Skip to main content
Article
Stopping Randomized Trials Early for Benefit: A Protocol of the Study Of Trial Policy Of Interim Truncation-2 (STOPIT-2)
Trials
  • Matthias Briel, McMaster University
  • Melanie Lane, Knowledge and Encounter Research Unit, Mayo Clinic, Rochester, MN
  • Victor M. Montori, Knowledge and Encounter Research Unit, Mayo Clinic, Rochester, MN
  • Dirk Bassler, University Children's Hospital Tuebingen, Tuebingen, Germany
  • Paul Glasziou, University of Oxford
  • German Malaga, Universidad Peruana Cayetano Heredia
  • Elie A. Akl, State University of New York at Buffalo
  • Ignacio Ferreira-Gonzalez, Vall d'Hebron Hospital, Spain
  • Pablo Alonso-Coello, Hospital Sant Pau, Barcelona, Spain
  • Gerard Urrutia, Hospital Sant Pau, Barcelona, Spain
  • Regina Kunz, University Hospital Basel, Basel, Switzerland
  • Carolina Ruiz Culebro, McMaster University
  • Suzana Alves da Silva, Teaching and Research Center of Pro-Cardiaco, Rio de Janeiro, Brazil
  • David N. Flynn, Knowledge and Encounter Research Unit, Mayo Clinic, Rochester, MN
  • Mohamed B. Elamin, Knowledge and Encounter Research Unit, Mayo Clinic, Rochester, MN
  • Brigitte Strahm, University Hospital Freiburg, Freiburg, Germany
  • M. Hassan Murad, Knowledge and Encounter Research Unit, Mayo Clinic, Rochester, MN
  • Benjamin Djulbegovic, USF Health Clinical Research, Tampa, FL
  • Neill K. J. Adhikari, University of Toronto
  • Edward J. Mills, University of British Columbia
  • Femida Gwadry-Sridhar, University of Western Ontario
  • Haresh Kirpalani, McMaster University
  • Heloisa P. Soares, Mount Sinai Medical Center, Miami Beach, FL
  • Nisrin O. Abu Elnour, Knowledge and Encounter Research Unit, Mayo Clinic, Rochester, MN
  • John J. You, McMaster University
  • Paul J. Karanicolas, University of Western Ontario
  • Heiner C. Bucher, University Hospital Basel, Basel, Switzerland
  • Julianna F. Lampropulos, Knowledge and Encounter Research Unit, Mayo Clinic, Rochester, MN
  • Alain J. Nordmann, University Hospital Basel, Basel, Switzerland
  • Karen E. A. Burns, University of Toronto
  • Sohail M. Mulla, McMaster University
  • Heike Raatz, University Hospital Basel, Basel, Switzerland
  • Amit Sood, Knowledge and Encounter Research Unit, Mayo Clinic, Rochester, MN
  • Jagdeep Kaur, McMaster University
  • Clare R. Bankhead, University of Oxford
  • Rebecca J. Mullan, Knowledge and Encounter Research Unit, Mayo Clinic, Rochester, MN
  • Kara A. Nerenberg, McMaster University
  • Per Olav Vandvik, Innlandet Hospital Health Authority, Norway
  • Fernando Coto-Yglesias, Hospital Nacional de Geriatría y Gerontología San José, Costa Rica
  • Holger Schünemann, McMaster University
  • Fabio Tuche, Teaching and Research Center of Pro-Cardiaco, Rio de Janeiro, Brazil
  • Pedro Paulo M. Chrispim, National School of Public Health (ENSP), Rio de Janeiro, Brazil
  • Deborah J. Cook, McMaster University
  • Kristina Lutz, McMaster University
  • Christine M. Ribic, McMaster University
  • Noah Vale, McMaster University
  • Patricia J. Erwin, Knowledge and Encounter Research Unit, Mayo Clinic, Rochester, MN
  • Rafael Perera, University of Oxford
  • Qi Zhou, McMaster University
  • Diane Heels-Ansdell, McMaster University
  • Tim Ramsay, University of Ottawa
  • Stephen D. Walter, McMaster University
  • Gordon H. Guyatt, McMaster University
Document Type
Article
Publication Date
7-6-2009
URL with Digital Object Identifier
http://dx.doi.org/10.1186/1745-6215-10-49
Abstract
Background: Randomized clinical trials (RCTs) stopped early for benefit often receive great attention and affect clinical practice, but pose interpretational challenges for clinicians, researchers, and policy makers. Because the decision to stop the trial may arise from catching the treatment effect at a random high, truncated RCTs (tRCTs) may overestimate the true treatment effect. The Study Of Trial Policy Of Interim Truncation (STOPIT-1), which systematically reviewed the epidemiology and reporting quality of tRCTs, found that such trials are becoming more common, but that reporting of stopping rules and decisions were often deficient. Most importantly, treatment effects were often implausibly large and inversely related to the number of the events accrued. The aim of STOPIT-2 is to determine the magnitude and determinants of possible bias introduced by stopping RCTs early for benefit. Methods/Design: We will use sensitive strategies to search for systematic reviews addressing the same clinical question as each of the tRCTs identified in STOPIT-1 and in a subsequent literature search. We will check all RCTs included in each systematic review to determine their similarity to the index tRCT in terms of participants, interventions, and outcome definition, and conduct new meta-analyses addressing the outcome that led to early termination of the tRCT. For each pair of tRCT and systematic review of corresponding non-tRCTs we will estimate the ratio of relative risks, and hence estimate the degree of bias. We will use hierarchical multivariable regression to determine the factors associated with the magnitude of this ratio. Factors explored will include the presence and quality of a stopping rule, the methodological quality of the trials, and the number of total events that had occurred at the time of truncation.Finally, we will evaluate whether Bayesian methods using conservative informative priors to "regress to the mean" overoptimistic tRCTs can correct observed biases. Discussion: A better understanding of the extent to which tRCTs exaggerate treatment effects and of the factors associated with the magnitude of this bias can optimize trial design and data monitoring charters, and may aid in the interpretation of the results from trials stopped early for benefit.
Citation Information
Matthias Briel, Melanie Lane, Victor M. Montori, Dirk Bassler, et al.. "Stopping Randomized Trials Early for Benefit: A Protocol of the Study Of Trial Policy Of Interim Truncation-2 (STOPIT-2)" Trials Vol. 10 Iss. 49 (2009)
Available at: http://works.bepress.com/paul_glasziou/11/