Nonregistration, Discontinuation, and Nonpublication of Randomized Trials
Benjamin Speich, Ala Taji Heravi, Christof Schönenberger, L. Hausheer, Dmitry Gryaznov, Jason W. Busse, Manuela Covino, Szimonetta Lohner, Malena Chiaborelli, Johannes M. Schwenke, Ruben Ramirez Zegarra, Ramon Saccilotto, Julia Hüllstrung, Erik von Elm, Arnav Agarwal, Julian Hirt, David Mall, Alain Amstutz, Selina Epp, Dominik Mertz, Anette Blümle, Belinda von Niederhäusern, Ayodele Odutayo, Alexandra Griessbach, Sally Hopewell, Matthias Briel, ASPIRE Study Group, Benjamin Speich, Dmitry Gryaznov, Belinda von Niederhäusern, Benjamin Kasenda, Elena Ojeda–Ruiz, Anette Blümle, Stefan Schandelmaier, Dominik Mertz, Ayodele Odutayo, Yuki Tomonaga, Alain Amstutz, Christiane Pauli‐Magnus, Viktoria Gloy, Szimonetta Lohner, Karin Bischoff, Katharina Wollmann, Laura Rehner, Joerg J Meerpohl, Alain Nordmann, Katharina Klatte, Nilabh Ghosh, Ala Taji Heravi, Jacqueline Wong, Ngai Chow, Patrick Jiho Hong, Kimberly Mc Cord, Sirintip Sricharoenchai, Jason W. Busse, Lukas Kübler, Pooja Gandhi, Zsuzsanna Némethné Kontár, Julia Hüllstrung, Mona Elafy, Arnav Agarwal, Ramon Saccilotto, Alexandra Griessbach, Christof Schönenberger, Matthias Schwenkglenks, Giusi Moffa, Lars G. Hemkens, Sally Hopewell, Erik von Elm, Matthias Briel
Abstract
Importance: Previous work found that 25% to 30% of randomized clinical trials (RCTs) with protocols approved in 2012 or between 2000 and 2003 were discontinued prematurely, most commonly due to inadequate participant recruitment. To minimize research waste, RCTs should be registered and their results made available. Objectives: To assess the fate of RCTs approved by ethics committees in 2016 in terms of nonregistration, discontinuation, and nonpublication, and to examine RCT characteristics associated with discontinuation due to poor recruitment and nonpublication of RCT results. Evidence Review: As a prespecified project of the Adherence to SPIRIT Recommendations (ASPIRE) study, this systematic review had access to 347 RCT protocols approved in 2016 by research ethics committees in the UK, Switzerland, Germany, and Canada. Eligible RCTs were defined as prospective studies randomly assigning participants to interventions to study effects on health outcomes. RCTs were excluded that never started, were ongoing at time of follow-up, were duplicates, or were labeled as pilot, feasibility, or phase 1 trials. Key trial characteristics were extracted from the approved trial protocols. In July 2024, pairs of reviewers systematically searched for trial registrations and results publications. When the status of either was unclear, the corresponding ethics committee or the principal investigator was contacted for clarification. Findings: Of 347 included RCTs, 20 (5.8%) were unregistered, 108 (31.1%) were discontinued, most often due to poor recruitment (49 [45.4%]), and 276 (79.5%) made their results publicly available. Results from industry-sponsored trials were more often available than non-industry-sponsored trials (166 of 181 [92.3%] vs 110 of 166 [66.3%]). This difference was attributable to a higher prevalence of industry-sponsored trials that reported results in trial registries (153 of 181 [84.5%]) vs nonindustry RCTs (17 of 166 [10.2%]). Multivariable logistic regression indicated that industry-sponsored trials were less frequently discontinued due to poor recruitment than non-industry-sponsored RCTs (adjusted odds ratio, 0.32 [95% CI, 0.15-0.71]). Conclusions and Relevance: Findings from this systematic review indicated that nonregistration, premature discontinuation due to poor recruitment, and nonpublication of RCT results remained major challenges, especially for non-industry-sponsored trials. To mitigate these challenges, requirements enforced by funders and ethics committees also taking into account legal obligations should be considered and empirically evaluated.