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)

This article empirically examines how healthy volunteers evaluate and make sense of the risks of phase I clinical drug trials. This is an ethically important topic because healthy volunteers are exposed to risk but can gain no medical benefit from their trial participation. Based on in-depth qualitative interviews with 178 healthy volunteers enrolled in various clinical trials, we found that participants focus on myriad characteristics of clinical trials when assessing risk and making enrolment decisions. These factors include the short-term and (...) long-term effects; required medical procedures; the type of trial, including its design, therapeutic area of investigation, and dosage of the drug; the amount of compensation; and trust in the research clinic. In making determinations about the study risks, participants rely on information provided during the consent process, their own and others’ experiences in clinical trials, and comparisons among studies. Our findings indicate that the informed consent process succeeds in communicating well about certain types of risk information while simultaneously creating lacunae that are problematically filled by participants through their collective experiences and assumptions about risk. We discuss the ethical implications of these findings and make recommendations for improving the consent process in healthy volunteer trials. (shrink)

Healthy Volunteers (HVs) who participate in clinical trials are a vulnerable group that deserves specific protection. We assessed the number and types of studies that involve HVs around the world and outline the methodological barriers to their analysis. We found that tens of thousands of HVs are involved every year in clinical trials in a large variety of countries and that the overwhelming majority of studies are not “first-in-human” but pharmacokinetic studies. The two cornerstones for both ethical and safe participation (...) of HVs in clinical trials are properly obtained informed consent, and a minimization of exposure to risk, in particular by avoiding concealed participation in multiple trials. To minimize the risk of exploitation of HVs and their exposure to risk, we propose ways to ensure genuine informed consent, and advocate setting up national Healthy Volunteer volunteer registries as established in France and the U.K. (shrink)

This article empirically examines how healthy volunteers evaluate and make sense of the risks of phase I clinical drug trials. This is an ethically important topic because healthy volunteers are exposed to risk but can gain no medical benefit from their trial participation. Based on in-depth qualitative interviews with 178 healthy volunteers enrolled in various clinical trials, we found that participants focus on myriad characteristics of clinical trials when assessing risk and making enrolment decisions. These factors include the short-term and (...) long-term effects; required medical procedures; the type of trial, including its design, therapeutic area of investigation, and dosage of the drug; the amount of compensation; and trust in the research clinic. In making determinations about the study risks, participants rely on information provided during the consent process, their own and others’ experiences in clinical trials, and comparisons among studies. Our findings indicate that the informed consent process succeeds in communicating well about certain types of risk information while simultaneously creating lacunae that are problematically filled by participants through their collective experiences and assumptions about risk. We discuss the ethical implications of these findings and make recommendations for improving the consent process in healthy volunteer trials. (shrink)

This article empirically examines how healthy volunteers evaluate and make sense of the risks of phase I clinical drug trials. This is an ethically important topic because healthy volunteers are exposed to risk but can gain no medical benefit from their trial participation. Based on in-depth qualitative interviews with 178 healthy volunteers enrolled in various clinical trials, we found that participants focus on myriad characteristics of clinical trials when assessing risk and making enrolment decisions. These factors include the short-term and (...) long-term effects; required medical procedures; the type of trial, including its design, therapeutic area of investigation, and dosage of the drug; the amount of compensation; and trust in the research clinic. In making determinations about the study risks, participants rely on information provided during the consent process, their own and others’ experiences in clinical trials, and comparisons among studies. Our findings indicate that the informed consent process succeeds in communicating well about certain types of risk information while simultaneously creating lacunae that are problematically filled by participants through their collective experiences and assumptions about risk. We discuss the ethical implications of these findings and make recommendations for improving the consent process in healthy volunteer trials. (shrink)

Phase 1 healthy volunteer clinical trials—which financially compensate subjects in tests of drug toxicity levels and side effects—appear to place pressure on each joint of the moral framework justifying research. In this article, we review concerns about phase 1 trials as they have been framed in the bioethics literature, including undue inducement and coercion, unjust exploitation, and worries about compromised data validity. We then revisit these concerns in light of the lived experiences of serial participants who are income-dependent on phase (...) 1 trials. We show how participant experiences shift attention from discrete exchanges, behaviors, and events in the research enterprise to the ongoing and dynamic patterns of serial participation in which individual decision-making is embedded in collective social and economic conditions and shaped by institutional policies. We argue in particular for the ethical significance of structurally diminished voluntariness, routine powerlessness in setting the terms of exchange, and incentive structures that may promote pharmaceutical interests but encourage phase 1 healthy volunteers to skirt important rules. (shrink)

Lowering compensation to research subjects to protect them from “undue inducement” is a misguided attempt to shoehorn a concern about exploitation into the framework of autonomy. We suggest that oversight bodies should be less concerned about undue influence than about exploitation of subjects. Avoiding exploitation in human subjects research requires not only increasing compensation, but enhancing the dignity of research participation.

This special issue of Science, Technology, & Human Values contains articles concerned with ethics in and around scientific practice. These articles ask how organizational routines both produce and diffuse concerns about the risks and benefits of scientific research and products, and why context remains elusive in formal ethical analysis. These cases are from diverse settings, with several touching on issues of economic inequality and participation in scientific research. Each article describes in some way how cultural and institutional configurations shape ethical (...) thinking and the distribution of goods and harms in science. (shrink)