Modifications in many of the cardiac implantable electronic devices (CIEDs) currently used in clinical practice were approved through processes that did not require new clinical data, a study published in the Jan. 22-29 issue of JAMA found.
The FDA’s premarket approval (PMA) process allows manufacturers to introduce iterations of approved devices through supplemental applications to determine safety and effectiveness. The changes may be in design or material, for instance, and evidence may be based on preclinical testing or animal studies rather than clinical trials.
The team of researchers from Harvard Medical School focused their study on CIEDs because cardiovascular devices lead the pack for PMA and PMA supplemental applications for high-risk medical devices. CIEDs in their analysis included pacemakers, implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy devices.
The analysis spanned 1979—the year the first CIED was approved through a PMA by the FDA—through 2012 and included all CIED PMAs and PMA supplements identified in the FDA database. They broke supplements down by five review tracks which evolved over time in the FDA.
Panel-track supplements involved significant changes and included clinical testing and a panel review. The 180-day supplemental review track might include a design modification and include preclinical data. A more efficient real-time review addressed design changes and did not require additional clinical study and special review allowed for label changes. The 30-day notice supplemental review process allowed companies to submit applications for changes in manufacturing processes which could be implemented if the FDA did not require any action within 30 days.
The Harvard team found that between 1979 and 2012, the FDA approved 77 PMA CIED applications and 5,829 supplements, for a median of 50 supplements for every PMA. Forty-seven percent of the supplements were 30-day notice applications, followed by 180-day supplements (26 percent), real-time supplements (23 percent) and special supplements (2 percent).
Only 15 applications, or 0.3 percent, fell under the panel-track review category.
Looking at trends over time, they noted that the number of supplements approved annually increased almost 10-fold. Of the 77 PMAs, 79 percent had a supplemental application in 2012. “The most recent original PMA for any transvenous ICD system was approved in 2000, indicating that all ICD models released since then have been supplements to existing PMAs,” they wrote.
They emphasized that the results don’t suggest the FDA is slacking in its duty to ensure safety and efficacy, since many of the supplemental processes allow manufacturers to bring incremental improvements more swiftly to patients and physicians. But patients and physicians should be aware that most approvals didn’t hinge on new human trial data, which underscores the need for rigorous surveillance after approvals.
“Physicians should weigh the potential benefits offered by new device models against possible harms in the context of established alternatives, particularly for lifesaving or life-sustaining interventions,” they wrote. “Indeed, greater attention to this issue by the clinical community may motivate manufacturers to conduct much-needed comparative effectiveness studies, because currently little prospective testing of this sort exists to guide physicians’ decision making.”
The incremental changes made to CIEDs over time may alter devices substantially from their PMA-approved designs. The researchers suggested the FDA could require manufacturers to have CIEDs reviewed by expert panels every five to seven years or conduct more widespread postmarket studies.