Feasibility of Emulating Clinical Trials Supporting US FDA Supplemental Indication Approvals of Drugs and Biologics.

This cross-sectional study evaluates the supporting clinical trials for supplemental new drug applications and supplemental biologics license applications from 2017 to 2019.

Comparison of Clinical Study Results Reported in medRxiv Preprints vs Peer-reviewed Journal Articles.

Importance: Preprints have been widely adopted to enhance the timely dissemination of research across many scientific fields. Concerns remain that early, public access to preliminary medical research has the potential to propagate misleading or faulty research that has been conducted or interpreted in error. Objective: To evaluate the concordance among study characteristics, results, and interpretations described in preprints of clinical studies posted to medRxiv that are subsequently published in peer-reviewed journals (preprint-journal article pairs). Design, Setting, and Participants: This cross-sectional study assessed all preprints describing clinical studies that were initially posted to medRxiv in September 2020 and subsequently published in a peer-reviewed journal as of September 15, 2022. Main Outcomes and Measures: For preprint-journal article pairs describing clinical trials, observational studies, and meta-analyses that measured health-related outcomes, the sample size, primary end points, corresponding results, and overarching conclusions were abstracted and compared. Sample size and results from primary end points were considered concordant if they had exact numerical equivalence. Results: Among 1399 preprints first posted on medRxiv in September 2020, a total of 1077 (77.0%) had been published as of September 15, 2022, a median of 6 months (IQR, 3-8 months) after preprint posting. Of the 547 preprint-journal article pairs describing clinical trials, observational studies, or meta-analyses, 293 (53.6%) were related to COVID-19. Of the 535 pairs reporting sample sizes in both sources, 462 (86.4%) were concordant; 43 (58.9%) of the 73 pairs with discordant sample sizes had larger samples in the journal publication. There were 534 pairs (97.6%) with concordant and 13 pairs (2.4%) with discordant primary end points. Of the 535 pairs with numerical results for the primary end points, 434 (81.1%) had concordant primary end point results; 66 of the 101 discordant pairs (65.3%) had effect estimates that were in the same direction and were statistically consistent. Overall, 526 pairs (96.2%) had concordant study interpretations, including 82 of the 101 pairs (81.2%) with discordant primary end point results. Conclusions and Relevance: Most clinical studies posted as preprints on medRxiv and subsequently published in peer-reviewed journals had concordant study characteristics, results, and final interpretations. With more than three-fourths of preprints published in journals within 24 months, these results may suggest that many preprints report findings that are consistent with the final peer-reviewed publications.