Testimony by Brandel France de Bravo
December 5, 2012
I am Brandel France de Bravo, and I am pleased to have the opportunity to speak a second time today on behalf of the National Research Center for Women & Families. Our Center does not accept funding from device companies, and I have no conflict of interest.
Our nonprofit Center analyzes and reviews research on medical issues, and provides objective and understandable information to patients and providers. We are an active member of the Alliance for a Stronger FDA, a nonprofit coalition of corporations and nonprofit organizations that has successfully increased resources for the FDA by billions of dollars.
I have a Master’s in Public Health from Columbia University and have been working on health and safety issues for over 20 years.
We strongly agree with the FDA that IABP devices used to treat septic shock and Intraoperative Pulsatile Flow Generation should remain Class III, with PMAs required. The evidence of safety and effectiveness for these indications has yet to be established.
The difficult question panel members must answer today is whether the evidence base is sufficient to down-classify IABPs to Class II (special controls) for acute coronary syndrome; cardiac and non-cardiac surgery, and complication of heart failure—both ischemic and non-ischemic, which is what the FDA is recommending.
The safety record for 75,000 IABPs used per year in the U.S. is respectable given, as the FDA notes, “that the intended population is a group of patients with high morbidity.” We agree with the FDA when they say that the number of reported deaths, which were 189 during the last 10 years, “is not necessarily reflective of the device itself but the very sick population in whom it is used.” Of course, there may be many deaths that were not reported.
An important question is how effective IABPs are for the uses specified under their proposed down-classification. According to the Code of Federal regulations, “There is reasonable assurance that a device is effective when it can be determined, based upon valid scientific evidence, that in a significant portion of the target population, the use of the device for its intended uses and conditions of use, when accompanied by adequate directions for use and warnings against unsafe use, will provide clinically significant results.”
The FDA research summary uses words like “no benefit,” “conflicting,” “equivocal,” “may improve,” “may have a beneficial effect,” over and over in the sections pertaining to proposed Class II indications. For instance, a concluding paragraph on page 24 says: “While the literature may at times be equivocal, FDA contends that sufficient data has been provided …” This sounds more like wishful thinking than science. We therefore disagree with the FDA’s recommendation to down-classify.
After a semi-implanted device has been in use for over 40 years, it’s hard to admit that we don’t know much about its effectiveness. Isn’t it time we change that? About IABPs for acute coronary syndrome—a Class II indication—the FDA writes: “Trials performed to investigate the benefit of IABP using the modern standard of care have been underpowered to demonstrate improvement, or have had other limitations, such as variability in the timing of IABP usage.” The reference to timing is an attempt to explain the results from the IABP SHOCK II trial, which pardon the pun, were quite shocking. The researchers found no significant difference in mortality between the IABP and control group. Apparently in the U.S., IABPs are placed earlier—often before revascularization—than in Germany where that trial was conducted, and this, to use FDA’s language, “may affect effectiveness.”
FDA decisions are supposed to be based on science, and your recommendations to the FDA should be based on scientific evidence. We are not helping patients if we approve devices based on speculation or wishful thinking rather than science.
The specified controls are not adequate, given the confusing and conflicting evidence. These products should not be sold if there is no clear evidence that they work.
As I mentioned this morning, the court decision this week would allow companies to promote their medical products for off label uses. Therefore, we should not be splitting these classifications unless there is a very strong rationale to do so.
In this case, there is insufficient evidence that the device works for the so-called Class II indications. Even if the control stipulated a post-market study, it could take more than a decade before we have clinically useful information. Meanwhile, a product that could be ineffective would be used by thousands of patients, and when a product doesn’t deliver a real benefit, no level of harm or risk is acceptable
In conclusion, IABPs should have been studied in clinical trials decades ago. The companies have had an almost free ride, and it is time that the FDA demanded research evidence, so that doctors would be sure that patients will be helped by these products rather than harmed