Informed consent forms (hereinafter, forms), part of a larger consent process that serves multiple bioethical functions,1 are intended to provide potential research volunteers with sufficient written information about a clinical trial to help them decide about participation. Despite concerns about their overall quality, broadly generalizable samples of forms have been difficult to access for quality improvement.2,3 Since July 2017, ClinicalTrials.gov has allowed voluntary posting of forms4 for registered studies. Subsequently (January 21, 2019), the revised Common Rule form-posting requirement (45 CFR 46.116[h])5 became effective (eAppendix in the Supplement). To explore how access to forms has increased on ClinicalTrials.gov after these initiatives, we sought to characterize registered trials with available forms and posting trends. We also assessed the frequency of form posting by funder type for trials initiated since the revised Common Rule compliance date.
We conducted cross-sectional analyses using 2 data sets downloaded from ClinicalTrials.gov on July 7, 2021. Set 1 was used to characterize all registered clinical trials with at least 1 US site and a posted form. Set 2 consisted of registered US trials with start dates on or after January 21, 2019; study completion dates on or before June 30, 2021; and with or without a posted form. We assessed the percentage of trials with a posted form by funder type among registered trials initiated since the revised Common Rule general compliance date. Institutional review board approval was not required because this study did not involve any human participants (and only assessed publicly posted clinical trial records). This report followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.
Of 2088 trials with forms posted on ClinicalTrials.gov (set 1), 986 (47.2%) listed funding only by “other” nonfederal and nonindustry sources (eg, foundations) while another 846 (40.5%) listed funding by US federal agencies (including the National Institutes of Health [NIH]) (Table). Furthermore, 976 trials (46.7%) listed at least 1 drug, biologic, or genetic intervention; 468 (22.4%) listed at least 1 device, diagnostic, or radiation intervention (ie, likely products regulated by the US Food and Drug Administration); 1520 (72.8%) had completed or terminated enrollment; 1050 (50.3%) had 0 to 50 participants; and the most listed conditions were obesity, depression, prostate cancer, breast cancer, and stroke. In addition, 1972 (94.4%) of set 1 trials were associated with 542 nonindustry sponsors, and the remaining 116 (5.6%) were associated with 85 industry sponsors. The Figure shows the cumulative number of forms available at ClinicalTrials.gov for set 1 trials.
Among 4754 registered trials in set 2 (ie, initiated since the revised Common Rule compliance date), trials with posted forms by key funder type were 17.7% (71 of 401) funded by the NIH, 12.5% (16 of 128) funded by another US federal agency, 5.1% (113 of 2209) funded by another organization (eg, foundation), and 0.9% (19 of 2016) funded by industry. Overall, the percentage of set 2 trials with posted forms was 4.6% (219 of 4574).
As of July 7, 2021, forms were publicly available on ClinicalTrials.gov for nearly 2100 US trials for a range of intervention types and conditions from across 600 mostly nonindustry sponsors. Many of these trials (1243 of 2088 [59.5%]) did not list funding by a US federal agency and, among those 1243 trials, some were initiated before the compliance date, suggesting that their forms were likely not required to be posted under the revised Common Rule.
The absolute percentages of federally funded trials initiated since the Common Rule compliance date in set 2 remain relatively low, with fewer than 87 of 529 trials (16.5%) listing a key funder type of “NIH” or “other US federal agency” having posted forms. Although forms for a range of trials are now available on ClinicalTrials.gov, most appear to have been posted voluntarily.
Limitations of this cross-sectional study include that retrieved trials were likely skewed toward those required by federal reporting requirements. Trials may have also been miscategorized because of errors or incomplete information in data self-reported by study sponsors. Further research is needed because it is likely too soon to assess the full impact of the revised Common Rule requirement.
Accepted for Publication: September 22, 2021.
Published: November 18, 2021. doi:10.1001/jamanetworkopen.2021.35146
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Tse T et al. JAMA Network Open.
Corresponding Author: Deborah A. Zarin, MD, Multi-Regional Clinical Trials Center of Brigham and Women’s Hospital and Harvard, 14 Story St, Cambridge, MA 02138 (dzarin@bwh.harvard.edu).
Author Contributions: Drs Tse and Zarin had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: All authors.
Acquisition, analysis, or interpretation of data: Tse, Bierer.
Drafting of the manuscript: Tse, Zarin.
Critical revision of the manuscript for important intellectual content: All authors.
Administrative, technical, or material support: Tse, Gelinas, Morrell, Bierer, Zarin.
Supervision: Gelinas, Zarin.
Conflict of Interest Disclosures: Dr Tse reported being employed by the National Institutes of Health (NIH) as an analyst for ClinicalTrials.gov. Dr Zarin reported receiving personal fees from ClinicalTrials.gov and providing technical consultation to ClinicalTrials.gov outside the submitted work. No other disclosures were reported.
Funding/Support: This study was supported by grants from the Intramural Research Program funded through the NIH, National Library of Medicine (Tse).
Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Disclaimer: The views expressed in this article are those of the authors and do not necessarily reflect the positions of the NIH.
Additional Contributions: The authors thank Russell Loane, PhD (Thoughtful Solutions), for assistance with data collection. No compensation was received for his contributions to the study.
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