A Tale of Three Cultures

Despite similar financial goals among healthy volunteers, there are regional differences in the culture of Phase I participation. Chapter 3 focuses on this theme to further unpack variations in how patterns of imbricated stigma influence healthy volunteers’ perceptions of Phase I trials, particularly with respect to the longevity of their study involvement. Specifically, East Coast participants tend to be well-networked as part of their long-term, active pursuit of clinical trials, but they often also express anti-capitalist critiques of the industry. In comparison, Midwesterners tend to be more passive about their trial participation, thinking of it as a short-term financial opportunity to counterbalance a temporary setback. West Coast participants occupy a hybrid culture between those of the East Coast and Midwest participants, actively seeking out new studies but expressing a distrust in the clinics and wanting to limit their study involvement. These regional cultures act as a prism for healthy volunteers’ perceptions of Phase I trials, shaping whether and how they adopt identities as research participants.

“Doing the Lab Rat Thing”

Chapter 2 focuses on the economic motivations of healthy volunteers. Drawing upon the concept of imbricated stigma, it describes how social inequalities shape participants’ views of Phase I trials. It examines not only the catalysts in their lives that lead to study enrollment but also how economic need, employment opportunities, and consumer culture influence how participants view the value of study compensation. The chapter details three uses to which study compensation is typically put: revenue to make ends meet, investments in the future, and disposable income for consumption. Because clinical trial participation is stigmatized, healthy volunteers often feel the need to cover up their participation, and the chapter illustrates the lengths some go to keep their study involvement secret.

Conclusion

The book’s conclusion reflects on the political and economic context of US Phase I trials. A society characterized by deeply imbricated stigmas ensures that there will always be healthy volunteers willing to enroll in Phase I trials, whether these are the same or new participants who need the financial compensation. Ultimately, attending to the underlying social inequalities animating the Phase I industry is critical to understand what is at stake when healthy volunteers are used in drug development.

The Dark Side of the Model

The clinic practices that make healthy volunteers into model organisms also raise important validity concerns about Phase I trials. Chapter 6 concentrates particularly on the ways in which healthy volunteers, clinics, and the pharmaceutical industry all have incentives to make investigational drugs appear safer than they really might be. The chapter considers intrinsic validity concerns, extrinsic validity concerns, and adverse event reporting as a validity calamity. Intrinsic concerns have to do with the sex, race/ethnicity, age, and seriality of healthy volunteers and raise the question of whether and to what extent healthy volunteers can be considered representative of the general population. Extrinsic concerns include staff and healthy volunteer practices, such as treating the inclusion-exclusion criteria for studies as more malleable than intended or failing to adhere to or enforce the waiting period before healthy volunteers can enroll in their next study. The chapter concludes with a treatment of adverse event reporting as an in-depth case of validity problems that emerge in clinical trials when all the actors have an economic interest in underreporting any symptoms that occur in healthy volunteers during these studies.

Entering the Clinic

Chapter 1 provides ethnographic detail about entering and being confined to a Phase I clinic. It provides a sense of place: what one such clinic looks like and how it operates as well as the clinic’s social world, including the camaraderie and conflicts among healthy volunteers. The project methods are described, including how access to the six clinics was gained for the study, how field work was conducted, and the demographic information for the research staff and healthy volunteers who were included in the study.

Consenting to Adverse Events

Chapter 7 draws on secondary data about the safety of Phase I trials to discuss how research staff and healthy volunteers alike struggle to make sense of the omnipresent hypothetical risks of studies, outlined in informed consent forms, in the face of tangible evidence of the trials’ relative safety. Serial participation fundamentally shapes healthy volunteers’ view of trial risks. This is because repeated enrollment diminishes the importance of the formal consent process as healthy volunteers’ own experiences take priority. As long as participants are unharmed in the studies they complete, they become desensitized to the risks and place trust in the research process, believing that the clinics will keep them safe. At the same time, as model organisms, healthy volunteers are often regarded as being indifferent to risks. They are even stigmatized as desperate people too focused on the money that they will earn from a study to assess appropriately the harms that might occur. From this vantage point, study participation is viewed contradictorily as safe unless someone is not taking the consent process seriously.

A Laboratory for Human Animals

The Phase I clinic can be seen as a type of laboratory for human animals. Chapter 5 further develops the concept of the healthy volunteer as a model organism, and it explores how standardization and control are imposed on healthy volunteers who are confined for studies. In Phase I clinics, what happens, and how often, to participants differs dramatically from later-phase clinical trials. Additionally, the strict inclusion-exclusion criteria for studies define “healthy” in terms of narrow physiological markers that volunteers must meet in order to participate. In the process, the healthy volunteer becomes a type of model organism that is maximally suited to Phase I research. The chapter also illustrates how research staff’s practices in selecting and managing healthy volunteers define who can enroll at their clinics and normalize those participants to the demands of Phase I trials.

Constructing Risk Knowledge

Healthy volunteers’ construction of trials as safe is enabled by their categorization of some studies as riskier than others. Chapter 8 describes this process as a type of model organism epistemology and illustrates how this knowledge comes from personal experiences as well as stories and rumors healthy volunteers hear from other participants. This information accretes into what could be thought of as collective “risk filters” when the same types of investigational drugs or clinical procedures continuously emerge at the center of healthy volunteers’ stories. A risk filter acts as a preliminary basis for evaluating the risk of a specific Phase I study by comparing it to the collective experience of participants in similar clinical trials. Regardless of their claims about inherent risk, healthy volunteers mobilize this information in their decision-making about which Phase I trials to join and which to avoid.

Speculating on Health

While healthy volunteers are concerned about the risks of studies, they are often much more vocal about the economic risk of not qualifying for studies. This chapter examines how being disqualified from studies through screen failures heightens their sense of risk as they attempt to earn income through clinical trials. It also considers how the screening process itself profoundly influences their health behaviors even outside of their study participation, including maintaining a healthy weight, eating nutritious food, consuming vitamins and supplements, and abstaining from deleterious substances, such as alcohol, tobacco, and illicit drugs. These actions on the part of healthy volunteers, which contribute to their model organism status, indicate that Phase I participation could counterintuitively improve their general health even as they expose themselves to the unknown risks of investigational drugs.

The Commercialization of Phase I Trials

Shifting focus from the healthy volunteers to the clinics themselves, Chapter 4 provides a brief history of the Phase I industry to contextualize the opportunistic nature of many of the clinics that are currently operating in the United States. Clinics’ concerns about profitability and/or reputation lead to different investments in their facilities and staffing, which in turn result in a wide variation in experiences for healthy volunteers depending on where they enroll. In short, some clinics are perceived as state-of-the-art facilities that are comfortable and professional spaces, whereas others are rundown and have few amenities, indicating that participants’ needs are clearly not the priority. The material configurations of Phase I clinics communicate to healthy volunteers important messages about their safety and worth.