The required studies have been slow to get under way, and "methodologic issues will limit the usefulness of the information that emerges from these studies," wrote Joshua Rising, MD, MPH, of the Pew Charitable Trusts in Washington, D.C., and two colleagues in an online New England Journal of Medicine Perspective article.
Unexpectedly high rates of device failure and local and systemic inflammatory reactions associated with metal-on-metal hip replacements have prompted regulators in the U.S. and Europe to take a closer look at these products.
In May 2011, the FDA ordered manufacturers of metal-on-metal devices to conduct surveillance studies on patients who had received their products, requiring them to submit protocols for the agency's approval.
But as of Monday, Rising and colleagues wrote, protocols for fewer than one-quarter of the 104 devices covered by the FDA order had been approved. For 80 of the products, the FDA listed the study plans as "pending" or "overdue."
Even for those that had been approved, Rising and colleagues indicated, "it was unclear whether any studies had begun."
More seriously, the group argued, the FDA's requirements for the studies were excessively loose.
"One significant shortcoming is that each manufacturer is permitted to conduct its own independent study on its product or products. The resulting lack of harmonization among studies will lead to challenges in pooling the data and making cross-product comparisons," Rising and colleagues wrote.
They pointed out, for example, that the FDA did not specify how the companies should measure chromium and cobalt ions in blood -- a key marker of metal-on-metal implant dysfunction. The resulting variability will "introduce uncertainty into attempts to pool results," the group contended.
Rising and colleagues also worried that the FDA does not have authority to require post-marketing studies to extend more than 3 years, which may be inadequate to judge the performance of devices that are supposed to last 15 years, as is the case with metal-on-metal hip implants. Even the worst-performing of such implants have shown 5-year failure rates of less than 5%.
One advantage to the slow start for most of the studies is that it is not too late for the FDA to require more harmonization of protocols, Rising and colleagues suggested.
They also called for the U.S. to establish comprehensive device registries -- not limited to metal-on-hip implants -- like those in other countries. They noted that the first warning signals about metal-on-metal devices emerged from an Australian registry.
Such registries could benefit device manufacturers, Rising and colleagues contended, by reducing their costs for post-marketing surveillance and by providing better clinical feedback that, in turn, helps them develop safer and more effective products.
Next week, the FDA will hold an advisory committee meeting about metal-on-metal implants to review the existing data and future research needs.
This meeting "would be an opportune time for the FDA to address the slow start to these studies -- and to signal that substantial penalties may be assessed against any manufacturer that is responsible for delays in finalizing protocols," Rising and colleagues wrote.