Good afternoon. Thank you for the opportunity to testify on behalf of the National Research Center for Women & Families. My name is Sonia Nagda. I am a physician, and I received my training in public health at Harvard University. Our Center is dedicated to improving the health of adults and children, and we do that by scrutinizing scientific research. We do not accept contributions from companies that make medical products, so I have no conflicts of interest.
The key question today is whether the ASO (AMPLATZER Septal Occluder) and HSO (HELEX Septal Occluder) devices that are used in the occlusion of atrial septal defects in adults and children offer greater benefits OR fewer complications than surgery alone. Surgical success rates are extremely high, but they offer serious risks in the short term, including pericardial effusion with tamponade, pulmonary edema, repeat surgery, and surgical wound complications. In the studies comparing the ASO and HSO to the surgical procedure, success rates are still greater than 95%, but the short-term complications are fewer and less serious.
However, atrial septal defects are a congenital disorder, so the devices should be safe in the long-term for children and young adults who could have them implanted for decades. Unfortunately, there is no evidence to support long-term safety.
The most common complications for the ASO included cardiac arrhythmias and device embolization requiring device removal. The most common complications during the initial HSO trial were device embolization, wire frame fractures, migraines, parasthesias, allergic reaction, and inappropriate device size.
I am very concerned about the interim data showing that these devices can fracture and become dislodged. This requires another surgery to retrieve the broken device, and finding another way to repair the cardiac defect. These fractures occur increasingly often as the size of the device increases.
Another alarming adverse event, which was only discovered during the 5-year post-approval study, is the erosion of the cardiac tissue that can occur as the device remains in the heart year after year. We don’t know why this erosion sometimes happens, so we can’t predict or prevent it. While few tissue erosion examples are documented, long-term data are lacking. The only way to know how pervasive a problem this can be for ASD patients is to continue to evaluate the devices that have already been implanted in study participants. This should be done, but meanwhile surgeons, patients, and family members need to know that the long-term risks of these devices may be substantial, especially for patients needing larger devices.
FDA stated on pg 6, “septal occluders are also commonly used “off-label.” Although off-label use is NOT the subject of this meeting, the devices are so widely used off-label that the adverse reactions for the FDA-approved uses must be considered in the context of these off-label problems. Labeling changes are needed to address the problems associated with common off-label uses, so that surgeons can accurately inform their patients of the risks and benefits.
Since the FDA has asked you about the clinical significance of adverse events, we want to point out that the 2-year, 30-month and 3-year reports on the fatigue and corrosion testing schedule are overdue for the STARFlex Septal Occluder device [PMA P000049 S016].
Similarly, the 2-year report for the Amplatzer Muscular VSD Occluder [P040040] was overdue prior to termination of the long- term study.
These reports are needed so that you can provide informed advice to the FDA. Frankly, when companies don’t provide required data, one has to wonder whether they have something to hide.
The failure of companies to appropriately complete required post-market studies is common at FDA, especially for devices. Even when the studies are completed, the loss to follow-up can make the findings useless to patients and surgeons who want to know the true long-term risks and benefits. Stronger incentivization to complete long-term studies could improve participant retention.
I urge you to express your concerns about the known and unknown risks of these permanent implanted devices, and the widespread inappropriate use off-label. FDA needs to do more to provide long-term data and to warn patients and their surgeons about the risks.