- Email: [email protected]
Automatic External Defibrillators and the United States Food and Drug Administration: An Invited Commentary
SPECIAL CONTRIBUTION
AutomaticExternal Defibrillators and the United States Food and Drug Administration: An Invited Commentary Dr Burlington is the director of the Centerfor Devices and Radiological Health, U5 Food and Drug Administration, Rockville, Maryland. Copyright © by the American College of Emergency Physicians.
632
D Bruce Burlington, MD
[Burlington DB: Automatic external defibrillators and the United States Foodand Drug Administration: An invited commentary. Ann Emergbled November 1995;26:632-634.] In criticizing the actions of the US Food and Drug Administration (FDA) with regard to Laerdal automatic external defibrillators (AEDs), the article by Cummins, White, and Pepe [November 1995;26:621-631] focuses narrowly on the electrocardiographic findings of two cases in which these devices malfunctioned. This is misleading in that the FDA's decision to take action with regard to the Laerdal products was based on a substantial number of reports of malfunction, along with evidence of serious deficiencies in the manufacturing process. Before elaborating on these findings, let me explain a little about this agency's mandate under the law. Congress has charged the FDA (and therefore its Center for Devices and Radiological Health) with responsibility for assuring that medical devices are well manufactured, safe, effective, and adequately labeled for use. Essential to this function is the agency's role as an independent public health advocate for consumers. As a government agency with strict prohibitions against financial conflicts, the FDA is protected from outside influences, whether from the industry or from narrowly focused interest groups. Two important elements in our effort to assure safe and effective products were brought into play in the Laerdal case. First, we consider it essential to carefully monitor reports of patient injuries and serious product malfunctions provided by practitioners, user facilities, and manufacturers. This monitoring function is vital because the laboratory and clinical data derived during premarket testing of a device cannot rule out product failures from the demands of real-world use, nor can they predict rare or unanticipated adverse effects after a device is marketed and used in large patient populations. Reports of adverse events and malfunctions are often our only clue that a product in use may not be delivering the expected benefit or is creating unanticipated injuries or safety problems. Yet we are keenly aware that such
ANNALS OF EMERGENCY MEDICINE
26:5 NOVEMBER 1995
FDA RESPONSE
Burlington
reports are merely signals that problems are occurring. Despite the existence of mandatory adverse-event reporting programs for manufacturers and a voluntary reporting system for practitioners, we recognize that the reports we receive may represent only a limited fraction of the adverse events that are actually occurring in clinical practice. Thus they are often inadequate for evaluation of the magnitude of the problem (the total number of products that fail) or the rate of failure (the percentage of products that fail over a given time period). Nevertheless, our public health mandate requires us to evaluate these reports and to use our best judgment as to how to protect the public. Then, when it is warranted, we must take timely action to correct the problem. This is what occurred in the Laerdal situation. Although Cummins, White, and Pepe minimize the significance of the small number of failures of the widely used Laerdal AED, we viewed the reported failures as the tip of a possibly much larger iceberg. In fact, in the case of Laerdal's AEDs, we had received more than 350 reports of malfunctions, more than for any other maker of AEDs, and 40 reports of malfunctions confirmed by Laerdal as device-related problems. Although many of the reports did not involve patient injury attributable to the product, it was incumbent on us to investigate further. It is never easy, on the basis of sketchy reports of adverse incidents, to determine how common, how systematic, and how systemic medical device malfunctions are. Getting the answers requires full cooperation from the manufacturer. In this instance, as this issue was initially considered, cooperation was not fully forthcoming from Laerdal, particularly with regard to the company's making available electrocardiographic recordings relevant to the reports of rhythm misdiagnosis. Full evaluation also requires an estimate of how many products are in use and how often they are used, so that the rate of adverse events can be determined. Despite our requests, this information, too, was not made readily available by the manufacturer. A second key element in our effort to assure safe and effective devices, and one that played an important part in both the Laerdal and Physio-Control cases, is the inspection of manufacturing facilities to ensure that device firms are adhering to quality-control systems (known in FDA parlance as '~good manufacturing practices"). The importance of this function is often underestimated by the public and even by health care practitioners because the relationship between manufacturer quality control and the potential for patient injury is not always self
NOVEMBER 1995
26:5
ANNALS OF EMERGENCY MEDICINE
evident. In fact, such quality-control systems are not intended to correct injury-producing product problems; rather, when they are carried out properly, they prevent product failures. For a life-supporting or lifesaving device, it is especially important that we prevent problems rather than correct them after patient deaths and irremediable injuries have occurred. In the case of Laerdal, inspection of the firm's facilities disclosed inadequate quality control in the manufacture of these products. In particular, agency investigators found systemic problems in component acceptance and evaluation, in product-failure analysis, and in implementation of corrective action. Outside expert quality-systems consultants supported our findings during the subsequent litigation. We were therefore faced with two kinds of evidence that Laerdal AEDs were problematic: the number of sketchy but alarming reports of product malfunction and the quality-control problems we had found during inspections of the company. Our own staff of electrical engineers and cardiologists balanced the benefits and risks of the situation as it was known at that time and decided there was sufficient concern about the performance of Laerdal AEDs to take action. On the basis of our conclusions, we issued a Safety Alert to AED users and facilities, warning them about potential malfunctions and listing safety checks that might alert personnel to problems with these devices. For one product, the Heartstart 1000S, which had been documented in one case to have delivered an unneeded shock, we asked users to exercise clinical judgment before allowing the machine to deliver a second shock. We realize that this was a controversial recommendation, but we judged it to be warranted until we had more information about the performance of the machine's diagnostic algorithm. Our actions in both the Laerdal and Physio-Control cases were not intended or expected to remove the devices from areas of obvious need. We clearly understand the benefits of early, appropriate defibrillation and agree with the thesis that for those with ventricular fibrillation, a defibrillator that may not work perfectly is better than none. On the other hand, in the Laerdal case we also had to be concerned about the potentially dire consequences of inappropriate electrical countershock. It is important to understand that our goal in issuing the Safety Alert was not to cause health care facilities to stop using the Laerdal devices but simply to warn trained personnel that they should not allow their clinical judgment to be supplanted by that of a potentially real-
633
FDA RESPONSE
Burlington
functioning device, even if the malfunction was poorly understood and might be rare. It also should be noted that during early interactions with the FDA, the company was reluctant to notify users of these concerns. After multiple inspections, notices of quality-systems deficiencies, and attempted negotiations with Laerdal, we decided to take legal action against the firm. Our position was that although AEDs in the field should not be withdrawn from use, the corporation should fully investigate reported problems, institute appropriate quality-control steps before resuming shipment of new units, and correct the known problems with the defibrillators already m use. It is important to note that over the course of the FDBIs investigation, negotiations, and litigation, the corporation took steps to correct its quality-system deficiencies. By the time the trial was over, as the judge noted, Laerdal had corrected the quality-system problems and upgraded units in use. It is unfortunate that this case resulted m an adversarial proceeding in court. We far prefer to work with a company to determine the cause and extent of problems and then take cooperative action to protect consumers. Likewise, although our actions did not take AEDs out of service, it is clear in retrospect that the 2-year suspension of deliveries of Physio-Control AEDs was not a desirable result. It would have been preferable for the company and the FDA, working together, to correct the problem and get the firm back on line much sooner. Since the kaerdal incident, we have attempted to work closely with the user community and the industry to develop the defibrillator field in an efficient and scientific manner. We convened two meetings, one with health care professionals and consumers and another with all AED manufacturers, to promote the development of an accessible library of abnormal rhythms and. to promote consensus on an acceptable level of performance for these devices. We continue to work with the American Heart Association to improve defibrillator technology and reliability. I would like to close with a personal observation. In addition to my duties as the director of the FDA medical device program, I regularly practice emergency medicine. Thus I am keenly aware of the importance of AEDs and early defibrillation in the treatment of cardiac arrest. However, I am just as aware of the high expectations practitioners and patients have for such equipment. When a patient needs treatment in an emergency situation and the defibrillator won't work, the frustration can be intense and the time lost fiddling with it critical. Having experience on both sides of the
63 4
fence, I recognize the importance (and the difficulty) of achieving a proper balance in FDA decisionmaking--a balance between seeing to it that medical devices work properly and at the same time assuring that clinicians have available the critical devices they need. Reprint no 47/1169084 Address for reprints: Center for Devicesand Radialogical Health US Foodand Drug Administration HFZ-3 9200 CorporateBoulevard Rockville, Maryland 20850
ANNALS OF EMERGENCY MEDICINE
26:5
NOVEMBER 1995
AutomaticExternal Defibrillators and the United States Food and Drug Administration: An Invited Commentary Dr Burlington is the director of the Centerfor Devices and Radiological Health, U5 Food and Drug Administration, Rockville, Maryland. Copyright © by the American College of Emergency Physicians.
632
D Bruce Burlington, MD
[Burlington DB: Automatic external defibrillators and the United States Foodand Drug Administration: An invited commentary. Ann Emergbled November 1995;26:632-634.] In criticizing the actions of the US Food and Drug Administration (FDA) with regard to Laerdal automatic external defibrillators (AEDs), the article by Cummins, White, and Pepe [November 1995;26:621-631] focuses narrowly on the electrocardiographic findings of two cases in which these devices malfunctioned. This is misleading in that the FDA's decision to take action with regard to the Laerdal products was based on a substantial number of reports of malfunction, along with evidence of serious deficiencies in the manufacturing process. Before elaborating on these findings, let me explain a little about this agency's mandate under the law. Congress has charged the FDA (and therefore its Center for Devices and Radiological Health) with responsibility for assuring that medical devices are well manufactured, safe, effective, and adequately labeled for use. Essential to this function is the agency's role as an independent public health advocate for consumers. As a government agency with strict prohibitions against financial conflicts, the FDA is protected from outside influences, whether from the industry or from narrowly focused interest groups. Two important elements in our effort to assure safe and effective products were brought into play in the Laerdal case. First, we consider it essential to carefully monitor reports of patient injuries and serious product malfunctions provided by practitioners, user facilities, and manufacturers. This monitoring function is vital because the laboratory and clinical data derived during premarket testing of a device cannot rule out product failures from the demands of real-world use, nor can they predict rare or unanticipated adverse effects after a device is marketed and used in large patient populations. Reports of adverse events and malfunctions are often our only clue that a product in use may not be delivering the expected benefit or is creating unanticipated injuries or safety problems. Yet we are keenly aware that such
ANNALS OF EMERGENCY MEDICINE
26:5 NOVEMBER 1995
FDA RESPONSE
Burlington
reports are merely signals that problems are occurring. Despite the existence of mandatory adverse-event reporting programs for manufacturers and a voluntary reporting system for practitioners, we recognize that the reports we receive may represent only a limited fraction of the adverse events that are actually occurring in clinical practice. Thus they are often inadequate for evaluation of the magnitude of the problem (the total number of products that fail) or the rate of failure (the percentage of products that fail over a given time period). Nevertheless, our public health mandate requires us to evaluate these reports and to use our best judgment as to how to protect the public. Then, when it is warranted, we must take timely action to correct the problem. This is what occurred in the Laerdal situation. Although Cummins, White, and Pepe minimize the significance of the small number of failures of the widely used Laerdal AED, we viewed the reported failures as the tip of a possibly much larger iceberg. In fact, in the case of Laerdal's AEDs, we had received more than 350 reports of malfunctions, more than for any other maker of AEDs, and 40 reports of malfunctions confirmed by Laerdal as device-related problems. Although many of the reports did not involve patient injury attributable to the product, it was incumbent on us to investigate further. It is never easy, on the basis of sketchy reports of adverse incidents, to determine how common, how systematic, and how systemic medical device malfunctions are. Getting the answers requires full cooperation from the manufacturer. In this instance, as this issue was initially considered, cooperation was not fully forthcoming from Laerdal, particularly with regard to the company's making available electrocardiographic recordings relevant to the reports of rhythm misdiagnosis. Full evaluation also requires an estimate of how many products are in use and how often they are used, so that the rate of adverse events can be determined. Despite our requests, this information, too, was not made readily available by the manufacturer. A second key element in our effort to assure safe and effective devices, and one that played an important part in both the Laerdal and Physio-Control cases, is the inspection of manufacturing facilities to ensure that device firms are adhering to quality-control systems (known in FDA parlance as '~good manufacturing practices"). The importance of this function is often underestimated by the public and even by health care practitioners because the relationship between manufacturer quality control and the potential for patient injury is not always self
NOVEMBER 1995
26:5
ANNALS OF EMERGENCY MEDICINE
evident. In fact, such quality-control systems are not intended to correct injury-producing product problems; rather, when they are carried out properly, they prevent product failures. For a life-supporting or lifesaving device, it is especially important that we prevent problems rather than correct them after patient deaths and irremediable injuries have occurred. In the case of Laerdal, inspection of the firm's facilities disclosed inadequate quality control in the manufacture of these products. In particular, agency investigators found systemic problems in component acceptance and evaluation, in product-failure analysis, and in implementation of corrective action. Outside expert quality-systems consultants supported our findings during the subsequent litigation. We were therefore faced with two kinds of evidence that Laerdal AEDs were problematic: the number of sketchy but alarming reports of product malfunction and the quality-control problems we had found during inspections of the company. Our own staff of electrical engineers and cardiologists balanced the benefits and risks of the situation as it was known at that time and decided there was sufficient concern about the performance of Laerdal AEDs to take action. On the basis of our conclusions, we issued a Safety Alert to AED users and facilities, warning them about potential malfunctions and listing safety checks that might alert personnel to problems with these devices. For one product, the Heartstart 1000S, which had been documented in one case to have delivered an unneeded shock, we asked users to exercise clinical judgment before allowing the machine to deliver a second shock. We realize that this was a controversial recommendation, but we judged it to be warranted until we had more information about the performance of the machine's diagnostic algorithm. Our actions in both the Laerdal and Physio-Control cases were not intended or expected to remove the devices from areas of obvious need. We clearly understand the benefits of early, appropriate defibrillation and agree with the thesis that for those with ventricular fibrillation, a defibrillator that may not work perfectly is better than none. On the other hand, in the Laerdal case we also had to be concerned about the potentially dire consequences of inappropriate electrical countershock. It is important to understand that our goal in issuing the Safety Alert was not to cause health care facilities to stop using the Laerdal devices but simply to warn trained personnel that they should not allow their clinical judgment to be supplanted by that of a potentially real-
633
FDA RESPONSE
Burlington
functioning device, even if the malfunction was poorly understood and might be rare. It also should be noted that during early interactions with the FDA, the company was reluctant to notify users of these concerns. After multiple inspections, notices of quality-systems deficiencies, and attempted negotiations with Laerdal, we decided to take legal action against the firm. Our position was that although AEDs in the field should not be withdrawn from use, the corporation should fully investigate reported problems, institute appropriate quality-control steps before resuming shipment of new units, and correct the known problems with the defibrillators already m use. It is important to note that over the course of the FDBIs investigation, negotiations, and litigation, the corporation took steps to correct its quality-system deficiencies. By the time the trial was over, as the judge noted, Laerdal had corrected the quality-system problems and upgraded units in use. It is unfortunate that this case resulted m an adversarial proceeding in court. We far prefer to work with a company to determine the cause and extent of problems and then take cooperative action to protect consumers. Likewise, although our actions did not take AEDs out of service, it is clear in retrospect that the 2-year suspension of deliveries of Physio-Control AEDs was not a desirable result. It would have been preferable for the company and the FDA, working together, to correct the problem and get the firm back on line much sooner. Since the kaerdal incident, we have attempted to work closely with the user community and the industry to develop the defibrillator field in an efficient and scientific manner. We convened two meetings, one with health care professionals and consumers and another with all AED manufacturers, to promote the development of an accessible library of abnormal rhythms and. to promote consensus on an acceptable level of performance for these devices. We continue to work with the American Heart Association to improve defibrillator technology and reliability. I would like to close with a personal observation. In addition to my duties as the director of the FDA medical device program, I regularly practice emergency medicine. Thus I am keenly aware of the importance of AEDs and early defibrillation in the treatment of cardiac arrest. However, I am just as aware of the high expectations practitioners and patients have for such equipment. When a patient needs treatment in an emergency situation and the defibrillator won't work, the frustration can be intense and the time lost fiddling with it critical. Having experience on both sides of the
63 4
fence, I recognize the importance (and the difficulty) of achieving a proper balance in FDA decisionmaking--a balance between seeing to it that medical devices work properly and at the same time assuring that clinicians have available the critical devices they need. Reprint no 47/1169084 Address for reprints: Center for Devicesand Radialogical Health US Foodand Drug Administration HFZ-3 9200 CorporateBoulevard Rockville, Maryland 20850
ANNALS OF EMERGENCY MEDICINE
26:5
NOVEMBER 1995