Austin Due

Empirical research in psychology on the harms of talk therapies has recently been increasing. Much of this research aims to measure the prevalence of such harms. The measurement of these harms assumes the ability to causally distinguish between distinct kinds of harms, e.g., side effects, malpractice effects, nocebo effects, etc. If it were to be shown that there is no distinction between some of these harms, it would fundamentally challenge this field of work. Or, at least, it would present a significant problem that any future work on talk therapy harms must reckon with. My aim here is to offer such an argument, i.e., that in the context of talk therapies, some of these harms become causally indistinct.

Drugs given to reduce suffering in palliative care often cause adverse consciousness diminishment. The causing of this consciousness diminishment is often justified appealing to the Doctrine of Double Effect. This justification relies on consciousness diminishment being unintended and a side effect in such cases. Arima (2025) argues that in many of these cases, consciousness diminishment is actually intended and not a side effect at all. If that is so, in those cases the use of drugs that cause consciousness diminishment cannot be justified by appeal to the Doctrine of Double Effect alone. Here I aim to challenge two points that play a central role bolstering Arima’s conclusion. The first I call the ‘instrumental rationality’ point: if something is causally necessary to bring about an intended end, that causally necessary thing must likewise be intended. The second I call the ‘dissimilarity’ point: consciousness diminishment in this context is unlike a side effect insofar as side effects do not contribute causally to the intended aims of an intervention. I challenge both of these points by appealing to recent work on defining medical side effects. I conclude that Arima is likely right that the number of instances where the Doctrine of Double Effect justifies consciousness diminishment in palliative care is less than commonly thought, though it is not as rare as Arima’s argument leads one to believe.

A common criticism of medicine is that there is often too much focus on treating symptoms instead of treating patients. This criticism and its sentiment - among other factors – have motivated many 'humanistic' or 'non-reductionist' approaches to medicine. My aim here is not to detail or defend any of these approaches, but rather to better understand what is at the heart of the 'common criticism.' I contend that this criticism is best understood as a criticism of a kind of bias I here introduce: symptom bias. Symptom bias occurs when treating symptoms becomes the ends of intervening instead of the means towards health or well-being. Without naming and understanding this bias, even the 'non-reductionist' approaches to medicine may perpetuate it.

Post-market pharmaceutical surveillance or ‘pharmacovigilance’ relies on the reporting of suspected adverse drug reactions to regulatory databases. Recently, more ‘active’ methods that directly involve patients in identifying and reporting suspected adverse drug reactions have been suggested. This is different than traditional ‘passive’ methods, e.g., using databases without contacting patients directly. Though there are benefits to active pharmacovigilance, it is not without its potential risks. Here I highlight one of those risks – the nocebo effect. Nocebo effects are harms that are thought to arise by conditioning or negative expectation. If a patient engaged in active pharmacovigilance is improperly motivated to seek out and report suspected adverse drug reactions, nocebo harms can occur. Not only is this a bioethical concern about harm, but it is also an epistemic or data-quality problem. Since nocebo effects are not due to the pharmacological properties of the drugs under investigation, nocebo effects reported as suspected adverse drug reactions constitute false positives in these databases.

Precision medicine functions by grouping patients along genetic, molecular, and related ‘-omics’ factors. This stratification relies on large, growing databases of patient-volunteered information. Both private companies and government bodies incentivize patients to volunteer this genetic information appealing to the creation of collaborative patient partnerships and the concept of empowerment. This paper aims to address two related questions: (1) what is the actual nature of patient participation in precision medicine research? And (2) is this participation in precision medicine research really that empowering for the average patient? I contend that firstly, the nature of this participation is best conceived of as merely contributory. Contributory participation, as it will be shown, falls short of collaboration. The partnership created by participation in precision medicine research is not one of sharing values, equal say in decisions, or shared benefit. Secondly, I contend that there are important caveats to claims that patient participation in precision medicine is empowering. Empowerment is hindered by the type of participation, the practical use or actionability of genetic data, genetic literacy, the cost of precision drugs for patients that qualify for them, and bioethical considerations of informed consent.

The underreporting of suspected adverse drug reactions remains a primary issue for contemporary post-market drug surveillance or ‘pharmacovigilance.’ Pharmacovigilance pioneer W.H.W. Inman argued that ‘deadly sins’ committed by clinicians are to blame for underreporting. Of these ‘sins,’ ignorance and lethargy are the most obvious and impactful in causing underreporting. However, recent analyses show that diffidence, insecurity, and indifference additionally play a major role. I aim to augment our understanding of diffidence, insecurity, and indifference by arguing these sins are underwritten by value judgments arising via epistemic risk. I contend that ‘evidence-based’ medicine codifies these sins.

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.