FDA Okayed Cardiac Devices on Weak Evidence, Researchers Charge (CME/CE, with audio)

A review of data summaries from the FDA revealed that, of the premarket approvals of cardiovascular devices over an eight-year period, nearly two-thirds (65%) were supported by a single study.

Only 27% of studies used as the basis for device approvals were randomized and just 14% were blinded, Rita Redberg, MD, MSc, of the University of California San Francisco, and colleagues reported in the Dec. 23/30 issue of the Journal of the American Medical Association.

“Premarket approval of cardiovascular devices by the FDA is often based on studies that lack adequate strength and may be prone to bias,” they wrote.

“This study suggests that the emphasis for the FDA in 2009 and beyond must be approvals based on research that meets rigorous scientific standards for evidence of benefit and lack of harm to patients,” they concluded.

Although use of cardiovascular devices is widespread, the evidence backing premarket approval had not been systematically scrutinized, according to Redberg and her colleagues.

So they reviewed 123 FDA data summaries for 78 cardiovascular devices that received premarket approval from 2000 through 2007, including closure devices and implanted and invasive devices.

Although few studies used in the approval process were randomized or blinded, that varied by device type. For stents, for example, 54% of studies were randomized and 46% were blinded.

But only 5% of premarket approvals were supported by at least two blinded, randomized studies.

The mean number of studies used to justify an approval was 1.6 (range one to five), “which suggests that there may not be adequate evidence prior to FDA approval,” the researchers wrote.

Of the studies included in the approval process, 14% did not state a primary endpoint.

In studies that stated primary endpoints, only half (52%) of them were compared with control groups, 31% of which were selected retrospectively.

“The common use of retrospectively selected controls can introduce bias by allowing for the selection of control groups that favor the device,” Redberg and her colleagues noted.

Studies lacking control groups compared the performance of the device with prespecified and objective safety and efficacy targets.

The vast majority (88%) of the primary endpoints in the studies were surrogate measures — for example, target lesion revascularization for stents — which “may not be reliable predictors of actual patient benefit,” the researchers wrote.

More than half (56%) of the primary endpoints were composites and 15% were noninterpretable.

“The findings in this study raise questions about the quality of data on which some cardiovascular device approvals are based,” Redberg and her colleagues wrote.

They speculated that standards for device approval might be less stringent than those for drug approvals because the FDA has been evaluating devices for a shorter period of time and because the number and complexity of new devices has been increasing in recent years.

Also, they wrote, on an approval continuum, devices fall between drugs (strict approval criteria) and new surgical procedures (no approval required).

The authors suggested that standards for approval for devices should actually be stricter than those for drugs “because they are implanted and cannot simply be discontinued, as drugs can.”

Suboptimal scrutiny of devices before approval could have implications on the healthcare system, they wrote, because once a device is approved, many manufacturers immediately encourage widespread use.

Using weak evidence to support device approvals might also affect patient safety.

Redberg and her colleagues noted that manufacturers are not required to actively seek out device malfunctions as part of postmarketing surveillance studies, and adverse events are thus under-reported.

They acknowledged that the study was limited by the use of publicly available summaries from the FDA, which might not contain all information presented to the agency, as the primary data source.

In a statement, Janet Trunzo, executive vice president for technology and regulatory affairs of the Advanced Medical Technology Association (AdvaMed), a trade group for medical device manufacturers, agreed.

A complete premarket approval filing contains “full reports of all investigations of the safety and effectiveness of the device, a full statement of the components, ingredients, properties, and principles of operation of the device, a full description of the methods used in the manufacture and processing of the device, information about performance standards of the device, samples of the device, specimens of the proposed labeling for the device, and any other relevant information,” she said.

“Clinical trial data is but one piece of the overall approval process for medical devices, as the FDA requires data to determine biocompatibility, mechanical strength testing, among others, which are not available through clinical trials,” she said.

Redberg reported being a member of the FDA Circulatory System Devices Panel and a member of the California Technology Assessment Forum.

source : www.medpagetoday.com

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