November 7, 2024
I’m Dr. Diana Zuckerman, president of the National Center for Health Research. Our center is a nonprofit public health research center that scrutinizes the safety and effectiveness of medical products, and we don’t accept funding from companies that make those products so we have no conflicts of interest.
We thank FDA and this Committee for your important work. My expertise is in clinical trial design and data analysis and as a breast cancer survivor. Prior to my current position, I was a post-doc in epidemiology and public health at Yale Med School, and was a faculty member and PI at Yale and Harvard. I also investigated FDA approval standards while working in the US Congress, HHS, and the White House. I’m on the Board of the nonprofit Alliance for a Stronger FDA, which educates Congress about the need to financially support the essential work of the FDA.
As a survivor of T1 breast cancer, I appreciate the desire for less invasive treatment. But I am concerned that this cryoablation system was studied in a small, one-arm trial instead of a larger randomized clinical trial. We also share FDA concerns about serious data irregularities– including missing data that weren’t analyzed correctly — and lack of racial diversity of the patients in the study.
A breast cancer diagnosis is a traumatic experience and our research center has talked to hundreds of patients who tell us how overwhelming it is to consider all their treatment options. What matters most is overall survival, but recurrence also matters. Quality of life is very important but requires validated tests to be meaningful, and that was not done here. Most important, since 5-year recurrence is low for these kinds of early-stage breast cancers regardless of treatment, we can’t know the long-term success without a larger, longer term, randomized trial.
On a personal note, I went into my surgery with a diagnosis of DCIS. The tiny invasive cancer was found only as a result of the surgical specimen. Very small tumors can be difficult to find, and a randomized trial with post-market follow-up for a longer period of time would make it possible for patients to make better informed decisions, choosing the treatment that’s best for them.
Breast cancer treatment teams try to give patients the best possible information, but many patients tell us they are confused by the treatment options. They’re confused by the implications of terms like recurrence, disease-free survival, overall survival, primary and secondary cancer.
In addition, we also need to be concerned about how a new treatment that does not require surgery might be inappropriately promoted and used for larger or higher-risk tumors than those in the indication, and an indication that includes women who are younger than those studied. That use might be off label or included in the label, so if this product is approved the label should clearly specify what the data indicate and the indication should be consistent with that. We also urge FDA to require a short, simple patient checklist to maximize informed consent.
After her presentation, Advisory Panel members asked Dr. Zuckerman two questions as part of the panel discussion. Her answers are included below.
A: Thank you for asking about the patient checklist. FDA has sometimes used checklists to help provide understandable information about a medical device. Checklists should include facts that are short, simple, and easy to understand. For example, a checklist for this Cryoablation System could include facts such as:
1. “Research shows that _% of women using this product have a recurrence of breast
cancer within 5 years, compared to _% for women undergoing lumpectomy surgery.
2. There are no studies indicating how often recurrence of breast cancer occurs within 10 years of using this product.
The patient would initial each statement to show that she read it, and the physician should also sign it to show their explanations were consistent with the checklist. Keep in mind that informed consent is a process, not just a document, and it is important that the physician not make statements inconsistent with the checklist.
A: Thank you for asking why I said randomized controlled clinical trials were needed to help women make informed choices. We all know that randomized controlled trials are the gold standard and there is no reason why that wasn’t done with this product, since the alternative is clear: the standard of care is lumpectomy. You’ve heard that women wouldn’t want to participate in a randomized trial if they could choose cryoablation instead, but that is not true if they were accurately told that this is a clinical trial, and we are conducting it to find out whether or not Cryoablation is as effective as surgery. Patients need to know that it is study being done to find out if the product is effective; they should not be told that it is as effective as surgery when that is not known.