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Evidence‐based medicine has changed clinical practice by incorporating data from randomised controlled trials (RCTs). While some biases in RCTs are well recognised, we discuss some less acknowledged. Selection bias may arise in the consent stage. Industry‐funded studies more often report a positive outcome. Post‐hoc changes of outcome measures and other mis‐reporting lowers the reliability of outcome data. Finally, even the GRADE system retains subjectivity. Conclusion: Moving from "intuition" into "evidence‐based" medicine involves grappling with several pitfalls. These pose challenges for authors, editors, reviewers, and readers. All require vigilance before drawing conclusions from presented data. [ABSTRACT FROM AUTHOR]

Context: Randomized controlled trials (RCTs) are among the cornerstones for generation of high-quality clinical evidence. However, incomplete or biased reporting of trials can hamper the process of review of trials and their results. Outcome switching, intentional, or otherwise leads to biased reporting and can result in false inferences. Aims: The aim of this study was to analyze the completeness of reporting Consolidated Standards of Reporting Trials (CONSORT) 2010 checklist items and detect if outcome switching had occurred. Settings and Design: This cross-sectional study was conducted in the department of pharmacology. Methods: Online editions of journals published by the Indian association of medical specialties from 2017 to 2019 were accessed, and the full-text versions of the published RCTs in them were downloaded. Reporting of each item in the CONSORT checklist was recorded. The effect of trial registration and CONSORT endorsement on reporting of key methodological parameters was also determined. Protocols of registered trials were accessed, and the outcome switching was assessed. Statistical Analysis Used: Descriptive statistics were used to summarize the data. Results: Average completeness of reporting has significantly improved from 2017 to 2019. Major areas of underreporting were generalizability, protocol availability, trial registration, date of recruitment, allocation concealment, and the patient flow diagram. CONSORT endorsing journals had worse, whereas registered trials had better reporting of key methodological indicators. No overt switching of outcomes was observed in 84 out of 86 registered trials where trial protocols were available online for comparison. Conclusions: Quality of clinical trial reporting in the Indian medical journals has improved but remains inadequate. CONSORT nonendorsement prevents completeness of trial reporting.

Undisclosed discrepancies often exist between study registrations and their associated publications. Discrepancies can increase risk of bias, and when undisclosed, they disguise this increased risk of bias from readers. To remedy this issue, we developed an intervention called discrepancy review. We provided journals with peer reviewers specifically assigned to check for undisclosed discrepancies between registrations and manuscripts submitted to journals. We performed discrepancy review on 18 manuscripts submitted to Nicotine and Tobacco Research and three manuscripts submitted to the European Journal of Personality. We iteratively refined the discrepancy review process based on feedback from discrepancy reviewers, editors and authors. Authors addressed the majority of discrepancy reviewer comments, and there was no opposition to running a trial from authors, editors or discrepancy reviewers. Outcome measures for a trial of discrepancy review could include the presence of primary or secondary outcome discrepancies, whether publications that are not the primary report from a clinical trial registration are clearly described as such, whether registrations are permanent, and an overarching subjective assessment of the impact of discrepancies in published articles. We found that discrepancy review could feasibly be introduced as a regular practice at some journals interested in this process. A full trial of discrepancy review would be needed to evaluate its impact on reducing undisclosed discrepancies.

Context: Randomized controlled trials (RCTs) are among the cornerstones for generation of high-quality clinical evidence. However, incomplete or biased reporting of trials can hamper the process of review of trials and their results. Outcome switching, intentional, or otherwise leads to biased reporting and can result in false inferences. Aims: The aim of this study was to analyze the completeness of reporting Consolidated Standards of Reporting Trials (CONSORT) 2010 checklist items and detect if outcome switching had occurred. Settings and Design: This cross-sectional study was conducted in the department of pharmacology. Methods: Online editions of journals published by the Indian association of medical specialties from 2017 to 2019 were accessed, and the full-text versions of the published RCTs in them were downloaded. Reporting of each item in the CONSORT checklist was recorded. The effect of trial registration and CONSORT endorsement on reporting of key methodological parameters was also determined. Protocols of registered trials were accessed, and the outcome switching was assessed. Statistical Analysis Used: Descriptive statistics were used to summarize the data. Results: Average completeness of reporting has significantly improved from 2017 to 2019. Major areas of underreporting were generalizability, protocol availability, trial registration, date of recruitment, allocation concealment, and the patient flow diagram. CONSORT endorsing journals had worse, whereas registered trials had better reporting of key methodological indicators. No overt switching of outcomes was observed in 84 out of 86 registered trials where trial protocols were available online for comparison. Conclusions: Quality of clinical trial reporting in the Indian medical journals has improved but remains inadequate. CONSORT nonendorsement prevents completeness of trial reporting. [ABSTRACT FROM AUTHOR]

Publication bias (the tendency for studies with positive results to be more easily published than studies with null or negative results) and outcome switching (the adjustment of study aims to match results) have long been problematic in medical research. Recent legislation, protocol-registration sites, and agreements by medical journals have led to a reduction of these problems in medical research. In medical education specifically, however, there is no such legislation, registration, or agreement. This paper argues for the creation of such a registration site and agreement by medical education journals as a matter of ethical necessity.

Background: Progestogens have been evaluated in numerous trials and meta-analyses, many of which concluded they were effective. However, two large trials PROMISE and OPPTIMUM have recently concluded that progesterone was ineffective. This raises the possibility that earlier studies and reviews had been biased by either selective publication or selective choice of outcomes, so called "P-hacking".Objectives: To compare the findings all progestogen trials and systematic reviews with those of trials with pre-registered primary outcomes which avoided selective outcome reporting.Search Strategy: Search of PubMed, the Cochrane Library and trial registries. Registration PROSPERO CRD42016035303.Selection Criteria: Systematic reviews of randomised trials comparing progestogen with placebo in pregnancy and the individual trials included in those reviews. The subset of trials reporting a pre-registered primary outcome were compared with the totality of trials and reviews.Data Collection and Analysis: For reviews all outcomes were included. For individual trials all outcomes reported in the systematic reviews were included. For the comparison group we recorded the registered primary outcome from trials that were either registered before they started, or registered during the recruitment phase and also double blind.Main Results: Nineteen of twenty-nine meta-analyses concluded that progestogens were effective. Twenty-two trials reported their pre-registered primary outcomes. There was no effect of progesterone on primary registered dichotomous outcome RR 1.00 (95% CI 0.94-1.07). Only one of the 22 showed a nominally statistically significant benefit.Author's Conclusions: When evaluated in registered double-blind trials with analysis restricted to predefined primary outcomes, progestational agents in pregnancy are ineffective.Tweetable Abstract: Progestogens to prevent pregnancy loss, an example of P-hacking. [ABSTRACT FROM AUTHOR]

Background Homeopathy is gaining popularity globally, despite a lack of convincing evidence of its efficacy. For example, a 2015 review by the Australian National Health and Medical Research Council (NHMRC) found no discernible convincing effects beyond placebo. However, a concern was that publication bias and outcome reporting bias could have influenced the results of the included systematic reviews. Objectives To study (i) the rates of non-publication and (ii) rates and types of alteration of planned outcomes of homeopathy studies registered in ClinicalTrials.gov. Methods We searched ClinicalTrials.gov for all homeopathy trials completed more than 2 years ago. We then checked the trial's publication status by examining the publication field in ClinicalTrials.gov, searching PubMed and finally Google Scholar. We also checked whether the registered primary outcome matched the published primary outcome. Results We found 35 registered homeopathy trials, from 11 countries, completed at least 2 years ago. Of these 35, we found 16 (46%) publications in MEDLINE and Google Scholar. In four (of 16), the primary outcome measures had been switched or modified. Conclusions Of all homeopathy trials registered in ClinicalTrials.gov, only 46% appear to have published within 2 years of completion, of which a quarter altered their primary endpoint. Further research is warranted on the nature and reasons for non-publication. [ABSTRACT FROM AUTHOR]

Undisclosed discrepancies often exist between study registrations and their associated publications. Discrepancies can increase risk of bias, and when undisclosed, they disguise this increased risk of bias from readers. To remedy this issue, we developed an intervention called discrepancy review . We provided journals with peer reviewers specifically assigned to check for undisclosed discrepancies between registrations and manuscripts submitted to journals. We performed discrepancy review on 18 manuscripts submitted to Nicotine and Tobacco Research and three manuscripts submitted to the European Journal of Personality . We iteratively refined the discrepancy review process based on feedback from discrepancy reviewers, editors and authors. Authors addressed the majority of discrepancy reviewer comments, and there was no opposition to running a trial from authors, editors or discrepancy reviewers. Outcome measures for a trial of discrepancy review could include the presence of primary or secondary outcome discrepancies, whether publications that are not the primary report from a clinical trial registration are clearly described as such, whether registrations are permanent, and an overarching subjective assessment of the impact of discrepancies in published articles. We found that discrepancy review could feasibly be introduced as a regular practice at some journals interested in this process. A full trial of discrepancy review would be needed to evaluate its impact on reducing undisclosed discrepancies., (© 2022 The Authors.)

Objectives: To determine the incidence of outcome switching in follow-up publications of randomized controlled trials. Outcome switching leads to bias where treatment benefits are more likely to be overestimated or based on chance., Study Design and Setting: Meta-research study including all follow-up publications 2014-2018 in the New England Journal of Medicine, The Lancet, the Journal of the American Medical Association, and the British Medical Journal. Two independent reviewers compared the primary outcomes of follow-up publications with the original RCT publication and the trial protocol., Results: Seventy-eight follow-up publications were identified. Thirty-one (40%) used different primary outcomes in the follow-up publication compared with the original RCT. In seventeen (55%) of these the outcome switch was neither pre-specified nor explained in the journal publication. The incidence of outcome switching in follow-up studies rose to 70% when preceded by outcome switching in the corresponding initial RCT (P< 0.001)., Conclusion: In this study, outcome switching occurred in 40% of follow-up publications of previously published RCTs. The majority is neither pre-specified nor explained., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)