Medical Device Scandal in UK: U.S. ?????

EDITOR'S CHOICE

The scandal of medical device regulation

BMJ 2012; 345 doi: http://dx.doi.org/10.1136/bmj.e7180 (Published 24 October 2012)

Cite this as: BMJ 2012;345:e7180    FiDA highlight

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1. Fiona Godlee, editor, BMJ

1. fgodlee@bmj.com

Try describing Europe’s system for regulating medical devices and, as Peter McCulloch says in his editorial this week, the response from your audience will be incredulous (doi:10.1136/bmj.e7126). Read his description and see if you too find yourself asking, “How could this have come about?” It’s a question that now demands urgent remedy. If this was not already clear from recent BMJ investigations (BMJ 2011;342:d2748, BMJ 2012;344:e1410), a new investigation makes it uncontrovertibly so. Working with undercover reporters from the Telegraphnewspaper, the BMJ’s Deborah Cohen has exposed a fragmented, poorly regulated, market driven system, with financial incentives to prioritise manufacturers’ interests over those of patients, and with no requirement for clinical evaluation of a device’s safety or effectiveness (doi:10.1136/bmj.e7090).

Armed with a fictitious hip implant modelled on one that was recalled on safety grounds in 2010, the reporters approached 14 of the 78 “notified bodies” to which the European Union delegates the job of certifying medical devices. The one to which they eventually submitted their glossy dossier was happy with the design and confirmed that it would approve the device subject to manufacturing documents and a factory visit.

Why did we decide to work with the Telegraph on this “secret shopping” exercise? Firstly, there was a clear and pressing public interest. Secondly, we took the view that the information could not have been obtained by other means. Thirdly, we were reassured by the fact that the BMJ has successfully used fake information to test various systems in the past. As part of a randomised trial published in 1998 (JAMA1998;280:237-40), we sent out for peer review hundreds of copies of a research paper into which we had inserted errors. The reviewers were not told that the paper was a fake. For this study, as with the fictitious hip implant, we obtained approval for our plans from the BMJ’s ethics committee.

More famously, in 1868, the BMJ’s then editor Ernest Hart placed a newspaper advertisement in which he posed as a father seeking a foster mother for his illegitimate child. His aim was to expose the notorious Victorian practice of baby farming, in which unwanted infants were taken in to be nursed in exchange for payment, but were instead neglected and often killed. The advertisement received 333 replies and sparked a series of articles calling for reform (BMJ 28 March 1868, 301-2). According to the historian Peter Bartrip, the journal’s influence was crucial in achieving legislation.

If the latest undercover operation has similar effect, we will consider the means worthy of the end. Because legislation is what is now urgently needed to protect patients. McCulloch says this must go beyond the tinkering reforms proposed by the EU. Instead, he calls for a system of provisional licensing in which devices could only be marketed if they were being used within clinical studies of their safety and effectiveness. Whatever new system is proposed, he is right to say that it must have patient safety, not trade, at its heart.

Notes

Cite this as: BMJ 2012;345:e7180

Footnotes

• Follow BMJ Editor Fiona Godlee on Twitter @fgodlee and the BMJ@bmj_latest

FDA: Metal on Metal Hips, higher failure rates for women

FDA Panel Discussing Safety of Metal-On-Metal Hip Implants

Published June 27, 2012

Dow Jones Newswires

The Food and Drug Administration on Wednesday convened a two-day advisory panel meeting to discuss the safety of metal hip implants, amid concerns there are more side effects than with implants made out of such materials as ceramic or plastic.

The advisory panel is being asked to make recommendations whether additional warnings and other information is needed for metal hip systems, and to make recommendations about which types of patients would benefit the most from metal implants as well those who shouldn't get them. The panel is not being asked to discuss regulatory changes like requiring the devices to go through more stringent clinical testing.

In 2010, Johnson & Johnson's (JNJ) DePuy Orthopaedics Inc. recalled 93,000 of its ASR total hip implants after they were linked to higher failure rates than other implants. The ASR device is no longer sold but is still implanted in many patients, and the company faces about 6,000 lawsuits.

One of the safety concerns involves the wear on the implants and its breaking down of the metal, which in some patients causes joint and muscle destruction and other health problems.

Elizabeth Frank, an FDA medical reviewer, said Tuesday that patients vary in their reactions to metal particulate, with some having a severe inflammatory response to having no reaction.

Because hip implants were on the market before FDA started regulating medical devices in 1976, such companies as DePuy and Wright Medical Group Inc. (WMGI) only need to show a hip implant is similar to a device already on the market and don't need to conduct clinical studies showing safety and effectiveness, a process that has been criticized by some policy makers and many patients.

Major changes to devices, however, do require additional testing, and hip resurfacing systems, including ones made by Smith & Nephew PLC (SNN), are required to go through FDA's premarket approval process, which requires companies to conduct clinical studies in humans looking at the devices' performance. The FDA said other companies with metal hip implants on the market include Biomet Inc., Zimmer Holdings Inc. (ZMH) and Encore Medical L.P.

There are about 400,000 hip implant surgeries in the U.S. each year. About 25% of surgeries involve metal-on-metal implants, according to recent U.S. government data.

Information from patient registries outside of the U.S. suggest more patients need to have the metal implants fixed than other types of implants. The U.S. doesn't have a national registry and studies looking at implant failure rates in the U.S. have been mixed. Some data suggest women have higher failure, or revision rates, compared to men while other data suggests there might be more problems with implants that have a larger component, called the femoral head, than smaller components.

"Could it be the size of the head when we are attributing all the problems to metal?" said Raj Rao, a panel member from the orthopaedic surgery department of the Medical College of Wisconsin.

Although the panel had not formally started addressing FDA's questions Wednesday, preliminary discussion suggests the panel may struggle to adopt clear recommendations given the number of products and conflicting data.

"I don't believe the failure mechanism of these devices is the same," said Edward Cheng, a panelist from the University of Minnesota Medical School and Cancer Center.

Information prepared for the meeting by the FDA showed there's been almost 17,000 adverse-event reports submitted to FDA involving the metal-on-metal implants from 1992 through 2011. There were 22,000 for nonmetal hip implants. Of the metal-on-metal reports, about 12,000 were submitted in 2011 with 9,000 attributed to the DePuy ASR. The reports cited problems including the need for revision--or additional surgery to fix or replace the implant--pain, dislocation and bone infections.

In a presentation to the panel, Paul Voorhorst, the director for biostatistics and data management for DePuy Orthopaedics, said not all "metal-on-metal implants are the same and each should be evaluated on its own merits." Mr. Voorhorst didn't specifically mention the recalled ASR product and instead focused on another product. However, he said the company believes all patients with joint replacements need to be monitored.

Read more: http://www.foxbusiness.com/news/2012/06/27/fda-panel-discussing-safety-metal-on-metal-hip-implants/#ixzz1z3LUiUKx           LINK

J&J ignores FDA rules: women outraged!

J&J Sold Vaginal Mesh Implant After Sales Halt Ordered LINK

By David Voreacos and Alex Nussbaum on June 26, 2012  Bloomberg News

Manufacturers including J&J sold about $175 million worth of prolapse mesh worldwide and another $295 million for incontinence treatments in 2010, C.R. Bard executives estimated on a conference call that year. Even for top sellers of the devices, the products made up no more than 2 percent of company sales, said Michael Matson, a Mizuho Securities USA analyst in New York.

The numbers declined as lawsuits were filed, he said in a phone interview.

“The doctors aren’t implanting them,” Matson said. “The patients don’t want them.”

On June 5, J&J said it will stop selling four vaginal mesh implants including the Prolift. The move wasn’t a recall and J&J remains confident in the safety and effectiveness of the devices, Johnson said. The company will not withdraw the Prolift before its “planned discontinuation” of the mesh products over the next three to nine months, he said.

“Our decision to discontinue these products is based on their commercial viability in light of changing market dynamics,” he said.

16 Questions

In letters to state and federal judges, the company said that it will update labeling for one device, the Gynemesh, to allow only abdominal, not vaginal, insertion.

The FDA learned of the Prolift after J&J cited it in an application to sell a related device, the Prolift+M, Liscinsky said. The agency told J&J to file for the Prolift as well, and it combined the review for both devices before the August 2007 letter.

“Due to the complexity of this procedure and potential high risk for organ perforation, bench testing is not sufficient to demonstrate device safety and efficacy,” the FDA said in the letter. Bench testing refers to laboratory testing to determine how a device will function in a person.

In the August 2007 letter, the FDA asked 16 questions about the Gynemesh and Prolift, which are made of the same nonabsorbable polymer. The Prolift kit includes pre-shaped mesh and instruments to help surgeons implant the device.

Infection, Abscess

One FDA query was about a “significant number” of complications from 2004 to 2007 on the earlier device, the Gynemesh. The agency got 174 such reports, including for infection, abscess and organ perforation. Most of the cases required additional surgery.

The agency’s letter also found that labeling for the Prolift+M device was deficient because it couldn’t support claims that the mesh has “elastic properties that allow adaptation to physiological stresses.” In its response, J&J agreed to remove that claim.

Many of the documents unsealed last month include e-mails between J&J and the FDA over the wording of product labeling about the benefits and risks.

Six days before the FDA cleared the Prolift, J&J agreed in a written response to say in the label that the safety and effectiveness of the device, compared to conventional surgical repair without mesh, “have not been demonstrated in randomized controlled clinical trials.”

Rather, J&J wrote, the substantial equivalence to earlier approved devices had been demonstrated through other tests.

The federal cases are In re Ethicon Inc., Pelvic Repair System Products Liability Litigation, 12-md-2327, U.S. District Court, Southern District of West Virginia (Charleston).

To contact the reporters on this story: David Voreacos in Newark, New Jersey at dvoreacos@bloomberg.net; Alex Nussbaum in New York at Anussbaum1@bloomberg.net

To contact the editors responsible for this story: Michael Hytha at mhytha@bloomberg.net; Reg Gale at rgale5@bloomberg.ne

Comment by retrievethis (FiDA blog/Joleen Chambers)

I am outraged that Congress will not remove the legislative loophole that allows untested medical devices to be implanted in the human body and has removed citizen rights to justice by providing "cover" for the industry.  Congress also has withheld adequate funding for the FDA so that it is weak and filled with industry insiders who have little compassion for the patient harm that is produced.  Consumer beware!

FDA Approval Is Faster!

LINK

FORBES   BUSINESS | 6/19/2012 @ 10:15AM

More Proof FDA Is Faster Than Other Drug Regulators

This guest post was written by Joseph Ross, an assistant professor of medicine at the Yale University School of Medicine and Nicholas Downing, a third year medical student, also of Yale University School of Medicine. Ross has done extensive study of how new drugs are approved. In this article, they provide more evidence that the FDA’s review process is not longer than that in other countries.  (FiDA blog bold added.)

Last month, we published with our colleagues a study in the New England Journal of Medicine examining the time required by three prominent pharmaceutical regulators to review applications for new drugs that have never before had medical uses.

Our main finding: the FDA was nearly two months faster than the European Medicines Agency and Health Canada, the primary regulators for the European Union and Canada. This is true both for the time it takes for the FDA to do the first regulatory review and for total regulatory review time of these applications.

But our original measure of regulatory review time only included the time an application actually spends being reviewed by the FDA and its peers. For some drugs, the total time can be longer, as a company may need to conduct additional research before resubmitting a drug to regulators. Investors and industry are focused on the total time it takes to go from submission to approval.

So we re-crunched the numbers. Our analysis is limited because it included only applications that were eventually approved, since only this information is made publicly available by all three regulators.

But we found more proof that the FDA is faster than its peers. 

As can be seen in the accompanying figure(on website), the FDA was the fastest of the three agencies, even when we look at the total time from submission to approval, including time when both the agency and the industry applicant were “on the clock”. The median time to approval was 322 days at the FDA, compared to 366 days at the EMA and 409 days at Health Canada.

Our comparison is complicated by the fact that all three regulators do not behave in the same way, but we would expect that to make the FDA look slower – and it doesn’t. Among these applications that were eventually approved, the EMA approved almost every one in a single review cycle, 96%, whereas 3% required two cycles and 1% required three cycles. In contrast, 62% and 69% of applications were approved by the FDA and Health Canada in a single review cycle, respectively. More than 30% of applications required multiple reviews before approval. For the FDA, 36% required two cycles and 1% required three cycles; for Health Canada, 24% required two cycles, 4% required three cycles and 3% required four or more cycles.

You might think that extra requests for statistical analysis, data collection, or even new clinical trials would make the FDA process more time-consuming than that in other countries, but it doesn’t.

Nevertheless, there are more nuances to this story. You can see in the Figure that there was much more variation in time to approval among applications to the FDA. More than half of approvals were complete within one year, but there were many examples of the FDA requiring 800, 1000, even 1200 total days before approval. For instance, the well-known anti-cancer drugs Sanofi‘s Eloxatin and Novartis‘ Gleevec were both approved in less than 80 days, however it took more than 10 years from initial submission to approval for Sabril, and anti-seizure medication, and Asclera, a sclerosing agent to treat varicose veins.

A lot of the variation in FDA time to approval can be attributed to whether one or more cycles of review were required. Among the 62% of applications the FDA approved after a single review, the median time to approval was 278 days. In contrast, the median time to approval was 765 days among the 38% of applications that required multiple cycles of review.

Interestingly, applications within the hematology, oncology, and immune-modulating and anti-infective therapeutic classes were most likely to receive FDA approval after a single review. Applications within the musculoskeletal and pain and psychiatry and central nervous system therapeutic classes were most likely to require multiple cycles of review.

It is important to point out that there is no right review speed or right number of cycles of review. The FDA may have been acting appropriately in these slower reviews that required additional cycles. These applications could have raised important safety concerns or included poorly designed trials that could not support approval. Perhaps the FDA was right to request more statistical analysis, additional data collection, or even new trials, from the applicants.

One can argue that FDA has been cautious in ways that benefit the public. There are certainly cases where the FDA did not approve a drug, and other countries did only to have to withdraw it for safety reasons. Examples would include Acomplia for obesity and Thelin for pulmonary arterial hypertension. On the other hand, some medicines, like AstraZeneca‘s Iressa for lung cancer or perfenidone for idiopathic pulmonary fibrosis, are being used in other countries but are restricted or not approved by the FDA. But either way, a tortoise-like pace is not one of the FDA’s problems.

Comment:  Joleen Chambers

Thank you for your research!  After a family member experienced a serious adverse event from a failed implanted medical device designed by the Mayo surgeon and approved by FDA without clinical testing, I began advocating for safer implanted medical devices.  Legislation to renew MDUFA must be complete by September 2012, yet the medical device industry is balking at contributing financially to oversight that would protect patients from harm.  The 'talking points' are focused on speeding 'innovations' to a (unconfirmed & DTC marketed) demanding and growing pool of desperate patients and the need to maintain jobs-at-all-cost for workers in the profitable medical device industry.  Bill Walton has been hired to lobby Congress. The industry threatens that if it is not placated they will go to other countries.  Let them go so there are fewer American victims in medical and legal purgatory!