STUDY OF COHORT-SPECIFIC CONSENT AND PATIENT CONTROL IN PHASE-I CANCER TRIALS

Purpose: To address the challenging ethical dilemmas created from the participation of advanced cancer patients in phase I trials, we assess ed the feasibility of a clinical trial design that uses an interactive informed consent process in which patient-subjects can choose to beco me directly involved in decisions of dose escalation. Patients and Met hods: Subjects were advanced cancer patients in the Hematology/Oncolog y Clinics at the University of Chicago who were eligible to participat e in a phase I trial in which they underwent a three-step informed con sent process that used cohort-specific consent and allowed them the op tion to choose their own doses of the chemotherapeutic agents under st udy, vinorelbine (NVB) and paclitaxel (TAX), within predetermined limi ts. NVB and TAX were administered in conventional 21- to 28-day cycles for two cycles while on study. Dose escalation occurred when a patien t subject chose a higher untested dose after they received information on all previously assessable patient subjects. In addition to the pha se I trial itself, a survey that consisted of structured interviews, w hich sought to evaluate patients' experiences with the interactive sub ject-choice phase I trial design and consent process, was conducted wi th participating subjects, The phase I trial itself sought to determin e the associated toxicities of the agents under study. The survey resu lts were compared with a similar survey of a matched control populatio n of subjects who participated in other concurrently active convention al phase I trials at our institution. Results: Twenty-nine patient-sub jects participated in the phase I trial, with 24 who agreed to and com pleted the survey interviews. Seventy-six percent of patient-subjects opted to choose their dose of the agents under study, and 28% chose th e highest available doses. More than half of the patient-subjects (56% ) felt some degree of comfort in being asked to choose their dose of c hemotherapy, with 53% stating that being asked to choose their dose ma de them feel in control, fully informed, or content. However, there we re no statistically significant improvements in objective measures of the informed consent process, which included surveyed subjects' stated understanding of either provided information about phase I trials and alternatives to trial participation or of the research purpose of pha se I trials. By making choices, the group of patients in the interacti ve subject choice trial changed the size of the dose cohorts and modif ied the process of dose escalation in this phase I study Conclusion: A lthough complex, our innovative phase I trial design is feasible. In a ddition to the use of cohort-specific consent, the trial design may re duce the magnitude of many of the commonly recognized ethical dilemmas associated with this form of clinical research, which include difficu lties with information provision and the understanding of possible ris ks and benefits of phase I trial participation, through direct subject involvement in research decision making by otherwise potentially vuln erable cancer patients. (C) 1998 by American Society of Clinical Oncol ogy.