The Conduct and Reporting of Child Health Research: An ... · Study design For 300 RCTs, we extracted design and reporting characteristics and assessed RoB. We as-sessed 5-year changes

The Conduct and Reporting of Child Health Research: An Analysis ofRandomized Controlled Trials Published in 2012 and Evaluation of

Change over 5 YearsAllison Gates, PhD1, Lisa Hartling, PhD1, Ben Vandermeer, MSc1, Patrina Caldwell, PhD2,

Despina G. Contopoulos-Ioannidis, MD3, Sarah Curtis, MD4, Ricardo M. Fernandes, MD, PhD5,6, Terry P. Klassen, MD7,Katrina Williams, PhD8, and Michele P. Dyson, PhD1

Objectives For child health randomized controlled trials (RCTs) published in 2012, we aimed to describe designand reporting characteristics and evaluate changes since 2007; assess the association between trial design andregistration and risk of bias (RoB); and assess the association between RoB and effect size.Study design For 300 RCTs, we extracted design and reporting characteristics and assessed RoB. We as-sessed 5-year changes in design and reporting (based on 300 RCTs we had previously analyzed) using the Fisherexact test. We tested for associations between design and reporting characteristics and overall RoB and registra-tion using the Fisher exact, Cochran-Armitage, Kruskal-Wallis, and Jonckheere-Terpstra tests. We pooled effectsizes and tested for differences by RoB using the c2 test for subgroups in meta-analysis.Results The 2012 and 2007 RCTs differed with respect to many design and reporting characteristics. From 2007to 2012, RoB did not change for random sequence generation and improved for allocation concealment (P < .001).Fewer 2012 RCTs were rated high overall RoB and more were rated unclear (P = .03). Only 7.3% of 2012 RCTswere rated low overall RoB. Trial registration doubled from 2007 to 2012 (23% to 46%) (P < .001) and was asso-ciated with lower RoB (P = .009). Effect size did not differ by RoB (P = .43)Conclusions Random sequence generation and allocation concealment were not often reported, and selectivereporting was prevalent. Measures to increase trialists’ awareness and application of existing reporting guidance,and the prospective registration of RCTs is needed to improve the trustworthiness of findings from this field. (J Pediatr2018;193:237-44).

See editorial, p 11

R andomized controlled trials (RCTs) provide the best evidence to guide clinical practice when carried out appropriately.1

Conversely, RCTs that are poorly conducted may yield biased estimates of treatment effects,1,2 potentially leading tomisinformed clinical decisions that could pose harm.3 Especially for pe-

diatric populations, where the quantity of relevant data lags behind that of adults,4

there exists a need for well-conducted and reported RCTs. A review of a randomsample (n = 300) of child health RCTs published in 2007 by our group5 revealedthat 92% were rated high or unclear risk of bias (RoB) based on Cochranestandards.6 Though registered RCTs yielded superior Jadad scores7 and lower RoBcompared with those that were not registered, registration was declared in only12% of publications.5

Since the time of our review, substantial effort has been applied to improvingthe conduct and reporting of health research. For example, the Cochrane RoB tool,which facilitates the appraisal of systematic error in RCTs based on their conductand reporting qualities, was only in its infancy at that time.6 The Enhancing theQuality and Transparency of Health Research Network,8 which supports the de-velopment, dissemination, and implementation of robust reporting guidelines

CONSORT Consolidated Standards of Reporting TrialsDMC Data monitoring committeeRCTs Randomized controlled trialsRoB Risk of biasSMD Standardized mean difference

From the 1Department of Pediatrics and the AlbertaResearch Centre for Health Evidence (ARCHE),University of Alberta, Edmonton, Alberta, Canada; 2Centerfor Kidney Research and Discipline of Pediatrics andChild Health, University of Sydney, Sydney, New SouthWales, Australia; 3Department of Pediatrics, Division ofInfectious Diseases, Stanford University School ofMedicine and Meta Research Innovation Center atStanford (METRICS), Stanford, CA; 4Department ofPediatrics and Emergency Medicine, Women andChildren’s Health Research Institute, University of Alberta,Edmonton, Alberta, Canada; 5Instituto de MedicinaMolecular, Faculdade de Medicina, Universidade deLisboa, Lisbon, Portugal; 6Department of Pediatrics,Hospital de Santa Maria, Centro Hospitalar Lisboa Norte,Lisbon, Portugal; 7Children’s Hospital Research Instituteof Manitoba, University of Manitoba, Winnipeg, Manitoba,Canada; and 8Department of Pediatrics, Royal Children’sHospital and Murdoch Childrens Research Institute,University of Melbourne, Victoria, Australia

Funded by the Canadian Institutes of Health Research(#KRS 140989). The authors declare no conflicts ofinterest.

0022-3476/$ - see front matter. © 2017 The Author(s). Published by

Elsevier Inc. This is an open access article under the CC BY-NC-ND

license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

https://doi.org10.1016/j.jpeds.2017.09.014

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including the Consolidated Standards of Reporting Trials(CONSORT)1,2 and Standard Protocol Items: Recommenda-tions for Intervention Trials9,10 statements, was launched in 2009.In response to a call for reduced research waste,11-15

adherence to the CONSORT checklist as a condition ofpublication is being adopted by an increasing number ofjournals.16

Specific to pediatric health research, Standards for Re-search in Child Health was founded in 2009 with the missionof improving the design, conduct, and reporting of RCTsthrough the development and dissemination of evidence-based standards.3,17-22 Moreover, a number of international pe-diatric trial networks have been established since the early 2000sto improve infrastructure and research capacity.23 In light ofthese developments, we sought to investigate the conduct andreporting of child health RCTs published in 2012, 5 years fol-lowing our 2007 analysis.5 Specifically, for a random sampleof 300 child health RCTs, we aimed to describe their designand reporting characteristics, including RoB; evaluate changesin trial design and reporting characteristics from 2007 to 2012;assess the association between trial design and reporting char-acteristics, and trial registration and RoB, respectively; and assessthe association between RoB and magnitude of effect for theprimary outcome.

Methods

On November 4, 2013, we searched the Cochrane Central Reg-ister of Controlled Trials for RCTs published in 2012 using pe-diatric subject headings and keywords (Appendix 1; availableat www.jpeds.com). The search was modeled from that usedto identify the 2007 sample (searched October 7, 2009).5 Co-chrane Central Register of Controlled Trials includes random-ized and quasi-randomized controlled trials indexed inMEDLINE and EMBASE, hand-searched results, gray litera-ture sources, and Cochrane Review Groups Specialized Reg-isters of trials.24

The search yielded 2296 unique records, which we up-loaded to EndNote (Clarivate Analytics, Philadelphia, Penn-sylvania) reference management software. From EndNote, wetransferred the records (ordered alphabetically by author) toa Microsoft Office Excel (IBM Corporation, Armonk, NewYork) workbook, with each record allocated to an individualrow. To order the records randomly, we allocated a numberto each record using Excel’s random number generator (ie, theRAND function), which returns a random number between0 and 1. We then reordered the records from smallest to largestto yield a randomly ordered list.

To ensure comparability to our 2007 findings,5 we em-ployed identical selection criteria. A single researcher screenedthe records by title and abstract and selected RCTs that re-ported on outcomes of participants ≤21 years of age. We didnot restrict the sample by language, condition, intervention,nature of the comparator, nor outcome type. To be consis-tent with the 2007 sample size, we included the first 300 (13%)eligible records from the randomly ordered list (Appendix 2;available at www.jpeds.com).

We used the data extraction form from our 2007 study,5 withadditional items added following consultation with clinicaland methodological experts (Appendix 3; available atwww.jpeds.com). From each record we extracted characteris-tics of the publication, study design, intervention, trial conduct,study sample, sample size, data monitoring committee (DMC)and follow-up, outcomes and conclusions, methodologicalquality, and registration and protocol. We extracted data forthe primary outcome. When not specified, we inferred theprimary outcome as the (1) objective outcome, (2) outcomeused to calculate the sample size, or (3) first outcome re-ported in the results. All extracted data were verified by a secondresearcher to identify and resolve errors.

When available, we used the trial register, published pro-tocol, and/or companion article(s) to supplement data extrac-tion. If not cited in the publication, we searched for trial registersin the International Clinical Trials Registry Platform(http://apps.who.int/trialsearch/), the ISRCTN Registry(http://www.isrctn.com/), and via Google (https://www.google.ca/). We used protocols or companion articles onlywhen cited in the publications.

We used the 2010 Cochrane RoB tool25 to assess RoB for theprimary outcome among 7 domains: random sequence gen-eration, allocation concealment, blinding of participants andpersonnel, blinding of outcome assessors, incomplete outcomedata, selective reporting, and other bias. We assessed eachdomain as low, unclear, or high risk following Cochraneprocedures6 and internal decision rules (Appendix 4; avail-able at www.jpeds.com). Overall RoB was determined as follows:low when all domains were assessed as low; unclear when atleast 1 domain was assessed as unclear and no domains wereassessed as high; and high if any domain was assessed as high.6

Two reviewers assessed each record and discussed the judg-ments until consensus was reached or a third party providedarbitration.

Statistical AnalysesWe analyzed the data using StatXact (v 10.0; Cytel, Cam-bridge, Massachusetts) and Stata (v 11.2; StataCorp, CollegeStation, Texas). We analyzed trial characteristics descrip-tively. To assess for 5- year changes in trial design, reporting,and RoB, we compared the 2012 sample with 300 RCTs pub-lished in 2007 on which we had previously extracted compa-rable data.5 We assessed differences in trial design and reportingusing the Fisher exact test. We assessed differences in RoB usingthe Cochran-Armitage test.

For the 2012 sample, we tested for associations between bothregistration status and overall RoB, and the following: conti-nent of the corresponding author, funding source, sample sizecalculation, presence of a DMC, outcomes, adverse events, andconclusions. We assessed differences using the Fisher exact testfor registration status and Cochrane-Armitage test for overallRoB, when appropriate. Otherwise, we used the Kruskal-Wallis or Jonckheere-Terpstra test.

We calculated pooled effect sizes across 203 RCTs with ad-equate data to test for an association between overall RoB andthe magnitude of effect for the primary outcome. We

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computed the standardized mean difference (SMD) for studieswhere the primary outcome was continuous. The mean dif-ference, or difference in means, is a statistic that measures theabsolute difference between the mean outcome value in 2groups (eg, intervention group and control group) in a trial.6

This is known as the effect size. In this study, the contribut-ing trials reported various outcomes that were measured in dif-ferent ways (eg, using different scales), so we used the SMD.The SMD standardizes the results of the contributing trials byexpressing the size of the intervention effect for each trial rela-tive to its variability.6 This yields standardized effects that canbe pooled.6 For studies where the primary outcome was di-chotomous (eg, events), we calculated effect size using themethods described by Borenstein et al.26 Effect sizes were pooledusing DerSimonian-Laird random effects for each of the 3 levelsof RoB (low, unclear, high). We assessed differences across levelsof RoB using the c2 test for subgroups in meta-analysis.

Results

Table I shows the characteristics of the 2012 sample. Most RCTswere from North America (41.3%) or Europe (24.3%), werepublished in specialty medical journals (53.0%), used paral-lel designs (80.7%), and were superiority trials (93.0%). Morethan one-half (52.7%) evaluated “other” interventions (eg, com-munication, organizational, or educational programs; reha-bilitation or psychosocial interventions). Few (17.3%) wereplacebo controlled. Following the International Statistical Clas-sification of Diseases and Related Health Problems, TenthRevision,27 the most common diagnostic categories includedmental, psychosocial, and behavioral disorders (16.7%), in-fectious and parasitic diseases (13.0%), the respiratory system(10.0%), and conditions originating during the neonatal or peri-natal period (10.0%). Of those RCTs where it was reported(90.3%), 48.3% were multicenter.

The funder was reported in 80.3% of the RCTs. Of these,20.7% reported industry or pharmaceutical funding. About one-fifth of RCTs (18.7%) reported the presence of a DMC, 44.6%reported a plan to collect adverse events data, 42.0% re-ported data on at least one adverse event, and 51.6% re-ported a sample size calculation. In 62.3% of RCTs, the primaryoutcome was specified. Most RCTs (81.7%) reported a statis-tically significant outcome. Of those RCTs where the primaryoutcome was significant (50.3%), 93.4% favored the experi-mental intervention. In most RCTs, the authors’ conclusionsfavored the experimental intervention (58.7%). Less than one-half of the RCTs (46.3%) were registered.

Most RCTs were rated high or unclear RoB for random se-quence generation (51.3%), allocation concealment (61.7%),blinding of participants and personnel (66.7%), and selec-tive reporting (68.0%) (Table II). Most RCTs were rated lowRoB for blinding of outcome assessors (68.3%), incompleteoutcome data (55.7%), and other bias (77.3%). Only 7.3% ofRCTs were rated low risk for overall RoB.

Compared with 2007 (Table I),5 more RCTs in the 2012sample were from North America (41.3% vs 29.0%) and lesswere from Europe (24.3% vs 40.3%) (P = .001). Fewer 2012

Table I. Characteristics of pediatric trials from 2007(n = 300) and 2012 (n = 300)*

Characteristicsn (%)

in 2007n (%)

in 2012 P†

Continent of corresponding authorAfrica 11 (3.7) 10 (3.3) .001Asia 58 (19.3) 66 (22.0)Australia 16 (5.3) 19 (6.3)Europe 121 (40.3) 73 (24.3)North America 87 (29.0) 124 (41.3)South America 7 (2.3) 8 (2.7)

Type of journalGeneral medical journal 19 (6.3) 27 (9.0) .001Specialty medical journal 165 (55.0) 159 (53.0)General pediatric journal 45 (15.0) 43 (14.3)Specialty pediatric journal 70 (23.3) 55 (18.3)Other‡ 1 (0.3) 16 (5.3)

Trial typeRCT parallel 269 (89.7) 242 (80.7) <.001RCT crossover 19 (6.3) 15 (5.0)RCT factorial 5 (1.7) 8 (2.7)RCT split body§ 0 (0.0) 1 (0.3)RCT cluster 0 (0.0) 32 (10.7)Unclear 7 (2.3) 2 (0.7)

Study designSuperiority 248 (82.7) 279 (93.0) <.001Equivalence 9 (3.0) 4 (1.3)Noninferiority 13 (4.3) 8 (2.7)Unclear 5 (1.7) 5 (1.7)Other¶ 25 (8.3) 4 (1.3)

Nature of interventionDrug 121 (40.3) 85 (28.3) <.001Vaccine 16 (5.3) 14 (4.7)Alternative therapeutic** 26 (8.7) 14 (4.7)Device 44 (14.7) 29 (9.7)Other†† 93 (31.0) 158 (52.7)

Placebo controlledYes 90 (30.0) 52 (17.3) <.001No 210 (70.0) 248 (82.7)

ConditionsInfectious/parasitic diseases 19 (6.3) 39 (13.0) <.001Endocrine/metabolic diseases 15 (5.0) 25 (8.3)Mental/psychosocial/behavioral 31 (10.3) 50 (16.7)Respiratory system 31 (10.3) 30 (10.0)Neonatal/perinatal 28 (9.3) 30 (10.0)Oral health 23 (7.7) 19 (6.3)Other‡‡ 153 (51.0) 107 (35.7)

Number of centersSingle center 179 (59.7) 140 (46.7) .003Multiple centers 105 (35.0) 131 (43.7)Unclear 16 (5.3) 29 (9.7)

Data monitoring committeePresence reported 14 (4.7) 56 (18.7) <.001Presence not reported 286 (95.3) 244 (81.3)

Adverse eventsReported 129 (43.0) 126 (42.0) .87Not reported 171 (57.0) 174 (58.0)

Funding sourceReported 194 (64.7) 241 (80.3) <.001Not reported 106 (35.3) 59 (19.7)Industry or pharmaceutical 67/194 (34.5) 50/241 (20.7) .002Government — 135/241 (56.0) —Academic or research institute — 71/241 (29.5) —Private — 81/241 (33.6) —No external funding — 12/241 (5.0) —

Primary outcomeExplicitly reported 122 (40.7) 187 (62.3) <.001Not explicitly reported 178 (59.3) 113 (37.7)

Statistically significant outcome effectReported 230 (76.7) 245 (81.7) .16Not reported 70 (23.3) 55 (18.3)

(continued)

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239The Conduct and Reporting of Child Health Research: An Analysis of Randomized Controlled Trials Publishedin 2012 and Evaluation of Change over 5 Years

RCTs were published in specialty pediatric journals (18.3% vs23.3%) and more were published in general medical (9.0% vs6.3%) and “other” journals (ie, not medical or health jour-nals, such as Computers in Human Behavior, PLoS One, andCell Biochemistry and Function) (5.3% vs 0.3%) (P = .001). More2012 RCTs used cluster designs (10.7% vs 0%) and fewer usedparallel designs (80.7% vs 89.7%) (P < .001). In the 2012sample, there were more superiority trials (93.0% vs 82.7%)(P < .001) and fewer RCTs of pharmacologic interventions (ie,drugs or vaccines) (33% vs 45.7%) (P < .001). Fewer 2012 RCTswere placebo controlled (17.3% vs 30.0%) (P < .001), and fewerwere single center (46.7% vs 59.7%) (P = .003).

Compared with 2007,5 more 2012 RCTs reported the fundingsource (80.3% vs 64.7%) (P < .001), less were industry-sponsored (20.7% vs 34.5%) (P = .002), and more reported aDMC (18.7% vs 4.7%) (P < .001). More 2012 RCTs specifiedthe primary outcome (62.3% vs 40.7%) (P < .001), and re-ported findings that favored the experimental intervention(93.4% vs 82.2%) (P = .007). More 2012 RCTs were regis-tered (46.3% vs 23.0%) (P < .001).

Compared with 2007,5 more 2012 RCTs were rated low(38.3% vs 25.0%) and less were rated unclear (59.7% vs 72.3%)risk for allocation concealment (P < .001) (Table II). Fewer 2012RCTs were rated low (33.3% vs 50.3%) and more were ratedhigh (30.0% vs 13.7%) risk for blinding of participants andpersonnel (P < .001). More 2012 RCTs were rated low risk forblinding of outcome assessors (68.3% vs 50.3%) (P < .001) andother bias (77.3% vs 35.3%) (P < .001). Fewer were rated low

risk for selective reporting (32.0% vs 82.0%) (P < .001). Thougha similar proportion of 2012 RCTs were rated low risk for overallRoB (7.3%) compared with 2007 (7.7%), a greater propor-tion were rated unclear (45.0% vs 33.0%) and less were ratedhigh (47.7% vs 59.3%) (P = .030).

Table III shows the characteristics of the 2012 RCTs strati-fied by trial registration and overall RoB. Registration variedsignificantly by continent. For example, 58.1% of RCTs fromNorth America were registered compared with 22.7% of thosefrom Asia (P < .001). More RCTs that specified the fundingsource were registered (54.8%) compared with those that didnot (11.9%) (P < .001). More RCTs that reported a sample sizecalculation were registered (63.2%) compared with those thatdid not (28.3%) (P < .001). More RCTs that reported a DMCwere registered (96.4%) compared with those that did not(35.1%) (P < .001). More RCTs that specified the primaryoutcome were registered (58.8%) compared with those that

Table I. Continued

Characteristicsn (%)

in 2007n (%)

in 2012 P†

Statistically significant primaryoutcomeYes — 151 (50.3) n/aNo 149 (49.7)

Intervention favored§§

Experimental intervention favored 189/230 (82.2) 141/151 (93.4) .007Control intervention favored 19/230 (8.3) 5/151 (3.3)Neither experimental nor control

intervention favored22/230 (9.6) 5/151 (3.3)

Trial registration¶¶

Registered 69 (23.0) 139 (46.3) <.001Not registered 231 (77.0) 161 (53.7)

*Data from 2007 have been previously reported.5 Values from 2012 are novel. Data were ex-tracted for the primary outcome, as cited in the manuscript or inferred by the reviewers.†Assessed using the Fisher exact test.‡Journals that did not fit into any of the 4 other categories (eg, Cell Biochemistry and Func-tion, Computers in Human Behavior, Journal of Child and Family Studies, PLoS One).§A split body design entails testing different interventions (or a placebo) on separate body partsfor each participant (eg, intervention vs placebo, each on 1 of 2 molar teeth within 1 mouth).¶Other study designs included pilot trials and mixed designs (eg, equivalence and noninferiority).**Alternative therapeutic interventions included complementary and alternative treat-ments (eg, yoga, music therapy).††Other interventions included prevention and screening, rehabilitation or psychosocial, surgeryor radiotherapy, and communication, organizational, or educational programs.‡‡Other conditions included injuries, poisoning, external causes of morbidity and mortality, con-ditions of the eye and adnexa, and digestive disorders, among others.27 Conditions were cat-egorized to be comparable with the 2007 data.§§Data from 2007 and 2012 are not directly comparable because in 2012, only trials that re-ported a statistically significant primary outcome were assessed. In 2007, any trial that re-ported a statistically significant outcome (primary or otherwise) was assessed.¶¶Includes trial registration cited in the publication (n = 130) and registers located via an onlinesearch (n = 9).

Table II. Risk of bias assessments by domain in 2007(n = 300) and 2012 (n = 300)*

Risk of bias domainsn (%)

in 2007n (%)

in 2012 P†

Random sequence generationLow 149 (49.7) 146 (48.7) 1.00Unclear 143 (47.7) 148 (49.3)High 8 (2.7) 6 (2.0)

Allocation concealmentLow 75 (25.0) 115 (38.3) <.001Unclear 217 (72.3) 179 (59.7)High 8 (2.7) 6 (2.0)

Blinding: participants and personnel‡

Low 151 (50.3) 100 (33.3) <.001Unclear 108 (36.0) 110 (36.7)High 41 (13.7) 90 (30.0)

Blinding: outcome assessors‡

Low 151 (50.3) 205 (68.3) <.001Unclear 108 (36.0) 76 (25.3)High 41 (13.7) 19 (6.3)

Incomplete outcome dataLow 187 (62.3) 167 (55.7) .96Unclear 53 (17.7) 95 (31.7)High 60 (20.0) 38 (12.7)

Selective reporting§

Low 246 (82.0) 96 (32.0) <.001Unclear 6 (2.0) 185 (61.7)High 48 (16.0) 19 (6.3)

Other bias¶

Low 106 (35.3) 232 (77.3) <.001Unclear 109 (36.3) 49 (16.3)High 85 (28.3) 19 (6.3)

Overall risk of biasLow 23 (7.7) 22 (7.3) .03Unclear 99 (33.0) 135 (45.0)High 178 (59.3) 143 (47.7)

*Data from 2007 have been previously reported.5 Values from 2012 are novel.†Assessed using the Cochran-Armitage trend test.‡In 2007, only 1 blinding domain was reported. For trials published in 2012, we have reported2 blinding domains to reflect 2010 Cochrane standards.25 Though identical values from 2007have been reported for both blinding domains, it is acknowledged that these are not directlycomparable to the 2012 data.§In 2007, selective reporting was assessed by comparing the outcomes reported to those inthe Methods section of the publication. In 2012, selective reporting was assessed by compar-ing the outcomes reported in the publication to those reported in the registry or protocol. Un-registered trials and those without protocols were assessed as unclear risk for this domain.¶In 2007, other bias included the funding source (ie, trials funded by industry would be ratedat high risk of bias). In 2012, the funding source was not considered in assessment of risk ofbias.

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did not (25.7%) (P < .001). More RCTs that planned to collectdata on adverse events were registered (63.4%) compared withthose that did not (32.5%) (P < .001), and more that re-ported at least 1 adverse event were registered (61.9%) com-pared with those that did not (35.1%) (P < .001). More RCTsat low risk of bias were registered (90.9%) compared with thoseat unclear (42.2%) or high risk (43.4%) (P = .009).

More RCTs that reported a sample size calculation were atlow RoB (12.9%) compared with those that did not (1.4%)(P < .001). More RCTs that reported a DMC were at low RoB(21.8%) compared with those that did not (4.1%) (P < .001).More RCTs that specified the primary outcome were at lowRoB (9.6%) compared with those that did not (3.5%)

(P = .002), and more RCTs that reported no significant out-comes were at low RoB (12.7%) compared with those that re-ported at least 1 significant outcome (6.1%) (P = .008). MoreRCTs that planned to collect adverse events data were at lowRoB (11.9%) compared with those that did not (3.6%)(P < .001), and more RCTs that reported at least 1 adverse eventwere at low RoB (11.1%) compared with those that did not(4.6%) (P < .001). More RCTs that reported conclusions notin favor of the experimental intervention were at low RoB(15.8%) compared with those that reported neutral conclu-sions (9.5%) or those in favor of the intervention (5.1%)(P = .030). Registered RCTs were more likely to be at low RoB(14.4%) compared with nonregistered ones (1.2%) (P = .009).

Table III. Trial characteristics and quality measures by trial registration and overall risk of bias (n = 300)

Characteristics N

Registered, n (%)

P*

Overall risk of bias, n (%)

P†Yes

139 (46.3)No

161 (53.7)Low

22 (7.3)Unclear

135 (45.0)High

143 (47.7)

Continent of corresponding authorAfrica 10 7 (70.0) 3 (30.0) <.001 2 (20.0) 4 (40.0) 4 (40.0) .22‡

Asia 66 15 (22.7) 51 (77.3) 4 (6.1) 40 (60.6) 22 (33.3)Australia 19 9 (47.4) 10 (52.6) 1 (5.3) 6 (31.6) 12 (63.2)Europe 73 33 (45.2) 40 (54.8) 3 (4.1) 38 (52.1) 32 (43.8)North America 124 72 (58.1) 52 (41.9) 11 (8.9) 44 (35.5) 69 (55.6)South America 8 3 (37.5) 5 (62.5) 1 (12.5) 3 (37.5) 4 (50.0)

Funding sourceSpecified 241 132 (54.8) 109 (45.2) <.001 21 (8.7) 104 (43.2) 116 (48.1) .64Not specified 59 7 (11.9) 52 (88.1) 1 (1.7) 31 (52.5) 27 (45.8)

BlindingTrial described as blinded 162 85 (52.5) 77 (47.5) .027 n/a n/a n/a n/a§

Trial not described as blinded 138 54 (39.1) 84 (60.9) n/a n/a n/aSample size calculation

Reported 155 98 (63.2) 57 (36.8) <.001 20 (12.9) 83 (53.5) 52 (33.5) <.001Not reported 145 41 (28.3) 104 (71.7) 2 (1.4) 52 (35.9) 91 (62.8)

Presence of a data monitoring committeeReported 55 53 (96.4) 2 (3.6) <.001 12 (21.8) 25 (45.5) 18 (32.7) <.001Not reported 245 86 (35.1) 159 (64.9) 10 (4.1) 110 (44.9) 125 (51.0)

Primary outcomeSpecified 187 110 (58.8) 77 (41.2) <.001 18 (9.6) 92 (49.2) 77 (41.2) .002Not specified 113 29 (25.7) 84 (74.3) 4 (3.5) 43 (38.1) 66 (58.4)

Significant outcomesAt least 1 reported 245 109 (44.5) 136 (55.5) .182 15 (6.1) 105 (42.9) 125 (51.0) .008None reported 55 30 (54.5) 25 (45.5) 7 (12.7) 30 (54.5) 18 (32.7)

AEsPlanned to collect AE data 134 85 (63.4) 49 (36.6) <.001 16 (11.9) 76 (56.7) 42 (31.3) <.001Did not plan to collect AE data 166 54 (32.5) 112 (67.5) 6 (3.6) 59 (35.5) 101 (60.8)

AEs reportedAt least 1 AE reported 126 78 (61.9) 48 (38.1) <.001 14 (11.1) 73 (57.9) 39 (31.0) <.001No AEs reported 174 61 (35.1) 113 (64.9) 8 (4.6) 62 (35.6) 104 (59.7)

Overall conclusionsIn favor of the experimental intervention 176 72 (40.9) 104 (59.1) .16¶ 9 (5.1) 76 (43.2) 91 (51.7) .03**Not in favor of the experimental intervention 19 7 (36.8) 12 (63.2) 3 (15.8) 10 (52.6) 6 (31.6)Neutral 105 60 (57.1) 45 (42.9) 10 (9.5) 49 (46.7) 46 (43.8)

Trial registrationRegistered 139 n/a n/a n/a 20 (14.4) 57 (41.0) 62 (44.6) .009Not registered 161 2 (1.2) 78 (48.4) 81 (50.3)

Overall risk of biasLow 22 20 (90.9) 2 (9.1) .009¶ n/a n/a n/a n/aUnclear 135 57 (42.2) 78 (57.8)High 143 62 (43.4) 81 (56.6)

AE, adverse events.*Assessed using the Fisher exact test unless noted otherwise.†Assessed using the Cochran-Armitage trend test unless noted otherwise.‡Assessed using the Kruskal-Wallis test.§Not assessed because blinding is a component of the Cochrane Risk of Bias tool.¶Assessed using the Cochran-Armitage trend test.**Assessed using the Jonckheere-Terpstra test.



For 203 RCTs where sufficient data were reported (68 withdichotomous and 135 with continuous data), the absolute effectsize for those at low RoB was 0.70 (95% CI 0.28, 1.13), com-pared with 0.46 (0.37, 0.56) and 0.58 (0.42, 0.73) for RCTs atunclear and high RoB, respectively (Table IV). There was noassociation between effect size and RoB.

Discussion

Our data indicate that the landscape of pediatric research ischanging. Compared with 2007, the 2012 RCTs differed sig-nificantly with respect to many design characteristics. Notably,the 2012 sample included more cluster RCTs, which were absentin the 2007 sample. The 2012 sample also included more su-periority trials, and fewer drug trials and placebo-controlledtrials. Compared with 2007, in 2012 a significantly larger pro-portion of trials were multicenter. With respect to reporting,more 2012 RCTs reported the funding source, the presence ofa DMC, and specified the primary outcome.

We also noted significant changes with respect to RoB. Somechanges may be attributable to genuine differences in conduct,reporting, or trial design between samples. For some domains,changes are more likely attributable to how RoB was as-sessed. In 2007, we used an earlier version of the Cochrane RoBtool (Appendix 5; available at www.jpeds.com), precludingdirect comparisons. In 2007, blinding was assessed as a singledomain. Selective reporting was assessed by checking for con-sistency between the outcomes reported in the methods andresults sections of the publication. In 2012, judging selectivereporting required comparing the outcomes reported in thepublication to those in the protocol. With respect to othersources of bias, in 2007 judging RoB included accounting forfinancial interests. In 2012, the funders were not consideredin the judgment of risk in this domain.

Random sequence generation and allocation concealmentwere more consistently assessed at both time points. Stabilityor change in these domains is more likely attributable to char-acteristics of the conduct, reporting, or design of the RCTs.We observed no change over time with respect to random se-quence generation. Akin to 2007, approximately one-half of2012 RCTs were rated unclear risk, likely because of report-ing shortfalls (eg, stating that the participants were “random-ized” without specifying how). With respect to allocationconcealment, from 2007 to 2012 we observed an increase inthe proportion of RCTs rated low risk, however nearly two-thirds of RCTs remained at high or unclear risk. Similarly, in

2010 Crocetti et al28 reported that 41% and 57% of pediatrictrials published in high impact journals were at high or unclearRoB for random sequence generation and allocation conceal-ment, respectively.

Insufficient blinding of participants and personnel waspresent in two-thirds of the 2012 RCTs. Most RCTs rated highrisk evaluated rehabilitation or psychosocial interventions, andcommunication, organizational, or educational programs. Inthese types of interventions, blinding of participants and per-sonnel is often infeasible.29 Blinding of the outcome asses-sors is more often realistic, and most 2012 RCTs were ratedlow risk on this domain. Selective reporting was present in two-thirds of the 2012 RCTs. In 2004, the International Commit-tee of Medical Journal Editors published a statement supportingcomprehensive registration of trials in an effort to improve re-porting, and 11 of its member journals adopted a registra-tion policy.30 In our sample, registration was associated withmore complete reporting of the funding source, sample sizecalculation, a priori primary outcome(s), and adverse events.Selective reporting, however, was observed even among reg-istered trials.

Selective reporting introduces biases that often favor a sta-tistically significant primary outcome.31,32 In our study, moreregistered than unregistered trials were at low RoB. Using theCochrane RoB tool, trial registration or a published protocolare necessary components of judging the selective reportingdomain. When these are unavailable, the potential for bias dueto selective reporting is at least unclear, and accordingly, overallRoB cannot be low. In the study by Crocetti et al,28 registeredtrials were less likely to be at high risk of bias for random se-quence generation. Similarly, registered trials in our study per-formed better on the random sequence generation, allocationconcealment, blinding, and selective reporting domains. Al-though registered trials made up over 90% of those judged lowoverall RoB in this study, still 86% of registered trials were athigh or unclear RoB. Similarly, in a sample of pediatric trialspublished in 2013, Rosati et al32 noted serious discrepanciesbetween the trial registry and the published study, includingselective outcome reporting. Registration is thus necessary, butnot sufficient alone to eliminate threats to the internal valid-ity of the results of child health trials.31-35

We identified a number of shortfalls in the reporting (andpotentially conduct) of child health RCTs that should be ad-dressed. Random sequence generation and allocation conceal-ment are always feasible in RCTs.29 These were not often carriedout and/or reported appropriately, potentially resulting in ex-aggerated treatment effects.29,36,37 Signs of selective reporting,

Table IV. Absolute effect size by level of overall risk of bias in 2007 (n = 237) compared with in 2012 (n = 203)*

Overall riskof bias

Absolute effect size (95% CI)in 2007 P†

Absolute effect size (95% CI)in 2012 P†

Difference from 2007 to 2012(95% CI)

Low 0.16 (0.07, 0.25) .13 0.70 (0.28, 1.13) .43 0.54 (0.10, 0.98)Unclear 0.22 (0.15, 0.29) 0.46 (0.37, 0.56) 0.24 (0.12, 0.36)High 0.28 (0.21, 0.35) 0.58 (0.42, 0.73) 0.30 (0.13, 0.47)

*Data from 2007 have been previously reported.5 Values from 2012 are novel.†Test for association between overall risk of bias and absolute effect size. Assessed using the c2 test for subgroups in meta-analysis.


242 Gates et al


identified as a common issue in RCTs published in leadingmedical journals,38 was prevalent in our sample.

Clear guidance exists to support the complete and trans-parent reporting of RCTs,1 however, these are inadequatelyadopted and adhered to.14 Journals that endorse CONSORTpublish RCTs that are more completely reported compared withthose that do not.16 Nevertheless, even CONSORT- endors-ing journals do not consistently enforce reporting issues,39 andsupport to guide peer reviewers in assessing reporting qualityis often inadequate.40 As indicated by our data, registered childhealth RCTs are more likely to be at low RoB and to be morecompletely reported.

Steps toward improvement would include measures to in-crease trialists’ awareness and application of reporting guid-ance, and the prospective41 registration of all RCTs. Strategiesthat translate the guidance for complete and transparent re-porting into clear and concise messages for trialists may be re-quired. Enforcement of CONSORT by a greater proportion ofjournals, including guidance for peer reviewers on how to iden-tify reporting inadequacies, may help to improve the qualityof published child health RCTs. The adoption of trial regis-tration as a requirement for publication by a greater propor-tion of journals may also help to improve transparency andreduce bias. As the landscape of pediatric health research con-tinues to evolve, quality should be continuously evaluated toidentify trends and areas for improvement.

The 2007 sample differed from the 2012 one with respectto many design features, which may have impacted RoB. Tomaximize comparability, we employed a similar search strat-egy and identical sampling scheme in both years. Assessmentof RoB is inherently subjective, and concordance of assess-ments by independent author groups are moderate, at best.42,43

To maximize consistency, MPD, who completed the 2007 as-sessments, trained the 2012 reviewers and standard decisionrules were used. In 2007 an earlier version of the RoB tool wasused, precluding direct comparisons for some domains. Becausethe majority of the variables investigated were related to re-porting, our findings may not account completely for trialconduct.

The data presented herein represent only a small subset ofthose collected as part of this study. Because of resource andstaffing constraints, the timelines for data collection and veri-fication, statistical analyses, and manuscript writing were rela-tively lengthy, accounting for use of a sample from 2012. Insubsequent updates to this work, more focused data collec-tion (eg, a smaller subset of high-priority variables) will allowfor timelier reporting of the findings.

Though improvements with respect to some RoB domainswere observed, others were unchanged and the majority of RCTsremained at unclear or high overall RoB. Although clear andtransparent reporting is important, methodological rigor inthe design and conduct of trials is critical to ensuring rel-evant and valid results. This study has identified a number ofkey design elements that need further improvement. Opti-mizing the design, conduct, and reporting of trials will reduceresearch waste in a field where quality findings to support clini-cal decision-making are limited.4 ■

The authors thank Anne Junker, MD, FRCPC, BC, (Children’s Hospi-tal, Vancouver, Canada), An-Wen Chan, PhD, MD, FRCPC, (Women’sCollege Research Institute, Toronto, Canada), David Moher, PhD, (TheOttawa Hospital, Ottawa, Canada), Lawrence Richer, MD, (Univer-sity of Alberta, Edmonton, Canada), Martin Offringa, MD, PhD, (TheHospital for Sick Children, Toronto, Canada), and Shannon Scott, RN,PhD, (University of Alberta, Edmonton, Canada) for contributing tothe design of the study; Dr Shannon Scott for providing revisions to anearly version of the manuscript; Robin Featherstone, MLIS, (Univer-sity of Alberta, Edmonton, Canada) for running the search; and SarahBryson, Huiru Dong, Aimee Gonzalez, Hamza Jafri, Karandeep Jassal,Megan Nuspl, Kassi Shave, Jocelyn Shulhan, and Jaskiran Sidhu (sala-ried research assistants at the University of Alberta, Edmonton, Canada)for contributing to data extraction.

Submitted for publication Jun 6, 2017; last revision received Aug 10, 2017;accepted Sep 7, 2017

Reprint requests: Michele P. Dyson, PhD, University of Alberta, ECHA 4-474,11405-87 Ave NW, Edmonton, AB, T6G 1C9, Canada. E-mail: [email protected]

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Summary of Search

Database Date Searched Number Retrieved After Duplicate RemovalCochrane Central Register of Controlled Trials (Wiley)

November 4, 2013 2343 2296

Total 2343 2296

Database: Cochrane Central Register of Controlled Trials (Wiley)

Date Searched: 4 November 2013 at 21:07:57.057

Results: 2343 records (2296 following duplicate removal)

Search Strategy:

#1 (Infant* or infancy or Newborn* or Baby* or Babies or Neonat* or Preterm* or Prematur* or Postmatur* or Child* or Schoolchild* or School age* or Preschool* or Kid or kids or Toddler* or Teen* or Boy* or Girl* or Minors* or Pubert* or Pubescen* or Prepubescen* or Pediatric* or Paediatric* or Peadiatric* or Nursery school* or Kindergar* or Primary school* or Secondary school* or Elementary school* or High school* or Highschool*):ti,ab,kw

#2 (Adolesc*):ti,ab

#3 (Infant or Child or Minors or Puberty or Pediatrics or Schools):kw

#4 #1 or #2 or #3

#5 adolescent*:kw

#6 (adolescent* and (adult* or elderly or "middle aged" or "aged, 80 and over")):kw

#7 #6 and not #4

#8 #4 or #5

#9 #8 and not #7 from 2012 to 2012, in Trials

Appendix 1. Search Strategy to Identify Randomized Controlled Trials of Child Health Published in 2012.


244.e1The Conduct and Reporting of Child Health Research: An Analysis of Randomized Controlled Trials Publishedin 2012 and Evaluation of Change over 5 Years

Record # Author(s) Title Journal

2050 Baker-Henningham H, Scott S, Jones K and Walker SReducing child conduct problems and promoting social skills in a middle-income country: cluster randomised controlled trial

The British journal of psychiatry : the journal of mental science

2056Gerald LB, Gerald JK, Zhang B, McClure LA, Bailey WC and Harrington KF

Can a school-based hand hygiene program reduce asthma exacerbations among elementary school children?

The Journal of allergy and clinical immunology

2061Bhandari N, Mazumder S, Taneja S, Sommerfelt H and Strand TA

Effect of implementation of Integrated Management of Neonatal and Childhood Illness (IMNCI) programme on neonatal and infant mortality: cluster randomised controlled trial

BMJ (Clinical research ed.)

2062Spencer-Smith MM, Spittle AJ, Doyle LW, Lee KJ, Lorefice L, Suetin A, Pascoe L and Anderson PJ

Long-term benefits of home-based preventive care for preterm infants: a randomized trial

Pediatrics

2066Snyder FJ, Vuchinich S, Acock A, Washburn IJ and Flay BR

Improving elementary school quality through the use of a social-emotional and character development program: a matched-pair, cluster-randomized, controlled trial in Hawai'i

The Journal of school health

2075Watson-Jones D, Baisley K, Ponsiano R, Lemme F, Remes P, Ross D, Kapiga S, Mayaud P, Sanjosé S, Wight D, Changalucha J and Hayes R

Human papillomavirus vaccination in Tanzanian schoolgirls: cluster-randomized trial comparing 2 vaccine-delivery strategies

The Journal of infectious diseases

2077 Velandia M, Uvnas-Moberg K and Nissen ESex differences in newborn interaction with mother or father during skin-to-skin contact after Caesarean section

Acta paediatrica (oslo, norway : 1992)

2090O'Brien K, Campbell C, Brown L, Wenger L and Shah V

Infant flow biphasic nasal continuous positive airway pressure (BP- NCPAP) vs. infant flow NCPAP for the facilitation of extubation in infants' </= 1,250 grams: a randomized controlled trial

BMC pediatrics

2102Gitto E, Aversa S, Salpietro CD, Barberi I, Arrigo T and Trimarchi G

Pain in neonatal intensive care: role of melatonin as an analgesic antioxidant

Journal of pineal research

2107Dani C, Lori I, Favelli F, Frosini S, Messner H and Wanker P

Lutein and zeaxanthin supplementation in preterm infants to prevent retinopathy of prematurity: a randomized controlled study

The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians

2113Bueno M, Stevens B, Camargo PP, Toma E, Krebs VL and Kimura AF

Breast milk and glucose for pain relief in preterm infants: a noninferiority randomized controlled trial

Pediatrics

2116Halterman JS, Fagnano M, Montes G, Fisher S, Tremblay P, Tajon R, Sauer J and Butz A

The school-based preventive asthma care trial: results of a pilot study

The Journal of pediatrics

2120Ang JY, Lua JL, Mathur A, Thomas R, Asmar BI, Savasan S, Buck S, Long M and Shankaran S

A randomized placebo-controlled trial of massage therapy on the immune system of preterm infants

Pediatrics

2122 Alsweiler JM, Harding JE and Bloomfield FHTight glycemic control with insulin in hyperglycemic preterm babies: a randomized controlled trial

Pediatrics

2125 Fucile S, McFarland DH, Gisel EG and Lau COral and nonoral sensorimotor interventions facilitate suck-swallow-respiration functions and their coordination in preterm infants

Early human development

2129Campbell SK, Gaebler-Spira D, Zawacki L, Clark A, Boynewicz K, deRegnier RA, Kuroda MM, Bhat R, Yu J, Campise-Luther R, Kale D, Bulanda M and Zhou XJ

Effects on motor development of kicking and stepping exercise in preterm infants with periventricular brain injury: a pilot study

Journal of pediatric rehabilitation medicine

2130Veereman-Wauters G, Staelens S, Rombaut R, Dewettinck K, Deboutte D and Brummer RJ

Milk fat globule membrane (INPULSE) enriched formula milk decreases febrile episodes and may improve behavioral regulation in young children

Nutrition (Burbank, Los Angeles County, Calif.)

2139Jago R, Sebire SJ, Cooper AR, Haase AM, Powell J, Davis L, McNeill J and Montgomery AA

Bristol girls dance project feasibility trial: outcome and process evaluation results

The international journal of behavioral nutrition and physical activity

2142Batton BJ, Li L, Newman NS, Das A, Watterberg KL, Yoder BA, Faix RG, Laughon MM, Meurs KP, Carlo WA, Higgins RD and Walsh MC

Feasibility study of early blood pressure management in extremely preterm infants


2150 Moya F, Sisk PM, Walsh KR and Berseth CLA new liquid human milk fortifier and linear growth in preterm infants

Pediatrics

Appendix 2. Records Included in the 2012 Study (n = 300). (Continues)


244.e2 Gates et al

2155Merry SN, Stasiak K, Shepherd M, Frampton C, Fleming T and Lucassen MF

The effectiveness of SPARX, a computerised self help intervention for adolescents seeking help for depression: randomised controlled non-inferiority trial


2162 McLaughlin KA, Zeanah CH, Fox NA and Nelson CAAttachment security as a mechanism linking foster care placement to improved mental health outcomes in previously institutionalized children

Journal of child psychology and psychiatry, and allied disciplines

2164 Zhang C, Zhang L, Huang L, Luo R and Wen JClinical pharmacists on medical care of pediatric inpatients: a single-center randomized controlled PloS onetrial

2171 Ryzin MJ, Stormshak EA and Dishion TJ Engaging parents in the family check-up in middle school: longitudinal effects on family conflict and problem behavior through the high school transition

The Journal of adolescent health : official publication of the Society for Adolescent Medicine

2178 Shamah Levy T, Morales Ruán C, Amaya Castellanos C, Salazar Coronel A, Jiménez Aguilar A and Méndez Gómez Humarán I

Effectiveness of a diet and physical activity promotion strategy on the prevention of obesity in Mexican school children

BMC public health

2188 Sosenko IR, Fajardo MF, Claure N and Bancalari E Timing of patent ductus arteriosus treatment and respiratory outcome in premature infants: a double-blind randomized controlled trial


2190

Alvarez O, Miller ST, Wang WC, Luo Z, McCarville MB, Schwartz GJ, Thompson B, Howard T, Iyer RV, Rana SR, Rogers ZR, Sarnaik SA, Thornburg CD and Ware RE

Effect of hydroxyurea treatment on renal function parameters: results from the multi-center placebo-controlled BABY HUG clinical trial for infants with sickle cell anemia

Pediatric blood & cancer

2200 Tyson JE, Pedroza C, Langer J, Green C, Morris B, Stevenson D, Meurs KP, Oh W, Phelps D, O'Shea M, McDavid GE, Grisby C and Higgins R

Does aggressive phototherapy increase mortality while decreasing profound impairment among the smallest and sickest newborns?

Journal of perinatology : official journal of the California Perinatal Association

2202 Wilson DB, Jones RM, McClish D, Westerberg AL and Danish S

Fruit and vegetable intake among rural youth following a school-based randomized controlled trial

Preventive medicine

2203 Soofi S, Cousens S, Imdad A, Bhutto N, Ali N and Bhutta ZA

Topical application of chlorhexidine to neonatal umbilical cords for prevention of omphalitis and neonatal mortality in a rural district of Pakistan: a community-based, cluster-randomised trial

Lancet

2205 Espada JP, Orgilés M, Morales A, Ballester R and Huedo-Medina TB

Effectiveness of a school HIV/AIDS prevention program for Spanish adolescents

AIDS education and prevention : official publication of the International Society for AIDS Education

2206 Rogers SJ, Estes A, Lord C, Vismara L, Winter J, Fitzpatrick A, Guo M and Dawson G

Effects of a brief Early Start Denver model (ESDM)-based parent intervention on toddlers at risk for autism spectrum disorders: a randomized controlled trial

Journal of the American Academy of Child and Adolescent Psychiatry

2210 Alencar AJ, Sanudo A, Sampaio VM, Góis RP, Benevides FA and Guinsburg R

Efficacy of tramadol versus fentanyl for postoperative analgesia in neonates

Archives of disease in childhood. Fetal and neonatal edition

2212

Mesotten D, Gielen M, Sterken C, Claessens K, Hermans G, Vlasselaers D, Lemiere J, Lagae L, Gewillig M, Eyskens B, Vanhorebeek I, Wouters PJ and Berghe G

Neurocognitive development of children 4 years after critical illness and treatment with tight glucose control: a randomized controlled trial

JAMA : the journal of the American Medical Association

2218 Wong MC, Lau TC and Lee AThe impact of leadership programme on self-esteem and self-efficacy in school: a randomized controlled trial

PloS one

2221Carcillo JA, Dean JM, Holubkov R, Berger J, Meert KL, Anand KJ, Zimmerman J, Newth CJ, Harrison R, Burr J, Willson DF and Nicholson C

The randomized comparative pediatric critical illness stress-induced immune suppression (CRISIS) prevention trial

Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

2227Coleman KJ, Shordon M, Caparosa SL, Pomichowski ME and Dzewaltowski DA

The healthy options for nutrition environments in schools (Healthy ONES) group randomized trial: using implementation models to change nutrition policy and environments in low income schools


2228Fiadjoe JE, Gurnaney H, Dalesio N, Sussman E, Zhao H, Zhang X and Stricker PA

A prospective randomized equivalence trial of the GlideScope Cobalt® video laryngoscope to traditional direct laryngoscopy in neonates and infants

Anesthesiology

2229D'Amico EJ, Tucker JS, Miles JN, Zhou AJ, Shih RA and Green HD

Preventing alcohol use with a voluntary after-school program for middle school students: results from a cluster randomized controlled trial of CHOICE

Prevention science : the official journal of the Society for Prevention Research

Appendix 2. Continues.



2239Brody GH, Chen YF, Kogan SM, Yu T, Molgaard VK, DiClemente RJ and Wingood GM

Family-centered program deters substance use, conduct problems, and depressive symptoms in black adolescents

Pediatrics

2240

Vaucher YE, Peralta-Carcelen M, Finer NN, Carlo WA, Gantz MG, Walsh MC, Laptook AR, Yoder BA, Faix RG, Das A, Schibler K, Rich W, Newman NS, Vohr BR, Yolton K, Heyne RJ, Wilson-Costello DE, Evans PW, Goldstein RF, Acarregui MJ, Adams-Chapman I, Pappas A, Hintz SR, Poindexter B, Dusick AM, McGowan EC, Ehrenkranz RA, Bodnar A, Bauer CR, Fuller J, O'Shea TM, Myers GJ and Higgins RD

Neurodevelopmental outcomes in the early CPAP and pulse oximetry trial

The New England journal of medicine

2250Verloigne M, Bere E, Lippevelde W, Maes L, Lien N, Vik FN, Brug J, Cardon G and Bourdeaudhuij I

The effect of the UP4FUN pilot intervention on objectively measured sedentary time and physical activity in 10-12 year old children in Belgium: the ENERGY-project

BMC public health

2257Arifeen SE, Mullany LC, Shah R, Mannan I, Rahman SM, Talukder MR, Begum N, Al-Kabir A, Darmstadt GL, Santosham M, Black RE and Baqui AH

The effect of cord cleansing with chlorhexidine on neonatal mortality in rural Bangladesh: a community-based, cluster-randomised trial

Lancet

2259Raynor HA, Osterholt KM, Hart CN, Jelalian E, Vivier P and Wing RR

Efficacy of U.S. paediatric obesity primary care guidelines: two randomized trials

Pediatric obesity

2262Todd DA, Wright A, Broom M, Chauhan M, Meskell S and Cameron C

Methods of weaning preterm babies <30 weeks gestation off CPAP: a multicentre randomised controlled trial


2264Day C, Michelson D, Thomson S, Penney C and Draper L

Evaluation of a peer led parenting intervention for disruptive behaviour problems in children: community based randomised controlled trial


2268Blanco CL, Gong AK, Schoolfield J, Green BK, Daniels W and Liechty EA

Impact of early and high amino acid supplementation on ELBW infants at 2 years

Journal of pediatric gastroenterology and nutrition

2272Habibi M, Mahyar A, Ayazi P, Ahmadabadi F and Javadi A

The effect of clofibrate on hyperbilirubinemia of term neonates

Acta medica Iranica

2285McCain GC, Moral T, Duncan RC, Fontaine JL and Pino LD

Transition from gavage to nipple feeding for preterm infants with bronchopulmonary dysplasia

Nursing research

2286Rosenfeld M, Ratjen F, Brumback L, Daniel S, Rowbotham R, McNamara S, Johnson R, Kronmal R and Davis SD

Inhaled hypertonic saline in infants and children younger than 6 years with cystic fibrosis: the ISIS randomized controlled trial


2298 Garrison MM and Christakis DAThe impact of a healthy media use intervention on sleep in preschool children

Pediatrics

2303 Quiambao B, Meeren O, Kolhe D and Gatchalian S

A randomized, dose-ranging assessment of the immunogenicity and safety of a booster dose of a combined diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Hemophilus influenzae type b (DTPw-HBV-IPV/Hib) vaccine vs. co-administration of DTPw-HBV/Hib and IPV vaccines in 12 to 24 months old Filipino toddlers

Human vaccines & immunotherapeutics

2309 Iwasaki T, Nonoda Y and Ishii MLong-term outcomes of children and adolescents who had cerebral palsy with secondary osteoporosis

Current medical research and opinion

2315Haiden N, Norooz F, Klebermass-Schrehof K, Horak AS, Jilma B, Berger A and Repa A

The effect of an osmotic contrast agent on complete meconium evacuation in preterm infants

Pediatrics

2322 Xia W, Zhang X, Wang J, Sun C and Wu L

Survey of anaemia and Helicobacter pylori infection in adolescent girls in Suihua, China and enhancement of iron intervention effects by H. pylori eradication

The British journal of nutrition

2329Wyse R, Wolfenden L, Campbell E, Campbell KJ, Wiggers J, Brennan L, Fletcher A, Bowman J and Heard TR

A cluster randomized controlled trial of a telephone-based parent intervention to increase preschoolers' fruit and vegetable consumption

The American journal of clinical nutrition

2335Trudeau L, Spoth R, Randall GK, Mason WA and Shin C

Internalizing symptoms: effects of a preventive intervention on developmental pathways from early adolescence to young adulthood

Journal of youth and adolescence

2354Lee S, Bacha F, Hannon T, Kuk JL, Boesch C and Arslanian S

Effects of aerobic versus resistance exercise without caloric restriction on abdominal fat, intrahepatic lipid, and insulin sensitivity in obese adolescent boys: a randomized, controlled trial

Diabetes

2356Tamam S, Bellissimo N, Patel BP, Thomas SG and Anderson GH

Overweight and obese boys reduce food intake in response to a glucose drink but fail to increase intake in response to exercise of short duration

Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme



244.e4 Gates et al

2366 Wheeler KI, Morley CJ, Hooper SB and Davis PGLower back-up rates improve ventilator triggering during assist-control ventilation: a randomized crossover trial


2375Ngerncham S, Jirapaet K, Suvonachai R, Chaweerat R, Wongsiridej P and Kolatat T

Effectiveness of conventional phototherapy versus Super light-emitting diodes phototherapy in neonatal hyperbilirubinemia

Journal of the Medical Association of Thailand = Chotmaihet thangphaet

2381

Cholette JM, Henrichs KF, Alfieris GM, Powers KS, Phipps R, Spinelli SL, Swartz M, Gensini F, Daugherty LE, Nazarian E, Rubenstein JS, Sweeney D, Eaton M, Lerner NB and Blumberg N

Washing red blood cells and platelets transfused in cardiac surgery reduces postoperative inflammation and number of transfusions: results of a prospective, randomized, controlled clinical trial


2383

Kayentao K, Doumbo OK, Pénali LK, Offianan AT, Bhatt KM, Kimani J, Tshefu AK, Kokolomami JH, Ramharter M, Salazar PM, Tiono AB, Ouédraogo A, Bustos MD, Quicho F, Borghini-Fuhrer I, Duparc S, Shin CS and Fleckenstein L

Pyronaridine-artesunate granules versus artemether-lumefantrine crushed tablets in children with Plasmodium falciparum malaria: a randomized controlled trial

Malaria journal

2389Kajbafzadeh AM, Sharifi-Rad L, Nejat F, Kajbafzadeh M and Talaei HR

Transcutaneous interferential electrical stimulation for management of neurogenic bowel dysfunction in children with myelomeningocele

International journal of colorectal disease

2396Davis CL, Pollock NK, Waller JL, Allison JD, Dennis BA, Bassali R, Meléndez A, Boyle CA and Gower BA

Exercise dose and diabetes risk in overweight and obese children: a randomized controlled trial


2399

Marcus CL, Beck SE, Traylor J, Cornaglia MA, Meltzer LJ, DiFeo N, Karamessinis LR, Samuel J, Falvo J, DiMaria M, Gallagher PR, Beris H and Menello MK

Randomized, double-blind clinical trial of two different modes of positive airway pressure therapy on adherence and efficacy in children

Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine

2402Ismayilova L, Ssewamala FM and Karimli L Family support as a mediator of change in sexual The Journal of adolescent health :

risk-taking attitudes among orphaned adolescents in rural Uganda

official publication of the Society for Adolescent Medicine

2403Bergh IH, Stralen MM, Grydeland M, Bjelland M, Lien N, Andersen LF, Anderssen SA and Ommundsen Y

Exploring mediators of accelerometer assessed physical activity in young adolescents in the Health In Adolescents Study - a group randomized controlled trial

BMC public health

2406

Coovadia HM, Brown ER, Fowler MG, Chipato T, Moodley D, Manji K, Musoke P, Stranix-Chibanda L, Chetty V, Fawzi W, Nakabiito C, Msweli L, Kisenge R, Guay L, Mwatha A, Lynn DJ, Eshleman SH, Richardson P, George K, Andrew P, Mofenson LM, Zwerski S and Maldonado Y

Efficacy and safety of an extended nevirapine regimen in infant children of breastfeeding mothers with HIV-1 infection for prevention of postnatal HIV-1 transmission (HPTN 046): a randomised, double-blind, placebo-controlled trial

Lancet

2412Angold A, Erkanli A, Copeland W, Goodman R, Fisher PW and Costello EJ

Psychiatric diagnostic interviews for children and adolescents: a comparative study


2415Chedid NR, Bourgeois D, Kaloustian H, Pilipili C and Baba NZ

Caries risk management: effect on caries incidence in a sample of Lebanese preschool children

Odonto-stomatologie tropicale = Tropical dental journal

2426Ssewamala FM, Neilands TB, Waldfogel J and Ismayilova L

The impact of a comprehensive microfinance intervention on depression levels of AIDS-orphaned children in Uganda

The Journal of adolescent health : official publication of the Society for Adolescent Medicine

2427 Kushnir J and Sadeh AAssessment of brief interventions for nighttime fears in preschool children

European journal of pediatrics

2434 Sancho-Garnier H, Pereira B and Césarini PA cluster randomized trial to evaluate a health education programme "Living with Sun at School"

International journal of environmental research and public health

2435Spergel JM, Rothenberg ME, Collins MH, Furuta GT, Markowitz JE, Fuchs G, O'Gorman MA, Abonia JP, Young J, Henkel T, Wilkins HJ and Liacouras CA

Reslizumab in children and adolescents with eosinophilic esophagitis: results of a double-blind, randomized, placebo-controlled trial


2440Sattar S, Ahmed T, Rasul CH, Saha D, Salam MA and Hossain MI

Efficacy of a high-dose in addition to daily low-dose vitamin A in children suffering from severe acute malnutrition with other illnesses

PloS one

2441Laserson KF, Nyakundi D, Feikin DR, Nyambane G, Cook E and Oyieko J

Safety of the pentavalent rotavirus vaccine (PRV), RotaTeq((R)), in Kenya, including among HIV-infected and HIV-exposed infants

Vaccine

2450 Shamir M, Dickstein R and Tirosh EIntensive intermittent physical therapy in infants with cerebral palsy: a randomized controlled pilot study

The Israel Medical Association journal : IMAJ




2457Ülgey A, Aksu R, Bicer C, Akin A, Altunta R, Esmao?lu A, Baykan A and Boyaci A

Is the addition of dexmedetomidine to a ketamine-propofol combination in pediatric cardiac catheterization sedation useful?

Pediatric cardiology

2459Gupta K, Gupta VK, Jayashree M, Muralindharan J and Singhi S

Randomized controlled trial of interrupted versus continuous sedative infusions in ventilated children


2460Maserejian NN, Hauser R, Tavares M, Trachtenberg FL, Shrader P and McKinlay S

Dental composites and amalgam and physical development in children

Journal of dental research

2464Roggero P, Gianni ML, Amato O, Liotto N, Morlacchi L and Orsi A

Growth and fat-free mass gain in preterm infants after discharge: a randomized controlled trial

Pediatrics

2465Rosário R, Oliveira B, Araújo A, Lopes O, Padrão P, Moreira A, Teixeira V, Barros R, Pereira B and Moreira P

The impact of an intervention taught by trained teachers on childhood overweight

International journal of environmental research and public health

2472Mays D, Peshkin BN, Sharff ME, Walker LR, Abraham AA, Hawkins KB and Tercyak KP

Correlates of adherence to a telephone-based multiple health behavior change cancer preventive intervention for teens: the Healthy for Life Program (HELP)

Health education & behavior : the official publication of the Society for Public Health Education

2482Khalsa SB, Hickey-Schultz L, Cohen D, Steiner N and Cope S

Evaluation of the mental health benefits of yoga in a secondary school: a preliminary randomized controlled trial

The journal of behavioral health services & research

2486Khatun S, Akram Hussain SM, Chowdhury S, Ferdous J, Hossain F, Begum SR, Jahan M, Tabassum S and Karim AB

Safety and immunogenicity profile of human papillomavirus-16/18 AS04 adjuvant cervical cancer vaccine: a randomized controlled trial in healthy adolescent girls of Bangladesh

Japanese journal of clinical oncology

2491Gabrhelik R, Duncan A, Lee MH, Stastna L, Furr-Holden CDM and Miovsky M

Sex specific trajectories in cigarette smoking behaviors among students participating in the Unplugged school-based randomized control trial for substance use prevention

Addictive behaviors

2497Redwine K, Howard L, Simpson P, Li SH, Yan K, James L, Blumer J, Sullivan J, Ward R and Wells T

Effect of placebo on ambulatory blood pressure monitoring in children

Pediatric nephrology (Berlin, Germany)

2503Kam S, Swarthout T, Niragira O, Froud A, Sompwe EM, Mills C, Roll S, Tinnemann P and Shanks L

Ready-to-use therapeutic food for catch-up growth in children after an episode of Plasmodium falciparum malaria: an open randomised controlled trial

PloS one

2504Newcombe PA, Dunn TL, Casey LM, Sheffield JK,

Breathe Easier Online: evaluation of a randomized Journal of medical Internet

Petsky H, Anderson-James S and Chang ABcontrolled pilot trial of an Internet-based intervention to improve well-being in children and adolescents with a chronic respiratory condition

research

2505Keating J, Hutchinson P, Miller JM, Bennett A, Larsen DA, Hamainza B, Changufu C, Shiliya N and Eisele TP

A quasi-experimental evaluation of an interpersonal communication intervention to increase insecticide-treated net use among children in Zambia

Malaria journal

2507Shelleby EC, Shaw DS, Cheong J, Chang H, Gardner F, Dishion TJ and Wilson MN

Behavioral control in at-risk toddlers: the influence of the family check-up

Journal of clinical child and adolescent psychology : the official journal for the Society of Clinical Child and Adolescent Psychology, American Psychological Association, Division 53

2513 Mohamed WA and Ismail MA randomized, double-blind, placebo-controlled, prospective study of bosentan for the treatment of persistent pulmonary hypertension of the newborn


2523Kieran EA, Twomey AR, Molloy EJ, Murphy JF and O'Donnell CP

Randomized trial of prongs or mask for nasal continuous positive airway pressure in preterm infants

Pediatrics

2528Rynders C, Weltman A, Delgiorno C, Balagopal P, Damaso L, Killen K and Mauras N

Lifestyle intervention improves fitness independent of metformin in obese adolescents

Medicine and science in sports and exercise

2536

Geller B, Luby JL, Joshi P, Wagner KD, Emslie G, Walkup JT, Axelson DA, Bolhofner K, Robb A, Wolf DV, Riddle MA, Birmaher B, Nusrat N, Ryan ND, Vitiello B, Tillman R and Lavori P

A randomized controlled trial of risperidone, lithium, or divalproex sodium for initial treatment of bipolar I disorder, manic or mixed phase, in children and adolescents

Archives of general psychiatry

2541Ozdemir R, Canpolat FE, Yurttutan S, Oncel MY, Erdeve O and Dilmen U

Effect of needle length for response to hepatitis B vaccine in macrosomic neonates: a prospective randomized study

Vaccine



244.e6 Gates et al

2543

Scahill L, McDougle CJ, Aman MG, Johnson C, Handen B, Bearss K, Dziura J, Butter E, Swiezy NG, Arnold LE, Stigler KA, Sukhodolsky DD, Lecavalier L, Pozdol SL, Nikolov R, Hollway JA, Korzekwa P, Gavaletz A, Kohn AE, Koenig K, Grinnon S, Mulick JA, Yu S and Vitiello B

Effects of risperidone and parent training on adaptive functioning in children with pervasive developmental disorders and serious behavioral problems


2547Veenemans J, Schouten LR, Ottenhof MJ, Mank TG, Uges DR, Mbugi EV, Demir AY, Kraaijenhagen RJ, Savelkoul HF and Verhoef H

Effect of preventive supplementation with zinc and other micronutrients on non-malarial morbidity in Tanzanian pre-school children: a randomized trial

PloS one

2548 Lacey DJ, Stolfi A and Pilati LEEffects of hyperbaric oxygen on motor function in children with cerebral palsy

Annals of neurology

2552Schultz A, Sly PD, Zhang G, Venter A, Souëf PN and Devadason SG

Incentive device improves spacer technique but not clinical outcome in preschool children with asthma

Journal of paediatrics and child health

2555

Puthanakit T, Saphonn V, Ananworanich J, Kosalaraksa P, Hansudewechakul R, Vibol U, Kerr SJ, Kanjanavanit S, Ngampiyaskul C, Wongsawat J, Luesomboon W, Ngo-Giang-Huong N, Chettra K, Cheunyam T, Suwarnlerk T, Ubolyam S, Shearer WT, Paul R, Mofenson LM, Fox L, Law MG, Cooper DA, Phanuphak P, Vun MC and Ruxrungtham K

Early versus deferred antiretroviral therapy for children older than 1 year infected with HIV (PREDICT): a multicentre, randomised, open-label trial

The Lancet infectious diseases

2565Young JF, Makover HB, Cohen JR, Mufson L, Gallop RJ and Benas JS

Interpersonal psychotherapy-adolescent skills training: anxiety outcomes and impact of comorbidity

Journal of clinical child and adolescent psychology : the official journal for the Society of Clinical Child and Adolescent Psychology, American Psychological Association, Division 53

2566Sullivan PB, Alder N, Shrestha B, Turton L and Lambert B

Effectiveness of using a behavioural intervention to improve dietary fibre intakes in children with constipation

Journal of human nutrition and dietetics

2574Arpadi SM, McMahon DJ, Abrams EJ, Bamji M, Purswani M, Engelson ES, Horlick M and Shane E

Effect of supplementation with cholecalciferol and calcium on 2-y bone mass accrual in HIV-infected children and adolescents: a randomized clinical trial


2576Butz AM, Halterman JS, Bellin M, Kub J, Frick KD, Lewis-Land C, Walker J, Donithan M, Tsoukleris M and Bollinger ME

Factors associated with completion of a behavioral intervention for caregivers of urban children with asthma

The Journal of asthma : official journal of the Association for the Care of Asthma

2578Patten CA, Hughes CA, Lopez KN, Thomas JL, Brockman TA, Smith CM, Decker PA, Rock E, Clark LP and Offord KP

Web-based intervention for adolescent nonsmokers to help parents stop smoking: a pilot feasibility study

Addictive behaviors

2579

Lipshultz SE, Miller TL, Lipsitz SR, Neuberg DS, Dahlberg SE, Colan SD, Silverman LB, Henkel JM, Franco VI, Cushman LL, Asselin BL, Clavell LA, Athale U, Michon B, Laverdière C, Schorin MA, Larsen E, Usmani N and Sallan SE

Continuous Versus Bolus Infusion of Doxorubicin in Children With ALL: Long-term Cardiac Outcomes

Pediatrics

2585Ganmaa D, Giovannucci E, Bloom BR, Fawzi W, Burr W, Batbaatar D, Sumberzul N, Holick MF and Willett

Vitamin D, tuberculin skin test conversion, and latent tuberculosis in Mongolian school-age The American journal of clinical

nutritionWC children: a randomized, double-blind, placebo-controlled feasibility trial

2589Carvalho Onofre PS, Luz Gonçalves Pedreira M and Peterlini MA

Placement of peripherally inserted central catheters in children guided by ultrasound: a prospective randomized, and controlled trial


2598Karagiozoglou-Lampoudi T, Daskalou E, Agakidis C, Savvidou A, Apostolou A and Vlahavas G

Personalized Diet Management Can Optimize Compliance to a High-Fiber, High-Water Diet in Children with Refractory Functional Constipation

Journal of the Academy of Nutrition and Dietetics

2626Guglani L, Havstad SL, Johnson CC, Ownby DR and Joseph CLM

Effect of depressive symptoms on asthma intervention in urban teens

Annals of allergy, asthma & immunology

2629Costa-Katz CL, Livnat G, Hakim F, Vilozni D, Bentur Y and Bentur L

The effect of beclomethasone dipropionate in ultrafine particles on bronchial hyper-reactivity in young children

Acta Paediatrica

2630 Salem Y, Gropack SJ, Coffin D and Godwin EMEffectiveness of a low-cost virtual reality system for children with developmental delay: a preliminary randomised single-blind controlled trial

Physiotherapy




2631Porro LJ, Herndon DN, Rodriguez NA, Jennings K, Klein GL, Mlcak RP, Meyer WJ, Lee JO, Suman OE and Finnerty CC

Five-year outcomes after oxandrolone administration in severely burned children: a randomized clinical trial of safety and efficacy

Journal of the American College of Surgeons

2643Ong EG, Eaton S, Wade AM, Horn V, Losty PD, Curry JI, Sugarman ID, Klein NJ and Pierro A

Randomized clinical trial of glutamine-supplemented versus standard parenteral nutrition in infants with surgical gastrointestinal disease

The British journal of surgery

2644 Wanke M and Szajewska HLack of an effect of Lactobacillus reuteri DSM 17938 in preventing nosocomial diarrhea in children: a randomized, double-blind, placebo-controlled trial

Journal of pediatrics

2658

Magnasco A, Ravani P, Edefonti A, Murer L, Ghio L, Belingheri M, Benetti E, Murtas C, Messina G, Massella L, Porcellini MG, Montagna M, Regazzi M, Scolari F and Ghiggeri GM

Rituximab in children with resistant idiopathic nephrotic syndrome

Journal of the American Society of Nephrology : JASN

2661Basnet S, Shrestha PS, Sharma A, Mathisen M, Prasai R, Bhandari N, Adhikari RK, Sommerfelt H, Valentiner-Branth P and Strand TA

A randomized controlled trial of zinc as adjuvant therapy for severe pneumonia in young children

Pediatrics

2662Achan J, Kakuru A, Ikilezi G, Ruel T, Clark TD, Nsanzabana C, Charlebois E, Aweeka F, Dorsey G, Rosenthal PJ, Havlir D and Kamya MR

Antiretroviral agents and prevention of malaria in HIV-infected Ugandan children


2665Mahler B, Kamperis K, Schroeder M, Frøkiær J, Djurhuus JC and Rittig S

Sleep deprivation induces excess diuresis and natriuresis in healthy children

American journal of physiology. Renal physiology

2672Wells JC, Jonsdottir OH, Hibberd PL, Fewtrell MS, Thorsdottir I, Eaton S, Lucas A, Gunnlaugsson G and Kleinman RE

Randomized controlled trial of 4 compared with 6 mo of exclusive breastfeeding in Iceland: differences in breast-milk intake by stable-isotope probe


2677Strehlau R, Coovadia A, Abrams EJ, Martens L, Arpadi S, Meyers T and Kuhn L

Lipid profiles in young HIV-infected children initiating and changing antiretroviral therapy

Journal of acquired immune deficiency syndromes (1999)

2678

Katsunuma T, Ohya Y, Fujisawa T, Akashi K, Imamura N, Ebisawa M, Daikoku K, Kondo N, Terada A, Doi S, Nishimuta T, Noma T, Hamasaki Y, Kurihara K, Masuda K, Yamada T, Yamada M, Yoshihara S, Watanabe K, Watanabe T, Kitabayashi T, Morikawa A and Nishima S

Effects of the tulobuterol patch on the treatment of acute asthma exacerbations in young children

Allergy and asthma proceedings : the official journal of regional and state allergy societies

2679

Rubiano LC, Miranda MC, Muvdi Arenas S, Montero LM, Rodríguez-Barraquer I, Garcerant D, Prager M, Osorio L, Rojas MX, Pérez M, Nicholls RS and Gore Saravia N

Noninferiority of miltefosine versus meglumine antimoniate for cutaneous leishmaniasis in children


2680Fritz SA, Hogan PG, Hayek G, Eisenstein KA, Rodriguez M, Epplin EK, Garbutt J and Fraser VJ

Household versus individual approaches to eradication of community-associated Staphylococcus aureus in children: a randomized trial

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2682Fraser IP, Han L, Han TH, Li CC, Hreniuk D, Stoch SA, Wagner JA, Linder S and Winner P

Pharmacokinetics and tolerability of rizatriptan in pediatric migraineurs in a randomized study

Headache

2683Tabak RG, Tate DF, Stevens J, Siega-Riz AM and Ward DS

Family ties to health program: a randomized intervention to improve vegetable intake in children

Journal of nutrition education and behavior

2688 Toral N and Slater B

Intervention based exclusively on stage-matched printed educational materials regarding healthy eating does not result in changes to adolescents' dietary behavior

TheScientificWorldJournal

2689Sampanthavivat M, Singkhwa W, Chaiyakul T, Karoonyawanich S and Ajpru H

Hyperbaric oxygen in the treatment of childhood autism: a randomised controlled trial

Diving and hyperbaric medicine : the journal of the South Pacific Underwater Medicine Society

2693Chaudhary V, Chauhan S, Choudhury M, Kiran U, Vasdev S and Talwar S

Parasternal intercostal block with ropivacaine for postoperative analgesia in pediatric patients undergoing cardiac surgery: a double-blind, randomized, controlled study

Journal of cardiothoracic and vascular anesthesia

2696 Hosseinpour M, Fazeli A and Agabeigi MEfficacy of Acacia senegal for stoma care in children

European journal of pediatric

with colostomy

surgery : official journal of Austrian Association of Pediatric Surgery ... [et al] = Zeitschrift für Kinderchirurgie

2703

Guinovart C, Dobaño C, Bassat Q, Nhabomba A, Quintó L, Manaca MN, Aguilar R, Rodríguez MH, Barbosa A, Aponte JJ, Mayor AG, Renom M, Moraleda C, Roberts DJ, Schwarzer E, Souëf PN, Schofield L, Chitnis CE, Doolan DL and Alonso PL

The role of age and exposure to Plasmodium falciparum in the rate of acquisition of naturally acquired immunity: a randomized controlled trial

PloS one



244.e8 Gates et al

2704Aizire J, Fowler MG, Wang J, Shetty AK, Stranix-Chibanda L, Kamateeka M, Brown ER, Bolton SG, Musoke PM and Coovadia H

Extended prophylaxis with nevirapine and cotrimoxazole among HIV-exposed uninfected infants is well tolerated

AIDS (London, England)

2713

Steele AD, Neuzil KM, Cunliffe NA, Madhi SA, Bos P, Ngwira B, Witte D, Todd S, Louw C, Kirsten M, Aspinall S, Doorn LJ, Bouckenooghe A, Suryakiran PV and Han HH

Human rotavirus vaccine Rotarix? provides protection against diverse circulating rotavirus strains in African infants: a randomized controlled trial

BMC infectious diseases

2735Hicks PD, Hawthorne KM, Berseth CL, Marunycz JD, Heubi JE and Abrams SA

Total calcium absorption is similar from infant formulas with and without prebiotics and exceeds that in human milk-fed infants

BMC pediatrics

2762Lalwani S, Chatterjee S, Chhatwal J, Verghese VP, Mehta S, Shafi F, Borys D, Moreira M and Schuerman L

Immunogenicity, safety, and reactogenicity of the 10-valent pneumococcal non-typeable Hemophilus influenzae protein D conjugate vaccine (PHiD-CV) when co-administered with the DTPw-HBV/Hib vaccine in Indian infants: a single-blind, randomized, controlled study

Human vaccines & immunotherapeutics

2769Phipps S, Peasant C, Barrera M, Alderfer MA, Huang Q and Vannatta K

Resilience in children undergoing stem cell transplantation: results of a complementary intervention trial

Pediatrics

2775 Byon HJ, Lee SJ, Kim JT and Kim HSComparison of the antiemetic effect of ramosetron and combined ramosetron and midazolam in children: a double-blind, randomised clinical trial

European journal of anaesthesiology

2781Larsen BM, Goonewardene LA, Joffe AR, Aerde JE, Field CJ and Olstad DL

Pre-treatment with an intravenous lipid emulsion containing fish oil (eicosapentaenoic and docosahexaenoic acid) decreases inflammatory markers after open-heart surgery in infants: a randomized, controlled trial

Clinical nutrition (Edinburgh, Scotland)

2790 Vitolo MR, Bortolini GA, Campagnolo PD and Maternal dietary counseling reduces consumption of

Journal of nutrition education and Hoffman DJ

energy-dense foods among infants: a randomized controlled trial behavior

2805Thivel D, Isacco L, Montaurier C, Boirie Y, Duché P and Morio B

The 24-h energy intake of obese adolescents is spontaneously reduced after intensive exercise: a randomized controlled trial in calorimetric chambers

PloS one

2807Soukhathammavong PA, Sayasone S, Phongluxa K, Xayaseng V, Utzinger J, Vounatsou P, Hatz C, Akkhavong K, Keiser J and Odermatt P

Low efficacy of single-dose albendazole and mebendazole against hookworm and effect on concomitant helminth infection in Lao PDR

PLoS neglected tropical diseases

2814Knuf M, Zepp F, Helm K, Maurer H, Prieler A, Kieninger-Baum D, Douha M and Willems P

Antibody persistence for 3 years following two doses of tetravalent measles-mumps-rubella-varicella vaccine in healthy children

European journal of pediatrics

2826 Rohde P, Stice E, Gau JM and Marti CNReduced substance use as a secondary benefit of an indicated cognitive-behavioral adolescent depression prevention program

Psychology of addictive behaviors : journal of the Society of Psychologists in Addictive Behaviors

2828Dicko A, Konare M, Traore D, Testa J, Salamon R, Doumbo O and Rogier C

The implementation of malaria intermittent preventive trialtreatment with sulphadoxine-pyrimethamine in infants reduced all-cause mortality in the district of Kolokani, Mali: results from a cluster randomized control

Malaria journal

2840 Ozcengiz D, Unlügenç H, Güne Y and Karacaer FThe effect of dexmedetomidine on bispectral index monitoring in children

Middle East journal of anesthesiology

2841Deschildre A, Béghin L, Salleron J, Iliescu C, Thumerelle C, Santos C, Hoorelbeke A, Scalbert M, Pouessel G, Gnansounou M, Edmé JL and Matran R

Home telemonitoring (forced expiratory volume in 1 s) in children with severe asthma does not reduce exacerbations

The European respiratory journal

2852Chang S, Huang Z, Ma Y, Piao J, Yang X, Zeder C, Hurrell RF and Egli I

Mixture of ferric sodium ethylenediaminetetraacetate (NaFeEDTA) and ferrous sulfate: an effective iron fortificant for complementary foods for young Chinese children

Food and nutrition bulletin

2853Power TJ, Mautone JA, Soffer SL, Clarke AT, Marshall SA, Sharman J, Blum NJ, Glanzman M, Elia J and Jawad AF

A family-school intervention for children with ADHD: results of a randomized clinical trial

Journal of consulting and clinical psychology

2860 Atasavun Uysal S and Düger TVisual perception training on social skills and activity performance in low-vision children

Scandinavian journal of occupational therapy

2864Deribew A, Birhanu Z, Sena L, Dejene T, Reda AA, Sudhakar M, Alemseged F, Tessema F, Zeynudin A, Biadgilign S and Deribe K

The effect of household heads training on long-lasting insecticide-treated bed nets utilization: a cluster randomized controlled trial in Ethiopia

Malaria journal




2866Hyams J, Damaraju L, Blank M, Johanns J, Guzzo C and Winter HS

Induction and maintenance therapy with infliximab for children with moderate to severe ulcerative colitis

Clinical gastroenterology and hepatology

2868

Hyams JS, Griffiths A, Markowitz J, Baldassano RN, Faubion WA, Colletti RB, Dubinsky M, Kierkus J, Rosh J, Wang Y, Huang B, Bittle B, Marshall M and Lazar A

Safety and efficacy of adalimumab for moderate to severe Crohn's disease in children

Gastroenterology

2869Myers AL, Williams RF, Giles K, Waters TM, Eubanks JW, Hixson SD, Huang EY, Langham MR and Blakely ML

Hospital cost analysis of a prospective, randomized trial of early vs interval appendectomy for perforated appendicitis in children

Journal of the American College of Surgeons

2877Aouad MT, Nasr VG, Yazbeck-Karam VG, Bitar MA, Bou Khalil M, Beyrouthy O, Harfouche D, Terrin N and Siddik-Sayyid S

A comparison between dexamethasone and methylprednisolone for vomiting prophylaxis after tonsillectomy in inpatient children: a randomized trial

Anesthesia and analgesia

2878Mäkelä MJ, Malmberg LP, Csonka P, Klemola T, Kajosaari M and Pelkonen AS

Salmeterol and fluticasone in young children with multiple-trigger wheeze

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology

2879Kundra P, Yuvaraj K, Agrawal K, Krishnappa S and Kumar LT

Surgical outcome in children undergoing hypospadias repair under caudal epidural vs penile block

Paediatric anaesthesia

2897 Choudhary N and Gupta PVitamin D supplementation for severe pneumonia--a randomized controlled trial

Indian pediatrics

2898Lippold C, Moiseenko T, Drerup B, Schilgen M, Végh A and Danesh G

Spine deviations and orthodontic treatment of asymmetric malocclusions in children

BMC musculoskeletal disorders

2899 Wu F, Yao MH and Zhu Y[Clinical study on prevention of recurrence of asthma in children by Xiaochuangao acupoint paste: treating winter diseases in summer]

Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica

2917Mauras N, Beck R, Xing D, Ruedy K, Buckingham B, Tansey M, White NH, Weinzimer SA, Tamborlane W and Kollman C

A randomized clinical trial to assess the efficacy and safety of real-time continuous glucose monitoring in the management of type 1 diabetes in young children aged 4 to <10 years

Diabetes care

2925 Dalum P, Paludan-Muller G, Engholm G and Kok GA cluster randomised controlled trial of an adolescent smoking cessation intervention: short and long-term effects

Scandinavian journal of public health

2930Hirschtritt ME, Pagano ME, Christian KM, Moderators of fluoxetine treatment response for

Journal of substance abuse McNamara NK, Stansbrey RJ, Lingler J, Faber JE, Demeter CA, Bedoya D and Findling RL

children and adolescents with comorbid depression and substance use disorders

treatment

2941Baranowski T, Abdelsamad D, Baranowski J, O'Connor TM, Thompson D, Barnett A, Cerin E and Chen TA

Impact of an active video game on healthy children's physical activity

Pediatrics

2947Steele RG, Aylward BS, Jensen CD, Cushing CC, Davis AM and Bovaird JA

Comparison of a family-based group intervention for youths with obesity to a brief individual family intervention: a practical clinical trial of positively fit

Journal of pediatric psychology

2948Kuethe MC, Sixma HJ, Vaessen-Verberne A, Booij JC, van A and Wmc

Assessing quality of care in pediatric asthma: Applicability of a revised version of the QUOTE-CNSLD questionnaire

Journal of asthma

2954Derosier FJ, Lewis D, Hershey AD, Winner PK, Pearlman E, Rothner AD, Linder SL, Goodman DK, Jimenez TB, Granberry WK and Runken MC

Randomized trial of sumatriptan and naproxen sodium combination in adolescent migraine

Pediatrics

2955Della Negra M, Carvalho AP, Aquino MZ, Silva MT, Pinto J, White K, Arterburn S, Liu YP, Enejosa JV, Cheng AK, Chuck SL and Rhee MS

A randomized study of tenofovir disoproxil fumarate in treatment-experienced HIV-1 infected adolescents

The Pediatric infectious disease journal

2956Murray KF, Szenborn L, Wysocki J, Rossi S, Corsa AC, Dinh P, McHutchison J, Pang PS, Luminos LM, Pawlowska M and Mizerski J

Randomized, placebo-controlled trial of tenofovir disoproxil fumarate in adolescents with chronic hepatitis B

Hepatology (Baltimore, Md.)

2959Florsheim P, Burrow-Sánchez JJ, Minami T, McArthur L, Heavin S and Hudak C

Young parenthood program: supporting positive paternal engagement through coparenting counseling

American journal of public health

2964 Monti JM, Hillman CH and Cohen NJAerobic fitness enhances relational memory in preadolescent children: the FITKids randomized control trial

Hippocampus

2978Lemonnier E, Degrez C, Phelep M, Tyzio R, Josse F, Grandgeorge M, Hadjikhani N and Ben-Ari Y

A randomised controlled trial of bumetanide in the treatment of autism in children

Translational psychiatry



244.e10 Gates et al

2979Arnold LE, Aman MG, Hollway J, Hurt E, Bates B, Li X, Farmer C, Anand R, Thompson S, Ramadan Y and Williams C

Placebo-controlled pilot trial of mecamylamine for treatment of autism spectrum disorders

Journal of child and adolescent psychopharmacology

2983Knuf M, Pankow-Culot H, Grunert D, Rapp M, Panzer F, Köllges R, Fanic A, Habib A, Borys D, Dieussaert I and Schuerman L

Induction of immunologic memory following primary vaccination with the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine in infants

The Pediatric infectious disease journal

2987Cha MH, Eom JH, Lee YS, Kim WY, Park YC, Min SH and Kim JH

Beneficial effects of adding ketamine to intravenous patient-controlled analgesia with fentanyl after the Yonsei medical journalNuss procedure in pediatric patients

2989Gabbay V, Babb JS, Klein RG, Panzer AM, Katz Y, Alonso CM, Petkova E, Wang J and Coffey BJ

A double-blind, placebo-controlled trial of ?-3 fatty acids in Tourette's disorder

Pediatrics

2997Park JH, Miyashita M, Kwon YC, Park HT, Kim EH, Park JK, Park KB, Yoon SR, Chung JW, Nakamura Y and Park SK

A 12-week after-school physical activity programme improves endothelial cell function in overweight and obese children: a randomised controlled study

BMC pediatrics

3010 Bhatnagar S, Das UM and Bhatnagar GComparison of oral midazolam with oral tramadol, triclofos and zolpidem in the sedation of pediatric dental patients: an in vivo study

Journal of the Indian Society of Pedodontics and Preventive Dentistry

3014Huybregts L, Houngbé F, Salpéteur C, Brown R, Roberfroid D, Ait-Aissa M and Kolsteren P

The effect of adding ready-to-use supplementary food to a general food distribution on child nutritional status and morbidity: a cluster-randomized controlled trial

PLoS medicine

3027Vesikari T, Becker T, Gajdos V, Fiquet A, Thomas S, Richard P and Baudin M

Immunogenicity and safety of a two-dose regimen of a combined measles, mumps, rubella and varicella live vaccine (ProQuad(®)) in infants from 9 months of age

Vaccine

3030Reix P, Aubert F, Werck-Gallois MC, Toutain A, Mazzocchi C, Moreux N, Bellon G, Rabilloud M and Kassai B

Exercise with incorporated expiratory manoeuvres was as effective as breathing techniques for airway clearance in children with cystic fibrosis: a randomised crossover trial

Journal of physiotherapy

3032Aquino AG, Brito MG, Doniz CE, Herrera JF, Macias M, Zambrano B, Plennevaux E and Santos-Lima E

A fully liquid DTaP-IPV-Hep B-PRP-T hexavalent vaccine for primary and booster vaccination of healthy Mexican children

Vaccine

3038Eakin MN, Rand CS, Bilderback A, Bollinger ME, Butz A, Kandasamy V and Riekert KA

Asthma in Head Start children: effects of the Breathmobile program and family communication on asthma outcomes


3046 Inal S and Kelleci MDistracting children during blood draw: looking through distraction cards is effective in pain relief of children during blood draw

International journal of nursing practice

3062Hawkins JD, Oesterle S, Brown EC, Monahan KC, Abbott RD, Arthur MW and Catalano RF

Sustained decreases in risk exposure and youth problem behaviors after installation of the Communities That Care prevention system in a randomized trial

Archives of pediatrics & adolescent medicine

3065Sharma TS, Bechard LJ, Feldman HA, Venick R, Gura K, Gordon CM, Sonis A, Guinan EC and Duggan C

Effect of titrated parenteral nutrition on bodycomposition after allogeneic hematopoietic stem cell transplantation in children: a double-blind,


randomized, multicenter trial

3073 Kupersmidt JB, Scull TM and Benson JW

Improving media message interpretation processing skills to promote healthy decision making about substance use: the effects of the middle school media ready curriculum

Journal of health communication

3078

Lannering B, Rutkowski S, Doz F, Pizer B, Gustafsson G, Navajas A, Massimino M, Reddingius R, Benesch M, Carrie C, Taylor R, Gandola L, Björk-Eriksson T, Giralt J, Oldenburger F, Pietsch T, Figarella-Branger D, Robson K, Forni M, Clifford SC, Warmuth-Metz M, Hoff K, Faldum A, Mosseri V and Kortmann R

Hyperfractionated versus conventional radiotherapy followed by chemotherapy in standard-risk medulloblastoma: results from the randomized multicenter HIT-SIOP PNET 4 trial

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

3087Green CT, Long DL, Green D, Iosif AM, Dixon JF, Miller MR, Fassbender C and Schweitzer JB

Will working memory training generalize to improve off-task behavior in children with attention-deficit/hyperactivity disorder?

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics

3090Toscos TR, Ponder SW, Anderson BJ, Davidson MB, Lee ML, Montemayor-Gonzalez E, Reyes P, Link E and McMahon KL

Integrating an Automated Diabetes Management System into the family management of children with type 1 diabetes: results from a 12-month randomized controlled technology trial

Diabetes care




3096Showkatbakhsh R, Jamilian A, Taban T and Golrokh M

The effects of face mask and tongue appliance on maxillary deficiency in growing patients: a randomized clinical trial

Progress in orthodontics

3103

Lujan-Zilbermann J, Warshaw MG, Williams PL, Spector SA, Decker MD, Abzug MJ, Heckman B, Manzella A, Kabat B, Jean-Philippe P, Nachman S and Siberry GK

Immunogenicity and safety of 1 vs 2 doses of quadrivalent meningococcal conjugate vaccine in youth infected with human immunodeficiency virus


3104Borsting E, Mitchell GL, Kulp MT, Scheiman M, Amster DM, Cotter S, Coulter RA, Fecho G, Gallaway MF, Granet D, Hertle R, Rodena J and Yamada T

Improvement in academic behaviors after successful treatment of convergence insufficiency

Optometry and vision science : official publication of the American Academy of Optometry

3107Friedman M, Samuelson CG, Hamilton C, Maley A, Taylor D and Kelley K

Modified adenotonsillectomy to improve cure rates for pediatric obstructive sleep apnea: a randomized controlled trial

Otolaryngology--head and neck surgery

3108Kirk S, Brehm B, Saelens BE, Woo JG, Kissel E, D'Alessio D, Bolling C and Daniels SR

Role of carbohydrate modification in weight management among obese children: a randomized clinical trial


3111Martínez MC, Tolcachir B, Lescano de Ferrer A, Bojanich MA, Barembaum SR, Calamari SE and Azcurra AI

Comparative study of preventive protocols in children at high cariogenic risk

Acta odontologica latinoamericana : AOL

3113Yousef E, Hossain J, Mannan S, Skorpinski E and McGeady S

Early intervention with high-dose inhaled corticosteroids for control of acute asthma exacerbations at home and improved outcomes: a randomized controlled trial

Allergy and asthma proceedings : the official journal of regional and state allergy societies

3117Labcharoenwongs P, Jirapongsananuruk O, Visitsunthorn N, Kosrirukvongs P, Saengin P and Vichyanond P

A double-masked comparison of 0.1% tacrolimus ointment and 2% cyclosporine eye drops in the treatment of vernal keratoconjunctivitis in children

Asian Pacific journal of allergy and immunology / launched by the Allergy and Immunology Society of Thailand

3128Seid M, D'Amico EJ, Varni JW, Munafo JK, Britto MT, Kercsmar CM, Drotar D, King EC and Darbie L

The in vivo adherence intervention for at risk adolescents with asthma: report of a randomized pilot trial

Journal of pediatric psychology

3132Wood F, Martin L, Lewis D, Rawlins J, McWilliams T and Burrows S

A prospective randomised clinical pilot study to compare the effectiveness of Biobrane synthetic wound dressing, with or without autologous cell suspension, to the local standard treatment regimen in paediatric scald injuries

Burns

3134Brams M, Turnbow J, Pestreich L, Giblin J, Childress A, McCague K and Muniz R

A randomized, double-blind study of 30 versus 20 mg dexmethylphenidate extended-release in children with attention-deficit/hyperactivity disorder: late-day symptom control

Journal of clinical psychopharmacology

3138Schulz KP, Fan J, Bédard AC, Clerkin SM, Ivanov I, Tang CY, Halperin JM and Newcorn JH

Common and unique therapeutic mechanisms of stimulant and nonstimulant treatments for attention-deficit/hyperactivity disorder

Archives of general psychiatry

3141 El-Sharkawi HF, El-Housseiny AA and Aly AMEffectiveness of new distraction technique on pain associated with injection of local anesthesia for children

Pediatric Dentistry

3153Bessems KM, Assema P, Martens MK, Paulussen TG, Raaijmakers LG, Rooij M and Vries NK

Healthier food choices as a result of the revised healthy diet programme Krachtvoer for students of prevocational schools


3158

Osunkwo I, Ziegler TR, Alvarez J, McCracken C, Cherry K, Osunkwo CE, Ofori-Acquah SF, Ghosh S, Ogunbobode A, Rhodes J, Eckman JR, Dampier C and Tangpricha V

High dose vitamin D therapy for chronic pain in children and adolescents with sickle cell disease: results of a randomized double blind pilot study

British journal of haematology

3170 Hoek W, Schuurmans J, Koot HM and Cuijpers PEffects of Internet-based guided self-help problem-solving therapy for adolescents with depression and anxiety: a randomized controlled trial

PloS one

3186 Algra SO, Schouten AN, Oeveren W, Tweel I, Schoof Low-flow antegrade cerebral perfusion attenuates Journal of thoracic and PH and Jansen NJ early renal and intestinal injury during neonatal

aortic arch reconstructioncardiovascular surgery

3193Speich B, Ame SM, Ali SM, Alles R, Hattendorf J, Utzinger J, Albonico M and Keiser J

Efficacy and safety of nitazoxanide, albendazole, and nitazoxanide-albendazole against Trichuris trichiura infection: a randomized controlled trial

PLoS neglected tropical diseases

3198 Somech LY and Elizur YPromoting self-regulation and cooperation in pre-kindergarten children with conduct problems: A randomized controlled trial




244.e12 Gates et al

3202Ebbeling CB, Feldman HA, Chomitz VR, Antonelli TA, Gortmaker SL, Osganian SK and Ludwig DS

A randomized trial of sugar-sweetened beverages and adolescent body weight


3216 Mohebbi SZ, Virtanen JI and Vehkalahti MMA community-randomized controlled trial against sugary snacking among infants and toddlers

Community dentistry and oral epidemiology

3225Kurlan R, Crespi G, Coffey B, Mueller-Vahl K, Koval S and Wunderlich G

A multicenter randomized placebo-controlled clinical trial of pramipexole for Tourette's syndrome

Movement disorders : official journal of the Movement Disorder Society

3230 Abdelmaaboud M and Mohammed A

A randomized controlled trial on early versus late minimal enteral feeding in preterm growth-restricted neonates with abnormal antenatal Doppler studies

Journal of neonatal-perinatal medicine

3249Wuthrich VM, Rapee RM, Cunningham MJ, Lyneham HJ, Hudson JL and Schniering CA

A randomized controlled trial of the Cool Teens CD-ROM computerized program for adolescent anxiety


3295Danielson CK, McCart MR, Walsh K, Arellano MA, White D and Resnick HS

Reducing substance use risk and mental health problems among sexually assaulted adolescents: a pilot randomized controlled trial

Journal of family psychology : JFP : journal of the Division of Family Psychology of the American Psychological Association (Division 43)

3299 Liao G, Li R, Li C, Sun M, Li Y, Chu J, Jiang S and Li QSafety and immunogenicity of inactivated poliovirus vaccine made from Sabin strains: a phase II, randomized, positive-controlled trial


3334O'Connor DL, Weishuhn K, Rovet J, Mirabella G, Jefferies A and Campbell DM

Visual development of human milk-fed preterm infants provided with extra energy and nutrients after hospital discharge

JPEN. Journal of parenteral and enteral nutrition

3348 Lau, Smith and EoInterventions to improve the oral feeding performance of preterm infants

Acta Paediatricia

3356 Kemal OHarmonic scalpel versus bipolar tonsillectomy: a double-blind clinical trial

European archives of oto-rhino-laryngology

3371 Burgess IF, Lee PN, Kay K, Jones R and Brunton ER1,2-Octanediol, a novel surfactant, for treating head louse infestation: identification of activity, formulation, and randomised, controlled trials

PloS one

3394 Jia YS, Lin ZL, Lv H, Li YM, Green R and Lin JEffect of delivery room temperature on theadmission temperature of premature infants: a randomized controlled trial

Journal of perinatology

3413 Burleson JA, Kaminer Y and Burke RHTwelve-month follow-up of aftercare for adolescents with alcohol use disorders

Journal of substance abuse treatment

3420 Gupta S, Ahmed F, Lodha R, Gupta YK and Kabra SKComparison of effects of 3 and 7% hypertonic saline nebulization on lung function in children with cystic fibrosis: a double-blind randomized, controlled trial

Journal of tropical pediatrics

3434Chrzanowska-Liszewska D, Seliga-Siwecka J and Kornacka MK

The effect of Lactobacillus rhamnosus GG supplemented enteral feeding on the microbiotic flora of preterm infants-double blinded randomized control trial


3468 Suwansingha O and Rirattanapong PEffect of fluoride varnish on caries prevention of partially erupted of permanent molar in high caries risk

The Southeast Asian journal of tropical medicine and public health

3479 Wang Y, Wang B, Jiang X, Jiang M, Xu C and Shao CPolyethylene glycol 4000 treatment for children with constipation: A randomized comparative multicenter study

Experimental and therapeutic medicine

3490Ganesh M, Shah S, Parikh D, Choudhary P and Bhaskar V

The effectiveness of a musical toothbrush for dental plaque removal: a comparative study

Journal of the Indian Society of Pedodontics and Preventive Dentistry

3505Shefali-Patel D, Murthy V, Hannam S, Lee S, Rafferty GF and Greenough A

Randomised weaning trial comparing assist control to pressure support ventilation


3515Yukselen A, Kendirli SG, Yilmaz M, Altintas DU and Karakoc GB

Effect of one-year subcutaneous and sublingual immunotherapy on clinical and laboratory parameters in children with rhinitis and asthma: A randomized, placebo-controlled, double-blind, double-dummy study

International archives of allergy and immunology

3520Dos Santos Jr VE, Vasconcelos FMN, Ribeiro AG and Rosenblatt A

Paradigm shift in the effective treatment of caries in schoolchildren at risk

International dental journal

3528 Purdy MSSC and Kelly ASA randomized control trial of interventions in school-aged children with auditory processing disorders

International journal of audiology

3534Malamiri RA, Ghaempanah M, Khosroshahi N, Nikkhah A, Bavarian B and Ashrafi MR

Efficacy and safety of intravenous sodium valproate versus phenobarbital in controlling convulsive status

European journal of paediatric neurology: EJPN

epilepticus and acute prolonged convulsive seizures in children: A randomised trial




3545 Srof BJ, Velsor-Friedrich B and Penckofer SThe effects of coping skills training among teens with asthma

Western journal of nursing research

3548

Jeschke MG, Williams FN, Finnerty CC, Rodriguez NA, Kulp GA, Ferrando A, Norbury WB, Suman OE, Kraft R, Branski LK, Al-mousawi AM and Herndon DN

The effect of ketoconazole on post-burn inflammation, hypermetabolism and clinical outcomes

PloS one

3550Larsson PG, Bakke KA, Bjørnæs H, Heminghyt E, Rytter E, Brager-Larsen L and Eriksson AS

The effect of levetiracetam on focal nocturnal epileptiform activity during sleep--a placebo-controlled double-blind cross-over study

Epilepsy & behavior : E&B

3559Ghoddusi J, Shahrami F, Alizadeh M, Kianoush K and Forghani M

Clinical and radiographic evaluation of vital pulp therapy in open apex teeth with MTA and ZOE

The New York state dental journal

3567Ford JD, Steinberg KL, Hawke J, Levine J and Zhang W

Randomized trial comparison of emotion regulation and relational psychotherapies for PTSD with girls involved in delinquency

Journal of clinical child and adolescent psychology

3568 Leutgeb V and Schienle AChanges in facial electromyographic activity in spider-phobic girls after psychotherapy

Journal of psychiatric research

3569Bitton Jonathan Y, Sauerwein Hannelore C, Weiss Shelly K, Donner Elizabeth J, Whiting S and Dooley Joseph M

A randomized controlled trial of flunarizine as add-on therapy and effect on cognitive outcome in children with infantile spasms

Epilepsia

3594Pedersen C, Breindahl M, Aggarwal N, Berglund J, Oroszlan G and Silfverdal SA

Randomized Trial: Immunogenicity and Safety of Coadministered Human Papillomavirus-16/18 AS04-Adjuvanted Vaccine and Combined Hepatitis A and B Vaccine in Girls

Journal of adolescent health

3660 Talapaneni AK, Supraja G, Prasad M and Kommi PBComparison of sagittal and vertical dental changes during first phase of orthodontic treatment with MBT vs ROTH prescription

Indian journal of dental research

3661Ratjen F, Saiman L, Mayer-Hamblett N, Lands LC, Kloster M, Thompson V, Emmett P, Marshall B, Accurso F, Sagel S and Anstead M

Effect of azithromycin on systemic markers of inflammation in patients with cystic fibrosis uninfected with Pseudomonas aeruginosa

Chest

3673 Halicio?lu K, Kiki A and Yavuz ISubjective symptoms of RME patients treated with three different screw activation protocols: a randomised clinical trial

Australian orthodontic journal

3707

Frazier JA, Giuliano AJ, Johnson JL, Yakutis L, Youngstrom EA, Breiger D, Sikich L, Findling RL, McClellan J, Hamer RM, Vitiello B, Lieberman JA

Neurocognitive outcomes in the Treatment of Early-Onset Schizophrenia Spectrum Disorders study

Journal of the American Academy of Child and Adolescent Psychiatryand Hooper SR

3716 Matthey S and Crncec R

Comparison of two strategies to improve infant sleep problems, and associated impacts on maternal experience, mood and infant emotional health: a single case replication design study


3720 Burke K, Brennan L and Cann WPromoting protective factors for young adolescents: ABCD Parenting Young Adolescents Program randomized controlled trial

Journal of adolescence

3723S Y Park DYSSLAFHKKYHBYSKNKTHCBDRKSKBJP and Han J

Yoga training improves metabolic parameters in obese boys

The Korean journal of physiology & pharmacology

3729 Cheon SH, Reeve J and Moon IS

Experimentally based, longitudinally designed, teacher-focused intervention to help physical education teachers be more autonomy supportive toward their students

Journal of sport & exercise psychology

3746 Fallah R, Islami Z and Lotfi SRSingle dose of 50 mg/kg clofibrate in jaundice of healthy term neonates: randomised clinical trial of efficacy and safety

Indian journal of pediatrics

3769 Bharadwaj SK and Vishnu Bhat B

Therapeutic Hypothermia Using Gel Packs for Term Neonates with Hypoxic Ischaemic Encephalopathy in Resource-limited Settings: a Randomized Controlled Trial

Journal of tropical pediatrics

3792Campbell-Yeo ML, Johnston CC, Joseph KS, Feeley N, Chambers CT and Barrington KJ

Cobedding and recovery time after heel lance in preterm twins: results of a randomized trial

Pediatrics

3832

Hasson RE, Adam TC, Davis JN, Kelly LA, Ventura EE, Byrd-Williams CE, Toledo-Corral CM, Roberts CK, Lane CJ, Azen SP, Chou CP, Spruijt-Metz D, Weigensberg MJ, Berhane K and Goran MI

Randomized controlled trial to improve adiposity, inflammation, and insulin resistance in obese African-American and Latino youth

Obesity (Silver Spring, Md.)

3844Ryman TK, Briere EC, Cartwright E, Schlanger K, Wannemuehler KA, Russo ET, Kola S, Sadumah I, Nygren BL, Ochieng C, Quick R and Watkins ML

Integration of routine vaccination and hygiene interventions: a comparison of 2 strategies in Kenya


3849 Sierpina HDLWDKM and YaronovLaryngeal mask airway versus endotracheal tube in pediatric adenotonsillectomy

Laryngoscope



244.e14 Gates et al

3861Lello J, Liang A, Robinson E, Leutenegger D and Wheat A

Treatment Of Children's Asthma With A Lipid Extract Of The New Zealand Green Lipped Mussel (Perna Canaliculus) (Lyprinol®)--A Double Blind, Randomised Controlled Trial In Children With Moderate To Severe Chronic Obstructive Asthma

Internet Journal of Asthma, Allergy & Immunology

3883 Mirlohi SMHSZ and Hashemi SJComparison of the preventive analgesic effect of rectal ketamine and rectal acetaminophen after pediatric tonsillectomy

International journal of preventive medicine

3897 Ge YS, Liu J, Chen L, Han JL and Guo XDentofacial effects of two facemask therapies for maxillary protraction

The Angle orthodontist

3921Tüzüner T, Alacam A, Altunbas DA, Gokdogan FG and Gundogdu E

Clinical and radiographic outcomes of direct pulp capping therapy in primary molar teeth following haemostasis with various antiseptics: a randomised controlled trial

European journal of paediatric dentistry : official journal of European Academy of Paediatric Dentistry

3925Mathew B, Lakshminrusimha S, Sengupta S and Carrion V

Randomized controlled trial of vinyl bags versus thermal mattress to prevent hypothermia in extremely low gestational age infants

American journal of perinatology

3926Showkatbakhsh R, Jamilian A, Ghassemi M, Ghassemi A, Taban T and Imani Z

The effects of facemask and reverse chin cup on maxillary deficient patients

Journal of orthodontics

3953 Vandervord Nixon Reginald D, Sterk J and Pearce A

A randomized trial of cognitive behaviour therapy and cognitive therapy for children with posttraumatic stress disorder following single-incident trauma

Journal of abnormal child psychology: an official publication of the international society for research in child and adolescent psychopathology

3958 Diab AAThe role of forward head correction in management of adolescent idiopathic scoliotic patients: a randomized controlled trial

Clinical rehabilitation

3960Walden M, Atroshi I, Magnusson H, Wagner P and Hagglund M

3963 Brukiene V and Aleksejuniene JIs the authoritative parenting model effective in changing oral hygiene behavior in adolescents?

Health education research

3964Ghavane S, Murki S, Subramanian S, Gaddam P, Kandraju H and Thumalla S

Kangaroo Mother Care in Kangaroo ward for improving the growth and breastfeeding outcomes when reaching term gestational age in very low birth weight infants

Acta Paediatrica

3975Gabrhelik R, Duncan A, Miovsky M, Furr-Holden CDM, Stastna L and Jurystova L

'Unplugged': A school-based randomized control trial to prevent and reduce adolescent substance use in the Czech Republic

Drug and alcohol dependence

3977 Niederhofer H and Klitzing KBright light treatment as mono-therapy of non-seasonal depression for 28 adolescents

International journal of psychiatry in clinical practice

3981Kim Sun M, Han Doug H, Lee Young S and Renshaw Perry F

Combined cognitive behavioral therapy and bupropion for the treatment of problematic on-line Computers in human behaviorgame play in adolescents with major depressive disorder. [References]

3982Mason WA, Haggerty Kevin P, Fleming Andrew P and Casey-Goldstein M

Family intervention to prevent depression and substance use among adolescents of depressed parents

Journal of child and family studies

3983Ryan SR, Stanger C, Thostenson J, Whitmore JJ and Budney AJ

The impact of disruptive behavior disorder on substance use treatment outcome in adolescents

Journal of substance abuse treatment

Guoji Yanke Zazhhi4006Yang ZY, Pei FB, Yang JJ, Lu BW, Ming CP and Zhang XY

Clinical research on application of compound anisodine in adolescent patients with acute optic neuritis

4024 Rossello J, Bernal G and Rivera-Medina CIndividual and group CBT and IPT for Puerto Rican adolescents with depressive symptoms

Journal of latina/o psychology

4034Somri M, Parisinos CA, Kharouba J, Cherni N, Smidt A and Abu Ras Z

Optimising the dose of oral midazolam sedation for dental procedures in children: a prospective, randomised, and controlled study

International Journal of Paediatric Dentistry / the British Paedodontic Society [and] the International Association of Dentistry for Children

4045Alamoudi NM, Hanno AG, Sabbagh HJ, Masoud MI, Almushayt AS and Derwi DA

Impact of maternal xylitol consumption on mutans streptococci, plaque and caries levels in children

Journal of clinical pediatric dentistry

4046Reaven J, Blakeley-Smith A, Culhane-Shelburne K and Hepburn S

Group cognitive behavior therapy for children with high-functioning autism spectrum disorders and anxiety: A randomized trial

Journal of Child Psychology and Psychiatry

4049 Jindal P, Khurana G, Oberoi D and Sharma JPRecovery profile and emergence delirium following sevoflurane and isoflurane anesthesia in children posted for cleft lip surgery

Middle East journal of anesthesiology

A Randomized Trial of Anterior Cruciate Ligament British medical journal Injury Prevention in Adolescent Female Soccer




4089Kaddoum RN, Anghelescu DL, Parish ME, Wright BB, Trujillo L and Wu J

A randomized controlled trial comparing the AccuVein AV300 device to standard insertion technique for intravenous cannulation of anesthetized children

Paediatric anaesthesia

4090El-Habashy HR, El-Negmy E, El-Moteleb LA, El-Hadidy R and Hafad M

Effect of laser therapy on electrophysiological parameters in children with facial palsy

Egyptian journal of neurology, psychiatry and neurosurgery

4128Kazemi S, Ghazimoghaddam K, Besharat S and Kashani L

Music and anxiety in hospitalized childrenJournal of clinical and diagnostic research

4129Agustina R, Kok FJ, Rest O, Fahmida U, Firmansyah A and Lukito W

Randomized trial of probiotics and calcium on diarrhea and respiratory tract infections in Indonesian children

Pediatrics

4135 Willadsen EInfluence of timing of hard palate repair in a two-stage procedure on early speech development in The cleft palate-craniofacial

journaldanish children with cleft palate

4144 Cildir SK, Sandalli N, Nazli S, Alp F and Caglar EA novel delivery system of probiotic drop and its effect on dental caries risk factors in cleft lip/palate children

The cleft palate-craniofacial journal

4151 Janbaz FHKH and Qureshi MAAnalgesic effect of ketamine and morphine after tonsillectomy in children

Pakistan journal of pharmaceutical sciences

4157 Greive KA, Lui AH, Barnes TM and Oppenheim VMSafety and efficacy of a non-pesticide-based head lice treatment: results of a randomised comparative trial in children

Australasian journal of dermatology

4158Stalvey MS, Anbar RD, Konstan MW, Jacobs JR, Bakker B and Lippe B

A multi-center controlled trial of growth hormone treatment in children with cystic fibrosis

Pediatric pulmonology

4161 Schottelkorb, Doumas AA and Garcia DMTreatment for childhood refugee trauma: A randomized, controlled trial

International Journal of Play Therapy

4178 Cobham and VeDo anxiety-disordered children need to come into the clinic for efficacious treatment? [References]

Journal of consulting and clinical psychology

4185Meir Y, Slone M, Levis M, Reina L and Livni Yael Ben D

Crisis intervention with children of illegal migrant workers threatened with deportation

Professional psychology, research and practice

4242Ostlie DJ, Juang D, P A, Pettiford-Cunningham JP, Erkmann EA and Rash DE

Topical silver sulfadiazine vs collagenase ointment for the treatment of partial thickness burns in children: A prospective randomized trial

Journal of pediatric surgery

4245Mattila PS, Hammaren-Malmi S, Saxen H, Kaijalainen T, Kayhty H and Tarkkanen J

Adenoidectomy in young children and serum IgG antibodies to pneumococcal surface protein A and choline binding protein A

International journal of pediatric otorhinolaryngology

4253 Korpela LLMS-VJN-KHTKBKHTPR and Pitkaranta AHuman bocavirus in the nasopharynx of otitis-prone children

International journal of pediatric otorhinolaryngology

4256 Ching TY, Dillon H, Hou S, Zhang V, Day J et al

A randomized controlled comparison of NAL and DSL prescriptions for young children: Hearing-aid characteristics and performance outcomes at three years of age

International journal of audiology

4268 Hsu KGWTHLTYWCL and Chen CJ

A comparative study of loratadine syrup and cyproheptadine HCL solution for treating perennial allergic rhinitis in Taiwanese children aged 2-12 years

International journal of immunopathology and pharmacology

4283 Al-Shehri AMSPost-tonsillectomy pain and bleeding in children: A comparison of traditional tonsillectomy with electrodissection tonsillectomy

Current Pediatric Research

4285 Diao M, Li L and Cheng W

To drain or not to drain in Roux-en-Y

Journal of pediatric surgeryhepatojejunostomy for children with choledochal cysts in the laparoscopic era: A prospective randomized study

4322 Stice E, Rohde P, Gau J and Shaw HEffect of a dissonance-based prevention program on risk for eating disorder onset in the context of eating disorder risk factors

Prevention science : the official journal of the Society for Prevention Research

4348Fabiszewski de Aceituno AM, Stauber CE, Walters AR, Meza Sanchez RE and Sobsey MD

A randomized controlled trial of the plastic-housing BioSand filter and its impact on diarrheal disease in Copan, Honduras

The American journal of tropical medicine and hygiene

4374 Esenlik E, Naziroglu M, Acikalin C and Ovey ISVitamin E supplementation modulates gingival crevicular fluid lipid peroxidation and antioxidant levels in patients with orthodontic tooth movement

Cell biochemistry and function

4391Kuroki H, Ishiwada N, Inoue N, Ishikawa N, Suzuki H, Himi K, Kurosaki T

Comparison of clinical efficacy between 3day combined clavulanate amoxicillin preparation treatment and 10day amoxicillin treatment in children with pharyngolaryngitis

JPRN [accessed 2 September 2013]

Appendix 2. Continued.


244.e16 Gates et al

General Instructions for REDCap

- To select the record you want to work on, click the drop-down arrow beside the record list (probably Incomplete Records unless you want to make changes to a record that you have designated Unverified) and scroll down to select the record that matches the reference ID you are working on. You can also type the record number in the “Enter a new or existing Record ID” space and then click the matching record that pops up – note that this is probably faster but can only be done from the “Publication Characteristics” form.- At the bottom of every page within the data extraction form, there are buttons to “Save Record,” “Save and Continue,” and “Save and go to Next Form.” “Save Record” will save the page you are currently on and take you back to the main menu. “Save and Continue” will allow you to save your work and continue on the same page. “Save and go to Next Form” will save your work and take you to the next page in the data extraction form. REDCap times out after approximately 15 minutes of inactivity and will log you out of the program, so please save your work regularly as you go.- At the bottom of every page, there is a drop down menu where you can indicate whether the page is “Incomplete,” “Unverified,” or “Complete.” As you complete each page, please change this from “Incomplete” to “Complete.” If you have an outstanding question, mark it as “Unverified.” Please also let me know as questions arise.- At the bottom of each page, there is a text box for comments. If you have a comment or question about any of the fields as they pertain to the study you are extracting data from, leave a response here, and the data can be checked.- To navigate back and forth through the data extraction form, use the list of each of the pages found on the left-hand side of the screen.

Data Extraction Guidelines

*USE ALL AVAILABLE INFORMATION (INCLUDING PROTOCOLS OR COMPANION ARTICLES REFERENCED IN THE PUBLICATION, AND RECORD OF TRIAL REGISTRATION) TO COMPLETE DATA EXTRACTION, RISK OF BIAS, AND CONSORT ASSESSMENTS.

- We will include a MAXIMUM OF THREE sources per trial:1. The trial identified as part of our sample;2. The trial register, if available; and3. EITHER the published protocol or methods document, if cited in our original study (first choice) OR the sentinel trial in the case of multiple

publications, if cited in our original study (second choice).

When the trial included in our study sample references companion articles that are used to complete data extraction, please save a copy in Dropbox (Skyfall > Supplementary Articles). For quality assessment and data verification, please check Dropbox for any additional articles prior to starting.

Please note the differences in the use of ‘no’ and ‘N/A.’ Use ‘no’ when something hasn’t been done when it could have been possible; use ‘N/A’ when it doesn’t apply to that particular trial. For example, to report whether the treatment effect was reported by a subgroup other than age, use ‘no’ if there is another subgroup, but the treatment effect hasn’t been reported accordingly, and use ‘N/A’ if there are no other subgroups.

All references cited in this file are saved to: Z:\common\StaRChildHealth_2012_Trials\Data Extraction\Background

Field Response CommentsPublication characteristicsPlease enter the following publication characteristics:

Publication title:Full journal title:First author:Volume ID:Issue ID:Pages:Country of correspondingauthor:

Type of journal:

Language of publication:

□General medical journal□Specialty medical journal□General pediatric journal□Specialty pediatric journal□Other

Abbreviate United States as USA; United Kingdom as UK. Omit ‘the’ (e.g., just enter in ‘Netherlands’).General medical: e.g., Lancet, BMJ, JAMA, CMAJ, NEJMSpecialty medical: e.g., Journal of Clinical Oncology, CirculationGeneral pediatric: e.g., Pediatrics, Archives of Pediatrics & Adolescent MedicineSpecialty pediatric: e.g., Pediatric Emergency Care, Journal of Pediatric Orthopedics

Study designWhat was the design of the RCT? □Parallel

□Crossover□Factorial□Split body□Cluster□Other (specify):

Parallel: A trial that compares two groups of people concurrently, one of which receives the intervention of interest and one of which is a control group. Some parallel trials have more than two comparison groups and some compare different interventions without including a non-intervention control group. (Also called independent group design.)

Crossover: A type of clinical trial comparing two or more interventions in which the participants, upon completion of the course of one treatment, are switched to another. For example, for a comparison of treatments A and B, the participants are randomly allocated to receive them in either the order A, B or the order B, A.Particularly appropriate for study of treatment options for relatively stable health problems. The time during which the first intervention is taken is known as the first period, with the second intervention being taken during the second period.

Appendix 3. General Instructions for REDCap. (Continues)



Factorial: A trial design used to assess the individual contribution of treatmentsgiven in combination, as well as any interactive effect they may have. Most trials only consider a single factor, where an intervention is compared with one or more alternatives, or a placebo. In a trial using a 2x2 factorial design, participants are allocated to one of four possible combinations. For example in a 2x2 factorial RCT of nicotine replacement and counselling, participants would be allocated to: nicotine replacement alone, counselling alone, both, or neither. In this way it is possible to test the independent effect of each intervention on smoking cessation and the combined effect of (interaction between) the two interventions. This type of study is usually carried out in circumstances where no interaction is likely.

Split body: A trial in which separate body parts within each participant (e.g., eyes) were randomized to receive or not receive an intervention.

Cluster: A trial in which pre-existing groups of participants (e.g., schools, villages) are randomly selected to receive or not receive an intervention.

Based on the study hypothesis/objectives, which study type was described?

□Efficacy/Superiority□Equivalence□Non-inferiority□None of the above□Unclear

Efficacy/Superiority: A study in which the authors intended to demonstrate asignificant difference between treatments.Equivalence: A study in which the authors intended to show that there was no significant difference between treatments.Non-inferiority: A study in which the authors intended to show that the new treatment effect is not worse than the standard treatment effect.

In your opinion, what study type is consistent with the methods described?

□Efficacy/Superiority□Equivalence□Non-inferiority□None of the above□Unclear

InterventionWhat was the nature of the intervention? □Drug

□Vaccine□Rehabilitation or psychosocial□Prevention or screening□Surgery or radiotherapy□Communication, organizational, or educational□Alternative therapeutic□Device□Other (specify):

(Wood BMJ 2008)

Was a complex intervention being studied?

□Yes□No

A complex intervention is one “made up of various interconnecting parts.” (Campbell BMJ 2000)

How many arms did the study have?What intervention(s)/comparator(s) were evaluated?

*Make a note of how you’ve labelled each study arm (i.e., Arms 1-6) – this numbering system will appear on a later page for extracting outcome data. Where possible, enter the name of the control group as Arm 1 and the name of the intervention as Arm 2. In trials with more than two arms, try to order from control intervention.

What type of control was used? □No intervention□Placebo□Active intervention□Wait-list control

Select all that apply.

□Other (specify):Trial conductWas the study multicentre? □Yes

□No□Unclear

If yes, how many study sites were involved?Was the study multinational? □Yes

□NoThe term “multinational” pertains to the countries from which patients were enrolled; not to the authors’ affiliations.

Where were participants recruited from? □Established market economy□Transitional country□Developing country

Select all that apply.Established market economy: United States, Canada, Australia, New Zealand, Israel, Japan, Western European countriesTransitional country: Eastern European countries: Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Hungary, Kosovo, Latvia, Lithuania, FYR Macedonia, Montenegro, Poland, Romania, Serbia, TurkeyDeveloping country: All others

(Panagiotou BMJ 2013; International Monetary Fundhttp://www.imf.org/external/pubs/ft/weo/2013/02/weodata/groups.htm)

Was the funding source specified? □Yes□No



244.e18 Gates et al

-Opt in or opt out recruitment (consent was sought for participation or non-participation)

Who first approached the patient about participating in the trial?

□Child’s clinician□Researcher/clinician unknown to patient□Other (specify):□Not reported

Other professionals could include individuals such as teachers.

How did the family first hear about the trial?

□Approached during healthcare visit□Generalized mailing□Targeted mailing□Personalized mailing□Phone calls□Media□Pamphlets□Not reported□Other (specify):


Generalized mailing: mail out to a large populationTargeted mailing: mail out to a targeted groupPersonalized mailing: mailing addressed to the individualMedia: Internet, newspaper, radio, TVPamphlets: given to the families or left out for participants to pick up

Who was the trial information targeted to?

□Parents□Children□Both□Not reported

“Trial information” refers to recruitment materials.

Did the authors report that consent was obtained?

□Yes□No

If yes, who obtained consent from the participants?

□Child’s clinician□Researcher/clinician unknown to patient□Other (specify):□Not reported

Other professionals could include individuals such as teachers.

If yes, how was consent provided in the study?

□Parental permission□Parental permission and participant assent□Consent of a mature minor□N/A

Can assume parental consent if consent reported but not specified, and no other indication that another model was used.

Were any incentives used in the study? □Yes□No□Not reported

If yes, what incentives were used? □Reimbursement□Parents□Child□Families (no other detail)


Reimbursement: costs associated with participation in the study (e.g., travel, parking) are paid back.

Who funded the study? □Government□Academic or research institute□Private□Pharmaceutical□Industry for device□No external funding□Unclear□Other (specify):


*Canadian Institutes of Health Research and National Institutes of Health are considered government funding.*If a foundation is listed as a source of funding, report as “Private.”*Include all UN agencies under “Other.”

(Klassen Arch Pediatr Adolesc Med 2002)What recruitment strategies were used? □Standard

□Not standardStandard: Participants provide consent and then are randomized in a typical 1:1, 1:2, etc. manner.Not standard: Any of:-Open trial design (randomization occurs before participants are approached, so that participants are informed of the treatment they were randomized to receive prior to consent)-Increasing or decreasing the chance of receiving the experimental treatment-Experimental treatment for all participants and standard treatment for non-participants-Standard care for all participants and experimental treatment for non-participants-Random assignment of treatment for participants and choice of treatment for non-participants

□Not reported□Compensation

□Parents□Child□Families (no other detail)□Not reported

□Appreciation□Parents□Child□Families (no other detail)□Not reported

Compensation: participants are paid a modest amount for their time/effort.Appreciation: a small token gift given at the end of the study, usually not known beforehand.Payment: typically known before study participation and used as a strategy to enhance recruitment.

*Use “families” only if specified as such in the publication, with no information provided on whether the incentives were meant for the parents or child.




□Payment□Parents□Child□Families (no other detail)□Not reported

□N/AHow long were participants given to decide whether or not to enroll in the trial?

□No restriction□Limited□No time□Not reported

No restriction: hours to weeksLimited: immediately to less than a few hoursNo time: retrospective consent

Were any delays, shortfalls, or difficulties in recruitment reported once the trial was underway?

□Yes□No

If yes, what were the reasons for the delays or difficulties?

□Trial level factors□Site level factors□Patient level factors□Clinical team level factors□Information and consent factors□Study team level factors□Other (specify):□N/A

Examples (for more detail, see Kaur Trials 2012):Trial level: funding, trial management, feasibilitySite level: competing projects, time to open up sitePatient level: travel, costs, duration of trial and follow-up, preferences, language or cultural barrierInformation and consent: amount and complexity of trial information provided, experience of clinical team seeking consentStudy team level: experience and training of team, clinical workload, clinician attitude towards research or treatment

How were the recruitment delays or difficulties addressed?

□Described (specify):□Not described□No difficulties

Was the use of patient or family involvement in the design or conduct of the study reported?

□Yes (specify):□No

For involvement in the conduct of the study, consider involvement past the point where a decision is made to participate, i.e., the participant/family has already enrolled prior to the involvement referred to.

Study sampleWas the presence of subgroups reportedin the Methods section?

□Yes□No

Subgroups refers to authors creating distinct subgroups within their recruited population.

If yes, how was the subgroup(s) defined? E.g., by age, disease severity, etc.If yes, was the subgroup analysis declared:

□A priori□Post hoc□Not reported□N/A

Was a target age range described (e.g. in the inclusion criteria)?

□Yes□No

Include units. Report years as “yr,” months as “mo,” weeks as “wk,” and days as “d.”

If yes, what was the target age range? Report years as “yr,” months as “mo,” weeks as “wk,” and days as “d.”What was the described age group? -Mean

-SD-Median-Range-IQR-Other

Include any numerical values given for randomized patients and include relevant measures and units. Report years as “yr,” months as “mo,” weeks as “wk,” and days as “d.”

For range, extract the range of the actual trial participants, not the target age range or inclusion criteria.

If values are reported by group, combine where possible (e.g., age range of 8-10 in one group and 9-12 in the other, record 8-12), and extract data from each group where data cannot be combined. Indicate in each field whether you are recording the value for the study sample as a whole, or individual values by group.

Was stratification by age done during randomization?

□Yes□No

Was stratification done during randomization by any other criterion?

□Yes (specify):□No

Do not include age; other factors may include things like disease severity.

How was the study population selected? □Inpatients□NICU□PICU□Not reported□Other (specify):

□Outpatients□Clinicians’ office□School□Community□Unclear□Other (specify):


In the case of selection from a dental clinic, report “Doctor’s office.”

What primary diagnostic category wasinvolved in the study?

□Infectious and parasitic diseases□Neoplasms□Blood, blood forming organs,

Select the primary diagnostic category of the study using the ICD-10 classification system.

(ICD-10 Version:2010 http://apps.who.int/classifications/icd10/browse/2010/en)



244.e20 Gates et al

and immune mechanism□Endocrine, nutritional, and metabolic diseases□Mental and behavioural disorders□Nervous system□Eye and adnexa□Ear and mastoid process□Circulatory system□Respiratory system□Digestive system□Skin and subcutaneous tissue□Musculoskeletal system and connective tissue□Genitourinary system□Pregnancy, childbirth, and the puerperium□Conditions originating in the perinatal period□Congenital malformations, deformations, and chromosomal abnormalities□Symptoms, signs, and abnormal clinical and laboratory findings, not elsewhere classified□Injury, poisoning, and consequences of external causes□External causes of morbidity and mortality□Factors influencing health status and contact with health services□Oral health□Other (specify):

Did the study exclude participants who had at least one chronic condition (other than the condition that was the focus of the trial) or a co-morbid condition?

□Yes□No□Unclear

Sample sizeHow many patients were approached to participate in the study?

Use NR if applicable.

How many patients consented to participate in the study?

Use NR if applicable.

*This is not necessarily the same number as randomized.How many participants were randomized?

Total study n.

How many participants were analyzed? Total study n.If the numbers differ for different outcomes or time points, report the number of participants analyzed for the primary outcome. If not specified, use the time of the first measurement.

Was a sample size calculation reported? □Yes□ No

If yes, what was the calculated sample size?If yes, was the sample size inflated to adjust for loss of participants?

□Yes□No□Unclear□N/A

If yes, was the sample size calculation based on the primary outcome?

□Yes (primary outcome specified by authors)□Yes (primary outcome inferred by data extractor)□No□Unclear

Which parameter values were reported for the sample size calculation?

□Type I error (α)□Power (1-β)□SD□Control event rate□Expected treatment difference





□Minimal clinically important difference□Not reported□N/A

From where was the information for the sample size calculation obtained?

□Similar pediatric populations□Other pediatric populations□Adult populations□Internal pilot study□Expert opinion□Not reported□N/A

Was the power of the trial reported? □Yes□No

*Answer “yes” if the authors report the actual power of the study – distinct from using the desired power to calculate the sample size.

Did the authors report a minimal clinically important difference?


Minimal clinically important difference (MCID): the smallest difference in score in the domain of interest which patients perceive as beneficial and which would mandate, in the absence of troublesome side effects and excessive cost, a change in the patient’s management.

(Jaeschke Control Clin Trials 1989)

*Answer “yes” if the authors imply that they considered what a clinically meaningful difference would be.

If yes, did they provide a reference for the minimal clinically important difference?

□Yes□No

Data Monitoring Committee and Follow-upWas the presence of a Data Monitoring Committee reported?


May be referred to as a Data Monitoring Committee (DMC), Data Monitoring Safety Board (DSMB), or Data Monitoring Board (DMB).

If yes, who were the members? □Physician□Nurse□Allied health specialist□Statistician□Clinical trial methodologist□Clinical pharmacologist□Bioethicist□Public health practitioner□Consumer/community advocate□Other (specify):□Not reported□N/A


Were any interim analyses reported? □Yes, planned a priori□Yes, not planned a priori□Yes, unclear when planned□No

What responsibilities were reported for the Data Monitoring Committee?

□Dose adjustment□Adjustment to enrollment□Study termination□Review/approve protocol□Review/make


recommendations regarding quality of study conduct□Release interim data□Review/approve manuscripts or presentations□Other (specify):□Not reported□N/A

Were stopping rules reported? □Yes□No□Unclear

Was the trial stopped early? □Yes□No□Not reported

If yes, what was the reason for early stopping?

□Benefit□Harm□Futility□Funding

Benefit: stopped because of benefit seen in intervention groupHarm: stopped because of harm seen in intervention groupFutility: stopped because enrolling enough patients to show difference would not be feasible or no difference found in interim analysis



244.e22 Gates et al

□Recruitment□Unclear□N/A

Funding: select if funding was for a specific time frame, not if funding inadequate to enroll the higher than anticipated number of participants required (that would be futility)Recruitment: stopped because of lower than anticipated recruitment

Outcomes and conclusionsWas the primary outcome explicitly specified?

□Yes□No

In the case of multiple, connected papers with different areas of focus, base the choice of primary outcome on the trial originally identified in our search, regardless of whether or not this matches the primary outcome of the trial as a whole.

If not, can the primary outcome be inferred from the title, study objective, or hypothesis?

□Yes□No□N/A

What type of data was collected for the primary outcome?

□Continuous□Dichotomous

What was the effect estimate of the primary outcome?

n/mean/SDn/# of events

To select primary outcome, if necessary:1. Choose the objective over the subjective outcome.2. If the sample size calculation is based on an outcome, use it as the

primary outcome.3. If 1 and 2 aren’t met, use the first outcome listed in the Results section

as the primary outcome.

If results are reported for multiple groups (e.g., male and female reported separately), extract data from first group reported.

If results are reported at multiple time points, extract data from the time of the first measurement.

If outcome data was not reported in this format, enter the SMD and SE (SMD) calculated from the worksheet.

SMD/SE (SMD)□Other (specify):□N/A

If the outcome data is not presented as described above, use the Effect Size Calculator spreadsheet provided to calculate the SMD and SE.

Only select “other” if the data does not fit into any categories provided in the spreadsheet and you would like to enter a comment.

Use “N/A” if the data reported fits into the standard n/mean/SD categories for continuous outcomes and n/# of events for dichotomous outcomes.

To use the spreadsheet:1. Fill out any available information only in the sections highlighted in

yellow. Any other cells in the spreadsheet will automatically populate with the relevant calculations.

2. Scrolling down on the sheet, use the section labelled “Standardized Mean Difference Computations” to obtain the results to report. Take the calculated value for SMD and SE (SMD) and enter into the DE form. If there are values for multiple sections, use the one closer to the top of the list (e.g., take the value under “based on reported treatment difference”over “based on reported CFB in both treatment and control”).

3. If there are more than two study arms, extract data for one treatment and one control group, based on (in order):

a. the authors’ specified intent; orb. the control group with the least intervention (e.g., placebo,

rather than a low dose) and the treatment group with the most intervention (e.g., a high dose rather than a low dose).

Was the treatment effect reported by age subgroups?

□Yes□No□N/A

*This section (next 7 items) applies to reporting of subgroups in the Resultssection. Use “no” if age subgroups are specified in the Methods, but results aren’t reported by subgroups in the Results. Use “N/A” if there are no age subgroups in the trial.

Was the treatment effect reported by another subgroup(s)?

□Yes□No□N/A

Applicable to any subgroups other than age (e.g., gender).

If yes, specify how the subgroup(s) was defined.

E.g., gender, disease severity

Was the treatment effect statistically adjusted for age?

□Yes□No

I.e., age was included in the statistical model.

Was the treatment effect adjusted for another subgroup factor?

□Yes□No□N/A

I.e., a subgroup factor other than age was included in the statistical model.

Was a formal test for a subgroup interaction effect conducted?

□Yes□No□N/A

Test involves statistical testing with a measure of significance (p value).

If yes, was the test of interaction significant?

□Yes□No□N/A




Was the primary outcome: □Objective□Subjective

Objective outcomes include all cause mortality, measures based on a recognized laboratory procedure, surgical or instrumental outcomes and other objective measures.Subjective outcomes include patient reported outcomes, physician assessed disease outcomes, measures combined from several outcomes, and withdrawals or study dropouts.

(Wood BMJ 2008)If the primary outcome was subjective, do the authors report that the outcome measurement tool used is valid?

□Yes□No□N/A

If yes, is the measurement tool valid in: □Children□Adults□Both□Not reported

As reported by the authors.

If yes, was the validation of the measurement tool supported by a reference?

□Yes□No

Which category best describes the type of primary outcome measured?

□Behavioural□Biomarker□Pain□Physiological□Psychological□Techniques/training□Quality of life□Other (specify):□N/A

Behavioural: e.g. attitudes, eating behavioursBiomarker: NIH definition: A characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. E.g. blood glucose, urine cultures.Pain: e.g. pain relief, pain preventionPhysiological: adapted from NIH definition: A characteristic or variable that reflects how a patient feels, functions, or survives. E.g. disease progression, mortalityPsychological: e.g. depression assessment scores, neuropsychological test performanceTechniques/training: method of intubation, effectiveness of a focus groupQuality of life: e.g. SF-36, patient satisfaction

Was the study described as a pilot or □Yesexploratory study? □NoWas there at least one outcome that is statistically significant?

□Yes□No

Was the primary outcome statistically significant?

□Yes□No

If the primary outcome was significant, which intervention was favoured?

□Treatment□Control□N/A

Were any significant subgroup differences identified?

□Yes□No□N/A

If there was a subgroup effect, was it in the same direction as the overall effect?

□Yes□No□Unclear□N/A

Did the authors report planning to collect data on adverse effects/events or side effects?

□Yes□No

Was a method for collecting data on adverse effects stated?

□Yes□No

Were any harms reported? □Yes□No

If yes, which harms were reported? □Severe harms□Any harm (not individually described)□Organ system-level harms□Specific harms□N/A


Rely on the authors’ terminology. For example, “severe harms” will capture general phrases like those listed below (major adverse events, etc.); however, if there is a severe harm that is clearly specified, check “specific harms” instead. Using this framework, we can capture what the authors reported, rather than having to make judgments.

If mortality is listed as an outcome (e.g., survival study in oncology), do not count as a harm – this will be captured below.

Severe harms (could pertain to specific or organ system-level harms): may use terms such as “severe adverse events,” “major adverse events,” “severe nephrotoxiticy,” etc. A “serious adverse event” is an undesirable experience associated with the use of a medical product in a patient that results in a patient outcome that is: death, life-threatening, hospitalization (initial or prolonged), disability or permanent damage, congenital anomaly/birth defect, required intervention to prevent permanent impairment or damage (devices), or other



244.e24 Gates et al

serious important medical events. (U.S. Food and Drug Administrationhttp://www.fda.gov/safety/medwatch/howtoreport/ucm053087.htm)Any harm: may include terms such as “side effects,” “any adverse event,” “total adverse events,” “overall adverse events”Organ system-level harms (in general, without further report of individual adverse events in those organ systems): e.g. cardiovascular adverse events; gastrointestinal adverse events; bone and joint pain; systemic allergic reactions (anaphylaxis, asthma, rhinitis, or urticaria); local allergic reactions (large or delayed wheals at injection site)Specific harms: e.g., headache, nausea, vomiting, diarrhea, drowsiness, fatigue, dizziness, tremor, neutropenia

Were any harm-related endpoints reported?

□Discontinuations due to adverse effects□Any discontinuations□Mortality□N/A


Discontinuations due to adverse effects: explicitly stated (examples of terminology: “withdrawals due to harms,” “adverse events requiring discontinuation of study drug,” “hematologic adverse events requiring discontinuation of study drug,” “patient withdrawal due to adverse events”)Any discontinuations: reasons for discontinuations not explicitly stated (e.g., could be due to adverse events or lack of efficacy)Mortality: deaths from any cause, e.g., could be due to disease progression, lack of efficacy, or adverse events

List the harms or harm-related endpoints that were reported.Were harms or harm-related endpoints reported by group?

□Yes□No□General statement

Select all that apply (relevant if harms are NOT reported by group, but a general statement is provided).

Use “general statement” for statements such as “No adverse events were reported,” the where breakdown by group is not specified.

What were the authors’ overall conclusions?

□Positive□Negative□Neutral□Indeterminate

Positive: authors stated that there is evidence of utilityNegative: authors advised against the use of the interventionNeutral: no evidence of utility/authors reported no opinionIndeterminate: authors stated there is insufficient evidence

(Tricco et al. J Clin Epi 2009)Methodological qualityWas the analysis described as intention to treat?

□Yes□No

Was the study described as blinded? □Yes□No

If yes, was the method of blinding described?

□Yes□No□N/A

Who was blinded in the study (check all that apply)?

□Participants□Healthcare providers□Outcome assessors□Analysts□Parents/caregivers□No blinding□Unclear

Registration and protocol characteristicsIn the publication, was registration of the trial declared?

□Yes□No

Was the trial registered with a clinical trial registry?

□Yes□No

If trial registration is not declared, search, in order, the trial title/key words, corresponding author, first author, and/or last author in each of:1. ICTRP (apps.who.int/trialsearch/)2. Current Controlled Trials (www.controlled-trials.com/mrct/ -- select all 5 registers included in the meta-register)3. Google

If yes, which registry was used?Were the primary outcomes specified in the trial registry?

□Yes□No

I.e., does the registry specify primary outcomes for the trial, whether or not they match up with what is reported in the publication.

If specified, what primary outcomes were reported in the trial registry?Was the primary outcome stated in the trial registry the same as in the publication?

□Yes□No□Partially□N/A

Was the primary outcome stated in the trial registry made a secondary outcome in the publication?





Was the primary outcome stated in the trial registry omitted from the publication?


Was a non-primary outcome in the trial registry changed to primary in the publication?


Was an outcome that was not included in the trial registry a primary outcome in the

□Yes□No

publication? □N/AWere any subgroup analyses planned in the trial registry?

□Yes□No□N/A



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CONSORT 2010 Checklist of Information to Include When Reporting a Randomized Trial

Section/Topic Item Number Checklist ItemTitle and abstract 1a

1b Identification as a randomized trial in the titleStructured summary of trial design, methods, results, and conclusions (for specific guidance, see CONSORT for abstracts)

IntroductionBackground and objectives 2a

2bScientific background and explanation of rationaleSpecific objectives or hypotheses

MethodsTrial design 3a

3b

Description of trial design (such as parallel, factorial), including allocation ratio.*Look for 3 components: parallel/factorial/etc.; superiority/equivalence/etc.; allocation ratioImportant changes to methods after trial commencement (such as eligibility criteria), with reasons*Use protocol/trial registry if available.

Participants 4a4b

Eligibility criteria for participantsSettings and locations where the data were collected

Interventions 5 The interventions for each group with sufficient details to allow replication, including how and when they were actually administered

Outcomes 6a

6b

Completely defined prespecified primary and secondary outcome measures, including how and when they were assessedAny changes to trial outcomes after the trial commenced, with reasons*Use protocol/trial registry if available.

Sample size 7a7b

How sample size was determinedWhen applicable, explanation of any interim analyses and stopping guidelines*Use protocol/trial registry if available.

RandomizationSequence generation 8a

8bMethod used to generate the random allocation sequenceType of randomization; details of any restriction (such as blocking and block size)

Allocation concealment mechanism

9 Mechanism used to implement the random allocation sequence (such as sequentially numbered containers), describing any steps taken to conceal the sequence until interventions were assigned

Implementation 10 Who generated the random allocation sequence, who enrolled participants, and who assigned participants to interventions

Blinding 11a

11b

If done, who was blinded after assignment to interventions (for example, participants, care providers, those assessing outcomes) and howIf relevant, description of the similarity of interventions

Statistical methods 12a12b

Statistical methods used to compare groups for primary and secondary outcomesMethods for additional analyses, such as subgroup analyses and adjusted analyses

ResultsParticipant flow (a diagram is strongly recommended)

13a For each group, the numbers of participants who were randomly assigned, received intended treatment, and were analyzed for the primary outcome

13b For each group, losses and exclusions after randomization, together with reasonsRecruitment 14a

14bDates defining the periods of recruitment and follow-upWhy the trial ended or was stopped*YES: if the trial reports the intended (e.g., 3 year trial) and actual (e.g., mean length of follow-up 35 months) length of follow-up; OR if the reason for early stopping is reported. UNABLE TO ASSESS: if there is no supporting detail*Use protocol/trial registry if available.

Baseline data 15 A table showing baseline demographic and clinical characteristics for each groupNumbers analyzed 16 For each group, number of participants (denominator) included in each analysis and whether the analysis was

by original assigned groupsOutcomes and estimation 17a

17b

For each primary and secondary outcome, results for each group, and the estimated effect size and its precision (such as 95% confidence interval)For binary outcomes, presentation of both absolute and relative effect sizes is recommended

Ancillary analyses 18 Results of any other analyses performed, including subgroup analyses and adjusted analyses, distinguishing prespecified from exploratory

Harms 19 All important harms or unintended effects in each group (for specific guidance, see CONSORT for harms)DiscussionLimitations 20 Trial limitations; addressing sources of potential bias; imprecision; and, if relevant, multiplicity of analysesGeneralizability 21 Generalizability (external validity, applicability) of the trial findingsInterpretation 22 Interpretation consistent with results, balancing benefits and harms, and considering other relevant evidenceOther informationRegistration 23 Registration number and name of trial registryProtocol 24 Where the full trial protocol can be accessed, if availableFunding 25 Sources of funding and other support (such as supply of drugs), role of funders

*For further guidance, please see Schulz Ann Intern Med 2010;152 and Moher BMJ 2010;340:c8




*For further guidance, please refer to Chapter 8 of the Cochrane Handbook (http://handbook.cochrane.org/) or the StaR Child Health Risk of Bias wiki (http://starchildhealth-riskofbias.wikispaces.com/).

Types of Biases and ROB Domains

Bias ROB DomainSelection Bias Sequence generation

Allocation concealmentPerformance Bias Blinding study participants and personnelDetection Bias Blinding outcome assessorsAttrition Bias Incomplete outcome dataReporting Bias Selective outcome reportingOther Bias “Other sources” of bias

Sequence Generation

Was the allocation sequence adequately generated?Randomization ensures that the groups being compared are balanced for known and unknown confounders.Inadequate sequence generation can overestimate treatment effects by 12% (ROR 0.88, 95% CI 0.79, 0.99).1

ROB Decision CriteriaLow Description of a random component in sequence generation process (e.g., computer-

generated random numbers, coin toss, random number table).Unclear Insufficient data is provided to make a judgment (e.g., only described as: random, randomly

generated, randomized, etc.).

Statements that groups were blocked or stratified should NOT be considered sufficient for a ‘yes/low risk’ rating unless accompanied by a description indicating the sequence was computer generated,

High No randomization or inappropriate randomization (e.g. alternation, assignment based on birth date or day of hospital admission).

Allocation Concealment

Was allocation adequately concealed?Allocation concealment ensures that the randomization sequence is unknown to the person entering participants into a trial until allocation to an intervention has occurred.Inadequate allocation concealment can exaggerate treatment effects by 18% (ROR 0.82, 95% CI 0.71, 0.94).2

ROB Decision CriteriaLow Sequentially numbered, opaque, sealed envelopes.

Sequentially numbered drug containers of identical appearance.Central allocation with description (i.e. pharmacy, web-based, call-in).Randomization sequence maintained by a 3rd party uninvolved in the investigation or off-site.Central allocation, but no further description is provided. Use context to determine whether this better fits in ‘low’ or ‘unclear.’

Unclear No statement.Includes 1 or 2 of: opaque, sealed, sequentially numbered envelopes is described, but does not use ALL 3 descriptors.Randomization sequence is kept on site (with no further description).

High Open allocation schedule.Any method in which the investigators could foresee the group assignment (e.g. alternation, date of birth, etc.).

Blinding – 1) Participants and personnel; 2) Outcome assessors

Was knowledge of the allocated intervention adequately prevented during the study?Blinding of key individuals in a trial can minimize performance and detection bias.Studies not described as “double-blind” can overestimate treatment effects by 9% (ROR 0.91, 95% CI 0.83, 1.0).3

Results not consistent across studies.

Appendix 4. Decision Rules for Risk of Bias Assessments. (Continues)


244.e28 Gates et al

ROB Decision CriteriaLow No blinding or incomplete blinding, but the outcome is unlikely to be influenced by lack of

blinding.Blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken.Description of “double-blinding” with specification that the participants and study personnel are blinded.Description of the use of “double-dummy” or “matched placebo.”

Unclear Insufficient information to permit judgment.The study did not address blinding.

High No blinding or incomplete blinding and the outcome is likely to be influenced.Blinding attempted, but likely that it could have been broken and the outcome is likely to be influenced.




Blinding of participants and personnel (Performance bias)

Risk of biasOutcome typeBlinding description

Category of bias

Personnel/Participants

(Performance bias)

Open-label

Objective outcome Unclear

Subjective outcome High

Double-blinded (no description)

Objective outcome Unclear

Subjective outcome Unclear

Description that personnel &

participants are blinded

Objective outcome Low

Subjective outcome Low

Blinding of outcome assessment (Detection bias)

Used when 3rd party assessor is mentioned.When 3rd party assessor is not mentioned, use the same assessment as for blinding of participants and personnel.

Risk of biasOutcome typeBlinding descriptionCategory of bias

Outcome Assessment(Detection

bias)

Assessor blinded


Subjective outcome Low

Assessor un-blinded


Subjective outcome High

Unclear on assessor blinding


Subjective outcome Unclear



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Incomplete Outcome Data

• Were incomplete outcome data adequately addressed?• Per protocol analyses may yield more favourable estimates compared to intention-to-treat (ITT) analyses.• “Modified” ITT* may overestimate treatment effects by 15% (ROR 0.85, 95% CI 0.81, 0.88).4

• Results not consistent across studies.

ROB Decision CriteriaLow ROB ITT and dropout rate <10%.

No ITT, dropout rate <10%, and number and reasons for withdrawal balanced between groups.

Unclear ROB ITT and/or dropout rate between 10 and 30%.High ROB Dropout rate ≥30%.

Dropout rate <30%, but number and reason for dropouts very imbalanced between groups.Per protocol analysis only (unless under of patients switching groups is too small to make any important difference to the estimated intervention effect).

*Modified ITT is not consistently defined, but may refer to how participants contribute outcome data (e.g., all participants available for follow-up at timepoint X), and whether all or a subset of randomized participants are included in the analysis (e.g., excluding participants that did not receive a specified minimum amount of the intended intervention). In assessing this domain, closely consider the description of what was done, the dropout rate, and the likelihood for bias.

Selective outcome reporting

• Is there an indication that the reports are free of selective outcome reporting (SOR)?• SOR occurs when a subset of the original variables recorded for investigation in the protocol is presented in

the publication.• It may also be indicated by discrepancies in the primary outcomes proposed and those reported.• Statistically significant outcomes are more likely to be completely reported than non-significant outcomes

(range of odds ratios 2.2 to 4.7).5

ROB Decision CriteriaLow ROB No discrepancies between outcomes listed in the protocol and those described in the results.Unclear ROB N/AHigh ROB Outcomes are identified in the protocol or methods section that are not described in the

results section of the report.

When to search for protocols:Cochrane recommendations

Protocol should be compared with results.

In a previous study, we found that searching for protocols had little yield, but often changed assessment when found.

Protocol or registry number is reported

Look for the protocol and compare outcomes in protocol with the results.

Protocol registries: clinicaltrials.gov, ISRCTN, WHO, Australia/New Zealand registryNo protocol reported Do not look for protocols – assess as unclear.

Request guidance from clinical leads to determine if there are key outcomes that should be reported according to the report topic. Decisions on searching for protocols and how to use them should be made at the outset of each review, based on the specific context.

Other sources of bias

• “Catch-all” domain.• Source of funding or early stopping should not be assessed in “other sources” of bias; however, continue

to extract these items and report them in the results/discussion sections. o Conduct a sensitivity analysis for studies that received industry funding versus no industry

funding.o Conflict of interest can be assessed in the “publication bias” domain of GRADE.

• Specific “other sources” of bias will not be identified to assess for each project.




ROB Decision CriteriaLow ROB No other sources of bias are identified.

This is the default assessment.Unclear ROB N/AHigh ROB Other sources of bias such as: participant characteristics (baseline imbalances), study design

characteristics (crossover, cluster randomized, blocked randomization in unblinded trials).

Overall ROB Assessment

ROB Decision CriteriaLow ROB All domains are assessed as low.Unclear ROB At least one domain is assessed as unclear and no domains are assessed as high.High ROB At least one domain is assessed as high.

1 Als-Nielsen B, Gluud LL, Gluud C. Methodological quality and treatment effects in randomised trials: a review of six empirical studies. 12th Cochrane Colloquium Oct 2-6, Ottawa, Ontario, Canada, 20042 Pildal J, Hrobjartsson A, Jorgensen KJ, Hilden J, Altman DG, Gotzsche PC. Impact of allocation concealment on conclusions drawn from meta-analyses of randomized trials. Int J Epidemiol 2004; 36(4):847-4573 Pildal J, Hrobjartsson A, Jorgensen KJ, Hilden J, Altman DG, Gotzsche PC. Impact of allocation concealment on conclusions drawn from meta-analyses of randomized trials. Int J Epidemiol 2004; 36(4):847-4574 Abraha I, Duca PG, Montedori A. Empirical evidence of bias: modified intention to treat analysis of randomised trials affects estimates of intervention efficacy. Z Evid Fortbild Qual Gesundhwes 2008; 102[Suppl VI]:9.5 Dwan K, Altman DG, Arnaiz JA, Bloom J, Chan AW, Cronin E, et al. Systematic review of the empirical evidence of study publication bias and outcome reporting bias. PLoS ONE 2008; 3(80):e3081.



244.e32 Gates et al

RISK OF BIAS FOR CHILDREN IN TRIALS – 007

Guidelines and Decision Rules for Risk of Bias Assessments

*Use these decision rules in addition to the guidelines outlined in the Cochrane criteria (attached).

Sequence generation:- If blocked randomization, permutation, or stratification is specified, assume the randomization

sequence was computer-generated and answer YES.- If the description only includes ‘random’, ‘randomly generated’, ‘randomized’, etc, do not assume

additional details and answer UNCLEAR.

Allocation concealment:- If the randomization is conducted by central telephone, pharmacy, etc, assume this is adequate and

answer YES.

Blinding:- Determine whether the blinding is likely to be broken, and whether the outcomes in unblinded

studies are likely to be influenced by the lack of blinding.- If a study is described as “double-dummy”, assume that this is appropriate and answer YES. If it

is described as “double-blind” without further details, answer UNCLEAR.

Incomplete outcome data:- Look for intention-to-treat analysis. If this was done appropriately, answer YES.- If all participants were accounted for (i.e. no drop-outs or censored analysis conducted), answer

YES.- If the numbers and reasons for withdrawal/drop-outs were described and comparable across

groups (and ≤ approximately 10%), answer YES.- If there is greater than 10% drop-out, consider UNCLEAR or NO.

Selective outcome reporting:- If the study protocol is available, compare the outcomes reported in the publication to those

specified in the protocol. Answer YES if the outcomes in the two documents match.- If the study protocol is not available, compare the outcomes reported in the Methods and Results

sections. Answer YES if these match.

Other sources of bias:- Assess for baseline imbalances that could have biased the results (or were not accounted for).- Assess for early stopping for benefit.- Assess for appropriateness of cross-over design (e.g. inadequate wash-out period).- Assess for inappropriate influence of funders that could have biased the results.

If sponsor is acknowledged and there is a clear statement regarding no involvement of sponsor in trial conduct or data management/analysis, answer YES.If sponsor is acknowledged and no one from the sponsoring agency was an author, answer YES.If sponsor is acknowledged and someone from the sponsoring agency was an author, answer NO.If a drug/intervention is provided by industry, but the trial has no other inappropriate influence of funding, answer YES.If there is no mention of funding source, answer UNCLEAR.

- Note any “other” sources of bias.

Appendix 5. Risk of Bias Decision Rules for the 2007 Study. (Continues)



Table 8.5.c: Criteria for judging risk of bias in the ‘Risk of bias’ assessment tool

SEQUENCE GENERATION Was the allocation sequence adequately generated? [Short form: Adequate sequence generation?]

Criteria for a judgement of ‘YES’ (i.e. low risk of bias).

The investigators describe a random component in the sequence generation process such as:

Referring to a random number table;

Using a computer random number generator;

Coin tossing;

Shuffling cards or envelopes;

Throwing dice;

Drawing of lots;

Minimization*.

*Minimization may be implemented without a random element, and this is considered to be equivalent to being random.

Criteria for the judgement of ‘NO’ (i.e. high risk of bias).

The investigators describe a non-random component in the sequence generation process. Usually, the description would involve some systematic, non-random approach, for example:

Sequence generated by odd or even date of birth;

Sequence generated by some rule based on date (or day) of admission;

Sequence generated by some rule based on hospital or clinic record number.

Other non-random approaches happen much less frequently than the systematic approaches mentioned above and tend to be obvious. They usually involve judgement or some method of non-random categorization of participants, for example:

Allocation by judgement of the clinician;

Allocation by preference of the participant;

Allocation based on the results of a laboratory test or a series of tests;

Allocation by availability of the intervention.

Criteria for the judgement of ‘UNCLEAR’ (uncertain risk of bias).

Insufficient information about the sequence generation process to permit judgement of ‘Yes’ or ‘No’.



244.e34 Gates et al

ALLOCATION CONCEALMENTWas allocation adequately concealed? [Short form: Allocation concealment?]


Participants and investigators enrolling participants could not foresee assignment because one of the following, or an equivalent method, was used to conceal allocation:

Central allocation (including telephone, web-based, and pharmacy-controlled, randomization);

Sequentially numbered drug containers of identical appearance;

Sequentially numbered, opaque, sealed envelopes.


Participants or investigators enrolling participants could possibly foresee assignments and thus introduce selection bias, such as allocation based on:

Using an open random allocation schedule (e.g. a list of random numbers);

Assignment envelopes were used without appropriate safeguards (e.g. if envelopes were unsealed or nonopaque or not sequentially numbered);

Alternation or rotation;

Date of birth;

Case record number;

Any other explicitly unconcealed procedure.


Insufficient information to permit judgement of ‘Yes’ or ‘No’. This is usually the case if the method of concealment is not described or not described in sufficient detail to allow a definite judgement – for example if the use of assignment envelopes is described, but it remains unclear whether envelopes were sequentially numbered, opaque and sealed.

BLINDING OF PARTICIPANTS, PERSONNEL AND OUTCOME ASSESSORSWas knowledge of the allocated interventions adequately prevented during the study? [Short form: Blinding?]


Any one of the following:

No blinding, but the review authors judge that the outcome and the outcome measurement are not likely to be influenced by lack of blinding;

Blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken;

Either participants or some key study personnel were not blinded, but outcome assessment was blinded and the non-blinding of others unlikely to introduce bias.



No blinding or incomplete blinding, and the outcome or outcome measurement is likely to be influenced by lack of blinding;

Blinding of key study participants and personnel attempted, but likely that the blinding could have been broken;

Either participants or some key study personnel were not blinded, and the non-blinding of others likely to introduce bias.



Insufficient information to permit judgement of ‘Yes’ or ‘No’;

The study did not address this outcome.




INCOMPLETE OUTCOME DATAWere incomplete outcome data adequately addressed? [Short form: Incomplete outcome data addressed?]



No missing outcome data;

Reasons for missing outcome data unlikely to be related to true outcome (for survival data, censoring unlikely to be introducing bias);

Missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups;

For dichotomous outcome data, the proportion of missing outcomes compared with observed event risk not enough to have a clinically relevant impact on the intervention effect estimate;

For continuous outcome data, plausible effect size (difference in means or standardized difference in means) among missing outcomes not enough to have a clinically relevant impact on observed effect size;

Missing data have been imputed using appropriate methods.



Reason for missing outcome data likely to be related to true outcome, with either imbalance in numbers or reasons for missing data across intervention groups;

For dichotomous outcome data, the proportion of missing outcomes compared with observed event risk enough to induce clinically relevant bias in intervention effect estimate;

For continuous outcome data, plausible effect size (difference in means or standardized difference in means) among missing outcomes enough to induce clinically relevant bias in observed effect size;

‘As-treated’ analysis done with substantial departure of the intervention received from that assigned at randomization;

Potentially inappropriate application of simple imputation.



Insufficient reporting of attrition/exclusions to permit judgement of ‘Yes’ or ‘No’ (e.g. number randomized not stated, no reasons for missing data provided);

The study did not address this outcome.



244.e36 Gates et al

SELECTIVE OUTCOME REPORTINGAre reports of the study free of suggestion of selective outcome reporting? [Short form: Free of selective reporting?]


Any of the following:

The study protocol is available and all of the study’s pre-specified (primary and secondary) outcomes that are of interest in the review have been reported in the pre-specified way;

The study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre-specified (convincing text of this nature may be uncommon).



Not all of the study’s pre-specified primary outcomes have been reported;

One or more primary outcomes is reported using measurements, analysis methods or subsets of the data (e.g. subscales) that were not pre-specified;

One or more reported primary outcomes were not pre-specified (unless clear justification for their reporting is provided, such as an unexpected adverse effect);

One or more outcomes of interest in the review are reported incompletely so that they cannot be entered in a meta-analysis;

The study report fails to include results for a key outcome that would be expected to have been reported for such a study.


Insufficient information to permit judgement of ‘Yes’ or ‘No’. It is likely that the majority of studies will fall into this category.

OTHER POTENTIAL THREATS TO VALIDITYWas the study apparently free of other problems that could put it at a risk of bias? [Short form: Free of other bias?]


The study appears to be free of other sources of bias.


There is at least one important risk of bias. For example, the study:

Had a potential source of bias related to the specific study design used; or

Stopped early due to some data-dependent process (including a formal-stopping rule); or

Had extreme baseline imbalance; or

Has been claimed to have been fraudulent; or

Had some other problem.


There may be a risk of bias, but there is either:

Insufficient information to assess whether an important risk of bias exists; or

Insufficient rationale or evidence that an identified problem will introduce bias.




Documents

The Conduct and Reporting of Child Health Research: An ... · Study design For 300 RCTs, we extracted design and reporting characteristics and assessed RoB. We as-sessed 5-year changes