Gendered Logics of Biomedical Research: Women in U.S. Phase I Clinical Trials.

Despite the importance of including diverse populations in biomedical research, women remain underrepresented as healthy volunteers in the testing of investigational drugs in Phase I trials. Contributing significantly to this are restrictions that pharmaceutical companies place on the participation of women of so-called childbearing potential. These restrictions have far-reaching effects on biomedical science and the public health of women. Using 191 interviews collected over 3 years, this article explores the experiences of 47 women who navigate restrictions on their participation in U.S. Phase I trials. Women in this context face a number of contradictory criteria when trying to enroll, which can curtail their participation, justify additional surveillance, and deny pregnant women reproductive agency. The pharmaceutical industry's putative protections for hypothetical fetuses exacerbate inequalities and attenuate a thorough investigation of the safety of their drugs for public consumption. We use the framework of "anticipatory motherhood" within a gendered organizations approach to make sense of women's experiences in this context.

Phase I trial compensation: How much do healthy volunteers actually earn from clinical trial enrollment?

BACKGROUND/AIMS: Financial compensation for research participation is a major focus of ethical concern regarding human subject recruitment. Phase I trials are sometimes considered to be a lucrative source of income for healthy volunteers, encouraging some people to become "professional guinea pigs." Yet, little is known about how much these clinical trials actually pay and how much healthy volunteers earn from them. METHODS: As part of a mixed-methods, longitudinal study of healthy volunteers, we required participants to complete clinical trial diaries, or surveys that captured detailed information about screening and enrollment in Phase I trials. Over a 3-year period, participants provided information online or via telephone about each clinical trial for which they screened (e.g. the clinic name, the study's therapeutic area, the length of the trial, the number of nights spent in the clinic, and the study compensation), and whether they qualified for trial inclusion. Clinical trial diaries generated data about whether participants continued to screen for and enroll in clinical trials and how much money they earned from their participation. RESULTS: 131 participants routinely completed clinical trial diaries or confirmed that they had not screened for any new clinical trials. Together, these participants screened for 1001 clinical trials at 73 research facilities during a 3-year period. Overall, the median clinical trial compensation was US$3070 (range = US$150-US$13,000). Participants seeking new healthy volunteer trials tended to screen for three studies per year, participate in one or two studies, and earn roughly US$4000 annually. Participants who were unemployed earned the most income from clinical trials compared to those with full-time or part-time jobs, and those individuals whom we label "occupational" participants because of their persistent pursuit of clinical trials earned more than people who screened occasionally. Notably, the median annual trial compensation was well below US$10,000 for all employment groups, and most occupational healthy volunteers also earned less than US$10,000 each year. The 10% of participants who earned the most had a median annual income of US$18,885 from clinical trials, and there was significant volatility in these individuals' earnings from year to year. CONCLUSION: Despite the perception that Phase I enrollment can generate significant earnings, it was exceedingly rare for anyone in this study to make more than US$20,000 in a single year, and unusual to earn even between US$10,000 and US$20,000. From an ethics perspective, individual trials might appear to unduly induce enrollment by offering significant sums of money, but given our findings, the larger problem for low-income participants may be the unrealistic perception that clinical trials alone could be a way of earning a living.

Sacrificial Labour: Social Inequality, Identity Work, and the Damaging Pursuit of Elusive Futures.

This article explores the relationship between personal sacrifice and identity work within conditions of profound structural insecurity. We develop the concept of sacrificial labour to describe how individual self-sacrifice aligns workers' identities to the needs of organizations while gradually foreclosing the actualization of individuals' desired future selves. Drawing upon qualitative data from a longitudinal study of healthy individuals who enrol in paid clinical trials for the pharmaceutical industry, we make two contributions to the identity-work literature. First, we argue that the ongoing project of building stable and secure identities may become damaging when structural and cultural conditions defy even provisional, fragile attainment of this goal. Second, we reflect on how racialization and social marginalization erode identities and constrain possibilities for identity recuperation. Whereas the identity-work literature often focuses on the agential accomplishments of individuals, we provide a troubling account of how persistent social and economic inequalities confound identity realization efforts.

Healthy volunteers' perceptions of risk in US Phase I clinical trials: A mixed-methods study.

BACKGROUND: There is limited research on healthy volunteers' perceptions of the risks of Phase I clinical trials. In order to contribute empirically to long-standing ethical concerns about healthy volunteers' involvement in drug development, it is crucial to assess how these participants understand trial risks. The objectives of this study were to investigate (1) participants' views of the overall risks of Phase I trials, (2) their views of the risk of personally being harmed in a trial, and (3) how risk perceptions vary across participants' clinical trial history and sociodemographic characteristics. METHODS AND FINDINGS: We qualitatively and quantitatively analyzed semi-structured interviews conducted with 178 healthy volunteers who had participated in a diverse range of Phase I trials in the United States. Participants had collective experience in a reported 1,948 Phase I trials (mean = 10.9; median = 5), and they were interviewed as part of a longitudinal study of healthy volunteers' risk perceptions, their trial enrollment decisions, and their routine health behaviors. Participants' qualitative responses were coded, analyzed, and subsequently quantified in order to assess correlations between their risk perceptions and demographics, such as their race/ethnicity, gender, age, educational attainment, employment status, and household income. We found that healthy volunteers often viewed the overall risks of Phase I trials differently than their own personal risk of harm. The majority of our participants thought that Phase I trials were medium, high, or extremely high risk (118 of 178), but most nonetheless felt that they were personally safe from harm (97 of 178). We also found that healthy volunteers in their first year of clinical trial participation, racial and ethnic minority participants, and Hispanic participants tended to view the overall trial risks as high (respectively, Jonckheere-Terpstra, -2.433, p = 0.015; Fisher exact test, p = 0.016; Fisher exact test, p = 0.008), but these groups did not differ in regard to their perceptions of personal risk of harm (respectively, chi-squared, 3.578, p = 0.059; chi-squared, 0.845, p = 0.358; chi-squared, 1.667, p = 0.197). The main limitation of our study comes from quantitatively aggregating data from in-depth interviews, which required the research team to interpret participants' nonstandardized risk narratives. CONCLUSIONS: Our study demonstrates that healthy volunteers are generally aware of and reflective about Phase I trial risks. The discrepancy in healthy volunteers' views of overall and personal risk sheds light on why healthy volunteers might continue to enroll in clinical trials, even when they view trials on the whole as risky.

Serial Participation and the Ethics of Phase 1 Healthy Volunteer Research.

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.

Risk and Emotion Among Healthy Volunteers in Clinical Trials.

Theorized as objective or constructed, risk is recognized as unequally distributed across social hierarchies. Yet the process by which social forces shape risk and risk emotions remains unknown. The pharmaceutical industry depends on healthy individuals to voluntarily test early-stage, investigational drugs in exchange for financial compensation. Emblematic of risk in late modernity, Phase I testing is a rich site for examining how class and race shape configurations of emotion and risk. Using interview data from 178 healthy trial participants, this article examines emotion and risk as mutually constituting processes linked to biographical context and social structure. Biographical events like economic insecurity and incarceration influence how risk is felt by providing comparative experiences of felt risk and felt benefits. Such events, in turn, are structured by class-based and racial inequalities, linking class and race positions to primary emotional experiences of risk.

Stopped hearts, amputated toes and NASA: contemporary legends among healthy volunteers in US phase I clinical trials.

The first stage of testing new pharmaceuticals in humans is referred to as a phase I clinical trial. The purpose of these studies is to test the safety of the drugs and to establish appropriate doses that can later be given to patients. Most of these studies are conducted under controlled, in-patient conditions using healthy volunteers who are paid for their participation. To explore healthy volunteers' experiences in clinical trials, an ethnographic study was conducted at six in-patient phase I clinics in the USA. In addition to the observation of clinic activities (from informed consent procedures to dosing to blood draws), 268 semi-structured interviews were conducted, 33 with clinic staff and 235 with healthy volunteers. Drawing on this dataset, this article explores healthy volunteers' exchange of contemporary legends about phase I clinical trials. In addition to potentially scaring the listener and communicating distrust in the medical community, these incredible stories help participants cope with perceived stigma and establish a gradient of risk of trial participation, creating potential boundaries to their participation in medical research. The article argues that contemporary legends play a productive role in society, shaping how people view themselves and others and influencing their decisions about risky activities.

Feeding and Bleeding: The Institutional Banalization of Risk to Healthy Volunteers in Phase I Pharmaceutical Clinical Trials.

Phase I clinical trials are the first stage of testing new pharmaceuticals in humans. The majority of these studies are conducted under controlled, inpatient conditions using healthy volunteers who are paid for their participation. This article draws on an ethnographic study of six phase I clinics in the United States, including 268 semistructured interviews with research staff and healthy volunteers. In it, I argue that an institutional banalization of risk structures the perceptions of research staff and healthy volunteers participating in the studies. For research staff, there are three mechanisms by which risk becomes banal: a perceived homogeneity of studies, Fordist work regimes, and data-centric discourse. For healthy volunteers, repeat study participation contributes to the institutional banalization of risk both through the process of desensitization to risk and the formation of trust in the clinics. I argue that the institutional banalization of risk also renders invisible ethical concerns about exploitation of underprivileged groups in pharmaceutical research.

Strategies for Obtaining Access to Secretive or Guarded Organizations.

Establishing contacts and gaining permission to conduct ethnographic or qualitative research can be time-consuming and stressful processes. Gaining access can be especially challenging when representatives of prospective research sites see their work as being sensitive and would prefer to avoid outside scrutiny altogether. One result of this dynamic is that many organizations that exert a profound influence in governing populations and regulating individuals' access to basic needs are relatively invisible to the public and shielded from meaningful public accountability. Therefore, it is vital to effectively study secretive or guarded organizations and fill out the empirical record, which in turn could create the conditions for greater public awareness and debate. To that end, this paper draws on our collective research experience and the scholarship of others to present nine strategies that we have found to be especially effective for securing access to secretive organizations.

Expanding the frame of "voluntariness" in informed consent: structural coercion and the power of social and economic context.

This paper introduces the term "structural coercion" to underscore the ways in which broader social, economic, and political contexts act upon individuals to compel them to enroll as subjects in clinical research. The paper challenges the adequacy of the concepts of "coercion" and "undue influence" in determining when research participation is voluntary. Acknowledging structural coercion shifts the frame of ethical deliberation away from specific individuals and specific studies to see important patterns in research participation by salient demographic characteristics. The effects of structural coercion manifest themselves in particular research settings, but unlike the conventional form of coercion, it is not rooted in the researcher-participant relationship or linked to particular study protocols. By extracting voluntariness from entrenched conceptions of the researcher-participant dyad, this paper proposes approaches to minimize the effects of structural coercion while creating new ethical imaginaries for review boards and researchers alike.

Global Efforts to Protect Healthy Volunteers.

Clinical trials on healthy volunteers generate unique ethical challenges both because participants accept potential physical risks without the possibility of direct medical benefit and because participants' financial motivations to enroll in trials could lead to their exploitation. Despite the large volume of published empirical studies and ethical analyses of healthy volunteer research, there has been little concerted effort to change how healthy-volunteer research is overseen or regulated. A new collaborative effort to do so is the VolREthics (Volunteers in Research and Ethics) Initiative. Launched in 2022, this initiative brings together an international community to engage questions about how healthy volunteers could best be protected from the risks of harm and exploitation while the validity of clinical trials is optimized.

Mission Creep or Mission Lapse? Scientific Review in Research Oversight.

BACKGROUND: The ethical use both of human and non-human animals in research is predicated on the assumption that it is of a high quality and its projected benefits are more significant than the risks and harms imposed on subjects. Yet questions remain about whether and how IRBs and IACUCs should consider the scientific value of proposed research studies. METHODS: We draw upon 45 interviews with IRB and IACUC members and researchers with oversight experience about their perceptions of their own roles in reviewing the quality and value of scientific protocols. Interview transcripts were memoed to highlight specific findings, which were then used to identify key themes through an iterative process. RESULTS: IRB and IACUC members expressed broad trust in the need for and value of research, and they often assumed that protocols had social value or that prior review, especially when associated with funding, affirmed both the rigor and merit of those protocols. Some oversight members also took an explicit stance against scientific review by stating that such review is not within the regulatory mandates governing their parts in the oversight system. Yet other interviewees expressed uneasiness about the current paradigm for evaluating the quality and overall value of science, suggesting that IRB and IACUC members perceive gaps in the oversight systems. CONCLUSIONS: These findings reveal many similarities in how IRB and IACUC members understand the roles and limitations of their respective oversight committees. We conclude with a discussion of how the lack of a clear mandate regarding scientific review within US federal regulations may undermine ethical engagement of whether human and animal research is scientifically justified, resulting in a "mission lapse" wherein no organizational body is clearly responsible for ensuring that the research being conducted has the potential to advance science and benefit society.

"Death and Taxes": Why Financial Compensation for Research Participants is an Economic and Legal Risk.

In the US, research payments are technically taxable income. This article argues that tax liability is a form of possible economic and legal risk of paid research participation. Findings are presented from empirical research on Phase I healthy volunteer trials. The article concludes by discussing the implications of these findings for the informed consent process, as well as for broader ethical issues in whether and how payments for research participation should be regulated.

Exclusion of Women from Phase I Trials: Perspectives from Investigators and Research Oversight Officials.

Over the past 30 years, progress has been made in increasing women's representation in clinical research. However, women continue to be underrepresented in phase I clinical trials-those trials that test the safety and tolerability of investigational drugs, often on healthy individuals. As sex-based differences in adverse drug reactions are often linked to drug dose, pivotal safety information in phase I trials is often insufficiently-and inequitably-captured for females. Yet there has been little attention to how clinical investigators and those charged with overseeing the ethical conduct of these trials perceive the barriers to women's inclusion in phase I trials. To address this gap, we report on 22 interviews with U.S. phase I investigators and institutional review board (IRB) members. Our findings indicate that although these investigators and IRB members acknowledged the importance of including women in clinical trials, they justified women's exclusion from phase I trials by citing the need to manage their reproductive potential. In particular, we identified four key themes that informants used to warrant women's exclusion from phase I trials: the structure of the drug-development system itself, fears about risks to potential fetuses, distrust of women to prevent pregnancy, and concerns about risks and burdens to institutions from resulting pregnancies. We argue that these rationales reflect structural and cultural barriers to women's inclusion in clinical research that ultimately fail to respect female research participants as persons, highlighting the need for broad-based solutions.

United States private-sector physicians and pharmaceutical contract research: a qualitative study.

BACKGROUND: There have been dramatic increases over the past 20 years in the number of nonacademic, private-sector physicians who serve as principal investigators on US clinical trials sponsored by the pharmaceutical industry. However, there has been little research on the implications of these investigators' role in clinical investigation. Our objective was to study private-sector clinics involved in US pharmaceutical clinical trials to understand the contract research arrangements supporting drug development, and specifically how private-sector physicians engaged in contract research describe their professional identities. METHODS AND FINDINGS: We conducted a qualitative study in 2003-2004 combining observation at 25 private-sector research organizations in the southwestern United States and 63 semi-structured interviews with physicians, research staff, and research participants at those clinics. We used grounded theory to analyze and interpret our data. The 11 private-sector physicians who participated in our study reported becoming principal investigators on industry clinical trials primarily because contract research provides an additional revenue stream. The physicians reported that they saw themselves as trial practitioners and as businesspeople rather than as scientists or researchers. CONCLUSIONS: Our findings suggest that in addition to having financial motivation to participate in contract research, these US private-sector physicians have a professional identity aligned with an industry-based approach to research ethics. The generalizability of these findings and whether they have changed in the intervening years should be addressed in future studies. Please see later in the article for the Editors' Summary.

Altruism in clinical research: coordinators' orientation to their professional roles.

OBJECTIVE: Research coordinators have significant responsibilities in clinical trials that often require them to find unique ways to manage their jobs, thus reshaping their professional identities. The purpose of this study was to identify how research coordinators manage role and ethical conflicts within clinical research trials. METHODS: A qualitative study combining observation and 63 semistructured interviews at 25 research organizations was used. RESULTS: Altruism is a recurring theme in how research coordinators define and view their work. CONCLUSION: Altruism is adopted by research coordinators to: (1) Teach patient-subjects the appropriate reasons to participate in clinical research, (2) minimize the conflict between research and care, and (3) contest the undervaluation of coordinating. Altruism is a strategy used to handle the various conflicts they experience in a difficult job, and it has become part of the professional identity of clinical research coordinators.