Prominent Docs Urge Senators To Limit Conflicts of Interest From FDA Advisory Panels
13 CommentsBy Ed Silverman // September 12th, 2007 // 4:04 pm
The group, which includes two formers editors of The New England Journal of Medicine, is urging Ted Kennedy and Chris Dodd to reconsider their opposition to limiting conflicted scientists from serving on FDA advisory committees. The Senate version of the forthcoming FDA bill doesn’t include any restriction. Under the House version, which permits one waiver per committee, ‘conflicted’ experts would be able to ask questions, but they couldn’t vote or participate in a committee’s discussion. Here’s their letter.
And so, the docs write: “Allowing conflicted members of an advisory committee to vote can have serious public health consequences. For example, in early 2005, an 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 (drugmakers). Had their votes been eliminated, two of three drugs in that class would have been voted down…”
They go on to note that, in an FDA report to Congress last January, the agency granted waivers to 24 percent of the 928 members of its 47 advisory committees that met during the 14-month period Nov. 10, 2005 through Jan. 4, 2007. Since then, the FDA has proposed a new policy in which panels will include 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. Still, to the average American, $50,000 is a lot of money.
The FDA ignored its own proposal recently when convening a panel to review Biogen’s Tysabri med. And the agency is conducting an internal probe into allegations that members of a panel that reviewed Dendreon’s controversial Provenge prostate-cancer vaccine had undisclosed conflicts of interest, according to sources familiar with the situation.
The docs - including Jerome Kassirer, Marcia Angell, Howard Brody and Roy Poses - argue “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 US and public-health experts at other federal agencies such as the National Institutes of Health, the Centers for Disease Control and the Veterans Administration.” And they note that other agencies bar conflicts. “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.”
MyPharmalotID
Here’s an op-ed piece that recently was published in the Bucks County (PA) Courier Times and that specifically addresses the failure of the U.S. Senate to address the issue of COIs. That legislative body’s failure to pass the Durbin Amendment on May 9, 2007, is a travesty of major proportions and suggests that senators are more concerned about funding their reelection campaigns than fair and honest reviews of much needed drugs. The op-ed is reproduced here with the permission of the author.
GUEST OPINION
Congress must take action to end FDA abuses, conflicts
By Theodore J. Cohen, Ph.D.
The so-called “Durbin Amendment,†Amendment SA 1034, was proposed in the U.S. Senate on May 9, 2007, to amend the Federal Food, Drug, and Cosmetic Act and, specifically, to ensure that participants in FDA advisory committees (AC) are free of financial conflicts of interest that would compromise their participation as unbiased Government employees.
Just what kind of situation might the Durbin amendment have protected against? Consider the recent case in which Dendreon Corporation brought its prostate cancer drug Provenge to an AC for review on March 29, 2007. One of the members of the AC was participating as a special Government employee under an approved waiver request in which he had first been required to declare his relevant conflicts of interest (COIs).
However, the COIs declared did not reveal the full extent of the conflicts. For example, they did not reveal that he was on Novacea, Inc.’s, scientific advisory board and is co-chair of the company’s ASCENT Phase III clinical trials investigating the use of Novacea’s Asentar drug together with Sanofi-Aventis’ chemotherapy drug Taxotere (docetaxel) to treat prostate cancer – a trial that some in the prostate cancer community believe would be adversely affected by Provenge approval. (Asentar is an oral treatment for prostate cancer.)
Further, he also is listed as a scientific advisor to ProQuest Investments., which owns a substantial interest in Novacea. Interesting, too, is the fact that in a highly unusual move for a special Government employee, this AC member wrote a letter to the FDA following the March 29th meeting, calling upon the agency not to approve Provenge.
More surprisingly, this letter was leaked by party or parties unknown to a non-peer-reviewed newsletter, and published in an obvious move to discredit the AC’s recommendation of approval (the AC voted 17-0 that the drug was safe and 13-4 that is demonstrated substantial efficacy). And finally, just three weeks after the FDA issued a Complete Response (CR) letter to Dendreon, asking for more data before it would approve Provenge, Schering Plough signed a $440 million deal with Novacea for the development of Asentar. What’s wrong with this picture?!
This is what the Durbin Amendment was meant to stop. “Was†is the operative word, because on May 9, 2007, the Amendment was rejected by a vote of 47 to 47, with 6 senators not voting. Senator Bob Casey (D, PA) voted “Yea;†Senator Arlen Specter (R, PA), for some inexplicable reason known only to him, voted “Nay.â€
You’ll have to ask the senator why he rejected an amendment that was intended to stop egregious abuses such as that described above. But until Congress acts, we can expect more of the same from members of FDA ACs, who fail to reveal significant conflicts of interest before sitting in judgment of drugs that potentially could save the lives of tens of thousands of patients every year.
Durbin Amendment
The actual language of the Durbin Amendment included the following:
“(1) In general, prior to a meeting of an advisory committee regarding a `particular matter’…each member of the committee who is a full-time Government employee or special Government employee shall disclose to the Secretary financial interests in accordance with subsection (b) of such section 208.
“(2) financial interest of advisory committee member or family member: No member of an advisory committee may vote with respect to any matter considered by the advisory committee if such member (or an immediate family member of such member) has a financial interest that could be affected by the advice given to the Secretary with respect to such matter.
“(3) participation of guest expert with financial interest: Notwithstanding any other provision of this section, an individual with a financial interest with respect to any matter considered by an advisory committee may be allowed to participate in a meeting of an advisory committee as a guest expert if the Secretary determines that the individual has particular expertise required for the meeting. An individual participating as a guest expert may provide information and expert opinion, but shall not participate in the discussion or voting by the members of the advisory committee.â€
phil_vardena (Pharm. D.)
Take Provenge for example, the drug developed by Seattle-based Dendreon. Provenge achieved a 200% increase in overall survival measured at 3 years… with multiple recipients alive and well over 6 years later.
27,000 men with end-stage prostate cancer will die needlessly early (some will die needlessly period) each year the Provenge is delayed by the FDA.
On March 29, 2007, an Advisory Committee panel voted to recommend Provenge for Approval by the FDA by an overwhelming margin. On the matter of safety, the vote was 17-0 for Provenge. On the matter of Efficacy, the vote was 13-4 for Provenge.
Some of those doctors that voted “NO” as to the effectiveness evidence even had letters (urging the FDA NOT to approve Provenge) “leaked” to the media. They were Dr. Sher and Dr. Hussain.
Who leaked the letters?
More, why write those letters in the first place?
Between the AC panel vote and the CR letter, some “shorts” - ie people that sell a stock without actually having it, hoping to buy it back later at a lower price - sold more Dendreon common stock. How did they know their bet was safe? After all, never before the FDA rejected a panel recommendation.
On May 9, 2007, “Black Wednesday”, the FDA said “NO” to Provenge, issuing a Complete Response letter. A few weeks after the FDA delaying letter regarding Provenge, on May 30, 2007, news was that Schering-Plough Corp. said it had agreed pay Novacea Inc. (a competitor to Dendreon) up to $440 million for rights to develop the smaller drugmaker’s prostate cancer treatment, causing Novacea shares to double.
Both Dr. Sher and Dr. Hussain are Novacea consultants.
Do you think Schering-Plough would have paid $60 million immediately and an additional $380 million to Novacea if Provenge was on the market?
Also, did Novacea and Schering-Plough Corp. arrange the deal in a couple of weeks? What kind of due diligence was Schering-Plough able to do in twenty days?
What did Dr. Sher and Dr. Hussain know when they sat at the panel?
Subsequent research shows Dr. Sher is also involved in Proquest, a healthcare venture capital firm with over $875 million under management.
Dr. Howard Scher is a Scientific Advisory Board member for Proquest Investments
Proquest owns shares in Novacea (now, an interesting question would be: Does Dr. Howard Sher own shares in Novacea?).
I would be curious to know if, at the time, Proquest was short Dendreon.
Why the FDA - for the first time in its history - did not approve a drug deemed safe and effective by its own panel?
How is that Dr. Sher and Dr. Hussain - with their obvious and enormous conflicts of interest - took part in the panel?
Only two oncologists took part in the Advisory Committe panel (the others being immunotherapists, urologists, etc.) and BOTH have substantial relationship with a competing company!
Who did choose to have Dr. Sher and Dr. Hussain in the panel, out of thousands of good oncologists out there? And why?
We already have proof that Provenge works (two phase III trials). Many people are going to die due to the delay. Who is accountable?
Why isn’t this revolutionary and extremely safe treatment available NOW?
Dear Dr. Ed Silverman, I wish to thank you for you effort in shedding more light on the matter of conflicted doctors sitting in AC panels.
Regards,
phil vardena
Cary
If $50,000 dollars is not enough money to pose a conflict of interest, I would hate to know how much each FDA panel member is getting paid. If the FDA wishes to regain the trust of the American public, it must eliminate all conflicts for every drug approval, no matter how big or small.
The FDA claims that doctors with conflicts of interest only serve when their expertise outweighs there conflict, but who is to know how much each doctor is personally affected by their own COI.
paul1149
The heat continues to build, and the outcry now comes from higher authority levels. This story is not going away.
Great coverage, Ed.
p.
Laurie
“If the FDA wishes to regain the trust of the American public, it must eliminate all conflicts for every drug approval, no matter how big or small. ”
Couldn’t have said it better myself. If we had never seen voting from an advisory committee along COI lines, this wouldn’t even be an issue. The fact that COI has been VERY much a part of FDA decisions regarding many drugs. The Prozac hearings in 1991 were a perfect example.
Kyoto27
Dear Ed,
Bravo that Docs are finally standing up and telling Congress “Thank you, but no thank you regarding the seating of conflicted scientists.â€
Now it’s Congress’ turn to address their own ‘conflicted’ relations with Big Pharma, and the BP money that helps them get elected…and that no doubt helped doom the passage of the Durbin Amendment. I have no problem with BP money contributions; I just don’t want that money shaping the outcome of legislation like the Durbin Amendment. As MyPharmalotID wisely noted above: “… until Congress acts, we can expect more of the same from members of FDA ACs, who fail to reveal significant conflicts of interest before sitting in judgment of drugs that potentially could save the lives of tens of thousands of patients every year.â€
Ed, keep “keeping†everyone honest!
Stephen
Surely the FDA was not intended to be an investment club.
No Conflicts of Interest!
Tony F
Two wonderful things happened when I logged in tonight:
1. Ed’s got yet another article about the FDA and Confict of Interests which, of course, includes the Scher-Provenge, ahhh, “situation” where Scher told the FDA he had 3 conflicts and net research started out at 10 alleged COI’s and has ballooned up to 17 as noted below. The 17 below do NOT include that he’s on the Board of Directors at Sloan Kettering.
2. Physicians are now joining the advocates in asking Congress to rectify this unholy alliance between potentially conflicted doctors and treatments they’ve been hired to evaluate.
Thanks, Ed!
Thanks, Doctors!
SCHER COI POSSIBILITIES
I have previously posted about Scher allegedly having 10 COI found on the net… then, it was 13. Further research found 15 and then 16 and now, the possible list sits at 17…. and here they are:
Scher reported only 3 COI’s to the FDA per his filing in late February available at the FDA website which appears to be composed of ownership of 1 stock and 2 competing industry interest.
Internet research shows the following for Scher thus far and please 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
There appears to be a significant and disturbing difference between his 3 disclosures to the FDA and the alleged 17 COI’s found so far on the internet. It seems incomprehensible for someone with the training and education Scher has to “forget†so many apparent COIs… that is simply beyond all reasonableness and suggests intentional dishonesty or deceit.
Even more disturbing is the FDA’s Office of Inspector General and others at the FDA to whom this information has been supplied and their apparent failure to investigate these charges that Scher has more COI’s than he disclosed to them. When such information is provided and such allegations of potential federal law violation is involved, any ordinary citizen has the right to expect our government to investigate such allegations timely and thoroughly.
Hopefully, the new info provided in this article suggests that MAYBE, FINALLY the FDA investigative arm’s attention to this matter has been caught!
Now, if those Doctors can just convinence the “Chappaquadic Kid” of their stance, that would be fabulous for patients and victim’s families.
AMMASS
Ed,
I love your honest coverage. Keep it up.
Sisyphus
17 Conflicts of Interest! Sound like COI activities make up the majority of this person’s activities.
There are plenty of people who are just as smart and who do not have COIs…that can be more objective in their decision making.
Hank
The “scariest” thing to me is to think hard about why Kennedy and Dodd, along with several other Senators who obviously “know the score” on these issues, continue to vote as they do.
We see it time and time again. What I have called, “bi-pharmasanship” in another context.
Someone
Dear Ed,
Thanks so much for what you do to keep this at the front.
I agree with Hank - Sen. Kennedy worked hard in the past to reform healthcare in the US and specifically looked to the Canadian model of universality. When did he “turn”?
Bravo on great reporting!
MyPharmalotID
Here’s the roll call…how did your senator vote? Amazing that even one senator voted NAY? How can a person be against COIs such as those found for Dr. Scher?! What can these people be thinking?!
U.S. Senate Roll Call Votes 110th Congress - 1st Session
as compiled through Senate LIS by the Senate Bill Clerk under the direction of the Secretary of the Senate
Vote Summary
Question: On the Amendment (Durbin Amdt. No. 1034 )
Vote Number:
156
Required For Majority:
1/2
Amendment Number:
S.Amdt. 1034 to to S. 1082 (Prescription Drug User Fee Amendments of 2007 )
Statement of Purpose:
To reduce financial conflict of interest in FDA Advisory Panels.
Vote Counts:
YEAs
47
NAYs
47
Not Voting
6
Alphabetical by Senator Name
Akaka (D-HI), Yea
Alexander (R-TN), Nay
Allard (R-CO), Nay
Baucus (D-MT), Yea
Bayh (D-IN), Yea
Bennett (R-UT), Nay
Biden (D-DE), Yea
Bingaman (D-NM), Yea
Bond (R-MO), Nay
Boxer (D-CA), Yea
Brown (D-OH), Yea
Brownback (R-KS), Not Voting
Bunning (R-KY), Nay
Burr (R-NC), Nay
Byrd (D-WV), Nay
Cantwell (D-WA), Yea
Cardin (D-MD), Yea
Carper (D-DE), Yea
Casey (D-PA), Yea
Chambliss (R-GA), Nay
Clinton (D-NY), Yea
Coburn (R-OK), Nay
Cochran (R-MS), Nay
Coleman (R-MN), Nay
Collins (R-ME), Yea
Conrad (D-ND), Yea
Corker (R-TN), Nay
Cornyn (R-TX), Nay
Craig (R-ID), Nay
Crapo (R-ID), Not Voting
DeMint (R-SC), Nay
Dodd (D-CT), Nay
Dole (R-NC), Nay
Domenici (R-NM), Nay
Dorgan (D-ND), Yea
Durbin (D-IL), Yea
Ensign (R-NV), Nay
Enzi (R-WY), Nay
Feingold (D-WI), Yea
Feinstein (D-CA), Yea
Graham (R-SC), Nay
Grassley (R-IA), Yea
Gregg (R-NH), Nay
Hagel (R-NE), Nay
Harkin (D-IA), Yea
Hatch (R-UT), Nay
Hutchison (R-TX), Nay
Inhofe (R-OK), Nay
Inouye (D-HI), Yea
Isakson (R-GA), Nay
Johnson (D-SD), Not Voting
Kennedy (D-MA), Nay
Kerry (D-MA), Nay
Klobuchar (D-MN), Yea
Kohl (D-WI), Yea
Kyl (R-AZ), Nay
Landrieu (D-LA), Yea
Lautenberg (D-NJ), Yea
Leahy (D-VT), Yea
Levin (D-MI), Yea
Lieberman (ID-CT), Yea
Lincoln (D-AR), Yea
Lott (R-MS), Nay
Lugar (R-IN), Nay
Martinez (R-FL), Nay
McCain (R-AZ), Not Voting
McCaskill (D-MO), Yea
McConnell (R-KY), Nay
Menendez (D-NJ), Yea
Mikulski (D-MD), Yea
Murkowski (R-AK), Nay
Murray (D-WA), Yea
Nelson (D-FL), Yea
Nelson (D-NE), Nay
Obama (D-IL), Yea
Pryor (D-AR), Yea
Reed (D-RI), Yea
Reid (D-NV), Yea
Roberts (R-KS), Not Voting
Rockefeller (D-WV), Nay
Salazar (D-CO), Yea
Sanders (I-VT), Yea
Schumer (D-NY), Yea
Sessions (R-AL), Nay
Shelby (R-AL), Nay
Smith (R-OR), Nay
Snowe (R-ME), Yea
Specter (R-PA), Nay
Stabenow (D-MI), Yea
Stevens (R-AK), Nay
Sununu (R-NH), Nay
Tester (D-MT), Yea
Thomas (R-WY), Nay
Thune (R-SD), Nay
Vitter (R-LA), Not Voting
Voinovich (R-OH), Nay
Warner (R-VA), Nay
Webb (D-VA), Yea
Whitehouse (D-RI), Yea
Wyden (D-OR),