title: Randomized trials stopped early for benefit: a systematic review.
abstract: BACKGROUND
  Randomized clinical trials (RCTs) that stop earlier than planned because of apparent benefit often receive great attention and affect clinical practice. Their prevalence, the magnitude and plausibility of their treatment effects, and the extent to which they report information about how investigators decided to stop early are, however, unknown.
  
  
  OBJECTIVE
  To evaluate the epidemiology and reporting quality of RCTs involving interventions stopped early for benefit.
  
  
  METHODS
  Systematic review up to November 2004 of MEDLINE, EMBASE, Current Contents, and full-text journal content databases to identify RCTs stopped early for benefit.
  
  
  METHODS
  Randomized clinical trials of any intervention reported as having stopped early because of results favoring the intervention. There were no exclusion criteria.
  
  
  METHODS
  Twelve reviewers working independently and in duplicate abstracted data on content area and type of intervention tested, reporting of funding, type of end point driving study termination, treatment effect, length of follow-up, estimated sample size and total sample studied, role of a data and safety monitoring board in stopping the study, number of interim analyses planned and conducted, and existence and type of monitoring methods, statistical boundaries, and adjustment procedures for interim analyses and early stopping.
  
  
  RESULTS
  Of 143 RCTs stopped early for benefit, the majority (92) were published in 5 high-impact medical journals. Typically, these were industry-funded drug trials in cardiology, cancer, and human immunodeficiency virus/AIDS. The proportion of all RCTs published in high-impact journals that were stopped early for benefit increased from 0.5% in 1990-1994 to 1.2% in 2000-2004 (P<.001 for trend). On average, RCTs recruited 63% (SD, 25%) of the planned sample and stopped after a median of 13 (interquartile range [IQR], 3-25) months of follow-up, 1 interim analysis, and when a median of 66 (IQR, 23-195) patients had experienced the end point driving study termination (event). The median risk ratio among truncated RCTs was 0.53 (IQR, 0.28-0.66). One hundred thirty-five (94%) of the 143 RCTs did not report at least 1 of the following: the planned sample size (n = 28), the interim analysis after which the trial was stopped (n = 45), whether a stopping rule informed the decision (n = 48), or an adjusted analysis accounting for interim monitoring and truncation (n = 129). Trials with fewer events yielded greater treatment effects (odds ratio, 28; 95% confidence interval, 11-73).
  
  
  CONCLUSIONS
  RCTs stopped early for benefit are becoming more common, often fail to adequately report relevant information about the decision to stop early, and show implausibly large treatment effects, particularly when the number of events is small. These findings suggest clinicians should view the results of such trials with skepticism.
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Victor M
authors.initials: VM
authors.lastname: Montori
authors.forename: P J
authors.initials: PJ
authors.lastname: Devereaux
authors.forename: Neill K J
authors.initials: NK
authors.lastname: Adhikari
authors.forename: Karen E A
authors.initials: KE
authors.lastname: Burns
authors.forename: Christoph H
authors.initials: CH
authors.lastname: Eggert
authors.forename: Matthias
authors.initials: M
authors.lastname: Briel
authors.forename: Christina
authors.initials: C
authors.lastname: Lacchetti
authors.forename: Teresa W
authors.initials: TW
authors.lastname: Leung
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Darling
authors.forename: Dianne M
authors.initials: DM
authors.lastname: Bryant
authors.forename: Heiner C
authors.initials: HC
authors.lastname: Bucher
authors.forename: Holger J
authors.initials: HJ
authors.lastname: Schünemann
authors.forename: Maureen O
authors.initials: MO
authors.lastname: Meade
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Cook
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Erwin
authors.forename: Amit
authors.initials: A
authors.lastname: Sood
authors.forename: Richa
authors.initials: R
authors.lastname: Sood
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lo
authors.forename: Carly A
authors.initials: CA
authors.lastname: Thompson
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.forename: Edward
authors.initials: E
authors.lastname: Mills
authors.forename: Gordon H
authors.initials: GH
authors.lastname: Guyatt
mesh_terms: D026661:Clinical Trials Data Monitoring Committees; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome