Evidence-appraisal glossary
Indirectness
Indirectness is the gap between the evidence you have and the question you are asking, for example when the studied patients, treatments, comparisons, or outcomes differ from the ones you care about. It is one of the reasons certainty in a body of evidence gets rated down.
Also called: applicability, directness.
Even well-conducted trials can be indirect: they may enroll a different population, measure a surrogate outcome instead of the one that matters to patients, compare against a treatment no longer in use, or require an indirect comparison because no head to head trial exists. In the GRADE framework, indirectness lowers confidence because applying such evidence to the real question demands an inferential leap. Spotting it means asking how closely the studies match the decision at hand, not just how rigorous they were.
This is a plain-language methodology definition for reading research. It is general education, not medical advice.