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Methods.DefinitionsThere is currently no generally accepted definition of “minimally invasive” spine surgery. For purposes of this systematic review, “minimally invasive surgery” will operationally be defined as surgery conducted through a tube, cylindrical retractor blades or sleeves via a muscle dilating or muscle splitting approach and bundled as “minimal access spine surgery” (MAS). Conventional or open spine surgery is defined as surgery conducted through an approach that includes elevating or stripping the paraspinal muscles to gain access to the spine even if by a limited midline incision. These definitions have been used in previous focus issues.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Gb3VybmV5PC9BdXRob3I+PFllYXI+MjAxMDwvWWVhcj48

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ADDIN EN.CITE.DATA 1Electronic Literature SearchA systematic search of PubMed, EMBASE, the Cochrane Collaboration data base, University of York Centre for Reviews and Dissemination (NHS-EED and HTA), and the Tufts CEA Registry was conducted to identify full economic studies conducted through December 24, 2013 based on the key questions and PICO criteria established a priori (Table 1). Search terms included spinal disorders (radiculopathy, stenosis, degeneration, scoliosis and spondylolisthesis) and the surgical treatments (minimally invasive or minimal access or open procedures) combined with terms specific to economic studies such as cost benefit, cost effectiveness, cost utility, QALYs and medical economics. The search strategy is further documented in the supplementary digital material. Studies in English published in peer reviewed journals or contained within health technology assessments (HTAs) were considered. Abstracts that did not overtly describe cost effectiveness or that did not explicitly state that the intervention was minimally invasive or through minimal access techniques, were excluded. Only economic studies that evaluated and synthesized the costs and consequences of MAS compared with conventional open procedures (i.e. cost-minimization, cost-benefit, cost-effectiveness, or cost-utility) were considered for inclusion. Data Extraction From the included articles, the following data were extracted: study design, funding source, patient demographics (if reported), treatment interventions, perspective of economic model, type of economic model (if used), follow-up duration and the rate of follow-up for each treatment group (if reported or calculable), time horizon of economic model, assumptions and specifications of the model, cost sources, discounting and currency type, source of clinical, outcomes and utility data, primary findings (including costs, QALYs, cost effectiveness information e.g. cost per surgery avoided, ICERs and sensitivity analysis information) and limitations or risk of bias within the study.Data AnalysisDescriptive data and economic findings were reported as presented in the articles. Critical appraisalThe Quality of Health Economic Studies (QHES) instrument developed by Ofman, et al. was used to provide an initial basis for critical appraisal of included economic studies. ADDIN EN.CITE <EndNote><Cite><Author>Ofman</Author><Year>2003</Year><RecNum>3</RecNum><DisplayText><style face="superscript" font="Times New Roman">2</style></DisplayText><record><rec-number>3</rec-number><foreign-keys><key app="EN" db-id="frsd955zzzafs8e0v5rxtd2hd5tp9s9az5tf" timestamp="1394572941">3</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ofman, J. J.</author><author>Sullivan, S. D.</author><author>Neumann, P. J.</author><author>Chiou, C. F.</author><author>Henning, J. M.</author><author>Wade, S. W.</author><author>Hay, J. W.</author></authors></contributors><auth-address>Zynx Health Inc., 9100 Wilshire Blvd, East Tower, Suite 655, Beverly Hills, CA 90212, USA. jofman@</auth-address><titles><title>Examining the value and quality of health economic analyses: implications of utilizing the QHES</title><secondary-title>Journal of managed care pharmacy : JMCP</secondary-title><alt-title>J Manag Care Pharm</alt-title></titles><periodical><full-title>Journal of managed care pharmacy : JMCP</full-title><abbr-1>J Manag Care Pharm</abbr-1></periodical><alt-periodical><full-title>Journal of managed care pharmacy : JMCP</full-title><abbr-1>J Manag Care Pharm</abbr-1></alt-periodical><pages>53-61</pages><volume>9</volume><number>1</number><edition>2003/11/14</edition><keywords><keyword>*Cost-Benefit Analysis</keyword><keyword>Delivery of Health Care/*economics</keyword><keyword>Economics, Pharmaceutical</keyword><keyword>Humans</keyword><keyword>United States</keyword></keywords><dates><year>2003</year><pub-dates><date>Jan-Feb</date></pub-dates></dates><isbn>1083-4087 (Print)&#xD;1083-4087 (Linking)</isbn><accession-num>14613362</accession-num><work-type>Research Support, Non-U.S. Gov&apos;t&#xD;Review</work-type><urls><related-urls><url> QHES is a sixteen 'yes' or 'no' question instrument that assesses multiple aspects of economic study design, modeling and reporting to determine internal validity (See Supplemental Digital Material). QHES was assessed prospectivelyPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5PZm1hbjwvQXV0aG9yPjxZZWFyPjIwMDM8L1llYXI+PFJl

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ADDIN EN.CITE.DATA 5 The QHES does not provide insight into study external validity (generalizability) nor does it directly assess the validity of clinical assumptions and inputs. A study may receive a high score based on factors assessed in QHES, but ultimately may not be applicable to a broader range of clinical populations. Thus, in addition to assessment of criteria in the QHES, other factors are important in critical appraisal of studies from an epidemiologic perspective to assist in evaluation of generalizability and consideration of potential sources of bias related to clinical inputs into the economic model. Two reviewers (KEM, ACS) independently applied the QHES to included studies. Discrepancies in ratings were discussed so that consensus could be reached and a final score obtained. ADDIN EN.REFLIST 1.Fourney DR, Dettori JR, Norvell DC, et al. Does minimal access tubular assisted spine surgery increase or decrease complications in spinal decompression or fusion? Spine. 2010 Apr 20;35(9 Suppl):S57-65. PMID: 20407352.2.Ofman JJ, Sullivan SD, Neumann PJ, et al. Examining the value and quality of health economic analyses: implications of utilizing the QHES. J Manag Care Pharm. 2003 Jan-Feb;9(1):53-61. PMID: 14613362.3.Chiou CF, Hay JW, Wallace JF, et al. Development and validation of a grading system for the quality of cost-effectiveness studies. Med Care. 2003 Jan;41(1):32-44. PMID: 12544542.4.Gerkens S, Crott R, Cleemput I, et al. Comparison of three instruments assessing the quality of economic evaluations: a practical exercise on economic evaluations of the surgical treatment of obesity. Int J Technol Assess Health Care. 2008 Summer;24(3):318-25. PMID: 18601800.5.Spiegel BM, Targownik LE, Kanwal F, et al. The quality of published health economic analyses in digestive diseases: a systematic review and quantitative appraisal. Gastroenterology. 2004 Aug;127(2):403-11. PMID: 15300571.Search Strategy.PubMed SearchDate: 12-24-13Completed by: KEM1“Radiculopathy” [MeSH] OR “Spinal Stenosis” [MeSH] OR “Spondylolisthesis” [MeSH] OR “Scoliosis” [MeSH] OR “Intervertebral Disc Degeneration” [MeSH] OR “intervertebral disc disease” OR “spin* trauma” OR “radiculopathy” OR “spin* stenosis” OR “spondylolisthesis” OR “scoliosis” OR “brachial plexus neuritis” [MeSH] OR “cervicobrachial neuralgia” OR “vertebra* stenosis” OR “neurogenic claudication”36,3622“Laminectomy” [MeSH] OR “Foraminotomy” [MeSH] OR “Spinal Fusion” [MeSH] OR “Diskectomy” [MeSH] OR “Decompression, surgical” [MeSH] OR “laminectomy” OR “foraminotomy” OR “fusion” OR “discectomy” OR “diskectomy” OR “decompression” OR “lateral lumbar fusion” OR “laminoforamintomy”255,6423“Diskectomy, Percutaneous” [MeSH] OR “Surgical Procedures, Minimally Invasive” [MeSH] OR “minimally invasive” OR “minimal surgery” OR “minimal access” OR (minimal* AND invasive) OR (minimal* AND surg*) OR (minimal* AND access*)417,2534(#1 OR #2) AND #37,6695“Spine” [MeSH] OR “back” [MeSH] OR “neck” [MeSH] OR “lumbar” OR “cervical” OR “thoracic” OR “spin*” OR “vertebra*”595,6046#4 AND #53,5757"Cost-Benefit Analysis"[Mesh] OR "Quality-Adjusted Life Years"[Mesh] OR "cost utility" OR “Economics, Medical” [MeSH] OR “economic evaluation” OR “QALY” OR “cost benefit” OR “cost effective*”114,8368#6 AND #736Abstract available and Human and English27EMBASE Search*Date: 12-24-13Completed by: KEMFilters activated: Abstract available, Humans, English, As Explosive Keywords and Free Text1“Radiculopathy” OR “Cervicobrachial neuralgia” OR “Vertebral Canal Stenosis” OR “Spondylolisthesis” OR “Scoliosis” OR “Intervertebral Disc Disease” OR (intervertebral disc degeneration) OR (spin* trauma) OR (spin* stenosis) OR (brachial plexus neuritis) OR (vertebra* stenosis) OR (neurogenic claudication)41,5392“Laminectomy” OR “Foraminotomy” OR “Spine Fusion” OR “Intervertebral Diskectomy” OR “Spinal Cord Decompression” OR “Spine Surgery” OR (fusion) OR (discectomy) OR (discectomy) OR (decompression) OR (lateral lumbar fusion) OR (laminoforamintomy)33,6303“Microsurgery” OR “Laparoscopy” OR “Minimally Invasive Procedure” OR (percutaneous) OR (minimal* invasive) OR (tubular) OR (microdiscectomy) OR (minimal* surg*) OR (minimal* access)95,3884(#1 OR #2) AND #31,9085“Spine” OR “back” OR “neck” OR (lumbar) OR (cervical) OR (thoracic) OR (spin*) OR (vertebra*)7,915,5376#4 AND #51,9087"Cost-Benefit Analysis" OR “Cost Effectiveness Analysis” OR “Cost Utility Analysis” OR Economic Evaluation” OR “Health Economics” OR (cost utility) OR (cost benefit) OR (cost effective*) OR (QALY) OR (quality adjusted life year) OR (medical economics)256, 5948#6 AND #787* Phrases in parentheses are not Emtree words or free text, they were searched using AND phrases (e.g. Neurogenic AND (claudication/exp OR claudication)).Cochrane SearchDate: 12-24-13Completed by: KEM1“Radiculopathy” [MeSH] OR “Spinal Stenosis” [MeSH] OR “Spondylolisthesis” [MeSH] OR “Scoliosis” [MeSH] OR “Intervertebral Disc Degeneration” [MeSH] OR “intervertebral disc disease” OR “spin* trauma” OR “radiculopathy” OR “vertebra* stenosis” OR “spin* stenosis” OR “spondylolisthesis” OR “scoliosis” OR “brachial plexus neuritis” [MeSH] OR “cervicobrachial neuralgia” OR “neurogenic claudication”2,1152“Laminectomy” [MeSH] OR “Foraminotomy” [MeSH] OR “Spinal Fusion” [MeSH] OR “Diskectomy” [MeSH] OR “Decompression, surgical” [MeSH] OR “laminectomy” OR “foraminotomy” OR “fusion” OR “discectomy” OR “diskectomy” OR “decompression” OR “lateral lumbar fusion” OR “laminoforamintomy”4,4103“Diskectomy, Percutaneous” [MeSH] OR “Surgical Procedures, Minimally Invasive” [MeSH] OR “Microsurgery”[MeSH] OR “Laparoscopy”[MeSH] OR “percutaneous” OR “microsurgery” OR “laparoscopy” OR “tubular” OR “minimal* invasive” OR “minimal* surg*” OR “minimal* access”27,5324(#1 OR #2) AND #35485“Spine” [MeSH] OR “back” [MeSH] OR “neck” [MeSH] OR “lumbar” OR “cervical AND spin*” OR “spin*” OR “thoracic” OR “back” OR “neck” OR “vertebra*”47,9806#4 AND #53887"Cost-Benefit Analysis"[Mesh] OR "Quality-Adjusted Life Years"[Mesh] OR "cost utility" OR “Economics, Medical” [MeSH] OR “economic evaluation” OR “QALY” OR “cost benefit” OR “cost effective*”28,9258#6 AND #775Abstract available and Human and English75CEA Registry 12-24-13Search “lumbar” – found 28 studies, 2 unique (plus duplicates from PubMed)Search “cervical spine” – found 1 study (not of treatment interest, diagnostic) University of York, Centre for Reviews and Dissemination 12-24-13Search (minimally invasive) AND (cervical OR lumbar) AND (cost)Found 14 studies, 1 unique (plus duplicates from CEA, Cochrane or PubMed)Table 1. Exclusion Table.Author, DateRationale for ExclusionExcluded at abstractAckerman SJ, Polly Jr DW, Knight T, Schneider K, Holt T, Cummings J. Comparison of the costs of nonoperative care to minimally invasive surgery for sacroiliac joint disruption and degenerative sacroiliitis in a united states medicare population: Potential economic implications of a new minimally-invasive technology. ClinicoEconomics and Outcomes Research. 2013;5(1):575-587.Wrong patient population – sacroiliac jointCharles YP, Vouaillat H, Marcaud M, Ihara Z. Minimally invasive surgery in spinal fusion : Clinical and economical impact from hospital perspective. Value in Health. 2012;15(7):A404.Abstract only, not full studyCorbo M, Marchese E, Ihara Z. Mast (minimal access spinal technologies) versus open surgery: Activity-based cost analysis of spinal fusion procedure from hospital perspective. Value in Health. 2011;14(7):A247.Abstract only, not full studyNellensteijn, J., R. Ostelo, et al. (2010) Transforaminal endoscopic surgery for symptomatic lumbar disc herniations: a systematic review of the literature. European Spine Journal 181-204(Systematic review) Wrong study type, cost not in abstractRampersaud RY, Goldstein CL, Macwan K, Sundararajan K. Comparative clinical and economic outcomes of minimally invasive surgery for posterior lumbar fusion: A systematic review and meta-analysis. Spine Journal. 2013;13(9):151S.Abstract only, not full studyRodriguez, H. E., M. M. Connolly, et al. (2002). "Anterior access to the lumbar spine: laparoscopic versus open." The American surgeon 68(11): 978-982; discussion 982-983.Wrong intervention – anterior approachSlotman GJ, Stein SC. Laparoscopic L5-S1 diskectomy: A cost-effective, minimally invasive general surgery-neurosurgery team alternative to laminectomy. American Surgeon. 1996;62(1):64-68.Wrong intervention – anterior approachSlotman GJ, Stein SC. Laminectomy compared with laparoscopic diskectomy and outpatient laparoscopic diskectomy for herniated L5-S1 intervertebral disks. Journal of Laparoendoscopic and Advanced Surgical Techniques - Part A. 1998;8(5):261-267.Wrong intervention – anterior approachSmith, W., G. Christian, et al. (2011). "A comparison of perioperative charges and outcome between open anterior and mini-open lateral approaches for lumbar discectomy and fusion." Spine Journal 11(10): 102S.Wrong intervention – anterior approachSmith, W. D., G. Christian, et al. (2012) A comparison of perioperative charges and outcome between open and mini-open approaches for anterior lumbar discectomy and fusion. Journal of Clinical Neuroscience 673-680.Wrong intervention – anterior approachSpoor, A. B. and F. C. Oner (2013). "Minimally invasive spine surgery in chronic low back pain patients." Journal of Neurosurgical Sciences 57(3): 203-218.(Systematic review) Wrong study type, literature reviewVertuani S, Ihara Z, Musayev A, Nilsson J. A cost-effectiveness analysis of minimally invasive versus open surgery techniques for lumbar spine fusion. Value in Health. 2012;15(7):A405.Abstract only, not full studyExcluded at full textAllen, R. T. and S. R. Garfin (2010). "The economics of minimally invasive spine surgery: The value perspective." Spine 35(SUPPL. 26S): S375-S382.(Systematic review) Wrong study type, literature reviewDullerud, R., H. Lie, et al. (1999). "Cost-effectiveness of percutaneous automated lumbar nucleotomy. Comparison with traditional macro-procedure discectomy." Interventional Neuroradiology 5(1): 35-42.Doesn’t fit MAS definitionHuang, T. J., R. W. Hsu, et al. (1997). "Video-assisted thoracoscopic treatment of spinal lesions in the thoracolumbar junction." Surg Endosc 11(12): 1189-1193.Wrong patient population –patients with metastatic diseaseLucio JC, van Conia RB, de Luzio KJ, Lehmen JA, Rodgers JA, Rodgers WB. Economics of less invasive spinal surgery: An analysis of hospital cost differences between open and minimally invasive instrumented spinal fusion procedures during the perioperative period. Risk Management and Healthcare Policy. 2012;5:65-74.Wrong intervention – XLIF procedureParker, S. L., O. Adogwa, et al. (2011). Post-operative infection after minimally invasive versus open transforaminal lumbar interbody fusion (TLIF): literature review and cost analysis. Minim Invasive Neurosurg 54, 33–37.Preliminary subpopulation, updated report found for same population.Pelton MA, Phillips FM, Singh K. A comparison of perioperative costs and outcomes in patients with and without workers' compensation claims treated with minimally invasive or open transforaminal lumbar interbody fusion. Spine. 2012(22):1914-1919. Costing onlySingh K, Nandyala SV, Marquez-Lara A, et al. A Peri-Operative Cost Analysis Comparing Single-Level Minimally Invasive and Open Transforaminal Lumbar Interbody Fusion. Spine J. 2013;16(13):01723-01723Costing onlyStevens, C. D., R. W. Dubois, et al. (1997). "Efficacy of lumbar discectomy and percutaneous treatments for lumbar disc herniation." Soz Praventivmed 42(6): 367-379.(Systematic review) Wrong study type, cost not included full textStevenson, R. C., C. J. McCabe, et al. (1995) An economic evaluation of a clinical trial to compare automated percutaneous lumbar discectomy with microdiscectomy in the treatment of contained lumbar disc herniation. Spine 739-742 Doesn’t fit MAS definitionWang, M. Y., M. D. Cummock, et al. (2010). "An analysis of the differences in the acute hospitalization charges following minimally invasive versus open posterior lumbar interbody fusion." J Neurosurg Spine 12(6): 694-699.Costing only Wang, M. Y., J. Lerner, et al. (2012). "Acute hospital costs after minimally invasive versus open lumbar interbody fusion: Data from a US national database with 6106 patients." Journal of Spinal Disorders and Techniques 25(6): 324-328.Costing only Zachary, A. M. and J. D. Fortin (2003). "Minimally invasive options to disc surgery." Pain Physician 6(4): 467-471.(Systematic review) Wrong study type, cost not included full textTable 2. Detailed abstraction table of economic studies.Author (year) CountryFunding QHESPopulation InterventionsDesignPerspectiveTime horizonModelAssumptionsEconomic Model specificationsYear, CurrencyCost SourcesDiscountingClinical Data Source (e.g Utility, other)source Primary Findings(ICER (or other cost/outcome); dominance, Sensitivity analysis results)Limitations, risk of biasVan den Akker (2011)NetherlandsFunding of work: Dutch Health Care Insurance BoardQHES: 79From previously reported multicenter RCT*N= 325 assessed % F/U: NRTubular discectomy:n = 166males: NRage: NRConventional microdiscectomy:n = 159males: NRage: NRInclusion:Patients between 18-70 years oldPatients with sciatica caused by LDH, lasting >6-8 weeksRadiologically confirmed disk herniation with distinct nerve root compressionExclusion: Patient with cauda equina syndrome, central canal stenosis, pregnancy, severe somatic or psychiatric diseases, inadequate knowledge of Dutch language or emigration planned w/in 1 year of inclusionCUASocietal (healthcare and non-healthcare costs)Also report just healthcare costs1 year F/U period1 year time horizon Economic model: NRCosts of anesthesia and use of awakening room were assumed to be equal for both procedures and therefore omittedEconomic model: NR1 yr time horizon, divided into 4 quartersRegression models used for clinical outcomes with imputation for missing values for cost or outcomes2008 Euros to US dollarsCost source: Cost diaries, patient reportedMean cost per operating room minute, provided by each participating hospitalCost of equipment based on initial purchasing prices, yearly use and depreciationDutch standard prices to represent societal costs and standardizeCosts used for analysis:Including but not limited to: admission to hospital, operating room costs (staff, room, equipment, overhead), visits (specialists, general practitioner, physical therapy, alternative health care), home care, paid domestic help, informal care, drugs and aids, out of pocket expenses as a result of sciatica and hours absent from work, patients’ time and travel costsCost discounted: not discountedClinical measures (derived from RCT data):EuroQol EQ-5DSF-36 (calculated for SF-6D utilities)VAS (0-100)Modified Roland Disability QuestionnaireReoperation rateEQ-5D and VAS measured at intake, randomization and 2,4,6,8,12,26,38,52 weeks after randomizationSF-36 measured at intake and 4,8,26,52 weeks after randomizationMean Societal Costs: Costs:1 yr. cumulative costs per patient ($ US ± SD)?Tubular: 16,858 ± 12,759Conventional: 15,367 ± 12,165P = NS? Cost (95% CI): 1,491 (-1,335 – 4,318)QALYs:Utility measures similar for both groups, P = NS? QALY (95% CI): US EQ-5D: -0.012 (-0.046 – 0.021)Dutch EQ-5D: -0.014 (-0.056 – 0.029)SF-6D: -0.11 (-0.037 – 0.014)VAS: -0.021(-0.058 – 0.016)Sensitivity Analysis: Willingness to pay per QALYProbability that tubular is cost-effective was stable, ranged from 15% -22% for various levelsUse of different utility measures (Dutch EQ-5D, SF-6D or VAS)Results not detailed; probability of being cost-effective favors conventionalPerspective (health care or societal)Results not detailed; tubular not preferred overs conventional from health care perspectiveSettings may differ between the 7 hospitals included in the studyDuration of study only 1 yr, very short time horizonCosts of surgery used, instead of hospital pricesDetails of one-way sensitivity analysis data presented graphically only; No sensitivity analysis regarding cost drivers Conversion of Euros to USD may not accurately reflect actual costs in either countryUnclear to what extent future revisions may influence longer termSubstantial variability (large standard deviations) for cost and utility estimatesParker (2013)USAAuthors disclose no COI Funding of work: NRQHES: 52 Retrospective cohort studyN= 54 assessed males: 53.7%age: 57 ± 11.4 years % F/U: NRMAS multilevel hemilaminectomy:n = 27males: 67%age: 59.5 ± 9.3Open multilevel hemilaminectomy:n = 27males: 41.7%age: 54 ± 12.7Inclusion:Patients age 18-70 years oldUnilateral radicular symptoms involving 2 or more nerve rootsMRI evidence of multilevel lumbar stenosis corresponding to radicular symptomsFailed at least 6 weeks of conservation therapyExclusion:Mechanical instabilityHistory of a previous back operationExtraspinal cause of back or leg painActive medical or workman’s compensation lawsuitAny preexisting spinal pathologyUnwilling or unable to participate in F/UCUASocietal2 year F/U period2 year time horizon Economic model: NRAssumptions NREconomic model: NR; provided formula for ICER; clinical outcome means, SD evaluated with t-test; nonparametric data with Mann-Whitney U; nominal data with chi-square(Time NR) USCost source: Patient reported resource utilization dataSelf-reported instances of medical resource use were multiplied by unit costs for each component, based on Medicare national allowable payment amountsMedication prices based on Redbook pricesSurgeon costs based on Medicare allowable amounts using the resource-based relative value scaleIndirect costs estimated using the standard human capital approachCosts used for analysis:Direct costs (including but not limited to: outpatient visits (surgeons, chiropractors, other physicians, physical therapists, acupuncturists, or other health care providers), spine-related diagnostic tests (radiograph, computed tomographic scan, MRI, and electromyography), injections, devices (braces, canes, walkers, shoe inserts), emergency room visits, rehabilitation, nursing home days, medicationsIndirect costs (including but not limited to: productivity losses due to spine-related problems, work or homemaking days)Cost discounted: NRClinical measures (derived from retrospective cohort data):EQ-5DPre and post-op pain (VAS leg and LBP)Disability (ODI)SF-12Duration of narcotic useTime to return to workComplicationsMean costs: Costs:2 yr. cumulative costs per patient, $ US (95% CI)MAS: 23,109 (23,078 – 23,140)Open: 25,420 (25,389 – 25,450)P = NS? Cost: 2,311QALYs2 yr. cumulative QALYs per patient: MAS: 0.72 (CI NR)Open: 0.72 (CI NR)P = NS? QALY: 0ICER ?$US/?QALY: NC, no difference in QALYIndirect costs accounted for 43% of total cost for MAS and 63% for openSensitivity Analysis: NRThird party payer perspective (Medicare national allowable payments) may not be as accurate as hospital and private payer cost estimations, since hospitals may influence the decision whether an MAS versus open approach may be usedNo sensitivity analysis performedRetrospective patient interview conducted for outcome measures, may be biased since patients were aware of the treatment they hadBaseline characteristics similar between groups but potential for selection bias still existsSmall sample size may preclude ability to detect statistical differencesAll procedures performed by one surgeon – unclear how variability across providers could influence resultsNo sensitivity analysis performed; model limitations or assumptions not described Rampersaud (2011)CanadaAuthors do not disclose COIFunding of work: The W. Garfield Weston FoundationQHES: 74Retrospective cohortN = 78 assessed % F/U for outcomes data:MAS fusion: 75.7%Open fusion: 70.7%MAS fusion:n = 37males: 48.6 %age: 55.11 ± 14.98Open fusion:n = 41males: 51.2%age: 57.02 ± 13.38 Inclusion:Grade I-II degenerative or isthmic spondylolisthesisExclusion:Other causes of spondylolisthesis (iatrogenic)High-grade spondylolisthesisRevision surgeryCUAHealth care system/single payer1 year F/U period1 year time horizon Projected to 2 and 4 yrsEconomic model: NRBecause the groups were the same with regard to diagnosis, institution and health care system, costs of pre and post-op physician visits and imaging were assumed to be the sameOutcomes remain relatively stable for 4 years, thus cost utility should improve at 2 and 4 yearsEconomic model: NR; clinical outcomes used multivariate regression modeling 4 variables per model, predictor variables on total direct cost (primary), LOS and clinical outcome Projected cost utility analysis for 2 and 4 years2011 $CDNCost source: Hospital financial department, micro-case costing per individual patientPhysician reimbursement NRCosts used for analysis:Direct costs (including but not limited to: operative costs, nursing (post-anesthetic care, step-down unit, ICU and ward), medical imaging, laboratories, pharmacy, allied health, management of any inpatient adverse eventsIndirect costs: NRQALY discounted 5% per yearClinical measures (derived from retrospective cohort data):SF-6D (derived from SF 36) at 1 yearComplicationsODIHospital LOSMean case: Costs:1 yr. cumulative costs per patient ($CND ± SD)MAS: 14,171.93 ± 3,269.73?Open: 18,632.91 ± 6,197.32P = 0.0009? Cost: 4,460.98QALYs:5% annual discount on QALY1 yr. cumulative QALYs gained per patient ± SD: MAS: 0.113 ± 0.10Open: 0.079 ± 0.08P = 0.08? QALY: 0.0342 yr. cumulative QALYs gained per patient: MAS: 0.20 Open: 0.15? QALY: 0.054 yr. cumulative QALYs gained per patient: MAS: 0.38 Open: 0.28? QALY: 0.10Cost/QALY: (5% discount on QALY)1 yrMAS: $128,936Open: $232,9122 yrMAS: $70,915 Open: $122,5854 yrMAS: $37,720 Open: $67,510ICER ?$CDN/?QALY: Not performed; new strategy costs less or equivalent and NS difference in outcomeSensitivity Analysis: NRPre and post-op rehabilitation or other outpatient health system costs were not collectedRevision costs not included in 2 or 4 year projectionsNo sensitivity analysis Range of SD was very large for costs and QALYsBaseline differences in outcome measures, more disabled open fusion cohortCosts only from institutional perspective, no indirect societal or direct out of pocket patient costs% follow-up of <80% Limited sample size Detail of which variables were included in multivariate regression equations not providedDiscounted quality but not costParker (2013)USAIndividual authors disclose COI related to industryFunding of work: NRQHES: 70Prospective cohortN= 100 assessed males: 34%age: 53 ± 12.0 years% F/U: NRMAS TLIF:n = 50males: 32%age: 53.5 ± 12.5Open TLIF:n = 50males: 36%age: 52.6 ± 11.6Inclusion:Patients aged 18-70 years oldEvidence on MRI of grade I DLSMechanical LBP and radicular symptomsNonresponse to ≥ 6 weeks of conservative therapyExclusion:History of previous back operationExtraspinal cause of back pain or sciaticaAn active medical or workmans’ compensation lawsuitAny preexisting spinal pathologyUnwilling or unable to participate in f/uNotable associated abnormalities (i.e. inflammatory arthritis or metabolic bone disease)CUASocietal2 year F/U period2 year time horizonEconomic model: NRAssumptions NREconomic model: NR; provided formula for ICER, describe 2 year change in mean EQ-5D; clinical outcome means, SD evaluated with t-test; nonparametric data with Mann-Whitney U; nominal data with chi-square(Time NR) $USCost source: Hospital accounting and billing office provided hospital expenditures for delivery of carePatient reported resource utilization dataSelf-reported instances of medical resource use were multiplied by unit costs for each component, based on Medicare national allowable payment amountsMedication prices based on Redbook pricesSurgeon costs based on Medicare allowable amounts using the resource-based relative value scaleIndirect costs estimated using the standard human capital approachCosts used for analysis:Direct costs (including but not limited to: surgeons, chiropractors, other physicians, physical therapists, acupuncturists, or other health care providers, spine-related diagnostic tests (radiograph, computed tomographic scan, MRI, and electromyography), injections, devices (braces, canes, walkers, shoe inserts), emergency room visits, rehabilitation, nursing home days, medications)Indirect costs (including but not limited to: productivity losses due to spine-related problems, work or homemaking days)Cost discounted: NRClinical measures (derived from prospective cohort data):QoL (EQ-5D)Pre and post-op pain (VAS leg and LBP)Disability (ODI)SF-12 (mental and physical component scores)Zung depression indexDuration of narcotic useTime to return to workComplicationsMean case: Costs:2 yr. cumulative costs per patient, $US ± SDMAS: 38,563 ± 10,594Open: 47,858 ± 20,148P = 0.03? Cost: $9,295QALYs (2 year change in mean EQ-5D):2 yr. cumulative QALYs per patient: MAS: 0.771 Open: 0.695P = NS? QALY: 0.076ICER ?$US/?QALY: NA, no significant difference in QALYIndirect costs accounted for 28% of total costs for MAS, 41% for openSensitivity Analysis: NR Third party payer perspective (Medicare national allowable payments) may not be as accurate as hospital and private payer cost estimations, since hospitals may influence the decision whether an MAS versus open approach may be usedNo sensitivity analysisDifferences in complication rates across providers may influence resultsRetrospective patient interview conducted for outcome measures, may be biased since patients were aware of the treatment they hadPotential for selection bias – authors do not describe number of eligible and numbers excluded and rationaleSmall sample size may preclude ability to detect statistical differencesCost of MAS implant was excluded from cost analysisParker (2011)USASurgical site infections?Authors do not disclose COIFunding of work: NRQHES: 55Retrospective review of case series literature (SSI)% F/U: NRMAS TLIF:n = 362males: 42.4%age: 53.6 yearsOpen TLIF:n = 1,133males: 46.4%age: 47.8 yearsInclusion (literature):MAS vs. open TLIF for treatment of grade I-II spondylolisthesis or DDDFirst-time TLIF onlyEnglish articles, 1975 – 2009TLIF with tubular retractor and supplemented with pedicle screws were considered MASExclusion:Case reports, technical notes, animal or lab studiesPLIF studiesPatients with revision surgeryNot mentioning SSIRetrospective cohort from own institution (costs)% F/U: NRMAS TLIF:n = 0Open TLIF:n = 120males: 41.7%age: 48.4 ± 13.2Inclusion (cost):Open TLIF procedures for treatment of DDD or grade I spondylolisthesisExclusion:NRCEASingle provider perspective (Hospital)Time horizon NREconomic model: NRDirect medical costs were defined at 70% of billing valuesEconomic model: NR; clinical outcomes were assessed using multivariate analysis(Time NR) $USACost source: Institutional billing and accounting recordsPhysician reimbursement not includedCosts used for analysis:Direct costs (including but not limited to: all SSI related hospital charges )Indirect costs: NRCost discounted NRClinical measures (derived from literature):Incidence of reported SSI, MAS vs open cohorts and institutional rates for open TLIFClinical measures (derived from retrospective cohort):Length of hospitalizationCT, MRI scans and radiographsComplications (DVT, dermatological reaction)Length of intravenous antibioticsMean case: Costs:(Time NR) Cumulative costs per 6 patients ($US)MAS: NROpen: $29,1103.4% decrease in reported SSI incidence for MAS vs. OpenCost savings of $98,974 per 100 MAS-TLIF procedures, $989 per MAS-TLIF performedSensitivity Analysis: NRLiterature review data are from case series and indirect comparison of MAS vs. open procedures is subject to biasCost of SSI extrapolated from 6 open-TLIF patients who developed SSI at the author’s institutionAnalysis does not consider other minimally invasive tubular approachesNo model completed, costs were projected based on risk of SSI from literature and costs of patients with SSI from institutional case reviewUnclear definition of MAS procedureSSI represents 1 possible complication or outcome; To evaluate broader cost-effectiveness of MAS, efficacy and other outcomes should be consideredSSI appears to be a rare event and sample size of 362 may not adequately capture infection riskNo sensitivity analysis performedMcGirt (2011)USASurgical site infections**Individual authors disclose COI; some authors employed by industryFunding of work: NRQHES: 66Administrative data base study% F/U: NRMAS T/PLIF:1 leveln = 848males: 45%age: 52.4 ± 13.42 leveln = 588males: 46%age: 51.9 ± 13.4Open T/PLIF:1 leveln = 1,595males: 45%age: 53.7 ± 13.72 leveln = 2,139males: 46%age: 56.7 ± 13.7Inclusion:Patients undergoing 1 or 2 level T/PLIF procedures between 2003 – 2009Presence of all ICD-9-CM codes: 81.08, 81.62 and 84.51Patients with lumbar spondylotic disease, disc degeneration or spondylolisthesisExclusion:Fusion revisionDeformity diagnosisConcurrent anterior fusion> 2 level fusionCEASingle provider perspective (Hospital)8 week post-op F/UEconomic model: NRAssumptions NREconomic model: NR; clinical outcomes used univariate and multivariate logistical regression for evaluation of associations between factors and presence of SSI 2009 $USACost source: Hospital discharge and billing records obtained from Premier Perspective DatabasePhysician reimbursement not includedCosts used for analysis:Direct costs (including but not limited to: infection costs incurred by the hospital for care provided during inpatient or hospital-outpatient encounters)Indirect costs (including but not limited to: )Cost discounted NRClinical measures (derived from retrospective cohort):Incidence of SSICharlson Comorbidity IndexMean case: Direct Costs:Cumulative SSI-associated cost per procedure ($US)1 level:MAS: $684Open: $724P = NS? Cost: $402 level:MAS: $756Open: $1,140P = 0.030? Cost: $384Adjusted OR for increased SSI with open 1.5 (1.0-2.3) (any level assumed)For 1 level fusion:SSI risk 4.5% MAS vs. 4.8% with openFor 2 level fusion:SSI risk 4.6% MAS vs. 7.0% with openCost savings of $4,000 per 100 MAS-T/PLIF procedures for 1-level fusionCost savings of $38,400 per 100 MAS-T/PLIF procedures for 2-level fusionSensitivity Analysis: NROnly evaluates perioperative infections (w/in 8 weeks of surgery)Administrative database used, potential for misclassification Identification of surgery type by ICD-9-CM codes and number of pedicle screws for number of levels fusedVery short time horizon, in-hospital costs only includedNot designed to detect infection after 8 weeksUnclear definition of MAS technique (hospital charge field had US FDA approval for percutaneousposterior fusion)For multivariate regression, unclear what factors were used in final modelSSI represents one possible complication or outcome; To evaluate broader cost-effectiveness of MAS, efficacy and other outcomes should be consideredCES: cost effectiveness study; CI: confidence interval; COI: conflicts of interest; CUA: cost utility analysis; DDD: degenerative disc disease; DLS: degenerative lumbar spondylolisthesis; DVT: deep venous thrombosis; ICER: incremental cost effectiveness ratio; LBP: low back pain; LDH: lumbar disc herniation; LOS: length of stay; MAS: minimal access surgery; NC: not calculable; NR: not reported; ODI: Oswestry Disability Index; PLIF: posterior lumbar interbody fusion; QALY: quality-adjusted life years; QHES: Quality of Health Economic Studies; RCT: randomized control trial; SD: standard deviation; TLIF: transforaminal lumbar interbody fusion; VAS: visual analog scale; SR: systematic review; SSI: surgical site infections* Demographic information from RCT is not reported in economic study.? Mean cost of MAS is inconsistently reported throughout the article text.? Definition of surgical site infection, as defined by Parker et al. (2011): erythematous or purulent wound that was culture-positive requiring long term intravenous antibiotics or surgical debridement.** Definition of surgical site infection, as defined by McGirt et al. (2011): an ICD-9-CM diagnosis code indicative of a postoperative infection during or within 8 weeks of the index hospitalization for lumbar fusion, or administration of parenteral antibiotics 7 or more days after index fusion surgery within the 8-week postoperative periodTable 3. Quality of Health Economic Studies (QHES) score of included articlesQHES Question (pts possible)Van den Akker 2011Parker 2013(Hemi)Parker 2013 (TLIF)Rampersaud 2011McGirt 2011Parker 2011Was the study objective presented in a clear, specific, and measurable manner? (7 pts)777777Were the perspective of the analysis (societal, third-party payer, etc.) and reasons for its selection stated? (4 pts)444444Were variable estimates used in the analysis from the best available source (i.e. randomized controlled trial = best, expert opinion = worst)? (8 pts)800000If estimates came from a subgroup analysis, were the groups prespecified at the beginning of the study? (1 pt)111111Was uncertainty handled by (1) statistical analysis to address random events, (2) sensitivity analysis to cover a range of assumptions? (9 pts)000000Was incremental analysis performed between alternatives for resources and costs? (6 pts)666666Was the methodology for data abstraction (including the value of health states and other benefits) stated? (5 pts)555550Did the analytic horizon allow time for all relevant and important outcomes? Were benefits and costs that went beyond 1 year discounted (3% to 5%) and justification given for the discount rate? (7 pts)700770Was the measurement of costs appropriate and the methodology for the estimation of quantities and unit costs clearly described? (8 pts)888888Were the primary outcome measure(s) for the economic evaluation clearly stated and did they include the major short-term, long-term and negative outcomes included? (6 pts)006066Were the health outcomes measures/scales valid and reliable? If previously tested valid and reliable measures were not available, was justification given for the measures/scales used? (7 pts)777777Were the economic model (including structure), study methods and analysis, and the components of the numerator and denominator displayed in a clear, transparent manner? (8 pts)808888Were the choice of economic model, main assumptions, and limitations of the study stated and justified? (7 pts)707770Did the author(s) explicitly discuss direction and magnitude of potential biases? (6 pts)060600Were the conclusions/recommendations of the study justified and based on the study results? (8 pts)888808Was there a statement disclosing the source of funding for the study? (3 pts)303000Total QHES score:795270746655Cost-Effectiveness Analysis Registry, Quality Score*:3 / 73.5 / 7NRNRNRNR*Scale of 1 (low) to 7 (high), organized by the Tufts Medical Center, Institute for Clinical Research and Health Policy Studies, The Center for Evaluation of Value and Risk in Health ................
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