Table 2.

Problems with mechanistic reasoning

Problem		Example
1. Problems with the mechanism	1a. Mechanism derived from a fanciful theory	Blood-letting
	1b. Mechanism sounds plausible but has no supporting evidence	Dr Spock's advice to place babies to sleep on their stomachs to reduce SIDS
	1c. Mechanism is partially supported by evidence, but some factors are ignored	Antiarrhythmic drug example (see text)
2. Problems with the inference from the mechanism to the conclusion of efficacy	2a. Failure to consider the probabilistic nature of the mechanism	Antiarrhythmic drug mechanism
	2b. Failure to consider the complexity of the mechanisms (including failure to consider mechanisms that might produce adverse events)	Paradoxical responses