Barbara Osimani

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.

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.

Medical diagnosis has been traditionally recognized as a privileged field of application for so called probabilistic induction. Consequently, the Bayesian theorem, which mathematically formalizes this form of inference, has been seen as the most adequate tool for quantifying the uncertainty surrounding the diagnosis by providing probabilities of different diagnostic hypotheses, given symptomatic or laboratory data. On the other side, it has also been remarked that differential diagnosis rather works by exclusion, e.g. by modus tollens, i.e. deductively. By drawing on a case history, this paper aims at clarifying some points on the issue. Namely: 1) Medical diagnosis does not represent, strictly speaking, a form of induction, but a type, of what in Peircean terms should be called ‘abduction’ (identifying a case as the token of a specific type); 2) in performing the single diagnostic steps, however, different inferential methods are used for both inductive and deductive nature: modus tollens, hypothetical-deductive method, abduction; 3) Bayes’ theorem is a probabilized form of abduction which uses mathematics in order to justify the degree of confidence which can be entertained on a hypothesis given the available evidence; 4) although theoretically irreconcilable, in practice, both the hypothetical- deductive method and the Bayesian one, are used in the same diagnosis with no serious compromise for its correctness; 5) Medical diagnosis, especially differential diagnosis, also uses a kind of “probabilistic modus tollens”, in that, signs (symptoms or laboratory data) are taken as strong evidence for a given hypothesis not to be true: the focus is not on hypothesis confirmation, but instead on its refutation [Pr (¬ H/E1, E2, …, En)]. Especially at the beginning of a complicated case, odds are between the hypothesis that is potentially being excluded and a vague “other”. This procedure has the advantage of providing a clue of what evidence to look for and to eventually reduce the set of candidate hypotheses if conclusive negative evidence is found. 6) Bayes’ theorem in the hypothesis-confirmation form can more faithfully, although idealistically, represent the medical diagnosis when the diagnostic itinerary has come to a reduced set of plausible hypotheses after a process of progressive elimination of candidate hypotheses; 7) Bayes’ theorem is however indispensable in the case of litigation in order to assess doctor’s responsibility for medical error by taking into account the weight of the evidence at his disposal.