The FDA/CDRH FAILURE: unsafe & ineffective high risk devices cause PREVENTABLE patient harm

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 One device was voluntarily withdrawn from the market.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

http://www.medscape.com/viewarticle/849349

Gender targeting by (sometimes criminal) medical device industry? Breast implants, birth control, transvaginal surgical mesh?

Maker of faulty French breast implants given fouryears in jail

BY JEAN-FRANCOIS ROSNOBLET AND ALEXANDRIA SAGE

MARSEILLE/PARIS Tue Dec 10, 2013 8:00am EST Reuters FiDA highlight

(Reuters) - The founder of a French breast implant company was sentenced to four years in prison on Tuesday for hiding the true nature of the sub-standard silicone used in implants sold to 300,000 women around the world.

Jean-Claude Mas, 74, founder and long-time chief executive of Poly Implant Prothese (PIP), was prosecuted after a worldwide panic in 2011 when France recommended that women with such implants should have them removed due to an abnormally high rupture rate.

Worries about the implants launched a flurry of international lawsuits and prompted calls for Europe to toughen controls on medical devices and fix its fractured oversight system.

Once the third-largest global supplier of breast implants, the company was shut in 2010 and its implants ordered off the market after inspectors pursuing a tip-off discovered vats of industrial-grade silicone outside the PIP factory in the southern town of La-Seyne-sur-Mer.

A Marseille criminal court also ordered Mas, who had been pursued for aggravated fraud, to pay a 75,000-euro ($103,000) fine. His lawyer, Yves Haddad, said he would appeal.

Four other executives, including the chief financial officer, were sentenced to between one-and-a-half and three years in prison, some of it suspended, and fined.

"It's a strong signal. This decision is what victims were waiting for," said one of their lawyers, Philippe Courtois.

The president of a PIP victims group, Alexandra Blachere, called it a "symbolic sentence" that challenged any prejudice that there was "a ditzy bimbo behind every pair of silicone breasts."

The two-month trial in April and May was held in an exhibition center to accommodate the 7,400 civil plaintiffs and 300 lawyers. Jeers from the crowd greeted Mas' appearance in the makeshift courtroom.

For less serious felonies in France, the criminal court hands down a sentence without pronouncing a guilty or not guilty verdict, which is implicit.

HIDDEN EVIDENCE

Mas admitted using silicone created by trial and error that was never approved by regulators and which cost a seventh of the price of silicone approved for use in medical devices.

He has insisted the gel he had relied on since the founding of the company in 1991 was non-toxic and has said women who complain about their PIP implants are "fragile people, or people who are doing it for the money."

A police investigation revealed a sophisticated fraud at PIP, which managed to conceal the implants' ingredients from regulators, thereby allowing them to be sold on international markets.

Before annual audits to the PIP factory by private certification company TUV Rheinland, employees would clear away evidence of the cheaper gel it used to fill implants.

For a special report on the PIP scandal, click here:

TUV sued PIP for fraud, but a French court ruled last month the German company had failed in its obligations of "vigilance and caution" and ordered it to pay 3,000 euros to each of the 1,600 plaintiffs, women wearing PIP implants who had sued.

Health experts insist that no link has been established between PIP implants and breast cancer.

Still, women around the world with PIP implants, whether in Venezuela, France or Britain, have rushed to their surgeons to have them removed, fearing health complications.

Since France recommended removal, some 14,729 women in France - nearly half of all French women with PIP implants - have chosen this option, according to French regulators.

Regulators say a quarter of PIP implants removed were found to be faulty, most having ruptured.

Only one case of anaplastic large cell lymphoma, a rare type of cancer originating in the lymphatic system, has been documented in France from a women wearing PIP implants.

National health agencies have given differing advice. While France and Venezuela offered to reimburse women who have their PIP implants removed, other countries, such as Britain, recommended that women merely have them checked.

Other legal cases related to PIP are still pending in France, including one related to the 2010 death of a woman wearing PIP implants. Another relates to tax fraud by Mas, his former girlfriend and Chief Executive Claude Couty.

(Writing By Alexandria Sage; Editing by Mark John and Ruth Pitchford)