According to current hierarchies of evidence for EBM, evidence of correlation is always more important than evidence of mechanisms when evaluating and establishing causal claims. We argue that evidence of mechanisms needs to be treated alongside evidence of correlation. This is for three reasons. First, correlation is always a fallible indicator of causation, subject in particular to the problem of confounding; evidence of mechanisms can in some cases be more important than evidence of correlation when assessing a causal claim. Second, (...) evidence of mechanisms is often required in order to obtain evidence of correlation. Third, evidence of mechanisms is often required in order to generalise and apply causal claims. While the EBM movement has been enormously successful in making explicit and critically examining one aspect of our evidential practice, i.e., evidence of correlation, we wish to extend this line of work to make explicit and critically examine a second aspect of our evidential practices: evidence of mechanisms. (shrink)

Even though the evidence‐based medicine movement (EBM) labels mechanisms a low quality form of evidence, consideration of the mechanisms on which medicine relies, and the distinct roles that mechanisms might play in clinical practice, offers a number of insights into EBM itself. In this paper, I examine the connections between EBM and mechanisms from several angles. I diagnose what went wrong in two examples where mechanistic reasoning failed to generate accurate predictions for how a dysfunctional mechanism would respond to intervention. (...) I then use these examples to explain why we should expect this kind of mechanistic reasoning to fail in systematic ways, by situating these failures in terms of evolved complexity of the causal system(s) in question. I argue that there is still a different role in which mechanisms continue to figure as evidence in EBM: namely, in guiding the application of population‐level recommendations to individual patients. Thus, even though the evidence‐based movement rejects one role in which mechanistic reasoning serves as evidence, there are other evidentiary roles for mechanistic reasoning. This renders plausible the claims of some critics of evidencebased medicine who point to the ineliminable role of clinical experience. Clearly specifying the ways in which mechanisms and mechanistic reasoning can be involved in clinical practice frames the discussion about EBM and clinical experience in more fruitful terms. (shrink)

After a decade of intense debate about mechanisms, there is still no consensus characterization. In this paper we argue for a characterization that applies widely to mechanisms across the sciences. We examine and defend our disagreements with the major current contenders for characterizations of mechanisms. Ultimately, we indicate that the major contenders can all sign up to our characterization.

The philosophy of evidence-based medicine -- What is EBM? -- What is good evidence for a clinical decision? -- Ruling out plausible rival hypotheses and confounding factors : a method -- Resolving the paradox of effectiveness : when do observational studies offer the same degree of evidential support as randomized trials? -- Questioning double blinding as a universal methodological virtue of clinical trials : resolving the Philip's paradox -- Placebo controls : problematic and misleading baseline measures of effectiveness -- Questioning (...) the methodological superiority of "placebo" over "active" controlled trials -- Examining the paradox that traditional roles for mechanistic reasoning and expert -- Judgment have been up-ended by EBM -- A qualified defence of the EBM stance on mechanistic reasoning -- Knowledge that versus knowledge how : situating the EBM position on expert clinical judgment -- Moving EBM forward. (shrink)

Inferences like these are known as extrapolations.

We argue that the health sciences make causal claims on the basis of evidence both of physical mechanisms, and of probabilistic dependencies. Consequently, an analysis of causality solely in terms of physical mechanisms or solely in terms of probabilistic relationships, does not do justice to the causal claims of these sciences. Yet there seems to be a single relation of cause in these sciences - pluralism about causality will not do either. Instead, we maintain, the health sciences require a theory (...) of causality that unifies its mechanistic and probabilistic aspects. We argue that the epistemic theory of causality provides the required unification. (shrink)

Although decision‐making algorithms are not new to medicine, the availability of vast stores of medical data, gains in computing power, and breakthroughs in machine learning are accelerating the pace of their development, expanding the range of questions they can address, and increasing their predictive power. In many cases, however, the most powerful machine learning techniques purchase diagnostic or predictive accuracy at the expense of our ability to access “the knowledge within the machine.” Without an explanation in terms of reasons or (...) a rationale for particular decisions in individual cases, some commentators regard ceding medical decision‐making to black box systems as contravening the profound moral responsibilities of clinicians. I argue, however, that opaque decisions are more common in medicine than critics realize. Moreover, as Aristotle noted over two millennia ago, when our knowledge of causal systems is incomplete and precarious—as it often is in medicine—the ability to explain how results are produced can be less important than the ability to produce such results and empirically verify their accuracy. (shrink)

The use of evidence in medicine is something we should continuously seek to improve. This book seeks to develop our understanding of evidence of mechanism in evaluating evidence in medicine, public health, and social care; and also offers tools to help implement improved assessment of evidence of mechanism in practice. In this way, the book offers a bridge between more theoretical and conceptual insights and worries about evidence of mechanism and practical means to fit the results into evidence assessment procedures.

Published research findings are sometimes refuted by subsequent evidence, says Ioannidis, with ensuing confusion and disappointment.

Traditionally, mechanistic reasoning has been assigned a negligible role in standard EBM literature, although some recent authors have argued for an upgrade. Even so, the mechanistic reasoning that has received attention has almost exclusively been positive—both in an epistemic sense of claiming that there is a mechanistic chain and in a health-related sense of there being claimed benefits for the patient. Negative mechanistic reasoning has been neglected, both in the epistemic and in the health-related sense. I distinguish three main types (...) of negative mechanistic reasoning and subsume them under a new definition of mechanistic reasoning in the context of assessing medical interventions. This definition is wider than a previous suggestion in the literature. Each negative type corresponds to a range of evidential strengths, and it is argued that there are differences with respect to typical evidential strengths. The variety of negative mechanistic reasoning should be acknowledged in EBM, and it presents a serious challenge to proponents of so-called medical hierarchies of evidence. (shrink)

Evidence-based medicine (EBM) has thus far failed to adequately account for the appropriate incorporation of other potential warrants for medical decision making into clinical practice. In particular, EBM has struggled with the value and integration of other kinds of medical knowledge, such as those derived from clinical experience or based on pathophysiologic rationale. The general priority given to empirical evidence derived from clinical research in all EBM approaches is not epistemically tenable. A casuistic alternative to EBM approaches recognizes that five (...) distinct topics, 1) empirical evidence, 2) experiential evidence, 3) pathophysiologic rationale, 4) patient goals and values, and 5) system features are potentially relevant to any clinical decision. No single topic has a general priority over any other and the relative importance of a topic will depend upon the circumstances of the particular case. The skilled clinician must weigh these potentially conflicting evidentiary and non-evidentiary warrants for action, employing both practical and theoretical reasoning, in order to arrive at the best choice for an individual patient. (shrink)

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. (shrink)

Wesley Salmon is renowned for his seminal contributions to the philosophy of science. He has powerfully and permanently shaped discussion of such issues as lawlike and probabilistic explanation and the interrelation of explanatory notions to causal notions. This unique volume brings together twenty-six of his essays on subjects related to causality and explanation, written over the period 1971-1995. Six of the essays have never been published before and many others have only appeared in obscure venues. The volume includes a section (...) of accessible introductory pieces, as well as more advanced and technical pieces, and will make essential work in the philosophy of science readily available to both scholars and students. (shrink)

In this chapter we explore the process of extrapolating causal claims from model organisms to humans in pharmacology. We describe and compare four strategies of extrapolation: enumerative induction, comparative process tracing, phylogenetic reasoning, and robustness reasoning. We argue that evidence of mechanisms plays a crucial role in several strategies for extrapolation and in the underlying logic of extrapolation: the more directly a strategy establishes mechanistic similarities between a model and humans, the more reliable the extrapolation. We present case studies from (...) the research on atherosclerosis and the development of statins, that illustrate these strategies and the role of mechanistic evidence in extrapolation. (shrink)

Russo and Williamson put forward the following thesis: in order to establish a causal claim in medicine, one normally needs to establish both that the putative cause and putative effect are appropriately correlated and that there is some underlying mechanism that can account for this correlation. I argue that, although the Russo-Williamson thesis conflicts with the tenets of present-day evidence-based medicine, it offers a better causal epistemology than that provided by present-day EBM because it better explains two key aspects of (...) causal discovery. First, the thesis better explains the role of clinical studies in establishing causal claims. Second, it yields a better account of extrapolation. (shrink)

Both clinical research and basic science rely on the epistemic practice of extrapolation from surrogate models, to the point that explanatory accounts presented in review papers and biology textbooks are in fact composite pictures reconstituted from data gathered in a variety of distinct experimental setups. This raises two new challenges to previously proposed mechanistic-similarity solutions to the problem of extrapolation: one pertaining to the absence of mechanistic knowledge in the early stages of research and the second to the large number (...) of extrapolations underpinning explanatory accounts. An analysis of the strategies deployed in experimental research supports the conclusion that while results from validated surrogate models are treated as a legitimate line of evidence supporting claims about target systems, the overall structure of research projects also demonstrates that extrapolative inferences are not considered definitive or sufficient evidence, but only partially justified hypotheses subjected to further testing. 1 Introduction2 Surrogate Models2.1 What exactly is a surrogate model?2.2 Why use surrogate models?3 Prior Validation of Surrogate Models3.1 The validation and ranking of surrogate models in the early stages of basic research3.2 The validation of surrogate models in later stages of basic research and in clinical research4 ‘Big Picture’ Accounts and the Extrapolations Underpinning Them4.1 The mosaic nature of mechanistic descriptions in basic science4.2 Challenges for mechanistic-similarity-based validation protocols5 Retrospective Testing of Extrapolated Knowledge5.1 Holistic confirmation5.2 Fallback strategies6 Conclusions. (shrink)