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

Autor: Speich B; Meta-Research Centre, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.; Oxford Clinical Trials Research Unit / Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom., Gryaznov D; Meta-Research Centre, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland., Busse JW; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.; Department of Anesthesia, McMaster University, Hamilton, Canada., Gloy VL; Meta-Research Centre, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland., Lohner S; Cochrane Hungary, Clinical Centre of the University of Pécs, Medical School, University of Pécs, Pécs, Hungary.; Department of Public Health Medicine, Medical School, University of Pécs, Pécs, Hungary., Klatte K; Clinical Trial Unit, Department of Clinical Research, University of Basel and University Hospital Basel, Basel, Switzerland., Taji Heravi A; Meta-Research Centre, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.; Swiss Tropical and Public Health Institute, Basel, Switzerland., Ghosh N; Meta-Research Centre, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland., Lee H; Oxford Clinical Trials Research Unit / Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom., Mansouri A; Oxford Clinical Trials Research Unit / Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom., Marian IR; Oxford Clinical Trials Research Unit / Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom., Saccilotto R; Clinical Trial Unit, Department of Clinical Research, University of Basel and University Hospital Basel, Basel, Switzerland., Nury E; Institute for Evidence in Medicine (for Cochrane Germany Foundation), Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.; Department of General Practice and Primary Care, Medical Center Hamburg-Eppendorf-UKE, Hamburg, Germany., Kasenda B; Department of Medical Oncology, University of Basel and University Hospital Basel, Basel, Switzerland., Ojeda-Ruiz E; Meta-Research Centre, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.; Bioaraba Health Research Institute, Health Prevention, Promotion and Care Area; Osakidetza Basque Health Service, Araba University Hospital, Preventive Medicine Department, Vitoria-Gasteiz, Spain., Schandelmaier S; Meta-Research Centre, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada., Tomonaga Y; Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland., Amstutz A; Meta-Research Centre, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.; Swiss Tropical and Public Health Institute, Basel, Switzerland.; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland., Pauli-Magnus C; Clinical Trial Unit, Department of Clinical Research, University of Basel and University Hospital Basel, Basel, Switzerland., Bischoff K; Institute for Evidence in Medicine, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Cochrane Germany, Cochrane Germany Foundation, Freiburg, Germany., Wollmann K; Cochrane Germany, Cochrane Germany Foundation, Freiburg, Germany., Rehner L; Institute for Evidence in Medicine, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Institute for Nursing Science and Interprofessional Learning, University Medicine Greifswald, Greifswald, Germany., Meerpohl JJ; Institute for Evidence in Medicine, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Cochrane Germany, Cochrane Germany Foundation, Freiburg, Germany., Nordmann A; Meta-Research Centre, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland., Wong J; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada., Chow N; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada., Hong PJ; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.; Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, Canada., Mc Cord-De Iaco K; Meta-Research Centre, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.; Multifactorial and Complex Diseases Research Area, Bambino Gesù Children's Hospital IRCCS, Rome, Italy., Sricharoenchai S; Meta-Research Centre, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland., Agarwal A; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.; Division of General Internal Medicine, Department of Medicine, McMaster University, Hamilton, Ontario, Canada., Schwenkglenks M; Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland.; Institute of Pharmaceutical Medicine (ECPM), University of Basel, Basel, Switzerland., Hemkens LG; Meta-Research Centre, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.; Meta-Research Innovation Center Berlin (METRICS-B), Berlin Institute of Health, Berlin, Germany.; Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, California, United States of America., von Elm E; Cochrane Switzerland, Centre for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland., Copsey B; Oxford Clinical Trials Research Unit / Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom., Griessbach AN; Meta-Research Centre, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland., Schönenberger C; Meta-Research Centre, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland., Mertz D; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.; Department of Medicine, McMaster University, Hamilton, Canada., Blümle A; Swiss Tropical and Public Health Institute, Basel, Switzerland.; Clinical Trials Unit, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany., von Niederhäusern B; Department of Public Health Medicine, Medical School, University of Pécs, Pécs, Hungary.; Roche Pharma AG, Grenzach-Wyhlen, Germany., Hopewell S; Oxford Clinical Trials Research Unit / Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom., Odutayo A; Oxford Clinical Trials Research Unit / Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom.; Applied Health Research Centre, Li Ka Shing Knowledge Institute of St Michael's Hospital, Toronto, Ontario, Canada., Briel M; Meta-Research Centre, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.
Jazyk: angličtina
Zdroj: PLoS medicine [PLoS Med] 2022 Apr 27; Vol. 19 (4), pp. e1003980. Date of Electronic Publication: 2022 Apr 27 (Print Publication: 2022).
DOI: 10.1371/journal.pmed.1003980
Abstrakt: 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.
Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: DG contributed to the ASPIRE project as part of his PhD thesis before his current employment with Idorsia Pharmaceuticals Ltd. (his current employer had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript). BvN contributed to the ASPIRE project as part of her PhD thesis before her current employment with Roche (her current employer had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript). All authors have declared that no competing interests exist.
Databáze: MEDLINE
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