Evidence Limited for Most High-risk Device Approvals

Marcia Frellick

August 11, 2015

The quality and amount of evidence used by the US Food and Drug Administration (FDA) to support bringing high-risk devices to market varies greatly, new research indicates.

A study by Joseph S. Ross, MD, MHS, from the Yale University School of Medicine in New Haven, Connecticut, and colleagues, published in the August 11 issue of JAMA, found that nearly all devices the authors studied from 2010 to 2011 were cleared on the basis of two studies: one pivotal study (studies that served as the basis of FDA approval) and one nonpivotal study. Nonpivotal studies are typically conducted to assess device feasibility, enrolling a limited number of patients to examine performance and guide premarket development and clinical use.

"[M]ost devices have been or will be evaluated through only a few studies, which often focus on surrogate markers of disease in small numbers of patients followed up over short periods of time and study indications that differ from the original FDA-approved indication," the authors write.

In the United States, the FDA most often grants marketing approval through the premarket approval pathway for high-risk medical devices, which the authors describe "as those that support or sustain human life, prevent illness, or present potential, unreasonable risk to patients."

The premarket approval pathway requires that premarket clinical evidence provide reasonable assurance the device is safe and effective.

The FDA has been expediting patient access to new technologies by being more flexible with premarket evidence requirements for devices, but concerns have been raised that the studies supporting approval lack adequate rigor and are prone to bias.

The current study shows that between 2010 and 2011, the FDA granted initial marketing approval for 28 high-risk therapeutic devices through the premarket approval pathway.

Ten of those devices (35.7%) were recalled at least once, with 1 (3.6%) being the subject of a class 1 recall, meaning it presented the highest risk (reasonable probability of serious health problems or death). One device was voluntarily withdrawn from the market.

Emphasis Shifts to Postmarket Studies

"As the FDA adopts more flexible premarket evidence requirements for devices in an effort to expedite patient access to new technologies, the information generated from post market studies will become increasingly important in guiding regulatory and clinical decisions," the authors write.

However, they note that only about 13% of postmarket studies were completed between 3 and 5 years after FDA approval.

No postmarket studies were identified for 17.9% of devices, and three studies or fewer were identified for 13 (46.4%) of devices overall.

"Our findings of limited premarket evidence generation and few FDA-required postmarket studies highlight the need for continued study, either through manufacturer-initiated or investigator-initiated studies, to advance postmarket understanding of device safety and effectiveness," the authors write.

About 85% of the postmarket studies the authors identified "were not initiated in response to FDA requirements, and 40% were conducted without manufacturer support."

Dr Ross has received grants from the Pew Charitable Trusts and is supported by the National Institute on Aging and the American Federation for Aging Research. He and a coauthor receive support through Yale University from Medtronic and Johnson & Johnson; from the Centers of Medicare & Medicaid Services; and from the FDA to develop methods for postmarket surveillance of medical devices. Another coauthor is supported by the National Heart, Lung, and Blood Institute Cardiovascular Outcomes Center. Another coauthor reports he chairs a scientific advisory board for UnitedHealthcare. Another reports having received a contract (through the University of Colorado) from the American College of Cardiology.

JAMA. 2015;314:604-612. Abstract


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