Stephanie Fox-Rawlings, PhD, National Center for Health Research: September 27, 2018
Thank you for the opportunity to speak today on behalf of the National Center for Health Research. I am Dr. Stephanie Fox-Rawlings. Our Center analyzes scientific and medical data to provide objective health information to patients, health professionals, and policy makers. We do not accept funding from drug and medical device companies, so I have no conflicts of interest.
New safe and effective treatments for the treatment of aneurysms could benefit patients. But new products need to clearly demonstrate this before they are approved.
In addition to FDA scientists’ concerns over the values of the performance goals, the results of the WEB-IT trial are difficult to interpret due to the lack of a comparison-treatment arm. The performance goals were chosen based on clinical trials for related devices, so that the data from those other trials could be used as a comparison group. However, even trials that have a similar design can have dramatically different results. Differences in the percentage of participants who are older, of specific races, characteristics of aneurysms, or have comorbidities or genetic conditions can affect how well the device works and the rate of adverse events. Thus, it is possible that the results of this new device met these performance goals because the participants are relatively healthier or less likely to have .stroke or other adverse event. There is no way to know if there are such confounding variables or not. In addition, the surgeons’ experience and the practice of medicine can vary dramatically in between countries or hospitals and over time.
These concerns are compounded because the evaluation of this device is based on a single pivotal trial. Having at least two trials with similar results would support the conclusion that the results are not due to chance or artifact.
In addition to these other shortcomings, the patients in the clinical trial are not racially or ethnically diverse. Racial and cultural background may alter the effect of the treatment. The trial only included 14 black, 4 Asian, and 2 Hispanic patients, which are too few to evaluate the effectiveness or safety in any of those populations.
It is important to look at the results for patients over 65 years old. Even if the device worked equally well for younger and older patients, the benefit-risk balance may not support its use in older patients if the risks are higher.
Another shortcoming is that there did not appear to be any patients with genetic vascular disease in the clinical trial. These conditions are risk factors for intracranial aneurysms and may predispose patients to more adverse events.
These are all important issues that could have been resolved with better research. If you believe that this device should be approved anyway, I urge you to advise the FDA to require a long-term post-market study and make sure that it is completed in a reasonable time. These devices are intended to be permanent, so patients will live with the device for potentially decades. However, we only have one year of data for this device. The required post-market study should address the long-term prognosis, recurrence rate, and adverse events. These issues cannot be properly assessed using only voluntary adverse events reporting nor should it wait for a registry or for the FDA’s NEST program.
In summary, there are important aspects of the clinical trial that make it difficult to determine if the WEB device is effective and safe for the indicated population. Alternatively, it may be appropriate only for a specific, well-defined population, but this should be determined before approval. If the FDA does not demand better research, patients and their physicians may never know the answers to those questions.