Dear Acting Commissioner Dr. Stephen Ostroff,
Breast Cancer Action (BCAction) is national education and activist organization working to achieve health justice for all women at risk of and living with breast cancer. Since our founding 25 years ago, we work to ensure that women have access to evidence based information about breast cancer, free of industry influence. BCAction has over 60,000 members across the U.S.
BCAction offers neither treatment nor medical advice. However, we do provide accurate, unbiased information that allows patients to make well-informed decisions about available treatments based on personal needs. We advocate for treatments that put patients’ interests before those of corporations.
We expect the FDA to fulfill its mission to protect the public’s health. Patients and consumers depend on the FDA to ensure that medical drugs and devices are safe and effective.
We believe that any new drug approved for the treatment of breast cancer must be able do at least one of the following three things:
- Should be more effective in that it extend the life of a patient which is shown by improved overall survival (OS) or
- Be less toxic in that it improve the patient’s quality of life or
- It should cost less than therapies already available.
No one is more concerned than patients with bringing effective new drugs and devices to the market as quickly as possible. And, as the watchdog of the breast cancer movement, we are the voice of safety and will demand the strongest standards, but we recognize that this must be a balanced approach. Any effort to streamline the FDA’s approval process must also uphold the strongest safety standards. Patients and their physicians need adequate data to make informed decisions. For that reason, BCAction is alarmed by 1) the increased use of surrogate endpoints, 2) accelerated approvals based on limited data and failure to conduct post-market studies, 3) the limitations of the 510(k) pathway for device approval, 4) the lack of diversity in clinical trials and 5) the high cost of drugs and the financial burden for patients.
Surrogate End Points
The FDA’s accelerated approval program allows drugs for serious conditions, which fill an unmet medical need, to be approved based on a surrogate endpoint. The over use of surrogate end points such as progressive free survival (PFS) rather than overall survival means that too often, drugs that seem promising based on surrogate endpoints like PFS ultimately fail to extend overall survival. In an effort to speed approvals, the FDA’s reliance on a lower approval standard means approval can come at the expense of accurate efficacy information.
Overall survival (OS) is the gold standard primary end point. It focuses on the meaningful patient outcome of preventing death rather than preventing tumor progression (which may or may not lead to lower death rates). Mounting evidence shows that progression free survival may not be an adequate substitute for overall survival. These potentially lower approval standards to expedite approval move the “evidence of safety and effectiveness” from the pre-market stage to the post-market stage. Another surrogate endpoint that we are particularly alarmed by is the current move to push Pathologic Complete Response (pCR) as the endpoint in neoadjuvant trials.
Accelerated approvals that rely on preliminary data to bring drugs to market may be premature. Important safety signals can be lost in smaller, shorter trials. And, as we have seen in the case of Avastin and other drugs, unfortunately the promising results from early trials do not always translate to better outcomes. These drugs are better continued in clinical trials with compassionate access programs.
Another problem that can arise with accelerated approval is the failure to follow-up with post-market studies. Many of the side effects and harms of treatment are not immediately observable. The FDA needs to double down on post-market studies to ensure that the immediate benefit of treatment does not come at the cost of longer-term health harms.
501(k) Drug & Device Approval Process
Another concern is the FDA’s 510(k) pathway for device approval, which allows manufacturers of medical devices to skip a premarket approval of their device if they can show that it is substantially equivalent to other devices already on the market. This creates a system where approved medical devices are on the market, that have not undergone any clinical trials or manufacturing inspections to demonstrate safety and efficacy.
Diversity in Clinical Trials
When done well, clinical trials can help answer research questions and provide access to cutting edge treatments. Unfortunately, if not enough women and people of color are included in clinical trials, determining how diverse populations of people are affected by a new drug or device is impossible. Without all the information, women, particularly women of color, can’t make informed decisions about available treatments, devices and products. We would like to see more diversity represented in clinical trials. This will assure that treatments that are developed benefit the larger community of women living with and at risk of breast cancer
Cost of Breast Cancer Treatment
Cost is also an important concern. The cost of treating breast cancer can be a significant financial burden. This burden can cause distress and potentially can prevent women from receiving recommended treatment. We have seen over the last few decades’ breast cancer treatments get more and more expensive with less and less overall survival benefits. If newer medications will continue to cost more and more, it is important that they confer larger and larger improvements in quality of life and/or overall survival. Additionally, we need to assure that these new treatments are affordable and accessible to all women.
Thank you for this opportunity to submit our comments on patient-focused drug development for breast cancer.
Program Manager, Breast Cancer Action