Stopping clinical trials early for futility: retrospective analysis of several randomised clinical studies

Br J Cancer. 2012 Sep 4;107(6):910-7. doi: 10.1038/bjc.2012.344. Epub 2012 Aug 9.


Background: Many clinical trials show no overall benefit. We examined futility analyses applied to trials with different effect sizes.

Methods: Ten randomised cancer trials were retrospectively analysed; target sample size reached in all. The hazard ratio indicated no overall benefit (n=5), or moderate (n=4) or large (n=1) treatment effects. Futility analyses were applied after 25, 50 and 75% of events were observed, or patients were recruited. Outcomes were conditional power (CP), and time and cost savings.

Results: Futility analyses could stop some trials with no benefit, but not all. After observing 50% of the target number of events, 3 out of 5 trials with no benefit could be stopped early (low CP ≤ 15%). Trial duration for two studies could be reduced by 4-24 months, saving £44 000-231 000, but the third had already stopped recruiting, hence no savings were made. However, of concern was that 2 of the 4 trials with moderate treatment effects could be stopped early at some point, although they eventually showed worthwhile benefits.

Conclusions: Careful application of futility can lead to future patients in a trial not being given an ineffective treatment, and should therefore be used more often. A secondary consideration is that it could shorten trial duration and reduce costs. However, studies with modest treatment effects could be inappropriately stopped early. Unless there is very good evidence for futility, it is often best to continue to the planned end.

MeSH terms

  • Clinical Trials, Phase II as Topic / economics
  • Clinical Trials, Phase II as Topic / statistics & numerical data
  • Early Termination of Clinical Trials*
  • Humans
  • Medical Futility*
  • Neoplasms / drug therapy*
  • Neoplasms / radiotherapy*
  • Odds Ratio
  • Patient Selection
  • Randomized Controlled Trials as Topic* / economics
  • Randomized Controlled Trials as Topic* / statistics & numerical data
  • Research Design
  • Retrospective Studies
  • Treatment Outcome