 A controversial issue is the role of mechanistic knowledge, that is, knowledge about the biological and physiological mechanisms responsible for medical outcomes (and thus treatment efficacy) should play in EBM. As mentioned above, the RCT provides evidence for black-box causal claims of the form “In population p, intervention X is effective in the treatment of condition Y”. As we have seen, proponents of EBM also believe EBM to de-emphasize patho-physiologic rationale (a different term for “mechanistic knowledge”). Nevertheless, a number of philosophers of medicine have pointed out that mechanistic knowledge is in fact important in EBM or that it should receive more attention. Federica Russo and Jon Williamson have, for instance, argued that causal claims need both statistical evidence as well as evidence about the mechanisms that connect an intervention with the outcome variable in order to be established (Russo and Williamson 2007). Others disagree (Reiss 2012) or qualify the claim (Gillies 2011; Howick 2011a; Illari 2011). Further, it has been pointed out that mechanistic knowledge plays an important role in the design and preparation of an RCT, as well as in the interpretation and application of RCT results (La Caze 2011; Solomon 2015). Especially when it comes to extrapolating research results from a test to another population, mechanistic knowledge is supposed to be vital (Steel 2008; see also next section). On the other hand, knowledge about mechanisms is often highly problematic and should not be relied on too heavily in applications (Andersen 2012).