FDA Enacts New Conflict Of Interest Policy
15 CommentsBy Ed Silverman // November 12th, 2007 // 12:24 pm
The agency recently posted a notice in the Federal Register about its new guidance on conflict of interest issues for advisory committee members. Although comments are being accepted until Dec. 31, some aspects of the policy are apparently already in place, according to the guidance (which you can read here).
A key change: the FDA will begin publicly disclosing all financial conflict-of-interest information for advisory committee members, along with copies of waivers the agency grants to allow participation on the committee. The agency has drafted a template of the form panel members are to submit, and it includes such things as stock holdings, consulting and speaking fees, research grants and patents. Until now, only a waiver was posted on the FDA site.
At least one issue remains controversial. The FDA will continue to include on its advisory committees anyone who takes less than $50,000 in corporate grants, contracts and consulting fees, or holds less than that amount in stock. This would only happen if the FDA decides the need for that person outweighs a potential conflict. And even then, they couldn’t vote. But as noted in the past, $50,000 is still a lot of money.
Also, it remains unclear the extent to which the FDA has the capability to fully vet these disclosure forms in the event of omissions. For instance, a controversy continues over last spring’s panel meeting to review the Provenge prostate-cancer vaccine in which one dissenting panel member allegedly held undisclosed financial conflicts of interest.
Hat tip to FDANews
Kerry
I sure hope Dr. Scher signs up for another AC panel. There are a lot of us who would really like to see the full extent of his financial holdings.
Those include my client CareToLive.
Kerry Donahue, counsel CareToLive, a not for profit corporation
Advocating for cancer patients, their families and the Doctors who wish to prescribe Provenge to their terminal patients now. More at Caretolive.com.
Kyoto27
Ed,
If the FDA really wants to get serious, then they will admit they cannot police (vet) the disclosure forms themselves — but should have the docs on notice that if ’serious’ violations are found—there will be penalities. Seriously ‘conflicted’ docs like Mr Scher should be fined and publicly chastised; they should also be publicly censored by their peers in an on -record -review. Scher-like tumors should be radiated by the medical community before they destroy the entire community. The fallout from Scher’s COI violations has already cast too big a shadow over the entire oncology community–rightly, or wrongly. Serving the nation should be an honor, not an opportunity to mock the principals of due process. And should certainly not be an opportunity to enrich ones stock portfolio.
Thank Ed as always for taking the high ground!
Nathan
I understand people’s concern with conflicts of interest. But people need to be aware that the FDA advisory boards need experts in the area of drug safety & efficacy. Where are these experts going to come from? The vast majority of scientists trained in drug safety & efficacy likely work in the drug industry or work in academic labs that are partially funded by the drug industry.
It’s kindof like saying that your NBA referee can’t be a basketball fan. Certainly you don’t want someone with $50k of Novartis stock to decide on a Novartis drug. But what about someone with a $50k/year pension plan from GSK voting on the fate of a J&J drug? I don’t see a big problem there…
There has to be open lines of communication between the government and the industry. Many times these “conflict of interest” rules hinder good communication. I’ll give you a real life example: I work as a researcher at a top 10 big pharma company. We wanted to invite a researcher from the NIH to give a lecture about some of the cancer research that he’s been doing. We generally pay $1000 “honorarium” along with his/her travel expenses. The person would give a 1 hour lectue and then meet with various scientists from my company for the afternoon. Unfortunately, this was deemed to be a “conflict of interest” by the NIH and he was unable to share his research with us. How is this benificial to anyone? The NIH researcher wants people in the field to be aware of what he is doing. My company wants to be aware of the latest cancer research so that we can do the best job we can developing anticancer drugs. Unfortunately the government doesn’t allow such communication….
Conflicts of interest have to be monitored… but we need to be careful not to hinder communication and transfer of valuable knowledge between government and industry.
Karma
Its common sense really. If there is a COI that is a small numeration and the *expert* is professional enough to offer a scientific-based objective opinion thats one thing. But, c’mon, Scher reported 3 COIs on his waiver out of a total of 14!!! And Proquest and Novacea, c’mon Howie, how ignorant do you think the public is? Further, how arrogant
is good Dr. Scher? Well, I guess anyone in collusion with Dick Pazdur’s “chemo cartel” has at best, questionable integrity.
FDA will do its best to keep good Doc Scher behind the pallisades of big govn’t and big pharma. But this thing is gonna steam roll out of control. Its time for the crooks at the FDA to reap what they have sown. And everyone knows
Karma is one bad mutha.
MyPharmalotID
What would a “prudent man” have done in Scher’s case…
A prudent person, faced with Dr. Scher’s connections, would have avoided all perceptions (!) of conflicts of interest by not even asking for a waiver.
My gut feeling is that he was pushed into asking for the waiver and reluctantly agreed to participate in the Advisory Committee meeting (perhaps feeling that if he did not participate, it would jeopardize his consultancy at the FDA).
Regardless, he will rue the day that he ever sat on that panel, much less voted, because for whatever he has accomplished in his professional life (and his contributions are significant), his reputation will forever be sullied by the part he played in the rejection of Provenge on May 8, 2007.
Kyoto27
Nathan,
The following letter –and note the docs who signed it, clearly notes that there is a big enough pool of qualified docs out there without COI issues, and warns the Senate & House to not bend over to allow ‘experts’ to serve on AC panels. In the case of Howard Scher –his COI conflicts were over the top and made a mockery of the waiver granted to him (& he knew it!). This letter IMO strikes the right balance–but politicians are afraid to hurt their Big Pharma $$$ contribuitions. Is this the way to look after the nation’s health?
September 12, 2007
The Honorable Edward M. Kennedy
Chairman
Committee on Health, Education, Labor, and Pensions
Room 644
Dirksen Senate Office Building
Washington, D.C. 20510
The Honorable Christopher J. Dodd
Room 448
Russell Senate Office Building
Washington, D.C. 20510
Att: David Dorsey and Tamar Magarik
Dear Senator Kennedy and Senator Dodd:
We write to urge you to reconsider your position and to support in the Senate-House
conference on the drug safety bill a provision in the House version of the bill (Title VII of H.R.
2900) that restricts conflicts of interest on advisory committees of the Food and Drug
Administration (“FDAâ€). As you know, the Senate did not adopt this provision on May 9 when
it defeated, by a vote of 47-47, the amendment offered by Senators Durbin (D-IL) and Bingaman
(D-NM).
The House bill and the Durbin-Bingaman amendment permit only one waiver of a
conflict of interest per advisory committee. Conflicted experts would, however, still be allowed
to present evidence and answer questions, but they would not be allowed to vote or participate in
the committee’s discussion.
According to its January 2007 report to Congress, the FDA granted waivers to 24 percent
of the 928 members of its 47 advisory committees that met during the 14-month period
November 10, 2005 through January 4, 2007.
Allowing conflicted members of an advisory committee to vote can have serious public
health consequences. For example, in early 2005 a FDA advisory committee reviewed the safety
of COX-2 inhibitors and concluded that all three of these drugs, including Vioxx, were safe
enough to keep on the market. Ten of 32 scientists on that panel had financial ties to
manufacturers of the drugs. Had their votes been eliminated, two of the three drugs in that class
would have ben voted down by the panel. (Vioxx was, of course, voluntarily withdrawn from
the market by Merck in September 2004 because of safety concerns).
It is possible to find unconflicted experts. The FDA could choose its committee members
from among the 123,000 faculty at the 125 medical schools in the United States and public
2
health experts at other federal agencies such as the National Institutes of Health (“NIHâ€), the
Centers for Disease Control, and the Veterans Administration. The NIH’s Office of Medical
Applications of Research and the Agency for Healthcare Research and Quality’s U.S. Preventive
Services Task Force bar any conflicted scientists from serving on the panels that develop
consensus statements on the implications of clinical trial evidence. The Center for Evidence-
Based Policy at Oregon Health Sciences University bars any conflicted expert from its analysis
of clinical trial evidence to determine what drugs, biologics, and devices provide the best
medical outcomes; this evidence is then turned over to states for use in establishing what
Medicaid will pay for, among other uses.
In March 2007 the FDA asked for public comment on a proposal to bar all conflicted
experts from voting at an advisory committee meeting and to permit only those with conflicts
below $50,000 to participate in the committee’s discussion. The New York Times editorialized
on March 23 that this proposal was “encouraging†but “may still need to be strengthened.†The
FDA has not yet made a final decision and, in event, could change its mind later.
In conclusion, it is important to restore the public’s confidence in the integrity of the
FDA’s decisions by having Congress restrict the number of waivers the FDA grants.
Thank you for considering our views.
Sincerely,
Marcia Angell, MD
Senior Lecturer in Social Medicine
Harvard Medical School
Howard Brody, MD, PhD
John P. McGovern Chair in Family Medicine
Director, Institute for the Medical Humanities
University of Texas Medical Branch
Jerome R. Hoffman, MA MD
Professor of Medicine
UCLA School of Medicine
Jean Silver-Isenstadt, MD, PhD
Executive Director
National Physicians Alliance
Jerome P. Kassirer, MD
Distinguished Professor
Tufts University School of Medicine
Roy M. Poses, MD
President, Foundation for Integrity and
Responsibility in Medicine
Clinical Associate Professor
Brown University School of Medicine
Stephen R. Smith, MD, MPH
Associate Dean of Medicine
Professor of Family Medicine
Warren Alpert Medical School of Brown University
Adam C. Urato, MD
Attending Physician
Assistant Professor
Tufts University
New England Medical Center
Michael Wilkes, MD, PhD
Vice Dean, Education
Professor of Medicine
University of California, Davis School of Medicine
Ed Silverman
Hi Nathan,
You make some good points. I don’t think pensions are mentioned specifically on the FDA list, for better or worse, although it’s not clear if a pension would be considered an investment.
In any event, I understand the issues surrounding KOL’s. I think the industry and the agency have been slow to acknowledge the need for disclosure, of any sort. So any step toward that goal is a positive development.
Unfortunately, I think a reasonable group of people could go round and round on this subject all day long and not easily come up with a way to distinguish between conflicted a little and conflicted a lot. But to not engage in the exercise could allow unacceptable conflicts to occur. One problem - what’s a lot of money to some folks isn’t a lot to others. Trying to find a reasonable cut-off, I’m sure, is challenging; you can’t satisfy all the people all the time.
I can’t really speak to the NIH example you offered, not knowing anything else about it. But I get your point. Perhaps other forums or venues would have existed to hear that scientist’s insights.
In any event, thanks for writing in.
ed at Pharmalot
Kerry
I disagree. If these doctors want the privilege to sit on an AC panel then don’t become financially involved in the areas in which they work. For example if Dr. Shcer wants to be involved with ProQuest Investments then fine but stay away from the FDA then. Part of his value to Proquest was in part because he WAS ON FDA PANELS.
It comes down to nothing but greed. Some of these panelists are not happy unless they are maximizing their profits evry which way they can. It comes down to one thing: pure and simple greed.
They want paid by the FDA then also paid to be advisors to investment funds and for sitting on various boards. They run around providing their buddies with inside info from the FDA.
There are plenty of AC experts that do not feel that they have to profit in every way they can from what they do. There were 13 on the Provenge AC. Most AC experts are good honest people with the only goal being the best interest of patients but thats not all of them. We do not need greedy people on the AC’s. The message is don’t apply to be on AC’s anymore if you are out there profiting in the market from what you are doing whether its directly or indirectly.
How many millions do people like Scher need?
The FDA band aid will work because those with extensive financial interest will no longer apply. Scher will never apply again because to do so he would have to diclose the 17 ways he personally benefitted by Provenge non-approval which he helped sabotage based on his own personal interests and agenda.
For more go to Caretolive.com
Kyoto27
Ed,
You note in your reply to Nathan:
“…I think a reasonable group of people could go round and round on this subject all day long and not easily come up with a way to distinguish between conflicted a little and conflicted a lot.” If a ‘reasonable group of people’ have a problem seeing that Howard Scher was “conflicted a lot” as a nation, I would argue we have a serious problem with our moral compass. Thankfully, we have the Ed Silverman’s of this nation who are still the guardians of that compass–otherwise I think we would be going round and round all day.
Howard Scher has unknowingly exposed the real depths of corruption and depravity that exist in any soul, and nation and IMO it is not enough to just reel from the horror of it–it has to be expunged. Hopefully, and thanks to the work you are doing as one of the few remaining members of the Fourth Estate willing to tackle the real issues in this nation–the DOJ, and other regulatory agencies are looking into the Provenge Story. If they are not, God help us all.
Tony F
Two thoughts strike me about this change in direction by the FDA on Conflict of Interests:
1. It’s past time to clean up this potential for illegality or, at least, the appearance of the same
2. What is Howard going to do now with regards to ever being a “Special Government Employee” again?
I can envision it now at a future deposition:
SCHER: “What is the meaning of Conflict of Interest?” (a la Slick Willy’s depo in the Monica scandal)
(Under his breath)”Why don’t my peers stand up for me?”
I certainly agree with a poster above; it’s a genuine shame that Scher appears to have prostituted himself, his reputation, his life’s work for money…
Just so no one is under the false illusion that Scher is an innocent lamb being led to the slaughterhouse…. He listed, in writing, to the FDA in order to sit in judgment of Provenge on March 29th that he had 3 COIs…. 2 company grants and 1 stock holding.
My internet research shows he has 17—so far:
particularly note #1 and #17:
1. NOVACEA: grants & research support; STUDY CHAIR of DN-101; Direct competitor to Provenge
2. GPB BIOTECH: financial conflict of interest per Scher in MedPage
3. PHARMION: financial conflict of interest per Scher in MedPage
4. SANOFI-AVENTIS: grants & research support
5. BRISTOL MYERS SQUIBB: consultant, grants & research
6. MILLENNIUM PHARMCEUTICALS: grant of research support
7. COUGAR BIOTECHNOLOGY: principal investigator; advisory board;
8. INNOVIVE PHARMACEUTICALS: principal investigator
9. INFINITY PHARMACEUTICALS: principal investigator
10. BIOGEN-IDEC: jointly held stock with spouse
11. PFIZER: jointly held stock with spouse
12. GENTA: scientific advisory board (as of March 6, 2007; since removed from web, but cached)
13. CONFOMA THERAPEUTICS: scientific advisory board
14. DEPARTMENT of DEFENSE: Principal Investigator PC Clinical Trials-P1 and P2
15. AMBRILIA BIOPHARMA INC: Principal Investigator PCK3145, Phase I/II
16. MEDIVATION, INC: principal investigator MDV3100
17. PROQUEST INVESTMENTS: consultant, scientific advisory board; Limited Partner FINANCIAL interest
Make you own judgments about Howard Isadore Scher of Sloan-Kettering in NYC based on these findings.
Tom Smith
I written the FDA/SEC/DOJ numerous times asking when are you going to investigate HOWARD SCHER??? He has many COI’s but his Novacea/Proquest is most important one. If he broke the law then he needs to pay for it! IMHO he should be wearing a orange jump suit!
Tom Smith
I have written the FDA/SEC/DOJ many times asking them when they are going to investigate Howard Scher’s coi’s with the Proquest/Novacea being the most important one! No response from any of them! If this guy broke the law then I say he should do some time in an orange jump suit!
MyPharmalotID
Look at this review of the proposed new FDA rules that was published earlier this year; under the new rules, neither Dr. Scher nor Dr. Hussain would have been permitted to participate in the Provenge AC!
BioCentury, THE BERNSTEIN REPORT ON BIOBUSINESS MARCH 26, 2007
By Steve Usdin
Washington Editor
When FDA’s Cellular, Tissue and Gene Therapies Advisory Committee meets this week to discuss whether the agency should approve the first cancer vaccine, a product that could establish proof of principle for an important new therapeutic class, several of the votes will be cast by internationally respected experts who were invited to join the committee on an ad hoc basis because of their specific expertise.
The picture might look quite different if FDA’s new draft guidance for determining conflict of interest and eligibility for participation on its advisory committees were in force. Under the proposed policies, three of the invited experts probably would be ineligible to vote on Provenge sipuleucel-T from Dendreon Corp. (DNDN, Seattle, Wash.).
And two might be completely barred from participating in the discussions.
The new, more stringent criteria for participating in advisory committee meetings will limit or preclude the participation of “a significant fraction†of serving committee members, Associate Commissioner for Policy and Planning Randall Lutter told reporters last week.
The policies are needed “so that the public has confidence in the integrity of the recommendations†made by the committees, Lutter said. They are intended to strike a balance between “having the best possible access to scientific experts who may by the nature of their work have had ties to private industry that is driving biomedical innovation in this country, and at the same time seeking to ensure we have the fullest public confidence in our advisory committee process.â€
FDA critics praised the announcement as vindication of their claims that the advisory process has been corrupted, while some former senior agency officials warned it will harm public health by preventing or deterring highly qualified scientists from participating on committees.
New filters
The draft guidance replaces previous policies, which did not spell out criteria for granting waivers from government COI regulations, with an algorithm for determining eligibility to participate (see “Conflict-of-Interest Algorithm,†A18). Generally, the decision tree would exclude individuals who have financial interests of $50,000 or more that might be directly affected by a meeting’s outcome — or have had such interests in the previous 12 months.
In addition to the potential advisor’s financial interests, the criteria apply to spouses; minor children; current or prospective employers; general partners; and organizations for which the individual serves as an officer, director, trustee, or general partner. The draft guidance defines a prospective employer as “anyone with whom the employee has any arrangement concerning future employment or with whom he/she is seeking or negotiating for employment.â€
Under the new policies, individuals with a relevant direct financial interest in a meeting’s outcome of less than $50,000 could be permitted to participate on a non-voting basis if they have unique qualifications and relevant expertise, and it is difficult to find someone with similar qualifications without a disqualifying financial interest.
Although FDA has left itself flexibility to waive these criteria in exceptional circumstances, the agency has stated it generally will apply its guidelines more stringently than required.
For example, the guidelines state that the calculation of potential COI should exclude ownership of up to $15,000 of stock in a company with a product under discussion, or in a company with a competing product. Nonetheless, according to the guidance, because “the public may perceive some financial interests involving securities in organizations potentially affected by advisory committee recommendations as problematic,†FDA intends to “implement a policy of generally limiting participation to non voting in such circumstances even where full participation would be permitted.â€
Test case
The COI waivers for the Provenge meeting posted on FDA’s website on March 13 — eight days before the draft guidance was released — illustrate the potential impact of the new policies.
The Cellular, Tissue and Gene Therapies Advisory Committee is oriented toward specific technologies, not a specific therapeutic field. No one on the committee specializes in prostate cancer.
FDA has granted a waiver to Maha Hussain, a professor at the University of Michigan Health System, who will participate as a voting consultant to the committee.
The waiver document notes that Hussain “has a national reputation in the fields of cancer research and clinical care for advanced genitourinary cancers†and is a member of FDA’s Oncology Drugs Advisory Committee (ODAC).
“There is a critical need on the Committee for clinical care expertise in the treatment of advanced, metastatic prostate cancer patients who don’t respond to standard treatment,†according to the waiver. It also asserts that her “clinical trial expertise will contribute to the Committee’s discussion of appropriate patient populations and study end points.â€
The waiver notes that Hussain is the principal investigator on a research contract awarded by a competing company for a product that is not related to Provenge. Under the draft guidance this probably would not be considered a conflict. However, the fact that her husband owns stock in three competing companies, valued at $15,000-$300,000, would at minimum prevent her from voting. If the total value of the stock exceeds $50,000, Hussain wouldn’t even be at the table if the new policy were in effect.
Another oncologist with extensive experience in prostate cancer clinical trials, Howard Scher, received a waiver for the Provenge meeting. He is chief of genitourinary oncology services at the Sidney Kimmel Center for Prostate Cancer, Memorial Sloan-Kettering Cancer Center. Scher has served as a consultant to ODAC, so he “understands the FDA mission to move new therapies forward at the same time protecting the welfare of patients,†the waiver form states.
Under the draft guidance, Scher either would be prevented from voting or excluded from the meeting.
He owns stock in a firm that competes with DNDN valued at $5,000-$100,000. In addition, Memorial Sloan-Kettering has a grant from a competing company valued at $100,000-$300,000 to study a licensed, approved drug in prostate cancer trials.
——————————————————-
Note that this article was dated prior to the March 29, 2007, Provenge AC meeting. It’s clear that the FDA knew then that it had a serious problem. In fact, the agency had the responsibility then, regardless of whether or not the new rules were in effect, to screen AC members carefully for conflicts of interest. Dr. Scher, in particular, as can be seen above, significantly underreported his COIs, which could - and were - easily uncovered through searches on the Internet. That CBER was lax in vetting the members of the Provenge AC can’t be argued? Why the Office of the Inspector General, HHS, is not investigating this matter continues to puzzle the patient and investor communities alike. Even stranger is the fact that DOJ is representing the very people in the CTL lawsuit that it should be investigating, proving once again that life within the Beltway is the closest thing to living with Alice in Wonderland.
R.A.S. MD
The “prudent man” approach to the COI issue is eminently reasonable.
I am both a practicing physician and active clinical researcher in my specialty field of expertise.
An HONEST and HONORABLE man would immediately know when his requested expert advice would be tainted by conflict of interest. There NEVER would be a question of what is “right or wrong.”
Especially when one has a financial interest in or is actively involved in ANY level of development of a competing technology or product.
De facto BIAS is ALWAYS present in those situations.
In regards to the Dendreon case, it is shocking that the several “experts” with such egregious conflicts of interest
and innate BIAS against ProVenge were ever allowed to sit on the AC panel and then advise the FDA against PV approval.
Believe me, these physicians KNEW they were conflicted and still made an eventually successful effort to quash a safe and substantially effective vaccine that would have had a POSITIVE effect on tens of thousands of PCa victims!!
Despicable behavior, indeed!!
fpdoc
Now, with Rep. Michaud’s request that Energy and Commerce hold hearings on the Provenge COI case, we will hopefully see these issues resolved.
I think that what the appologists for Dr. Scher ignore is, that in failing to list his most significant conflicts (Novacea and ProQuest), he proved that he knew they would have disqualified him from serving on the AC and he could not afford to have no influence on the panel decision. His boss, Dr. Pazdur would have been very unhappy.