EBM Critical Appraisal Articles

This is a collection of papers that I found useful when trying to understand how to critically appraise papers.

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:

  • Does a P value of <0.05 provide strong enough evidence?
  • 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?

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 sister article the one above. Here, they address 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?

Ridgeon EE, Young PJ, Bellomo R, Mucchetti M, Lembo R, Landoni G. The Fragility Index in Multicenter Randomized Controlled Critical Care Trials. Critical care medicine. 44(7):1278-84. 2016. PMID: 26963326

This paper covers the fragility index: an important statistical test when there are small numbers of events in trials. The Fragility Index is the minimum number of patients whose status would have to change from a nonevent to an event that is required to turn a statistically significant result to a nonsignificant result