Primary outcome is positive – is that good enough?

Pocock SJ, Stone GW. The Primary Outcome Is Positive – Is That Good Enough? The New England journal of medicine. 375(10):971-9. 2016. PMID: 27602669 [free full text]

The key questions to ask when a trials primary outcome is positive:

  • Is a P value less than 0.05 good enough?
  • What is the magnitude of the treatment benefit?
  • Is the primary outcome clinically important (and internally consistent)?
  • Are secondary outcomes supportive?
  • Are the principal findings consistent across important subgroups?
  • Is the trial large enough to be convincing?
  • Was the trial stopped early?
  • Do concerns about safety counterbalance positive efficacy?
  • Is the efficacy–safety balance patient-specific?
  • Are there flaws in trial design and conduct?
  • Do the findings apply to my patients?