Randomized trials addressing a similar question are commonly published after a trial stopped early for benefit

M Hassan Murad; Gordon H Guyatt; Juan Pablo Domecq; Robin W M Vernooij; Patricia J Erwin; Joerg J Meerpohl; Gabriela J Prutsky; Elie A Akl; Katharina Mueller; Dirk Bassler; Stefan Schandelmaier; Stephen D Walter; Jason W Busse; Benjamin Kasenda; Gennaro Pagano; Hector Pardo-Hernandez; Victor M Montori; Zhen Wang; Matthias Briel

doi:10.1016/j.jclinepi.2016.10.006

Randomized trials addressing a similar question are commonly published after a trial stopped early for benefit

J Clin Epidemiol. 2017 Feb:82:12-19. doi: 10.1016/j.jclinepi.2016.10.006. Epub 2016 Nov 8.

Authors

M Hassan Murad¹, Gordon H Guyatt², Juan Pablo Domecq³, Robin W M Vernooij⁴, Patricia J Erwin⁵, Joerg J Meerpohl⁶, Gabriela J Prutsky⁷, Elie A Akl⁸, Katharina Mueller⁹, Dirk Bassler¹⁰, Stefan Schandelmaier¹¹, Stephen D Walter², Jason W Busse¹², Benjamin Kasenda¹³, Gennaro Pagano¹⁴, Hector Pardo-Hernandez⁴, Victor M Montori¹⁵, Zhen Wang¹⁶, Matthias Briel¹⁷

Affiliations

¹ 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.
² Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario L8S 4L8, Canada.
³ Department of Internal Medicine, Henry Ford Hospital, Detroit, MI, USA; Unidad de Conocimiento y Evidencia, CONEVID, UPCH, Lima, Peru.
⁴ Iberoamerican Cochrane Centre, Institute of Biomedical Research (IIB Sant Pau), Barcelona, Spain.
⁵ Mayo Clinic Libraries, Mayo Clinic, 200, 1st street, Rochester, MN 55905, USA.
⁶ Cochrane Germany, Medical Center-University of Freiburg, Berliner Allee 29, 79110 Freiburg, Germany.
⁷ Unidad de Conocimiento y Evidencia, CONEVID, UPCH, Lima, Peru; Department of Pediatrics, Children's Hospital of Michigan, Detroit, MI, USA.
⁸ Department of Internal Medicine, American University of Beirut, Beirut, Lebanon; Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
⁹ Center for Clinical Pediatric Studies, University Children's Hospital Tuebingen, Frondsbergstraße 23, 72070 Tuebingen, Germany.
¹⁰ Department of Neonatology, University Hospital Zurich and University of Zurich, Frauenklinikstrasse 10, 8091 Zurich, Switzerland.
¹¹ Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Switzerland.
¹² 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.
¹³ Basel Institute for Clinical Epidemiology; Department of Medicine, Royal Marsden Hospital, London, UK.
¹⁴ Federico II University of Naples, Naples, Italy.
¹⁵ Knowledge and Evaluation Research Unit, Mayo Clinic, 200, 1st street, Rochester, MN 55905, USA.
¹⁶ Evidence-Based Practice Center, Mayo Clinic, 200, 1st street, Rochester, MN 55905, USA.
¹⁷ Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Switzerland; Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario L8S 4L8, Canada.

PMID: 27832953
DOI: 10.1016/j.jclinepi.2016.10.006

Abstract

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.

Study design and setting: 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).

Conclusion: 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.

Keywords: Early termination of trials; Methodology; Randomized controlled trials; Systematic review; Trial design; Trials stopped early for benefit.

Publication types

Review
Systematic Review

MeSH terms

Databases, Factual / statistics & numerical data
Early Termination of Clinical Trials*
Epidemiologic Studies*
Humans
Publishing / statistics & numerical data*
Randomized Controlled Trials as Topic / statistics & numerical data*