How do I assess indirectness when trial settings differ from my patient population?

Assess indirectness by comparing the trial's setting, care pathway, and baseline risk with your population, then record a stated decision on whether the mismatch warrants a GRADE certainty downgrade. GRADE rates certainty of evidence with explicit criteria and outcome-level judgements, so the indirectness judgement belongs at the outcome level and should be written down with its reasons.

Build the comparison

1. Extract the trial's setting, eligibility criteria, locations, and care pathway from the registration and results fields, such as those defined by ClinicalTrials.gov for design, eligibility, locations, and outcomes. Expected result: a short profile of who was studied and how care was delivered.
2. Compare that profile with your population on the three axes in the brief: setting, care pathway, and baseline risk. Expected result: a list of specific differences, each tied to a trial feature and a feature of your patients.
3. Judge each difference at the outcome level, asking whether it would plausibly change the effect for that outcome. Expected result: a per-outcome note of which differences matter and which are minor.
4. Decide whether the mismatch is serious enough to downgrade certainty for that outcome, and state the reasons. Expected result: an indirectness note with an explicit downgrade decision and its justification.

What changes the decision

A difference in baseline risk can change the absolute effect even when the relative effect holds, so report absolute effects alongside relative ones when interpreting applicability, as the Cochrane Handbook Chapter 15 guidance on absolute and relative effects and applicability describes. A care pathway difference matters when the trial's comparator or co-interventions differ from what your patients receive. A setting difference matters when it changes who is treated or how outcomes are ascertained.

Write the note

Record the outcome, the trial feature, the population feature, the direction of the mismatch, and the downgrade decision. Keep the note short enough to attach to a GRADE evidence table and specific enough that a second reviewer can see which comparison drove the judgement.