FDA Device Panels: Undisclosed Conflicts and Loss of Public Trust

FDA Advisers’ Financial Ties Not Disclosed

Many Doctors Who Sit on Food and Drug Administration Panels Reviewing Medical Devices Have Links to Device Makers Undisclosed by the FDA

The FDA, which operates from these headquarters offices in Silver Spring, Md., seeks advice on medical-device approvals from a number of doctors and scientists with financial ties to device makers that the agency doesn’t publicly disclose. REUTERS

By JOSEPH WALKER

Dec. 8, 2014 10:33 p.m. ET

David Kandzari, an Atlanta cardiologist, also has worked as a consultant to makers of medical devices. He received at least $100,000 from them in five years, according to corporate and government data.

Another organization he works with, the Food and Drug Administration, doesn’t appear to mind. In October, the FDA put Dr. Kandzari on a panel reviewing a medical device made by Boston Scientific Corp. , one of the companies he has advised.The FDA didn’t disclose the connection. It was among numerous financial ties the FDA hasn’t disclosed between medical-device makers and the doctors and other experts who review devices for it, a Wall Street Journal analysis of corporate, state and federal data shows.

In panels evaluating devices involved in cardiology, orthopedics and gynecology from 2012 through 2014, a third of 122 members had received compensation—such as money, research grants or travel and food—from medical-device companies, an examination of databases shows.

Nearly 10% of the FDA advisers received something of value from the specific company whose product they were evaluating.

The FDA disclosed roughly 1% of these corporate connections.

The situation concerns critics. “Undisclosed conflicts raise questions about the decision-making capacity of the committees and whether the public can have confidence in their recommendations,” said Joseph Ross, an associate professor at Yale School of Medicine.

The FDA follows the committees’ advice in a large majority of instances, on prescription drugs as well as on medical devices. On devices, it has convened more than 20 meetings this year for recommendations on whether to approve novel products or put new regulations on older ones.

The issue arose most recently in July regarding a panel evaluating surgical tools called power morcellators that cut up uterine fibroid growths. A gynecologist stepped down from the panel not long after the Journal inquired about payments he had received from a maker of the devices, a connection the FDA hadn’t disclosed.

The FDA said under current law and policy, it discloses advisers’ financial interests only when it has determined the experts need a waiver in order to serve.

In making this determination, it has discretion. Having done paid work for a medical-device company doesn’t disqualify a doctor or scientist from sitting on an advisory panel, nor require public disclosure, as long as the work wasn’t related to the specific topic or product the panel focuses on, FDA officials said.

Current consulting work that is directly related to a panel topic is typically a disqualifying conflict, as is ownership of a large amount of the device maker’s stock, said FDA Associate Commissioner Jill Hartzler Warner. Still, if the FDA believes the individual’s expertise can’t be found elsewhere, it can issue a waiver.

It posts such waivers on its website. The agency said it can’t reveal any other financial ties or potential conflicts because what its scientific advisers tell it is confidential.

“Our challenge and our goal is to retain public confidence in the advisory-committee process and at the same time to obtain the very best advice,” Ms. Hartzler Warner said.

“If you have a financial interest with a sponsor or a related firm, but it’s not related to the product at the meeting, it’s not disqualifying,” she said. “The firms are often large and diverse, and whatever position the FDA takes, it won’t affect the relationship between the firm and the” expert adviser.

Doctors said their consulting work doesn’t affect their panel decisions. “I’ve never sat there on a panel and thought, ‘I wonder what my friends at companies X, Y and Z would say.’ I just don’t view it that way,” Dr. Kandzari said.

In the panel in October, he voted to approve a heart device from Boston Scientific, a firm that has paid him between $5,700 and $8,190 in consulting fees and expenses for food, travel and lodging since 2011, according to company data. The consulting didn’t concern the kind of device the October panel evaluated, so it posed no conflict, he said.

Dr. Kandzari confirmed he has consulted for various device makers. He questioned the accuracy of payment data posted by companies, saying, among other things, that some payments were actually made to his employer.

As for Boston Scientific, it said that device makers “are not consulted, or engaged in any way in the selection of panel members.”

The FDA said broader disclosure could discourage people from sitting on advisory panels. The agency already has a challenge getting highly qualified experts to sign on, Ms. Hartzler Warner said. Edward Y. Cheng, an orthopedic surgeon at the University of Minnesota Medical School and Cancer Center, said doctors have a strong financial disincentive to serve because they must take time away from their practices.

Among ties not disclosed by the FDA were $6,666 in consulting fees Dr. Cheng received from a maker of all-metal hip implants a year before he sat on a panel evaluating the safety of that type of hip. Dr. Cheng said the work was unrelated to all-metal hips.

Dr. Cheng said it is the FDA’s job to gauge whether a conflict exists but added: “if I personally thought a conflict existed that would affect my ability to remain unbiased, I would decline to participate.” The FDA said it doesn’t comment on individual panel advisers or their finances.

There is no central way for the public to learn of ties between panel members and makers of medical devices or drugs, which pay hundreds of millions of dollars a year to physicians in consulting, speaking and other fees, according to data from the Centers for Medicare and Medicaid Services. Concerns that such ties could affect doctors’ medical decisions have led to calls for greater transparency.

Many large drug and device companies post their payments to doctors online, often as part of legal settlements over fraud allegations. Some states, including Massachusetts and Vermont, post payments to physicians in their areas.

Doctors often must disclose potential conflicts when writing for scientific journals or giving presentations at medical meetings. The federal government this year launched a database called Open Payments, which so far has five months of 2013 data on company payments to doctors and teaching hospitals. The Journal used all these sources as well as archives maintained by PharmaShine, a service of Obsidian Healthcare Disclosure Services LLC.

No database reveals doctors’ and medical scientists’ stockholdings, so any search can give only a partial picture of financial ties.

The Journal’s tally of payments to members of panels on cardiology, orthopedic and gynecology devices in 2014 found that 64% received no value from device makers in the past five years. The rest did, varying from less than $15 for food and beverage to more than $500,000 in research funding.

Of doctors who received something from companies, 32% got less than $500 in value and 26% received $10,000 of value or greater.

Before advisory-panel meetings, the FDA asks potential members to report all financial ties, including consulting fees, research grants and stock, in companies with business before the panel and their competitors. In general, if the value of current interests exceeds $50,000, a person will be excluded, said an FDA guidance document.

If the agency decides a payment isn’t truly a conflict, it can issue what is called a “502 authorization” letting the person serve, said Ms. Hartzler Warner.

The 502 authorizations, unlike waivers, aren’t publicly disclosed.

The FDA declined to say how many 502 authorizations it issues annually.

“The problem with the FDA’s policy is you don’t know how they use their discretion,” said Celia Wexler, a lobbyist for the Union of Concerned Scientists, a group that opposes political interference in scientific and regulatory matters.

“It’s very difficult for us to know to what extent the FDA probes, and the extent to which panel members take the disclosure requirements seriously.”

Shortly before the July panel on morcellator surgical devices—which reviewed concerns they could spread hidden uterine cancers—the Journal discovered that panel member Andrew Brill had received nearly $100,000 in consulting fees in 2013 from Johnson & Johnson , then the largest maker of morcellators. The information was on a J&J-run public database, which also shows that another J&J unit paid $6,000 to Dr. Brill in 2013.

Dr. Brill resigned from the panel just before it met. The FDA said he recused himself because of his financial interests with companies. It declined to discuss why it initially appointed him to the panel. Dr. Brill declined to comment.

Documents posted on the website of the American Association of Gynecologic Laparoscopists show Dr. Brill also had ties to another morcellator maker, Karl Storz GmbH of Germany, for which he was a consultant and speaker in 2012.

Another corporate connection the FDA didn’t disclose: Dr. Brill sat on a panel examining risks of surgical mesh products, which are used to support internal organs and treat urinary incontinence, in 2011—a year when he received $82,600 from J&J subsidiaries, including one that makes surgical mesh. The information is on J&J’s website.

J&J declined to comment. It pulled its morcellators from the market earlier this year. Karl Storz didn’t respond to requests for comment.

Keith Isaacson, a doctor who served on the morcellator panel, had received nearly $12,000 in consulting fees from a J&J subsidiary in 2013, the Journal reported in July. Further review of databases shows that Dr. Isaacson also got $9,500 from J&J from 2010 through 2012 for consulting, food and education and training; and that he received $148,400 in consulting fees and other compensation from Karl Storz from 2009 through 2013. The information came from websites of J&J, a Massachusetts health agency and Open Payments.

At the panel’s meeting, Dr. Isaacson expressed doubt about data showing that women getting surgery for fibroids have a 1 in 350 chance of having malignant tumors that morcellators could spread, a panel transcript shows. He noted a recent study that found the risk was closer to 1 in 7,450.

Dr. Isaacson declined to comment. The FDA wouldn’t discuss the payments or why it placed Dr. Isaacson on the panel in view of these corporate ties.

Dr. Kandzari, the cardiologist who served on an October FDA panel evaluating a heart device, is the director of interventional cardiology and chief scientific officer at Piedmont Heart Institute in Atlanta. He has published many medical-journal articles. He said his consulting for device companies is aimed at helping firms design more-efficient clinical trials.

RELATED

1. Deadly Medicine: Read the free WSJ e-book
2. Women’s Cancer Risk Raises Doubts About FDA Oversight (July 18)
3. Doctor Quits Uterine Device Safety Panel Over Conflict of Interest (July 10)
4. Fate of Uterine Device Now in Hands of FDA (July 11)
5. Gynecologists Resist FDA Over Popular Surgical Tool (Sept. 21)
6. Surgical Tool Gets Strongest Warning (Nov. 24)

One FDA panel Dr. Kandzari sat on last year considered a pacemaker and a defibrillator made by Medtronic Inc. That is a company from which Dr. Kandzari received between $76,600 and $130,600 for consulting work, teaching, travel, lodging and meals from 2010 through 2013, according to company and federal databases. A panel transcript shows he abstained from voting on whether to approve expanded use of the devices because he wasn’t sure whether the benefits outweighed the risks.

Dr. Kandzari said his past consulting for Boston Scientific, the maker of the device that was being evaluated at the October panel, had concerned an arterial stent. The October panel focused on a different Boston Scientific product: a plug that seals a heart appendage to cut the risk of strokes caused by clots.

That plug, called the Watchman, had been backed by previous FDA panels but was being reviewed again because a study showed patients receiving it had more strokes caused by blood clots than patients getting the blood thinner warfarin.

While the panel in October deemed the device safe, a narrow majority that included Dr. Kandzari judged it not as effective as warfarin. Still, he voted yes in a 6-5 panel vote concluding its benefits outweighed its risks, tantamount to a recommendation of marketing approval.

Dr. Kandzari said despite his concerns that “stroke was not necessarily reduced with this technology,” he believed it should be available for patients who are at high risk of complications from warfarin.

Following the advisers’ vote, Boston Scientific told analysts it expected the Watchman to win FDA approval in the first half of 2015 and eventually reach $500 million in yearly sales.

—Andrea Fuller contributed to this article.

Write to Joseph Walker at joseph.walker@wsj.com

Harmed Patients Notified of/Included in a 'Groundbreaking Conference'?

June 13th, 2014 Conference

Evidence for New Medical Products:
Implications for Patients and Health Policy

Date: June 13th, 2014
Time: 8:30 a.m. – 6:00 p.m.
Location: American Association for the Advancement of Science, Washington, D.C.
Register here: http://www.aaas.org/oZT

This event is co-sponsored by the American Association for the Advancement of Science, Division of Pharmacoepidemiology and Pharmacoeconomics of Brigham and Women’s Hospital/Harvard Medical School, and National Center for Health Research.

Conference Focus

Better implementation of evidence-based medicine can improve the quality and cost-effectiveness of health care in the U.S. This can be challenging in evaluating newly approved drugs and medical devices. While current law requires that medical products be proven safe and effective, there is growing pressure to expedite access to promising therapies and to lessen the research and regulatory requirements for manufacturers. Unmet medical needs and patient demands call for a flexible approach to prescription drug and device regulation, but truncated premarket review may also lead to approval of products that are less effective than expected or have unanticipated safety problems. This groundbreaking conference will review the growing body of research on the medical and public health implications of medical product approval criteria, and examine these findings in the context of patient outcomes, costs, and health policy.

Confirmed Speakers Include (where are the harmed patient speakers?)

Jerry Avorn, MD, Professor, Harvard Medical School; Greg Curfman, MD, Executive Editor, New England Journal of Medicine; Congresswoman Rosa DeLauro; Aaron Kesselheim, MD, Harvard Medical School; Bernard Lo, MD, President, Greenwall Foundation; Rita Redberg, MD, Editor, JAMA Internal Medicine; Joseph Ross, MD, Yale Medical School; Patrick Ryan, PhD, Janssen Research and Development; Sebastian Schneeweiss, MD, Harvard Medical School; Lisa Schwartz, MD, Dartmouth; Joe Selby, MD, Executive Director, Patient Centered Outcomes Research Institute; Steven Woloshin, MD, Dartmouth; Robert Yarchoan, MD, National Cancer Institute; Diana Zuckerman, PhD, National Center for Health Research.

For more details on the program and registration, please go to http://www.aaas.org/oZT. There is no cost for attending the event, but space is limited and advance registration is required.

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!