A study published as a research letter in JAMA Internal Network has found a “substantial misclassification” of patient deaths for the Sapien 3 and MitraClip devices in the US Food and Drug Administration (FDA) database which, the authors say, resulted in the under reporting of deaths.
Lily Meier (Bates College, Lewiston, Maine, USA) et al say: “Our findings raise concerns about the accuracy of adverse-event reports for high-risk devices. The results complement recent news reports that the FDA allowed device manufacturers to file reports of malfunctions in a hidden database, known as alternative summary reporting.”
The authors say that moves by the FDA to hasten approval of medical devices mean that data from postmarketing studies and registries are increasingly relied upon to inform decision-making. As there is less time for premarketing clinical studies, the principal way for adverse events and risks to become apparent is through postmarketing data. But, they point out: “Although the FDA’s medical device reporting regulations require that device-user facilities report adverse events to the FDA, physician reporting is voluntary. Adverse event data may be recorded in registries such as the Transcatheter Valve Therapy database, which gathers national data on interventional cardiology devices. However, the Transcatheter Valve Therapy registry does not make its data publicly available, which limits its value. Instead, the Transcatheter Valve Therapy registry submits reports to the FDA in summaries that may omit redacted information and obscure important data.”
Publicly accessible adverse event reports are classified in the FDA’s Manufacturer and User Facility Device Experience (MAUDE) database as malfunction, injury, or death events. Meier and colleagues examined the misclassification of death reports for the Sapien 3 and MitraClip devices within the MAUDE database.
The authors used the software Device Events, which collates adverse event reports from MAUDE in a more accessible format, to examine adverse event reports on the Sapien 3 and MitraClip devices from their FDA approval dates (in 2013 and 2015, respectively) to 31 December 2018.
The critical-events thesaurus within Device Events identifies reports that have been characterised as injuries and malfunctions, and searches for terms that indicate that a death may have occurred. Meier et al used this to gather reports in which a patient may have died but the event was misclassified as an injury or malfunction. They then analysed the reports to determine whether, in fact, a death had occurred.
For the Sapien 3 device, the authors found 9,320 reports of injury and malfunction and 1,021 reports of deaths; 217 (2.3%) of the injury and malfunction reports also stated that the patient had died during or after the implantation of the device. As well as “died”, the most commonly used terms to describe the death of a patient were “expired”, “passed away”, and “autopsy”. Thus, they say, “misclassified reports made up 217 of 1238 (17.5%) total patient deaths”.
There were 5,323 injury and malfunction reports for the MitraClip device, 97 (1.8%) of which also stated that the patient had died. The terms used in reports to describe patient deaths included “expired”, “hospice”, and “passed away”. For the MitraClip, write the authors, “97 of 392 (24.7%) patient deaths were misclassified as injury or malfunction events”.
They conclude: “Both the miscategorisation of deaths in FDA adverse-event reporting and hidden adverse-events reports can lead to inaccurate public and physician perception of the safety of medical devices, and can compromise informed decision-making. Given the increased reliance on postmarketing surveillance, improving the accuracy and clarity of adverse-event reporting should be a high priority for both the FDA and industry.”
Co-author Rita F Redberg (University of California, San Francisco, USA), editor of JAMA Internal Medicine, told Cardiovascular News that the study team intended to evaluate other devices in a similar fashion. She added: “Adverse event reporting could be improved in many ways, centered around the themes of completeness and timeliness of reporting and transparency. Currently, most adverse events go unreported to the only publicly available FDA database (MAUDE), and the accuracy and completeness of the adverse event reporting cannot be ascertained. It is critical for patient safety that we have accurate and available data on adverse events associated with use of medical devices. We cannot know the safety and effectiveness of medical devices without knowing this data, and it is paramount in the FDA’s mission to protect the public health. However, we know that, until a few months ago, the FDA allowed industry to file ‘alternative’ reports which hid millions of reports of harms and malfunctions from the public. When the existence of these hidden reports were made public eight months ago, the FDA pledged to make all of the safety data available. However, that data is still not publicly available. Furthermore, there is required reporting for some high-risk devices, but it is to proprietary databases, such as the Transcatheter Valve or TVT Registry, which are not transparent. This registry data should be transparent as well.”