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.