Most high-risk CV devices approved without clinical data

Many cardiac implantable electronic device models currently in use were approved via a Food and Drug Administration review process in which the models were assumed safe and effective based on approval of prior versions of the device, according to a study in the January 22/29 issue of JAMA.

"In the United States, the Food and Drug Administration (FDA) reviews high-risk medical devices-those that support human life, prevent illness, or present an unreasonable risk-via the premarket approval (PMA) pathway, through which manufacturers collect preclinical and clinical data as necessary to provide 'reasonable assurance' of the device's safety and effectiveness," according to background information in the article. That process has attracted attention in recent years after recall of device components, like leads from Medtronic Sprint Fidelis and St. Jude Medical Riata implantable cardioverter-defibrillators (ICDs), that were not tested clinically in human trials prior to approval because they were design changes to prior-marketed devices and considered 'supplements' to PMA applications submitted almost a decade earlier.

The process of approval by premarket approval supplement "allow[s] patients to benefit from incremental innovation in device technology by providing efficient and inexpensive FDA review pathways for smaller device changes. Supplements may include major or minor design changes as well as routine changes in labeling, materials, or packaging. By statute, the FDA must seek only the 'least burdensome' supporting data necessary for review."

Benjamin N. Rome, B.A., of Harvard Medical School and Brigham and Women's Hospital, Boston, and colleagues used the FDA's PMA database to review CIEDs (including pacemakers, ICDs, and cardiac resynchronization therapy [CRT] devices) approved as PMA supplements from 1979 through 2012. They identified the number of supplements to each original PMA and characterized the nature of the changes in each supplement.

Seventy-seven approved PMA applications for CIEDs (46 pacemaker devices, 19 ICDs, and 12 CRT devices) were the basis for 5,829 PMA supplement applications, with a median (midpoint) of 50 supplements per original PMA. In the last decade, the number of approved supplements annually increased to 704. Excluding manufacturing changes that do not alter device design, the number of supplements approved each year averaged 2.6 per PMA per year.

Thirty-seven percent of supplements represented at least minor alterations to the device's design or materials. Among 180-day supplements (a type of FDA review process) approved between 2010 and 2012, 23 percent included new clinical data to support safety and effectiveness.

"- Our results should not be interpreted to indicate that the FDA is failing to review PMA supplement applications to determine safety and effectiveness," the authors conclude. However, clinicians and patients should - be aware - that clinical data are rarely collected as part of PMA supplement applications prior to marketing. The recalled Medtronic Sprint Fidelis and St. Jude Riata ICD leads were both PMA supplements - Fidelis a 180-day supplement and Riata a real-time supplement [a type of FDA review process]. Neither lead was studied in human trials prior to FDA approval. The FDA's approval of many supplements without new human trials, as in the case of these recent ICD changes, highlights the importance of collecting rigorous postapproval performance data," the authors write.