Public participation in new drug approval process, beneficial role of expanded access programs for experimental cancer drugs
Chronic failure on most fronts of the "war on cancer" coupled with the recent introduction of a few dramatically successful new drugs has raised public awareness of, and frustration with, the process whereby experimental cancer drugs are developed and approved for marketing.
The highly publicized tribulations of ImClone Systems, the subsequent reorganization of Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) within the Federal Drug Administration (FDA), and the controversy over the incongruity between public testimony about individual clinical benefit and unimpressive efficacy statistics presented at the Oncology Drug Advisory Committee (ODAC) review of AstraZeneca's Iressa, are recent examples of why the underlying issues are important to consider.
The Feb. 21, 2003 issue of "The Cancer Letter" provides useful insight into this topic and raises at least two questions: What is the proper role of "the public" in the complex process of new drug approval, and how can promising new medicine best be made available to patients who need it as rapidly as possible?
Public participation
The right of Americans to directly participate in their government is fundamental to the democratic process. In the case of drug development, patient advocates have a long history of fighting to have their voices added to the process. Their input has been beneficial — accelerating the pace of research, broadening drug availability, and speeding the timeframes for new drug approval.
We believe that had advocates and activists waited to be invited into the process, these advances would have occurred much more slowly, or not at all.
Input from the public should be an important part of the work that occurs during ODAC deliberations. The fact that some FDA advisors do not perceive public input as central to their deliberations suggests that the process should be improved.
How? One simple improvement would be to make the FDA briefing documents available to the public earlier so patients and advocates can more accurately comment on the data.
Specialists and lay people working together can undoubtedly suggest other modifications that might improve the utility of "advice" provided by ODAC for use by the FDA in its decision-making process.
Expanded access
The Marti Nelson Cancer Foundation is an advocate of expanded access and compassionate use programs. Our organization's origins trace back to Marti's unsuccessful attempt to obtain compassionate access to Herceptin for which there were promising phase II efficacy and safety data. Her first choice was to enroll in a clinical trial. Unfortunately, she was ineligible for existing trials.
She faced a situation experienced by many cancer patients The logic behind her quest for compassionate use is equally valid now.
We periodically work with companies willing to voluntarily establish expanded access protocols and with individual patients seeking compassionate use of promising therapies.
Properly designed expanded access programs, implemented during the late stages of the cancer drug development process, can be beneficial to individual cancer patients, to the overall drug development process, and to the individual drug sponsor. Despite the benefits, there are many critics of the concept.
The Feb. 21, 2003 issue of "The Cancer Letter" refers to a National Breast Cancer Coalition (NBCC) Position Statement which begins with the following sentence: "Access to investigational interventions outside of clinical trials undermines the clinical trials system and the principle of evidence-based medicine." Actual experience over several years with a variety of cancer drugs suggests that this claim is incorrect on both counts.
Properly designed expanded access protocols do not undermine the clinical trials system and may actually contribute to both speeding clinical trial accrual and accumulating safety and efficacy data relevant to a broad population. The claim of incompatibility between clinical trials and compassionate use, or expanded access, can be permanently laid to rest by making sure expanded access programs are designed to prevent such conflict. In fact, the FDA works with companies to assure compatibility between expanded access protocols and efficacy-determining clinical trials.
Dr. Sackett's definition of evidence-based medicine, as quoted by NBCC, is "the conscientious, explicit and judicious use of current best evidence in making clinical decisions about the care of individual patients." Unfortunately, current reality is that most oncology drugs, even new drugs, do not provide clinical benefit to a majority of the individuals who receive them.
While many of the experimental agents currently in development may prove to be equally disappointing, we prefer to be optimistic about the future of cancer treatment. Even a drug demonstrating merely incremental benefit, as measured in large, randomized studies, may prove valuable to an individual patient with the right molecular profile and disease parameters.
Clinical trials are an important way for patients to access promising investigational agents (especially clinical trials designed with a cross-over provision). However, other valid ways to obtain innovative therapy include participation in expanded access protocols, individual compassionate use, off-label use of drugs approved for other indications, and importation of drugs approved in other countries.
Working out the best way to use this combination of routes is an important and legitimate topic for public debate and one in which the voices of both specialists and non-specialist members of the public are equally likely to contribute to progress.
Moving forward
The government's role in drug development and approval must be responsive to the evolving needs of both drug sponsors and patients. To improve the current system, it makes sense to bring together a variety of people representing diverse views to consider what is possible.
Do drug sponsors benefit from expanded access programs? Maybe. Do patients? Probably. While it is easy to focus on "conflicts of interest," it might be more productive to acknowledge "combinations of interest" and redouble our efforts to make meaningful progress in the "war on cancer" for everyone's benefit.
Bob Erwin, President
Nancy Roach, Director
Marti Nelson Cancer Foundation
Articles:
"ODAC Under Attack From FDA Official And Patients Seeking Fast Drug Approvals." The Cancer Letter, Feb. 21, 2003 29(8): 1-7. Subscription required, single issue purchase price is $10 and can be purchased online at www.cancerletter.com.
Fromer, M. "Being ODAC Chair: Personal Recollections From Five Who've Had the Job." "Oncology Times," May 2, 2002 24(5): 1. Subscription required.
Fromer, M. "FDA InSight: How Patients & Consumers Affect the Development of Cancer Drugs." "Oncology Times," Jan. 25, 2003 25(2): 13-14. Subscription required.
