Comparison of effect estimates between preprints and peer-reviewed journal articles of COVID-19 trials

Preprints are increasingly used to disseminate research results, providing multiple sources of information for the same study. We assessed the consistency in effect estimates between preprint and subsequent journal article of COVID-19 randomized controlled trials.

The study utilized data from the COVID-NMA living systematic review of pharmacological treatments for COVID-19 (covid-nma.com) up to July 20, 2022. We identified randomized controlled trials (RCTs) evaluating pharmacological treatments vs. standard of care/placebo for patients with COVID-19 that were originally posted as preprints and subsequently published as journal articles. Trials that did not report the same analysis in both documents were excluded. Data were extracted independently by pairs of researchers with consensus to resolve disagreements. Effect estimates extracted from the first preprint were compared to effect estimates from the journal article.

The search identified 135 RCTs originally posted as a preprint and subsequently published as a journal article. We excluded 26 RCTs that did not meet the eligibility criteria, of which 13 RCTs reported an interim analysis in the preprint and a final analysis in the journal article. Overall, 109 preprint-article RCTs were included in the analysis. The median (interquartile range) delay between preprint and journal article was 121 (73-187) days, the median sample size was 150 (71-464) participants, 76% of RCTs had been prospectively registered, 60% received industry or mixed funding, 72% were multicentric trials. The overall risk of bias was rated as 'some concern' for 80% of RCTs. We found that 81 preprint-article pairs of RCTs were consistent for all outcomes reported. There were nine RCTs with at least one outcome with a discrepancy in the number of participants with outcome events or the number of participants analyzed, which yielded a minor change in the estimate of the effect. Furthermore, six RCTs had at least one outcome missing in the journal article and 14 RCTs had at least one outcome added in the journal article compared to the preprint. There was a change in the direction of effect in one RCT. No changes in statistical significance or conclusions were found.

Effect estimates were generally consistent between COVID-19 preprints and subsequent journal articles. The main results and interpretation did not change in any trial. Nevertheless, some outcomes were added and deleted in some journal articles.