Learning from failure - rationale and design for a study about discontinuation of randomized trials (DISCO study)

BMC Medical Research Methodology

Matthias Briel⁸  Gordon H Guyatt⁸  Heiner C Bucher¹  Matthias Schwenkglenks^1,16  Bernard Burnand⁴  Martin A Walter⁷  Bradley C Johnston³  Per O Vandvik^1,17  Xin Sun^1,11  Stefan Schandelmaier^1,10  Rachel Rosenthal^1,13  Alain Nordmann¹  Francois Lamontagne⁶  Ignacio Ferreira-González^1,12  Jason W Busse⁸  Dirk Bassler⁹  Elie A Akl^1,14  Dominik Mertz⁸  Sohail Mulla⁸  Markus Faulhaber⁸  Alonso Carrasco-Labra⁸  Ignacio Neumann⁸  Kari A O Tikkinen²  Mihaela Stegert¹  Jörg Meerpohl⁵  Theresa Bengough⁴  Alain Amstutz¹  Ramon Saccilotto¹  Yuki Tomonaga^1,16  Anette Blümle⁵  John You^1,15  Erik B von Elm⁵  Benjamin Kasenda¹ 

[1] Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Hebelstrasse 10, 4031, Basel, Switzerland;Department of Urology, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland;Department of Anesthesia & Pain Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada;Cochrane Switzerland, Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Lausanne, Switzerland;German Cochrane Centre, Institute of Medical Biometry and Medical Informatics, University Medical Centre Freiburg, Freiburg, Germany;Centre de Recherche Clinique Étienne-Le Bel and Department of Medicine, Université de Sherbrooke, Sherbrooke, Quebec, Canada;Department of Nuclear Medicine, University Hospital Bern, Bern, Switzerland;Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada;Department of Neonatology and Center for Pediatric Clinical Studies, University Children’s Hospital Tübingen, Tübingen, Germany;Academy of Swiss Insurance Medicine, University Hospital Basel, Basel, Switzerland;Center for Health Research, Kaiser Permanente Northwest, Portland, OR, USA;Epidemiology Unit, Department of Cardiology, Vall d'Hebron Hospital and CIBER de Epidemiología y Salud Publica (CIBERESP), Barcelona, Spain;Department of Surgery, University Hospital Basel, Basel, Switzerland;Departments of Medicine and Family Medicine, State University of New York at Buffalo, Buffalo, NY, USA;Department of Medicine, McMaster University, Hamilton, Ontario, Canada;Institute for Social and Preventive Medicine, Zurich, Switzerland;Norwegian Knowledge Centre for the Health Services, Oslo, Norway

关键词: Trial protocols;    Ethics committees;    Slow recruitment;    Trial discontinuation;    Randomized controlled trial;   

Others  :  1126881
DOI  :  10.1186/1471-2288-12-131

 received in 2012-07-23, accepted in 2012-08-01,  发布年份 2012

【 摘 要 】

Background

Randomized controlled trials (RCTs) may be discontinued because of apparent harm, benefit, or futility. Other RCTs are discontinued early because of insufficient recruitment. Trial discontinuation has ethical implications, because participants consent on the premise of contributing to new medical knowledge, Research Ethics Committees (RECs) spend considerable effort reviewing study protocols, and limited resources for conducting research are wasted. Currently, little is known regarding the frequency and characteristics of discontinued RCTs.

Methods/Design

Our aims are, first, to determine the prevalence of RCT discontinuation for specific reasons; second, to determine whether the risk of RCT discontinuation for specific reasons differs between investigator- and industry-initiated RCTs; third, to identify risk factors for RCT discontinuation due to insufficient recruitment; fourth, to determine at what stage RCTs are discontinued; and fifth, to examine the publication history of discontinued RCTs.

We are currently assembling a multicenter cohort of RCTs based on protocols approved between 2000 and 2002/3 by 6 RECs in Switzerland, Germany, and Canada. We are extracting data on RCT characteristics and planned recruitment for all included protocols. Completion and publication status is determined using information from correspondence between investigators and RECs, publications identified through literature searches, or by contacting the investigators. We will use multivariable regression models to identify risk factors for trial discontinuation due to insufficient recruitment. We aim to include over 1000 RCTs of which an anticipated 150 will have been discontinued due to insufficient recruitment.

Discussion

Our study will provide insights into the prevalence and characteristics of RCTs that were discontinued. Effective recruitment strategies and the anticipation of problems are key issues in the planning and evaluation of trials by investigators, Clinical Trial Units, RECs and funding agencies. Identification and modification of barriers to successful study completion at an early stage could help to reduce the risk of trial discontinuation, save limited resources, and enable RCTs to better meet their ethical requirements.

【 授权许可】

   
2012 Kasenda et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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