We're unable to sign you in at this time. Please try again in a few minutes.
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Review |

Stopping Randomized Trials Early for Benefit and Estimation of Treatment Effects Systematic Review and Meta-regression Analysis

Dirk Bassler, MD, MSc; Matthias Briel, MD, MSc; Victor M. Montori, MD, MSc; Melanie Lane, BA; Paul Glasziou, MBBS, PhD; Qi Zhou, PhD; Diane Heels-Ansdell, MSc; Stephen D. Walter, PhD; Gordon H. Guyatt, MD, MSc; and the STOPIT-2 Study Group
JAMA. 2010;303(12):1180-1187. doi:10.1001/jama.2010.310.
Text Size: A A A
Published online

Context Theory and simulation suggest that randomized controlled trials (RCTs) stopped early for benefit (truncated RCTs) systematically overestimate treatment effects for the outcome that precipitated early stopping.

Objective To compare the treatment effect from truncated RCTs with that from meta-analyses of RCTs addressing the same question but not stopped early (nontruncated RCTs) and to explore factors associated with overestimates of effect.

Data Sources Search of MEDLINE, EMBASE, Current Contents, and full-text journal content databases to identify truncated RCTs up to January 2007; search of MEDLINE, Cochrane Database of Systematic Reviews, and Database of Abstracts of Reviews of Effects to identify systematic reviews from which individual RCTs were extracted up to January 2008.

Study Selection Selected studies were RCTs reported as having stopped early for benefit and matching nontruncated RCTs from systematic reviews. Independent reviewers with medical content expertise, working blinded to trial results, judged the eligibility of the nontruncated RCTs based on their similarity to the truncated RCTs.

Data Extraction Reviewers with methodological expertise conducted data extraction independently.

Results The analysis included 91 truncated RCTs asking 63 different questions and 424 matching nontruncated RCTs. The pooled ratio of relative risks in truncated RCTs vs matching nontruncated RCTs was 0.71 (95% confidence interval, 0.65-0.77). This difference was independent of the presence of a statistical stopping rule and the methodological quality of the studies as assessed by allocation concealment and blinding. Large differences in treatment effect size between truncated and nontruncated RCTs (ratio of relative risks <0.75) occurred with truncated RCTs having fewer than 500 events. In 39 of the 63 questions (62%), the pooled effects of the nontruncated RCTs failed to demonstrate significant benefit.

Conclusions Truncated RCTs were associated with greater effect sizes than RCTs not stopped early. This difference was independent of the presence of statistical stopping rules and was greatest in smaller studies.

Figures in this Article

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?


Place holder to copy figure label and caption
Figure 1. Selection Process for Study Inclusion
Graphic Jump Location

RCT indicates randomized controlled trial; RR, relative risk.

Place holder to copy figure label and caption
Figure 2. Pooled Ratio of Relative Risks (RRs) and 95% Confidence Intervals (CIs) for Truncated vs Nontruncated Randomized Controlled Trials (RCTs)
Graphic Jump Location

First column indicates number associated with the question addressed by each review that included 1 or more truncated and matching nontruncated RCTs. Results ordered by P values associated with results of nontruncated RCTs; size of the data markers indicates weight of review questions in meta-analysis.

Place holder to copy figure label and caption
Figure 3. Weighted Bubble Plot Showing the Ratio of Relative Risks (RRs) vs the Total Number of Outcome Events in Truncated Randomized Controlled Trials (RCTs)
Graphic Jump Location

The size of each bubble is proportional to the magnitude of the inverse of the variance of the ratio of RR in the log scale. The dashed line indicates a ratio of RR of 0.71; the dotted line, a ratio of RR of 1.00. The shaded areas numbered 1 through 3 correspond to different degrees of overestimates of effect (ratios of RRs, 0.05-0.5; 0.5-0.75; 0.75-1.00): in area 1, very large overestimation (ratio of RR, 0.37; 95% confidence interval [CI], 0.31-0.44; P < .001) occurred in truncated trials with fewer than 200 events. In area 2, large overestimation (ratio of RR, 0.65; 95% CI, 0.56-0.77; P < .001) occurred in truncated trials stopped between 200 and 500 events. In area 3, truncated trials with more than 500 events led to moderate overestimation (ratio of RR, 0.88; 95% CI, 0.80-0.96; P = .003).



Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.


Some tools below are only available to our subscribers or users with an online account.

176 Citations

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles