This application responds to PA-11-180: Research on Ethical Issues in Biomedical, Social and Behavioral Research with a focus on seriously ill cancer patients enrolled in cancer clinical trials (CCTs) and the ethics of science. Risk-benefit assessment is an essential component of informed consent and provides information central to patient-participants' research-related decisions in CCTs. Indeed, institutional review boards are charged with discerning whether the risks are reasonable in relation to anticipated benefits, if any, to subjects. However, patient-participants' risk-benefit assessments may differ in significant ways, especially if they are confronted with a life-limiting illness such as cancer, have no other means to receive cancer care, or simply place their trust in the physician investigator and other study team members. A critical gap exists between the theoretical ideal of informed consent (i.e., all information processed and risks and benefits thoroughly evaluated) and how people, particularly those with serious illnesses, make research participation decisions. When patient-participants do not weigh the risks and benefits of trial participation, it may lead to compromised study outcomes, participant withdrawal, and sub-optimal patient and investigator experiences. Building on the work of a recently completed R21 study, this R01 application will innovatively examine how patient-participant, investigator, clinical characteristics and other external factors (pressure from others) influence risk-benefit assessment and subsequent retention in CCTs. To fully capture the experiences of patient-participants, we uniquely measure both the prevalence (assessed versus not assessed) and the extent/degree (extent of assessment and intensity of perceptions) of participants' risk-benefit assessment.
Our specific aims i ntend to: 1) examine the relationship between patient-participant, clinical, and investigator characteristics and other external influences on patient-participants' risk-benefit assessment; 2) examine the relationship between risk-benefit assessment and retention in CCTs after adjusting for important prognostic factors a priori; and 3) define, name, and profile (through cluster analysis techniques) a typology of patient- participants based on their CCT risk-benefit assessment. Moreover, we will model/map via perceptual mapping (multidimensional scaling) how each patient type conceptualizes the risks and benefits involved in CCTs. We will also explore whether risk-benefit perceptions change during the course of CCT enrollment among the first time cohort of participants we enroll (baseline: 30-59 days since consent; second assessment: 90 days since CCT enrollment) in order to help assess potential differential informational or recall bias.
These aims will be met through a mixed methods approach with 432 participants enrolled in CCTs. The complementary qualitative semi-structured interviews will lead to a deeper understanding of risk-benefit assessment as well as examine the factors that influence participant withdrawal. Thus, this project will fundamentally advance our theoretical, empirical, and clinical understanding of risk-benefit assessment in CCTs for those who are seriously ill.
Seriously ill cancer patients make difficult decisions every day regarding their health and well-being, including whether to participate in clinical trials. Informed consent is an essential part of this process, specifically risk-benefit assessment. This project will increase our understanding of the contribution of patient-participant, investigator, clinical, and external factors that influence risk-benefit assessment in cancer clinical trials to advance our understanding of patient-participants' decision-making, to better guide the presentation of information, and to optimize recruitment and retention.
| Ulrich, Connie M; Zhou, Qiuping Pearl; Ratcliffe, Sarah J et al. (2018) Development and Preliminary Testing of the Perceived Benefit and Burden Scales for Cancer Clinical Trial Participation. J Empir Res Hum Res Ethics 13:230-238 |
