I am Dr. Jennifer Yttri and I am pleased to be here to speak on behalf of myself and Dr. Diana Zuckerman, representing the National Research Center for Women & Families. We do not have any conflict of interest.
Our nonprofit research center analyzes and reviews research on a range of health issues, and provides objective and understandable information to patients and providers. My doctorate is from Washington University in St. Louis. Dr. Zuckerman’s perspective is as a former faculty member at Vassar and Yale and research director at Harvard. Dr. Zuckerman was trained in epidemiology at Yale Med School. Our Center is an active member of CUE, Consumers United for Evidence-based Healthcare, which is part of the US Cochrane Center at Johns Hopkins School of Public Health.
Our perspective is to focus on meaningful data – scientific evidence of real benefits and risks. We urge you to do the same at today’s meeting, focusing on the outcome measures that mean the most to patients: survival and quality of life.
The primary safety endpoint for the clinical trial was a comparison between the treatment and control groups in the incidence of serious adverse events from time of enrollment through 90 days of follow-up. The SENTIS study did achieve its primary safety endpoint by demonstrating no statistically significant difference in the number of SAEs between the NeuroFlo and control groups. However, the FDA scientists stated in their summary that “serious and nonserious adverse events (including, but not limited to, new fatal stroke with hemorrhage, limb ischemia necessitating amputation, aortic injury, and hematoma) were determined to be device/procedure-related by an independent DSMB.” The SENTIS study did NOT have a significant benefit to patients with the primary or secondary efficacy endpoints, including faster and better recovery or survival.
From a scientific perspective, the results are not surprising. The NeuroFlo device works to create a block in blood flow and allow blood to be diverted into the upper body, and potentially the brain. The only way the NeuroFlo device could have had a measurable change would have been in increasing cerebral blood flow, something that could have been measured by MRI or PET. As cerebral blood flow was NOT measured in the clinical study, there is no evidence of the device being effective. But let’s think about the device’s utility from a theoretical standpoint. In a best case scenario, the device would change blood flow in the brain wouth any confirmed benefit to stroke patients. At worst, the device would cause vessel rupture, potentially brain hemorrhage, another stroke, and failure of lower body organs such as the liver and kidneys, adverse events that were reported with the SENTIS trial.
Thus, the clinical utility of the NeuroFlo device for the SENTIS subject population should be carefully assessed, considering both the lack of benefits and increased risks with an unnecessary procedure.
The goal here should be a better outcome, not an outcome that is not significantly worse but where there are very serious risks that might be significantly worse in a larger sample.
Today’s meeting is especially important because it will set a precedent for other decisions that the FDA makes. Lives are at stake.
The law requires the FDA to have 2 different pathways to approval for medical devices. The PMA pathway is similar to the one for prescription drugs, and requires scientific evidence of safety and efficacy. Only high-risk devices – those that are implantable, life-sustaining or potentially life-saving are reviewed through the PMA process. The 510(k) process is very different: those devices must be substantially equivalent to other medical devices on the market, which are called predicates. As the FDA explained in their memo, medical devices submitted for 510(k) clearance for which no suitable predicate was identified can be reviewed through a 3rd pathway, called the de novo review, which, to quote the FDA, allows “moderate risk devices without a suitable predicate” to be reviewed with “adequate special controls.”
We don’t believe that this device, used for the treatment of acute ischemic stroke within 14 hours of symptom onset, is a moderate risk device. Since people’s lives are at stake, we believe it is a high-risk device and therefore should not be approved through a de novo review.
And, given the ambiguity of the research results, we believe this potentially life-saving or life-threatening device absolutely needs to be held to the higher standard of a PMA review.
I’d like to mention that our Center’s president is on the Board of Directors of 2 non-profit organizations that are dedicated to providing needed resources to the FDA: The Alliance for a Stronger FDA and the Reagan Udall Foundation, which was created by Congress to provide support for the FDA. We are dedicated to ensuring that the FDA has the resources that it needs to do its job to make sure that all medical products are safe and effective. Allowing a life-saving device that is NOT eligible for a 510(k) review to go through a de novo review sets a dangerous precedent under any circumstances. It is even more worrisome when the data do not clearly indicate that the device is beneficial in saving lives or improving the quality of life.
If this Advisory Committee supports a de novo review for this product and if it determines that these ambiguous research results are not great but good enough to recommend approval, patients will be harmed. The harm is because of the potential risks such as a new fatal stroke or aortic injury, but also because of the cost of approving this device despite the lack of evidence of any benefit to the lives of patients.
Your task today is to determine the risks and benefits based on the research that is available. More than that, FDA has asked you to determine if the existing data is sufficient to support a de novo application – and that decision will have implications for FDA’s use of de novo reviews for hundreds of other devices in the years to come. Based on the data – not on subjective opinions or even clinical experience but actually on the data itself — it is clear that more research is needed. This device should not be approved for acute ischemic stroke during the first 14 hours until research clearly shows a benefit to patients’ lives. It therefore requires a PMA review with better safeguards to save your patients’ lives.