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

FOAM and web resources


CCC 700 6

Critical Care

Compendium

Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also the Innovation Lead for the Australian Centre for Health Innovation at Alfred Health and Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of two amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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