Research Letter
April 3, 2023
Sharing of Individual Patient-Level Data by Trialists of Randomized Clinical Trials of Pharmacological Treatments for COVID-19
Laura C. Esmail, Philipp Kapp, Rouba Assi, et al
JAMA. Published online April 3, 2023. doi:10.1001/jama.2023.4590
Access to individual patient-level data (IPD) of randomized clinical trials (RCTs) increases the reproducibility of research, facilitates exploration of effect modifiers, and leverages research investments beyond the original research question.1 This study aimed to describe access to IPD of RCTs of pharmacological treatments for COVID-19 and to determine whether the intent to share IPD as reported in the registry and publication or preprint was consistent with actual access to IPD.
This study is part of the COVID-NMA initiative, a living systematic review of COVID-19 RCTs.2For this study, RCTs in any language were included if they assessed pharmacological treatments for COVID-19 and were posted as a preprint or published in a peer-reviewed journal from March 1, 2020, through May 31, 2021.3
For each RCT, the trialists’ intent to share IPD was extracted from the trial registry and the preprint or peer-reviewed publication. To conduct an IPD meta-analysis,2 we sent email requests to corresponding authors and registry contacts of the RCTs followed by as many as 2 reminders as necessary from September 17, 2020, through September 22, 2021. They were asked to send us their trial IPD directly or through Vivli, an online data repository that offers free help to anonymize and archive COVID-19 data. Authors were offered the opportunity for coauthorship on the IPD-MA manuscript. To capture IPD for RCTs from nonresponding authors, we searched publicly available major data repositories Vivli, Yale Open Data Access, and Clinical Study Data Request. IPD was considered accessible if trialists sent us their database or made their database available through a clinical data repository with a clear data requisition process. All databases sent to us directly were checked for data quality. Characteristics of RCTs with accessible vs inaccessible IPD were compared post hoc with the 2-tailed Mann-Whitney U test or Fisher exact test with significance set at P < .05 using SAS version 9.4 (SAS Institute Inc).
Two hundred twenty-four RCTs were included; 121 trialists (54%) responded. Ninety studies (40%) were preprints (Table). The median study sample size was 95 (IQR, 53-214). Sixty-eight trialists (30%) declared in the registry that they intended to share IPD and 138 (62%) in the publication or preprint (Figure). Overall, IPD was accessible for 50 of 224 RCTs (22%). Of these, 27 trialists provided IPD directly and 23 were available through online data repositories. Ten trialists initiated sharing their data but did not complete the process by December 31, 2021. RCTs with accessible vs inaccessible IPD had a statistically significant larger sample size (median, 118 [IQR, 64-388] vs 86 [IQR, 49-199]; P = .03). Furthermore, funding sources differed between the 2 groups (Table). Six RCTs were subsequently retracted, of which 1 had accessible IPD. The Figure presents the intention to share IPD as declared in the registry, the preprint, or the publication and the actual access to data. Twenty-seven percent (37 of 138) of RCTs with a positive data sharing statement in the preprint or publication had accessible IPD and 21% (14 of 67) with a negative data sharing statement in the registry had accessible IPD.
In this study of a planned IPD-MA, IPD was only accessible for a small proportion of RCTs despite the majority of trialists declaring an intention to share their data in the preprint or publication. The planned IPD-MA was not feasible considering the low access to data.
Despite an increase in data sharing requirements by funders and journals and the establishment of several secure data repositories, more needs to be done to increase data accessibility.4,5 Investigators may hesitate to share their data because of concerns for patient consent or confidentiality, risk of data misinterpretation or misleading analyses, or lack of understanding of why and how to share IPD.6 Moreover, sharing IPD requires additional time and effort, and institutions do not sufficiently support researchers’ capacity to do so.5
Study limitations include that authors may not have received the request. Also, this research was conducted during the COVID-19 pandemic, so results may not be generalizable.
