We're unable to sign you in at this time. Please try again in a few minutes.
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Special Communication |

Ethics of Phase 1 Oncology Studies Reexamining the Arguments and Data

Manish Agrawal, MD; Ezekiel J. Emanuel, MD, PhD
JAMA. 2003;290(8):1075-1082. doi:10.1001/jama.290.8.1075.
Text Size: A A A
Published online

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.

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?




Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.


Some tools below are only available to our subscribers or users with an online account.

100 Citations

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles

Care at the Close of Life: Evidence and Experience
Moral and Legal Framework

Users' Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice, 3rd ed
Ethical Considerations