Research Article: Healthy volunteers’ perceptions of risk in US Phase I clinical trials: A mixed-methods study

Date Published: November 20, 2018

Publisher: Public Library of Science

Author(s): Jill A. Fisher, Lisa McManus, Marci D. Cottingham, Julianne M. Kalbaugh, Megan M. Wood, Torin Monahan, Rebecca L. Walker, Peter A. Newman

Abstract: BackgroundThere 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 findingsWe 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.ConclusionsOur 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.

Partial Text: Healthy volunteers are recruited using financial incentives to participate in Phase I clinical trials to evaluate the safety and tolerability of investigational drugs. These trials are generally considered quite safe [1], which justifies the enrollment of healthy participants who cannot personally benefit medically from their involvement. Meta-analyses of Phase I trial risks indicate that healthy volunteers are highly likely to experience short-term bodily changes, such as headaches or gastrointestinal problems, but serious or life-threatening problems are rare [2–5]. Yet, when tragedies occur in Phase I trials, news stories about deaths or permanent injury to healthy volunteers often circulate widely [6–9].

Similar to prior research on risk perceptions [26], our findings demonstrate that risk perception is multifaceted, with healthy volunteers perceiving the overall risks of clinical trials and the risks of personal harm as generally different. The majority of our participants characterized Phase I trials to be medium or high risk, but most nonetheless assumed they were personally safe from harm. Importantly, the dominant belief among participants that they are unlikely to be harmed is broadly reflective of the meta-analyses that support the relative safety of Phase I trials in terms of the risk of serious or life-threatening problems, although not in avoidance of unpleasant side effects [1–3].

Our study demonstrates that healthy volunteers are generally reflective about the risks of Phase I participation and distinguish between the overall risk of Phase I trials and their personal risk of harm. Racial and ethnic minorities as well as participants new to clinical trials typically saw the overall risks of trials as higher than did non-Hispanic whites and participants with more trial experience, respectively. However, there were no differences among groups in their perceptions of personal risk of harm. 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. While our goal was not to evaluate the accuracy of either set of perceptions, it cannot be the case both that clinical trials overall present significant risk of harm and yet each individual participant is safe from harm. More work needs to be done—whether for Phase I trials on healthy volunteers or later-phase trials on affected patients—to determine how participants close the gap between their perceptions of overall clinical trial risks and personal risk of harm. This is important in part because relying on improbable narratives of personal exemption from risk of harm may indicate that participants are unduly induced by the offer of compensation and that the voluntariness of their participation is therefore compromised. In future empirical studies, if researchers conflate the potentially differing views of risk, they may also fail to illuminate problems in how participants construct narratives of clinical trial risk or personal risk exemption, or in how clinical investigators present or diffuse risk information.

Source:

http://doi.org/10.1371/journal.pmed.1002698

 

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