Informed Consent and Decision Making Among Participants in Novel-Design Phase I Oncology Trials

Abstract

Background: Although phase I clinical trials are the gateway to progress in cancer therapies, this setting poses ethical challenges to ensure that patients provide consent free from misunderstandings of therapeutic intent or unrealistic expectations of benefit. The design of phase I oncology trials has evolved rapidly over time and today includes more targeted agents and combinations of experimental drugs with standard drugs, which may further complicate how patients understand phase I research participation. Methods: We conducted semistructured interviews regarding motivations, decision making, and understanding of trial purpose nested within a phase I clinical trial of a novel PI3kinase inhibitor combined with a standard oral chemotherapy in 18 participants. Results: Fewer than half of patients correctly identified the safety and dosing objectives. The inclusion of a targeted agent was attractive to participants and was perceived as an indicator of less toxic or more efficacious therapy, with less appreciation for added risks. The significance of a cellular drug target, without a known predictive biomarker of response, was unclear to patients. The inclusion of a standard drug in the regimen attracted patients with more treatment options than traditional first-in-human participants. Patients frequently expressed a realistic understanding of prognosis and uncertainty of benefit, but simultaneous hopes for extraordinary outcomes. Conclusion: Novel phase I oncology trial designs may attract patients with less constrained treatment options, but the inclusion of targeted drugs and combinations including standard chemotherapies is likely to complicate understanding of safety and dosing objectives and likelihood of personal benefit for purposes of informed consent.