Author Affiliations: Department of Clinical Bioethics, Warren G. Magnuson Clinical Center and National Cancer Institute, National Institutes of Health, Bethesda, Md.
Phase 1 oncology trials are critical to improving the treatment of cancer.
Critics have raised 2 fundamental ethical challenges about phase 1 cancer
research: the paucity of benefits with substantial risks and poor-quality
informed consent. Despite 3 decades of controversy about phase 1 oncology
research, there is little critical analysis of the arguments or of the data
relevant to these questions. Existing but old data reveal that about 5% of
patients in phase 1 trials experience shrinkage of their tumor, with a 0.5%
mortality rate. In some notable cases, patients in phase 1 trials have been
cured or sustained long-term remissions. Limited data suggest that patients
in phase 1 trials may have better quality of life than comparable patients
receiving supportive care. More important, the risks and benefits of phase
1 trials are not clearly worse than risk-benefit ratios used by the US Food
and Drug Administration to approve chemotherapeutic agents for clinical use.
The objections based on informed consent are deficiencies of disclosure, understanding,
and voluntariness. The available data do not support the claim that disclosure
is deficient. Although studies evaluating patient understanding have substantial
methodological problems, they demonstrate that more than 70% of patients understand
that they may not directly benefit even when they hope they will personally
benefit. Finally, a closer look at issues of voluntariness reveals that patients
with advanced cancer who participate in phase 1 research may have a different
set of values than do critics and are not coerced. Overall, it appears that
phase 1 oncology trials satisfy the requirement for a favorable risk-benefit
ratio and that patients who enroll provide adequate informed consent.
Agrawal M, Emanuel EJ. Ethics of Phase 1 Oncology StudiesReexamining the Arguments and Data. JAMA. 2003;290(8):1075-1082. doi:10.1001/jama.290.8.1075