymph nodes >1cm 37/53 (70%)CTDetection of disease activity:Jejunum 32/53 (60%)Ileum 46/53 (87%)Terminal Ileum 49/53 (92%)Detection of complicationsFistulas 25/53 (47%)Abscess 32/53 (60%)Enlarged lymph nodes >1cm 49/53 (92%)CT significantly superior to MRI for detecting enlarged lymph nodes (p<0.001).Conclusion: Patients with advanced CD presenting with acute abdominal pain may be sufficiently assessed with CT.NHMRC level of evidence: IVQuality: Q3 POOR Comparison: C1: direct comparisonApplicability: P2 limitedQUADAS n/aProspective: noConsecutive: yesExplicit selection criteria: noReference standard: n/aTest interval in days/weeks: 2 daysTests and ref std well described/reproducible: yesTests assessed and independent of ref std: n/aRef std assessed and blinded to other tests: n/aRoutine clinical data available: not statedUninterpretable/intermed results reported: noStudy withdrawals explained: not statedSufficient data for 2x2 table: noOverall Ranking: n/aRelevant population: yesApplicable comparator: yesApplicable intervention: yesSchwartz et al (2001)USA, single centreN= 34Objective: To determine accuracy of endoscopic ultrasound and MRI in detection of perianal fistulas in CD Study design:Prospective, diagnostic accuracy studyTiming: 07/1999-09/2000Index test: pelvic MR Comparator tests: endoscopic ultrasound, surgical examination under anaesthesiaTiming interval: not statedReference test: Consensus of combined three tests above.Test interpretation: Triple blind comparisons, 3 physicians. 85% accuracy with consensus reference was considered clinically usefulInclusion/exclusion criteriaInclusion: Patients with CD and suspected perianal fistulas. Exclusion: Pregnancy, contraindicated to pelvic MRI (implanted metal devices), those in need of immediate abdominal surgery for active gastrointestinal bleeding, obstruction, or intra-abdominal abscess, severe anal stenosis that precluded endoscopy.Patient characteristics:Age/Gender: 50% male, mean age 36 (age range 18-70 years)Length of time with Crohn’s disease: Not stated. Prior tests: No other preoperative imagingClinical characteristics:65% immunosuppressive therapy, 41% infliximab or antiTNF, 56% antibiotics18 (53%) patients had undergone previous surgery for perianal diseaseTest AccuracyN=32 available for analysis2 withdrew: 1 claustrophobia, 1 immediate surgeryRectal endoscopic ultrasound correct in 29/32 91% (CI 75%-98%)Pelvic MRI correct in 26/30 87% (CI 69%-96%)Surgical exam correct in 29/32 91% (CI 75%-98%)NHMRC level of evidence: IIQuality: Q3 POOR Comparison: CI: direct comparisonApplicability: P1 applicableQUADASProspective: yesConsecutive: unclearExplicit selection criteria: yesReference standard: endoscopyValid: no (includes index test)Applied to all patients: yesTest interval in days/weeks: Comparator: not statedRef std: not statedTests and ref std well described/reproducible: yesTests assessed and independent of ref std: yesRef std assessed and blinded to other tests: yesRoutine clinical data available: noUninterpretable/intermed results reported: noStudy withdrawals explained: yesSufficient data for 2x2 table: yesRelevant population: yesApplicable comparator: noApplicable intervention: yesAppendix EExcluded studiesIncorrect comparatorSinha R, Murphy P, et al. Diagnostic accuracy of high-resolution MR enterography in Crohn's disease: Comparison with surgical and pathological specimen. Clinical Radiology. 2013;68:917-27.Neubauer H, Pabst T, et al. Small-bowel MRI in children and young adults with Crohn disease: retrospective head-to-head comparison of contrast-enhanced and diffusion-weighted MRI. Pediatr Radiol. 2013;43:103-14.Wiarda BM, Mensink PB, et al. Small bowel Crohn's disease: MR enteroclysis and capsule endoscopy compared to balloon-assisted enteroscopy. Abdom Imaging. 2012;37:397-403.Sauer CG, Middleton JP, et al. Comparison of magnetic resonance enterography with endoscopy, histopathology, and laboratory evaluation in pediatric Crohn disease. J Pediatr Gastroenterol Nutr. 2012;55:178-84.Zappa M, Stefanescu C, et al. Which magnetic resonance imaging findings accurately evaluate inflammation in small bowel Crohn's disease? A retrospective comparison with surgical pathologic analysis. 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Comparison of MR enteroclysis with colonoscopy in Crohn's disease--first locust bean gum study from Turkey. Saudi J Gastroenterol. 2009;15:253-7.Crook DW, Knuesel PR, et al. Comparison of magnetic resonance enterography and video capsule endoscopy in evaluating small bowel disease. Eur J Gastroenterol Hepatol. 2009;21:54-65.Tillack C, Seiderer J, et al. Correlation of magnetic resonance enteroclysis (MRE) and wireless capsule endoscopy (CE) in the diagnosis of small bowel lesions in Crohn's disease. Inflamm Bowel Dis. 2008;14:1219-28.Negaard A, Sandvik L, et al. MRI of the small bowel with oral contrast or nasojejunal intubation in Crohn's disease: randomized comparison of patient acceptance. Scand J Gastroenterol. 2008;43:44-51.Masselli G, Casciani E, et al. Comparison of MR enteroclysis with MR enterography and conventional enteroclysis in patients with Crohn's disease. Eur Radiol. 2008;18:438-47.Malago R, Manfredi R, et al. 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A meta-analysis of the yield of capsule endoscopy compared to other diagnostic modalities in patients with non-stricturing small bowel Crohn's disease. Am J Gastroenterol. 2006;101:954-64.Masselli G, Vecchioli A, Gualdi GF. Crohn disease of the small bowel: MR enteroclysis versus conventional enteroclysis. Abdom Imaging. 2006;31:400-9.Maccioni F, Bruni A, et al. MR imaging in patients with Crohn disease: value of T2- versus T1-weighted gadolinium-enhanced MR sequences with use of an oral superparamagnetic contrast agent. Radiology. 2006;238:517-30.Gourtsoyiannis NC, Grammatikakis J, et al. Imaging of small intestinal Crohn's disease: comparison between MR enteroclysis and conventional enteroclysis. Eur Radiol. 2006;16:1915-25.Golder SK, Schreyer AG, et al. Comparison of capsule endoscopy and magnetic resonance (MR) enteroclysis in suspected small bowel disease. Int J Colorectal Dis. 2006;21:97-104.Frokjaer JB, Larsen E, et al. Magnetic resonance imaging of the small bowel in Crohn's disease. Scand J Gastroenterol. 2005;40:832-42.Albert JG, Martiny F, et al. Diagnosis of small bowel Crohn's disease: a prospective comparison of capsule endoscopy with magnetic resonance imaging and fluoroscopic enteroclysis. Gut. 2005;54:1721-7.Schreyer AG, Geissler A, et al. Abdominal MRI after enteroclysis or with oral contrast in patients with suspected or proven Crohn's disease. Clin Gastroenterol Hepatol. 2004;2:491-7.Darbari A, Sena L, et al. Gadolinium-enhanced magnetic resonance imaging: a useful radiological tool in diagnosing pediatric IBD. Inflamm Bowel Dis. 2004;10:67-72.Potthast S, Rieber A, et al. Ultrasound and magnetic resonance imaging in Crohn's disease: a comparison. Eur Radiol. 2002;12:1416-22.Neurath MF, Vehling D, et al. Noninvasive assessment of Crohn's disease activity: a comparison of 18F-fluorodeoxyglucose positron emission tomography, hydromagnetic resonance imaging, and granulocyte scintigraphy with labeled antibodies. Am J Gastroenterol. 2002;97:1978-85.Madsen SM, Thomsen HS, et al. Inflammatory bowel disease evaluated by low-field magnetic resonance imaging. Comparison with endoscopy, 99mTc-HMPAO leucocyte scintigraphy, conventional radiography and surgery. Scand J Gastroenterol. 2002;37:307-16.Beall DP, Fortman BJ, et al. Imaging bowel obstruction: a comparison between fast magnetic resonance imaging and helical computed tomography. Clin Radiol. 2002;57:719-24.Rieber A, Aschoff A, et al. MRI in the diagnosis of small bowel disease: use of positive and negative oral contrast media in combination with enteroclysis. Eur Radiol. 2000;10:1377-82.Halligan S, Bartram CI. MR imaging of fistula in ano: are endoanal coils the gold standard? AJR Am J Roentgenol. 1998;171:407-12.deSouza NM, Gilderdale DJ, et al. MRI of fistula-in-ano: a comparison of endoanal coil with external phased array coil techniques. J Comput Assist Tomogr. 1998;22:357-63.Anderson CM, Brown JJ, et al. MR imaging of Crohn disease: use of perflubron as a gastrointestinal contrast agent. J Magn Reson Imaging. 1994;4:491-6.Data duplicated in another studyLasocki A, Pitman A, et al. Relative efficacy of different MRI signs in diagnosing active Crohn's disease, compared against a histological gold standard. J Med Imaging Radiat Oncol. 2011;55:11-9.Fiorino G, Bonifacio C, et al. Prospective comparison of computed tomography enterography and magnetic resonance enterography for assessment of disease activity and complications in ileocolonic Crohn's disease. Inflamm Bowel Dis. 2011;17:1073-80.Siddiki HA, Fidler JL, et al. Prospective comparison of state-of-the-art MR enterography and CT enterography in small-bowel Crohn's disease. AJR Am J Roentgenol. 2009;193:113-21.Lee SS, Kim AY, , et al. Crohn disease of the small bowel: comparison of CT enterography, MR enterography, and small-bowel follow-through as diagnostic techniques. Radiology. 2009;251:751-61.Masselli G, Brizi MG, et al. Magnetic Resonance Enteroclysis imaging of Crohn's. Radiol Med. 2005;110:221-33.Ochsenkuhn T, Herrmann K, et al. Crohn disease of the small bowel proximal to the terminal ileum: detection by MR-enteroclysis. Scand J Gastroenterol. 2004;39:953-60.Laghi A, Borrelli O, et al. Contrast enhanced magnetic resonance imaging of the terminal ileum in children with Crohn's disease. Gut. 2003;52:393-7.Low RN, Francis IR, et al. Crohn's disease evaluation: comparison of contrast-enhanced MR imaging and single-phase helical CT scanning. J Magn Reson Imaging. 2000;11:127-35.Incorrect interventionde la Portilla F, Alba F, et al. Expanded allogeneic adipose-derived stem cells (eASCs) for the treatment of complex perianal fistula in Crohn's disease: results from a multicenter phase I/IIa clinical trial. Int J Colorectal Dis. 2013;28:313-23.Di Nardo G, Oliva S, , et al. Usefulness of single-balloon enteroscopy in pediatric Crohn's disease. Gastrointest Endosc. 2012;75:80-6.Savoye-Collet C, Savoye G, et al. Fistulizing perianal Crohn's disease: contrast-enhanced magnetic resonance imaging assessment at 1 year on maintenance anti-TNF-alpha therapy. Inflamm Bowel Dis. 2011;17:1751-8.Roumeguere P, Bouchard D, et al. Combined approach with infliximab, surgery, and methotrexate in severe fistulizing anoperineal Crohn's disease: results from a prospective study. Inflamm Bowel Dis. 2011;17:69-76.Muhlmann MD, Hayes JL, et al. Complex anal fistulas: plug or flap? ANZ J Surg. 2011;81:720-4.Di Nardo G, Oliva S, , et al. Usefulness of wireless capsule endoscopy in paediatric inflammatory bowel disease. Dig Liver Dis. 2011;43:220-4.Ciccocioppo R, Bernardo ME, et al. Autologous bone marrow-derived mesenchymal stromal cells in the treatment of fistulising Crohn's disease. Gut. 2011;60:788-98.Neye H, Ensberg D, et al. Impact of high-resolution transabdominal ultrasound in the diagnosis of complications of Crohn's disease. Scand J Gastroenterol. 2010;45:690-5.Grimaud JC, Munoz-Bongrand N, et al. Fibrin glue is effective healing perianal fistulas in patients with Crohn's disease. Gastroenterology. 2010;138:2275-81, 81.e1.Echarri A, Castro J, et al. Evaluation of adalimumab therapy in multidisciplinary strategy for perianal Crohn's disease patients with infliximab failure. J Crohns Colitis. 2010;4:654-60.Dionisio PM, Gurudu SR, et al. Capsule endoscopy has a significantly higher diagnostic yield in patients with suspected and established small-bowel Crohn's disease: a meta-analysis. Am J Gastroenterol. 2010;105:1240-8.Higashi D, Futami K, et al. Infliximab treatment for anal fistula in patients with Crohn's disease. Anticancer Res. 2009;29:927-33.Maconi G, Ardizzone S, et al. Transperineal ultrasound in the detection of perianal and rectovaginal fistulae in Crohn's disease. Am J Gastroenterol. 2007;102:2214-9.van der Hagen SJ, et al. Long-term outcome following mucosal advancement flap for high perianal fistulas and fistulotomy for low perianal fistulas: recurrent perianal fistulas: failure of treatment or recurrent patient disease? Int J Colorectal Dis. 2006;21:784-90.Schmidt T, Hohl C, et al. Phase-inversion tissue harmonic imaging compared to fundamental B-mode ultrasound in the evaluation of the pathology of large and small bowel. Eur Radiol. 2005;15:2021-30.Gonzalez-Lama Y, Abreu L, et al. Long-term oral tacrolimus therapy in refractory to infliximab fistulizing Crohn's disease: a pilot study. Inflamm Bowel Dis. 2005;11:8-15.Buchanan GN, Bartram CI, et al. Value of hydrogen peroxide enhancement of three-dimensional endoanal ultrasound in fistula-in-ano. Dis Colon Rectum. 2005;48:141-7.Ajaj W, Lauenstein TC, et al. Small bowel hydro-MR imaging for optimized ileocecal distension in Crohn's disease: should an additional rectal enema filling be performed? J Magn Reson Imaging. 2005;22:92-100.Guidi L, Minordi LM, et al. Clinical correlations of small bowel CT and contrast radiology findings in Crohn's disease. Eur Rev Med Pharmacol Sci. 2004;8:215-7.Boraschi P, Braccini G, et al. MR enteroclysis using iron oxide particles (ferristene) as an endoluminal contrast agent: an open phase III trial. Magn Reson Imaging. 2004;22:1085-95.Marcos HB, Semelka RC. Evaluation of Crohn's disease using half-fourier RARE and gadolinium-enhanced SGE sequences: initial results. Magn Reson Imaging. 2000;18:263-8.Rodier JF, Janser JC, et al. Prevention of radiation enteritis by an absorbable polyglycolic acid mesh sling. A 60-case multicentric study. Cancer. 1991;68:2545-9.Did not meet inclusion criteria regarding populationGourtsoyiannis N, Papanikolaou N, et al. Assessment of Crohn's disease activity in the small bowel with MR and conventional enteroclysis: preliminary results. Eur Radiol. 2004;14:1017-24.Maccioni F, Colaiacomo MC, et al. Value of MRI performed with phased-array coil in the diagnosis and pre-operative classification of perianal and anal fistulas. Radiol Med. 2002;104:58-67.Beets-Tan RG, Beets GL et al. Preoperative MR imaging of anal fistulas: Does it really help the surgeon? Radiology. 2001;218:75-84.Incorrect purposeJensen MD, Nathan T, et al. Ileoscopy reduces the need for small bowel imaging in suspected Crohn's disease. Dan Med J. 2012;59:A4491.Jensen MD, Ormstrup T, et al. Interobserver and intermodality agreement for detection of small bowel Crohn's disease with MR enterography and CT enterography. Inflamm Bowel Dis. 2011;17:1081-8.Koilakou S, Sailer J, et al. Endoscopy and MR enteroclysis: equivalent tools in predicting clinical recurrence in patients with Crohn's disease after ileocolic resection. Inflamm Bowel Dis. 2010;16:198-203.Cronin CG, Lohan DG, et al. Does MRI with oral contrast medium allow single-study depiction of inflammatory bowel disease enteritis and colitis? Eur Radiol. 2010;20:1667-74.Negaard A, Mulahasanovic A, et al. Crohn's disease evaluated with magnetic resonance enteroclysis: diagnostic performance of experienced and inexperienced readers before and after training. Acta Radiol. 2008;49:967-74.Herrmann KA, Michaely HJ, et al. The "star-sign" in magnetic resonance enteroclysis: a characteristic finding of internal fistulae in Crohn's disease. Scand J Gastroenterol. 2006;41:239-41.Incorrect study typeVan Weyenberg SJ, Bouman K, et al. Comparison of MR enteroclysis with video capsule endoscopy in the investigation of small-intestinal disease. Abdom Imaging. 2013;38:42-51.de Bie CI, Paerregaard A, et al. Disease phenotype at diagnosis in pediatric Crohn's disease: 5-year analyses of the EUROKIDS Registry. Inflamm Bowel Dis. 2013;19:378-85.Cullen G, Donnellan F, et al. Evaluation of the small bowel in inflammatory bowel disease. Expert Rev Gastroenterol Hepatol. 2013;7:239-51.Kopylov U, Amitai MM, et al. Clinical and radiographic presentation of superior mesenteric vein thrombosis in Crohn's disease: a single center experience. J Crohns Colitis. 2012;6:543-9.Daperno M, Castiglione F, et al. Results of the 2nd part Scientific Workshop of the ECCO. II: Measures and markers of prediction to achieve, detect, and monitor intestinal healing in inflammatory bowel disease. J Crohns Colitis. 2011;5:484-98.Ryan ER, Heaslip IS. Magnetic resonance enteroclysis compared with conventional enteroclysis and computed tomography enteroclysis: a critically appraised topic. Abdom Imaging. 2008;33:34-7.Martin DR, Lauenstein T, Sitaraman SV. Utility of magnetic resonance imaging in small bowel Crohn's disease. Gastroenterology. 2007;133:385-90.Masselli G, Casciani E, et al. Assessment of Crohn's disease in the small bowel: Prospective comparison of magnetic resonance enteroclysis with conventional enteroclysis. Eur Radiol. 2006;16:2817-27.Insufficient outcomes dataDagia C, Ditchfield M, et al. Imaging for Crohn disease: use of 3-T MRI in a paediatric setting. J Med Imaging Radiat Oncol. 2008;52:480-8.Bernstein CN, Greenberg H, et al. A prospective comparison study of MRI versus small bowel follow-through in recurrent Crohn's disease. Am J Gastroenterol. 2005;100:2493-502.Rieber A, Wruk D, et al. Diagnostic imaging in Crohn's disease: comparison of magnetic resonance imaging and conventional imaging methods. Int J Colorectal Dis. 2000;15:176-81.Incorrect diseaseDe Ridder M, Tournel K, , et al. Phase II study of preoperative helical tomotherapy for rectal cancer. Int J Radiat Oncol Biol Phys. 2008;70:728-34.Triester SL, Leighton JA, et al. A meta-analysis of the yield of capsule endoscopy compared to other diagnostic modalities in patients with obscure gastrointestinal bleeding. Am J Gastroenterol. 2005;100:2407-18.Tuech JJ, Chaudron V, et al. Prevention of radiation enteritis by intrapelvic breast prosthesis. Eur J Surg Oncol. 2004;30:900-4.Schaefer O, Lohrmann C, Langer M. Assessment of anal fistulas with high-resolution subtraction MR-fistulography: comparison with surgical findings. J Magn Reson Imaging. 2004;19:91-8.Narin B, Ajaj W, et al. Combined small and large bowel MR imaging in patients with Crohn's disease: a feasibility study. Eur Radiol. 2004;14:1535-42.Dwarkasing S, Hussain SM, et al.. Anovaginal fistulas: evaluation with endoanal MR imaging. Radiology. 2004;231:123-8.Appendix F Assessment of economic evaluation CHEERS Assessment of Cipriano (2012) economic evaluation of MR compared to CTNo.CHEERS criteriaAssessment1Identifies the study as an economic evaluation in title and interventions described p.12402Provides a structured summary of objectives, perspective, setting, methods (study design and inputs) results (base case and uncertainty analyses and conclusions. p.12403Provides an explicit statement of the broader context of the study. Presents the study question and its relevance for health policy or practice decisions p.12414Describes characteristics of the base case population and subgroups analysed and why they were chosen p.12425States relevant aspects of the system in which the decision needs to be madex6Describes the perspective of the study and relates this to the costs being evaluated p.12417Describes the interventions or strategies being compared and state why they were chosen. p.12418States the time horizon over which costs and consequences are being evaluated and says why appropriate p.1241, x9Reports the choice of discount rate(s) used for costs and outcomes and says why p.1242, x10Describes what outcomes were used as the measures of benefit and relevance for analysis Suppl file11Single-study – describes fully the design features and why single study was sufficient for clinical effectivenessSynthesis-based – describes the methods used for identification of included studies and synthesis of clinical effectiveness data- Suppl file12If applicable, describes the population and methods used to elicit preferences for outcomes Suppl file13Single-study – describes fully the approaches to estimate resource use, valuation methods and any adjustments made Synthesis-based – describes the methods used for resource use associated with model health states, valuation and adjustments made- Suppl file14Reports the dates of the estimated resource quantities and unit costs, year reported for unit costs, methods for converting costs into a common currency base and exchange rate Suppl file15Describes and gives reasons for the specific type of decision analytic model used. Illustration is highly recommended. p.124116Describes all structural or other assumptions underpinning the decision-analytical model. Suppl file17Describes all analytical methods supporting the evaluation (methods dealing with skewed, missing or censored data, extrapolation methods, pooling data and any adjustments) and methods for handing population heterogeneity and uncertainty. Suppl file18Reports the values, ranges, references and if used probability distributions used for all parameters. Reports reasons or sources for distributions used to represent uncertainty. A table showing these is highly recommended Suppl file19Reports the mean values for each intervention, mean values for main categories of costs and outcomes as well as mean differences between comparator groups and incremental cost effectiveness ratio if relevant Table 1, p.124420Single study-based economic evaluation: Describes and effects of sampling uncertainty for the incremental cost and effectiveness estimates and impact of any assumptionsModel-based economic evaluation: Describes the effects on the results of uncertainty for all input parameters, and related to structure of model and assumptions- p.1244-5 21If applicable, reports differences in costs, outcomes, input parameters that can be explained by variations between subgroups of patients with different baseline characteristicsX n/a22Summarises key study findings and describes how they support the conclusions reached. Discussed limitations and generalisability of the findings and how they fit with current knowledge pp1244-4723Source of funding and role of funder in study. Describes other non-monetary support p.124024.Describes any potential for conflict of interest of study contributors in accordance with journal policyunclearGlossary and abbreviations AHMAC Australian Health Ministers’ Advisory CouncilAIHW Australian Institute of Health and WelfareANZHSN Australian and New Zealand Horizon Scanning NetworkARTG Australian Register of Therapeutic GoodsAR-DRGAustralian Related Diagnosis Related GroupARPANSAAustralian Radiation Protection And Nuclear Safety AgencyCDCrohn’s diseaseCHEERSConsolidated Health Economic Evaluation Reporting StandardsCIconfidence intervalCRDCentre for Reviews and DisseminationCTcomputer tomographyDAPDecision Analytic ProtocolDHSDepartment of Human ServicesEQ-5DEuroQol-5DFNfalse NegativeFPfalse PositiveGPGeneral practitionerHESP Health Expert Standing HRQoL health-related quality of lifeHTA health technology assessmentICER incremental cost-effectiveness ratioLRlikelihood ratioMBS Medical Benefits ScheduleMD mean differenceMRImagnetic resonance imagingMREmagnetic resonance enterographyMSAC Medical Services Advisory CommitteeNHMRC National Health and Medical Research CouncilNHS National Health ServiceNPVnegative predictive valuePBSPharmaceutical Benefits SchemePPVpositive predictive valueQALYquality-adjusted life yearQUADASQuality Assessment of Studies of Diagnostic Accuracy Included in Meta-AnalysesRANZCRRoyal Australian and New Zealand College of RadiologistsSBFTsmall bowel follow throughTPtrue PositiveTNtrue NegativeReferences ADDIN EN.REFLIST AIHW 2011. 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