Consistency of covid-19 trial preprints with published reports and impact for decision making: retrospective review

OBJECTIVE: To assess the trustworthiness (ie, complete and consistent reporting of key methods and results between preprint and published trial reports) and impact (ie, effects of preprints on meta-analytic estimates and the certainty of evidence) of preprint trial reports during the covid-19 pandemic. DESIGN: Retrospective review. DATA SOURCES: World Health Organization covid-19 database and the Living Overview of the Evidence (L-OVE) covid-19 platform by the Epistemonikos Foundation (up to 3 August 2021). MAIN OUTCOME MEASURES: Comparison of characteristics of covid-19 trials with and without preprints, estimates of time to publication of covid-19 preprints, and description of differences in reporting of key methods and results between preprints and their later publications. For the effects of eight treatments on mortality and mechanical ventilation, the study comprised meta-analyses including preprints and excluding preprints at one, three, and six months after the first trial addressing the treatment became available either as a preprint or publication (120 meta-analyses in total, 60 of which included preprints and 60 of which excluded preprints) and assessed the certainty of evidence using the GRADE framework. RESULTS: Of 356 trials included in the study, 101 were only available as preprints, 181 as journal publications, and 74 as preprints first and subsequently published in journals. The median time to publication of preprints was about six months. Key methods and results showed few important differences between trial preprints and their subsequent published reports. Apart from two (3.3%) of 60 comparisons, point estimates were consistent between meta-analyses including preprints versus those excluding preprints as to whether they indicated benefit, no appreciable effect, or harm. For nine (15%) of 60 comparisons, the rating of the certainty of evidence was different when preprints were included versus being excluded—the certainty of evidence including preprints was higher in four comparisons and lower in five comparisons. CONCLUSION: No compelling evidence indicates that preprints provide results that are inconsistent with published papers. Preprints remain the only source of findings of many trials for several months—an unsuitable length of time in a health emergency that is not conducive to treating patients with timely evidence. The inclusion of preprints could affect the results of meta-analyses and the certainty of evidence. Evidence users should be encouraged to consider data from preprints.