DOI: 10.6084/m9.figshare.3464336
title: SRDR Master list (published and registered).xlsx

description: The primary outcome of this study was to examine discrepancies between the reported primary and secondary outcomes in registered and published randomized controlled trials in high impact-factor obesity journals. The secondary outcomes were to address whether outcome reporting discrepancies favor statistically significant outcomes, whether there was a correlation between funding source and likelihood of outcome reporting bias, and whether there were temporal trends in outcome reporting bias. We also catalogued any incidental findings during data extraction and analysis that warranted further examination. To accomplish these aims, we performed a methodological systematic review of the 4 highest impact-factor obesity journals from 2013-2015. This study did not meet the regulatory definition of human subjects research according to 45 CFR 46.102(d) and (f) of the Department of Health and Human Services’ Code of Federal Regulations 10 and was not subject to Institutional Review Board oversight. We consulted Li, et al.; the Cochrane Handbook for Systematic Reviews of Interventions; and the National Academies of Science, Engineering, and Medicine’s (previously the Institute of Medicine) Standards for Systematic Reviews to ensure best practices regarding data extraction and management. We applied PRISMA guideline items 1, 3, 5-11, 13, 16-18, 24-27 to ensure reporting quality for systematic reviews as well as SAMPL guidelines for reporting descriptive statistics. Prior to initiation of the study, we registered this study with the University hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) with registry number: R000025787UMIN000022576. After screening, the citations were imported into the Agency for Healthcare Research and Quality’s Systematic Review Data Repository (SRDR) for data extraction.Two investigators (J.R.,A.R.) independently reviewed the full-text articles for each study and extracted data using SRDR. At least once per day, these investigators would trade articles and repeat the other’s data extraction. This allowed each to cross-validate the other’s work and improve the accuracy and efficiency of data extraction. Any disagreements were resolved by discussion between the pair. A third party reviewer (M.V.) was available for further adjudication, but was not needed. We extracted the following items from the published randomized controlled trials: primary outcome(s), secondary outcome(s), date of subject enrollment, trial registry database and registration number, timing of assessment in primary outcomes (ex.change in weight at 5 months, change in HbA1c at 6 weeks), sample size, any discrepancies between publication and registry disclosed by the author in the publication, and funding source. For the purpose of our study we classified funding source into the following categories: (1) private (ex. Mayo Clinic or philanthropic), (2) public (government or university), (3) industry/corporate (ex. GlaxoSmithKline), (4) University Hospital, (5) mixed funding source, or (6) undisclosed funding source. For RCTs which reported multiple primary and secondary outcomes, we recorded each explicitly stated outcome. If a primary outcome was not explicitly stated as such in the publication, the outcome stated in the sample size estimation was used. If none was explicitly stated in the text or in the sample size calculation, the article was excluded from the study. When sample size was not explicitly stated in the article, we used the “number randomized”. If author’s failed to differentiate between primary and secondary outcomes in the publication, these non-delineated outcomes were coded as “unable to assess” and excluded from comparison. <br>The clinical trial registry or registration number was obtained from each published RCT, if stated, during full-text review/data extraction. If a registration number was listed in the RCT without a trial registry, a search was made of Clinicaltrials.gov, the International Standard Randomized Controlled Trial Number Register (ISRCTNR), the World Health Organization’s International Clinical Trial Registry Platform (ICTRP), and any country specific clinical trial registry identified in the publication. The following characteristics were used to match registered study to publication: title, author(s), keyword, country of origin, sponsoring organization, description of study intervention, projected sample size, and dates of enrollment. When a publication did not explicitly state information regarding registration of a study, the authors were contacted via email using a standardized email template and asked about registration status. If after 2 days there was no reply, a 2nd email was sent. If there was no reply from authors 1 week after the 2nd email, the study was considered unregistered and excluded from the study.<br>Each registered study was located within its respective registry and data was extracted individually by 2 independent investigators (J.R., A.R.). Prior to registry data extraction both investigators underwent trial registry training including: training videos on how to perform searches and access the history of changes in clinicaltrials.gov and the WHO trial registry, tutorial video about locating desired content from trial registry entry, access to a list of all WHO approved trial registries, and each had to successfully complete a sample data extraction from an unrelated study registry entry. The following data was extracted using a standardized form on SRDR: date of trial registration, date range of subject enrollment, original primary registered outcome(s), final primary registered outcome(s), date of initial primary outcome registration, secondary registered outcome(s), sample size if listed, and funding source, if disclosed, using previously defined categories. Although registration quality was not the focus of this study, registered trials lacking a clearly stated primary outcome and timing of assessment were excluded from consideration. Studies that were found to be registered after the end of subject enrollment were excluded from the study due to the inability to adequately assess outcome reporting bias.<br>To be approved by the WHO, a trial registry must meet ICMJE criteria, including documentation of when changes are made to that particular study’s registry entries. If an included study employed this feature, we recorded both the primary outcome from time of initial registration as well as the primary outcome listed in the final version in the registry entry. Departing from the methods of previous authors in this field of research, we did not exclude studies in WHO-approved registries that did not time-stamp the date of initial primary outcome registration. Per the International Standards for Clinical Trial Registries section 2.4, WHO-approved registries are required to time-stamp registry-approved changes to any registered trial including data additions, deletions, and revisions. Therefore, if a WHO-approved trial registry did not display a history of changes, we recorded the date the registry application was approved as the date of initial primary outcome registration. Additionally, the listed primary outcome was recorded as both the initial registered and final registered primary outcome. In non-WHO-approved trial registries, if a date of initial primary outcome registration was not listed, this trial was excluded from our study.<br>