Changes in evidence for studies assessing interventions for COVID-19 reported in preprints: meta-research study

Abstract

Background: The increasing use of preprints to disseminate evidence on the effect of interventions for the coronavirus disease 2019 (COVID-19) can lead to multiple evidence sources for a single study, which may differ in the reported evidence. We aim to describe the proportion of evidence on the effect of interventions for COVID-19 from preprints and journal articles and map changes in evidence between and within different sources reporting on the same study.

Methods: Meta-research study. We screened the Cochrane living systematic review and network meta-analysis (COVID-NMA) database to identify all preprints and journal articles on all studies assessing interventions for COVID-19 published up to 15 August 2020. We compared all evidence sources (i.e., preprint and associated journal article) and the first and latest versions of preprints for each study to identify changes in two evidence components: study results (e.g., numeric change in hazard ratio, odds ratio, event rate, or change in p value > or < 0.05 in any outcome) and abstract conclusions (classified as positive, negative or neutral regarding the intervention effect, and as reporting uncertainty in the findings or not). Changes in study results were further classified as important changes if they (1) represented a change in any effect estimate by ≥ 10% and/or (2) led to a change in the p value crossing the threshold of 0.05.

Results: We identified 556 studies. In total, 338 (61%) had been reported in a preprint: 66 (20%) of these had an associated journal article (median time to publication 76 days [interquartile range (IQR) 55-106]) and 91 (27%) had > 1 preprint version. A total of 139 studies (25% of the overall sample) were reported in multiple evidence sources or versions of the same source: for 63 (45%), there was a change in at least one evidence component between or within sources (42 [30%] had a change in study results, and in 29 [21%] the change was classified as important; 33 [24%] had a change in the abstract conclusion). For studies with both a preprint and an article, a median of 29% (IQR 14-50) of total citations were attributed to the preprint instead of the article.

Conclusions: Results on the effect of interventions for COVID-19 are often reported in multiple evidence sources or source versions for a single study. Evidence is not stable between and within evidence sources. Real-time linkage of all sources per study could help to keep systematic reviews up-to-date.

Keywords: COVID-19; Coronavirus; Meta-research; Preprint.

Fig. 1

Flow chart

Fig. 2

Survival plot depicting the probability of a preprint remaining unpublished as journal article for 338 studies initially published as preprints. This survival plot presents the probability that a study initially published as a preprint remains unpublished as a journal article. The x-axis represents the number of days elapsed since the preprint first appeared online. Of the 338 studies published as preprints from the onset of the COVID-19 pandemic to 15 August 2020, 66 had an associated journal article by 2 September 2020

Fig. 3

Direction of changes in the abstract conclusion of 139 studies assessing preventive, treatment, or post-acute care interventions for COVID-19, from the first preprint version to the associated journal article or latest preprint version of each study. This Sankey diagram presents the changes made to the abstract conclusion for the same study, between the first preprint version on the left, and the latest available source version on the right (journal article or latest preprint version for studies that have not been published in a journal). The colored flow lines represent the direction of the change: green lines represent change from negative to neutral or positive, or from neutral to positive, and red lines represent change from positive or neutral to negative, and from positive to neutral