Department of Social Medicine and Center for Bioethics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Department of Sociology and Anthropology, North Carolina State University, Raleigh, North Carolina, United States of America.
PLoS Med. 2018 Nov 20;15(11):e1002698. doi: 10.1371/journal.pmed.1002698. eCollection 2018 Nov.
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.
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.
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.
关于健康志愿者对 I 期临床试验风险的看法，目前相关研究有限。为了从经验上解决健康志愿者参与药物开发所引发的长期存在的伦理问题，评估这些参与者如何理解试验风险至关重要。本研究的目的是调查：（1）参与者对 I 期试验总体风险的看法；（2）他们对个人在试验中受到伤害的风险的看法；以及（3）风险认知如何因参与者的临床试验史和社会人口统计学特征而有所不同。
我们对 178 名曾参加过美国各种 I 期试验的健康志愿者进行了半结构式访谈，并对访谈内容进行了定性和定量分析。参与者在报告的 1948 项 I 期试验中共有经验（平均=10.9；中位数=5），他们作为健康志愿者风险认知、试验入组决策和日常健康行为的纵向研究的一部分接受了访谈。对参与者的定性反应进行了编码、分析，并随后进行量化，以评估他们的风险认知与种族/民族、性别、年龄、教育程度、就业状况和家庭收入等人口统计学特征之间的相关性。我们发现，健康志愿者对 I 期试验的总体风险的看法往往与他们个人受到伤害的风险不同。我们的大多数参与者认为 I 期试验的风险是中等、高或极高（178 名参与者中的 118 名），但大多数参与者仍然认为他们个人是安全的（178 名参与者中的 97 名）。我们还发现，首次参加临床试验的健康志愿者、少数族裔参与者和西班牙裔参与者往往认为总体试验风险很高（分别为 Jonckheere-Terpstra，-2.433，p=0.015；Fisher 精确检验，p=0.016；Fisher 精确检验，p=0.008），但这些群体在个人受到伤害的风险认知方面没有差异（分别为卡方检验，3.578，p=0.059；卡方检验，0.845，p=0.358；卡方检验，1.667，p=0.197）。本研究的主要限制来自于对深入访谈数据的定量汇总，这要求研究团队对参与者非标准化的风险叙述进行解释。
本研究表明，健康志愿者通常对 I 期试验风险有认识并能进行反思。健康志愿者对总体风险和个人风险的看法存在差异，这说明了为什么健康志愿者即使认为整个试验风险很高，仍可能继续参加临床试验。
