Theory of illness causation is an important issue in all biomedical sciences, and solid etiological explanations are needed in order to develop therapeutic approaches in medicine and preventive interventions in public health. Until now, the literature about the theoretical underpinnings of illness causation research has been scarce and fragmented, and lacking a convenient summary. This interdisciplinary book provides a convenient and accessible distillation of the current status of research into this developing field, and adds a personal flavor to the discussion (...) by proposing the etiological stance as a comprehensive approach to identify modifiable causes of illness. (shrink)

At least historically, it was common for medical practitioners to believe causal hypotheses on the basis of standalone mechanistic reasoning. However, it is now widely acknowledged that standalone mechanistic reasoning is insufficient for appropriately believing a causal hypothesis in medicine, thanks in part to the so-called problem of masking. But standalone mechanistic reasoning is not the only type of mechanistic reasoning. When exactly then is it appropriate to believe a causal hypothesis on the basis of mechanistic reasoning? In this paper, (...) I argue that it has proved difficult to provide a satisfying answer to this question. I also argue that this difficulty is predicted by recent work in knowledge-first epistemology. I think this shows that recent work in epistemology has important implications for practice in the philosophy of science. It is therefore worth paying closer attention in the philosophy of science to this recent work in knowledge-first epistemology. (shrink)

The mechanistic and causal accounts of explanation are often conflated to yield a ‘causal-mechanical’ account. This paper prizes them apart and asks: if the mechanistic account is correct, how can causal explanations be explanatory? The answer to this question varies according to how causality itself is understood. It is argued that difference-making, mechanistic, dualist and inferentialist accounts of causality all struggle to yield explanatory causal explanations, but that an epistemic account of causality is more promising in this regard.

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)

Establishing the effectiveness of medical treatments is one of the most important aspects of medical practice. Bradford Hill's viewpoints play an important role in inferring causality in medicine,...

According to Russo and Williamson (Int Stud Philos Sci 21(2):157–170, 2007, Hist Philos Life Sci 33:389–396, 2011a, Philos Sci 1(1):47–69, 2011b ), in order to establish a causal claim of the form, ‘_C_ is a cause of _E_’, one typically needs evidence that there is an underlying mechanism between _C_ and _E_ as well as evidence that _C_ makes a difference to _E_. This thesis has been used to argue that hierarchies of evidence, as championed by evidence-based movements, tend to (...) give primacy to evidence of difference making over evidence of mechanisms and are flawed because the two sorts of evidence are required and they should be treated on a par. An alternative approach gives primacy to evidence of mechanism over evidence of difference making. In this paper, we argue that this alternative approach is equally flawed, again because both sorts of evidence need to be treated on a par. As an illustration of this parity, we explain how scientists working in the ‘EnviroGenomarkers’ project constantly make use of the two evidential components in a dynamic and intertwined way. We argue that such an interplay is needed not only for causal assessment but also for policy purposes. (shrink)

Evidential pluralists, like Federica Russo and Jon Williamson, argue that causal claims should be corroborated by establishing both the existence of a suitable correlation and a suitable mechanism complex. At first glance, this fits well with mixed method research in the social sciences, which often involves a pluralist combination of statistical and mechanistic evidence. However, statistical evidence concerns a population of cases, while mechanistic evidence is found in individual case studies. How should researchers combine such general statistical evidence and specific (...) mechanistic evidence? This article discusses a very recent answer to this question, ‘multi-method large-N qualitative analysis’ or multi-method LNQA, popular in political science and international relations studies of rare events like democratic transitions and cease-fire agreements. Multi-method LNQA combines a comprehensive study of all relevant event cases with statistical analysis, in an attempt to solve the issues of generalization faced by other types of qualitative research, such as selection bias and lack of representativeness. I will argue that the kind of general causal claim that multi-method LNQA is after, however, is crucially different from the average treatment effect found in statistical analysis and can in fact only be supported with mechanistic evidence. I conclude from this that mixed method research, and thereby evidential pluralism, may be inappropriate in this context. (shrink)

The rapid, recent emergence of new medical knowledge models has engendered a dizzying number of new medical initiatives, programs and approaches. Fields such as evidence-based medicine and translational medicine all promise a renewed relationship between knowledge and medicine. The question for philosophy and other fields has been whether these new models actually achieve their promises to bring about better kinds of medical knowledge—a question that compels scholars to analyze each model’s epistemic claims. Yet, these analyses may miss critical components that (...) explain how these models actually work and function. Using the case of translational medicine, this paper suggests that analyses which treat these models as a primarily epistemic interventions miss the way that new approaches are increasingly shaped by specific financial and commercial agendas. Ultimately, social epistemological analyses that are attentive to market forces are required to make sense of emerging bioscientific research models, which are increasingly tethered to or a manifestation of increasingly financialized models of science research and innovation. (shrink)

This article addresses the contributions of the literature on the new mechanistic philosophy of science for the scientific practice of model building in ecology. This is reflected in a one-to-one interdisciplinary collaboration between an ecologist and a philosopher of science during science-in-the-making. We argue that the identification, reconstruction and understanding of mechanisms is context-sensitive, and for this case study mechanistic modeling did not present a normative role but a heuristic one. We expect our study to provides useful epistemic tools for (...) the improvement of empirically-riven work in the debates about mechanistic explanation of ecological phenomena. (shrink)

It is argued that in deterministic contexts evidence for causal relations states whether a boundary condition makes a difference or not to a phenomenon. In order to substantiate the analysis, I show that this difference/indifference making is the basic type of evidence required for eliminative induction in the tradition of Francis Bacon and John Stuart Mill. To this purpose, an account of eliminative induction is proposed with two distinguishing features: it includes a method to establish the causal irrelevance of boundary (...) conditions by means of indifference making, which is called strict method of agreement, and it introduces the notion of a background against which causal statements are evaluated. Causal statements thus become three-place-relations postulating the relevance or irrelevance of a circumstance C to the examined phenomenon P with respect to a background B of further conditions. To underline the importance of evidence in terms of difference/indifference making, I sketch two areas, in which eliminative induction is extensively used in natural and engineering sciences. One concerns exploratory experiments, the other engineering design methods. Given that a method is discussed that has been used for centuries, I make no claims to novelty in this paper, but hope that the combined discussion of several topics that are still somewhat underrepresented in the philosophy of science literature is of some merit. (shrink)

The problem of collecting, analyzing and evaluating evidence on adverse drug reactions (ADRs) is an example of the more general class of epistemological problems related to scientific inference and prediction, as well as a central problem of the health-care practice. Philosophical discussions have critically analysed the methodological pitfalls and epistemological implications of evidence assessment in medicine, however they have mainly focused on evidence of treatment efficacy. Most of this work is devoted to statistical methods of causal inference with a special (...) attention to the privileged role assigned to randomized controlled trials in Evidence Based Medicine. Regardless of whether the RCT’s privilege holds for efficacy assessment, it is nevertheless important to make a distinction between causal inference of intended and unintended effects, in that the unknowns at stake are heterogonous in the two contexts. This point has been emphasized by epidemiologists in the last decade. Their main focus is methodological, and regards the fact that bias and confounding do not affect studies on intended and unintended effects in the same way. However, deeper concerns ground the intuition for such a distinction; these are related to the constraints which we impose on evidence and their epistemological justification. My thesis is that such constraints ought to be understood to be different in the case of evidence for risk vs. benefit assessment. I present the recent debate on the causal association between acetaminophen and asthma in order to illustrate the point at issue. (shrink)

Philosophical discussions have critically analysed the methodological pitfalls and epistemological implications of evidence assessment in medicine, however they have mainly focused on evidence of treatment efficacy. Most of this work is devoted to statistical methods of causal inference with a special attention to the privileged role assigned to randomized controlled trials (RCTs) in evidence based medicine. Regardless of whether the RCT’s privilege holds for efficacy assessment, it is nevertheless important to make a distinction between causal inference of intended and unintended (...) effects, in that the unknowns at stake are heterogonous in the two contexts. However, although “lower level” evidence is increasingly acknowledged to be a valid source of information contributory to assessing the risk profile of medications on theoretical or empirical grounds, current practices have difficulty in assigning a precise epistemic status to this kind of evidence because they are more or less implicitly parasitic on the (statistical) methods developed to test drug efficacy. My thesis is that (1) “lower level” evidence is justified on distinct grounds and at different conditions depending on the different epistemologies which one wishes to endorse, in that each impose different constraints on the methods we adopt to collect and evaluate evidence; (2) such constraints ought to be understood to be different in the case of evidence for risk versus benefit assessment for a series of reasons which I will illustrate on the basis of the recent debate on the causal association between acetaminophen (a.k.a. paracetamol) and asthma. (shrink)

Social research, from economics to demography and epidemiology, makes extensive use of statistical models in order to establish causal relations. The question arises as to what guarantees the causal interpretation of such models. In this paper we focus on econometrics and advance the view that causal models are ‘augmented’ statistical models that incorporate important causal information which contributes to their causal interpretation. The primary objective of this paper is to argue that causal claims are established on the basis of a (...) plurality of evidence. We discuss the consequences of ‘evidential pluralism’ in the context of econometric modelling. (shrink)

Berichte zur Wissenschaftsgeschichte, Volume 45, Issue 3, Page 373-383, September 2022.

Berichte zur Wissenschaftsgeschichte, Volume 45, Issue 3, Page 373-383, September 2022.

Proponents of evidence-based medicine have argued convincingly for applying this scientific method to medicine. However, the current methodological framework of the EBM movement has recently been called into question, especially in epidemiology and the philosophy of science. The debate has focused on whether the methodology of randomized controlled trials provides the best evidence available. This paper attempts to shift the focus of the debate by arguing that clinical reasoning involves a patchwork of evidential approaches and that the emphasis on evidence (...) hierarchies of methodology fails to lend credence to the common practice of corroboration in medicine. I argue that the strength of evidence lies in the evidence itself, and not the methodology used to obtain that evidence. Ultimately, when it comes to evaluating the effectiveness of medical interventions, it is the evidence obtained from the methodology rather than the methodology that should establish the strength of the evidence. (shrink)

The results of econometric modeling are fragile in the sense that minor changes in estimation techniques or sample can lead to statistical models that support inconsistent causal hypotheses. The fragility of econometric results undermines making conclusive inferences from the empirical literature. I argue that the program of evidential pluralism, which originated in the context of medicine and encapsulates to the normative reading of the Russo-Williamson Thesis that causal claims need the support of both difference-making and mechanistic evidence, offers a ground (...) for resolving empirical disagreements. I analyze a recent econometric controversy regarding the tax elasticity of cigarette consumption and smoking intensity. Both studies apply plausible estimation techniques but report inconsistent results. I show that mechanistic evidence allows for discriminating econometric models representing genuine causal relations from accidental dependencies in data. Furthermore, I discuss the differences between biological and social mechanisms and mechanistic evidence across the disciplines. I show that economists mainly rely on mathematical models to represent possible mechanisms. Still, claiming the actuality of the represented mechanisms requires establishing that crucial assumptions of these models are descriptively adequate. I exemplify my approach to assessing the quality of mechanistic evidence in economics with an analysis of two models of rational addiction. (shrink)

The existing philosophical views on what is the meaning of causality adequate to medicine are vastly divided. We approach this question and offer two arguments in favor of pluralism regarding concepts of causality. First, we analyze the three main types of research designs (randomized-controlled trials, observational epidemiology and laboratory research). We argue, using examples, that they allow for making causal conclusions that are best understood differently in each case (in agreement with a version of manipulationist, probabilistic and mechanistic definitions, respectively). (...) Second, we analyze clinical practice and argue that these manipulationist, probabilistic and mechanistic causal claims can be used as evidence for different therapeutic decisions. We differentiate among ‘predicting’ that does not change the relata of causal claims, (mechanistic) ‘interferences’, and ‘interventions’ in the strict sense that act on causes to change effects. The central conclusion is that causal claims agreeing with diverse concepts of causality can deliver evidence for different types of therapeutic decisions. (shrink)

One of the most important contributions of Einstein to the philosophy of science is the distinction between two types of scientific theories: ‘principle’ and ‘constructive’ theories. More recently, Flores proposed a more general distinction, classifying scientific theories by their functional role into ‘framework’ and ‘interaction’ theories, attempting to solve some inadequacies in Einstein’s proposal. Here, based on an epistemic criterion, we present a generalised distinction which is an improvement over Flores approach. In this work (i) we evaluate the shortcomings related (...) to Flores’s proposal, (ii) we present an epistemological criterion that opens the door for a more general classification of any scientific theory in all of the natural science into two distinct groups, which we call ‘mechanistic theories’ and ‘structural theories’, and (iii) we show that such a criterion is connected to Flores’ proposal while overcoming issues of all previous approaches. (shrink)

Mechanistic information is used in the field of risk assessment in order to clarify two controversial methodological issues, the selection of inference guides and the definition of standards of evidence. In this paper we present an analysis of the concept of mechanistic information in risk assessment by recurring to previous philosophical analyses of mechanistic explanation. Our conclusion is that the conceptual analysis of mechanistic explanation facilitates a better characterization of the concept of mechanistic information. However, it also shows that the (...) use of this kind of information in risk assessment is heavily influenced by pragmatic factors, which have not been sufficiently taken into account in philosophical analysis. Mechanistic models are like hypothesis that have to be validated empirically. Due to their dependence on the standards of evidence, they are subject to the same pragmatic factors. Therefore, recurring to mechanistic information does not lead to closure of the methodological controversies in risk assessment. (shrink)

In the biomedical, behavioural and social sciences, the leading method used to estimate causal effects is commonly randomised controlled trials (RCTs) that are generally viewed as both the source and justification of the most valid evidence. In studying the foundation and theory behind RCTs, the existing literature analyses important single issues and biases in isolation that influence causal outcomes in trials (such as randomisation, statistical probabilities and placebos). The common account of biased causal inference is described in a general way (...) in terms of probabilistic imbalances between trial groups. This paper expands the common account of causal bias by distinguishing between the range of biases arising between trial groups but also within one of the groups or across the entire sample during trial design, implementation and analysis. This is done by providing concrete examples from highly influential RCT studies. In going beyond the existing RCT literature, the paper provides a broader, practice-based account of causal bias that specifies the between-group, within-group and across-group biases that affect the estimated causal results of trials – impacting both the effect size and statistical significance. Within this expanded framework, we can better identify the range of different types of biases we face in practice and address the central question about the overall validity of the RCT method and its causal claims. A study can face several smaller biases (related simultaneously to a smaller sample, smaller estimated effect, greater unblinding etc.) that generally add up to greater aggregate bias. Though difficult to measure precisely, it is important to assess and provide information in studies on how much different sources of bias, combined, can explain the estimated causal effect. The RCT method is thereby often the best we have to inform our policy decisions – and the evidence is strengthened when combined with multiple studies and other methods. Yet there is room for continually improving trials and identifying ways to reduce biases they face and to increase their overall validity. Implications are discussed. (shrink)

There are some philosophical questions that can be answered without attention to the social context in which evidence is produced and distributed.ing away from social context is an excellent way to ignore messy details and lay bare the underlying structure of the limits of inference. Idealization is entirely appropriate when one is essentially asking: In the best of all possible worlds, what am I entitled to infer? Yet, philosophers’ concerns often go beyond this domain. As an example I examine the (...) debate on mechanistic evidence and then reevaluate a canonical case study in this debate. I show that for the assessment of actual evidence, produced in a world that is far from ideal, omission of the social aspects of medical epistemology leads philosophers to draw the wrong lessons from cases they take as paradigmatic cases for their views. I close by arguing that social epistemology provides an avenue to incorporate these complications and provides the necessary framework to understand medical evidence. (shrink)

Arguments that medical decision making should rely on a variety of evidence often begin from the claim that meta-analysis has been shown to be problematic. In this paper, I first examine Stegenga’s argument that meta-analysis requires multiple decisions and thus fails to provide an objective ground for medical decision making. Next, I examine three arguments from social epistemologists that contend that meta-analyses are systematically biased in ways not appreciated by standard epistemology. In most cases I show that critiques of meta-analysis (...) fail to account for the full range of meta-analytic procedures. In the remainder of cases, I argue that the critiques identify problems that do not uniquely cut against meta-analysis. I close by suggesting one reason why it may be pragmatically rational to violate the principle of total evidence and by outlining the criteria for a successful argument against meta-analysis. A set of criteria I contend remain unmet. (shrink)

I argue that difference-making should be a crucial element for evaluating the quality of evidence for mechanisms, especially with respect to the robustness of mechanisms, and that it should take central stage when it comes to the general role played by mechanisms in establishing causal claims in medicine. The difference- making of mechanisms should provide additional compelling reasons to accept the gist of Russo-Williamson thesis and include mechanisms in the protocols for Evidence- Based Medicine, as the EBM+ research group has (...) been advocating. (shrink)

This article considers the prospects of inference to the best explanation as a method of confirming causal claims vis-à-vis the medical evidence of mechanisms. I show that IBE is actually descriptive of how scientists reason when choosing among hypotheses, that it is amenable to the balance/weight distinction, a pivotal pair of concepts in the philosophy of evidence, and that it can do justice to interesting features of the interplay between mechanistic and population level assessments.

Inference to the Best Explanation is usually employed in the Scientific Realism debates. As far as particular scientific theories are concerned, its most ready usage seems to be that of a theory of confirmation. There are however more uses of IBE, namely as an epistemological theory of testimony and as a means of categorising and justifying the sources of evidence. In this paper, I will present, develop and exemplify IBE as a theory of the quality of evidence - taking examples (...) from medicine and showing that IBE can thereby provide the epistemological underpinning and justify the criteria of grading quality of mechanistic evidence that have been recently provided in the Clarke et al. paper on how evidence of medical mechanisms is to be construed alongside population studies. (shrink)

This article examines two theses formulated by Russo and Williamson in their study of causal inference in the health sciences. The two theses are assessed against evidence from a specific case in the social sciences, i.e., research on the institutional determinants of the aggregate unemployment rate. The first Russo–Williamson Thesis is that a causal claim can only be established when it is jointly supported by difference-making and mechanistic evidence. This thesis is shown not to hold. While researchers in my case (...) study draw extensively on both types of evidence, one causal claim out of the three analyzed is established even though it is exclusively supported by mechanistic evidence. The second Russo–Williamson Thesis is that standard accounts of causality fail to handle the dualist epistemology highlighted in the first Thesis. I argue that a counterfactual-manipulationist account of causality—which is endorsed by many philosophers as well as many social scientists—can perfectly make sense of the typical strategy in my case study to draw on both difference-making and mechanistic evidence; it is just an instance of the common strategy of increasing evidential variety. (shrink)

Evidence-based medicine (EBM) makes use of explicit procedures for grading evidence for causal claims. Normally, these procedures categorise evidence of correlation produced by statistical trials as better evidence for a causal claim than evidence of mechanisms produced by other methods. We argue, in contrast, that evidence of mechanisms needs to be viewed as complementary to, rather than inferior to, evidence of correlation. In this paper we first set out the case for treating evidence of mechanisms alongside evidence of correlation in (...) explicit protocols for evaluating evidence. Next we provide case studies which exemplify the ways in which evidence of mechanisms complements evidence of correlation in practice. Finally, we put forward some general considerations as to how the two sorts of evidence can be more closely integrated by EBM. (shrink)

Philosophers of science and medicine now aspire to provide useful, socially relevant accounts of mechanism. Existing accounts have forged the path by attending to mechanisms in historical context, scientific practice, the special sciences, and policy. Yet, their primary focus has been on more proximate issues related to therapeutic effectiveness. To take the next step toward social relevance, we must investigate the challenges facing researchers, clinicians, and policy makers involving values and social context. Accordingly, we learn valuable lessons about the connections (...) between mechanistic processes and more fundamental reasons for medical interventions, particularly moral, ethical, religious, and political concerns about health, agency, and power. This paper uses debates over the controversial morning-after pill to gain insight into the deeper reasons for the production and use of mechanistic knowledge throughout biomedical research, clinical practice, and governmental regulation. To practice socially relevant philosophy of science, I argue that we need to account for mechanistic knowledge beyond immediate effectiveness, such as how it can also provide moral guidance, aid ethical categorization in the clinic, and function as a political instrument. Such insights have implications for medical epistemology, including the value-laden dimensions of mechanistic reasoning and the “epistemic friction” of values. Furthermore, there are broader impacts for teaching research ethics and understanding the role of science advisors as political advocates. (shrink)

Despite the consensus promoted by the evidence-based medicine framework, many authors continue to express doubts about the superiority of randomized controlled trials. This paper evaluates four objections targeting the legitimacy, feasibility, and extrapolation problems linked to the experimental practice of random allocation. I argue that random allocation is a methodologically sound and feasible practice contributing to the internal validity of controlled experiments dealing with heterogeneous populations. I emphasize, however, that random allocation is solely designed to ensure the validity of causal (...) inferences at the level of groups. By itself, random allocation cannot enhance test precision, doesn’t contribute to external validity, and limits the applicability of causal claims to individuals. (shrink)

This thesis analyses the use of 'Evidence-Based' methodologies of evidence assessment and intervention and policy design from medicine, and their use in sport and exercise science. It argues that problems exist with the application of Evidence-Based methodologies in sports science, meaning that the quality of evidence used to inform decision-making is lower than is often assumed. This thesis also offers realistic solutions to these problems, broadly arguing for the importance of taking evidence from mechanistic studies seriously, in addition to evidence (...) from RCTs. (shrink)

The US Food and Drug Administration (FDA) is fraught with controversies over the role of values and politics in regulatory science, especially with drugs in the realm of reproductive health. Philosophers and science studies scholars have investigated the ways in which social context shapes medical knowledge through value judgments, and feminist scholars and activists have criticized sexism and injustice in reproductive medicine. Nonetheless, there has been no systematic study of values and gender norms in FDA drug regulation. I focus on (...) three questions about values in regulatory science. First, how have societal values and gender norms shaped the way that the FDA regulates drugs in the realm of reproductive health, specifically with drug labels? Second, what are the ethical, epistemic, and social consequences of these influences on regulation for women and other marginalized groups? Third, which societal values and gender norms ought to influence drug regulation about reproductive health, and how ought this happen? Integrating philosophical analysis with historical archival research and in-depth interviews, I conduct three case studies of drug labeling about reproductive health: (1) the “drug fact” about the mechanism of the morning-after pill; (2) the package inserts for patients about the health risks of oral contraceptives; and (3) the special physician labels made for prescribing drugs to pregnant women. I identify three challenges for the FDA and suggest ways to reduce the influence of sexist values and facilitate feminist alternatives. First, across these cases, I have found that there are many ways in which other concerns in reproductive medicine (such as zygotic life, fetal health, and population control) have devalued women’s health. Second, both knowledge and ignorance xvi about their reproductive health have contributed to women’s oppression, especially poor women and women of color. Finally, by avoiding the epistemic dimensions of ethics, powerful, mostly male parties in medicine (such as doctors, pharmaceutical companies, and religious institutions) have misused “informed consent,” “religious freedom,” and “paternalism” for unethical purposes. For improvement, I suggest extracting sexist values and gender norms from regulatory science that cause epistemic injustices, and I point to success stories for reforming sexism with feminism at the FDA. (shrink)

Many researchers consider cancer to have molecular causes, namely mutated genes that result in abnormal cell proliferation (e.g. Weinberg 1998). For others, the causes of cancer are to be found not at the molecular level but at the tissue level where carcinogenesis consists of disrupted tissue organization with downward causation effects on cells and cellular components (e.g. Sonnenschein and Soto 2008). In this contribution, I ponder how to make sense of such downward causation claims. Adopting a manipulationist account of causation (...) (Woodward 2003), I propose a formal definition of downward causation and discuss further requirements (in light of Baumgartner 2009). I then show that such an account cannot be mobilized in support of non-reductive physicalism (contrary to Raatikainen 2010). However, I also argue that such downward causation claims might point at particularly interesting dynamic properties of causal relationships that might prove salient in characterizing causal relationships (following Woodward 2010). (shrink)