Primary outcome fails – what next?

Pocock SJ, Stone GW. The Primary Outcome Fails – What Next? The New England journal of medicine. 375(9):861-70. 2016. PMID: 27579636 [free full text]

The key questions to ask when the primary outcome is negative:

  • Is there some indication of potential benefit?
  • Was the trial underpowered?
  • Was the primary outcome appropriate (or accurately defined)?
  • Was the population appropriate?
  • Was the treatment regimen appropriate?
  • Were there deficiencies in trial conduct?
  • Is a claim of noninferiority of value?
  • Do subgroup findings elicit positive signals?
  • Do secondary outcomes reveal positive findings?
  • Can alternative analyses help?
  • Does more positive external evidence exist?
  • Is there a strong biologic rationale that favors the treatment?