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. (shrink)

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. (shrink)

Kevin Elliott and others separate two common arguments for the legitimacy of societal values in scientific reasoning as the gap and the error arguments. This article poses two questions: How are these two arguments related, and what can we learn from their interrelation? I contend that we can better understand the error argument as nested within the gap because the error is a limited case of the gap with narrower features. Furthermore, this nestedness provides philosophers with conceptual tools for analyzing (...) more robustly how values pervade science. (shrink)

This paper argues that there exists a collective epistemic state of ‘Broad Medical Uncertainty’ regarding the effectiveness of many medical interventions. We outline the features of BMU, and describe some of the main contributing factors. These include flaws in medical research methodologies, bias in publication practices, financial and other conflicts of interest, and features of how evidence is translated into practice. These result in a significant degree of uncertainty regarding the effectiveness of many medical treatments and unduly optimistic beliefs about (...) the benefit/harm profiles of such treatments. We argue for an ethical presumption in favour of openness regarding BMU as part of a ‘Corrective Response’. We then consider some objections to this position, including concerns that public honesty about flaws in medical research could undermine trust in healthcare institutions. We suggest that, as it stands, the Anti-Corrective Response is unconvincing. (shrink)

In times of crises, public health leaders may claim that trials of public health interventions are unethical. One reason for this claim can be that equipoise—i.e. a situation of uncertainty and/or disagreement among experts about the evidence regarding an intervention—has been disturbed by a change of collective expert views. Some might claim that equipoise is disturbed if the majority of experts believe that emergency public health interventions are likely to be more beneficial than harmful. However, such beliefs are not always (...) justified: where high quality research has not been conducted, there is often considerable residual uncertainty about whether interventions offer net benefits. In this essay we argue that high-quality research, namely by means of well-designed randomized trials, is ethically obligatory before, during, and after implementing policies in public health emergencies (PHEs). We contend that this standard applies to both pharmaceutical and non-pharmaceutical interventions, and we elaborate an account of equipoise that captures key features of debates in the recent pandemic. We build our case by analyzing research strategies employed during the COVID-19 pandemic regarding drugs, vaccines, and non-pharmaceutical interventions; and by providing responses to possible objections. Finally, we propose a public health policy reform: whenever a policy implemented during a PHE is not grounded in high-quality evidence that expected benefits outweigh harms, there should be a planned approach to generate high-quality evidence, with review of emerging data at preset time points. These preset timepoints guarantee that policymakers pause to review emerging evidence and consider ceasing ineffective or even harmful policies, thereby improving transparency and accountability, as well as permitting the redirection of resources to more effective or beneficial interventions. (shrink)

We simulate trial data to test speculative claims about research methods, such as the impact of publication bias.

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. (shrink)

Drug regulation is fraught with inductive risk. Regulators must make a prediction about whether or not an experimental pharmaceutical will be effective and relatively safe when used by typical patients, and such predictions are based on a complex, indeterminate, and incomplete evidential basis. Such inductive risk has important practical consequences. If regulators reject an experimental drug when it in fact has a favourable benefit/harm profile, then a valuable intervention is denied to the public and a company’s material interests are needlessly (...) thwarted. Conversely, if regulators approve an experimental drug when it in fact has an unfavourable benefit/harm profile, then resources are wasted, people are needlessly harmed, and other potentially more effective treatments are underutilized. Given that such regulatory decisions have these practical consequences, non-epistemic values about the relative importance of these consequences impact the way such regulatory decisions are made (similar to the analysis of laboratory studies on the toxic effects of dioxins presented in Douglas [2000]). To balance the competing demands of the pertinent non-epistemic values, regulators must perform what I call an “inductive risk calculus.” At least in the American context this inductive risk calculus is not well-managed. (shrink)

The US Food and Drug Administration (FDA) is fraught with controversies over the role of values and politics in regulatory science, especially with drugs in the realm of reproductive health. Philosophers and science studies scholars have investigated the ways in which social context shapes medical knowledge through value judgments, and feminist scholars and activists have criticized sexism and injustice in reproductive medicine. Nonetheless, there has been no systematic study of values and gender norms in FDA drug regulation. I focus on (...) three questions about values in regulatory science. First, how have societal values and gender norms shaped the way that the FDA regulates drugs in the realm of reproductive health, specifically with drug labels? Second, what are the ethical, epistemic, and social consequences of these influences on regulation for women and other marginalized groups? Third, which societal values and gender norms ought to influence drug regulation about reproductive health, and how ought this happen? Integrating philosophical analysis with historical archival research and in-depth interviews, I conduct three case studies of drug labeling about reproductive health: (1) the “drug fact” about the mechanism of the morning-after pill; (2) the package inserts for patients about the health risks of oral contraceptives; and (3) the special physician labels made for prescribing drugs to pregnant women. I identify three challenges for the FDA and suggest ways to reduce the influence of sexist values and facilitate feminist alternatives. First, across these cases, I have found that there are many ways in which other concerns in reproductive medicine (such as zygotic life, fetal health, and population control) have devalued women’s health. Second, both knowledge and ignorance xvi about their reproductive health have contributed to women’s oppression, especially poor women and women of color. Finally, by avoiding the epistemic dimensions of ethics, powerful, mostly male parties in medicine (such as doctors, pharmaceutical companies, and religious institutions) have misused “informed consent,” “religious freedom,” and “paternalism” for unethical purposes. For improvement, I suggest extracting sexist values and gender norms from regulatory science that cause epistemic injustices, and I point to success stories for reforming sexism with feminism at the FDA. (shrink)