title: 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.
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
  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.
  
  
  CONCLUSIONS
  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.
authors.forename: Gabriela J
authors.initials: GJ
authors.lastname: Prutsky
authors.affiliation: Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN 55905, USA. jpdomecq@gmail.com.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Domecq
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Erwin
authors.forename: Matthias
authors.initials: M
authors.lastname: Briel
authors.forename: Victor M
authors.initials: VM
authors.lastname: Montori
authors.forename: Elie A
authors.initials: EA
authors.lastname: Akl
authors.forename: Joerg J
authors.initials: JJ
authors.lastname: Meerpohl
authors.forename: Dirk
authors.initials: D
authors.lastname: Bassler
authors.forename: Stefan
authors.initials: S
authors.lastname: Schandelmaier
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Walter
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.forename: Pablo Alonso
authors.initials: PA
authors.lastname: Coello
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moja
authors.forename: Martin
authors.initials: M
authors.lastname: Walter
authors.forename: Kristian
authors.initials: K
authors.lastname: Thorlund
authors.forename: Paul
authors.initials: P
authors.lastname: Glasziou
authors.forename: Regina
authors.initials: R
authors.lastname: Kunz
authors.forename: Ignacio
authors.initials: I
authors.lastname: Ferreira-Gonzalez
authors.forename: Jason
authors.initials: J
authors.lastname: Busse
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
authors.forename: Annette
authors.initials: A
authors.lastname: Kristiansen
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kasenda
authors.forename: Osama
authors.initials: O
authors.lastname: Qasim-Agha
authors.forename: Gennaro
authors.initials: G
authors.lastname: Pagano
authors.forename: Hector
authors.initials: H
authors.lastname: Pardo-Hernandez
authors.forename: Gerard
authors.initials: G
authors.lastname: Urrutia
authors.forename: Mohammad Hassan
authors.initials: MH
authors.lastname: Murad
authors.forename: Gordon
authors.initials: G
authors.lastname: Guyatt
mesh_terms: D057239:Early Termination of Clinical Trials / Q000941:ethics; D019317:Evidence-Based Medicine / Q000941:ethics; D006801:Humans; D033181:Information Dissemination; D010506:Periodicals as Topic; D016032:Randomized Controlled Trials as Topic / Q000941:ethics / Q000379:methods*; D012107:Research Design; D013997:Time Factors