Late adverse event reporting from medical device manufacturers to the US Food and Drug Administration: cross sectional study

Principal findings

In this cross sectional analysis of over 4 000 000 medical device adverse event reports submitted by manufacturers to the FDA’s MAUDE database between 1 September 2019 and 31 December 2022, over 1 000 000 reports (nearly a third of all reports) were not demonstrably reported within the timeframe allowed by the FDA. Over 400 000 reports were reported more than six months (180 days) after manufacturer notification of the event, representing more than two thirds of all late reports. Many of the devices with large numbers of late reports were crucial to patient care, including devices like infusion pumps used in hospitals and continuous glucose monitors used by patients in ambulatory settings. Late reporting to the MAUDE database could preclude identification of patient safety concerns in a timely manner.

Policy implications

Late death reports are potentially the most serious omission from MAUDE and were concentrated in problematic areas. Breakthrough device deaths were reported late more often than non-breakthrough device deaths. This finding is concerning because breakthrough devices may have less developed premarket evidence supporting their safety and efficacy,124546 meaning any late reporting for breakthrough devices could have an outsized public health impact relative to late reporting for non-breakthrough devices. However, fewer than 100 death reports were made for breakthrough devices, and injuries and malfunctions were more often reported on time for breakthrough devices. Nonetheless, the program’s rapid growth in combination with the potential public health impact of any late reporting for breakthrough devices suggests greater attention is warranted regarding their safety and reporting practices.36

Class II and III (intermediate and high risk) recalled devices had a lower overall late reporting rate but higher late reporting rates for deaths and injuries compared with devices with no recalls. Put differently, recall initiation was followed by the reporting of serious adverse events that should already have been reported to the FDA, according to regulations. Additionally, late reports were disproportionately released in large batches and in short time periods rather than consistently over time. For example, 7% of late reports in the study were attributable to one glucose monitor (table 3). This device had a relatively constant flow of on-time reports during the sample period, but nearly 100% of its late reports were released in March 2021 (appendix fig 10), the same month the manufacturer issued a recall for the monitor.4748 This bunching pattern, observed both when looking at specific medical devices with large numbers of late reports and the entire sample (appendix fig 5-18), is consistent with media reports of manufacturers only reporting important safety information after recall initiation or other high profile events.1819 Releasing large batches of late reports may be especially concerning, as clinicians or patients may have been able to respond to the earliest reports of deaths and injuries within the batch and avoid later ones had the reports been released more consistently.

Reporting delays could stem from manufacturers knowingly withholding important safety information from the public, as has been previously reported.1819202122 At the same time, delays could also represent the time required for manufacturers to verify adverse events and gather additional information before reporting events to the FDA. Nonetheless, late reporting is not permitted under existing regulations, regardless of intent. Withholding safety information may cause avoidable patient harm given the role the MAUDE database currently has in identifying emerging safety issues.13

The findings from this study collectively show that while the MAUDE database often informs FDA safety actions,13 this data source is incomplete for understanding medical device safety issues due to late adverse event reporting from manufacturers. Besides impacting how policy makers, clinicians, and patients make medical decisions, this may affect future device development. In a draft guidance for its largest device authorization pathway, the FDA has proposed that manufacturers use MAUDE reports to establish safety profiles for devices under review.49 As these reports may be missing, manufacturers may incorrectly conclude that devices are safe by interpreting a lack of reports as a lack of adverse events rather than improper reporting.

Policy actions could address late reporting. Most reports were not late, and most late reports were submitted by just a few manufacturers, indicating that on time reporting is generally feasible under existing regulations. Accordingly, a limited number of FDA warning letters and follow-up enforcement actions related to consistently violative manufacturers may sufficiently deter late reporting. Mechanisms for enforcing manufacturer reporting requirements include “seizure, injunction, civil money penalties, and criminal prosecution.”50 However, the FDA instead typically “relies on the goodwill and cooperation” of manufacturers, rather than using the full set of sanctions available to the agency.51 Insufficient enforcement may give manufacturers the impression that late reporting will be tolerated and result in ultimately harming patients by delaying access to important safety information.

Apart from stronger enforcement, the FDA and other organizations have intermediate steps they could pursue. The FDA could require manufacturer notification dates on electronic submissions of reports.52 Given that almost all reports with invalid date information simply did not report the manufacturer notification date, this change would likely improve the quality of reports in MAUDE. Additionally, the FDA could consider regularly publishing a list of manufacturers or devices associated with large numbers of late reports. Such a list could help to inform patient and clinician decision making regarding medical device selection, as well as spur manufacturers to submit timely reports for the sake of avoiding negative media attention. The FDA has previously been reluctant to pursue strategies that involve singling out violative manufacturers.53 However, other government and non-government organizations could publish a similar list, given that the MAUDE database is publicly accessible.

More generally, this study highlights the limitations of passive postmarket surveillance systems that rely on manufacturers and other non-government entities to report safety information to regulators, as well as the need to develop more active postmarket surveillance mechanisms. The US is not unique in this regard, as many countries primarily use passive surveillance mechanisms to detect emerging device safety issues.54 Efforts to routinely collect standardized information on medical device usage and outcomes in national and global databases, such as integrating unique device identifiers into administrative claims and electronic health records, would likely provide a more comprehensive assessment of real-world safety outcomes compared with relying on manufacturers and others to passively report information.555657 Such efforts would also complement existing surveillance mechanisms such as device registries and postmarket studies ordered by the FDA, which are only available for a limited number of devices.5859

Efforts to implement safety surveillance systems based on unique device identifiers would require few additional resources from medical device manufacturers, as most manufacturers already comply with the FDA’s 2013 final rule to include unique device identifiers on all medical devices.60 Instead, the costs of implementing such systems would likely fall on federal regulators and health care providers. The FDA estimates that establishing and maintaining an active medical device postmarket surveillance system would cost the agency US$8 million per year.61 Health care providers also often face logistical difficulties in initially implementing safety surveillance system integration into medical records, but those that do report clinical and operational benefits as well as revenue potential.6062636465666768 In short, while establishing an active medical device surveillance system is not without its costs and challenges, doing so is feasible and would represent an important advance relative to the limitations of passive surveillance approaches as identified in this study.

Limitations

This study had several limitations. Firstly, measuring report times depended on dates reported by manufacturers, which may have been misreported. Secondly, MAUDE does not differentiate between reports with a five work day reporting requirement versus a 30 day requirement. This study only characterized report times greater than 30 days as late, meaning late reporting may be underestimated. However, an older analysis conducted by the FDA show that less than 0.1% of adverse event reports were subject to the five work day reporting requirement as of 2007, potentially indicating that the extent to which our study underestimates late reporting may be small.69 Thirdly, MAUDE cannot identify unreported adverse events, including events where manufacturers were not notified and events where manufacturers were notified but did not report.

Fourthly, this study did not directly identify harms caused by late reporting. Identifying such harms is difficult without a nationwide active surveillance infrastructure, as the relevant exposures (late reporting in MAUDE) and safety outcomes (for which MAUDE would be the likely data source) are necessarily linked. Fifthly, analyses examining associations between device characteristics and report times were exploratory and not causal. This study was unable to determine why manufacturers report late and their underlying motivations for doing so. However, late reporting is not permitted under existing regulations, meaning greater policy attention is warranted regardless of the cause.