Premature trial discontinuation often not accurately reflected in registries: comparison of registry records with publications.
One quarter of randomized clinical trials (RCTs) are prematurely discontinued and frequently remain unpublished. Trial registries can document whether a trial is ongoing, suspended, discontinued, or completed and therefore represent an important source for trial status information. The accuracy of this information is unclear.



To examine the accuracy of completion status and reasons for discontinuation documented in trial registries as compared to corresponding publications of discontinued RCTs and to investigate potential predictors for accurate trial status information in registries.



We conducted a cross-sectional study comparing information provided in publications (reference standard) to corresponding registry entries. First, we reviewed publications of RCTs providing information on both discontinuation and registration. We identified eligible publications through systematic searches of MEDLINE and EMBASE (2010-2014) and an international cohort of 1,017 RCTs initiated between 2000 and 2003. Second, pairs of investigators independently and in duplicate extracted data from publications and corresponding registry records. Third, for each discontinued RCT, we compared publication information to registry information. We used multivariable regression to examine whether accurate labeling of trials as discontinued (vs. other status) in the registry was associated with recent initiation of RCT, industry sponsorship, multicenter design, or larger sample size.



We identified 173 publications of RCTs that were discontinued due to slow recruitment (55%), harm (16%), futility (11%), benefit (5%), other reasons (3%), or multiple reasons (9%). Trials were registered with clinicaltrials.gov (77%), isrctn.com (14%), or other registries (8%). Of the 173 corresponding registry records, 77 (45%) trials were labeled as discontinued and 57 (33%) provided a reason for discontinuation (of which 53, 93%, provided the same reason as in the publication). Labeling of discontinued trials as discontinued (vs. other label) in corresponding trial registry records improved over time (adjusted odds ratio 1.16 per year, confidence interval 1.04-1.30) and was possibly associated with industry sponsorship (2.01, 0.99-4.07) but unlikely with multicenter status (0.81, 0.32-2.04) or sample size (1.07, 0.89-1.29).



Less than half of published discontinued RCTs were accurately labelled as discontinued in corresponding registry records. One-third of registry records provided a reason for discontinuation. Current trial status information in registries should be viewed with caution.
Department of Clinical Research, Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Spitalstrasse 12, 4031 Basel, Switzerland; Multi Organ Transplant Center, King Fahad Specialist Hospital-Dammam, P.O. Box 15215, Dammam 31444, Saudi Arabia.
Reem
R
Alturki
Department of Clinical Research, Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Spitalstrasse 12, 4031 Basel, Switzerland; Department of Clinical Epidemiology and Biostatistics, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4K1, Canada. Electronic address: stefan.schandelmaier@usb.ch.
Stefan
S
Schandelmaier
Department of Clinical Research, Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Spitalstrasse 12, 4031 Basel, Switzerland.
Kelechi Kalu
KK
Olu
Clinical Trial Unit, Department of Clinical Research, University Hospital Basel, Schanzenstrasse 55, Basel 4031, Switzerland.
Belinda
B
von Niederhäusern
Clinical Trial Unit, Department of Clinical Research, University Hospital Basel, Schanzenstrasse 55, Basel 4031, Switzerland.
Arnav
A
Agarwal
Department of Clinical Research, Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Spitalstrasse 12, 4031 Basel, Switzerland.
Roy
R
Frei
Clinical Trial Unit, Department of Clinical Research, University Hospital Basel, Schanzenstrasse 55, Basel 4031, Switzerland.
Neera
N
Bhatnagar
Cochrane Netherlands, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, University of Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands.
Lotty
L
Hooft
Cochrane Switzerland, Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Route de la Corniche 10, 1010, Lausanne, Switzerland.
Erik
E
von Elm
Department of Clinical Research, Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Spitalstrasse 12, 4031 Basel, Switzerland; Clinical Trial Unit, Department of Clinical Research, University Hospital Basel, Schanzenstrasse 55, Basel 4031, Switzerland.
Matthias
M
Briel
D003430:Cross-Sectional Studies; D057239:Early Termination of Clinical Trials / Q000706:statistics & numerical data*; D006801:Humans; D016017:Odds Ratio; D010506:Periodicals as Topic / Q000706:statistics & numerical data*; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D012042:Registries / Q000706:statistics & numerical data*; D015203:Reproducibility of Results
Early termination of clinical trials (MeSH); Randomized controlled trial as topic (MeSH); Reporting quality; Trial registration