ABSTRACT - McMaster University
SHORT-COURSE ANTIMICROBIALS FOR PAEDIATRIC PNEUMONIASHORT-COURSE ANTIMICROBIALS FOR THE TREATMENT OF PAEDIATRIC COMMUNITY-ACQUIRED PNEUMONIABy JEFFREY M. PERNICA, B.Sc. M.D.A Thesis Submitted to the School of Graduate Studies in Partial Fulfilment of the Requirements for the Degree Master of ScienceMcMaster University ? Copyright by Jeffrey M. Pernica, December 2014McMaster University MASTER OF SCIENCE (2014) Hamilton, Ontario (Health Research Methodologies)TITLE: Short-course antimicrobials for the treatment of paediatric community-acquired pneumonia AUTHOR: Jeffrey M. Pernica, B. Sc. (McGill) M.D. (Dalhousie) SUPERVISOR: Professor Mark Loeb NUMBER OF PAGES: 72ABSTRACTPaediatric community-acquired pneumonia (CAP) is common in North America. It is often treated with beta-lactam antimicrobials targeting S. pneumoniae, the most important cause of CAP in young children. Current guidelines recommend 10 days of therapy for paediatric CAP, regardless of severity; in contrast, mild CAP in adults is routinely treated with only 5 days of antimicrobials. There have been no definitive studies of 5-day vs. 10-day therapy for CAP in children.The objective of this thesis was to conduct a pilot RCT comparing 5 to 10 days of amoxicillin for the treatment of mild paediatric CAP and then design the multicentre follow-up trial.Children aged 6 months - 10 years with no significant past medical history presenting to the McMaster Children's Hospital emergency department with mild CAP were eligible for enrollment. All participants were randomized to either 10 days high-dose amoxicillin (90 mg/kg/day divided bid) or 5 days of high-dose amoxicillin + 5 days placebo. The primary outcome was clinical cure at day 14-18 post-enrollment.In total, 61 participants were recruited. The median participant age was 2.64 y. Only 60% of chest radiographs were reported by the radiologist as showing evidence of pneumonia. There were six treatment failures; one participant failed to defervesce on day 4, one participant had recurrent fevers leading to re-presentation to the emergency, and the other four participants did not meet clinical cure criteria but were essentially well at the time of follow-up. Study blinding has been maintained.The majority of previously healthy children with mild CAP who are well enough to be treated as outpatients appear to do well, regardless of duration of antimicrobial treatment. Feasibility and safety of the trial protocol have been demonstrated; the follow-up multicentre trial is slated to begin in mid-2015.ACKNOWLEDGEMENTSI would like to thank my thesis supervisor, Dr. Mark Loeb, for always being incredibly supportive and for making himself available at any time…regardless of the number of grants he had due the next day. I also could not have done this were it not for my other committee members, Drs. Marek Smieja and Eleanor Pullenayegum. Lastly, but most importantly, I am grateful for the love of my family and my beautiful children Avrah and Oren, without whom none of this would really matter.TABLE OF CONTENTS TOC \o "1-3" ABSTRACT PAGEREF _Toc280336694 \h iACKNOWLEDGEMENTS PAGEREF _Toc280336695 \h iiiTABLE OF CONTENTS PAGEREF _Toc280336696 \h ivPART 1: OUTLINE PAGEREF _Toc280336697 \h 1PART 2: INTRODUCTION PAGEREF _Toc280336698 \h 2PART 3: THE MAIN PROJECT PAGEREF _Toc280336699 \h 16PART 4 – THE COMPLETED PILOT TRIAL PAGEREF _Toc280336700 \h 41PART 5 – SELECTED METHODOLOGIC CONSIDERATIONS FOR NON-INFERIORITY STUDIES PAGEREF _Toc280336701 \h 53PART 6 – SELECTED METHODOLOGIC CONSIDERATIONS FOR PILOT STUDIES PAGEREF _Toc280336702 \h 59PART 7 – CONCLUSIONS AND FUTURE DIRECTIONS PAGEREF _Toc280336703 \h 64REFERENCES PAGEREF _Toc280336704 \h 66PART 1: OUTLINEThe focus of this thesis was the design of a multicentre non-inferiority randomized controlled trial comparing short-course antimicrobial therapy to standard-duration therapy for the treatment of mild community-acquired pneumonia in children. After a review of the literature (Part 2), a pilot trial was designed (Part 4) and conducted using funds from the Hamilton Health Sciences New Investigator Award. The data and experience acquired from the pilot trial were reviewed prior to the design of the main multicentre trial (Part 3). Specific methodologic considerations relevant to the design of the pilot and main trial will be discussed last (Parts 5 and 6).PART 2: INTRODUCTIONBurden of pneumonia in childhoodRespiratory infection is the leading cause of death for children worldwide PEVuZE5vdGU+PENpdGU+PFllYXI+MjAxMzwvWWVhcj48UmVjTnVtPjM4ODc8L1JlY051bT48RGlz
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ADDIN EN.CITE.DATA (5). It should be noted that morbidity and mortality from lower respiratory tract infections is substantially higher in native and Northern populations in Canada and the United States ADDIN EN.CITE <EndNote><Cite><Author>Long SS</Author><Year>2008</Year><RecNum>3677</RecNum><DisplayText>(6)</DisplayText><record><rec-number>3677</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1360588385">3677</key></foreign-keys><ref-type name="Book">6</ref-type><contributors><authors><author>Long SS, Pickering LK, Prober CG.</author></authors><tertiary-authors><author>Long SS, Pickering LK, Prober CG.</author></tertiary-authors></contributors><titles><title>Principles and Practice of Pediatric Infectious Diseases.</title></titles><edition>3rd.</edition><dates><year>2008</year></dates><pub-location>Philadelphia</pub-location><publisher>Elsevier</publisher><urls></urls></record></Cite></EndNote>(6).Issues relating to the clinical diagnosis of pneumonia. Though physicians commonly diagnose CAP, there are no consensus criteria for its diagnosis. Its most common definition, “inflammation of the parenchyma of the lungs [caused by infection],” ADDIN EN.CITE <EndNote><Cite><Year>2007</Year><RecNum>3947</RecNum><DisplayText>(7)</DisplayText><record><rec-number>3947</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1384688673">3947</key></foreign-keys><ref-type name="Book">6</ref-type><contributors><tertiary-authors><author>Kliegman, R. M., Behrman RE, Jenson HB, et al.</author></tertiary-authors></contributors><titles><title>Nelson Textbook of Pediatrics, 18th ed.</title></titles><dates><year>2007</year></dates><pub-location>Philadelphia</pub-location><publisher>Elsevier</publisher><urls></urls></record></Cite></EndNote>(7) is not useful in practice, as there is no way for clinicians to objectively evaluate whether inflammation is present in the lung parenchyma of their patient prior to autopsy. Symptoms and signs of respiratory disease are not specific for pneumonia ADDIN EN.CITE <EndNote><Cite><Author>Margolis</Author><Year>1998</Year><RecNum>3948</RecNum><DisplayText>(8)</DisplayText><record><rec-number>3948</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1384688861">3948</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Margolis, P.</author><author>Gadomski, A.</author></authors></contributors><auth-address>Division of Community Pediatrics, The University of North Carolina at Chapel Hill, 27599-7225, USA. margolis@med.unc.edu</auth-address><titles><title>The rational clinical examination. Does this infant have pneumonia?</title><secondary-title>JAMA</secondary-title><alt-title>JAMA : the journal of the American Medical Association</alt-title></titles><periodical><full-title>JAMA</full-title><abbr-1>JAMA : the journal of the American Medical Association</abbr-1></periodical><alt-periodical><full-title>JAMA</full-title><abbr-1>JAMA : the journal of the American Medical Association</abbr-1></alt-periodical><pages>308-13</pages><volume>279</volume><number>4</number><edition>1998/02/05</edition><keywords><keyword>Cough</keyword><keyword>Diagnosis, Differential</keyword><keyword>Humans</keyword><keyword>Infant</keyword><keyword>*Physical Examination</keyword><keyword>Pneumonia/*diagnosis/physiopathology/radiography</keyword><keyword>Respiratory Tract Infections/diagnosis</keyword></keywords><dates><year>1998</year><pub-dates><date>Jan 28</date></pub-dates></dates><isbn>0098-7484 (Print)
0098-7484 (Linking)</isbn><accession-num>9450716</accession-num><work-type>Research Support, Non-U.S. Gov't
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ADDIN EN.CITE.DATA (9,10); we note that fever was documented in only 18-26% of children admitted to intensive care units because of respiratory failure due to the emerging pathogen enterovirus-D68 in the summer of 2014 ADDIN EN.CITE <EndNote><Cite><Author>Midgley</Author><Year>2014</Year><RecNum>4217</RecNum><DisplayText>(11)</DisplayText><record><rec-number>4217</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1411572824">4217</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Midgley, C. M.</author><author>Jackson, M. A.</author><author>Selvarangan, R.</author><author>Turabelidze, G.</author><author>Obringer, E.</author><author>Johnson, D.</author><author>Giles, B. L.</author><author>Patel, A.</author><author>Echols, F.</author><author>Oberste, M. S.</author><author>Nix, W. A.</author><author>Watson, J. T.</author><author>Gerber, S. I.</author></authors></contributors><titles><title>Severe respiratory illness associated with enterovirus d68 - missouri and illinois, 2014</title><secondary-title>MMWR Morb Mortal Wkly Rep</secondary-title><alt-title>MMWR. Morbidity and mortality weekly report</alt-title></titles><periodical><full-title>MMWR Morb Mortal Wkly Rep</full-title><abbr-1>MMWR. Morbidity and mortality weekly report</abbr-1></periodical><alt-periodical><full-title>MMWR Morb Mortal Wkly Rep</full-title><abbr-1>MMWR. Morbidity and mortality weekly report</abbr-1></alt-periodical><pages>798-9</pages><volume>63</volume><number>36</number><dates><year>2014</year><pub-dates><date>Sep 12</date></pub-dates></dates><isbn>1545-861X (Electronic)
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ADDIN EN.CITE.DATA (12). A recent study enlisted 3 paediatric radiologists at both Boston Children’s Hospital and the Children’s Hospital of Philadelphia and provided them with a mix of chest radiographs (50 previously read as not having pneumonia, 25 previously read as having an alveolar infiltrate, 25 previously read as having an interstitial infiltrate, and 10 duplicates) taken from patients presenting with potential CAP to the emergency departments of these major children’s hospitals ADDIN EN.CITE <EndNote><Cite><Author>Neuman</Author><Year>2012</Year><RecNum>3981</RecNum><DisplayText>(13)</DisplayText><record><rec-number>3981</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1384689242">3981</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Neuman, M.I.</author><author>Lee, EY. </author><author>Bixby, S.</author><author>Diperna, S.</author><author>Hellinger, J.</author><author>Markowitz, R. </author><author>Servaes, S.</author><author>Monuteaux, M.C.</author><author>Shah, S.S.</author></authors></contributors><titles><title>Variability in the interpretation of chest radiographs for the diagnosis of pneumonia in children</title><secondary-title>J Hosp Med</secondary-title></titles><periodical><full-title>J Hosp Med</full-title><abbr-1>Journal of hospital medicine : an official publication of the Society of Hospital Medicine</abbr-1></periodical><pages>294-298</pages><volume>7</volume><dates><year>2012</year></dates><urls></urls></record></Cite></EndNote>(13). Inter-rater reliability was good for alveolar infiltrates (kappa 0.69 95% CI 0.60-0.78) but only slight for interstitial infiltrates (kappa 0.14 95%CI 0.05-0.23), a radiographic finding that is much more commonly found, and stratifying by institution had little effect on these estimates. Intra-rater reliability varied widely between the 6 respondents, with kappa 0.74-1.00 for alveolar infiltrates and kappa 0.21-1.00 for interstitial infiltrates. Please note that these estimates of inter-rater reliability are between paediatric radiologists; it has long been known that there are significant differences between the way radiologists and emergency physicians evaluate chest radiographs for pneumonia PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BbCBhc2VyaTwvQXV0aG9yPjxZZWFyPjIwMDk8L1llYXI+
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ADDIN EN.CITE.DATA (14,15). As the decision about whether a particular patient has CAP or not will generally be made by the emergency physician without consulting the radiologist, one might reasonably expect a dramatic decrease in overall inter-rater reliability for most chest radiographs. It should be emphasized that the ramifications of an emergency physician calling a given radiograph ‘negative’ for CAP and having the radiologist subsequently judging it to be ‘positive’ are much more significant than the converse, as the patient’s caregiver would have to be contacted to inform them of the ‘mistake’. Consequently, one could expect that emergency physicians will tend to judge more radiographs as ‘positive’ for CAP than radiologists. To further complicate the diagnostic process, a recent study involving adults presenting to emergency departments with suspected pulmonary embolism who received both chest radiographs and chest computed tomography (CT) scans demonstrated that the sensitivity of chest radiograph for the detection of ‘opacities’ was only 43.5% compared to the gold-standard CT. Furthermore, specificity of chest radiograph was also poor; the positive predictive value of seeing an ‘opacity’ on chest radiograph was only 26.9% PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TZWxmPC9BdXRob3I+PFllYXI+MjAxMzwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA (18). Sensitivity of chest radiography was found to be only 67% and, unsurprisingly, specificity of ultrasound findings was lower than that of chest radiography (57% vs 76%). A previous trial in children presenting to the emergency department with suspected pneumonia compared bedside ultrasound to chest radiograph evaluation by paediatric radiologists blinded to physical examination and ultrasound findings. Ultrasound was found to have sensitivity of 86% and specificity of 89%; specificity increased to 97% for lung consolidation when positives restricted to sonographic air bronchograms exceeding 1 cm PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TaGFoPC9BdXRob3I+PFllYXI+MjAxMzwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA (17). Despite all of these issues, observational studies and clinical trials in upper-income countries often use somewhat similar definitions for ‘community-acquired pneumonia’ using fever, clinical signs of respiratory disease, and chest radiographic criteria, though, as noted above, none of these are sensitive or specific individually PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5XaWxsaWFtczwvQXV0aG9yPjxZZWFyPjIwMTM8L1llYXI+
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ADDIN EN.CITE.DATA (19-22). Though radiographic criteria have been proposed by the WHO for epidemiologic studies for the diagnosis of pneumonia, no such clinical criteria exist; consequently, most studies have slightly differing case definitions. Though the single most sensitive and specific test for the diagnosis of pneumonia would probably be thoracic CT scan, this diagnostic test involves too much ionizing radiation to use on a routine basis.Issues relating to the microbiologic diagnosis of pneumonia. It is even more difficult to make a bacteriologic diagnosis than a clinical one. In adults, Gram stain/culture of sputum can be useful in identifying pathogens that may not be treated adequately with typical empiric antimicrobials, as well as permitting de-escalation of broad-spectrum therapy, though the utility of this diagnostic test is balanced by the difficulties inherent in the collection, transport, processing, and interpretation of these specimens PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NYW5kZWxsPC9BdXRob3I+PFllYXI+MjAwNzwvWWVhcj48
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ADDIN EN.CITE.DATA (23). Unsurprisingly, it is orders of magnitude more difficult to obtain an adequate sputum specimen from a preschooler than from an adult, essentially rendering this diagnostic test useless in young children. A positive blood culture for a typical pathogen in a child with CAP makes the microbiologic diagnosis, but this occurs so infrequently that current guidelines actively discourage venipuncture in children with mild disease, as harm probably outweighs benefit; an example of typical ‘harm’ would include hospitalization and initiation of intravenous antibiotic therapy prompted by a ‘positive’ blood culture for a contaminant pathogen PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CcmFkbGV5PC9BdXRob3I+PFllYXI+MjAxMTwvWWVhcj48
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ADDIN EN.CITE.DATA (24). Urinary pneumococcal antigen testing has been studied extensively in adults and is thought by many clinicians to be helpful in diagnosing CAP in older individuals. Sensitivity of this test was found to be 74.6% in a series of 350 immunocompetent adults with bacteraemic pneumococcal pneumonia ADDIN EN.CITE <EndNote><Cite><Author>Zalacain</Author><Year>2014</Year><RecNum>4222</RecNum><DisplayText>(25)</DisplayText><record><rec-number>4222</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1411588324">4222</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Zalacain, R.</author><author>Capelastegui, A.</author><author>Ruiz, L. A.</author><author>Bilbao, A.</author><author>Gomez, A.</author><author>Uranga, A.</author><author>Espana, P. P.</author></authors></contributors><auth-address>Department of Respiratory Medicine, Cruces University Hospital, Barakaldo, Bizkaia, Spain.</auth-address><titles><title>Streptococcus pneumoniae antigen in urine: diagnostic usefulness and impact on outcome of bacteraemic pneumococcal pneumonia in a large series of adult patients</title><secondary-title>Respirology</secondary-title><alt-title>Respirology</alt-title></titles><periodical><full-title>Respirology</full-title><abbr-1>Respirology</abbr-1></periodical><alt-periodical><full-title>Respirology</full-title><abbr-1>Respirology</abbr-1></alt-periodical><pages>936-43</pages><volume>19</volume><number>6</number><dates><year>2014</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1440-1843 (Electronic)
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ADDIN EN.CITE.DATA (27,28). A more recent report showed that there might be utility in performing urinary pneumococcal antigen testing in children suspected of having pneumonia who are first found to have elevated C-reactive protein or procalcitonin, but these results can only be called very preliminary due to the small size of the study PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HYWxldHRvLUxhY291cjwvQXV0aG9yPjxZZWFyPjIwMTM8
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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HYWxldHRvLUxhY291cjwvQXV0aG9yPjxZZWFyPjIwMTM8
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ADDIN EN.CITE.DATA (27).Results of different studies examining blood-based polymerase chain reaction (PCR) testing have been mixed, with most investigators finding many cases of culture-positive PCR-negative samples PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5EYWdhbjwvQXV0aG9yPjxZZWFyPjE5OTg8L1llYXI+PFJl
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ADDIN EN.CITE.DATA (27,29-31). Culture or PCR of nasopharyngeal swabs (NPS) can readily detect S. pneumoniae, but there is little evidence suggesting that these techniques can distinguish between active infection and colonization; the latter is common in young children ADDIN EN.CITE <EndNote><Cite><Author>Adegbola</Author><Year>2001</Year><RecNum>4043</RecNum><DisplayText>(28)</DisplayText><record><rec-number>4043</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1384690502">4043</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Adegbola, R. A.</author><author>Obaro, S. K.</author><author>Biney, E.</author><author>Greenwood, B. M.</author></authors></contributors><auth-address>MRC Laboratories, Banjul, The Gambia.</auth-address><titles><title>Evaluation of Binax now Streptococcus pneumoniae urinary antigen test in children in a community with a high carriage rate of pneumococcus</title><secondary-title>Pediatr Infect Dis J</secondary-title><alt-title>The Pediatric infectious disease journal</alt-title></titles><periodical><full-title>Pediatr Infect Dis J</full-title><abbr-1>The Pediatric infectious disease journal</abbr-1></periodical><alt-periodical><full-title>Pediatr Infect Dis J</full-title><abbr-1>The Pediatric infectious disease journal</abbr-1></alt-periodical><pages>718-9</pages><volume>20</volume><number>7</number><edition>2001/07/24</edition><keywords><keyword>Antigens, Bacterial/*urine</keyword><keyword>Carrier State/urine</keyword><keyword>Child, Preschool</keyword><keyword>Community-Acquired Infections/diagnosis/urine</keyword><keyword>Gambia</keyword><keyword>Humans</keyword><keyword>Nasopharynx/microbiology</keyword><keyword>Pneumococcal Infections/*diagnosis/immunology/*urine</keyword><keyword>Predictive Value of Tests</keyword><keyword>Streptococcus pneumoniae/*immunology/isolation & purification</keyword></keywords><dates><year>2001</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0891-3668 (Print)
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ADDIN EN.CITE.DATA (32). They defined CAP as requiring either crackles or bronchial breathing on auscultation in the presence of 2 or more of cough, dyspnoea, pleuritic chest pain, or fever, in combination with ‘any new radiographic infiltrate’; in their population, a pneumococcal load of >8000 copies/mL had a sensitivity of 82% and specificity of 92% for the diagnosis of CAP. However, as for urinary pneumococcal antigen testing, this assay must be investigated in children prior to making any recommendations for its routine use in paediatrics. Additionally, it should be emphasized that pneumococcus-specific diagnostic tests will always give false-negative results for CAP cases caused by other pathogens, such as group A Streptococcus; these occur much more rarely than pneumococcus-associated CAP but do occur PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Sb2JpbnNvbjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+
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ADDIN EN.CITE.DATA (33,34).Mycoplasma pneumoniae, an obligatory intracellular (“atypical”) pathogen, is a relatively common cause of CAP in older children ADDIN EN.CITE <EndNote><Cite><Author>Waites</Author><Year>2004</Year><RecNum>4045</RecNum><DisplayText>(35)</DisplayText><record><rec-number>4045</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1384690562">4045</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Waites, K. B.</author><author>Talkington, D. F.</author></authors></contributors><auth-address>Department of Pathology, WP 230, University of Alabama at Birmingham, 619 19th St. South, Birmingham, AL 35249, USA. waites@path.uab.edu.</auth-address><titles><title>Mycoplasma pneumoniae and its role as a human pathogen</title><secondary-title>Clin Microbiol Rev</secondary-title><alt-title>Clinical microbiology reviews</alt-title></titles><periodical><full-title>Clin Microbiol Rev</full-title><abbr-1>Clinical microbiology reviews</abbr-1></periodical><alt-periodical><full-title>Clin Microbiol Rev</full-title><abbr-1>Clinical microbiology reviews</abbr-1></alt-periodical><pages>697-728, table of contents</pages><volume>17</volume><number>4</number><edition>2004/10/19</edition><keywords><keyword>Asthma/drug therapy/etiology/*microbiology</keyword><keyword>Humans</keyword><keyword>Mycoplasma pneumoniae/*pathogenicity</keyword><keyword>*Pneumonia, Mycoplasma/complications/diagnosis/drug therapy/immunology</keyword></keywords><dates><year>2004</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>0893-8512 (Print)
0893-8512 (Linking)</isbn><accession-num>15489344</accession-num><work-type>Research Support, U.S. Gov't, P.H.S.
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ADDIN EN.CITE.DATA (24,37), though there have been no recent studies showing a change in the incidence or prevalence of respiratory infection with atypical pathogens in young children. Mycoplasma is not considered part of the normal respiratory flora, and so its detection in the nasopharynx via PCR is somewhat suggestive of causation ADDIN EN.CITE <EndNote><Cite><Author>Waites</Author><Year>2004</Year><RecNum>4045</RecNum><DisplayText>(35)</DisplayText><record><rec-number>4045</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1384690562">4045</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Waites, K. B.</author><author>Talkington, D. F.</author></authors></contributors><auth-address>Department of Pathology, WP 230, University of Alabama at Birmingham, 619 19th St. South, Birmingham, AL 35249, USA. waites@path.uab.edu.</auth-address><titles><title>Mycoplasma pneumoniae and its role as a human pathogen</title><secondary-title>Clin Microbiol Rev</secondary-title><alt-title>Clinical microbiology reviews</alt-title></titles><periodical><full-title>Clin Microbiol Rev</full-title><abbr-1>Clinical microbiology reviews</abbr-1></periodical><alt-periodical><full-title>Clin Microbiol Rev</full-title><abbr-1>Clinical microbiology reviews</abbr-1></alt-periodical><pages>697-728, table of contents</pages><volume>17</volume><number>4</number><edition>2004/10/19</edition><keywords><keyword>Asthma/drug therapy/etiology/*microbiology</keyword><keyword>Humans</keyword><keyword>Mycoplasma pneumoniae/*pathogenicity</keyword><keyword>*Pneumonia, Mycoplasma/complications/diagnosis/drug therapy/immunology</keyword></keywords><dates><year>2004</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>0893-8512 (Print)
0893-8512 (Linking)</isbn><accession-num>15489344</accession-num><work-type>Research Support, U.S. Gov't, P.H.S.
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ADDIN EN.CITE.DATA (23,24); however, a recent Cochrane review found no evidence to suggest that clinical diagnosis is reliable ADDIN EN.CITE <EndNote><Cite><Author>Wang</Author><Year>2012</Year><RecNum>4051</RecNum><DisplayText>(38)</DisplayText><record><rec-number>4051</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1384690744">4051</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Wang, K.</author><author>Gill, P.</author><author>Perera, R.</author><author>Thomson, A.</author><author>Mant, D.</author><author>Harnden, A.</author></authors></contributors><auth-address>Department of Primary Care Health Sciences,University of Oxford, Oxford, UK. kay.wang@phc.ox.ac.uk.</auth-address><titles><title>Clinical symptoms and signs for the diagnosis of Mycoplasma pneumoniae in children and adolescents with community-acquired pneumonia</title><secondary-title>Cochrane Database Syst Rev</secondary-title><alt-title>The Cochrane database of systematic reviews</alt-title></titles><periodical><full-title>Cochrane Database Syst Rev</full-title></periodical><pages>CD009175</pages><volume>10</volume><edition>2012/10/19</edition><keywords><keyword>Adolescent</keyword><keyword>Child</keyword><keyword>Community-Acquired Infections/diagnosis/microbiology</keyword><keyword>Humans</keyword><keyword>*Mycoplasma pneumoniae</keyword><keyword>Pneumonia, Mycoplasma/*diagnosis</keyword><keyword>Randomized Controlled Trials as Topic</keyword><keyword>Respiratory Sounds</keyword><keyword>Symptom Assessment/*methods</keyword></keywords><dates><year>2012</year></dates><isbn>1469-493X (Electronic)
1361-6137 (Linking)</isbn><accession-num>23076954</accession-num><work-type>Meta-Analysis
Research Support, Non-U.S. Gov't
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ADDIN EN.CITE.DATA (39). We note that a recent systematic review found that there is “insufficient evidence to support or refute treatment of Mycoplasma pneumoniae in [CAP]” ADDIN EN.CITE <EndNote><Cite><Author>Biondi</Author><Year>2014</Year><RecNum>4227</RecNum><DisplayText>(40)</DisplayText><record><rec-number>4227</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1411844343">4227</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Biondi, E.</author><author>McCulloh, R.</author><author>Alverson, B.</author><author>Klein, A.</author><author>Dixon, A.</author></authors></contributors><titles><title>Treatment of mycoplasma pneumonia: a systematic review</title><secondary-title>Pediatrics</secondary-title><alt-title>Pediatrics</alt-title></titles><periodical><full-title>Pediatrics</full-title><abbr-1>Pediatrics</abbr-1></periodical><alt-periodical><full-title>Pediatrics</full-title><abbr-1>Pediatrics</abbr-1></alt-periodical><pages>1081-90</pages><volume>133</volume><number>6</number><keywords><keyword>Anti-Bacterial Agents/*therapeutic use</keyword><keyword>Child</keyword><keyword>Community-Acquired Infections/diagnosis/*drug therapy</keyword><keyword>Diagnosis, Differential</keyword><keyword>Humans</keyword><keyword>Inappropriate Prescribing</keyword><keyword>*Mycoplasma pneumoniae</keyword><keyword>Pneumonia/*drug therapy/*etiology</keyword><keyword>Pneumonia, Mycoplasma/diagnosis/*drug therapy</keyword><keyword>Randomized Controlled Trials as Topic</keyword><keyword>Treatment Outcome</keyword></keywords><dates><year>2014</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>1098-4275 (Electronic)
0031-4005 (Linking)</isbn><accession-num>24864174</accession-num><urls><related-urls><url>;(40) and a recent Canadian guideline recommended against prescribing children azithromycin, the agent most often used for Mycoplasma treatment in adults ADDIN EN.CITE <EndNote><Cite><Author>Ovetchkine</Author><Year>2013</Year><RecNum>4229</RecNum><DisplayText>(41)</DisplayText><record><rec-number>4229</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1411844475">4229</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ovetchkine, P.</author><author>Rieder, M. J.</author><author>Canadian Paediatric Society, Drug Therapy</author><author>Hazardous Substances, Committee</author></authors></contributors><titles><title>Azithromycin use in paediatrics: A practical overview</title><secondary-title>Paediatr Child Health</secondary-title><alt-title>Paediatrics & child health</alt-title></titles><periodical><full-title>Paediatr Child Health</full-title><abbr-1>Paediatrics & child health</abbr-1></periodical><alt-periodical><full-title>Paediatr Child Health</full-title><abbr-1>Paediatrics & child health</abbr-1></alt-periodical><pages>311-6</pages><volume>18</volume><number>6</number><dates><year>2013</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>1205-7088 (Print)
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ADDIN EN.CITE.DATA (24). Diagnostics for viral respiratory pathogens are excellent and many centres routinely use multiplexed PCR panels that can detect almost all common important respiratory viruses in NPSs with high sensitivity and specificity PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Qb3Bvd2l0Y2g8L0F1dGhvcj48WWVhcj4yMDEzPC9ZZWFy
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ADDIN EN.CITE.DATA (42). However, it should be emphasized that the detection of a respiratory virus in a NPS does not rule out bacterial co-infection, a phenomenon that appears to be relatively common PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DaWxsYTwvQXV0aG9yPjxZZWFyPjIwMDg8L1llYXI+PFJl
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ADDIN EN.CITE.DATA (43). Clinically diagnosed CAP in a preschooler whose NPS is positive for a virus could indicate a primary viral pneumonia or a secondarily-infected bacterial pneumonia. Many clinicians have seen children with positive viral rapid tests who later are found to have positive blood cultures or who later develop features of severe pneumonia consistent with bacterial infection. Given the extreme difficulty in discerning between viral infection and viral and bacterial co-infection, it should not be surprising that radiographic criteria for distinguishing between viral and bacterial pneumonia have never been developed, though many clinicians would presume that a child who had an alveolar infiltrate on chest radiograph would have a bacterial pulmonary infection.Ramifications of these diagnostic uncertaintiesTo summarize the previous two sections: there are no standardized, published, clinical criteria for the diagnosis of paediatric pneumonia, laboratory testing (such as complete blood counts and C-reactive protein measurement) is often unhelpful for the individual patient, observer interpretation of chest radiographs varies widely, and it is often difficult, if not impossible, to establish a microbiologic diagnosis. Antimicrobial treatment for typical bacteria (eg. S. pneumoniae) is quite different than that for atypical pathogens, and there is no specific therapy available for viruses beside influenza; consequently, though the natural history of CAP of any aetiology (including pneumococcal) is to spontaneously resolve, the results of a treatment trial may vary depending on which pathogens are infecting the study participants. There are two potential ways of dealing with this issue: create extremely stringent inclusion criteria, in the hope that the majority of participants have typical bacterial disease, or use more permissive inclusion criteria, enroll many participants, and later analyze subgroups based on the distribution of various covariates postulated to be associated with typical bacterial infection. The first strategy is best suited to individuals with severe disease, of whom the vast majority can be presumed to have bacterial infections; the second is the only way of conducting a clinical trial relevant to children without infection significant enough to warrant hospitalization. Current recommendations for treatment of paediatric CAPIn August 2011, comprehensive guidelines for the diagnosis and treatment of paediatric CAP were published independently by the Infectious Disease Society of America (IDSA) PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CcmFkbGV5PC9BdXRob3I+PFllYXI+MjAxMTwvWWVhcj48
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ADDIN EN.CITE.DATA (24) and by the Canadian Paediatric Society (CPS) ADDIN EN.CITE <EndNote><Cite><Author>Le Saux</Author><Year>2011</Year><RecNum>3920</RecNum><DisplayText>(37)</DisplayText><record><rec-number>3920</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1381460228">3920</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Le Saux, N., Robinson JL.</author></authors></contributors><titles><title>Pneumonia in healthy Canadian children and youth: practice points for management.</title><secondary-title>Pediatr Child Health</secondary-title></titles><periodical><full-title>Pediatr Child Health</full-title></periodical><pages>417-20</pages><volume>16</volume><number>7</number><dates><year>2011</year></dates><urls></urls></record></Cite></EndNote>(37). Neither could make definitive recommendations for the optimal duration of therapy due to a paucity of evidence. The IDSA guideline states “Treatment courses of 10 days have been best studied ADDIN EN.CITE <EndNote><Cite><Year>2009</Year><RecNum>3921</RecNum><DisplayText>(44)</DisplayText><record><rec-number>3921</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1381460413">3921</key></foreign-keys><ref-type name="Web Page">12</ref-type><contributors></contributors><titles><title>US Department of Health and Human Services Food and Drug Administration, Centre for Drug Evaluation and Research. Guidance for industry. Community-acquired bacterial pneumonia: developing drugs for treatment. </title></titles><number>Sept 2011</number><dates><year>2009</year></dates><urls><related-urls><url>;(44), but shorter courses may be just as effective, particularly for more mild disease managed on an outpatient basis.” PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CcmFkbGV5PC9BdXRob3I+PFllYXI+MjAxMTwvWWVhcj48
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ADDIN EN.CITE.DATA (23,46). A recent survey of Canadian general paediatricians, emergency physicians, and infectious disease specialists showed that few use short courses of antimicrobials to treat paediatric CAP; 50% of all ED-based physicians using β-lactams treat mild pneumonia with 10 or more days of therapy ADDIN EN.CITE <EndNote><Cite><Author>Pernica</Author><Year>2013</Year><RecNum>3935</RecNum><DisplayText>(34)</DisplayText><record><rec-number>3935</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1381462278">3935</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Pernica, J. M.</author><author>Mah, J. K.</author><author>Kam, A. J.</author></authors></contributors><auth-address>1McMaster University, Hamilton, Ontario, Canada.</auth-address><titles><title>Canadian Pediatricians' Prescribing Practices for Community-Acquired Pneumonia</title><secondary-title>Clin Pediatr (Phila)</secondary-title><alt-title>Clinical pediatrics</alt-title></titles><periodical><full-title>Clin Pediatr (Phila)</full-title><abbr-1>Clinical pediatrics</abbr-1></periodical><alt-periodical><full-title>Clin Pediatr (Phila)</full-title><abbr-1>Clinical pediatrics</abbr-1></alt-periodical><edition>2013/05/17</edition><dates><year>2013</year><pub-dates><date>May 15</date></pub-dates></dates><isbn>1938-2707 (Electronic)
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ADDIN EN.CITE.DATA (46), and higher drug costs. Experience with short-course antimicrobial therapy – single trialsFew trials have compared long- (10 day) and short-course (<7 day) therapy for paediatric CAP. Peltola et al. PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5QZWx0b2xhPC9BdXRob3I+PFllYXI+MjAwMTwvWWVhcj48
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ADDIN EN.CITE.DATA (49). The 5-day arm was found to have similar rates of success (5-day 94.6% success, 10-day 96.2% success, confidence intervals and noninferiority margin not provided). However, macrolides are no longer the reference standard due to the increased prevalence of macrolide-resistant pneumococci today PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5SZWluZXJ0PC9BdXRob3I+PFllYXI+MjAwOTwvWWVhcj48
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ADDIN EN.CITE.DATA (50-52) and, as previously noted, the CPS has advocated against the routine use of this agent ADDIN EN.CITE <EndNote><Cite><Author>Ovetchkine</Author><Year>2013</Year><RecNum>4229</RecNum><DisplayText>(41)</DisplayText><record><rec-number>4229</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1411844475">4229</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ovetchkine, P.</author><author>Rieder, M. J.</author><author>Canadian Paediatric Society, Drug Therapy</author><author>Hazardous Substances, Committee</author></authors></contributors><titles><title>Azithromycin use in paediatrics: A practical overview</title><secondary-title>Paediatr Child Health</secondary-title><alt-title>Paediatrics & child health</alt-title></titles><periodical><full-title>Paediatr Child Health</full-title><abbr-1>Paediatrics & child health</abbr-1></periodical><alt-periodical><full-title>Paediatr Child Health</full-title><abbr-1>Paediatrics & child health</abbr-1></alt-periodical><pages>311-6</pages><volume>18</volume><number>6</number><dates><year>2013</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>1205-7088 (Print)
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ADDIN EN.CITE.DATA (54).Table 1: Summary of randomized trials of short-course vs. standard-course antibacterials for paediatric bacterial infections in upper-income countriesPublicationInfection typeExperimental armReference armOutcomeComparisonPeltola et al. PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5QZWx0b2xhPC9BdXRob3I+PFllYXI+MjAwMTwvWWVhcj48
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ADDIN EN.CITE.DATA (53)CAP5 days amoxicillin10 days amoxicillinclinical cure by 30 daysARR = 0%Systematic reviews of short-course antimicrobial therapy for paediatric CAPA Cochrane review ADDIN EN.CITE <EndNote><Cite><Author>Haider</Author><Year>2008</Year><RecNum>3931</RecNum><DisplayText>(55)</DisplayText><record><rec-number>3931</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1381461665">3931</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Haider, B. A.</author><author>Saeed, M. A.</author><author>Bhutta, Z. A.</author></authors></contributors><auth-address>Department of Paediatrics and Child Health, Aga Khan University, PO Box 3500, Stadium Road, Karachi, Pakistan, 74800.</auth-address><titles><title>Short-course versus long-course antibiotic therapy for non-severe community-acquired pneumonia in children aged 2 months to 59 months</title><secondary-title>Cochrane Database Syst Rev</secondary-title><alt-title>The Cochrane database of systematic reviews</alt-title></titles><periodical><full-title>Cochrane Database Syst Rev</full-title></periodical><pages>CD005976</pages><number>2</number><edition>2008/04/22</edition><keywords><keyword>Anti-Bacterial Agents/*administration & dosage</keyword><keyword>Child, Preschool</keyword><keyword>Community-Acquired Infections/drug therapy</keyword><keyword>Drug Administration Schedule</keyword><keyword>Humans</keyword><keyword>Infant</keyword><keyword>Pneumonia/*drug therapy</keyword><keyword>Randomized Controlled Trials as Topic</keyword><keyword>Recurrence</keyword><keyword>Treatment Outcome</keyword></keywords><dates><year>2008</year></dates><isbn>1469-493X (Electronic)
1361-6137 (Linking)</isbn><accession-num>18425930</accession-num><work-type>Meta-Analysis
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ADDIN EN.CITE.DATA (56), Pakistan ADDIN EN.CITE <EndNote><Cite><Year>2002</Year><RecNum>3933</RecNum><DisplayText>(57)</DisplayText><record><rec-number>3933</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1381461936">3933</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors></contributors><titles><title>Clinical efficacy of 3 days versus 5 days of oral amoxicillin for treatment of childhood pneumonia: a multicentre double-blind trial</title><secondary-title>Lancet</secondary-title><alt-title>Lancet</alt-title></titles><periodical><full-title>Lancet</full-title><abbr-1>Lancet</abbr-1></periodical><alt-periodical><full-title>Lancet</full-title><abbr-1>Lancet</abbr-1></alt-periodical><pages>835-41</pages><volume>360</volume><number>9336</number><edition>2002/09/24</edition><keywords><keyword>Administration, Oral</keyword><keyword>Amoxicillin/*administration & dosage</keyword><keyword>Child, Preschool</keyword><keyword>Developing Countries</keyword><keyword>Double-Blind Method</keyword><keyword>Drug Administration Schedule</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Infant</keyword><keyword>Male</keyword><keyword>Patient Compliance</keyword><keyword>Pneumonia, Bacterial/*drug therapy</keyword><keyword>Treatment Failure</keyword><keyword>Treatment Outcome</keyword></keywords><dates><year>2002</year><pub-dates><date>Sep 14</date></pub-dates></dates><isbn>0140-6736 (Print)
0140-6736 (Linking)</isbn><accession-num>12243918</accession-num><work-type>Clinical Trial
Comparative Study
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't</work-type><urls><related-urls><url>(02)09994-4</electronic-resource-num><language>eng</language></record></Cite></EndNote>(57), and Indonesia/Bangladesh ADDIN EN.CITE <EndNote><Cite><Author>Kartasasmita</Author><Year>2002</Year><RecNum>3934</RecNum><DisplayText>(58)</DisplayText><record><rec-number>3934</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1381462222">3934</key></foreign-keys><ref-type name="Report">27</ref-type><contributors><authors><author>Kartasasmita, C.</author><author>Saha, S.</author></authors></contributors><titles><title>Three days versus five days oral cotrimoxazole for non-severe pneumonia.</title></titles><number>Report no. WHO/FCH/CAH/04.2</number><dates><year>2002</year></dates><pub-location>Geneva</pub-location><publisher>Department of Child and Adolescent Health and Development, World Health Organization</publisher><urls></urls></record></Cite></EndNote>(58). No differences were found in clinical cure rate (RR 0.99; 95% CI 0.97-1.01), treatment failure (RR 1.07; 95% CI 0.92-1.25), or relapse rate (RR 1.09; 95% CI 0.83-1.42). Unfortunately, a meta-analysis showing that 3 days of therapy is non-inferior to 5 days of therapy for CAP is not relevant to Canadian physicians until it is shown that 5 days is non-inferior to 7-10 days, the current standard; it should also be emphasized that patient populations and algorithms for CAP diagnosis are very different in resource-limited settings ADDIN EN.CITE <EndNote><Cite><Year>2005</Year><RecNum>4115</RecNum><DisplayText>(59)</DisplayText><record><rec-number>4115</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1389755421">4115</key></foreign-keys><ref-type name="Book">6</ref-type><contributors></contributors><titles><title>Pocket book of hospital care for children: guidelines for the management of common illnesses with limited resources</title></titles><dates><year>2005</year></dates><pub-location>Geneva</pub-location><publisher>WHO Press</publisher><urls></urls></record></Cite></EndNote>(59). Antimicrobial stewardshipOptimizing antimicrobial prescribing, otherwise known as antimicrobial stewardship, has been noted to be the main strategy to deal with escalating antimicrobial resistance and has been called “a fiduciary responsibility for all healthcare institutions across the continuum of care.”PEVuZE5vdGU+PENpdGU+PFllYXI+MjAxMjwvWWVhcj48UmVjTnVtPjQxMTE8L1JlY051bT48RGlz
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ADDIN EN.CITE.DATA (60) The Canadian Paediatric Society has said in a recent statement that “the implementation of antimicrobial stewardship initiatives…is regarded as a key step in reducing Clostridium difficile risk [in children].” ADDIN EN.CITE <EndNote><Cite><Author>Allen</Author><Year>2014</Year><RecNum>4147</RecNum><DisplayText>(61)</DisplayText><record><rec-number>4147</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1393158379">4147</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Allen, U. D.</author></authors></contributors><titles><title>Clostridium difficile in paediatric populations</title><secondary-title>Pediatr Child Health</secondary-title></titles><periodical><full-title>Pediatr Child Health</full-title></periodical><pages>43-8</pages><volume>19</volume><number>1</number><dates><year>2014</year></dates><urls></urls></record></Cite></EndNote>(61) Many evidence-based guidelines published by Canadian and American authorities in the past ten years have sought to minimize the duration of systemic antimicrobials prescribed to both children and adults for the treatment of common infections such as acute otitis media ADDIN EN.CITE <EndNote><Cite><Author>Forgie</Author><Year>2009</Year><RecNum>4148</RecNum><DisplayText>(62)</DisplayText><record><rec-number>4148</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1393158831">4148</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Forgie, S.</author><author>Zhanel, G.</author><author>Robinson, J.</author></authors></contributors><auth-address>Canadian Paediatric Society, Infectious Diseases and Immunization Committee.</auth-address><titles><title>Management of acute otitis media</title><secondary-title>Paediatr Child Health</secondary-title><alt-title>Paediatrics & child health</alt-title></titles><periodical><full-title>Paediatr Child Health</full-title><abbr-1>Paediatrics & child health</abbr-1></periodical><alt-periodical><full-title>Paediatr Child Health</full-title><abbr-1>Paediatrics & child health</abbr-1></alt-periodical><pages>457-64</pages><volume>14</volume><number>7</number><edition>2010/09/03</edition><dates><year>2009</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>1918-1485 (Electronic)
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ADDIN EN.CITE.DATA (63), acute otitis externa ADDIN EN.CITE <EndNote><Cite><Author>Hui</Author><Year>2013</Year><RecNum>4149</RecNum><DisplayText>(64)</DisplayText><record><rec-number>4149</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1393159081">4149</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hui, C. P.</author></authors></contributors><titles><title>Acute otitis externa</title><secondary-title>Paediatr Child Health</secondary-title><alt-title>Paediatrics & child health</alt-title></titles><periodical><full-title>Paediatr Child Health</full-title><abbr-1>Paediatrics & child health</abbr-1></periodical><alt-periodical><full-title>Paediatr Child Health</full-title><abbr-1>Paediatrics & child health</abbr-1></alt-periodical><pages>96-101</pages><volume>18</volume><number>2</number><edition>2014/01/15</edition><keywords><keyword>Acute otitis externa</keyword><keyword>Swimmer’s ear</keyword></keywords><dates><year>2013</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>1205-7088 (Print)
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ADDIN EN.CITE.DATA (66). Shortening an antimicrobial course by 2-5 days may not seem like much of a difference on an individual patient basis, but when these few days are multiplied by tens of thousands of cases per year, one can begin to appreciate the potential substantial benefits to society in terms of minimizing both population drug resistance and societal health care costs.PART 3: THE MAIN PROJECT1. RationaleDespite the tremendous burden of CAP in children, the optimal duration of antimicrobial use for CAP in children is unknown. The use of 5-day treatment regimens for CAP in adults is now commonplace PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NYW5kZWxsPC9BdXRob3I+PFllYXI+MjAwNzwvWWVhcj48
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ADDIN EN.CITE.DATA (23,67), but evidence to support similar practices in children is almost nonexistent; this has been acknowledged as a key knowledge gap in paediatric infectious diseases PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CcmFkbGV5PC9BdXRob3I+PFllYXI+MjAxMTwvWWVhcj48
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ADDIN EN.CITE.DATA (24). This trial will address this knowledge gap and provide key information to all Ontario physicians who treat children with CAP; optimization of management of paediatric CAP will benefit the children affected, their families, and all Canadians. This trial, as the first adequately-powered study investigating the utility of short-course β-lactam therapy for paediatric CAP in the developed world, would have a substantial and immediate impact on paediatric medicine. 2. Research questionIn previously healthy children diagnosed with community-acquired pneumonia in the emergency department who are well enough to be treated as outpatients, does five days of oral high-dose amoxicillin lead to non-inferior rates of clinical cure at 14-18 days post-enrolment compared with the current standard, 10 days of oral high-dose amoxicillin?3. ObjectivesOur primary objective is to determine whether a short (5-day) course of oral high-dose amoxicillin, compared to a standard 10-day course of high-dose oral amoxicillin, will lead to non-inferior rates of early clinical cure in previously healthy children with mild community-acquired pneumonia. Our secondary objectives are to evaluate the following epidemiological features in children diagnosed with mild CAP in the current era of universal vaccination with the 13-valent pneumococcal vaccine (PCV13) and include:To establish the distribution of saliva C-reactive protein (CRP) values in a cohort of children meeting study criteria for CAP.To determine what proportion of study participants have Streptococcus pneumoniae high-level colonization or Mycoplasma pneumoniae detected in nasopharyngeal swab (NPS) specimens. To determine what proportion of study participants with alveolar consolidation documented on chest radiograph have NPS specimens positive for at least one virus. To investigate whether the results of (2) and (3) differ substantially when stratified by age group (6-59 months vs. 5-10 years of age).To explore whether any of the above factors appear to be more common in children who do not achieve early clinical cure.4. Methodology The current proposal is for a multicentre, randomized, controlled, double-blind, trial. Previously well children aged 6 months - 10 years presenting to the emergency departments (EDs) of McMaster Children’s Hospital (MCH) and the Children’s Hospital of Eastern Ontario (CHEO) with presumed CAP will be randomized to either a 10-day course of high-dose amoxicillin or a 5-day course of amoxicillin plus 5 days placebo.4.1 Study population4.1.1 Inclusion criteria Children aged 6 months to 10 years presenting with CAP will be eligible. This age range was selected for the following reasons: the current incidence of pneumonia in North America is highest in preschool-aged children PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5XaWxsaWFtczwvQXV0aG9yPjxZZWFyPjIwMTM8L1llYXI+
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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CcmFkbGV5PC9BdXRob3I+PFllYXI+MjAxMTwvWWVhcj48
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RW5kTm90ZT4A
ADDIN EN.CITE.DATA (24), but children under the age of five are also more likely to have purely viral infection PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CcmFkbGV5PC9BdXRob3I+PFllYXI+MjAxMTwvWWVhcj48
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ADDIN EN.CITE.DATA (53); however, as many more children aged 5-10 years will have pneumococcal pneumonia, the exclusion of this population – despite their decreased risk of progression to severe disease – would be an unnecessary barrier to effective recruitment.CAP will be defined as present if all four of the following numeric criteria are met: fever (>37.5 C axillary, > 37.7 C oral, or >38 C rectal) ADDIN EN.CITE <EndNote><Cite><Author>Leduc</Author><Year>2000</Year><RecNum>4250</RecNum><DisplayText>(68)</DisplayText><record><rec-number>4250</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1413057656">4250</key></foreign-keys><ref-type name="Web Page">12</ref-type><contributors><authors><author>Leduc, D., Woods, S.</author></authors></contributors><titles><title>Temperature measurement in paediatrics</title></titles><volume>2014</volume><number>October 1</number><dates><year>2000</year></dates><publisher>Community Paediatrics Committee, Canadian Paediatric Society</publisher><urls><related-urls><url>;(68) in the ED or recorded at home in the 48h prior to presentation; any one of: tachypnoea on exam (as per age-specific norms PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5GbGVtaW5nPC9BdXRob3I+PFllYXI+MjAxMTwvWWVhcj48
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ADDIN EN.CITE.DATA (69)); cough on exam or by history;increased work of breathing on exam; or auscultatory findings consistent with pneumonia; findings on chest radiograph consistent with bacterial CAP as judged by the ED physician; the attending ED physician diagnoses the child with primary CAP (a patient with “asthma exacerbation with possible pneumonia” would not be eligible). This definition is almost identical to the ‘reference standard’ in a recent study designed to investigate the accuracy of ICD-9-CM billing codes PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5XaWxsaWFtczwvQXV0aG9yPjxZZWFyPjIwMTM8L1llYXI+
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ADDIN EN.CITE.DATA (70-72); as detailed earlier, this approach is fraught with inaccuracies. The inclusion of fever as a necessary criterion will diminish the probability of recruiting participants with pertussis (which is much less likely to be associated with fever, ADDIN EN.CITE <EndNote><Cite><Author>Long SS</Author><Year>2008</Year><RecNum>3677</RecNum><DisplayText>(6)</DisplayText><record><rec-number>3677</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1360588385">3677</key></foreign-keys><ref-type name="Book">6</ref-type><contributors><authors><author>Long SS, Pickering LK, Prober CG.</author></authors><tertiary-authors><author>Long SS, Pickering LK, Prober CG.</author></tertiary-authors></contributors><titles><title>Principles and Practice of Pediatric Infectious Diseases.</title></titles><edition>3rd.</edition><dates><year>2008</year></dates><pub-location>Philadelphia</pub-location><publisher>Elsevier</publisher><urls></urls></record></Cite></EndNote>(6)) or noninfectious conditions, neither of which would be expected to respond to amoxicillin. The necessity for participants to display a respiratory symptom or sign will diminish the probability of recruiting those with infections of other organ systems who are erroneously diagnosed with pneumonia. The requirement for participants to have a chest radiograph displaying a pneumonic infiltrate will likely increase the probability that they have an infection caused by a bacterial pathogen. Finally – since the aim of this pragmatic trial is to answer a real-world question asked by emergency physicians – it is important that all study participants are actually diagnosed with CAP. To be included, participants must be well enough to be treated as outpatients (adequate volume status, able to tolerate oral medication, oxygen saturation >= 93%, no evidence of impending respiratory failure); obviously, if a child is ill enough to be admitted to hospital, it would be unwise to attempt short-course therapy. Additionally eligible participants must have no evidence of empyaema or necrotizing pneumonia, as routine management of these conditions would require parenteral antibacterials (and admission to hospital).4.1.2 Exclusion criteria Children will be excluded if they have any of the following: cystic fibrosis, anatomic lung disease, bronchiectasis, congenital heart disease, history of repeated aspiration or velopharyngeal incompetence or presence of tracheostomy, malignancy, conditions requiring treatment with immune suppressants (including organ or haematopoietic stem cell transplant, rheumatologic conditions, and inflammatory bowel disease, among others), primary immunodeficiency, advanced HIV infection; many clinicians would not treat any child with the aforementioned conditions with short-course antimicrobial therapy and, in many cases, would use more broad-spectrum antimicrobials due to key differences in potential infecting pathogens. Similarly, any child with prolonged admissions (>48 h) to hospital within the past 2 months, pneumonia previously diagnosed within the past month, or lung abscess diagnosed within the past six months would likely require a prolonged course of antimicrobials. Any participant treated with > 24 hours of beta-lactam antibiotics prior to presentation, that finished a course of amoxicillin < 72h prior to presenting to the ED, or received any intravenous cephalosporins or macrolide therapy in the ED would not be a suitable candidate for the study; receiving these medications in addition to the study antimicrobials could very well mask a ‘true’ difference in efficacy between long- and short-course therapy. Obviously, any child with a suspected allergy to penicillin or food colouring could not be ethically included in the study. Children who have previously been study participants will not be eligible to participate repeatedly, as their likelihood of treatment success or failure would likely be influenced by their success or failure at the time of their first enrolment.4.2 What are the planned trial interventions?4.2.1 Screening, enrolment, and intervention assignment. Education will be provided to ED staff (MDs, RNs, trainees) to inform them of the rationale and objectives of the study. These ED staff will then notify the research assistants (RAs) when a child is diagnosed with CAP; at CHEO, an organized network of volunteers will also participate in ED surveillance. Gift cards ($5) will be given to ED healthcare providers that notify study staff of potential study participants in order to incentivize notification; this strategy has worked well in the pilot at McMaster. Reviews and meta-analyses of strategies to improve retention in trials have consistently identified monetary incentives as being associated with higher rates of follow-up PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CcnVldG9uPC9BdXRob3I+PFllYXI+MjAxNDwvWWVhcj48
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ADDIN EN.CITE.DATA (73-75); smaller incentives provided to all participants have been found to be generally more effective than larger incentives only provided to a few participants via a lottery system ADDIN EN.CITE <EndNote><Cite><Author>Brueton</Author><Year>2014</Year><RecNum>4251</RecNum><DisplayText>(73)</DisplayText><record><rec-number>4251</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1413074258">4251</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Brueton, V. C.</author><author>Tierney, J. F.</author><author>Stenning, S.</author><author>Meredith, S.</author><author>Harding, S.</author><author>Nazareth, I.</author><author>Rait, G.</author></authors></contributors><auth-address>MRC Clinical Trials Unit at UCL, London, UK.</auth-address><titles><title>Strategies to improve retention in randomised trials: a Cochrane systematic review and meta-analysis</title><secondary-title>BMJ Open</secondary-title><alt-title>BMJ open</alt-title></titles><periodical><full-title>BMJ Open</full-title><abbr-1>BMJ open</abbr-1></periodical><alt-periodical><full-title>BMJ Open</full-title><abbr-1>BMJ open</abbr-1></alt-periodical><pages>e003821</pages><volume>4</volume><number>2</number><dates><year>2014</year></dates><isbn>2044-6055 (Electronic)</isbn><accession-num>24496696</accession-num><urls><related-urls><url>;(73). (Many of these studies were done to determine whether financial incentives increased the rate at which study participants returned survey questionnaires, but many of the conclusions are likely generalizable to our context.) The amount of money that generates the maximum incremental benefit per dollar will probably depend on the study population; however, somewhat counter-intuitively, multiple studies have not shown a significant dose-response relationship with financial incentives, with smaller incentives often leading to a similar response rate compared to larger incentives ADDIN EN.CITE <EndNote><Cite><Author>Brueton</Author><Year>2014</Year><RecNum>4251</RecNum><DisplayText>(73)</DisplayText><record><rec-number>4251</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1413074258">4251</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Brueton, V. C.</author><author>Tierney, J. F.</author><author>Stenning, S.</author><author>Meredith, S.</author><author>Harding, S.</author><author>Nazareth, I.</author><author>Rait, G.</author></authors></contributors><auth-address>MRC Clinical Trials Unit at UCL, London, UK.</auth-address><titles><title>Strategies to improve retention in randomised trials: a Cochrane systematic review and meta-analysis</title><secondary-title>BMJ Open</secondary-title><alt-title>BMJ open</alt-title></titles><periodical><full-title>BMJ Open</full-title><abbr-1>BMJ open</abbr-1></periodical><alt-periodical><full-title>BMJ Open</full-title><abbr-1>BMJ open</abbr-1></alt-periodical><pages>e003821</pages><volume>4</volume><number>2</number><dates><year>2014</year></dates><isbn>2044-6055 (Electronic)</isbn><accession-num>24496696</accession-num><urls><related-urls><url>;(73). After quickly obtaining some screening information over the phone, the RAs will then proceed to the ED to recruit the participant. All participants will be given an initial 5 days of amoxicillin. For potential participants who present at a time when an RA is not available, the attending ED physician will prescribe amoxicillin at the study dose and obtain consent for subsequent RA contact and potential enrolment at the participant’s home within 24 hours after ED discharge.4.2.2 Experimental (short course antimicrobials). Those randomized to the intervention will receive amoxicillin 90 mg/kg/day divided twice daily for 5 days (‘medication series A’) followed by placebo twice daily for 5 days (‘medication series B’). The placebo will be identical in appearance to the amoxicillin given as ‘medication series B’ to the control group and will be packaged identically.It was decided that five days of antibacterials was the most appropriate duration to test in the experimental arm, for the following reasons:5 days of antibacterials has been shown to be non-inferior to 10 days for the treatment of CAP in adults PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5EdW5iYXI8L0F1dGhvcj48WWVhcj4yMDAzPC9ZZWFyPjxS
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ADDIN EN.CITE.DATA (45)5 days of antibacterials has been shown to be non-inferior to 10 days for the treatment of bacterial meningitis in children, a much more severe infectious syndrome than mild CAP PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Nb2x5bmV1eDwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+
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ADDIN EN.CITE.DATA (76)3 days of antibacterials are routinely used for CAP treatment in lower-resourced settings. However, if a trial found that 3 days of treatment was inferior to the reference standard, this would not obviate the possibility that 5 days might be as effective as 10 days; it seems more practical (and ethical!) to us to conduct a trial comparing 5 days to 10 days first, and then address the issue of whether 3 days would be sufficient. Additionally, a similar trial found higher rates of treatment failure from 3-day courses of antibacterials than with 10 days of therapy PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HcmVlbmJlcmc8L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFy
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ADDIN EN.CITE.DATA (53). Many clinicians already use 7 days of therapy for mild CAP; we note that the CPS guideline states that 7-10 days of treatment is ‘standard’, despite a lack of evidence for this recommendation ADDIN EN.CITE <EndNote><Cite><Author>Le Saux</Author><Year>2011</Year><RecNum>3920</RecNum><DisplayText>(37)</DisplayText><record><rec-number>3920</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1381460228">3920</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Le Saux, N., Robinson JL.</author></authors></contributors><titles><title>Pneumonia in healthy Canadian children and youth: practice points for management.</title><secondary-title>Pediatr Child Health</secondary-title></titles><periodical><full-title>Pediatr Child Health</full-title></periodical><pages>417-20</pages><volume>16</volume><number>7</number><dates><year>2011</year></dates><urls></urls></record></Cite></EndNote>(37). It would therefore be a suboptimal use of resources to formally demonstrate the non-inferiority of 7 days compared to 10 days if this will not lead to any significant change in practice, especially if we suspect that 5 days of therapy will also be non-inferior.4.2.3 Control (standard course). Children presenting with study-defined CAP randomized to the control group will receive standard therapy, ie. amoxicillin 90 mg/kg/day divided twice daily for 5 days (‘medication series A’) followed by a second (altered in colour and consistency) course of amoxicillin 90 mg/kg/day divided twice daily for 5 days (‘medication series B’). Both arms require a distinct ‘medication series B’ to avoid unblinding since pharmacy is not able to precisely match the taste of liquid placebo to the amoxicillin of ‘medication series A.’ 4.2.4. Lab testing at enrollment. For study participants who have blood work drawn as part of routine care (as per the attending ED physician), a complete blood count and serum C-reactive protein (CRP) will be sent. Though these laboratory investigations are not sensitive or specific enough to rule CAP in or out in a given participant, their levels have been found to be proportional to the probability of having a bacterial infection, enabling stratification of participants in sensitivity analyses PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Lb3JwcGk8L0F1dGhvcj48WWVhcj4xOTk3PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA (77). For all other patients, a saliva CRP will be sent. This particular test has not been studied in the context of acute paediatric lower respiratory tract infection; consequently, at this stage, one cannot predict whether higher salivary CRP levels will be seen in children with bacterial pneumonia. However, we have received funding and are about to begin a prospective cohort study enrolling hospitalized children with viral bronchiolitis, bacterial complicated pneumonia, and community-acquired pneumonia (possibly bacterial) in whom salivary CRP will be assayed. It will therefore be known whether salivary CRP is truly higher in children with bacterial pneumonia prior to the analysis of this proposed multicentre randomized trial.All patients will have nasopharyngeal swabs collected and tested for respiratory viral pathogens. The multiplex respiratory virus polymerase chain reaction (PCR) testing panel in clinical use at McMaster Children’s Hospital detects parainfluenza 1/2/3, influenza A/B, RSV A/B, adenovirus, human metapneumovirus, rhinovirus, and enterovirus. Should the epidemiology of viral infections in Ontario change significantly during the study period we will also have access to the Luminex xTag RVP testing panel, which also detects coronaviruses. All NPS specimens will also have incidence density of Streptococcus pneumoniae (target is lytA) measured using a quantitative PCR assay; “high-level” colonization will be defined as > 10 000 genome equivalents/mL specimen. To detect ‘atypical’ organisms, a loop-mediated isothermal amplification (LAMP) assay will be used to simultaneously detect Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella pneumophila. It will be critically important to document what respiratory pathogens are present in each of the study participants both to expand our knowledge of the epidemiology of mild paediatric CAP in the current era as well as to permit sensitivity analyses; it is common to have viral-bacterial pulmonary coinfection, but logic would dictate that the probability of bacterial infection is higher in a child with no viral/atypical pathogens detected than in a child with a positive NPS for a viral pathogen.4.3 Randomization and group allocation. Dr. Thabane’s Biostatistics Unit at St Joseph’s Healthcare Hamilton will organize participant randomization using a centralized computer system accessible by phone 24 hours per day, 7 days per week. A randomization list stratified by centre will be generated such that participants can be assigned at random to one of the two study groups in a 1:1 ratio. The randomization will be blocked using random block sizes of 2, 4, and 6. The blocks will be of random sizes to provide another layer of protection to the blinding process, so that neither the RAs nor the investigators know into which groups the participants are randomized.4.4 Proposed methods for protecting against other sources of biasTo reduce the possibility of selection bias, all children who are diagnosed with CAP in the EDs of MCH and CHEO will be screened and approached to participate. It will be substantially harder to recruit potential participants who present in the middle of the night; this may introduce bias if those children are different than those who present during the day and early evening. We will attempt to minimize this threat to validity by contacting potential participants who present during the night at home the next day. Randomization and allocation will proceed as described above. As it is impossible to precisely match the taste and appearance of the placebo to the amoxicillin suspension, we have planned a two-series medication system (‘series A’ and ‘series B’) to prevent unblinding by ensuring that all participants change medications after 5 days. 4.5 Participant follow-up4.5.1 Frequency and duration of follow-up. Outcome data will be collected both by the participants’ caregivers in a symptom diary (previously pilot-tested) and by the RA. Diary forms will inquire to symptoms and signs relevant to the secondary outcomes (see 4.6.2, ‘Secondary outcomes’, below); caregivers will be asked to fill out a diary form daily for the 10 days post-enrolment. The RA will contact the participants three times (day 3-5, day 7-10, and one month after enrollment) to verify clinical stability, to reinforce adherence to the diary, and to troubleshoot problems. The first telephone contact is critical to ensure that no participants with persistent fever might possibly be randomized to short-course therapy; parents will also be reminded to contact the RA should they develop fever after day 4 and any participant with persistent/recrudescent illness will be invited to be assessed by a co-investigator. As noted above, any study participant with persistent fever >72h after beginning the study medication will be re-assessed as necessary and will complete at least 10 days of (open-label) amoxicillin. The phone call at 7-10 days will be used to verify the absence of recrudescent illness and to collect data in the event that the caregiver does not fully complete the symptom diary. Participants will return to the hospital for a visit between day 14-18 to deliver the symptom diaries, all medication containers, and to permit assessment by a physician or nurse either in the ED or a paediatric outpatient clinic. 4.6 Proposed outcome measures.4.6.1 Primary outcome - early clinical cure The primary outcome, early clinical cure, will be defined by meeting all of the following criteria: 1) significant improvement in dyspnoea and increased work of breathing, and no recorded tachypnoea, at the day 14-18 follow-up visit; 2) no more than 1 fever spike (as noted in the definition of CAP) as a result of bacterial respiratory illness from day 4 up to and including the day 14-18 follow-up visit; and 3) lack of a requirement for additional antibacterials or admission to hospital because of persistent/progressive lower respiratory illness during the 2 weeks after enrollment. 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ADDIN EN.CITE.DATA (45). Our definition was created using explicit criteria to ensure transparency and maximize the generalizability of the results. However, to optimize the appropriateness of the definition, the criteria are somewhat complex; this is to ensure that ‘failure’ in the trial would be associated with a clinical scenario that would merit a change in overall management, even if that change was as little as a requirement for additional follow-up by the treating clinician. The first criterion of the definition states ‘significant improvement’ in respiratory symptoms; this will be assumed to be present if the participant’s caregiver opines that the child has no functional limitation resulting from any residual dyspnoea/increased work of breathing. This was written in this way because the first iteration of this criterion in the pilot study stated ‘complete resolution’; there was one child who had very mild increased work of breathing at the follow-up visit and as such was judged to have ‘failed therapy’, though no further antimicrobials or follow-up was deemed necessary by the treating clinician. The second criterion notes that more than a single spike of fever is required for ‘failure’ to avoid erroneous conclusions resulting from an errant thermometer reading; two participants in the pilot ‘failed’ therapy because of a single spike of fever not leading to any management change. Fevers of unknown aetiology will be presumed to be associated with bacterial respiratory illness, but participants with fevers due to other discernible causes, whether viral (new respiratory illness documented by a NPS positive for a virus not present at the time of initial enrolment, clinical croup, stomatitis/herpangina, hand-foot-mouth disease, gastroenteritis with positive stool results, conjunctivitis, meningoencephalitis, viral hip synovitis, peri-or myocarditis, hepatitis) or bacterial (cellulitis and other soft tissue infections, septic arthritis/osteomyelitis, meningitis, urinary tract infection with positive urinalysis, or cholecystitis) would be considered to have met clinical cure criteria. Clearly, admission to hospital – even if antimicrobial treatment does not need to be changed – is not conducive to short-course therapy and merits a decision of treatment ‘failure.’For the measurement of the primary outcome, a physician or nurse, blinded to treatment allocation, will assess temperature, respiratory rate, and evident increased work of breathing in person using standardized protocols; these physical examination findings are the most important when assessing response to therapy. Lack of fever at home will be verified through assessment of the symptom diaries. Medical visits for persistent respiratory illness will be assessed by directly asking the participant’s caregiver; though caregiver report is not an entirely reliable modality, we believe that the sensitivity and specificity of the question ‘Did your child see another health professional because of a concern about respiratory illness within the past ten days?’ should be adequate.4.6.2 Secondary outcomes Secondary outcomes will include: the number of days the participant is absent from school; the total number of caregiver-days that their work is disrupted to care for the child; the number of days of mild drug adverse reactions; the incidence of severe drug adverse reactions (including anaphylaxis); participant adherence to the study medications; and recurrence of respiratory illness in the month after enrollment that leads to an ED visit or another antimicrobial course. We feel that these outcomes are important to children and their caregivers, especially for mild illness with an excellent prognosis. These will all be participant- or caregiver-report measures, and will be measured through participant documentation in the diaries; there will also be secondary verification by the research assistant at telephone contact on days 3-5 and 7-10 after enrollment. The symptom diary will include the following: temperature, dyspnoea (older participants), increased work of breathing, school attendance, caregiver absenteeism, days of mild diarrhoea, abdominal discomfort, vaginitis, rash) and severe (anaphylaxis) drug adverse reactions, and the number of missed medication doses. The caregivers will be instructed how to take their child’s temperature and assess increased work of breathing. Measuring adherence is a trial setting is not a simple matter. There are direct and indirect methods of assessing adherence; of these, direct methods are much more accurate. These include directly observed therapy or measurement of drug levels in blood, both of which are impractical for a study such as this, and would likely cause substantial inconvenience and/or pain to the study participants. Indirect methods include patient (or caregiver) (self-)report; pill counts; patient diaries; electronic medication monitors; rates of prescription refills; assessment of the patient’s clinical response; and measurement of physiologic markers ADDIN EN.CITE <EndNote><Cite><Author>Osterberg</Author><Year>2005</Year><RecNum>4110</RecNum><DisplayText>(78)</DisplayText><record><rec-number>4110</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1388958955">4110</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Osterberg, L.</author><author>Blaschke, T.</author></authors></contributors><auth-address>General Medicine Division, Veterans Affairs Palo Alto Health Care System, Palo Alto, California 94304, USA. larso@stanford.edu</auth-address><titles><title>Adherence to medication</title><secondary-title>N Engl J Med</secondary-title><alt-title>The New England journal of medicine</alt-title></titles><periodical><full-title>N Engl J Med</full-title><abbr-1>The New England journal of medicine</abbr-1></periodical><alt-periodical><full-title>N Engl J Med</full-title><abbr-1>The New England journal of medicine</abbr-1></alt-periodical><pages>487-97</pages><volume>353</volume><number>5</number><edition>2005/08/05</edition><keywords><keyword>Adolescent</keyword><keyword>Child</keyword><keyword>Chronic Disease/drug therapy</keyword><keyword>Drug Administration Schedule</keyword><keyword>*Drug Therapy/psychology/statistics & numerical data</keyword><keyword>HIV Infections/drug therapy</keyword><keyword>Humans</keyword><keyword>Hypertension/drug therapy</keyword><keyword>Mental Disorders/drug therapy</keyword><keyword>*Patient Compliance/psychology/statistics & numerical data</keyword></keywords><dates><year>2005</year><pub-dates><date>Aug 4</date></pub-dates></dates><isbn>1533-4406 (Electronic)
0028-4793 (Linking)</isbn><accession-num>16079372</accession-num><work-type>Review</work-type><urls><related-urls><url>;(78). Of these seven, we plan to use the first three, and the last four are not appropriate for the study (monitors are expensive, no refills are needed, and, in this case, neither patient assessment nor measurement of physiologic markers will inform adherence). Some investigators state that patient self-report is “simple, inexpensive, and the most useful method in the clinical setting,” though they note that the results are “easily distorted by the patient”; these same authors note that pill counts are “objective, quantifiable, and easy to perform,” again noting that participants can dump medication to conceal nonadherence ADDIN EN.CITE <EndNote><Cite><Author>Osterberg</Author><Year>2005</Year><RecNum>4110</RecNum><DisplayText>(78)</DisplayText><record><rec-number>4110</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1388958955">4110</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Osterberg, L.</author><author>Blaschke, T.</author></authors></contributors><auth-address>General Medicine Division, Veterans Affairs Palo Alto Health Care System, Palo Alto, California 94304, USA. larso@stanford.edu</auth-address><titles><title>Adherence to medication</title><secondary-title>N Engl J Med</secondary-title><alt-title>The New England journal of medicine</alt-title></titles><periodical><full-title>N Engl J Med</full-title><abbr-1>The New England journal of medicine</abbr-1></periodical><alt-periodical><full-title>N Engl J Med</full-title><abbr-1>The New England journal of medicine</abbr-1></alt-periodical><pages>487-97</pages><volume>353</volume><number>5</number><edition>2005/08/05</edition><keywords><keyword>Adolescent</keyword><keyword>Child</keyword><keyword>Chronic Disease/drug therapy</keyword><keyword>Drug Administration Schedule</keyword><keyword>*Drug Therapy/psychology/statistics & numerical data</keyword><keyword>HIV Infections/drug therapy</keyword><keyword>Humans</keyword><keyword>Hypertension/drug therapy</keyword><keyword>Mental Disorders/drug therapy</keyword><keyword>*Patient Compliance/psychology/statistics & numerical data</keyword></keywords><dates><year>2005</year><pub-dates><date>Aug 4</date></pub-dates></dates><isbn>1533-4406 (Electronic)
0028-4793 (Linking)</isbn><accession-num>16079372</accession-num><work-type>Review</work-type><urls><related-urls><url>;(78). In the proposed trial, adherence with medications will be assessed from the diaries but will also be measured by checking the (returned) medication containers; any left-over medication will be weighed. 4.7 Sample sizeWe estimate the baseline failure rate of standard therapy to be ~5%; this estimate is consistent with previous studies in children PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IYXJyaXM8L0F1dGhvcj48WWVhcj4xOTk4PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA (79). Setting at 5%, with 80% power, 135 participants in each arm will be required for this trial (PASS software package, NCSS LLC, Kayesville, UT); as we will have accrued ~ 60 subjects in the pilot to be ‘rolled-over’, an additional 210 participants will be required. 4.8 Anticipated recruitment rateThe pilot has had very low rates of loss to follow-up (2/61, 3%) presumably due to the acute nature of the problem and the fact that many caregivers appreciate the clinical service provided. We anticipate enrolling ~60 participants per year at McMaster Children’s Hospital, based on the pilot results. As CHEO has many more children presenting to their ED, we predict conservatively that we will be able to enroll at least 75 per year at that site. All estimates below are based on data from CHEO ED census Mar 2011 – Apr 2013.Children (aged 6 mos. – 10 y) with CAP to CHEO ED: 1442/yearAs above, restricted to those arriving 10 am – 10 pm: 986/yearProjected enrolment with MCH ineligibility/success rates: 124/yearDetailed review of 50 randomly selected charts of children aged 6 months – 10 years diagnosed with CAP at the CHEO ED in 2013 demonstrated that 22 (44%) met all inclusion and exclusion criteria. Assuming McMaster rates of missing/refusal of approach/refusal of consent, estimated enrolment would be 986*0.44*(55/(55+56+38+9)) = 151 participants/year. Overall, it is very likely that we will be able to recruit 50-75 participants/year at McMaster Children’s and 75-100 participants/year at the Children’s Hospital of Eastern Ontario.4.9 Data analysis. We will adopt CONSORT criteria in reporting the trial. The principal analysis will be per-protocol, as is recommended for noninferiority trials PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TbmFwaW5uPC9BdXRob3I+PFllYXI+MjAwMDwvWWVhcj48
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ADDIN EN.CITE.DATA (80-82). The principal analysis is not intention-to-treat (ITT) simply because the effect of ITT analysis is to reduce the difference seen between treatment groups; in a superiority trial, this functions to buttress a conclusion of superiority, but in a non-inferiority trial, ITT analysis could lead to a false conclusion of non-inferiority by masking a true difference between treatment arms. The baseline characteristics will be analyzed using descriptive statistics reported as mean (standard deviation) or median (first quartile, third quartile) for continuous variables depending on the distribution and count (percent) for categorical variables. As the primary outcome is binary, the chi-square test will be used; secondary outcomes will be analysed using chi-square or t-test depending on the distribution of the outcome variable. As this is a non-inferiority trial, the crucial statistical comparison will be between the 95%CI of the difference between the failure rate of the experimental arm and the standard therapy arm; should the upper bound of this difference be smaller than 7.5%, a conclusion of non-inferiority will be reached. Descriptive analyses will be used to compare rates of viral and atypical co-infections in the entire study population and between groups, stratified by age. We will use the t-test or chi-squared test to analyze secondary outcomes as appropriate (former for continuous variables, latter for dichotomous variables). These analyses will be exploratory. The following sensitivity analyses are planned: 1) intention-to-treat analysis; 2) strict per-protocol analysis including only those participants whose radiographs were reported by a radiologist to have alveolar infiltrates; 3) per-protocol analysis stratified by whether the saliva CRP was greater than the 75%ile; and 4) per-protocol analysis stratified by whether a virus, an atypical pathogen, or high-level S. pneumoniae colonization was found in the NPS. If evidence is found of effect modification or confounding related to the above parameters additional analyses will be undertaken. The results of all analyses will be reported as estimate of effect, corresponding 95% confidence interval and associated p-values. All p-values will be reported to three decimal places with those less than 0.001 reported as p<0.001. The criterion for statistical significance will be set at alpha = 0.05. 4.10 Anticipated results Given our clinical experience, as well as the results of the small Israeli trial PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HcmVlbmJlcmc8L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFy
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ADDIN EN.CITE.DATA (24). We will measure adherence by collecting used medication bottles and determining how many doses were taken; this method is not foolproof but is acceptable ADDIN EN.CITE <EndNote><Cite><Author>Osterberg</Author><Year>2005</Year><RecNum>4110</RecNum><DisplayText>(78)</DisplayText><record><rec-number>4110</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1388958955">4110</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Osterberg, L.</author><author>Blaschke, T.</author></authors></contributors><auth-address>General Medicine Division, Veterans Affairs Palo Alto Health Care System, Palo Alto, California 94304, USA. larso@stanford.edu</auth-address><titles><title>Adherence to medication</title><secondary-title>N Engl J Med</secondary-title><alt-title>The New England journal of medicine</alt-title></titles><periodical><full-title>N Engl J Med</full-title><abbr-1>The New England journal of medicine</abbr-1></periodical><alt-periodical><full-title>N Engl J Med</full-title><abbr-1>The New England journal of medicine</abbr-1></alt-periodical><pages>487-97</pages><volume>353</volume><number>5</number><edition>2005/08/05</edition><keywords><keyword>Adolescent</keyword><keyword>Child</keyword><keyword>Chronic Disease/drug therapy</keyword><keyword>Drug Administration Schedule</keyword><keyword>*Drug Therapy/psychology/statistics & numerical data</keyword><keyword>HIV Infections/drug therapy</keyword><keyword>Humans</keyword><keyword>Hypertension/drug therapy</keyword><keyword>Mental Disorders/drug therapy</keyword><keyword>*Patient Compliance/psychology/statistics & numerical data</keyword></keywords><dates><year>2005</year><pub-dates><date>Aug 4</date></pub-dates></dates><isbn>1533-4406 (Electronic)
0028-4793 (Linking)</isbn><accession-num>16079372</accession-num><work-type>Review</work-type><urls><related-urls><url>;(78) and appropriate for this trial. 5. Trial management5.1 Data Safety and Monitoring Board (DSMB). This committee, comprised of two clinical experts and a biostatistician, guided by a charter to be created, will be responsible for safety oversight of the study, including monitoring of adverse reactions. The DSMB will be responsible for making recommendations on safety issues, premature trial termination, and unblinding of study groups. The DSMB, which will be blinded to study group, will be asked to review safety data on an biannual basis for each arm of the study. If safety concerns arise, more frequent meetings will be initiated. The DSMB will receive immediate notification and reports of serious adverse reactions. There are no plans for an interim analysis as the estimated risk of harm associated with this trial is low. 5.2 Risks to the safety of trial participantsBoth arms of the trial will be given amoxicillin, the first-line agent for the treatment of paediatric CAP. The main theoretical risk to those in the short-course group will be relapse due to potential under-treatment, which will be minimized by maintaining close contact with all participants. As discussed above, although the CPS guideline states (without reference) that 7-10 days of antibiotic therapy for paediatric CAP is ‘standard’ for uncomplicated pneumonia ADDIN EN.CITE <EndNote><Cite><Author>Le Saux</Author><Year>2011</Year><RecNum>3920</RecNum><DisplayText>(37)</DisplayText><record><rec-number>3920</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1381460228">3920</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Le Saux, N., Robinson JL.</author></authors></contributors><titles><title>Pneumonia in healthy Canadian children and youth: practice points for management.</title><secondary-title>Pediatr Child Health</secondary-title></titles><periodical><full-title>Pediatr Child Health</full-title></periodical><pages>417-20</pages><volume>16</volume><number>7</number><dates><year>2011</year></dates><urls></urls></record></Cite></EndNote>(37), the IDSA guidelines explicitly say that it is likely that shorter courses will be just as effective and that further studies are needed PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CcmFkbGV5PC9BdXRob3I+PFllYXI+MjAxMTwvWWVhcj48
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ADDIN EN.CITE.DATA (76). It is for these reasons that it is critical to conduct a study such as this, in an effort to optimize the way we care for children. It should be noted that close monitoring will mitigate any of the possible risks of short-course therapy. For example, the research assistant, at the time of the first contact 3-5 days after enrollment, will ensure that the participant has defervesced; should this not be the case, blinding will be broken and the participant will be given a 10-day course of amoxicillin. We will also ensure that caregivers have detailed instructions outlining which medical professionals at McMaster Children’s Hospital to contact in the event of a clinical deterioration during the study period at all hours to facilitate re-evaluation of the participant and appropriate medical management. Overall, given that study participants will likely have much closer follow-up than non-participants, that medications will be provided free of charge, and that they will be guaranteed to receive appropriate antibiotic therapy, study participants stand to directly benefit from participating in the study. We note as well that a similar recently published study, though under-powered and terminated early for benefit, showed no difference in failure rate between 5- and 10-day therapy PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HcmVlbmJlcmc8L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFy
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ADDIN EN.CITE.DATA (53).6. Knowledge translation planThe nature of the proposed trial is strongly toward the pragmatic end of the clinical trial spectrum PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5UaG9ycGU8L0F1dGhvcj48WWVhcj4yMDA5PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA (83); consequently, the results of the trial will be positioned for rapid integration into clinical practice by Canadian physicians. To that end, both integrated and end-of-grant KT methods will be employed to facilitate communication of study results to healthcare practitioners – the main knowledge users for this study. The principal KT goal of the project will be, subsequent to the determination of whether short-course antimicrobial therapy is noninferior to the standard of care, to facilitate integration of trial results into current Canadian CAP guidelines and disseminate the information to the healthcare community. To do this, research team members will collaborate with established networks of clinicians experienced in the dissemination of clinical guidelines to healthcare practitioners, i.e. the Canadian Paediatric Society, Association of Medical Microbiology and Infectious Disease Canada, Infectious Disease Society of America, Canadian Association of Emergency Physicians, and Pediatric Emergency Research Canada (PERC). Given that PERC, a highly successful research network involving 15 children’s hospitals, represents a key group of knowledge users for this study, the executive was invited to the table in the design phase to ensure that the study objectives were relevant to Canadian emergency physicians and the study protocol was structured in such a way to optimize both internal and external validity. PERC has since unanimously endorsed the proposed study as one deserving of its support; furthermore, the study protocol was presented to the wider PERC community for more feedback at its annual meeting in 2014. The above-noted collaborations will be stimulated though presentation at major Canadian and American meetings (Pediatric Academic Societies, Canadian Paediatric Society, etc.); healthcare decision makers will be provided a one page synopsis of the results and invited to meet with study team members to discuss the implications. The end-of-grant KT strategy will also focus on publication of results in a peer-reviewed open-source journal (preferably a general paediatric journal because of the broad audience), oral and poster presentation at local and national meetings, and leveraging dissemination through the diverse professional networks of the research team members (the applicant and co-investigators are trained in disciplines including paediatric infectious disease, adult infectious disease, medical microbiology, clinical epidemiology, and paediatric emergency). In all cases, messages will be tailored to ensure relevance to the target audience. PART 4 – THE COMPLETED PILOT TRIALThe design of the pilot trial was very similar to that of the main follow-up study described in detail in Part 2. This section will outline aspects specific to the pilot and will describe problems encountered in the conduct of the pilot trial, with specific reference to design features that were modified for the main follow-up study; design features of the pilot that were not changed for the multicentre trial will not be listed, to avoid redundancy. Preliminary clinical and microbiologic results will be presented.ObjectiveThe main objective of the pilot trial was to investigate feasibility of the follow-up multicentre trial. The feasibility criteria of the pilot were:to enrol at least 70 participants during the 9-month study period; to complete the enrolment process within 90 minutes for >90% of participants; to ensure appropriate blood and respiratory specimens get sent in >90% of participants; to ensure >90% of participants complete the symptom diaries correctly; to contact >98% of participants at day 3-5 post-randomization; to ensure that 100% of contacted participants who do not defervesce by day 4 post-randomization are unblinded and are continued on a full 10 days of amoxicillin; to contact >95% of participants at day 7-10 post-randomization; to reassess >90% of participants at MCH at day 14-18 post-randomization; and to contact >90% of participants at ~ 1 month post-randomization. These feasibility objectives were constructed with reference to a seminal work on pilot studies ADDIN EN.CITE <EndNote><Cite><Author>Thabane</Author><Year>2010</Year><RecNum>4193</RecNum><DisplayText>(84)</DisplayText><record><rec-number>4193</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1407360118">4193</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Thabane, L.</author><author>Ma, J.</author><author>Chu, R.</author><author>Cheng, J.</author><author>Ismaila, A.</author><author>Rios, L. P.</author><author>Robson, R.</author><author>Thabane, M.</author><author>Giangregorio, L.</author><author>Goldsmith, C. H.</author></authors></contributors><auth-address>Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton ON, Canada. thabanl@mcmaster.ca</auth-address><titles><title>A tutorial on pilot studies: the what, why and how</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>1</pages><volume>10</volume><keywords><keyword>Clinical Trials, Phase III as Topic/methods</keyword><keyword>Humans</keyword><keyword>*Pilot Projects</keyword><keyword>Randomized Controlled Trials as Topic</keyword><keyword>*Research Design/standards</keyword></keywords><dates><year>2010</year></dates><isbn>1471-2288 (Electronic)
1471-2288 (Linking)</isbn><accession-num>20053272</accession-num><urls><related-urls><url>;(84). Our primary concern was the ability of a research assistant to contact, recruit, and enroll sufficient numbers; consequently, the majority of feasibility criteria were drawn from the ‘resource projections’ domain (see section on ‘feasibility criteria’ in Part 5). As the only potential disadvantage of short-course antimicrobial therapy would be an increased risk of treatment failure, there are also feasibility criteria specifying minimum rates of loss to follow-up and/or switches to rescue standard-course therapy. There were no feasibility criteria addressing the appropriateness of the study population or that of the appropriateness of the selected outcomes; the revisions to the primary outcome that occurred over the course of the trial will be covered in detail below. The trial enrolled 61 participants over a 14-month period. We had predicted a higher number of potentially eligible participants on the basis of reviewing previous McMaster Children’s Hospital emergency department (ED) data; the difference between predicted and actual enrolment is due in large part to the vagaries of coding for children with lower respiratory tract infection and the differences in the way different clinicians diagnose ‘pneumonia’ (please see the relevant sections detailing issues with the clinical and microbiologic diagnosis of pneumonia in Part 1). However, the fact that we recruited fewer than 70 participants in a nine-month period will not preclude proceeding with the main trial; it will simply lead to a modification of expectations (and consequent budgetary changes). Recruitment for the first 12.5 months of the trial (21 Dec 2012 – 11 Jan 2014) can be summarized as follows: Diagnosed with mild CAP, aged 1-10 years: 435Ineligible: 277came to ED already on β-lactam:89no fever on history or exam: 65asthma flare or Hx severe asthma:28pneumonia dx in past month: 24allergy to penicillin: 21no resp symptom or sign: 14got ceftriaxone or macrolide in ED: 13significant PMHx: 11no CXR done: 06recent admission to hospital: 02previously in study:02unimmunized: 01from another region (visiting): 01Remainder eligible: 158Missed: 56Refused approach: 9Refused consent:38Enrolled: 55Feasibility criterion #2 was established because of concerns from ED staff that recruitment and enrolment would interfere with flow in the ED; however, no problems were encountered, primarily because the recruitment process took approximately half an hour. It was therefore assumed that this feasibility criterion was met, though detailed time records were not kept. We did not foresee that only 7 of 61 participants would have blood work drawn by the attending ED physician. This is in contrast to clinical practice described at other sites conducting trials in optimizing treatment for paediatric CAP PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HcmVlbmJlcmc8L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFy
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ADDIN EN.CITE.DATA (24), we revised the inclusion criteria partway through the trial to permit enrolment of these infants. The exclusion criteria were not changed.Laboratory testing at enrolmentThe necessity of changing the protocol to include saliva-based C-reactive protein sampling (because of the rarity of venipuncture in these relatively well children) has already been discussed. RandomizationAs the pilot trial was based at a single centre, the study pharmacy was in charge of randomization; phone-based randomization was not used. At enrolment in the ED, all participants were given a five-day supply of amoxicillin. The study pharmacy then randomized the patient and provided either five more days of amoxicillin (different formulation) or five days of placebo; the participants returned to McMaster before day 5 to obtain the second set of medications. Clearly, this system will not work with multiple sites, and so it was modified for the main study.Proposed outcome measuresThe primary outcome in the pilot, composed of three separate items, was very similar to that described for the multicentre study, and was defined as follows:Complete resolution of dyspnoea, increased work of breathing, and tachypnoea, PLUSPersistent afebrile state from day 4 up to and including the day 14-18 follow-up visit, PLUSLack of a requirement for additional antibacterials or admission to hospital because of persistent/progressive lower respiratory illness during the 2 weeks after enrolment.It was modified slightly, however, as a few children who were essentially well at the time of follow-up were counted as ‘failures’, unnecessarily introducing noise into the analysis. Clinical trials should use outcomes that are relevant to individuals and clinicians; a definition of ‘failure’ that does not involve any requirement for a change of management or a change in prognosis should be modified. Item 1 was changed from ‘complete resolution’ to ‘significant improvement’, as there was one child who had mild residual increased work of breathing at day 14-18 but did not require any other medication and was normal at 1-month followup. Item 2 was expanded upon so that children with a documented new respiratory viral infection or an obvious alternate cause of fever would not be judged to have ‘failed’ antimicrobial therapy; the requirement for >1 fever spike was also added as there were two participants who had a single isolated fever spike during the second 5 days of therapy and were entirely well at day 14-18 follow-up. The effect of these changes will be to make antimicrobial failure more rare – and therefore increase the sample size requirements for the main study – but will decrease the ‘noise’ in the analysis, as non-meaningful ‘failures’ might occur by chance more commonly in one arm than another and produce spurious results in the main trial.Sample sizeThe sample size was selected in order to test study procedures, protocols, and resources, in an effort to verify that the feasibility criteria could be achieved. We did not calculate a sample size in order to estimate the variance of treatment failure for sample size calculations in the main follow-up study; please note that much of the literature on this topic has been developed for interval/ratio covariates that have normal distributions (see ‘Sample size considerations’ in Part 5).Pilot trial results (clinical)Blinding has been maintained; the following consist of the results in aggregate. The median age of participants was 2.64 years (Q1-Q3 1.64 – 4.33 y). As previously noted, only seven participants underwent venipuncture; the median peripheral WBC count was 13.5 x 109 cells/L (Q1-Q3 10.3 – 16.7 x 109 cells/L) and the median serum C-reactive protein level was 34.3 g/L (Q1-Q3 30.3 – 44.5 g/L). Though all participants were required to have a consolidation on chest radiograph as judged by the ED physician, only 60% of chest radiographs of study participants were reported to have findings consistent with pneumonia by the attending paediatric radiologist. Six children (10%) did not achieve clinical cure, as defined a priori. Two participants experienced significant clinical problems; one developed worsening respiratory symptoms and was hospitalized on the 4th day after enrolment and the other had persistent fever as so was given open-label amoxicillin to finish 10 days of therapy. The other four participants who did not achieve cure had less significant clinical illness: one had residual very mild work of breathing at day 14-18, one had recrudescent respiratory symptoms on day 8 and so was prescribed additional antibacterials (but had a new respiratory viral infection documented on repeat nasopharyngeal sampling), one had a single spike of fever on day 11 (but was well at followup), and one had a single spike of fever or day 17 (but was well at followup). Were we to follow the recommendations set out by Cocks and Torgerson, despite the fact that their theory was developed for use with interval/ratio outcome measures, the only scenario that would preclude proceeding with the main follow-up study would be if all 6 ‘failures’ occurred in the short-course antimicrobial treatment arm, as the risk difference would be 0.2 (lower bound of 80% CI 0.11, higher than the selected margin of 0.075) ADDIN EN.CITE <EndNote><Cite><Author>Cocks</Author><Year>2013</Year><RecNum>4209</RecNum><DisplayText>(85)</DisplayText><record><rec-number>4209</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1407757294">4209</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Cocks, K.</author><author>Torgerson, D. J.</author></authors></contributors><auth-address>York Trials Unit, Department of Health Sciences, University of York, Heslington, York YO10 5DD, UK.</auth-address><titles><title>Sample size calculations for pilot randomized trials: a confidence interval approach</title><secondary-title>J Clin Epidemiol</secondary-title><alt-title>Journal of clinical epidemiology</alt-title></titles><periodical><full-title>J Clin Epidemiol</full-title><abbr-1>Journal of clinical epidemiology</abbr-1></periodical><alt-periodical><full-title>J Clin Epidemiol</full-title><abbr-1>Journal of clinical epidemiology</abbr-1></alt-periodical><pages>197-201</pages><volume>66</volume><number>2</number><keywords><keyword>*Confidence Intervals</keyword><keyword>Evidence-Based Medicine/standards</keyword><keyword>Female</keyword><keyword>Great Britain</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>*Pilot Projects</keyword><keyword>Practice Guidelines as Topic/*standards</keyword><keyword>*Randomized Controlled Trials as Topic</keyword><keyword>Research Design</keyword><keyword>Sample Size</keyword><keyword>Statistics as Topic</keyword></keywords><dates><year>2013</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>1878-5921 (Electronic)
0895-4356 (Linking)</isbn><accession-num>23195919</accession-num><urls><related-urls><url>;(85). However, as two-thirds of these ‘failures’ were not clinically significant, and we have subsequently modified the definition of the primary outcome, we feel justified in continuing with the multicentre trial.Pilot trial testing results (microbiologic)Of 57 NPS specimens from participants in the pilot available for analysis, 33 (58%) were positive for at least one virus, with 2/30 positive for 2 viruses. Over half the samples (n=31, 55%) had high-level S. pneumoniae colonization (> 4 log copies/mL); this positivity rate is very similar to that seen in a recent observational study of children with CAP defined using clinical and radiographic parameters ADDIN EN.CITE <EndNote><Cite><Author>Chappuy</Author><Year>2013</Year><RecNum>4121</RecNum><DisplayText>(21)</DisplayText><record><rec-number>4121</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1390076781">4121</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Chappuy, H.</author><author>Keitel, K.</author><author>Gehri, M.</author><author>Tabin, R.</author><author>Robitaille, L.</author><author>Raymond, F.</author><author>Corbeil, J.</author><author>Maspoli, V.</author><author>Bouazza, N.</author><author>Alcoba, G.</author><author>Lacroix, L.</author><author>Manzano, S.</author><author>Galetto-Lacour, A.</author><author>Gervaix, A.</author></authors></contributors><auth-address>Child and Adolescent Department, University Hospital of Geneva, Geneva, Switzerland. helene.chappuy@nck.aphp.fr</auth-address><titles><title>Nasopharyngeal carriage of individual Streptococcus pneumoniae serotypes during pediatric radiologically confirmed community acquired pneumonia following PCV7 introduction in Switzerland</title><secondary-title>BMC Infect Dis</secondary-title><alt-title>BMC infectious diseases</alt-title></titles><periodical><full-title>BMC Infect Dis</full-title><abbr-1>BMC infectious diseases</abbr-1></periodical><alt-periodical><full-title>BMC Infect Dis</full-title><abbr-1>BMC infectious diseases</abbr-1></alt-periodical><pages>357</pages><volume>13</volume><edition>2013/08/01</edition><dates><year>2013</year></dates><isbn>1471-2334 (Electronic)
1471-2334 (Linking)</isbn><accession-num>23899390</accession-num><work-type>Multicenter Study</work-type><urls><related-urls><url>;(21). Just under half (15 of 31, 48%) specimens with high-level S. pneumoniae colonization were also positive for a virus.Unsurprisingly, only 2 (4%) were positive for Mycoplasma pneumoniae. Both of these were also positive for a virus, and neither of these were accompanied by high-level S. pneumoniae colonization. Not a single specimen was positive for the other atypical pathogens found more commonly in adults (Chlamydophila and Legionella spp). There were 8 (14%) NPS specimens that were not positive for any respiratory pathogens tested for in the study.Other problems encountered in the pilot trialIf enrolment is to be optimized, missing potentially eligible participants and refusal of consent need to be kept to a minimum. Missing participants was extremely common in the early stages of the pilot, primarily because all recruitment was dependent on ED staff notifying the research assistant that a potential participant was present in the department; not only were there not sufficient resources to enable the permanent presence of a study team member in the ED, but all potential participants must be diagnosed by an ED physician as having CAP to be eligible. Optimizing ED-study team communication was achieved by repeatedly approaching the numerous health care professionals (attending staff, nurses, trainee MDs, etc.) who work in the ED, posting relevant notices, and feeding back missed notifications. The original protocol was also clarified and expanded to permit the research assistant to approach potential participants in their homes after being discharged home on amoxicillin given by the ED physician; this was most useful for children who were discharged in the early hours of the morning.The most common reason for refusing consent was an unwillingness to return for the measurement of the primary outcome, especially for those who did not live in proximity to the hospital; there were also parents concerned that fewer days of antibiotics would have decreased efficacy. Unfortunately, there was nothing that could be done about the former, as it would be extremely difficult to induce physicians to visit participants in their home for a three-minute clinical examination. There is also little to be done about the latter, as there is still a widespread assumption among both health-care professionals and laypeople that taking an antimicrobial is essentially a zero-risk medical intervention, despite mounting evidence to the contrary. We are currently planning another trial exploring methods to better communicate the adverse events (including perturbation of the microbiome and colonization with resistant pathogens, among others) associated with antibacterial therapy to caregivers; however, the results from this trial will not be ready by the time the larger follow-up trial begins. PART 5 – SELECTED METHODOLOGIC CONSIDERATIONS FOR NON-INFERIORITY STUDIESAssay sensitivityThe issue of assay sensitivity (proper design of a trial, enabling it to distinguish an effective intervention from an ineffective one) is critical but often underappreciated in the appraisal of non-inferiority studies. A ‘successful’ superiority study that demonstrates that one treatment is superior to another has, by definition, adequate assay sensitivity ADDIN EN.CITE <EndNote><Cite><Year>2010</Year><RecNum>4180</RecNum><DisplayText>(81)</DisplayText><record><rec-number>4180</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1405790911">4180</key></foreign-keys><ref-type name="Web Page">12</ref-type><contributors><secondary-authors><author>US Department of Health and Human Services, Food and Drug Administration</author></secondary-authors></contributors><titles><title>Guidance for industry non-inferiority clinical trials (draft)</title></titles><volume>2014</volume><number>19 July</number><dates><year>2010</year></dates><publisher>Center for Drug Evaluation and Research</publisher><urls><related-urls><url>;(81). A superiority study that does not demonstrate that one treatment is superior to another may or may not have sufficient assay sensitivity; this study is properly referred to as having an ‘indeterminate’ result and the conclusions drawn from it depend on study characteristics, most importantly on whether or not the study was adequately powered to detect a clinically significant difference ADDIN EN.CITE <EndNote><Cite><Author>Altman</Author><Year>1995</Year><RecNum>4181</RecNum><DisplayText>(86)</DisplayText><record><rec-number>4181</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1405791296">4181</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Altman, D. G.</author><author>Bland, J. M.</author></authors></contributors><auth-address>Medical Statistics Laboratory, Imperial Cancer Research Fund, London.</auth-address><titles><title>Absence of evidence is not evidence of absence</title><secondary-title>BMJ</secondary-title><alt-title>Bmj</alt-title></titles><periodical><full-title>BMJ</full-title></periodical><alt-periodical><full-title>BMJ</full-title></alt-periodical><pages>485</pages><volume>311</volume><number>7003</number><keywords><keyword>Controlled Clinical Trials as Topic</keyword><keyword>Data Interpretation, Statistical</keyword><keyword>Randomized Controlled Trials as Topic/*standards</keyword><keyword>Sample Size</keyword><keyword>*Statistics as Topic</keyword></keywords><dates><year>1995</year><pub-dates><date>Aug 19</date></pub-dates></dates><isbn>0959-8138 (Print)
0959-535X (Linking)</isbn><accession-num>7647644</accession-num><urls><related-urls><url>;(86). In contrast, a ‘successful’ non-inferiority study that demonstrates no difference between one treatment and the reference standard may or may not have sufficient assay sensitivity and therefore may or may not be valid. This is clearly a major issue as poor assay sensitivity essentially invalidates a non-inferiority study, regardless of the care taken designing all other aspects of the trial. The draft guidance of the United States Food and Drug Administration (FDA) notes that “[it is critical] to know…that the active control had its expected effect in the trial” and indicates that one should reference previous placebo-controlled studies of the reference treatment ADDIN EN.CITE <EndNote><Cite><Year>2010</Year><RecNum>4180</RecNum><DisplayText>(81)</DisplayText><record><rec-number>4180</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1405790911">4180</key></foreign-keys><ref-type name="Web Page">12</ref-type><contributors><secondary-authors><author>US Department of Health and Human Services, Food and Drug Administration</author></secondary-authors></contributors><titles><title>Guidance for industry non-inferiority clinical trials (draft)</title></titles><volume>2014</volume><number>19 July</number><dates><year>2010</year></dates><publisher>Center for Drug Evaluation and Research</publisher><urls><related-urls><url>;(81). This same document notes that – if only a single non-inferiority study is to be completed – setting alpha at 0.001 constitutes additional evidence suggesting that a false conclusion of non-inferiority is unlikely ADDIN EN.CITE <EndNote><Cite><Year>2010</Year><RecNum>4180</RecNum><DisplayText>(81)</DisplayText><record><rec-number>4180</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1405790911">4180</key></foreign-keys><ref-type name="Web Page">12</ref-type><contributors><secondary-authors><author>US Department of Health and Human Services, Food and Drug Administration</author></secondary-authors></contributors><titles><title>Guidance for industry non-inferiority clinical trials (draft)</title></titles><volume>2014</volume><number>19 July</number><dates><year>2010</year></dates><publisher>Center for Drug Evaluation and Research</publisher><urls><related-urls><url>;(81).It is difficult to guarantee assay sensitivity for our proposed trial. As described extensively in the background, there is substantial inter-observer variability in the diagnosis of pneumonia and – even when this diagnosis is made – it is even harder to reliably determine if the infection is caused by a bacterial pathogen. This issue is important because the inclusion of too many participants with purely viral CAP would dramatically lower assay sensitivity, as neither short- nor standard-course antimicrobials have any effect on non-bacterial infections. We have attempted to optimize assay sensitivity by creating a definition of CAP with adequate face validity and that is consistent with others previously used in the literature. The other method that will be used to ensure study validity will be the use of sensitivity analyses; as noted in the protocol, comparisons will be made between short- and standard-course antimicrobial therapy in subgroups of participants who would be most likely to have bacterial infections (ie. alveolar infiltrates on chest radiograph, elevated C-reactive protein values, high-level pneumococcal colonization in nasopharyngeal specimens). The only way to absolutely guarantee that all participants had bacterial infections would be to include only those with blood cultures positive for CAP-causing pathogens; this would not only be infeasible (due to the extreme rarity of concomitant bacteraemia) but would result in the necessity of including those with more severe disease – who would not be eligible for short-course antimicrobial therapy anyway.The potential inclusion of children without bacterial infections is not the only threat to assay sensitivity. As the FDA states, it is important to compare the efficacy of the reference treatment in the trial to past RCTs ADDIN EN.CITE <EndNote><Cite><Year>2010</Year><RecNum>4180</RecNum><DisplayText>(81)</DisplayText><record><rec-number>4180</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1405790911">4180</key></foreign-keys><ref-type name="Web Page">12</ref-type><contributors><secondary-authors><author>US Department of Health and Human Services, Food and Drug Administration</author></secondary-authors></contributors><titles><title>Guidance for industry non-inferiority clinical trials (draft)</title></titles><volume>2014</volume><number>19 July</number><dates><year>2010</year></dates><publisher>Center for Drug Evaluation and Research</publisher><urls><related-urls><url>;(81); however, there are no known placebo-controlled trials of antibiotics for paediatric CAP in the literature. It is not even known what proportion of untreated paediatric bacterial CAP will self-resolve in the current era. There are records documenting mortality and morbidity from pneumonia in the pre-antibiotic era, but to use those to estimate baseline antibiotic efficacy would undoubtedly greatly exaggerate the impact of these medications, as the baseline health of children is much better today than in the early twentieth century.Determination of the non-inferiority marginIt is obvious that the selection of the non-inferiority margin has a significant impact on trial outcome. It is also clear that clinical considerations should inform the determination of the margin; if the margin is judged as unacceptably wide to clinicians, a ‘successful’ non-inferiority trial will have little impact on practice. However, selection of the margin based solely on the clinical experience of the principal investigator should probably be avoided, despite how commonly this has been done in the past ADDIN EN.CITE <EndNote><Cite><Author>Wangge</Author><Year>2010</Year><RecNum>4183</RecNum><DisplayText>(87)</DisplayText><record><rec-number>4183</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1405795553">4183</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Wangge, G.</author><author>Klungel, O. H.</author><author>Roes, K. C.</author><author>de Boer, A.</author><author>Hoes, A. W.</author><author>Knol, M. J.</author></authors></contributors><auth-address>Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Utrecht, The Netherlands.</auth-address><titles><title>Interpretation and inference in noninferiority randomized controlled trials in drug research</title><secondary-title>Clin Pharmacol Ther</secondary-title><alt-title>Clinical pharmacology and therapeutics</alt-title></titles><periodical><full-title>Clin Pharmacol Ther</full-title><abbr-1>Clinical pharmacology and therapeutics</abbr-1></periodical><alt-periodical><full-title>Clin Pharmacol Ther</full-title><abbr-1>Clinical pharmacology and therapeutics</abbr-1></alt-periodical><pages>420-3</pages><volume>88</volume><number>3</number><keywords><keyword>Data Interpretation, Statistical</keyword><keyword>Humans</keyword><keyword>Pharmaceutical Preparations/*administration & dosage/metabolism</keyword><keyword>Randomized Controlled Trials as Topic/*methods</keyword><keyword>*Research Design</keyword><keyword>Therapeutic Equivalency</keyword></keywords><dates><year>2010</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>1532-6535 (Electronic)
0009-9236 (Linking)</isbn><accession-num>20668448</accession-num><urls><related-urls><url>;(87). The FDA draft statement also provides guidance relating to statistical considerations affecting the selection of the non-inferiority margin; note that its main concern seems to be – if the experimental treatment is found to be non-inferior to the standard therapy – that there is sufficient evidence to be reasonably confident the experimental treatment is also superior to placebo ADDIN EN.CITE <EndNote><Cite><Year>2010</Year><RecNum>4180</RecNum><DisplayText>(81)</DisplayText><record><rec-number>4180</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1405790911">4180</key></foreign-keys><ref-type name="Web Page">12</ref-type><contributors><secondary-authors><author>US Department of Health and Human Services, Food and Drug Administration</author></secondary-authors></contributors><titles><title>Guidance for industry non-inferiority clinical trials (draft)</title></titles><volume>2014</volume><number>19 July</number><dates><year>2010</year></dates><publisher>Center for Drug Evaluation and Research</publisher><urls><related-urls><url>;(81). If the margin was greater than the predicted effect of the standard treatment, for example, a trial could successfully demonstrate non-inferiority for an experimental treatment that is not superior to placebo. The FDA draft guideline first instructs investigators to review meta-analyses of clinical trials of the standard therapy compared to placebo to discern the pooled estimate of efficacy; if only single trials are available, they can be used, but obviously there will be much less precision in the estimates of efficacy. In the ‘fixed margin method’, the key parameter M1 is then identified as the upper bound (ie. most conservative estimate, which for the risk difference is the least negative value, and for the relative risk is the value closest to unity) of the 95% CI surrounding the point estimate of either the risk difference or the relative risk ADDIN EN.CITE <EndNote><Cite><Year>2010</Year><RecNum>4180</RecNum><DisplayText>(81)</DisplayText><record><rec-number>4180</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1405790911">4180</key></foreign-keys><ref-type name="Web Page">12</ref-type><contributors><secondary-authors><author>US Department of Health and Human Services, Food and Drug Administration</author></secondary-authors></contributors><titles><title>Guidance for industry non-inferiority clinical trials (draft)</title></titles><volume>2014</volume><number>19 July</number><dates><year>2010</year></dates><publisher>Center for Drug Evaluation and Research</publisher><urls><related-urls><url>;(81). This assumes, of course, that the effect of standard therapy in trial participants will be comparable to that in past placebo-controlled RCTs, and that the non-inferiority trial will be of comparable quality to these past trials (as ‘noise’ in less well-designed trials can obscure the ‘signal’ of effect). The upper bound of the CI is used instead of the point estimate because “half of all trials, even if the historical estimate is correct, would be expected to have a smaller effect, so that one could not be reasonably sure such an effect of the control was present” ADDIN EN.CITE <EndNote><Cite><Year>2010</Year><RecNum>4180</RecNum><DisplayText>(81)</DisplayText><record><rec-number>4180</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1405790911">4180</key></foreign-keys><ref-type name="Web Page">12</ref-type><contributors><secondary-authors><author>US Department of Health and Human Services, Food and Drug Administration</author></secondary-authors></contributors><titles><title>Guidance for industry non-inferiority clinical trials (draft)</title></titles><volume>2014</volume><number>19 July</number><dates><year>2010</year></dates><publisher>Center for Drug Evaluation and Research</publisher><urls><related-urls><url>;(81). The noninferiority margin, M2, can then be calculated after determining what proportion of effect of the standard therapy is to be ‘preserved’. The suggested default proportion is 50%; some authors have recommended that greater proportions (resulting in smaller noninferiority margins) should be used when standard therapies have greater effects and when outcomes are serious and/or irreversible (eg. death), whereas smaller proportions can be used when the experimental treatment is expected to be safer or cheaper than standard treatment ADDIN EN.CITE <EndNote><Cite><Author>Wangge</Author><Year>2013</Year><RecNum>4184</RecNum><DisplayText>(88)</DisplayText><record><rec-number>4184</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1405801921">4184</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Wangge, G.</author><author>Roes, K. C.</author><author>de Boer, A.</author><author>Hoes, A. W.</author><author>Knol, M. J.</author></authors></contributors><auth-address>Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands.</auth-address><titles><title>The challenges of determining noninferiority margins: a case study of noninferiority randomized controlled trials of novel oral anticoagulants</title><secondary-title>CMAJ</secondary-title><alt-title>CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne</alt-title></titles><periodical><full-title>CMAJ</full-title><abbr-1>CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne</abbr-1></periodical><alt-periodical><full-title>CMAJ</full-title><abbr-1>CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne</abbr-1></alt-periodical><pages>222-7</pages><volume>185</volume><number>3</number><keywords><keyword>Antithrombins/therapeutic use</keyword><keyword>Humans</keyword><keyword>Randomized Controlled Trials as Topic/*methods</keyword><keyword>*Research Design</keyword><keyword>Venous Thromboembolism/prevention & control</keyword></keywords><dates><year>2013</year><pub-dates><date>Feb 19</date></pub-dates></dates><isbn>1488-2329 (Electronic)
0820-3946 (Linking)</isbn><accession-num>22908144</accession-num><urls><related-urls><url>;(88). The formulae for determining M2 are the following ADDIN EN.CITE <EndNote><Cite><Author>Wangge</Author><Year>2013</Year><RecNum>4184</RecNum><DisplayText>(88)</DisplayText><record><rec-number>4184</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1405801921">4184</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Wangge, G.</author><author>Roes, K. C.</author><author>de Boer, A.</author><author>Hoes, A. W.</author><author>Knol, M. J.</author></authors></contributors><auth-address>Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands.</auth-address><titles><title>The challenges of determining noninferiority margins: a case study of noninferiority randomized controlled trials of novel oral anticoagulants</title><secondary-title>CMAJ</secondary-title><alt-title>CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne</alt-title></titles><periodical><full-title>CMAJ</full-title><abbr-1>CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne</abbr-1></periodical><alt-periodical><full-title>CMAJ</full-title><abbr-1>CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne</abbr-1></alt-periodical><pages>222-7</pages><volume>185</volume><number>3</number><keywords><keyword>Antithrombins/therapeutic use</keyword><keyword>Humans</keyword><keyword>Randomized Controlled Trials as Topic/*methods</keyword><keyword>*Research Design</keyword><keyword>Venous Thromboembolism/prevention & control</keyword></keywords><dates><year>2013</year><pub-dates><date>Feb 19</date></pub-dates></dates><isbn>1488-2329 (Electronic)
0820-3946 (Linking)</isbn><accession-num>22908144</accession-num><urls><related-urls><url>;(88): If comparing absolute risk reductions, M2 = (1-preserved effects)*M1*(-1)If comparing relative risks, M2 = eln(1/M1)(1-preserved effects)(It should be noted that these methods will often lead to the generation of different non-inferiority margins. Absolute risk reductions (presented as number needed to treat) can be more useful for decision-making by clinicians, though relative risks are less susceptible to variation between studies.) If it is assumed that the failure rate of standard therapy is 5% and that of no therapy is 25% (ie. 75% of mild bacterial CAP in children will resolve of its own accord without any treatment), then the risk difference for standard therapy is -0.2; if 50% of the effect is desired to be preserved, then M2 for the proposed trial should be 0.1. However, there are no data to support this estimate of a 25% failure rate for no treatment; if the true failure rate was only 15%, then the M2 for the proposed trial would be 0.05. Estimates of child CAP-specific mortality from the pre-antibiotic era cannot be used to generate M1 since this would without doubt overestimate CAP-specific mortality in children today, leading to a far-too-large estimate of M1. We note the FDA draft statement explicitly states “where there is uncertainty about the historical effect size [of standard treatment]…it will usually be necessary to have more than one non-inferiority study to support effectiveness”, ADDIN EN.CITE <EndNote><Cite><Year>2010</Year><RecNum>4180</RecNum><DisplayText>(81)</DisplayText><record><rec-number>4180</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1405790911">4180</key></foreign-keys><ref-type name="Web Page">12</ref-type><contributors><secondary-authors><author>US Department of Health and Human Services, Food and Drug Administration</author></secondary-authors></contributors><titles><title>Guidance for industry non-inferiority clinical trials (draft)</title></titles><volume>2014</volume><number>19 July</number><dates><year>2010</year></dates><publisher>Center for Drug Evaluation and Research</publisher><urls><related-urls><url>;(81) though its primary concern appears to be for ensuring appropriate approval of new drugs.Interestingly, the FDA draft statement notes that – because of the way that M2 is calculated – if the 95% CI for the point estimate of the effectiveness of the experimental treatment crosses M2, it does not necessarily mean that this therapy is clearly inferior to the control treatment. (In contrast, if the CI crosses M1, there is no evidence that the experimental therapy is superior to placebo.) It seems to endorse the post-hoc logic in some instances of, for example, “assuring 48% retention [of the control effect]” since the a priori selection of 50% retention of effect is entirely arbitrary ADDIN EN.CITE <EndNote><Cite><Year>2010</Year><RecNum>4180</RecNum><DisplayText>(81)</DisplayText><record><rec-number>4180</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1405790911">4180</key></foreign-keys><ref-type name="Web Page">12</ref-type><contributors><secondary-authors><author>US Department of Health and Human Services, Food and Drug Administration</author></secondary-authors></contributors><titles><title>Guidance for industry non-inferiority clinical trials (draft)</title></titles><volume>2014</volume><number>19 July</number><dates><year>2010</year></dates><publisher>Center for Drug Evaluation and Research</publisher><urls><related-urls><url>;(81). This would seem to be somewhat dangerous, especially given the repeated concern about methodologic problems leading to a type I error in non-inferiority studies (rather than a type II error in superiority studies).PART 6 – SELECTED METHODOLOGIC CONSIDERATIONS FOR PILOT STUDIESThere is no one accepted definition for a ‘pilot’ or ‘vanguard’ study, but most would agree that this type of smaller study is important prior to embarking on a large and expensive randomized clinical trial. There are innumerable reasons for conducting a pilot study, most of which aim to verify that the study as designed is appropriate and that the investigators have a realistic estimate of resources (both human and otherwise) needed to complete the main follow-up study ADDIN EN.CITE <EndNote><Cite><Author>van Teijlingen E.R.</Author><Year>2001</Year><RecNum>4185</RecNum><DisplayText>(89)</DisplayText><record><rec-number>4185</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1407359084">4185</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>van Teijlingen E.R., Hundley V.</author></authors></contributors><titles><title>The importance of pilot studies</title><secondary-title>Social Research Update</secondary-title></titles><periodical><full-title>Social Research Update</full-title></periodical><pages>1-4</pages><number>35</number><dates><year>2001</year></dates><urls><related-urls><url>;(89). However, it is important to realize what the results of a pilot study can and should be used for. Feasibility criteriaAs the primary goal of a pilot study is to usually determine the feasibility of the follow-up main trial, these studies should usually have predetermined explicit feasibility criteria that will inform the decision to proceed with the larger trial. Interestingly, the importance of stating clear feasibility criteria has been highlighted in relatively few publications ADDIN EN.CITE <EndNote><Cite><Author>Thabane</Author><Year>2010</Year><RecNum>4193</RecNum><DisplayText>(84)</DisplayText><record><rec-number>4193</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1407360118">4193</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Thabane, L.</author><author>Ma, J.</author><author>Chu, R.</author><author>Cheng, J.</author><author>Ismaila, A.</author><author>Rios, L. P.</author><author>Robson, R.</author><author>Thabane, M.</author><author>Giangregorio, L.</author><author>Goldsmith, C. H.</author></authors></contributors><auth-address>Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton ON, Canada. thabanl@mcmaster.ca</auth-address><titles><title>A tutorial on pilot studies: the what, why and how</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>1</pages><volume>10</volume><keywords><keyword>Clinical Trials, Phase III as Topic/methods</keyword><keyword>Humans</keyword><keyword>*Pilot Projects</keyword><keyword>Randomized Controlled Trials as Topic</keyword><keyword>*Research Design/standards</keyword></keywords><dates><year>2010</year></dates><isbn>1471-2288 (Electronic)
1471-2288 (Linking)</isbn><accession-num>20053272</accession-num><urls><related-urls><url>;(84). Additionally, we have not been able to find published literature (Thabane L, personal communication) addressing related methodologic questions that would appear to be critical, such as: how should feasibility criteria be selected? Are there certain key feasibility domains that should always be represented among the criteria for every pilot study? If a particular feasibility criterion is not achieved in a pilot trial, is there any way of objectively assessing whether planned modifications could result in a successful follow-up larger trial (or are there certain types of failures that would preclude any further application for funding). This lack seems quite curious, given that anecdotal experience would suggest that pilot data are essentially required to successfully receive significant amounts of funding for a randomized trial. Building upon a previously-established paradigm ADDIN EN.CITE <EndNote><Cite><Author>Thabane</Author><Year>2010</Year><RecNum>4193</RecNum><DisplayText>(84)</DisplayText><record><rec-number>4193</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1407360118">4193</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Thabane, L.</author><author>Ma, J.</author><author>Chu, R.</author><author>Cheng, J.</author><author>Ismaila, A.</author><author>Rios, L. P.</author><author>Robson, R.</author><author>Thabane, M.</author><author>Giangregorio, L.</author><author>Goldsmith, C. H.</author></authors></contributors><auth-address>Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton ON, Canada. thabanl@mcmaster.ca</auth-address><titles><title>A tutorial on pilot studies: the what, why and how</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>1</pages><volume>10</volume><keywords><keyword>Clinical Trials, Phase III as Topic/methods</keyword><keyword>Humans</keyword><keyword>*Pilot Projects</keyword><keyword>Randomized Controlled Trials as Topic</keyword><keyword>*Research Design/standards</keyword></keywords><dates><year>2010</year></dates><isbn>1471-2288 (Electronic)
1471-2288 (Linking)</isbn><accession-num>20053272</accession-num><urls><related-urls><url>;(84), it seems reasonable to propose that pilot RCTs should all include feasibility criteria drawn from the following list:Appropriateness of study population. Do the inclusion and exclusion criteria adequately describe the population of interest? Are there participants who are technically eligible (or ineligible) that should not be? Appropriateness of outcomes. Is the primary outcome truly important? Are the instruments designed to measure the primary outcome able to be used efficiently and appropriately in the study population?Recruitment rate. Based on the eligibility criteria, is it reasonable to suppose that sufficient numbers will be recruited in a practical time-frame in order to assess a difference in the primary outcome between groups? If not, are there other outcomes that are important but more frequent? Can eligibility criteria be relaxed and yet still include only the population of interest?Resource projections. Will the resources – both human and otherwise – be sufficient to successfully conduct the trial or was the pilot obviously under-budgeted for? Is the infrastructure (especially information technology-related) adequate and workable in the study setting? Can study procedures actually take place within an appropriate time-frame? Are the co-investigators able to actually carry out their assigned tasks?Safety and ethics. Have any new safety problems been identified? Have any ethical issues arisen that were not foreseen?Sample size considerationsPlease note that the list in the previous section did not explicitly include feasibility criteria related to sample size projections. Some authorities would suggest that it is preferable to design the main study using parameters present in the literature, as point estimates of treatment effects in small studies can vary widely ADDIN EN.CITE <EndNote><Cite><Author>Thabane</Author><Year>2010</Year><RecNum>4193</RecNum><DisplayText>(84)</DisplayText><record><rec-number>4193</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1407360118">4193</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Thabane, L.</author><author>Ma, J.</author><author>Chu, R.</author><author>Cheng, J.</author><author>Ismaila, A.</author><author>Rios, L. P.</author><author>Robson, R.</author><author>Thabane, M.</author><author>Giangregorio, L.</author><author>Goldsmith, C. H.</author></authors></contributors><auth-address>Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton ON, Canada. thabanl@mcmaster.ca</auth-address><titles><title>A tutorial on pilot studies: the what, why and how</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>1</pages><volume>10</volume><keywords><keyword>Clinical Trials, Phase III as Topic/methods</keyword><keyword>Humans</keyword><keyword>*Pilot Projects</keyword><keyword>Randomized Controlled Trials as Topic</keyword><keyword>*Research Design/standards</keyword></keywords><dates><year>2010</year></dates><isbn>1471-2288 (Electronic)
1471-2288 (Linking)</isbn><accession-num>20053272</accession-num><urls><related-urls><url>;(84). However, many authors have attempted to promulgate statistically appropriate ways of using pilot data to inform the sample size decision-making for the larger follow-up study. Some of these apply to ‘internal’ pilot studies, otherwise described as statistical analysis partway through a large study in an effort to gauge if original sample size calculations (ie. variance of the outcome of interest) were correct, and some apply to ‘external’ pilot studies, which are entirely separate from and precede the larger follow-up trial. Wittes and Brittain suggested that large trials should – halfway through enrollment – recalculate the variance of the outcome of interest; should the variance be higher than the original estimates, the overall sample size would need to be increased to maintain nominal power ADDIN EN.CITE <EndNote><Cite><Author>Wittes</Author><Year>1990</Year><RecNum>4198</RecNum><DisplayText>(90)</DisplayText><record><rec-number>4198</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1407710221">4198</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Wittes, J.</author><author>Brittain, E.</author></authors></contributors><auth-address>Biostatistics Research Branch, National Heart, Lung, and Blood Institute, Bethesda, MD 20817.</auth-address><titles><title>The role of internal pilot studies in increasing the efficiency of clinical trials</title><secondary-title>Stat Med</secondary-title><alt-title>Statistics in medicine</alt-title></titles><periodical><full-title>Stat Med</full-title><abbr-1>Statistics in medicine</abbr-1></periodical><alt-periodical><full-title>Stat Med</full-title><abbr-1>Statistics in medicine</abbr-1></alt-periodical><pages>65-71; discussion 71-2</pages><volume>9</volume><number>1-2</number><keywords><keyword>*Pilot Projects</keyword><keyword>Randomized Controlled Trials as Topic/*methods</keyword><keyword>Research Design</keyword><keyword>*Statistics as Topic</keyword></keywords><dates><year>1990</year><pub-dates><date>Jan-Feb</date></pub-dates></dates><isbn>0277-6715 (Print)
0277-6715 (Linking)</isbn><accession-num>2345839</accession-num><urls><related-urls><url>;(90). Sandvik et al. developed a formula to calculate appropriate internal pilot trial size for normally-distributed outcomes; this size is at minimum 20 and potentially much larger, as it depends on the estimates of the standard deviation (SD) of the outcome variable in the literature, sizes of previous trials, etc. ADDIN EN.CITE <EndNote><Cite><Author>Sandvik</Author><Year>1996</Year><RecNum>4199</RecNum><DisplayText>(91)</DisplayText><record><rec-number>4199</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1407710965">4199</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Sandvik, L.</author><author>Erikssen, J.</author><author>Mowinckel, P.</author><author>Rodland, E. A.</author></authors></contributors><auth-address>Medstat Research A/S, Lillestrom, Norway.</auth-address><titles><title>A method for determining the size of internal pilot studies</title><secondary-title>Stat Med</secondary-title><alt-title>Statistics in medicine</alt-title></titles><periodical><full-title>Stat Med</full-title><abbr-1>Statistics in medicine</abbr-1></periodical><alt-periodical><full-title>Stat Med</full-title><abbr-1>Statistics in medicine</abbr-1></alt-periodical><pages>1587-90</pages><volume>15</volume><number>14</number><keywords><keyword>Bias (Epidemiology)</keyword><keyword>*Pilot Projects</keyword><keyword>*Probability</keyword><keyword>Randomized Controlled Trials as Topic/methods</keyword><keyword>*Sample Size</keyword></keywords><dates><year>1996</year><pub-dates><date>Jul 30</date></pub-dates></dates><isbn>0277-6715 (Print)
0277-6715 (Linking)</isbn><accession-num>8855484</accession-num><urls><related-urls><url>(SICI)1097-0258(19960730)15:14<1587::AID-SIM279>3.0.CO;2-F</electronic-resource-num></record></Cite></EndNote>(91) They note that their procedure – as for that of Wittes and Brittain – will affect the final estimate of treatment variance, which will change the significance level of the result ADDIN EN.CITE <EndNote><Cite><Author>Sandvik</Author><Year>1996</Year><RecNum>4199</RecNum><DisplayText>(91)</DisplayText><record><rec-number>4199</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1407710965">4199</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Sandvik, L.</author><author>Erikssen, J.</author><author>Mowinckel, P.</author><author>Rodland, E. A.</author></authors></contributors><auth-address>Medstat Research A/S, Lillestrom, Norway.</auth-address><titles><title>A method for determining the size of internal pilot studies</title><secondary-title>Stat Med</secondary-title><alt-title>Statistics in medicine</alt-title></titles><periodical><full-title>Stat Med</full-title><abbr-1>Statistics in medicine</abbr-1></periodical><alt-periodical><full-title>Stat Med</full-title><abbr-1>Statistics in medicine</abbr-1></alt-periodical><pages>1587-90</pages><volume>15</volume><number>14</number><keywords><keyword>Bias (Epidemiology)</keyword><keyword>*Pilot Projects</keyword><keyword>*Probability</keyword><keyword>Randomized Controlled Trials as Topic/methods</keyword><keyword>*Sample Size</keyword></keywords><dates><year>1996</year><pub-dates><date>Jul 30</date></pub-dates></dates><isbn>0277-6715 (Print)
0277-6715 (Linking)</isbn><accession-num>8855484</accession-num><urls><related-urls><url>(SICI)1097-0258(19960730)15:14<1587::AID-SIM279>3.0.CO;2-F</electronic-resource-num></record></Cite></EndNote>(91). This effect was expected to be ‘small’; a later work by Friede and Kieser attempted to quantify the projected magnitude of this effect for different study designs ADDIN EN.CITE <EndNote><Cite><Author>Friede</Author><Year>2006</Year><RecNum>4200</RecNum><DisplayText>(92)</DisplayText><record><rec-number>4200</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1407712185">4200</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Friede, T.</author><author>Kieser, M.</author></authors></contributors><auth-address>Novartis Pharma AG, Biostatistics and Statistical Reporting, Basel, Switzerland. tim.friede@</auth-address><titles><title>Sample size recalculation in internal pilot study designs: a review</title><secondary-title>Biom J</secondary-title><alt-title>Biometrical journal. Biometrische Zeitschrift</alt-title></titles><periodical><full-title>Biom J</full-title><abbr-1>Biometrical journal. Biometrische Zeitschrift</abbr-1></periodical><alt-periodical><full-title>Biom J</full-title><abbr-1>Biometrical journal. Biometrische Zeitschrift</abbr-1></alt-periodical><pages>537-55</pages><volume>48</volume><number>4</number><keywords><keyword>Clinical Trials as Topic/*statistics & numerical data</keyword><keyword>Confidence Intervals</keyword><keyword>Data Interpretation, Statistical</keyword><keyword>Pilot Projects</keyword><keyword>Research Design/*statistics & numerical data</keyword><keyword>Sample Size</keyword></keywords><dates><year>2006</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0323-3847 (Print)
0323-3847 (Linking)</isbn><accession-num>16972704</accession-num><urls><related-urls><url>;(92). Some authors have proposed simpler ways of calculating the appropriate size of a pilot study, either internal or external, with the ultimate goal of predicting SD/variance of the main follow-up study. Lancaster et al. referred to the (unreferenced) ‘rule of thumb’ stating that an n=30 is often sufficient for pilot trials ADDIN EN.CITE <EndNote><Cite><Author>Lancaster</Author><Year>2004</Year><RecNum>4201</RecNum><DisplayText>(93)</DisplayText><record><rec-number>4201</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1407750935">4201</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lancaster, G. A.</author><author>Dodd, S.</author><author>Williamson, P. R.</author></authors></contributors><auth-address>Department of Mathematical Sciences, University of Liverpool, UK. g.lancaster@liv.ac.uk</auth-address><titles><title>Design and analysis of pilot studies: recommendations for good practice</title><secondary-title>J Eval Clin Pract</secondary-title><alt-title>Journal of evaluation in clinical practice</alt-title></titles><periodical><full-title>J Eval Clin Pract</full-title><abbr-1>Journal of evaluation in clinical practice</abbr-1></periodical><alt-periodical><full-title>J Eval Clin Pract</full-title><abbr-1>Journal of evaluation in clinical practice</abbr-1></alt-periodical><pages>307-12</pages><volume>10</volume><number>2</number><keywords><keyword>Great Britain</keyword><keyword>Pilot Projects</keyword><keyword>*Randomized Controlled Trials as Topic</keyword><keyword>*Research Design</keyword></keywords><dates><year>2004</year><pub-dates><date>May</date></pub-dates></dates><isbn>1356-1294 (Print)
1356-1294 (Linking)</isbn><accession-num>15189396</accession-num><urls><related-urls><url>;(93); Julious suggested that including 12 participants per treatment arm would be sufficient to gauge the projected variance in the larger follow-up trial ADDIN EN.CITE <EndNote><Cite><Author>Julious</Author><Year>2005</Year><RecNum>4202</RecNum><DisplayText>(94)</DisplayText><record><rec-number>4202</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1407751427">4202</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Julious, S.A.</author></authors></contributors><titles><title>Sample size of 12 per group rule for a pilot study</title><secondary-title>Pharmaceut Statist</secondary-title></titles><periodical><full-title>Pharmaceut Statist</full-title></periodical><pages>287-291</pages><volume>4</volume><dates><year>2005</year></dates><urls></urls></record></Cite></EndNote>(94). Sim and Lewis did not overtly find fault with these recommendations but demonstrated quite elegantly the variability inherent in estimating SDs using small samples and alluded to the potential utility of an inflation factor, “the factor by which the SD derived from the pilot study should be increased to be x% confident of achieving at least the nominal power in the main study”; this is simply the ratio of the upper x% CI of the estimate of the pilot SD and the observed pilot SD ADDIN EN.CITE <EndNote><Cite><Author>Sim</Author><Year>2012</Year><RecNum>4208</RecNum><DisplayText>(95)</DisplayText><record><rec-number>4208</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1407752867">4208</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Sim, J.</author><author>Lewis, M.</author></authors></contributors><auth-address>Arthritis Research UK Primary Care Centre, Keele University, Keele, Staffordshire, UK. j.sim@keele.ac.uk</auth-address><titles><title>The size of a pilot study for a clinical trial should be calculated in relation to considerations of precision and efficiency</title><secondary-title>J Clin Epidemiol</secondary-title><alt-title>Journal of clinical epidemiology</alt-title></titles><periodical><full-title>J Clin Epidemiol</full-title><abbr-1>Journal of clinical epidemiology</abbr-1></periodical><alt-periodical><full-title>J Clin Epidemiol</full-title><abbr-1>Journal of clinical epidemiology</abbr-1></alt-periodical><pages>301-8</pages><volume>65</volume><number>3</number><keywords><keyword>Bias (Epidemiology)</keyword><keyword>Confidence Intervals</keyword><keyword>Data Interpretation, Statistical</keyword><keyword>Efficiency</keyword><keyword>Humans</keyword><keyword>*Pilot Projects</keyword><keyword>Randomized Controlled Trials as Topic/*methods/statistics & numerical data</keyword><keyword>Sample Size</keyword><keyword>*Statistics as Topic</keyword></keywords><dates><year>2012</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1878-5921 (Electronic)
0895-4356 (Linking)</isbn><accession-num>22169081</accession-num><urls><related-urls><url>;(95). Interestingly, one of the foundation concepts of their manuscript – that one should project the SD of the follow-up study to be close to the upper limit of the CI of the SD of the pilot study – was articulated almost 20 years earlier by Browne ADDIN EN.CITE <EndNote><Cite><Author>Browne</Author><Year>1995</Year><RecNum>4206</RecNum><DisplayText>(96)</DisplayText><record><rec-number>4206</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1407752725">4206</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Browne, R. H.</author></authors></contributors><auth-address>Texas Scottish Rite Hospital for Children, Research Department, Dallas 75219, USA.</auth-address><titles><title>On the use of a pilot sample for sample size determination</title><secondary-title>Stat Med</secondary-title><alt-title>Statistics in medicine</alt-title></titles><periodical><full-title>Stat Med</full-title><abbr-1>Statistics in medicine</abbr-1></periodical><alt-periodical><full-title>Stat Med</full-title><abbr-1>Statistics in medicine</abbr-1></alt-periodical><pages>1933-40</pages><volume>14</volume><number>17</number><keywords><keyword>Clinical Trials as Topic/*statistics & numerical data</keyword><keyword>Confidence Intervals</keyword><keyword>Humans</keyword><keyword>Monte Carlo Method</keyword><keyword>Pilot Projects</keyword><keyword>Reproducibility of Results</keyword></keywords><dates><year>1995</year><pub-dates><date>Sep 15</date></pub-dates></dates><isbn>0277-6715 (Print)
0277-6715 (Linking)</isbn><accession-num>8532986</accession-num><urls><related-urls><url>;(96). Sim and Lewis concluded by noting that using slightly different methodologies, pilot sample sizes of at least 55 are likely to be optimal for generating reliable estimates for the follow-up trial if the outcome variable is interval/ratio and potentially many more patients may be required when the outcome of interest is nominal or ordinal ADDIN EN.CITE <EndNote><Cite><Author>Sim</Author><Year>2012</Year><RecNum>4208</RecNum><DisplayText>(95)</DisplayText><record><rec-number>4208</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1407752867">4208</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Sim, J.</author><author>Lewis, M.</author></authors></contributors><auth-address>Arthritis Research UK Primary Care Centre, Keele University, Keele, Staffordshire, UK. j.sim@keele.ac.uk</auth-address><titles><title>The size of a pilot study for a clinical trial should be calculated in relation to considerations of precision and efficiency</title><secondary-title>J Clin Epidemiol</secondary-title><alt-title>Journal of clinical epidemiology</alt-title></titles><periodical><full-title>J Clin Epidemiol</full-title><abbr-1>Journal of clinical epidemiology</abbr-1></periodical><alt-periodical><full-title>J Clin Epidemiol</full-title><abbr-1>Journal of clinical epidemiology</abbr-1></alt-periodical><pages>301-8</pages><volume>65</volume><number>3</number><keywords><keyword>Bias (Epidemiology)</keyword><keyword>Confidence Intervals</keyword><keyword>Data Interpretation, Statistical</keyword><keyword>Efficiency</keyword><keyword>Humans</keyword><keyword>*Pilot Projects</keyword><keyword>Randomized Controlled Trials as Topic/*methods/statistics & numerical data</keyword><keyword>Sample Size</keyword><keyword>*Statistics as Topic</keyword></keywords><dates><year>2012</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1878-5921 (Electronic)
0895-4356 (Linking)</isbn><accession-num>22169081</accession-num><urls><related-urls><url>;(95). The foundation of the approach espoused by Cocks and Torgerson is different; they recommend selecting a pilot trial sample size large enough to produce a reasonably precise estimate of the treatment effect ADDIN EN.CITE <EndNote><Cite><Author>Cocks</Author><Year>2013</Year><RecNum>4209</RecNum><DisplayText>(85)</DisplayText><record><rec-number>4209</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1407757294">4209</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Cocks, K.</author><author>Torgerson, D. J.</author></authors></contributors><auth-address>York Trials Unit, Department of Health Sciences, University of York, Heslington, York YO10 5DD, UK.</auth-address><titles><title>Sample size calculations for pilot randomized trials: a confidence interval approach</title><secondary-title>J Clin Epidemiol</secondary-title><alt-title>Journal of clinical epidemiology</alt-title></titles><periodical><full-title>J Clin Epidemiol</full-title><abbr-1>Journal of clinical epidemiology</abbr-1></periodical><alt-periodical><full-title>J Clin Epidemiol</full-title><abbr-1>Journal of clinical epidemiology</abbr-1></alt-periodical><pages>197-201</pages><volume>66</volume><number>2</number><keywords><keyword>*Confidence Intervals</keyword><keyword>Evidence-Based Medicine/standards</keyword><keyword>Female</keyword><keyword>Great Britain</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>*Pilot Projects</keyword><keyword>Practice Guidelines as Topic/*standards</keyword><keyword>*Randomized Controlled Trials as Topic</keyword><keyword>Research Design</keyword><keyword>Sample Size</keyword><keyword>Statistics as Topic</keyword></keywords><dates><year>2013</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>1878-5921 (Electronic)
0895-4356 (Linking)</isbn><accession-num>23195919</accession-num><urls><related-urls><url>;(85). Their method involves construction of a one-sided 80% CI around the point estimate of effect and, if the upper limit for a superiority study excludes a clinically significant difference, proceeding with the main follow-up study would not be indicated ADDIN EN.CITE <EndNote><Cite><Author>Cocks</Author><Year>2013</Year><RecNum>4209</RecNum><DisplayText>(85)</DisplayText><record><rec-number>4209</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1407757294">4209</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Cocks, K.</author><author>Torgerson, D. J.</author></authors></contributors><auth-address>York Trials Unit, Department of Health Sciences, University of York, Heslington, York YO10 5DD, UK.</auth-address><titles><title>Sample size calculations for pilot randomized trials: a confidence interval approach</title><secondary-title>J Clin Epidemiol</secondary-title><alt-title>Journal of clinical epidemiology</alt-title></titles><periodical><full-title>J Clin Epidemiol</full-title><abbr-1>Journal of clinical epidemiology</abbr-1></periodical><alt-periodical><full-title>J Clin Epidemiol</full-title><abbr-1>Journal of clinical epidemiology</abbr-1></alt-periodical><pages>197-201</pages><volume>66</volume><number>2</number><keywords><keyword>*Confidence Intervals</keyword><keyword>Evidence-Based Medicine/standards</keyword><keyword>Female</keyword><keyword>Great Britain</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>*Pilot Projects</keyword><keyword>Practice Guidelines as Topic/*standards</keyword><keyword>*Randomized Controlled Trials as Topic</keyword><keyword>Research Design</keyword><keyword>Sample Size</keyword><keyword>Statistics as Topic</keyword></keywords><dates><year>2013</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>1878-5921 (Electronic)
0895-4356 (Linking)</isbn><accession-num>23195919</accession-num><urls><related-urls><url>;(85). They note that this procedure is only feasible if the variance of the main outcome variable is known; one might hypothesize that this would be true for only a minority of situations. After working through examples, they conclude that an appropriate ‘rule of thumb’ would be 9% of the projected sample size of the main study, or 20 participants, whichever is larger ADDIN EN.CITE <EndNote><Cite><Author>Cocks</Author><Year>2013</Year><RecNum>4209</RecNum><DisplayText>(85)</DisplayText><record><rec-number>4209</rec-number><foreign-keys><key app="EN" db-id="deds20xe32sxdme0ff3v5adc0vv2sxz0af2t" timestamp="1407757294">4209</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Cocks, K.</author><author>Torgerson, D. J.</author></authors></contributors><auth-address>York Trials Unit, Department of Health Sciences, University of York, Heslington, York YO10 5DD, UK.</auth-address><titles><title>Sample size calculations for pilot randomized trials: a confidence interval approach</title><secondary-title>J Clin Epidemiol</secondary-title><alt-title>Journal of clinical epidemiology</alt-title></titles><periodical><full-title>J Clin Epidemiol</full-title><abbr-1>Journal of clinical epidemiology</abbr-1></periodical><alt-periodical><full-title>J Clin Epidemiol</full-title><abbr-1>Journal of clinical epidemiology</abbr-1></alt-periodical><pages>197-201</pages><volume>66</volume><number>2</number><keywords><keyword>*Confidence Intervals</keyword><keyword>Evidence-Based Medicine/standards</keyword><keyword>Female</keyword><keyword>Great Britain</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>*Pilot Projects</keyword><keyword>Practice Guidelines as Topic/*standards</keyword><keyword>*Randomized Controlled Trials as Topic</keyword><keyword>Research Design</keyword><keyword>Sample Size</keyword><keyword>Statistics as Topic</keyword></keywords><dates><year>2013</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>1878-5921 (Electronic)
0895-4356 (Linking)</isbn><accession-num>23195919</accession-num><urls><related-urls><url>;(85). PART 7 – CONCLUSIONS AND FUTURE DIRECTIONSCommunity-acquired pneumonia is clearly an important problem for Canadian children, their caregivers, and clinicians. The proposed trial will likely provide important information relating to the optimal duration of therapy for mild CAP – however, as detailed in the previous sections, many relevant questions remain unanswered. Refining the criteria for diagnosis of pneumonia is critically important for clinicians, trialists, and epidemiologists. Almost all of the many additional modalities outlined in detail in previous sections require additional evaluation in diagnosis- or outcome-based studies to better gauge their potential contributions to the management of children with suspected CAP. We are about to begin one such study to systematically investigate the performance characteristics of both salivary C-reactive protein measurement and nasopharyngeal pneumococcal genomic loads in children with lower respiratory tract infections admitted to hospital; we have postulated that both of these indices will be higher in children with bacterial pneumonia than in those with viral bronchiolitis, but this hypothesis requires experimental verification. Additionally, even if high-level nasopharyngeal pneumococcal colonization is ‘in truth’ associated with pneumococcal CAP, it will not help to diagnose paediatric bacterial CAP caused by other organisms, such as group A Streptococcus – should assays be developed to measure these other pathogens as well? It seems quite reasonable to suppose that optimization of CAP diagnosis will be accomplished through a combination of clinical judgment, laboratory investigations (such as CRP and pneumococcal nasopharyngeal genomic load) and radiologic imaging (whether chest radiography or ultrasound). An appropriate evaluation of all of these modalities – plus practical combinations in series – will require a large (multicentre) cohort of children with presumed CAP whose treatment is standardized and whose outcomes are precisely documented. The proposed trial will be important to ensure that ‘standardized treatment’ is optimized prior to proceeding. There is much work to be done to improve our ability to diagnose and treat paediatric community-acquired pneumonia – best to start soon!REFERENCES ADDIN EN.REFLIST 1.World Health Organization. "Pneumonia fact sheet no. 331" . Last Accessed 2013 Oct 10.2.Wardlaw T, Salama P, Johansson EW & Mason E. Pneumonia: The leading killer of children. Lancet 2006; 368: 1048-1050 3.McIntosh K. Community-acquired pneumonia in children. N Engl J Med 2002; 346: 429-437 4.Rudan I, Boschi-Pinto C, Biloglav Z, Mulholland K & Campbell H. Epidemiology and etiology of childhood pneumonia. Bull World Health Organ 2008; 86: 408-416 5.Farha T & Thomson AH. The burden of pneumonia in children in the developed world. Paediatr Respir Rev 2005; 6: 76-82 6.Long SS PL, Prober CG. Principles and practice of pediatric infectious diseases., (Elsevier, Philadelphia, 2008).7.Nelson textbook of pediatrics, 18th ed., (Elsevier, Philadelphia, 2007).8.Margolis P & Gadomski A. The rational clinical examination. Does this infant have pneumonia? JAMA 1998; 279: 308-313 9.Leventhal JM. Clinical predictors of pneumonia as a guide to ordering chest roentgenograms. Clin Pediatr (Phila) 1982; 21: 730-734 10.Lynch T, Platt R, Gouin S, Larson C & Patenaude Y. Can we predict which children with clinically suspected pneumonia will have the presence of focal infiltrates on chest radiographs? Pediatrics 2004; 113: e186-189 11.Midgley CM, Jackson MA, Selvarangan R, Turabelidze G, Obringer E, Johnson D, Giles BL, Patel A, Echols F, Oberste MS, Nix WA, Watson JT & Gerber SI. Severe respiratory illness associated with enterovirus d68 - missouri and illinois, 2014. MMWR Morb Mortal Wkly Rep 2014; 63: 798-799 12.Cherian T, Mulholland EK, Carlin JB, Ostensen H, Amin R, de Campo M, Greenberg D, Lagos R, Lucero M, Madhi SA, O'Brien KL, Obaro S & Steinhoff MC. Standardized interpretation of paediatric chest radiographs for the diagnosis of pneumonia in epidemiological studies. Bull World Health Organ 2005; 83: 353-359 13.Neuman MI, Lee E, Bixby S, Diperna S, Hellinger J, Markowitz R, Servaes S, Monuteaux MC & Shah SS. Variability in the interpretation of chest radiographs for the diagnosis of pneumonia in children. J Hosp Med 2012; 7: 294-298 14.Al aseri Z. Accuracy of chest radiograph interpretation by emergency physicians. Emerg Radiol 2009; 16: 111-114 15.Gatt ME, Spectre G, Paltiel O, Hiller N & Stalnikowicz R. Chest radiographs in the emergency department: Is the radiologist really necessary? Postgrad Med J 2003; 79: 214-217 16.Self WH, Courtney DM, McNaughton CD, Wunderink RG & Kline JA. High discordance of chest x-ray and computed tomography for detection of pulmonary opacities in ed patients: Implications for diagnosing pneumonia. Am J Emerg Med 2013; 31: 401-405 17.Shah VP, Tunik MG & Tsung JW. Prospective evaluation of point-of-care ultrasonography for the diagnosis of pneumonia in children and young adults. JAMA Pediatr 2013; 167: 119-125 18.Bourcier JE, Paquet J, Seinger M, Gallard E, Redonnet JP, Cheddadi F, Garnier D, Bourgeois JM & Geeraerts T. Performance comparison of lung ultrasound and chest x-ray for the diagnosis of pneumonia in the ed. Am J Emerg Med 2014; 32: 115-118 19.Williams DJ, Shah SS, Myers A, Hall M, Auger K, Queen MA, Jerardi KE, McClain L, Wiggleton C & Tieder JS. Identifying pediatric community-acquired pneumonia hospitalizations: Accuracy of administrative billing codes. JAMA Pediatr 2013; 167: 851-858 20.Lukrafka JL, Fuchs SC, Fischer GB, Flores JA, Fachel JM & Castro-Rodriguez JA. Chest physiotherapy in paediatric patients hospitalised with community-acquired pneumonia: A randomised clinical trial. Arch Dis Child 2012; 97: 967-971 21.Chappuy H, Keitel K, Gehri M, Tabin R, Robitaille L, Raymond F, Corbeil J, Maspoli V, Bouazza N, Alcoba G, Lacroix L, Manzano S, Galetto-Lacour A & Gervaix A. Nasopharyngeal carriage of individual streptococcus pneumoniae serotypes during pediatric radiologically confirmed community acquired pneumonia following pcv7 introduction in switzerland. BMC Infect Dis 2013; 13: 357 22.Atkinson M, Lakhanpaul M, Smyth A, Vyas H, Weston V, Sithole J, Owen V, Halliday K, Sammons H, Crane J, Guntupalli N, Walton L, Ninan T, Morjaria A & Stephenson T. Comparison of oral amoxicillin and intravenous benzyl penicillin for community acquired pneumonia in children (pivot trial): A multicentre pragmatic randomised controlled equivalence trial. Thorax 2007; 62: 1102-1106 23.Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, Dowell SF, File TM, Jr., Musher DM, Niederman MS, Torres A & Whitney CG. Idsa/ats consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007; 44 Suppl 2: S27-72 24.Bradley JS, Byington CL, Shah SS, Alverson B, Carter ER, Harrison C, Kaplan SL, Mace SE, McCracken GH, Jr., Moore MR, St Peter SD, Stockwell JA, Swanson JT, Pediatric Infectious Diseases S & the Infectious Diseases Society of A. The management of community-acquired pneumonia in infants and children older than 3 months of age: Clinical practice guidelines by the pids and idsa. Clin Infect Dis 2011; 53: e25-76 25.Zalacain R, Capelastegui A, Ruiz LA, Bilbao A, Gomez A, Uranga A & Espana PP. Streptococcus pneumoniae antigen in urine: Diagnostic usefulness and impact on outcome of bacteraemic pneumococcal pneumonia in a large series of adult patients. Respirology 2014; 19: 936-943 26.Sinclair A, Xie X, Teltscher M & Dendukuri N. Systematic review and meta-analysis of a urine-based pneumococcal antigen test for diagnosis of community-acquired pneumonia caused by streptococcus pneumoniae. J Clin Microbiol 2013; 51: 2303-2310 27.Galetto-Lacour A, Alcoba G, Posfay-Barbe KM, Cevey-Macherel M, Gehri M, Ochs MM, Brookes RH, Siegrist CA & Gervaix A. Elevated inflammatory markers combined with positive pneumococcal urinary antigen are a good predictor of pneumococcal community-acquired pneumonia in children. Pediatr Infect Dis J 2013; 32: 1175-1179 28.Adegbola RA, Obaro SK, Biney E & Greenwood BM. Evaluation of binax now streptococcus pneumoniae urinary antigen test in children in a community with a high carriage rate of pneumococcus. Pediatr Infect Dis J 2001; 20: 718-719 29.Dagan R, Shriker O, Hazan I, Leibovitz E, Greenberg D, Schlaeffer F & Levy R. Prospective study to determine clinical relevance of detection of pneumococcal DNA in sera of children by pcr. J Clin Microbiol 1998; 36: 669-673 30.Isaacman DJ, Zhang Y, Reynolds EA & Ehrlich GD. Accuracy of a polymerase chain reaction-based assay for detection of pneumococcal bacteremia in children. Pediatrics 1998; 101: 813-816 31.Wolter N, Cohen C, Tempia S, Madhi SA, Venter M, Moyes J, Walaza S, Malope Kgokong B, Groome M, du Plessis M, Pretorius M, Dawood H, Kahn K, Variava E, Klugman KP & von Gottberg A. Hiv and influenza virus infections are associated with increased blood pneumococcal load: A prospective, hospital-based observational study in south africa, 2009-2011. J Infect Dis 2013; 32.Albrich WC, Madhi SA, Adrian PV, van Niekerk N, Mareletsi T, Cutland C, Wong M, Khoosal M, Karstaedt A, Zhao P, Deatly A, Sidhu M, Jansen KU & Klugman KP. Use of a rapid test of pneumococcal colonization density to diagnose pneumococcal pneumonia. Clin Infect Dis 2012; 54: 601-609 33.Robinson JL & Salvadori MI. Management of community-associated methicillin-resistant staphylococcus aureus skin abscesses in children. Paediatr Child Health 2011; 16: 115-118 34.Pernica JM, Mah JK & Kam AJ. Canadian pediatricians' prescribing practices for community-acquired pneumonia. Clin Pediatr (Phila) 2013; 35.Waites KB & Talkington DF. Mycoplasma pneumoniae and its role as a human pathogen. Clin Microbiol Rev 2004; 17: 697-728, table of contents 36.Jadavji T, Law B, Lebel MH, Kennedy WA, Gold R & Wang EE. A practical guide for the diagnosis and treatment of pediatric pneumonia. CMAJ 1997; 156: S703-711 37.Le Saux N, Robinson JL. Pneumonia in healthy canadian children and youth: Practice points for management. Pediatr Child Health 2011; 16: 417-420 38.Wang K, Gill P, Perera R, Thomson A, Mant D & Harnden A. Clinical symptoms and signs for the diagnosis of mycoplasma pneumoniae in children and adolescents with community-acquired pneumonia. Cochrane Database Syst Rev 2012; 10: CD009175 39.Hsieh SC, Kuo YT, Chern MS, Chen CY, Chan WP & Yu C. Mycoplasma pneumonia: Clinical and radiographic features in 39 children. Pediatr Int 2007; 49: 363-367 40.Biondi E, McCulloh R, Alverson B, Klein A & Dixon A. Treatment of mycoplasma pneumonia: A systematic review. Pediatrics 2014; 133: 1081-1090 41.Ovetchkine P, Rieder MJ, Canadian Paediatric Society DT & Hazardous Substances C. Azithromycin use in paediatrics: A practical overview. Paediatr Child Health 2013; 18: 311-316 42.Popowitch EB, O'Neill SS & Miller MB. Comparison of the biofire filmarray rp, genmark esensor rvp, luminex xtag rvpv1, and luminex xtag rvp fast multiplex assays for detection of respiratory viruses. J Clin Microbiol 2013; 51: 1528-1533 43.Cilla G, Onate E, Perez-Yarza EG, Montes M, Vicente D & Perez-Trallero E. Viruses in community-acquired pneumonia in children aged less than 3 years old: High rate of viral coinfection. J Med Virol 2008; 80: 1843-1849 44."Us department of health and human services food and drug administration, centre for drug evaluation and research. Guidance for industry. Community-acquired bacterial pneumonia: Developing drugs for treatment. " . Last Accessed Sept 201145.Dunbar LM, Wunderink RG, Habib MP, Smith LG, Tennenberg AM, Khashab MM, Wiesinger BA, Xiang JX, Zadeikis N & Kahn JB. High-dose, short-course levofloxacin for community-acquired pneumonia: A new treatment paradigm. Clin Infect Dis 2003; 37: 752-760 46.Low DE, Pichichero ME & Schaad UB. Optimizing antibacterial therapy for community-acquired respiratory tract infections in children in an era of bacterial resistance. Clin Pediatr (Phila) 2004; 43: 135-151 47.File TM, Jr. Clinical efficacy of newer agents in short-duration therapy for community-acquired pneumonia. Clin Infect Dis 2004; 39 Suppl 3: S159-164 48.Peltola H, Vuori-Holopainen E & Kallio MJ. Successful shortening from seven to four days of parenteral beta-lactam treatment for common childhood infections: A prospective and randomized study. Int J Infect Dis 2001; 5: 3-8 49.Harris JA, Kolokathis A, Campbell M, Cassell GH & Hammerschlag MR. Safety and efficacy of azithromycin in the treatment of community-acquired pneumonia in children. Pediatr Infect Dis J 1998; 17: 865-871 50.Reinert RR. The antimicrobial resistance profile of streptococcus pneumoniae. Clin Microbiol Infect 2009; 15 Suppl 3: 7-11 51.Karlowsky JA, Lagace-Wiens PR, Low DE & Zhanel GG. Annual macrolide prescription rates and the emergence of macrolide resistance among streptococcus pneumoniae in canada from 1995 to 2005. Int J Antimicrob Agents 2009; 34: 375-379 52.Jenkins SG & Farrell DJ. Increase in pneumococcus macrolide resistance, united states. Emerg Infect Dis 2009; 15: 1260-1264 53.Greenberg D, Givon-Lavi N, Sadaka Y, Ben-Shimol S, Bar-Ziv J & Dagan R. Short-course antibiotic treatment for community-acquired alveolar pneumonia in ambulatory children: A double-blind, randomized, placebo-controlled trial. Pediatr Infect Dis J 2014; 33: 136-142 54.Bassler D, Briel M, Montori VM, Lane M, Glasziou P, Zhou Q, Heels-Ansdell D, Walter SD, Guyatt GH, Group S-S, Flynn DN, Elamin MB, Murad MH, Abu Elnour NO, Lampropulos JF, Sood A, Mullan RJ, Erwin PJ, Bankhead CR, Perera R, Ruiz Culebro C, You JJ, Mulla SM, Kaur J, Nerenberg KA, Schunemann H, Cook DJ, Lutz K, Ribic CM, Vale N, Malaga G, Akl EA, Ferreira-Gonzalez I, Alonso-Coello P, Urrutia G, Kunz R, Bucher HC, Nordmann AJ, Raatz H, da Silva SA, Tuche F, Strahm B, Djulbegovic B, Adhikari NK, Mills EJ, Gwadry-Sridhar F, Kirpalani H, Soares HP, Karanicolas PJ, Burns KE, Vandvik PO, Coto-Yglesias F, Chrispim PP & Ramsay T. Stopping randomized trials early for benefit and estimation of treatment effects: Systematic review and meta-regression analysis. JAMA 2010; 303: 1180-1187 55.Haider BA, Saeed MA & Bhutta ZA. Short-course versus long-course antibiotic therapy for non-severe community-acquired pneumonia in children aged 2 months to 59 months. Cochrane Database Syst Rev 2008: CD005976 56.Agarwal G, Awasthi S, Kabra SK, Kaul A, Singhi S & Walter SD. Three day versus five day treatment with amoxicillin for non-severe pneumonia in young children: A multicentre randomised controlled trial. BMJ 2004; 328: 791 57.Clinical efficacy of 3 days versus 5 days of oral amoxicillin for treatment of childhood pneumonia: A multicentre double-blind trial. Lancet 2002; 360: 835-841 58.Kartasasmita C & Saha S. Three days versus five days oral cotrimoxazole for non-severe pneumonia. (Department of Child and Adolescent Health and Development, World Health Organization, Geneva, 2002).59.Pocket book of hospital care for children: Guidelines for the management of common illnesses with limited resources, (WHO Press, Geneva, 2005).60.Policy statement on antimicrobial stewardship by shea, idsa, and pids. Infect Control Hosp Epidemiol 2012; 33: 322-327 61.Allen UD. Clostridium difficile in paediatric populations. Pediatr Child Health 2014; 19: 43-48 62.Forgie S, Zhanel G & Robinson J. Management of acute otitis media. Paediatr Child Health 2009; 14: 457-464 63.Chow AW, Benninger MS, Brook I, Brozek JL, Goldstein EJ, Hicks LA, Pankey GA, Seleznick M, Volturo G, Wald ER, File TM, Jr. & Infectious Diseases Society of A. Idsa clinical practice guideline for acute bacterial rhinosinusitis in children and adults. Clin Infect Dis 2012; 54: e72-e112 64.Hui CP. Acute otitis externa. Paediatr Child Health 2013; 18: 96-101 65.Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, Miller LG, Moran GJ, Nicolle LE, Raz R, Schaeffer AJ, Soper DE, Infectious Diseases Society of A, European Society for M & Infectious D. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update. Clin Infect Dis 2011; 52: e103-120 66.Solomkin JS, Mazuski JE, Bradley JS, Rodvold KA, Goldstein EJ, Baron EJ, O'Neill PJ, Chow AW, Dellinger EP, Eachempati SR, Gorbach S, Hilfiker M, May AK, Nathens AB, Sawyer RG & Bartlett JG. Diagnosis and management of complicated intra-abdominal infection in adults and children: Guidelines by the sis and idsa. Clin Infect Dis 2010; 50: 133-164 67.DN G. The sanford guide to antimicrobial therapy, (Antimicrobial Therapy, Inc., Sperryville, 2011).munity Paediatrics Committee, Canadian Paediatric Society. "Temperature measurement in paediatrics" . Last Accessed 2014 October 169.Fleming S, Thompson M, Stevens R, Heneghan C, Pluddemann A, Maconochie I, Tarassenko L & Mant D. Normal ranges of heart rate and respiratory rate in children from birth to 18 years of age: A systematic review of observational studies. Lancet 2011; 377: 1011-1018 70.Queen MA, Myers AL, Hall M, Shah SS, Williams DJ, Auger KA, Jerardi KE, Statile AM & Tieder JS. Comparative effectiveness of empiric antibiotics for community-acquired pneumonia. Pediatrics 2014; 133: e23-29 71.Williams DJ, Hall M, Shah SS, Parikh K, Tyler A, Neuman MI, Hersh AL, Brogan TV, Blaschke AJ & Grijalva CG. Narrow vs broad-spectrum antimicrobial therapy for children hospitalized with pneumonia. Pediatrics 2013; 132: e1141-1148 72.Myers AL, Hall M, Williams DJ, Auger K, Tieder JS, Statile A, Jerardi K, McClain L & Shah SS. Prevalence of bacteremia in hospitalized pediatric patients with community-acquired pneumonia. Pediatr Infect Dis J 2013; 32: 736-740 73.Brueton VC, Tierney JF, Stenning S, Meredith S, Harding S, Nazareth I & Rait G. Strategies to improve retention in randomised trials: A cochrane systematic review and meta-analysis. BMJ Open 2014; 4: e003821 74.Brueton VC, Stevenson F, Vale CL, Stenning SP, Tierney JF, Harding S, Nazareth I, Meredith S & Rait G. Use of strategies to improve retention in primary care randomised trials: A qualitative study with in-depth interviews. BMJ Open 2014; 4: e003835 75.Brueton VC, Tierney J, Stenning S, Harding S, Meredith S, Nazareth I & Rait G. Strategies to improve retention in randomised trials. Cochrane Database Syst Rev 2013; 12: MR000032 76.Molyneux E, Nizami SQ, Saha S, Huu KT, Azam M, Bhutta ZA, Zaki R, Weber MW & Qazi SA. 5 versus 10 days of treatment with ceftriaxone for bacterial meningitis in children: A double-blind randomised equivalence study. Lancet 2011; 377: 1837-1845 77.Korppi M, Heiskanen-Kosma T & Leinonen M. White blood cells, c-reactive protein and erythrocyte sedimentation rate in pneumococcal pneumonia in children. Eur Respir J 1997; 10: 1125-1129 78.Osterberg L & Blaschke T. Adherence to medication. N Engl J Med 2005; 353: 487-497 79.Kaye KS, Harris AD, McDonald JR, Strausbaugh LJ & Perencevich E. Measuring acceptable treatment failure rates for community-acquired pneumonia: Potential for reducing duration of treatment and antimicrobial resistance. Infect Control Hosp Epidemiol 2008; 29: 137-142 80.Snapinn SM. Noninferiority trials. Curr Control Trials Cardiovasc Med 2000; 1: 19-21 81.Center for Drug Evaluation and Research. "Guidance for industry non-inferiority clinical trials (draft)" . Last Accessed 2014 19 July82.Oczkowski SJ. A clinician's guide to the assessment and interpretation of noninferiority trials for novel therapies. Open Med 2014; 8: e67-e72 83.Thorpe KE, Zwarenstein M, Oxman AD, Treweek S, Furberg CD, Altman DG, Tunis S, Bergel E, Harvey I, Magid DJ & Chalkidou K. A pragmatic-explanatory continuum indicator summary (precis): A tool to help trial designers. CMAJ 2009; 180: E47-57 84.Thabane L, Ma J, Chu R, Cheng J, Ismaila A, Rios LP, Robson R, Thabane M, Giangregorio L & Goldsmith CH. A tutorial on pilot studies: The what, why and how. BMC Med Res Methodol 2010; 10: 1 85.Cocks K & Torgerson DJ. Sample size calculations for pilot randomized trials: A confidence interval approach. J Clin Epidemiol 2013; 66: 197-201 86.Altman DG & Bland JM. Absence of evidence is not evidence of absence. BMJ 1995; 311: 485 87.Wangge G, Klungel OH, Roes KC, de Boer A, Hoes AW & Knol MJ. Interpretation and inference in noninferiority randomized controlled trials in drug research. Clin Pharmacol Ther 2010; 88: 420-423 88.Wangge G, Roes KC, de Boer A, Hoes AW & Knol MJ. The challenges of determining noninferiority margins: A case study of noninferiority randomized controlled trials of novel oral anticoagulants. CMAJ 2013; 185: 222-227 89.van Teijlingen E.R. HV. The importance of pilot studies. Social Research Update 2001: 1-4 90.Wittes J & Brittain E. The role of internal pilot studies in increasing the efficiency of clinical trials. Stat Med 1990; 9: 65-71; discussion 71-62 91.Sandvik L, Erikssen J, Mowinckel P & Rodland EA. A method for determining the size of internal pilot studies. Stat Med 1996; 15: 1587-1590 92.Friede T & Kieser M. Sample size recalculation in internal pilot study designs: A review. Biom J 2006; 48: 537-555 93.Lancaster GA, Dodd S & Williamson PR. Design and analysis of pilot studies: Recommendations for good practice. J Eval Clin Pract 2004; 10: 307-312 94.Julious SA. Sample size of 12 per group rule for a pilot study. Pharmaceut Statist 2005; 4: 287-291 95.Sim J & Lewis M. The size of a pilot study for a clinical trial should be calculated in relation to considerations of precision and efficiency. J Clin Epidemiol 2012; 65: 301-308 96.Browne RH. On the use of a pilot sample for sample size determination. Stat Med 1995; 14: 1933-1940 ................
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