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5 Postmarketing Surveillance, Compliance, and Enforcement M edical devices used both by professional healthcare providers and the public constitute a vital part of the healthcare environment. When used according to their manufacturers’ guidance, devices are expected to be safe and effective. Given that, as discussed in Chapter 1, it is not possible to create a premarket review process that could com- pletely ensure the safety of all devices before they enter the market, a strong surveillance system that monitors the safety of medical devices is essential. The identification of problems associated with a medical device can be an opportunity for various corrective actions, including improved device label- ing, instructions for use or better user training, or, if appropriate, removal from the market. This chapter reviews the current programs that the Food and Drug Administration (FDA) has in place, both passive and active, and some non-FDA surveillance programs that provide information on the safety and effectiveness of particular devices. It also examines how the FDA commu- nicates information gathered through postmarketing surveillance activities to consumers, such as healthcare providers and the public. The term postmarketing surveillance encompasses a wide array of pro- grams, including medical device reporting by manufacturers and user facili- ties, third-party safety monitoring, and FDA–academic collaborations. The term postmarket surveillance refers to a specific activity defined by statute. For medical devices, the FDA uses the term medical-device report (MDR) to encompass two types of reports—adverse-event reports are in- cidents resulting in a death or serious injury, and malfunction reports are incidents in which a device fails without an adverse event resulting. 123

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124 MEDICAL DEVICES AND THE PUBLIC’S HEALTH Postmarketing surveillance is either “passive” or “active.” In a pas- sive system, the regulator must depend on data from manufacturers and healthcare providers. The provision of data can be required by statute or be voluntary, but the role of the regulator is to collect and analyze the data that are provided. In an active system, in contrast, the regulator seeks informa- tion on adverse events, device malfunctions, and product effectiveness and takes advantage of opportunities to enhance data collection. It is important to note that for most of the programs discussed below there is no reliable information about the number of devices (referred to as the denominator) on the market in clinical use. The lack of denominator information limits the ability to analyze potential safety concerns. THE FOOD AND DRUG ADMINISTRATION’S CURRENT POSTMARKETING SURVEILLANCE ACTIVITIES Mandatory and Voluntary Adverse-Event Reporting Reporting requirements for the FDA are summarized in a 2009 Depart- ment of Health and Human Services (HHS) Office of the Inspector General (OIG) report (OIG, 2009), which states that regulations require device manufacturers to report to the FDA (1) within 30 calendar days of acquiring information that reasonably suggests one of their devices may have caused or contributed to a death, serious injury, or malfunction and (2) within 5 working days if an event requires action other than routine maintenance or service to prevent a public health is- sue. Regulations also require user facilities, such as hospitals and nursing homes, to report deaths to both the manufacturer, if known, and the FDA within 10 working days. User facilities must report serious injuries to the manufacturers (or the FDA if the manufacturer is unknown) within 10 working days. User facilities must also submit annual reports to the FDA of all adverse event reports sent to manufacturers or FDA in the past year. The vast majority of MDRs are reported by manufacturers; user facili- ties and others provide a small proportion of the reports received by the FDA (see Table 5-1). As a general matter, patients, caregivers, and healthcare professionals are not legally obliged to report adverse medical events. Con- sumers, such as healthcare providers and patients, can provide voluntary adverse-event reports to the FDA through its MedWatch program (FDA, 2009b).

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125 SURVEILLANCE, COMPLIANCE, AND ENFORCEMENT TABLE 5-1 Medical-Device Adverse-Event Reports, 2003–2007 Type of Adverse-Event Report 2003 2004 2005 2006 2007 Manufacturer report 65,217 70,718 90,157 109,676 141,065 Percentage of total 90% 90% 92% 93% 94% reports User-facility report 2,890 3,256 3,752 3,048 3,234 Percentage of total 4% 4% 4% 3% 2% reports Other reports 4,759 4,610 4,552 5,571 5,911 Percentage of total 7% 6% 4% 5% 4% reports Report total 72,866 78,584 98,461 118,295 150,210 NOTE: Other reports include FDA voluntary and distributor reports; percentages do not add to 100, because of rounding; 2005 and 2006 report totals do not include one report and five reports, respectively, because of missing data needed for analysis. SOURCE: OIG, 2009. Customary Data Sources Two fundamental steps in all MDRs are recognizing that an adverse event or malfunction has occurred and then associating the event with one or more possible diagnostic or therapeutic interventions as causal or con- tributing factors. Identifying the event can be problematic for many reasons. Some problems with medical devices can become apparent immediately (for example, in a procedural situation in an operating room or an intensive-care unit), but in other cases problems can take a long time to be manifested. For example, a patient can have a procedure in a hospital, be discharged, and seek follow-up care for an emerging medical problem from a physician who does not associate the problem with the earlier procedure. In such situ- ations, the event rarely is reported. Even when it is, the MDR often includes inadequate information about the situation or the device, which makes it difficult to link the device with the medical problem (IOM, 2011). When a medical problem is suspected to have occurred in association with use of a medical device, a bioengineer or risk manager may or may not be available to assist in the assessment of the role and potential responsibil- ity of the device and to take appropriate corrective action. When informa- tion is available about the role of the device in the event, healthcare facilities

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126 MEDICAL DEVICES AND THE PUBLIC’S HEALTH are required by the Safe Medical Devices Amendments of 1990 to report the problem to the manufacturer if the problem is a device-related death or serious injury. In addition, the onset of some medical problems may be de- layed, and the person using the potentially problematic device may no longer be a patient of a healthcare facility that is legally required to file an MDR. Physicians increasingly use higher-risk devices, including implantable devices, in their offices where there is no legal requirement for them to report adverse events and device failures to the FDA. Voluntary reports made by healthcare providers have always made up a very small fraction of the reports received by the FDA. In 1993, the MedWatch program was established to improve reporting by device users, but it has had little impact: only 5.6% of reports were voluntary in 2004 (Greenfield, 2007). The total number of events reported has increased steadily from 72,866 in 2003 to 150,210 in 2007 (OIG, 2009). Most initial reports of adverse medical events or device malfunctions lack critical information about the patient’s medical history. The Office of the Inspector General found that of the more than 140,000 MDRs filed by manufacturers in 2007, 50% of the reports were missing device identification information, such as model numbers, and 11% were missing descriptions of the adverse event or device malfunction (OIG, 1990). Follow-up inquiries are essential to fill in the gaps in information. Manufacturers are required by the FDA to perform follow- up for the majority of reports received to obtain the missing information for the medical-device reporting system. The agency also requires manufactur- ers to trend adverse events for reporting. Investigations of adverse events and device malfunctions can be ham- pered by refusals to provide further information on the part of the patient (who may now be involved in litigation for damages), the treating physician or the physician who used or implanted the device (who may become a de- fendant in litigation over alleged malpractice), and any healthcare facility involved (possibly also a defendant in litigation). The device itself might not be available for examination and testing. And the manufacturer of the device may become involved in product-liability litigation. There are other reasons, not related to liability or litigation, that also affect investigations, such as the unreimbursed cost to physicians and healthcare facilities of responding to requests for information. The next phase depends on how the manufacturer handles the infor- mation. There are regulations governing timely review and maintenance of records. Manufacturers determine whether the information meets the threshold for a reportable event. They may categorize an event as user er- ror (OIG, 1990). There have been instances in which manufacturers have underreported serious adverse events by not reporting them to their own regulatory staff (Bren, 2003). However, whenever any agent of a company

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127 SURVEILLANCE, COMPLIANCE, AND ENFORCEMENT knows of an adverse event, the company is deemed to have knowledge and is required to report. A company that does not report is in violation of the law. Manufacturers are required to report within 30 days if a device may have caused or contributed to a death or serious injury or, if a device mal- functioned and a death or serious injury could result if the malfunction were to recur, and within 5 days if a reportable event necessitates remedial action (other than routine maintenance or servicing) to prevent an unreasonable risk of substantial harm to public health. In 2007, 31% of the more critical 5-day reports were submitted late. Similarly, healthcare facilities submitted 39% of death and injury adverse-event reports late (OIG, 2009). The timeliness of the FDA review of MDRs is also problematic. Fewer than one-third of MDRs were reviewed for the first time within 30 days, and fewer than half were reviewed within 60 days in every year from 2003 to 2007. Documentation of the reviews is also inconsistent, and this makes it difficult to track the agency’s response to a specific event. Moreover, the FDA Office of Compliance does not link inspections to the adverse event that may have triggered them. In addition to the previously described system for mandatory and volun- tary reporting of adverse events and device malfunctions, summary report- ing from industry provides an abbreviated method that relies on established codes for events that are well known and categorized. Although they allow trending, the summaries provide little in the way of new information, and may have outlived their usefulness in that they hamper the function of an already overloaded system. Similarly, the compliance of user facilities with required annual reports is difficult to assess because CDRH was able to provide fewer than half the reports to the HHS OIG (OIG, 2009). These reports can also be repetitive with respect to individually submitted events. Larry Kessler, former director of CDRH’s Office of Surveillance and Bio- metrics, has suggested placing more emphasis on keeping the data in the manufacturers’ quality-reporting systems (Kessler, 2010). Data Management Each MDR is entered into an event database by an FDA contractor and then undergoes triage by a safety analyst (generally a nurse or engineer working for the FDA) to look for a signal of risk of potential substantial harm. That screening is made more difficult by the low signal-to-noise ratio, the MDR reviewers’ narrow experience with new technology, the absence of input to the reviewers by premarket staff more familiar with the device, and the sheer volume of reports, which exceeds the capacity of the current system (GAO, 2009b; IOM, 2011). Efforts to integrate the premarket and postmarket phases of review in a matrix approach have been proposed since 2005 (Schultz, 2007), but have proved difficult to sustain because staff were

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128 MEDICAL DEVICES AND THE PUBLIC’S HEALTH in different facilities and had a heavy workload. But an integrated approach is important when reports of adverse events and device malfunctions appear shortly after introduction of a new device (Mehran et al., 2004). As mentioned above, incomplete or poor quality MDRs makes it dif- ficult to have an informed review of the problem. To address this issue, the FDA has safety analysts, who have relevant technological or clinical experi- ence, attempt to contact reporters (for example, manufacturers, user facili- ties, or voluntary reporters) for additional information. In addition, safety analysts interact with each other for clinical or engineering expertise to more fully understand reports. All safety analysts attend internal FDA conferences or “group think” meetings where a decision on further investigation may be made (IOM, 2011). In addition, data-mining is being explored by a variety of staff as an additional tool that may help identify potential safety signals. A rule proposed in August 2009 to require manufacturers to submit MDRs in an electronic format to allow more timely access to emerging adverse event information was met with resistance from industry, which called for a longer timeframe to implement the changes (Williams, 2010). All signals are entered into a CDRH tracking system, but the main repository for adverse event reports is the Manufacturer and User Device Experience (MAUDE) database. This database is considered to be in need of reform because it is difficult to use and is not connected to any other CDRH database (FDA, 1999b). When William Maisel, former director of the Medical Device Safety Institute, attempted to use MAUDE for analysis of 510(k)-cleared devices, he found that the data were not well suited to analysis, because of incomplete reporting, insufficient information, and misclassification (IOM, 2011). Problems are also caused by the difficulty of aligning product-code assignments, but CDRH is trying to address this issue (FDA, 2010c). As discussed in Chapter 3, efforts to upgrade informa- tion technology (IT) facilities in CDRH in recent years have been less than successful, and, as documented in the FDA Center for Drug Evaluation and Research, the challenges are exacerbated by the lack of communication between IT management and users (Breckenridge Institute, 2006). The Government Accountability Office (formerly the General Account- ing Office) reported in 1989 and again in 2009 that the FDA was unable to manage its postmarket-surveillance responsibilities because of resource constraints, but the agency is also unable to estimate its current and future resource needs effectively because of a lack of reliable management informa- tion (GAO, 1989, 2009a). Finding 5-1 The FDA’s current postmarketing surveillance system relies on manufacturers, importers, and healthcare facilities to col- lect information, to investigate, and to make mandatory reports. Voluntary reporting of adverse events and device malfunctions

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129 SURVEILLANCE, COMPLIANCE, AND ENFORCEMENT depends on patients, caregivers, and healthcare providers and facili- ties to identify them, to associate them with medical devices, and to submit reports. Finding 5-2 The inadequacy of the current postmarketing surveil- lance system and the resulting lack of data make it impossible to confidently draw broad conclusions about the safety and effective- ness of products that are on the market. Finding 5-3 Data collected with the current postmarketing surveil- lance system is not systematically integrated into the premarket review process. Enhanced Surveillance In addition to the general reporting requirements described above, the FDA conducts postmarketing surveillance via several other mechanisms: tracking of medical devices, the MedSun program, the MD EpiNet program, the Sentinel Initiative, and Section 522 surveillance studies. Tracking Tracking of medical devices by manufacturers can assist in notification to users of potential problems with a device and can facilitate recalls when necessary. The FDA requires tracking of 12 implantable devices and four other devices that are used outside hospitals. They include joint prostheses, implantable pacemakers, implantable defibrillator, mechanical heart valves, ventricular-bypass-assist devices, and implantable infusion pumps (Diehl et al., 2010). Manufacturers are expected to be able to provide within 10 days information about the location of devices that have been distributed to patients and within 3 days information about devices that are in inventory. MedSun Recognition of underreporting of adverse events led to the initiation in 2002 of a pilot program, the Medical Product Surveillance Network (MedSun), in which trained risk managers could recognize and report adverse events electronically. That direct connection with the clinical com- munity in 350 hospitals, nursing homes, and outpatient diagnostic and treat- ment centers not only improved the quality of reports but also allowed the identification of “near-misses” (FDA, 2009a). In addition, focus networks were developed on specific subjects, such as LabNet, which focuses on hos- pital laboratories; TissueNet, on human cells, tissues, and their products;

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130 MEDICAL DEVICES AND THE PUBLIC’S HEALTH SightNet, on ophthalmic devices; HomeNet, on device training and prob- lems in the home environment; HeartNet, on electrophysiology laboratories; and KidNet, on neonatal and pediatric units. MedSun also conducts small sample surveys involving a small number of institutions to answer specific questions on product safety (FDA, 2009c). A plan to implement real-time adverse-event reporting and establish pathways to interactive information exchange with healthcare providers is included in the FDA Strategic Plan for 2010 (FDA, 2010c). Additional plans include unspecified expansion of the MedSun nets, further evaluation of the regional representative pilot, and the incorporation of “large providers.” There are currently no resources allocated to implement those plans. The value of the approach is well demonstrated by the fact that 252 of the 350 MedSun facilities reported adverse events in 2007, accounting for 72% of all facilities that reported. In contrast, only 267 of the remaining thousands of other facilities reported adverse events in 2007, and that number has been declining (OIG, 2009). The regional representative pilot has established valuable linkages to healthcare providers and has led to more adverse-event reports. A 285% increase in reported medical-device concerns originating in pediatric specialties was demonstrated (Desjardins, 2011). MD EpiNet The MD EpiNet program, which began in February 2010, is intended to improve epidemiologic assessment of device performance by establish- ing an extramural network with 10 leading academic institutions that have experience with medical-device studies. The stated long-term goal is to “substantially contribute to the understanding of medical device perfor- mance and CDRH decision making, thereby improving public health, with an FY-10 focus on building a research infrastructure by linking CDRH with leading academic organizations in the country that have experience with medical device studies” (FDA, 2011b). As of May 2011, the Web site for the program lists the accomplishments as “establishment of a partnership development team to develop a research plan,” holding a “kickoff work- shop with academic stakeholders” on April 30, 2010, and a workshop to discuss methodologic issues related to studying medical device performance on April 25, 2011, awarding contracts for administration of the program, and initiating pilot projects in the selected centers. Sentinel Initiative In 2007, Congress passed the FDA Amendments Act (FDAAA), Section 905 of which mandated that the FDA establish a postmarketing risk iden- tification and analysis system to support active monitoring of postmarket-

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131 SURVEILLANCE, COMPLIANCE, AND ENFORCEMENT ing drug safety. The FDA is responding to that mandate by developing the Sentinel system, which will harness clinical and administrative data held by existing health-information holders. Congress set a target for the system to include data on 100 million persons by July 2012 (FDA, 2011a). Although Section 905 of the FDAAA specifically authorized creation only of an ac- tive surveillance system for drugs, the FDA is using its general authority under Section 1003(b)(2)(c) of the Federal Food, Drug, and Cosmetic Act (FFDCA) to include medical devices in the Sentinel system. The Sentinel Initiative helps the FDA to fulfill its mission to “protect the public health by ensuring that . . . there is a reasonable assurance of the safety and effective- ness of devices intended for human use.”1 The FDA has already received deliverables from 10 small contracts that address various issues related to system planning and design, such as data availability, system architecture, methods, legal and privacy issues, and stakeholder engagement. In addition, it has entered a cooperative agreement with the Brookings Institution to convene meetings and workshops on ac- tive medical-product surveillance issues. Early in 2010, the FDA awarded a 5-year contract to the Harvard Pilgrim Health Care Institute to develop a “Mini-Sentinel” pilot project, a scaled-down version of the Sentinel sys- tem. The Mini-Sentinel Coordinating Center is identifying appropriate data sources, developing a scientific framework for obtaining real-time data, and developing procedures to ensure data quality and privacy protection (FDA, 2010d). As of January 2011, the electronic health records of more than 60 million people have been added to the system (Behrman et al., 2011). To protect personal information, the system relies on a distributed network architecture that keeps identifiable health data behind the existing privacy firewalls of the participating data sources; only summary results are sent to the coordinating center. The mini-Sentinel and Sentinel planned activities are public-health activities and the Common Rule2 does not require informed consent of individuals whose records are being examined (Rosati et al., 2010). These activities also fit within an existing exception to the Health Insurance Portability and Accountability Act privacy rule that allows dis- closures to public-health authorities without individual authorization.3 The first year of the Mini-Sentinel effort focused on developing a data model common to data sources with an initial focus on claims data (Mini-Sentinel Coordinating Center, 2010). The Sentinel system is expected to expand and gain additional functionality over the next several years. The Sentinel system will be able to provide data that are applicable to medical devices. For example, one Sentinel-related project identified, 1FFDCA § 1003(b)(2)(C). 2Federal policy for the protection of human subjects (Common Rule) (implemented by the Department of Health and Human Services at 45 CFR § 46.101–124). 345 CFR § 164.512(b)(1)(i).

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132 MEDICAL DEVICES AND THE PUBLIC’S HEALTH described, and evaluated potential US orthopedic-implant registries that could participate in the creation of a national network of such registries as part of the Sentinel Initiative (Outcome Sciences, 2009). Data related to medical devices include rates of selected outcomes (for example, myocar- dial infarction and stroke), rates of infection, and rates of implant revision and reintervention. They also may be able to address functional status and quality-of-life outcomes. However, some 510(k)-related issues—such as software problems, manufacturing defects, out-of-box failures, misconnects and disconnects, packaging and labeling errors, and design-induced use errors—will not be captured (IOM, 2011). As the FDA expands the scope of Sentinel to include medical devices, additional resources will be needed. Such an investment is expected to provide a rich source of clinical data from a much broader segment of the population and will prove cost-effective in the long term as adverse events associated with device use are identified and reduced (Behrman et al., 2011). Section 522 Surveillance Section 522 of the FFDCA is a discretionary tool that allows CDRH to require manufacturers to perform specified postmarket clinical studies of Class II and Class III products (Gross and Kessler, 1996).4 Such studies are justified when device failure is likely to cause serious health consequences, if the device would be implanted for more than a year, or if it is a life- sustaining device used outside a health facility. A Section 522 study can be used as a condition of clearance for a Class II device that is expected to have substantial use in pediatric populations.5 Section 522 studies are generally focused on only one or two aspects of performance rather than on overall risk and performance, and the duration of each study is limited to 3 years unless a longer period is agreed to by the manufacturer. That period is too short for the discovery of some late safety or effectiveness problems. Even when studies are completed, they may not require reporting of all critical information, including mortality (Lenzer and Brownlee, 2010). Unique Device Identifiers The FDAAA requires the FDA to develop a system of unique device identifiers (UDIs) for distribution and use. The FDA has conducted sev- eral meetings and public workshops with key stakeholders, including label manufacturers, device manufacturers, and hospitals. The agency has also 4FFDCA § 522(a)(1), 21 USC § 360l(a)(1) (2006). 5FFDCA §§ 522(a)(1)(A)–(B), 21 USC §§ 360l(a)(1)(A)-(B) (2006).

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133 SURVEILLANCE, COMPLIANCE, AND ENFORCEMENT conducted pilot activities on the effects of UDI implementation on FDA and labeler-organization business processes. It has also completed a pilot test of the usability and feasibility of a prototype UDI database (FDA, 2010h). Manufacturers want to ensure that the FDA’s standards are in alignment with those used in other regulatory systems. Advocates for the implementa- tion of UDIs argue that UDIs could substantially improve the FDA’s ability to track medical devices once they are on the market. Implementation of a comprehensive UDI system could also reduce medical device–related errors, improve the quality of MDRs, facilitate device recalls and tracking, stan- dardize device nomenclature among administrative databases and clinical registries, identify device use and compatibility issues, and enhance device postmarket surveillance (ERG, 2006). Finding 5-4 Several tools, such as device tracking and Section 522 surveillance studies, are available to the FDA to improve postmar- keting surveillance, but they are used only sparingly. Finding 5-5 The FDA has postmarketing surveillance programs— such as MedSun, MD EpiNet, and the Sentinel Initiative—that are scientifically promising, but achieving their full promise will require a commitment to provide stable, adequate resources and will require resolution of various technical issues, such as unique device identifiers. Compliance and Enforcement When there is a problem with an FDA-regulated product, the agency’s initial effort is to work with the manufacturer to have it corrected voluntari- ly. If that fails, a number of legal remedies are available: the manufacturer can be asked to recall the product, federal marshals can be used to seize the product, or an imported product can be detained at the port of entry until the problem is corrected. In addition, individual company officers that deliberately violate the law can be prosecuted, with the possibility of crimi- nal penalties. Chapter 3 contains a detailed description of the postmarket regulatory authorities that are available to the FDA. Each center has an office of compliance that ensures compliance with regulations for premarket or postmarket studies and for manufacturing and labeling. The Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD) is responsible for both premarket review and postmarket enforce- ment for in vitro diagnostic devices. For non–in vitro diagnostic devices, the Office of Device Evaluation (ODE) oversees premarket review, but the com- pliance function resides in the Office of Compliance (OC). Inspections can be made at any establishment where devices are manufactured, processed,

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138 MEDICAL DEVICES AND THE PUBLIC’S HEALTH data sources could potentially assist the FDA in postmarket surveillance of medical devices. The development of a network of existing administrative databases, electronic health records (EHRs), and clinical registries may en- hance the FDA’s ability to assess longitudinal device outcomes. Postmarketing Surveillance Programs The Department of Veterans Affairs (VA) Cardiovascular Assessment, Reporting, and Tracking (CART) system is a cardiovascular-disease sur- veillance program that is integrated into VA’s Computerized Patient Re- cord System. The CART program is used by VA for quality, management, patient-safety device surveillance, and research (IOM, 2011). VA shares with the FDA information collected through the CART program on signals or unexpected problems with devices reported by clinicians. The strengths of this program include the level of clinical, patient, device, and outcome data; VA-wide collaboration; integration of data collection into work flow; clinical tools, such as real-time report generation; VA-wide standardization; e-mail reporting of complications; monthly site reports; national reports; and Veterans Integrated Service Network reports (IOM, 2011). Although it is successful for cardiovascular surveillance within the VA system, the uti- lization of this system in other organizations that have different electronic health record (EHR) systems and levels of integration may limit generaliz- ability. Expansion of this model to other devices in the VA system may pro- vide an additional data source for the FDA’s postmarket surveillance efforts. It should be noted that this effort is restricted to devices associated with a small number of clinical diagnoses and procedures. Thus, a small number of personnel need to be trained and integrated into the effort. Expansion of this model to other disease states and device types, even within the same institution, may bring additional challenges. Another surveillance program is the Data Extraction and Longitudinal Trend Analysis (DELTA) system. DELTA is a software system that supports automated postmarket surveillance of cardiovascular devices (IOM, 2011). The software provides signal detection of adverse events with a generic structure, multiple analyses, and statistical applications for risk assessment (IOM, 2011). DELTA-detected signals must be followed up with interpreta- tion and further investigation. Although successful in cardiovascular signal detection, the system has not yet been applied to other medical specialties. The FDA, which provides research support for the DELTA project, is ex- ploring application of the DELTA system to orthopedic-device surveillance.

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139 SURVEILLANCE, COMPLIANCE, AND ENFORCEMENT Administrative Databases Several existing administrative databases could be used by the FDA for postmarket data collection on medical devices. For example, the FDA has used the Centers for Medicare and Medicaid Services (CMS) database to study the safety of implanted surgical mesh (IOM, 2011). The FDA’s MD EpiNet program has been established to leverage the use of existing administrative databases in combination with internal FDA premarket and postmarket surveillance studies (IOM, 2011). Extended use of CMS data could enhance the monitoring of new technologies in people 65 years old and older from a wide variety of healthcare facilities (Mehran et al., 2004) and has the potential for longitudinal device monitoring (Normand et al., 2010). Although CMS data are related to a large, representative sample of the older patient population, limitations in device monitoring include restriction in age range, lack of laterality, sparse clinical and implant data, and various limitations associated with administrative database coding. Other potential databases for assessing medical-device performance include the Nationwide Inpatient Sample (NIS) (HCUP, 2010), the Na - tional Hospital Discharge Survey (NHDS) (CDC, 2010), and state hospital- discharge databases. The NIS and the NHDS provide an opportunity to assess performance of classes of devices or specific procedures, but they lack detailed device information, such as manufacturer and catalog and lot numbers, that are necessary for evaluating the performance of specific de- vices. In addition to the need for linking devices to procedures or diagnosis codes, these databases contain few outpatient data and availability of recent data (Torrence, 2002). Clinical Registries Domestic and international clinical registries provide additional op- portunities for postmarket data collection. Registries are defined as “orga- nized systems that use observational study methods to collect uniform data (clinical and other) to evaluate specified outcomes for a population defined by a particular disease, condition, or exposure, and that serve one or more predetermined scientific, clinical, or policy purposes” (AHRQ, 2010). The strengths of patient registries include known denominators and the extent of clinical and implant detail necessary for assessing device outcomes. In ad- dition, registries can provide large samples for detecting rare adverse events and provide an alternative when randomized clinical trials are not practical, ethical, or feasible (AHRQ, 2010). Another benefit of clinical registries is the real-world assessment of medical-device performance in people who are in different care settings and have varied comorbidities. Medical professional groups, such as the American College of Car- diology (ACC), have developed national clinical registries, including the

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140 MEDICAL DEVICES AND THE PUBLIC’S HEALTH National Cardiovascular Data Registry for implantable cardioverter de- fibrillators (NCDR ICD). The NCDR ICD is an example of a successful registry that collects clinical, implant, and outcome data and allows risk stratification (IOM, 2011). NCDR ICD tracking is mandated by CMS, and this mandate results in high participation by hospitals. Other ACC registries—for example, CARE for carotid artery stenting and endarterec- tomy procedures and ACTION–Get with the Guidelines (GWTG) for acute myocardial infarction—have lower participation because of the lack of incentives (IOM, 2011). The FDA has established relationships with ACC and other medical professional groups to collaborate in medical-device assessment. Professional-society registries, such as the ACC NCDR, pro- vide an opportunity to capture the device and clinical data needed for risk adjustment and device assessment. Low participation, lack of longitudinal assessment, and the cost of implementation of these registries are potential barriers in expansion to other medical devices. Another potential limitation of societal registries is the lack of standardization among specialty registries that track the same medical devices. In those cases, there is no standard for such factors as data collection, nomenclature, and performance thresholds. In addition to professional-society registries, institutional, regional, and national device registries could be used for collecting postmarket informa- tion on medical devices. For example, in orthopedics, there are several total- joint-replacement registries, such as the University of Massachusetts Global Orthopedic Registry, the Harris Joint Registry, the HealthEast Orthopedic Joint Registry, the Hospital for Special Surgery Center for Education and Research on Therapeutics Total Joint Replacement Registry at Weill Cornell Medical College, the Kaiser Permanente National Total Joint Replacement Registry, the Mayo Clinic joint-replacement database, the MaineHealth Total Joint Replacement Registry, the Rush University Medical Center Joint Registry, and the Virginia Joint Registry (Outcome Sciences, 2009). The FDA has evaluated the quality of those registries and established collabora- tions to assess the safety and effectiveness of total-joint-replacement devices. Internationally, there are numerous national orthopedic registries, including the Swedish, Norwegian, and Australian joint-replacement reg- istries. Findings from those registries have initiated recalls and advisories in the United States. For example, a recent US DePuy ASR XL Acetabular Hip System and DePuy ASR Hip Resurfacing System recall was influenced by findings from several international total-joint-replacement registries. Problems associated with these devices were first identified in the Australian registry, which detected a higher than expected revision rate for these devices in 2007. The findings from the Australian registry and similar findings from the National Joint Registry of England and Wales prompted a recall of these devices. The ASR recall demonstrates the potential of implant registries for

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141 SURVEILLANCE, COMPLIANCE, AND ENFORCEMENT postmarket data collection. Recognizing the importance of device registries, the FDA is exploring the development of the scientific infrastructure for a consortium of existing domestic and international orthopedic registries. Registries may provide detailed clinical and device information, but they also have limitations, such as losses to follow-up, which adversely affect longitudinal tracking and potentially introduce selection bias in that they are not entirely random. Participation is also a challenge for some registries when incentives are lacking. Some clinical registries were developed for specific diseases or conditions, and this can limit their use for a wide variety of medical devices. And clinical registries are resource-intensive to develop and maintain. Despite the challenges associated with registry development, implementation, and maintenance, several regional and national efforts are under way in the United States to track orthopedic devices, such as total joints. The American Academy of Orthopaedic Surgeons American Joint Replacement Registry, a California state registry effort, and an Agency for Healthcare Research and Quality multicenter registry project may be able to assist the FDA in future postmarket surveillance efforts. Electronic Health Records EHRs are another possible means for monitoring medical-device per- formance. EHRs provide an opportunity to collect data prospectively at the point of care, integrate device information into the workflow, and assess clinical and device granularity needed for risk adjustment. Despite the po- tential for EHRs in medical-device postmarket surveillance, there are several challenges to implementation. First, EHRs have not yet been fully integrated into all health systems (DesRoches et al., 2008; Jha et al., 2009), although the use of electronic records by hospitals and healthcare professionals is expected to increase rapidly with resources allocated by the American Recovery and Reinvestment Act of 2009. In addition, there are more than 40 EHR systems, and they do not have standardized data-entry fields and formats. Most important, medical devices are not monitored in a consistent manner. Many EHRs lack discreet data fields for efficient data extraction and analysis. Concerns regarding privacy, security, and confidentiality are other challenges to the use of data from EHRs in postmarket surveillance. For EHRs to be used for future device monitoring and surveillance, data definitions and formats must be standardized, interoperability and data- exchange issues addressed, and privacy, regulatory compliance, and confi- dentiality ensured. The implementation of UDIs could substantially improve the FDA’s ability to track implants by using EHRs and standardizing device information among EHR systems.

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142 MEDICAL DEVICES AND THE PUBLIC’S HEALTH Finding 5-6 Existing non-FDA device data sources could enhance current passive FDA postmarketing surveillance systems but are variably used by the FDA and providers. Finding 5-7 The lack of standardization in clinical and device- specific data among existing non-FDA data sources and insufficient detail in administrative and clinical health records impede the evalu- ation of the performance of medical devices. COMMUNICATING WITH CONSUMERS When a problem with a medical device warrants action, communicating essential information to healthcare providers and the public is challenging for the FDA. Recalls and public-health notices are posted on the FDA’s weekly enforcement report (FDA, 2011e). A report is publicized when the FDA believes that there is a potential for serious public hazard. But neither safety alerts nor recalls are distributed to appropriate recipients in a timely fashion (GAO, 1998, 2007). Recall notices may be sent to a person order- ing supplies, to a loading dock, or to a billing department. Confusion about the appropriate course of action may occur when a recall notice is received. Poor communication among providers, industry, and the FDA was previ- ously noted by the Institute of Medicine in a report that focused on device problems in pediatric patients (IOM, 2005). Several third-party organizations offer services to ease communication between the FDA and consumers about recalls and other FDA notices, alerts, and reports. For example, the Emergency Care Research Institute is a nonprofit corporation that contracts with hospitals to provide advice on appropriate responses to FDA communications (Mantone, 2006). Com- mercial online tracking systems for recalls (for example, RASMAS, a recall management service for the healthcare sector [RASMAS, 2011]) also are available from other organizations. Delays in communication of recall notices leave patients at risk and hospitals with medicolegal liability. In 2002, contaminated bronchoscopes remained in use for more than 3 months after a warning was issued, and the blame for later infections was directed at both the manufacturer and the FDA (Patterson, 2002). The Transparency Initiative established in 2009 was intended to make public access to FDA information more widely available (FDA, 2011c). The initiative includes providing information about regulated products to the public through the CDRH Web site and making public the results of Section 522 and other postapproval studies. The site was launched in April 2010 and provides access to safety alerts, public-health notices, MedSun reports, and the MAUDE database. In the first month of its availability, however, it

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143 SURVEILLANCE, COMPLIANCE, AND ENFORCEMENT received only 46 comments despite a readily accessible response form and request for feedback (FDA, 2010b). In recognition of existing limitations, a recommendation from the CDRH Task Force on the Utilization of Science in Regulatory Decision Making was to use new science and available clini- cal experience to communicate necessary changes in device manufacturing and labeling (FDA, 2010a). Such communications might include letters to industry, public notices, ordering of a Section 522 study, or modifying premarket requirements. The process that has proved most effective in generating reliable MDRs also has advantages for communication of recalls (Kessler, 2010). Under the MedSun program, a trained risk manager serves as the point person for direct communication of recall information. That person can use hospital information systems to communicate risk notices to the appropriate per- sonnel rapidly and then ensure that the appropriate corrective actions take place. The committee believes that a major improvement in the removal of affected devices from the market could result from the proposed UDI system mandated by Section 519(f) of the FDAAA, depending on how such a system is implemented. This system would permit not only more rapid analysis and collation of adverse event reports but also would focus on removal of only the affected devices when necessary. The proposed UDI rule is being drafted (FDA, 2010f), and the UDI system is scheduled to be fully implemented in 2013 (FDA, 2010c). SUMMARY OF FINDINGS • inding 5-1 The FDA’s current postmarketing surveillance system F relies on manufacturers, importers, and healthcare facilities to collect information, to investigate, and to make mandatory reports. Volun- tary reporting of adverse events and device malfunctions depends on patients, caregivers, and healthcare providers and facilities to identify them, to associate them with medical devices, and to submit reports. • inding 5-2 The inadequacy of the current postmarketing surveil- F lance system and the resulting lack of data make it impossible to confidently draw broad conclusions about the safety and effective- ness of products that are on the market. • inding 5-3 Data collected with the current postmarketing surveil- F lance system is not systematically integrated into the premarket review process. • inding 5-4 Several tools, such as device tracking and Section 522 F surveillance studies, are available to the FDA to improve postmarket- ing surveillance, but they are used only sparingly. • inding 5-5 The FDA has postmarketing surveillance programs— F such as MedSun, MD EpiNet, and the Sentinel Initiative—that are

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144 MEDICAL DEVICES AND THE PUBLIC’S HEALTH scientifically promising, but achieving their full promise will require a commitment to provide stable, adequate resources and will re- quire resolution of various technical issues, such as unique device identifiers. • inding 5-6 Existing non-FDA device data sources could enhance F current passive FDA postmarketing surveillance systems but are vari- ably used by the FDA and providers. • inding 5-7 The lack of standardization in clinical and device-specific F data among existing non-FDA data sources and insufficient detail in administrative and clinical health records impede the evaluation of the performance of medical devices. REFERENCES AHRQ (Agency for Healthcare Research and Quality). 2010. Registries for evaluating patient outcomes: A users guide. 2nd edition. Rockville, MD: AHRQ. Behrman, R. E., J. S. Benner, J. S. Brown, M. McClellan, J. Woodcock, and R. Platt. 2011. Developing the sentinel system—a national resource for evidence development. New England Journal of Medicine 364(6):498-499. Breckenridge Institute. 2006. Independent verification and validation of AERS II requirements process. Breckenridge, CO: Breckenridge Institute. Bren, L. 2003. Company caught in coverup of medical device malfunctions. FDA Consumer. Nov/Dec. CDC (Centers for Disease Control and Prevention). 2010. National hospital discharge survey. http://www.cdc.gov/nchs/nhds/about_nhds.htm (accessed 12/28/2010). Desjardins, P. R. 2011. FDA response to information inquiry from the committee on the public health effectiveness of the 510(k) clearance process. Silver Spring, MD, 1/07/2011. DesRoches, C., K. Donelan, P. Buerhaus, and L. Zhonghe. 2008. Registered nurses’ use of electronic health records: Findings from a national survey. Medscape Journal of Medicine 10(7):164. Diehl, D. L., W. M. Tierney, D. G. Adler, J. D. Conway, F. A. Farraye, S. V. Kantsevoy, V. Kaul, S. R. Kethu, R. S. Kwon, P. Mamula, M. C. Pedrosa, and S. A. Rodriguez. 2010. The role of the U.S. Food and Drug Administration in device evaluation and monitoring. Gastrointestinal Endoscopy 72(1):5-10. Dorfman, G. S. 1990. Percutaneous inferior vena caval filters. Radiology 174 (3 Pt 2):987-992. ———. 1992. Evaluating the roles and function of vena caval filters: Will data be available before or after these devices are removed from the market? Radiology 185(1):15-17. ERG (Eastern Research Group). 2006. Unique identification for medical devices. Prepared for FDA by Eastern Research Group, Inc. FDA (Food and Drug Administration). 1999a. Guidance for cardiovascular intravascular filter 510(k) submissions. http://www.fda.gov/downloads/MedicalDevices/DeviceRegulation andGuidance/GuidanceDocuments/ucm073777.pdf (accessed 03/14/2011). ———. 1999b. Managing the risks from medical product use: Creating a risk management framework. Silver Spring, MD: Food and Drug Administration. ———. 2009a. About Medsun. http://www.fda.gov/MedicalDevices/Safety/MedSunMedical ProductSafetyNetwork/ucm112683.htm (accessed 02/3/2011). ———. 2009b. How to report a problem (medical devices). http://www.fda.gov/Medical Devices/Safety/ReportaProblem/default.htm (accessed 02/10/2011).

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