This revised grant application seeks to study, and address, the ethical dilemmas created by the participation of advanced cancer patients as research subjects in phase I trials of experimental agents. The ethical principles that provide the framework for study in this application are those principles that must guide all forms of clinical research. However, in the case of phase I cancer trials, these principles create particularly challenging dilemmas because of the perceived potential vulnerability of a terminally-ill patient population involved as research subjects, the very low likelihood of measurable clinical benefit achieved by phase I trial participation, and the available survey and interview research data regarding outcomes, i.e., understanding, of several crucial elements of the informed consent process for these trials. While participation in phase I trials remains a medically and socially acceptable alternative for many advanced cancer patients, these dilemmas lead to significant obstacles that prevent an ideal environment of effective communication and decision making among potential research subjects and the involved physician-investigators. Thus, the following dilemmas, phrased as questions, will become the specific research focus of this continuation application: Are patients being used as a means to an end without their full consent and understanding? Are subjects being inadvertently deceived by their own overwhelming desires for therapeutic benefits, their lack of acceptance of a terminal prognosis and poor communication with the involved phase I investigators? Can interventions improve these subjects understanding of key elements of the informed consent process for phase I trials? The research approach to these questions will incorporate both the recognition of the ethical importance of advanced cancer patients' understanding of their (life-ending) disease and their alternatives to research participation. This application will build upon the principal investigator's prior efforts in studying these difficult issues, employing a variety of descriptive, validated, and intervention research methods to improve our understanding of how best to provide meaningful information about treatment choices and clinical research opportunities to those with advanced cancer. ? ? ? ?
