Table 2

A suggested hierarchy of evidence for mechanistic evidence (drawing partly on previous publications)12 14

Level 1 (strongest)Necessary and sufficient conditions for causality (eg, multiple features of the causal chain) supported by multiple independent studies, confirmed by multiple independent research groups using accepted best research methods. No high-quality disconfirming studies found.
Level 2Indicators of causality (eg, more than one feature of the causal chain) supported, especially if by more than one method and confirmed by independent studies. No high-quality disconfirming studies found.
Level 3Suggestion of causality (eg, one feature of the causal chain) supported by multiple independent studies. No high-quality disconfirming studies found.
Level 4Sparse evidence supporting feature(s) of the causal chain. Disconfirming studies found but these are not definitive.
Level 5 (weakest)No supporting studies. High-quality disconfirming studies found.