Jon Williamson

While the importance of mechanisms in determining causality in medicine is currently the subject of active debate, the role of mechanistic reasoning in clinical practice has received far less attention. In this paper we look at this question in the context of the treatment of a particular individual, and argue that evidence of mechanisms is indeed key to various aspects of clinical practice, including assessing population-level research reports, diagnostic as well as therapeutic decision making, and the assessment of treatment effects. We use the pulmonary condition bronchiectasis as a source of examples of the importance of mechanistic reasoning to clinical practice.

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.

The teratogenicity of the Zika virus was considered established in 2016, and is an interesting case because three different sets of causal criteria were used to assess teratogenicity. This paper appeals to the thesis of Russo and Williamson (2007) to devise an epistemological framework that can be used to compare and evaluate sets of causal criteria. The framework can also be used to decide when enough criteria are satisfied to establish causality. Arguably, the three sets of causal criteria considered here offer only a rudimentary assessment of mechanistic studies, and some suggestions are made as to alternative ways to establish causality.

The role of mechanistic evidence tends to be under-appreciated in current evidencebased medicine (EBM), which focusses on clinical studies, tending to restrict attention to randomized controlled studies (RCTs) when they are available. The EBM+ programme seeks to redress this imbalance, by suggesting methods for evaluating mechanistic studies alongside clinical studies. Drug approval is a problematic case for the view that mechanistic evidence should be taken into account, because RCTs are almost always available. Nevertheless, we argue that mechanistic evidence is central to all the key tasks in the drug approval process: in drug discovery and development; assessing pharmaceutical quality; devising dosage regimens; assessing efficacy, harms, external validity, and cost-effectiveness; evaluating adherence; and extending product licences. We recommend that, when preparing for meetings in which any aspect of drug approval is to be discussed, mechanistic evidence should be systematically analysed and presented to the committee members alongside analyses of clinical studies.

Systems medicine is a promising new paradigm for discovering associations, causal relationships and mechanisms in medicine. But it faces some tough challenges that arise from the use of big data: in particular, the problem of how to integrate evidence and the problem of how to structure the development of models. I argue that objective Bayesian models offer one way of tackling the evidence integration problem. I also offer a general methodology for structuring the development of models, within which the objective Bayesian approach fits rather naturally.

This paper presents a new argument for the Principle of Indifference. This argument can be thought of in two ways: as a pragmatic argument, justifying the principle as needing to hold if one is to minimise worst-case expected loss, or as an epistemic argument, justifying the principle as needing to hold in order to minimise worst-case expected inaccuracy. The question arises as to which interpretation is preferable. I show that the epistemic argument contradicts Evidentialism and suggest that the relative plausibility of Evidentialism provides grounds to prefer the pragmatic interpretation. If this is right, it extends to a general preference for pragmatic arguments for the Principle of Indifference, and also to a general preference for pragmatic arguments for other norms of Bayesian epistemology.

This paper presents a new argument for the Principle of Indifference. This argument can be thought of in two ways: as a pragmatic argument, justifying the principle as needing to hold if one is to minimise worst-case expected loss, or as an epistemic argument, justifying the principle as needing to hold in order to minimise worst-case expected inaccuracy. The question arises as to which interpretation is preferable. I show that the epistemic argument contradicts Evidentialism and suggest that the relative plausibility of Evidentialism provides grounds to prefer the pragmatic interpretation. If this is right, it extends to a general preference for pragmatic arguments for the Principle of Indifference, and also to a general preference for pragmatic arguments for other norms of Bayesian epistemology.

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.

We consider the use of interventions for resolving a problem of unidentified statistical models. The leading examples are from latent variable modelling, an influential statistical tool in the social sciences. We first explain the problem of statistical identifiability and contrast it with the identifiability of causal models. We then draw a parallel between the latent variable models and Bayesian networks with hidden nodes. This allows us to clarify the use of interventions for dealing with unidentified statistical models. We end by discussing the philosophical and methodological import of our result.

The Recursive Bayesian Net formalism was originally developed for modelling nested causal relationships. In this paper we argue that the formalism can also be applied to modelling the hierarchical structure of mechanisms. The resulting network contains quantitative information about probabilities, as well as qualitative information about mechanistic structure and causal relations. Since information about probabilities, mechanisms and causal relations is vital for prediction, explanation and control respectively, an RBN can be applied to all these tasks. We show in particular how a simple two-level RBN can be used to model a mechanism in cancer science. The higher level of our model contains variables at the clinical level, while the lower level maps the structure of the cell's mechanism for apoptosis.

Inductive logic admits a variety of semantics (Haenni et al., 2011, Part 1). This paper develops semantics based on the norms of Bayesian epistemology (Williamson, 2010, Chapter 7). §1 introduces the semantics and then, in §2, the paper explores methods for drawing inferences in the resulting logic and compares the methods of this paper with the methods of Barnett and Paris (2008). §3 then evaluates this Bayesian inductive logic in the light of four traditional critiques of inductive logic, arguing (i) that it is language independent in a key sense, (ii) that it admits connections with the Principle of Indifference but these connections do not lead to paradox, (iii) that it can capture the phenomenon of learning from experience, and (iv) that while the logic advocates scepticism with regard to some universal hypotheses, such scepticism is not problematic from the point of view of scientific theorising

According to objective Bayesianism, an agent’s degrees of belief should be determined by a probability function, out of all those that satisfy constraints imposed by background knowledge, that maximises entropy. A Bayesian net offers a way of efficiently representing a probability function and efficiently drawing inferences from that function. An objective Bayesian net is a Bayesian net representation of the maximum entropy probability function. In this paper we apply the machinery of objective Bayesian nets to breast cancer prognosis. Background knowledge is diverse and comes from several different sources: a database of clinical data, a database of molecular data, and quantitative data from the literature. We show how an objective Bayesian net can be constructed from this background knowledge and how it can be applied to yield prognoses and aid translation of clinical knowledge to genomics research

It is tempting to analyse causality in terms of just one of the indicators of causal relationships, e.g., mechanisms, probabilistic dependencies or independencies, counterfactual conditionals or agency considerations. While such an analysis will surely shed light on some aspect of our concept of cause, it will fail to capture the whole, rather multifarious, notion. So one might instead plump for pluralism: a different analysis for a different occasion. But we do not seem to have lots of different concepts of cause – just one eclectic notion. The resolution of this conundrum, I think, requires us to accept that our causal beliefs are generated by a wide variety of indicators, but to deny that this variety of indicators yields a variety of concepts of cause. This focus on the relation between evidence and causal beliefs leads to what I call epistemic causality. Under this view, certain causal beliefs are appropriate or rational on the basis of observed evidence; our notion of cause can be understood purely in terms of these rational beliefs. Causality, then, is a feature of our epistemic representation of the world, rather than of the world itself. This yields one, multifaceted notion of cause

I present a formalism that combines two methodologies: objective Bayesianism and Bayesian nets. According to objective Bayesianism, an agent’s degrees of belief (i) ought to satisfy the axioms of probability, (ii) ought to satisfy constraints imposed by background knowledge, and (iii) should otherwise be as non-committal as possible (i.e. have maximum entropy). Bayesian nets offer an efficient way of representing and updating probability functions. An objective Bayesian net is a Bayesian net representation of the maximum entropy probability function.

In this paper, we examine what is to be said in defence of Machamer, Darden and Craver’s (MDC) controversial dualism about activities and entities (Machamer, Darden and Craver’s in Philos Sci 67:1–25, 2000). We explain why we believe the notion of an activity to be a novel, valuable one, and set about clearing away some initial objections that can lead to its being brushed aside unexamined. We argue that substantive debate about ontology can only be effective when desiderata for an ontology are explicitly articulated. We distinguish three such desiderata. The first is a more permissive descriptive ontology of science, the second a more reductive ontology prioritising understanding, and the third a more reductive ontology prioritising minimalism. We compare MDC’s entities-activities ontology to its closest rival, the entities-capacities ontology, and argue that the entities-activities ontology does better on all three desiderata

Russo and Williamson (Int Stud Philos Sci 21(2):157–170, 2007) put forward the thesis that, at least in the health sciences, to establish the claim that C is a cause of E, one normally needs evidence of an underlying mechanism linking C and E as well as evidence that C makes a difference to E. This epistemological thesis poses a problem for most current analyses of causality which, in virtue of analysing causality in terms of just one of mechanisms or difference making, cannot account for the need for the other kind of evidence. Weber (Int Stud Philos Sci 23(2):277–295, 2009) has suggested to the contrary that Giere’s probabilistic analysis of causality survives this criticism. In this paper, we look in detail at the case of medical imaging technology, which, we argue, supports the thesis of Russo and Williamson, and we respond to Weber’s suggestion, arguing that Giere’s account does not survive the criticism