Austin Due

The underreporting of suspected adverse drug reactions hinders pharmacovigilance. Solutions to underreporting are oftentimes directed at clinicians and health care professionals. However, given the recent rise of public inclusion in medical science, solutions may soon begin more actively involving patients. I aim to offer an evaluative framework for future possible proposals that would engage patients with the aim of mitigating underreporting. The framework may also have value in evaluating current reporting practices. The offered framework is composed of three criteria that are bioethical, social-epistemic, and pragmatic: (i) patients should not be exposed to undue harms, e.g., nocebo effects; (ii) data should be collected, analyzed, and communicated prioritizing pharmacovigilance’s aims, i.e., free from industry bias; and (iii) proposals should account for existing and foreseeable pragmatic constraints like clinician ‘buy in’ and existing reporting infrastructure. Proposals to engage patients in pharmacovigilance that fulfil or address these criteria are preferable to those that do not.

Side effects are a concern in medical decision making and a robust area of biomedical research. However, there is relatively little philosophical investigation into side effects as such, especially given that side effects are appealed to for various applications in philosophy of medicine. In addition, health authorities like the FDA, CDC, and WHO have contrary definitions of ‘side effect.’ Moreover, these definitions have clear counterexamples. This dissertation aims to provide a complete account of what side effects are. I posit that an account of side effects ought to draw clean conceptual lines between side effects and related treatment outcomes. I contend that an account of side effects must address two components: the reasons behind an intervention that produced the side effect, and the causal powers of the intervention that brought about that effect. With this account in mind, I address contemporary philosophical models that distinguish placebo effects from side effects. These arguments, respectively in chapters 2 and 3, yield a more complete, less problematic account of side effects than previous accounts. The dissertation then turns to the process of discovering side effects, specifically in the post-market context. Given the paucity of external validity in pre-market drug trials, chapter 4 argues that post-market ‘phase IV’ trials blur the received distinction of ‘confirmatory’ versus ‘exploratory’ experimentation in philosophy of science. The other component of post-market drug research is spontaneous reporting, or the voluntary reporting of a suspected side effect to a regulatory body. Chapter 5 uses the framework of risks and values in science to examine why clinicians underreport, which hinders our ability to prevent drug-related harms. Chapter 6 looks at how patients could mitigate underreporting and develops a social-epistemic, pragmatic, and ethical framework which can evaluate proposals to engage patients to spontaneously report their suspected side effects. In short, this dissertation aims to firstly address the conceptual problems in how we define ‘side effect’ and relate it to other treatment outcomes, and secondly it addresses issues that hinder the scientific investigation of side effects.

Side effects are ubiquitous in medicine and they often play a role in treatment decisions for patients and clinicians alike. Philosophers and health researchers often use side effects to illustrate issues with contemporary medical research and practice. However, technical definitions of ‘side effect’ differ among health authorities. Thus, determining the side effects of an intervention can differ depending on whose definition we assume. Here I review some of the common definitions of side effect and highlight their issues. In response, I offer an account of side effects as jointly (i) unintended and (ii) effects due to the causal capacities or invariances of an intervention. I discuss (i) by examining the intentions or reasons behind therapeutic interventions, and I discuss (ii) by appealing to a manipulationist model of causation. The analysis here highlights that side effects are conceptually distinct from related outcomes like adverse events, adverse drug reactions, and placebo effects. The analysis also allows for reflection on the utility of ‘side effect’ as a technical term in medical research and practice.

Exploratory experiments are widely characterized as experiments that do not test hypotheses. Experiments that do test hypotheses are characterized as confirmatory experiments. Philosophers have pointed out that research programmes can be both confirmatory and exploratory. However, these definitions preclude single experiments being characterized as both exploratory and confirmatory; how can an experiment test and not test a hypothesis? Given the intuition that some experiments are exploratory, some are confirmatory, and some are both, a recharacterization of the relationship between exploratory and confirmatory experimentation is needed. I discuss ‘phase IV’ trials to show what this recharacterization could look like. Phase IV trials can be exploratory and confirmatory insofar as they concurrently test hypotheses and explore for unforeseen phenomena. Even if it is uncontroversial that a single experiment can have multiple aims, the recharacterization of the relationship between exploratory and confirmatory experimentation is still required for these aims to be held together coherently. I offer an alternative characterization of the relationship between exploratory and confirmatory experimentation where the former remains a distinct kind of experimentation but is not characterized as non-hypothesis-testing.