Early Stopping of Trials
Reviewed and revised 26 August 2015
OVERVIEW
Clinical trials are planned to stop when one of the following is reached
- sample size
- event count
- length of follow up goal
- scheduled date of closure
Unplanned early stopping of trials may occur for a number of reasons (e.g. lack of funding, failure to recruit participants), which may affect the internal validity of the study
INTERIM ANALYSIS
- should be planned a priori
- ideally involve an independent data monitoring committee
- multiple statistical examinations of accumulating data without appropriate correction can lead to erroneous results and interpretations, this must be corrected for (e.g. if five interim analyses that use a P value of 0.05 are performed, the overall false positive rate is nearer to 19% than to the nominal 5%)
REASONS FOR EARLY STOPPING
- interim analysis showing larger than expected benefit or harm from an intervention
- futility (evidence of no important difference between experimental and control interventions)
- trial becomes non-viable (e.g. funding vanishes, researchers cannot access eligible patients or study interventions, or other studies make the research question irrelevant)
CONSEQUENCES
- Full reporting of why a trial ended is important for evidence based decision making
- Trials that stop early for reasons apparently independent of trial findings, and trials that reach their planned termination, are unlikely to introduce bias by stopping
References and Links
LITFL
- CCC — How to conduct a clinical trial
- CCC — Early stopping of clinical trial
- CCC — How to analyse a clinical trial
FOAM and web resources
- CONSORT Statement — Early Stopping and Reason for stopped trial
Critical Care
Compendium
Chris is an Intensivist and ECMO specialist at The Alfred ICU, where he is Deputy Director (Education). He is a Clinical Adjunct Associate Professor at Monash University, the Lead for the Clinician Educator Incubator programme, and a CICM First Part Examiner.
He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives. He was one of the founders of the FOAM movement (Free Open-Access Medical education) has been recognised for his contributions to education with awards from ANZICS, ANZAHPE, and ACEM.
His one great achievement is being the father of three amazing children.
On Bluesky, he is @precordialthump.bsky.social and on the site that Elon has screwed up, he is @precordialthump.
| INTENSIVE | RAGE | Resuscitology | SMACC