title: Problems with using mechanisms to solve the problem of extrapolation.
abstract: Proponents of evidence-based medicine and some philosophers of science seem to agree that knowledge of mechanisms can help solve the problem of applying results of controlled studies to target populations ('the problem of extrapolation'). We describe the problem of extrapolation, characterize mechanisms, and outline how mechanistic knowledge might be used to solve the problem. Our main thesis is that there are four often overlooked problems with using mechanistic knowledge to solve the problem of extrapolation. First, our understanding of mechanisms is often (and arguably, likely to remain) incomplete. Secondly, knowledge of mechanisms is not always applicable outside the tightly controlled laboratory conditions in which it is gained. Thirdly, mechanisms can behave paradoxically. Fourthly, as Daniel Steel points out, using mechanistic knowledge faces the problem of the 'extrapolator's circle'. At the same time, when the problems with mechanistic knowledge have been addressed, such knowledge can and should be used to mitigate (nothing can entirely solve) the problem of extrapolation.
authors.affiliation: Department of Primary Care Health Sciences, Centre for Evidence-Based Medicine, University of Oxford, New Radcliffe House, Radcliffe Observatory Quarter, Woodstock Road, Oxford, OX2 6GG, UK. jeremy.howick@phc.ox.ac.uk
authors.forename: Jeremy
authors.initials: J
authors.lastname: Howick
authors.forename: Paul
authors.initials: P
authors.lastname: Glasziou
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Aronson
mesh_terms: D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D019317:Evidence-Based Medicine; D006801:Humans; D019359:Knowledge; D010684:Philosophy; D011340:Problem Solving; D016032:Randomized Controlled Trials as Topic; D015203:Reproducibility of Results
chemical_list: D000889:Anti-Arrhythmia Agents