title: Learning from failure--rationale and design for a study about discontinuation of randomized trials (DISCO study).
abstract: 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
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kasenda
authors.forename: Erik B
authors.initials: EB
authors.lastname: von Elm
authors.forename: John
authors.initials: J
authors.lastname: You
authors.forename: Anette
authors.initials: A
authors.lastname: Blümle
authors.forename: Yuki
authors.initials: Y
authors.lastname: Tomonaga
authors.forename: Ramon
authors.initials: R
authors.lastname: Saccilotto
authors.forename: Alain
authors.initials: A
authors.lastname: Amstutz
authors.forename: Theresa
authors.initials: T
authors.lastname: Bengough
authors.forename: Jörg
authors.initials: J
authors.lastname: Meerpohl
authors.forename: Mihaela
authors.initials: M
authors.lastname: Stegert
authors.forename: Kari A O
authors.initials: KA
authors.lastname: Tikkinen
authors.forename: Ignacio
authors.initials: I
authors.lastname: Neumann
authors.forename: Alonso
authors.initials: A
authors.lastname: Carrasco-Labra
authors.forename: Markus
authors.initials: M
authors.lastname: Faulhaber
authors.forename: Sohail
authors.initials: S
authors.lastname: Mulla
authors.forename: Dominik
authors.initials: D
authors.lastname: Mertz
authors.forename: Elie A
authors.initials: EA
authors.lastname: Akl
authors.forename: Dirk
authors.initials: D
authors.lastname: Bassler
authors.forename: Jason W
authors.initials: JW
authors.lastname: Busse
authors.forename: Ignacio
authors.initials: I
authors.lastname: Ferreira-González
authors.forename: Francois
authors.initials: F
authors.lastname: Lamontagne
authors.forename: Alain
authors.initials: A
authors.lastname: Nordmann
authors.forename: Rachel
authors.initials: R
authors.lastname: Rosenthal
authors.forename: Stefan
authors.initials: S
authors.lastname: Schandelmaier
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
authors.forename: Per O
authors.initials: PO
authors.lastname: Vandvik
authors.forename: Bradley C
authors.initials: BC
authors.lastname: Johnston
authors.forename: Martin A
authors.initials: MA
authors.lastname: Walter
authors.forename: Bernard
authors.initials: B
authors.lastname: Burnand
authors.forename: Matthias
authors.initials: M
authors.lastname: Schwenkglenks
authors.forename: Heiner C
authors.initials: HC
authors.lastname: Bucher
authors.forename: Gordon H
authors.initials: GH
authors.lastname: Guyatt
authors.forename: Matthias
authors.initials: M
authors.lastname: Briel
mesh_terms: D028744:Ethics Committees, Research; D006801:Humans; D007258:Informed Consent; D018579:Patient Selection; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D012307:Risk Factors; D017211:Treatment Failure