In yesterday's first lesson of the mini- series, I presented the 5 domains GRADE uses to rate down your confidence in the quality of evidence derived from Randomized Controlled Trial studies (RCTs). Perhaps you've correctly surmised that GRADE starts RCT evidence at the highest level and then subtracts, or downgrades, for insufficiencies in that evidence for each specific outcome. 

Those 5 domains for downgrading are:

  1. Risk of bias = limitations in the design and conduct of the studies that impact validity
  2. Inconsistency = lack of reproducibility of the effect across multiple studies
  3. Indirectness = in any of the PICO elements; if tested in population that differs from the one of interest, if difference in the intervention itself, or use of surrogate outcomes
  4. Imprecision = when confidence intervals around the effect estimate include both benefit and harm and impact the clinical decision threshold
  5. Publication bias = difficult to assess, but GRADE provides some indicators for suspicion that positive studies have been selectively published for the topic

Are you wondering how the downgrading works? The starting point for RCT evidence is an overall rating of High, which is the highest rating possible under the GRADE approach.

Each domain can be downgraded by 1 or 2 levels depending on the seriousness of the deficiency. 

Each domain is considered equal.

So if the evidence is downgraded by one level for risk of bias and one level for inconsistency it would go from a rating of High to Low.

The rating levels in the GRADE approach are:

  • High
  • Moderate
  • Low 
  • Very low

So after being downgraded by 3 levels, the evidence rating cannot be further reduced.

Tomorrow I'll show you how to interpret these levels. Unless, of course you can't wait to find out. You know where to go for the answers - the official GRADE handbook

TheEvidenceDoc November 9, 2017