Nonregistration, discontinuation, and nonpublication of randomized trials: a repeated metaresearch analysis

Speich, B. and Gryaznov, D. and Busse, J. W. and Gloy, V. L. and Lohner, S. and Klatte, K. and Taji Heravi, A. and Ghosh, N. and Lee, H. and Mansouri, A. and Marian, I. R. and Saccilotto, R. and Nury, E. and Kasenda, B. and Ojeda-Ruiz, E. and Schandelmaier, S. and Tomonaga, Y. and Amstutz, A. and Pauli-Magnus, C. and Bischoff, K. and Wollmann, K. and Rehner, L. and Meerpohl, J. J. and Nordmann, A. and Wong, J. and Chow, N. and Hong, P. J. and Mc Cord-De Iaco, K. and Sricharoenchai, S. and Agarwal, A. and Schwenkglenks, M. and Hemkens, L. G. and von Elm, E. and Copsey, B. and Griessbach, A. N. and Schönenberger, C. and Mertz, D. and Blümle, A. and von Niederhausern, B. and Hopewell, S. and Odutayo, A. and Briel, M.. (2022) Nonregistration, discontinuation, and nonpublication of randomized trials: a repeated metaresearch analysis. PLoS Med, 19 (4). e1003980.

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BACKGROUND: We previously found that 25% of 1,017 randomized clinical trials (RCTs) approved between 2000 and 2003 were discontinued prematurely, and 44% remained unpublished at a median of 12 years follow-up. We aimed to assess a decade later (1) whether rates of completion and publication have increased; (2) the extent to which nonpublished RCTs can be identified in trial registries; and (3) the association between reporting quality of protocols and premature discontinuation or nonpublication of RCTs. METHODS AND FINDINGS: We included 326 RCT protocols approved in 2012 by research ethics committees in Switzerland, the United Kingdom, Germany, and Canada in this metaresearch study. Pilot, feasibility, and phase 1 studies were excluded. We extracted trial characteristics from each study protocol and systematically searched for corresponding trial registration (if not reported in the protocol) and full text publications until February 2022. For trial registrations, we searched the (i) World Health Organization: International Clinical Trial Registry Platform (ICTRP); (ii) US National Library of Medicine (ClinicalTrials.gov); (iii) European Union Drug Regulating Authorities Clinical Trials Database (EUCTR); (iv) ISRCTN registry; and (v) Google. For full text publications, we searched PubMed, Google Scholar, and Scopus. We recorded whether RCTs were registered, discontinued (including reason for discontinuation), and published. The reporting quality of RCT protocols was assessed with the 33-item SPIRIT checklist. We used multivariable logistic regression to examine the association between the independent variables protocol reporting quality, planned sample size, type of control (placebo versus other), reporting of any recruitment projection, single-center versus multicenter trials, and industry versus investigator sponsoring, with the 2 dependent variables: (1) publication of RCT results; and (2) trial discontinuation due to poor recruitment. Of the 326 included trials, 19 (6%) were unregistered. Ninety-eight trials (30%) were discontinued prematurely, most often due to poor recruitment (37%; 36/98). One in 5 trials (21%; 70/326) remained unpublished at 10 years follow-up, and 21% of unpublished trials (15/70) were unregistered. Twenty-three of 147 investigator-sponsored trials (16%) reported their results in a trial registry in contrast to 150 of 179 industry-sponsored trials (84%). The median proportion of reported SPIRIT items in included RCT protocols was 69% (interquartile range 61% to 77%). We found no variables associated with trial discontinuation; however, lower reporting quality of trial protocols was associated with nonpublication (odds ratio, 0.71 for each 10% increment in the proportion of SPIRIT items met; 95% confidence interval, 0.55 to 0.92; p = 0.009). Study limitations include that the moderate sample size may have limited the ability of our regression models to identify significant associations. CONCLUSIONS: We have observed that rates of premature trial discontinuation have not changed in the past decade. Nonpublication of RCTs has declined but remains common; 21% of unpublished trials could not be identified in registries. Only 16% of investigator-sponsored trials reported results in a trial registry. Higher reporting quality of RCT protocols was associated with publication of results. Further efforts from all stakeholders are needed to improve efficiency and transparency of clinical research.
Faculties and Departments:03 Faculty of Medicine > Departement Public Health > Pharmazeutische Medizin ECPM > Pharmazeutische Medizin (Szucs)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Health Interventions > Malaria Interventions (Lengeler)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medicine (MED) > Clinical Research (Reither)
UniBasel Contributors:Taji Heravi, Ala and Amstutz, Alain and Schwenkglenks, Matthias
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:1549-1676 (Electronic)1549-1277 (Linking)
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:12 Jan 2023 04:11
Deposited On:27 Dec 2022 22:03

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