Randomized trials addressing a similar question are commonly published after a trial stopped early for benefit.
OBJECTIVE
We explored how investigators of ongoing or planned trials respond to the publication of a trial stopped early for benefit addressing a similar question.


METHODS
We searched multiple databases from the date of publication of the truncated trial through August, 2015. Independent reviewers selected trials and extracted data.


RESULTS
We identified 207 trials truncated for early benefit; of which 102 (49%) were followed by subsequent trials (262 subsequent trials, median 2 per truncated trial, range 1-13). Only 99 (38%) provided a rationale justifying conducting a trial despite prior stopping. The top reasons were to address different population or setting (33%), skepticism of truncated trials findings because of small sample size (12%), inconsistency with other evidence (11%), or increased risk of bias (7%). We did not identify significant associations between subsequent trials and characteristics of truncated ones (risk of bias, precision, funding, or rigor of stopping decision).


CONCLUSIONS
About half of the trials stopped early for benefit were followed by subsequent trials addressing a similar question. This suggests that future trialists may have been skeptic about the decision to stop prior trials. A more rigorous threshold for stopping early for benefit is needed.
Evidence-Based Practice Center, Mayo Clinic, 200, 1st street, Rochester, MN 55905, USA; Knowledge and Evaluation Research Unit, Mayo Clinic, 200, 1st street, Rochester, MN 55905, USA; Division of Preventive Medicine, Mayo Clinic, 200, 1st street, Rochester, MN 55905, USA. Electronic address: murad.mohammad@mayo.edu.
M Hassan
MH
Murad
Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario L8S 4L8, Canada.
Gordon H
GH
Guyatt
Department of Internal Medicine, Henry Ford Hospital, Detroit, MI, USA; Unidad de Conocimiento y Evidencia, CONEVID, UPCH, Lima, Peru.
Juan Pablo
JP
Domecq
Iberoamerican Cochrane Centre, Institute of Biomedical Research (IIB Sant Pau), Barcelona, Spain.
Robin W M
RWM
Vernooij
Mayo Clinic Libraries, Mayo Clinic, 200, 1st street, Rochester, MN 55905, USA.
Patricia J
PJ
Erwin
Cochrane Germany, Medical Center-University of Freiburg, Berliner Allee 29, 79110 Freiburg, Germany.
Joerg J
JJ
Meerpohl
Unidad de Conocimiento y Evidencia, CONEVID, UPCH, Lima, Peru; Department of Pediatrics, Children's Hospital of Michigan, Detroit, MI, USA.
Gabriela J
GJ
Prutsky
Department of Internal Medicine, American University of Beirut, Beirut, Lebanon; Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
Elie A
EA
Akl
Center for Clinical Pediatric Studies, University Children's Hospital Tuebingen, Frondsbergstraße 23, 72070 Tuebingen, Germany.
Katharina
K
Mueller
Department of Neonatology, University Hospital Zurich and University of Zurich, Frauenklinikstrasse 10, 8091 Zurich, Switzerland.
Dirk
D
Bassler
Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Switzerland.
Stefan
S
Schandelmaier
Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario L8S 4L8, Canada.
Stephen D
SD
Walter
The Michael G. DeGroote Institute for Pain Research and Care, Department of Anesthesia, and Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
Jason W
JW
Busse
Basel Institute for Clinical Epidemiology; Department of Medicine, Royal Marsden Hospital, London, UK.
Benjamin
B
Kasenda
Federico II University of Naples, Naples, Italy.
Gennaro
G
Pagano
Iberoamerican Cochrane Centre, Institute of Biomedical Research (IIB Sant Pau), Barcelona, Spain.
Hector
H
Pardo-Hernandez
Knowledge and Evaluation Research Unit, Mayo Clinic, 200, 1st street, Rochester, MN 55905, USA.
Victor M
VM
Montori
Evidence-Based Practice Center, Mayo Clinic, 200, 1st street, Rochester, MN 55905, USA.
Zhen
Z
Wang
Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Switzerland; Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario L8S 4L8, Canada.
Matthias
M
Briel
D016208:Databases, Factual / Q000706:statistics & numerical data; D057239:Early Termination of Clinical Trials; D016021:Epidemiologic Studies; D006801:Humans; D011643:Publishing / Q000706:statistics & numerical data*; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*
Early termination of trials; Methodology; Randomized controlled trials; Systematic review; Trial design; Trials stopped early for benefit