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.

The theory of belief revision and merging has recently been applied to judgement aggregation. In this paper I argue that judgements are best aggregated by merging the evidence on which they are based, rather than by directly merging the judgements themselves. This leads to a threestep strategy for judgement aggregation. First, merge the evidence bases of the various agents using some method of belief merging. Second, determine which degrees of belief one should adopt on the basis of this merged evidence base, by applying objective Bayesian theory. Third, determine which judgements are appropriate given these degrees of belief by applying a decision-theoretic account of rational judgement formation

This paper addresses questions about how the levels of causality (generic and single-case causality) are related. One question is epistemological: can relationships at one level be evidence for relationships at the other level? We present three kinds of answer to this question, categorised according to whether inference is top-down, bottom-up, or the levels are independent. A second question is metaphysical: can relationships at one level be reduced to relationships at the other level? We present three kinds of answer to this second question, categorised according to whether single-case relations are reduced to generic, generic relations are reduced to single-case, or the levels are independent. We then explore causal inference in autopsy. This is an interesting case study, we argue, because it refutes all three epistemologies and all three metaphysics. We close by sketching an account of causality that survives autopsy—the epistemic theory

Causal inference is perhaps the most important form of reasoning in the sciences. A panoply of disciplines, ranging from epidemiology to biology, from econometrics to physics, make use of probability and statistics to infer causal relationships. The social and health sciences analyse population-level data using statistical methods to infer average causal relations. In diagnosis of disease, probabilistic statements are based on population-level causal knowledge combined with knowledge of a particular person’s symptoms. For the physical sciences, the Salmon-Dowe account develops an analysis of causation based on the notion of process and interaction. In artificial intelligence, the development of graphical methods has leant impetus to a probabilistic analysis of causality. The biological sciences use probabilistic methods to look for evolutionary causes of the state of a current species and to look for genetic causal factors. This variegated situation raises at least two fundamental philosophical issues: about the relation between causality and probability, and about the interpretation of probability in causal analysis. In this book we bring philosophers and scientists together to discuss the relation between causality and probability, and the applications of these concepts within the sciences.

How is probability related to logic? Should probability and logic be combined? If so, how? Bayesianism tells us we ought to reason probabilistically. In that sense, probability theory is logic. How then does probability theory relate to classical logic and the various non-classical logics that also stake a claim on normative reasoning? Is probability theory to be preferred over other logics or vice versa? Is probability theory to be used in some situations, and the other logics in other situations? Or should probability be combined with other logics?

Objective Bayesian probability is often defined over rather simple domains, e.g., finite event spaces or propositional languages. This paper investigates the extension of objective Bayesianism to first-order logical languages. It is argued that the objective Bayesian should choose a probability function, from all those that satisfy constraints imposed by background knowledge, that is closest to a particular frequency-induced probability function which generalises the λ = 0 function of Carnap’s continuum of inductive methods.

Objective Bayesianism says that the strengths of one’s beliefs ought to be probabilities, calibrated to physical probabilities insofar as one has evidence of them, and otherwise sufficiently equivocal. These norms of belief are often explicated using the maximum entropy principle. In this paper we investigate the extent to which one can provide a unified justification of the objective Bayesian norms in the case in which the background language is a first-order predicate language, with a view to applying the resulting formalism to inductive logic. We show that the maximum entropy principle can be motivated largely in terms of minimising worst-case expected loss.

We present a new framework for combining logic with probability, and demonstrate the application of this framework to breast cancer prognosis. Background knowledge concerning breast cancer prognosis is represented using logical arguments. This background knowledge and a database are used to build a Bayesian net that captures the probabilistic relationships amongst the variables. Causal hypotheses gleaned from the Bayesian net in turn generate new arguments. The Bayesian net can be queried to help decide when one argument attacks another. The Bayesian net is used to perform the prognosis, while the argumentation framework is used to provide a qualitative explanation of the prognosis.