Thank you for the opportunity to speak today on behalf of the Cancer Prevention and Treatment Fund of the National Center for Health Research. My name is Dr. Anna Mazzucco, and after completing my Ph.D. in Cell and Developmental Biology from Harvard Medical School I conducted research at the National Cancer Institute. I speak from those perspectives today.
Our nonprofit organization conducts research, scrutinizes data in the research literature, and then explains the evidence of risks and benefits to patients and providers. Our president is on the Board of Directors of the Alliance for a Stronger FDA, which is a nonprofit dedicated to increasing the resources that the FDA needs to do its job. Our organization does not accept funding from medical device companies, and therefore I have no conflicts of interest.
About 600,000 hysterectomies are performed annually in the United States, according to the Centers for Disease Control and Prevention, and approximately 65,000 myomectomies. Of the hystectomies alone, the FDA estimates that 50,000 to 150,000 use power morcellation. The FDA also estimates that 1 in 350 women undergoing hysterectomy or myomectomy for the treatment of fibroids has unsuspected uterine sarcoma which could be spread and worsened if a power morcellator is used. Based on these numbers, as many as 400 women could have undiagnosed malignancy spread each year from hystectomy alone — when you add myomectomies, it is probably much higher. We agree with the FDA that there is currently no reliable method to distinguish between uterine fibroids and sarcoma before surgery. Training physicians is, unfortunately, not the answer.
The estimate of one in 350 women undergoing surgery having an unsuspected uterine cancer is based on recent studies and is much higher than the 1-in-10,000 chance of undiagnosed cancer typically quoted to patients. The FDA has also estimated that undiagnosed cancer will be spread or worsened by morcellation in 25-65% of cases. The estimated 5-year survival is 60% for patients with stage I disease, compared with 22% for those with stage III and 15% for those with stage IV.
Minimally invasive surgery can offer many advantages to patients, but as you have heard at this meeting, the mortality benefits of such procedures are unclear. In contrast, it is absolutely certain that malignancy spread by morcellation can be life-threatening. In light of these findings, we agree with the FDA’s statement in their safety communication that power morcellators should no longer be used during removal of uterine fibroids.
The question is whether this warning from the FDA is enough to save lives? Or, is this new evidence sufficient to alter the classification and labeling of these devices?
Power morcellators were originally approved as class II moderate -risk devices under the 510(k) process, which does not require clinical trials prior to allowing the device on the market. It also does not require inspections to make sure the device is made and working as designed — such inspections are required for all prescription drugs. Since morecellators were not studied in clinical trials, the risk of undiagnosed sarcoma spreading was not detected prior to clearance through the 510(K) pathway. As a result, patients were irreparably harmed. We’ve heard some of those tragic stories at this meeting.
Class III devices are defined as those which pose a significant risk of illness or injury, and require clinical testing for safety and efficacy. Clearly, power morcellators meet this definition and should be classified as Class III devices. Therefore, they should undergo clinical studies before any more patients are harmed. Non-clinical performance testing studies are simply not sufficient to address these safety concerns. If an adequate number of patients had been studied in clinical trials, we would have known years ago that morcellators could cause a fatal spread of uterine cancer.
I think everyone on this panel agrees that more research is needed. Clinical studies must evaluate risk mitigation strategies, such as use of a companion containment bag. However, as the FDA briefing material cites, there are adverse events associated with current specimen bags. For this reason, bags need to be specifically designed for use with power morcellators specifically for uterine fibroids. Surgical techniques must also be refined for use with these bags.
Clinical trials are also needed to improve the accuracy of patients’ diagnostic outcomes when morcellators are used.
After these studies are completed, the FDA should consider whether and under what circumstances power morcellators can be used for uterine fibroids. On the basis of research, black box warnings must inform physicians and patients of the risk of spreading malignancy and the required risk mitigation strategies. This label should also include the warning that these devices should never be used in patients with suspected malignancy. Training and certification should also be required before physicians can use power morcellators to ensure that these risk mitigation techniques have been mastered.
As the FDA has stated in its summary for today’s meeting, the current voluntary reporting system for medical devices is underused, and thus underreports adverse events for all medical devices, including power morcellators. Unfortunately, surgeons and other medical personnel are not reporting these incidents to the FDA, and their reporting is voluntary, so they don’t have to. On the other hand, the hospitals where these incidents occur are required to report them to the device companies, and the device companies are required to report them to the FDA. For some reason, those reports were not being made either. As a result, many more patients died before the risks of morcellation became known — primarily as the result of a physician whose life was put at risk when a morcellator used for a uterine fibroid resulted in Stage 4 uterine cancer.
We agree with the American Congress of Obstetricians and Gynecologists that a patient registry should be created to follow patients whose fibroids were previously removed with the assistance of power morcellation to more scientifically monitor their health outcomes. But, that is not enough. And the current FDA warnings are not enough.
We need higher standards to ensure that morcellation devices are safe and effective, and that require clinical trials with sufficient numbers of patients to determine the risks of rare but fatal outcomes.