Initiation and continuation of randomized trials after the publication of a trial stopped early for benefit asking the same study question: STOPIT-3 study design

Authors

Gabriela J. Prutsky, Knowledge and Evaluation Research Unit, Mayo ClinicFollow
Juan Domecq, Knowledge and Evaluation Research Unit, Mayo ClinicFollow
Patricia J. Erwin, Knowledge and Evaluation Research Unit, Mayo ClinicFollow
Matthias Briel, Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital BaselFollow
Victor M. Montori, Knowledge and Evaluation Research Unit, Mayo ClinicFollow
Elie A. Akl, McMaster UniversityFollow
Joerg J. Meerpohl, German Cochrane Centre, Institute of Medical Biometry and Medical Informatics, University Medical Center FreiburgFollow
Dirk Bassler, Center for Pediatric Clinical Studies, University Children’s Hospital TuebingenFollow
Stefan Schandelmaier, Academy of Swiss Insurance Medicine, University Hospital BaselFollow
Stephen D. Walter, McMaster UniversityFollow
Qi Zhou, McMaster UniversityFollow
Pablo Coello, Iberoamerican Cochrane Center, CIBER de Epidemiología y Salud PúblicaFollow
Lorenzo Moja, University of MilanFollow
Martin Walter, University Hospital BernFollow
Kristian Thorlund, McMaster UniversityFollow
Paul Glasziou, University of OxfordFollow
Regina Kunz, Academy of Swiss Insurance Medicine, University Hospital BaseFollow
Ignacio Ferreira-Gonzalez, Vall d’Hebron Hospital and CIBER de Epidemiología y Salud Publica (CIBERESP)Follow
Jason Busse, McMaster UniversityFollow
Xin Sun, Center for Health Research, Kaiser Permanente NorthwestFollow
Annette Kristiansen, Norwegian Knowledge Centre for the Health ServicesFollow
Benjamin Kasenda, Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital BaselFollow
Osama Qasim-Agha, Knowledge and Evaluation Research Unit, Mayo ClinicFollow
Gennaro Pagano, Federico II University of NaplesFollow
Hector Pardo-Hernandez, Iberoamerican Cochrane Center, CIBER de Epidemiología y Salud PúblicaFollow
Gerard Urrutia, Epidemiology and Public Health CIBER (CIBERESP), Hospital de la Sant Pau Creu iFollow
Mohammad Murad, Knowledge and Evaluation Research Unit, Mayo ClinicFollow
Gordon Guyatt, McMaster UniversityFollow

Document Type

Article

Abstract

Abstract

Background

Randomized control trials (RCTs) stopped early for benefit (truncated RCTs) are increasingly common and, on average, overestimate the relative magnitude of benefit by approximately 30%. Investigators stop trials early when they consider it is no longer ethical to enroll patients in a control group. The goal of this systematic review is to determine how investigators of ongoing or planned RCTs respond to the publication of a truncated RCT addressing a similar question.

Methods/design

We will conduct systematic reviews to update the searches of 210 truncated RCTs to identify similar trials ongoing at the time of publication, or started subsequently, to the truncated trials ('subsequent RCTs’). Reviewers will determine in duplicate the similarity between the truncated and subsequent trials. We will analyze the epidemiology, distribution, and predictors of subsequent RCTs. We will also contact authors of subsequent trials to determine reasons for beginning, continuing, or prematurely discontinuing their own trials, and the extent to which they rely on the estimates from truncated trials.

Discussion

To the extent that investigators begin or continue subsequent trials they implicitly disagree with the decision to stop the truncated RCT because of an ethical mandate to administer the experimental treatment. The results of this study will help guide future decisions about when to stop RCTs early for benefit.

Disciplines

Design of Experiments and Sample Surveys

Recommended Citation

Prutsky et al.: Initiation and continuation of randomized trials after the publication of a trial stopped early for benefit asking the same study question: STOPIT-3 study design. Trials 2013 14:335.