Nonregistration, Discontinuation, and Nonpublication of Randomized Trials: A Systematic Review

Speich, Benjamin and Taji Heravi, Ala and Schönenberger, Christof Manuel and Hausheer, Lena and Gryaznov, Dmitry and Busse, Jason W. and Covino, Manuela and Lohner, Szimonetta and Chiaborelli, Malena and Schwenke, Johannes M. and Ramirez Zegarra, Ruben and Saccilotto, Ramon and Hüllstrung, Julia M. and von Elm, Erik and Agarwal, Arnav and Hirt, Julian and Mall, David and Amstutz, Alain and Epp, Selina and Mertz, Dominik and Blümle, Anette and von Niederhäusern, Belinda and Odutayo, Ayodele and Griessbach, Alexandra and Hopewell, Sally and Briel, Matthias (2025) Nonregistration, Discontinuation, and Nonpublication of Randomized Trials: A Systematic Review. JAMA NETWORK OPEN, 2 (8). No.-e2524440. ISSN 2574-3805

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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. | A szisztematikus áttekintés célja annak vizsgálata volt, hogy mi történt azokkal a randomizált klinikai vizsgálatokkal (RCT), amelyeket 2016-ban hagytak jóvá etikai bizottságok az Egyesült Királyságban, Svájcban, Németországban és Kanadában. Az elemzés 347 RCT protokollt foglalt magában. Ezek közül 5,8%-ot nem regisztráltak, 31,1%-ot idő előtt megszakítottak – leggyakrabban a résztvevők elégtelen toborzása miatt (45,4%) –, és 79,5% esetében váltak a vizsgálati eredmények nyilvánosan elérhetővé. Az ipar által támogatott vizsgálatok eredményei gyakrabban voltak elérhetők (92,3%), mint a nem ipari támogatásúaké (66,3%), főként azért, mert az ipari vizsgálatok gyakrabban jelentették eredményeiket a vizsgálati regiszterekben. A statisztikai elemzés azt is kimutatta, hogy az ipar által támogatott vizsgálatokat ritkábban szakították meg alacsony toborzás miatt. Az eredmények alapján a vizsgálatok nem regisztrálása, idő előtti megszakítása és eredményeik publikálatlansága – különösen a nem ipari vizsgálatok esetén – továbbra is jelentős problémát jelentenek. A kutatási pazarlás csökkentése érdekében a támogatók és etikai bizottságok szigorúbb követelményei, jogi előírások figyelembevételével, indokoltak lehetnek.

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