Background. In the evidence evaluation process, evidence-based medicine tends to focus on clinical studies. Evidence of the mechanisms responsible for effectiveness which is produced by other means (e.g. in vitro laboratory research, biomedical imaging, simulation) tends to be treated implicitly by those charged with evaluating evidence, such as committees for approving drugs or public health actions. This goes against the tenets of evidence-based medicine: relevant evidence needs to be made explicit, in order that its quality can be scrutinised and, if need be, its conclusions challenged.
Objectives. This paper sets out a strategy for scrutinising evidence of mechanisms in medicine, developed by the EBM+ project (ebmplus.org).
Methods. This is a philosophical project supported by the UK Arts and Humanities Research Council. A team of researchers at the Universities of Kent, UCL, Amsterdam and Cambridge, together with practitioners at NICE and IARC, have developed a methodology for scrutinising evidence of mechanisms and using this evidence to help evaluate effectiveness in medicine. This methodology is in line with current philosophical work on mechanism discovery and quality of evidence.
Results. The resulting methodology tackles 2 questions: establishing efficacy and establishing external validity. In the first, scoping phase, a mechanism hypothesis is formulated and evidence of mechanisms is identified in the literature. Next, the evidence of mechanisms is evaluated by means of key quality indicators, to determine the status of the mechanistic hypothesis. Finally, this evidence evaluation is combined by the evaluation of the clinical studies (using, e.g. GRADE methods) in order to determine an overall evaluation of efficacy or external validity.
Conclusions. Although evidence of mechanisms is heterogeneous, involving sources other than clinical studies, we demonstrate that it is possible and practical to scrutinise and evaluate this evidence in line with the principles of evidence-based medicine.