Leading Article

International Journal of Pharmaceutical Medicine

, Volume 20, Issue 4, pp 233-242

Ethical Issues in Phase I Cancer Clinical Trials

  • Jeffrey PeppercornAffiliated withDivision of Hematology and Oncology, University of North Carolina at Chapel Hill Email author 

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Abstract

Phase I clinical trials in oncology are designed to study the toxicity of novel drugs and regimens in a small cohort of subjects and to establish a dose that can be used in future studies. Due to the toxicity of many antineoplastic therapies, these trials are typically conducted in subjects with advanced cancer and limited therapeutic options. Patients primarily enrol in phase I cancer trials with high expectations of personal medical benefit; however, the risks and benefits of these regimens are unknown and the benefit from enrolment in phase I cancer trials to date has been modest.

The use of a vulnerable population with high expectations of benefit in a scientific experiment creates challenges for the protection of human research subjects. To ethically use one human being for the benefit of others in a phase I oncology trial requires that the research subject never be viewed merely as a means to an end, but that their interests as a person are always respected and safeguarded. This process begins with trial conception and continues even after completion of the trial.

In trial design, particular attention should be given to the nature of the experimental agent or regimen and the most appropriate dose selection and escalation strategy and study endpoint. Older paradigms of inter-patient dose escalation and the establishment of maximally tolerated dose may not be appropriate for all studies. Once a well designed study has been established, the primary challenge is to ensure the voluntary informed consent of research participants. This process involves an explanation of the rationale for the study and details of what study participation actually involves in terms of schedules, drug administration, tests and procedures, and predicted toxicities. It also involves an explanation of the nature of phase I clinical trials with a focus on the nature of uncertainty in terms of risks and benefits, differences between trial care and prior care outside a trial, and the disclosure of any potential conflicts of interest and how these will be mediated.

Phase I oncology trials are critically important in the advance of the care of future cancer patients, but such advances must be achieved on a foundation of respect for today’s patients. Trial design and enrolment must be conducted in a way that lets those who choose to participate do so in a way that also maximises their chance of medical benefit, minimises their risk of harm, and maintains the principle of respect for persons at all times.