Editor’s Note
	Equipoise in Clinical Trials

The current practice of breast cancer medicine — and for that matter, medical care in general — is dominated by the need for research-based evidence to support clinical decision-making. At the core of relevant clinical investigation is the randomized trial, and one of the great challenges in designing these critical studies is the requirement for randomization arms that physicians can ethically and comfortably discuss with their patients. Researchers often state that they must be “in equipoise with the options”: all of the randomization arms are essentially equivalent, until proven otherwise.

In this issue, we follow up on a series of tumor panel discussions conducted at the 2003 Miami Breast Cancer Conference and interview two faculty participants, Drs Monica Morrow and Jay Harris. One of the fascinating aspects of the Miami meeting was the keypad polling related to a number of current randomized trials. We focused on some of the most controversial studies: RTOG-9915, which randomizes women with one to three positive axillary nodes to either postmastectomy radiation therapy or observation; American College of Surgeons ACOS-Z-11, which randomizes women with positive sentinel node biopsies to either axillary lymph node dissection or not; and IBIS-II, which randomizes high-risk postmenopausal women to either the aromatase inhibitor, anastrozole, or placebo.

During the Miami meeting, the attendees were asked what advice they would give to their own patients about participation in these studies. We were interested in this topic not only from a research perspective, but also to gain another view of what people consider standard of care. Both Drs Morrow and Harris support the postmastectomy radiation trial, but acknowledge how difficult this randomization is for both patients and physicians to accept. In this regard, they reflected on another study with a challenging randomization — the classic NSABP-B-06 trial — which randomized women to either lumpectomy or mastectomy.

Dr Morrow encourages patients to enter the ACOS sentinel node trial, but she has ethical reservations about IBIS-II because she finds the placebo arm problematic in the presence of NSABP data demonstrating a proven breast cancer risk reduction effect from tamoxifen. Another interviewee, Dr Michael Baum, staunchly defends IBIS-II because he feels the overall health benefit of tamoxifen in women who are at high risk of developing breast cancer is marginal or nonexistent.

The other speaker on this issue, Dr Bernard Fisher — who is widely viewed as the “father of breast cancer clinical research” — launched and championed NSABP-B-06 in a furor of controversy several decades ago. Dr Fisher supports trials evaluating aromatase inhibitors in women who are at high risk for developing breast cancer, but he is more interested in “paradigm-breaking” studies that will have a fundamental effect on our understanding of the disease.

These debates are relevant not only to the research community, but to all physicians providing care to breast cancer patients. The current Phase III randomized trials will set new standards for therapy over the next decade, and practitioners must be aware, in advance, of the issues and controversies likely to evolve as these trials mature. Perhaps of even greater relevance is that discussions about ongoing studies provide perspectives on how the most experienced breast cancer research leaders view the subtleties of the risks and benefits of current available interventions. Ultimately, the issue of equipoise with multiple treatment options is a daily part of breast cancer medicine. Through this series, we attempt to provide further perspectives on this challenging issue.

—Neil Love, MD

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