Compare each trial's eligibility criteria, baseline characteristics, and setting with your review question, then write a short applicability note stating which population differences could change the direction or size of the effect. Cochrane's guidance on interpreting results treats applicability as a judgement about how closely the evidence matches your review's population, intervention, and setting, so the note should name the specific mismatch and its likely consequence.
- Restate your review question's population in concrete terms: the condition, the defining participant characteristics, and any exclusions. This gives you a fixed reference for every comparison.
- Pull the trial's eligibility criteria from its registration record. ClinicalTrials.gov defines structured fields for eligibility, design, locations, and outcomes, so use those fields to list who was included and excluded, then mark any criterion that narrows the population beyond your question.
- Compare baseline characteristics across arms and against your population. Look for differences in severity, age, comorbidity, or prior treatment that could shift the baseline risk and therefore the absolute effect.
- Check the setting: care level, country, and delivery context recorded in the locations field. A trial run in a different care system may produce a different absolute effect even when the relative effect holds.
- Write the applicability note as a short table or paragraph per trial: the population difference, whether it plausibly changes direction or size, and your resulting judgement of indirectness.
GRADE's approach rates certainty at the outcome level using explicit criteria, and indirectness is one of those criteria, so record your population judgement per outcome rather than once for the whole review. Where a difference is plausible but untested, describe it as an open question and note what evidence would resolve it.