Medical Devices: Cancer Risk Led FDA to Warn Against Certain Uses of Power Morcellators and Recommend New Labeling
Released: 2017-02-08T00:00:00

Letter

Background

Uterine Fibroids and Treatment Uterine fibroids are noncancerous growths that develop from the muscular tissue of the uterus. Most women will develop uterine fibroids at some point in their lives, although most cause no symptoms. In some cases, however, uterine fibroids can cause symptoms, including heavy or prolonged menstrual bleeding, pelvic pressure or pain, or frequent urination, requiring medical or surgical therapy. Treatment for uterine fibroids includes surgical procedures to remove the uterus (hysterectomy) or to remove the fibroids (myomectomy). These surgical procedures can be done via minimally invasive laparoscopic procedures or through traditional surgical procedures, such as an abdominal hysterectomy. Other treatments for uterine fibroids include, for example, high-intensity focused ultrasound, and drug therapy.

Power morcellators are medical devices used during laparoscopic (minimally invasive) surgeries. Morcellation refers to the cutting of tissue into smaller fragments for removal from the body. In laparoscopic surgical procedures, morcellation facilitates the extraction of large pieces of tissue through small incisions. Over time, laparoscopic surgeons have applied different manual methods of morcellation using scalpels, forceps, and other tools that require repetitive manual motions, such as twisting. Power morcellators generally use an electromechanical motor to spin a cylindrical blade within a tube for cutting and removing tissue.

Power morcellators can be used during different types of laparoscopic surgeries, including general surgical procedures, such as spleen and liver surgeries; urological surgical procedures, such as kidney removal surgeries; and gynecological surgical procedures. These laparoscopic gynecological procedures include two types of surgeries used to treat uterine fibroids: (1) the removal of the uterus, known as hysterectomy; and (2) the removal of individual fibroids, known as myomectomy. Some women may prefer laparoscopic hysterectomies and myomectomies, because these procedures are associated with such benefits as a shorter post-operative recovery time and, for laparoscopic hysterectomies, a reduced risk of infection compared to open procedures.

Medical devices, including power morcellators, are regulated by FDA. The agency classified most power morcellators as class II devices, meaning that FDA generally considers them to be higher-risk than class I devices and lower-risk than class III devices. For most class II devices, FDA determines whether they should be legally marketed in the United States through the agency’s 510(k) premarket notification process. Specifically, the device manufacturer through a 510(k) submission must notify FDA at least 90 days before it intends to market a new device and establish that such device is substantially equivalent to a predicate device. To be substantially equivalent, a device must (1) have the same intended use as the predicate device; and (2) have the same technological characteristics as the predicate device, or have different technological characteristics but submitted information demonstrates the device is as safe and effective as the predicate device, and does not raise different questions of safety or effectiveness. Figure 1 shows FDA’s decision- making flowchart for its 510(k) premarket notification process in effect when FDA cleared the 510(k) submissions for power morcellators prior to July 2014.

Once a new medical device is on the market, medical device user facilities, manufacturers, and importers must comply with medical device reporting requirements. Under these requirements, these parties must report device-related adverse events, including events that reasonably suggest a device has or may have caused or contributed to a death or serious injury, in a timely manner. For example, user facilities must report such deaths and serious injuries within 10 work days of becoming aware of information reasonably suggesting the device may have caused or contributed to the death or serious injury. Within this time frame, deaths must be reported to both FDA and the manufacturer, if known, and serious injuries must be reported to the manufacturer, or, if the manufacturer is unknown, to FDA. Consumers and other parties may voluntarily report adverse events directly to FDA. The agency maintains databases that house both mandatory and voluntary reports of device- related adverse events.

While adverse event reports may provide the first signal that a problem exists with a device or its use, or both, FDA and others have reported that information from these reports can be limited. Examples of identified limitations include the following Incomplete or erroneous reporting. Adverse event reports can include incomplete reporting, where key data are not reported, or erroneous reporting, where the information provided is not accurate.

Reports that are not timely. Adverse event reporting does not always reflect real time reporting, as some reports document events that occurred years earlier.

Underreporting. Adverse events may not always be reported. (See app. I for additional information on medical device reporting requirements.)

In addition to adverse event reporting, FDA conducts other postmarket surveillance activities to obtain information about devices after they are on the market. For example, FDA may order a manufacturer to conduct a postmarket surveillance study if failure of a class II or class III device would be reasonably likely to have serious adverse health consequences.

FDA Cleared 25 Power Morcellators; Most Devices Had the Same Intended Use and Technological Characteristics, and Could Be Used for Gynecological Surgeries

FDA documentation shows the agency cleared 25 510(k) submissions for power morcellators to be marketed in the United States between 1991 and 2014. In clearing the first of the 25 power morcellators in 1991, FDA determined the new device was substantially equivalent to an electromechanical system for cutting tissue during minimally invasive surgeries performed on joints, known as an arthroscopic surgical system. (For more information on this predicate device, see app. II.) FDA determined the other 24 power morcellators—the most recent of which was cleared in May 2014—were substantially equivalent to at least one previously cleared power morcellator. We also found that for most power morcellators the documentation we reviewed referenced more than one predicate device. As shown in table 1, the additional devices referenced by manufacturers included other previously marketed devices, such as manual morcellators, forceps, and various accessories used for laparoscopic surgeries. FDA officials stated that the additional devices referenced likely informed FDA’s decision-making for all 25 power morcellators. However, FDA’s determinations of substantial equivalence were based on only one predicate device, the arthroscopic surgical system for the first power morcellator cleared and a previously cleared power morcellator for the other 24 devices, according to agency officials. (For more information on each of the 25 power morcellators cleared by FDA, see app. III.)

Among the 25 cleared morcellators, we found that FDA determined that all had the same intended use and 19 had the same technological characteristics as their predicate devices; the agency also reviewed performance data for 11 of them. (See fig. 2.)

In our review of the FDA documentation for power morcellators, we found that the agency determined that all 25 devices had the same intended use as their predicate devices. In making this determination, FDA also determined that 4 power morcellators had different indication statements compared to the predicate devices, but the differences did not alter the intended use of each device. In general, the indication statements for the 4 power morcellators identified new or fewer procedures during which the devices were to be used compared to the predicates. For example, the indication statement for a power morcellator FDA cleared in 2000 specifically identified use in hysterectomies where the predicate’s indication statement only identified myomectomies. In another example, the indication statement of a power morcellator cleared in 2011 only identified use in gynecological procedures where the predicate identified general surgical and urological procedures, in addition to gynecological. For all 4 devices, however, FDA determined that the differences in indication statements did not alter the intended effect of the devices or raise new questions of safety or effectiveness, and determined, overall, that the power morcellators had the same intended use as their predicates.

We also found that FDA determined that 19 of the 25 power morcellators had the same technological characteristics as their predicate devices, while 6 devices did not. According to FDA officials, the technological characteristics of these 6 power morcellators that were different included the change from the use of a vacuum to suction tissue into the morcellator to the use of forceps to grasp tissue for this purpose; the change from single use, disposable body or blade to ones that are reusable; the change from a rotary cutting action to one that is reciprocating; and the addition of the ability to control suction with a foot switch.

In addition, for 11 power morcellators, we found that FDA reviewed performance data. These included 3 power morcellators for which FDA determined that different technological characteristics could affect safety and effectiveness, and 8 other power morcellators for which the device description was not sufficient to determine whether the devices were substantially equivalent to predicate devices. For these 11 devices, FDA reviewed performance data—which, according to agency officials, included data such as those from testing the wear of components, electrical safety, and electromagnetic compatibility—and determined that the devices were substantially equivalent to predicates.

Based on our review of FDA documentation, we also found nearly all of the 25 power morcellators were indicated for use in gynecological surgical procedures. We found the indications for use for 14 power morcellators specifically identified laparoscopic gynecological procedures, such as myomectomies and hysterectomies: the indications for use of 4 devices identified gynecological procedures only, the indications for use of 2 devices identified general surgery and gynecological procedures, and the indications for use of 8 devices included general surgery, gynecological, and urological procedures.

For the 11 other devices, 9 power morcellators had indications for use for general surgical procedures, which could include gynecological procedures. (See table 2.)

FDA Understood the Risk of an Unsuspected Uterine Cancer That Could Be Spread When Using a Power Morcellator to be Low; Has Taken Actions in Response to Adverse Event Reports

FDA was aware of the potential for spreading tissue when using a power morcellator prior to receiving the first adverse event reports; however, the general understanding was that the risk of an unsuspected cancer that could be spread when using the device was low. In response to adverse event reports, FDA has taken several actions, including estimating cancer risk, warning against certain uses of power morcellators, and recommending new labeling. However, questions remain regarding the use of power morcellators to treat uterine fibroids, and FDA continues to monitor available information.

Prior to Adverse Event Reports, FDA Was Aware of the Potential for Power Morcellators to Spread Tissue, but Understood the Risk of Unsuspected Cancer that Could Be Spread to be Low

FDA officials were aware of the potential for spreading tissue during procedures that involved the use of power morcellators before receiving the first adverse event reports describing the spread of cancerous tissue after the use of a power morcellator to treat uterine fibroids. Specifically, according to FDA officials, the potential for spreading tissue—cancerous or noncancerous—following the use of a power morcellator has been known since the agency cleared the first device in 1991. We found that this awareness was reflected in the labeling for 12 of the 25 devices cleared by FDA. The labeling for these power morcellators recommended the use of a bag when cutting cancerous (diagnosed or suspected) tissue and any other tissue that may be considered harmful if spread.

FDA officials noted that articles reporting the risk of spreading tissue following the use of a power morcellator to treat uterine fibroids were published prior to the agency receiving the first adverse event reports in December 2013. Agency officials, however, noted that at the time, there was no consensus within the clinical community regarding the risk of this occurring, particularly for cancerous tissue. We identified 30 such articles published between 1980 and 2012 that mentioned or concluded a risk of tissue dissemination following the use of a power morcellator, or the need for a physician to remove all fragments of tissue following a surgery. Most of these articles involved case studies or were limited in scope. For example, one case study published in 2010 looked at a single patient who, after undergoing a hysterectomy to treat a uterine fibroid, was found to have a previously unsuspected sarcoma (a type of cancer), and concluded that there is a potential risk of spreading the unsuspected cancer following morcellation. None of the articles that we identified estimated the risk of spreading tissue, cancerous or noncancerous, during power morcellation.

Uterine Sarcoma Uterine sarcoma is a cancer of the muscle and supportive tissues of the uterus. Uterine sarcoma is one of two types of uterine cancer (endometrial carcinoma is the other, more common type of uterine cancer). The American Cancer Society estimates that less than 4 percent of uterine cancers are uterine sarcoma. Of the two types of uterine cancer, uterine sarcoma tends to be more aggressive, more difficult to diagnose before surgery, and have worse prognoses. Leiomyosarcoma is a type of uterine sarcoma that, similar to fibroids, develops in the muscular tissue of the uterus. Leiomyosarcoma can resemble a fibroid and, as a result, can be difficult to diagnose before surgery.

Though the risk of spreading tissue during power morcellation was known, FDA officials stated that prior to December 2013, the general understanding was that the risk of a woman undergoing treatment for fibroids having unsuspected cancer—specifically, a difficult to diagnose cancer called uterine sarcoma—was low. Therefore, the risk of a power morcellator spreading a uterine sarcoma would be expected to be low, as it could be no higher than the risk of having a uterine sarcoma. In addition, FDA officials were not aware of any definitive scientific publications regarding the actual risk of cancer in uterine fibroids (by definition presumed to be noncancerous), which is generally consistent with statements by two professional societies. FDA officials noted that published estimates for an unsuspected cancer (specifically uterine sarcoma) in a woman with a presumed uterine fibroid varied from about 1 in 1,000 women to 1 in about 10,000 women. These estimates of the risk of cancer depended on several factors, including the cancer diagnosis (e.g., uterine sarcoma or a category of uterine sarcoma called leiomyosarcoma), the type of treatment for uterine fibroids (e.g., hysterectomy or myomectomy), or the patient population included in the estimate (e.g., women of reproductive age or women who are older). One 2012 study that examined 1,091 instances of uterine morcellation at one hospital, however, reported that the rate of unsuspected cancer (uterine sarcoma) after laparoscopic morcellation was 9 times higher than the rate quoted to patients at the time (1 in 10,000), and concluded that uterine morcellation carries a risk of spreading unsuspected cancer.

FDA’s Response to First Adverse Event Reports Included Estimating Cancer Risk, Warning Against the Use of Power Morcellators, and Recommending New Labeling

FDA took several actions after receiving the first adverse event reports in December 2013 describing the spread of cancerous tissue after using a power morcellator to treat uterine fibroids. (See fig. 3.) See appendix IV for a more detailed timeline of FDA actions and other events related to power morcellators.

FDA’s actions included the following

Convening a signal review team. In December 2013, FDA began forming a signal review team to coordinate and lead the agency’s evaluation and response to the potential safety issue related to power morcellators. According to FDA officials, the team started meeting weekly and collecting information on the devices, adverse event reports, and scientific literature in January 2014.

Estimating the prevalence of cancer in women undergoing surgical treatment for uterine fibroids. In April 2014, FDA published the results of a review of scientific literature to estimate the prevalence of cancer (specifically sarcoma and leiomyosarcoma) in women undergoing surgical treatment for uterine fibroids. Based on this review, FDA estimated that about 1 in 350 women undergoing the surgical procedures of hysterectomy or myomectomy to treat uterine fibroids was at risk for having an unsuspected uterine sarcoma. FDA also estimated that about 1 in 500 such women were at risk for having one certain type of uterine sarcoma, leiomyosarcoma. FDA officials told us that these estimates were significantly higher than what had been traditionally quoted (1 in 1,000 to 1 in 10,000).

Issuing an initial safety communication. In April 2014, FDA issued a safety communication discouraging the use of power morcellators in surgical procedures (hysterectomies and myomectomies) to treat uterine fibroids. In discouraging this use, FDA cited the lack of a reliable method for predicting whether a woman with uterine fibroids may have an unsuspected cancer; specifically, a uterine sarcoma. The agency also noted that if a power morcellator is used on women with an unsuspected uterine sarcoma, the procedure may spread cancerous tissue within the abdomen and pelvis, significantly worsening the patient’s likelihood of long-term survival. The safety communication also recommended that health care providers carefully consider all the available treatment options for women with symptomatic uterine fibroids and thoroughly discuss the benefits and risks of all treatments with patients. FDA also noted that it had instructed manufacturers that produced power morcellators used to treat uterine fibroids to review their device labeling for accurate risk information for patients and providers.

Convening a meeting of the Obstetrics and Gynecology Devices Panel of FDA’s Medical Devices Advisory Committee. In July 2014, FDA convened an expert panel and guest speakers to present their views and available data related to the potential power morcellator safety issue. The panel discussed patient populations in which power morcellators should not be used, specifically mentioning patients with known or suspected cancer. The panel also discussed mitigation strategies, including the possibility of adding a warning to power morcellator labeling related to the risk of spreading an unsuspected cancer.

Issuing guidance. FDA issued an “immediately in effect” guidance document in November 2014. The guidance noted that recent discussions with the patient and clinical communities, as well as the peer-reviewed medical literature, had raised awareness of the risk of spreading unsuspected cancerous tissue beyond the uterus when power morcellators are used during surgeries intended to treat uterine fibroids. For power morcellators with a general or gynecologic indication for use, the guidance recommended the addition of specific safety statements to the product labeling for laparoscopic power morcellators, including two contraindications and a boxed warning that the use of power morcellators during fibroid surgery may spread cancer. (See fig. 4.) FDA also recommended that manufacturers submit their revised labeling language to FDA, as well as to the hospitals and other facilities that had previously purchased power morcellators. We found that the manufacturers of the 10 power morcellators with indications for use for general surgical or gynecological procedures marketed as of November 2016 followed the recommendation, providing FDA with updated labeling. Information provided by FDA indicated that manufacturers also contacted hospitals and other user facilities that purchased their power morcellators, providing the updated labeling and instructing them to switch out any old labeling. Half of the manufacturers also instructed the user facilities to mail back a receipt of acknowledgement regarding the safety alert to the manufacturer.

Issuing an updated safety communication. At the same time it issued guidance in November 2014, FDA issued an updated safety communication warning against the use of power morcellators in the majority of women undergoing surgery (hysterectomy or myomectomy) to treat uterine fibroids. This safety communication recommended that doctors thoroughly discuss the benefits and risks of all treatments with their patients. The updated safety communication also specified that FDA considers the spread of unsuspected cancer when using a power morcellator for hysterectomy or myomectomy to treat uterine fibroids as a serious injury, which is a reportable adverse event under the agency’s medical device reporting requirements.

Inspecting selected user facilities for compliance with adverse event reporting. In December 2015, FDA initiated inspections at selected hospitals to review their compliance with medical device reporting requirements, which specify that hospitals and other user facilities must report certain device-related events to FDA and to manufacturers when the manufacture is known. These inspections included five hospitals that, according to FDA officials, were chosen because there were reports of adverse events at these facilities related to the spread of uterine cancer from the use of power morcellators. FDA identified significant deviations from medical device reporting requirements at these hospitals based on its review of the inspection evidence. FDA investigators’ observations included user facilities’ failure to report adverse events within required time frames or to establish and maintain files for medical device reporting—that is, adverse event reports. The agency determined that corrective action plans presented by two of the five hospitals were adequate, and according to FDA officials, the agency worked with the three other hospitals to help ensure appropriate corrective actions were taken.

Questions Remain Regarding the Use of Power Morcellators to Treat Uterine Fibroids, and FDA Continues to Monitor Available Information

Questions remain regarding the use of power morcellators in the treatment of uterine fibroids, which include varying stakeholder opinions regarding the risks related to the use of power morcellators. For example, FDA officials noted there was limited information available to assess how the risk of spreading cancerous tissue is affected when the morcellation is performed using a power morcellator or through manual morcellation (e.g., using a scalpel). Similarly, officials from one professional society also stated that they were not aware of any reliable data showing that power morcellation spreads tissue any worse than other morcellation techniques. In addition, professional societies have questioned or noted concerns with FDA’s estimate of the risk of cancer (uterine sarcoma) in women who undergo surgical treatment of uterine fibroids, citing limitations related to FDA’s methodology. One professional society’s open letter to FDA included concerns regarding the keywords FDA officials used to find the studies included in their estimate, stating that those keywords may have limited the number of studies used to develop the agency’s estimate. The letter also asserted that FDA’s estimate was higher than a more appropriate estimated risk of uterine cancer of about 1 in 1,500 to 1 in 2,000. FDA officials have acknowledged limitations, such as the small number of studies, in their estimate, but stated that estimates in more recently representative published studies have generally been consistent with the agency’s estimate.

Continuing questions also include the long-term effects of FDA’s guidance on patients, according to the stakeholders we interviewed. Two professional societies we contacted have expressed concern that FDA’s decision to discourage the use of power morcellators in laparoscopic surgeries (hysterectomies and myomectomies) to treat uterine fibroids limits women’s health options. According to officials from the two societies, the reduction or elimination of laparoscopic surgery using a power morcellator to treat uterine fibroids—in response to FDA’s safety communication and guidance—may lead to an increased use of abdominal hysterectomies, a surgical procedure that typically does not involve the use of power morcellators, but is associated with other risks. One professional society noted that abdominal hysterectomies require larger incisions, slower recovery time, and present the patient with higher mortality rates and complications than laparoscopic hysterectomies. However, FDA officials noted that one 2016 study reported a decline in the use of power morcellators in hysterectomies since the agency issued its November 2014 guidance, and found no increase in complications from abdominal hysterectomies.

While these questions remain, FDA officials stated that the agency continues to review scientific literature regarding the use of power morcellators to treat uterine fibroids as new studies have been conducted since 2014. We found more than 50 articles on the risk of uterine cancer in women or the use of morcellation in women undergoing gynecologic surgeries like hysterectomy and myomectomy—including peer-reviewed articles, case studies, and opinion pieces—that have been published since December 2013.

FDA also continues to monitor available adverse event information regarding the use of power morcellators, while acknowledging the limitations of the available information. FDA reported that, as of September 2016, the agency had identified 285 adverse event reports about the spread of an unsuspected cancer following the use of a power morcellator. According to FDA officials, the majority (over 88 percent) of these reports were mandatory reports submitted by manufacturers. The remainder were voluntary reports from patients and their families, as well as physicians (about 10 percent) and mandatory reports from hospitals and other user facilities (less than 2 percent). According to FDA officials, of the 285 adverse event reports regarding power morcellators and the spread of unsuspected cancer that the agency received through September 2016, 5 were related to events occurring after FDA issued its guidance and updated safety communication in November 2014. FDA officials noted, however, the limitations in the current, passive, medical device reporting system, which relies on people to identify that a harm occurred or a risk is present, recognize that the harm or risk is associated with the use of a particular device, and take the time to report it. For power morcellators, officials from three health care providers (two hospitals and one physician group) that we spoke to stated that prior to November 2014, physicians would likely not have considered the spreading of an unsuspected cancer following the use of a power morcellator as a reportable adverse event, because the device would have performed as intended (e.g., cutting and extracting tissue). FDA’s inspections of manufacturers of power morcellators and hospitals that use them have also identified issues related to medical device reporting of adverse events. (See app. I for more information on FDA inspections related to medical device reporting.)

Recognizing the limitations in its current postmarket surveillance activities, the agency reported plans to generate better information in the future. For example, in October 2016, the agency reported plans to work with hospitals to identify a system that quickly identifies life-threatening problems caused by medical devices. FDA officials also noted they will continue to review new technologies, such as morcellation containment systems, and work on a national registry to collect data on the treatment of fibroids. In addition, FDA is working to establish a National Evaluation System for health Technology to more efficiently generate better evidence for medical device evaluation and regulatory decision-making.

Professional Societies Provided Guidance Regarding the Use of Power Morcellators, While Device Manufacturers Provided Instructions and Technical Training

The professional societies we contacted did not have any professional standards or training requirements for physicians specifically regarding the use of power morcellators, but some societies issued guidance to physicians related to procedures that could involve the use of power morcellators. The training requirements for physicians performing procedures like hysterectomies are typically determined at the hospital level. All power morcellator manufacturers provided instructions for use, and some offered technical training.

Professional Societies Do Not Have Specific Standards on the Use of Power Morcellators, but Some Provided Guidance on Procedures That Could Involve the Device

Officials from three professional societies we contacted—AAGL (formerly the American Association of Gynecologic Laparoscopists), the American Board of Obstetrics and Gynecology (ABOG), and the American Congress of Obstetricians and Gynecologists (ACOG)—stated that there are no professional standards issued by their societies that apply to member physicians specifically regarding the use of power morcellators. ABOG, which certifies obstetricians and gynecologists in the United States, does not deal directly with training recommendations or requirements related to the use of power morcellators. AAGL and ACOG, which are professional societies representing member physicians; The Joint Commission, which accredits hospitals; and three health care providers, which included two hospitals and a physician group, we contacted stated that training requirements for physicians performing specific procedures, such as procedures to treat uterine fibroids, are generally governed by hospital credentialing and privileging.

While the professional societies that we contacted did not set standards or requirements for using power morcellators, some provided guidance and educational resources for their members on the procedures that could involve the use of power morcellators. For example, in May 2014, the American College of Obstetricians and Gynecologists (ACOG’s companion organization) published a special report on clinical recommendations and scientific issues related to hysterectomies or myomectomies. This special report touched on topics related to proper diagnosis and evaluation before a hysterectomy or myomectomy, the use of a bag during morcellation in gynecologic surgery, and patient counseling and informed consent information that should be discussed with a patient if a power morcellator is being considered for use during the procedure.

Officials from the three health care providers that we interviewed indicated that physicians may receive training in using power morcellators during their medical residency (for example, if their attending physician used the device). The officials also noted that, after completing their medical residency, physicians who want to use power morcellators for laparoscopic surgery would likely seek out training, such as individual training from another physician with experience using the device. According to health care provider officials, physicians’ privileges to perform laparoscopic hysterectomies and myomectomies could be part of broader privileges—for example, they said that some hospitals may grant permission for a physician to use a power morcellator as part of a general list of procedures for gynecologists, or a hospital could require specific permission for use of the device.

Manufacturers Provided Instructions and Offered Technical Training on the Use of Power Morcellators

All of the 25 power morcellators cleared by FDA included instructions from the manufacturers for using the device, and some of the manufacturers offered technical training for physicians. FDA regulations require that the labeling for a prescription device like a power morcellator, which is not safe for use except under the supervision of a licensed practitioner, must provide information on the device’s use, including precautions under which practitioners can use the device safely and the purpose for which the device is intended. We found the labeling for the 25 power morcellators included instructions for use (submitted by the manufacturers to FDA as part of the agency’s premarket review of the devices), which provided information such as device assembly, use, disassembly, and safety information. One power morcellator manufacturer that responded to our request for information stated that it has a standard procedure to review the instructions for use with new users of its power morcellator. In addition to providing instructions for use, two manufacturers that provided us with information also offered technical training to physicians on their power morcellators, such as demonstrating how to set-up or operate their devices. FDA does not require manufacturers to provide clinical training for power morcellators, that is, training on the actual morcellation of tissue during a surgical procedure. One manufacturer we spoke to stated that clinical training is typically part of a surgeon’s accredited residency and fellowship program.

Agency Comments

We provided a draft of this report to the Secretary of Health and Human Services. HHS provided technical comments that were incorporated as appropriate.

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Appendix I: Food and Drug Administration’s Adverse Event Reporting System and Process for Monitoring Compliance

The Food and Drug Administration (FDA) uses information gathered through adverse event reporting to monitor and track potential safety issues associated with medical devices after they are marketed in the United States. According to FDA, adverse event reports are best used for two purposes. First, they are used to capture qualitative snapshots of adverse events for a particular device or device type, such as the types of malfunctions or clinical events, or both, associated with the device. Second, they are used to detect safety signals, such as identifying unexpected events associated with a particular device or device type.

Adverse event reports are submitted to FDA through mandatory and voluntary sources. Mandatory adverse event reporting by medical device importers, manufacturers, and user facilities enables FDA to obtain specific safety data related to medical devices from these reports. FDA regulations require medical device importers, manufacturers, and user facilities that become aware of information suggesting that a device may have caused or contributed to a death or serious injury to provide information to FDA. Manufacturers and importers also must report certain device malfunctions—manufacturers must report the information to FDA and importers must report the information to the manufacturer. (See table 3 for summaries of these reporting requirements.) FDA also encourages healthcare professionals, patients, caregivers, and consumers to submit voluntary adverse event reports or problems with medical devices.

According to FDA officials, while the agency has enforcement authority over mandatory adverse event reporting by user facilities, the agency has generally focused its enforcement resources on manufacturers—which are required to investigate each reportable event. According to FDA officials, of the 2,185 device inspections conducted in fiscal year 2015, 875 included a review of medical device reporting. Of these inspections, FDA reported that the agency found 284 to have inspection observations related to medical device reporting requirements. Of the 12 manufacturers of power morcellator medical devices, FDA reported inspecting 11 of them in the past 5 years (including inspections for devices other than power morcellators). As a result of these inspections, FDA reported identifying problems related to medical device reporting such as manufactures not reporting adverse events within required time frames or not implementing medical device reporting procedures. For three manufacturers, the inspections resulted in FDA issuing warning letters that cited, among other things, violations of medical device reporting requirements.

FDA may also inspect user facilities’ compliance with medical device reporting requirements, for example, in situations where the user facility perspective is essential to understanding the public health issue. Recently, in light of several high-profile device safety issues occurring in hospitals, the agency initiated inspections at 17 hospitals in December 2015. According to the director of FDA’s Center for Devices and Radiological Health, these hospitals were chosen because there were reports of events at these facilities related to the spread of uterine cancer from the use of power morcellators or the spread of infections associated with another device called a duodenoscope. The director noted that while these events appeared to be the kind that would have fallen under the agency’s medical device reporting requirements, the agency did not see corresponding adverse event reports submitted to FDA’s adverse event report database. He further reported that from these inspections, the agency learned several things, including

Some hospitals did not submit required reports for deaths or serious injuries related to devices used at their facilities; and in some cases, they did not have adequate procedures in place for reporting device- related deaths or serious injuries to FDA or to the manufacturers. Based on the number of user facilities in the United States and the number of reports FDA receives, the agency believes that these hospitals are not unique, in that there is limited to no reporting to FDA or to the manufacturers at some hospitals.

Hospital staff often were not aware of nor trained to comply with all of FDA’s medical reporting requirements.

The director also noted that FDA wants to work with hospitals to address issues of limited or nonreporting, and to work with hospitals to get the real-world information FDA needs. For example, following the inspections, FDA held regulatory meetings with certain hospitals to help identify corrective actions. In addition, FDA hosted a public workshop in December 2016 to discuss how to improve hospitals’ role in monitoring medical device safety.

Appendix II: History of Predicate Devices for the First Laparoscopic Power Morcellator

In clearing the first laparoscopic power morcellator in 1991 through the 510(k) premarket notification process, the Food and Drug Administration (FDA) determined the device was substantially equivalent to an electromechanical system for cutting tissue during minimally invasive surgeries performed on knees and other joints. According to FDA officials, this device, known as an arthroscopic surgical system, was one of a number of devices cited by the manufacturer in the 510(k) submission; however, the agency based its determination of substantial equivalence primarily on the arthroscopic surgical system. As shown in table 4, FDA documentation shows that the device can be traced back to a surgical system also used for cutting during knee surgeries that FDA determined in 1978 to be substantially equivalent to a predicate device that was marketed prior to the enactment of the Medical Device Amendments of 1976 (May 28, 1976).

Appendix III: General Characteristics of the 25 510(k) Submissions for Laparoscopic Power Morcellators Cleared by the Food and Drug Administration

Between 1991 and 2014, the Food and Drug Administration cleared 25 laparoscopic power morcellators to be marketed in the United States. Figure 5 shows the device type, medical specialty, and indications for use for 11 power morcellators still being marketed in the United States in November 2016. Figure 6 provides the same information for the other 14 devices that were no longer being marketed in November 2016.

Appendix IV: Detailed Timeline of Events Related to Laparoscopic Power Morcellators

Table 5 shows key events related to laparoscopic power morcellators and the actions the Food and Drug Administration has taken in relation to safety concerns of the spread of unsuspected uterine cancer following the use of power morcellators in the treatment of uterine fibroids.

Appendix V: GAO Contact and Staff Acknowledgments

GAO Contact

Staff Acknowledgments

In addition to the contact named above, Kim Yamane (Assistant Director), Aaron Holling (Analyst-in-Charge), Jazzmin Cooper, and Kate Tussey made key contributions to this report. Also contributing were Leia Dickerson, Sandra George, Drew Long, and Vikki Porter.