Christian Wallmann

Evaluating Evidence of Mechanisms in Medicine: Principles and Procedures

This book is the first to develop explicit methods for evaluating evidence of mechanisms in the field of medicine. It explains why it can be important to make this evidence explicit, and describes how to take such evidence into account in the evidence appraisal process. In addition, it develops procedures for seeking evidence of mechanisms, for evaluating evidence of mechanisms, and for combining this evaluation with evidence of association in order to yield an overall assessment of effectiveness. Evidence-based medicine seeks to achieve improved health outcomes by making evidence explicit and by developing explicit methods for evaluating it. To date, evidence-based medicine has largely focused on evidence of association produced by clinical studies. As such, it has tended to overlook evidence of pathophysiological mechanisms and evidence of the mechanisms of action of interventions. The book offers a useful guide for all those whose work involves evaluating evidence in the health sciences, including those who need to determine the effectiveness of health interventions and those who need to ascertain the effects of environmental exposures.

Four Approaches to the Reference Class Problem

We present and analyse four approaches to the reference class problem. First, we present a new objective Bayesian solution to the reference class problem. Second, we review Pollock’s combinatorial approach to the reference class problem. Third, we discuss a machine learning approach that is based on considering reference classes of individuals that are similar to the individual of interest. Fourth, we show how evidence of mechanisms, when combined with the objective Bayesian approach, can help to solve the reference class problem. We argue that this last approach is the most promising, and we note some positive aspects of the similarity approach.

The Principal Principle Implies the Principle of Indifference

We argue that David Lewis’s principal principle implies a version of the principle of indifference. The same is true for similar principles that need to appeal to the concept of admissibility. Such principles are thus in accord with objective Bayesianism, but in tension with subjective Bayesianism. 1 The Argument 2 Some Objections Met 1 The Argument 2 Some Objections Met

An Introduction to Mechanisms

This chapter offers a brief summary of mechanisms, as including complex-system mechanisms (a complex arrangement of entities and activities, organised in such a way as to be regularly or predictably responsible for the phenomenon to be explained) and mechanistic processes (a spatio-temporal pathway along which certain features are propagated from the starting point to the end point). The chapter emphasises that EBM+ is concerned with evidence of mechanisms, not mere just-so stories, and summarises some key roles assessing evidence of mechanisms can play, particularly with respect to assessing efficacy and external validity.

Using Evidence of Mechanisms to Evaluate Efficacy and External Validity

Previous chapters in Part III develop accounts of how to gather and evaluate evidence of claims about mechanisms. This chapter explains how this evaluation can be combined with an evaluation of evidence for relevant correlations in order to produce an overall evaluation of a causal claim. The procedure is broken down to address efficacy, external validity, and then the overall presentation of the claim.

Evaluating Evidence of Mechanisms

In this chapter, we discuss how to evaluate evidence of mechanisms. This begins with an account of how a mechanistic study provides evidence for features of specific mechanism hypotheses, laying out a three step procedure of evaluating: (1) the methods used, (2) the implementation of the methods, and (3), the stability of the results. The next step is to combine those evaluations to present the quality of evidence of the general mechanistic claim.

Gathering Evidence of Mechanisms

In this chapter we put forward more theoretical proposals for gathering evidence of mechanisms. Specifically, the chapter covers the identification of a number of mechanism hypotheses, formulation of review questions for search, and then how to refine and present the resulting evidence. Key issues include increased precision concerning the nature of the hypothesis being examined, attention to differences between the study population (or populations) and the target population of the evidence assessors, and being alert for masking mechanisms, which are other mechanisms which may mask the action of the mechanism being assessed. An outline example concerning probiotics and dental caries is given. (Databases that may be helpful for some searches can be found online in Appendix A).

Particularisation to an Individual

In Sect. 7.1, we discussed extrapolation from a study population to a target population. In this chapter, we treat particularisation from a study population to one of its members. In both cases, evidence of similarity of mechanisms plays a crucial role.

Assessing Mechanisms in Public Health

Further considerations need to be borne in mind for evidence appraisal in areas beyond clinical medicine, such as public health. This chapter looks at how public health has treated associations and correlations. Then it examines the importance to public health of mechanisms operating at the group and individual level, concerning social interactions and support, access to socio-sanitary infrastructures, psychological factors, and so on, which have to be explored in the appraisal of public health evidence. Finally, the chapter considers the relationship between biological and social factors, and the difference between mechanisms of disease and mechanisms of prevention.