The text below is taken from the GRADE workinggroup official JCE series, article number 8:
GRADE guidelines: 8. Rating the quality of evidence—indirectness
Four types of indirectness
We are more confident in the results when we have direct evidence. By direct evidence, we mean research that directly compares the interventions in which we are interested delivered to the populations in which we are interested and measures the outcomes important to patients. Thus, we can have concerns about indirectness when the population, intervention, or outcomes differ from those in which we are interested. A fourth, different type of indirectness, occurs when there are no head-to-head comparisons between the alternative management strategies under comparison. Indirectness of outcomes and indirect comparisons are equally relevant to systematic reviews and practice guidelines; indirectness related to populations and interventions (sometimes referred to as applicability) is more relevant to guidelines.
Question of interest: Colonoscopic screening for prevention of colon cancer mortality
Question of interest: Sevelamer- vs. calcium-based phosphate binders in chronic renal failure
Question of interest: Choice of antidepressant
Source of indirectness: Indirect comparison: Some antidepressants have been compared directly with others, but many have not
Indirectness: differences in outcome measures (surrogate outcomes)
GRADE specifies that both those conducting systematic reviews and those developing practice guidelines should begin by specifying every important outcome of interest. The available studies may have measured the impact of the intervention of interest on outcomes related to, but different from, those of primary importance to patients.
Table 2. Examples of surrogate outcomes
See the Assessing Indirectness Training video from McMaster CE&B GRADE site: http://cebgrade.mcmaster.ca/Indirectness/index.html