Table 2.

A checklist for using mechanisms to justify extrapolation of study results to target populations

Question	Y/N
Is the mechanism of action supported by evidence?
Are the mechanisms of action in study and target populations shared?
Even if shared, are the mechanisms of action likely to behave differently (paradoxically)?
Have we established that the mechanisms of action in the study and target populations are relevantly similar?

If the answer to all these questions is ‘Yes’, then extrapolation may be justified. Otherwise, extrapolation may be risky