FDA Issues New Rules For Advisory Committees
20 CommentsBy Ed Silverman // August 4th, 2008 // 11:56 am
The changes involve conflicts of interest and waivers for panel members; advisory committee voting procedures; the timing of committee briefing materials to be released and the procedures for deciding when an advisory committee meeting should be held. The policies and procedures are described in four final guidance documents, and proposed changes in policies are described in a draft guidance. Here is a summary, and you can look here to read the individual guidances.
The most contentious issue has to do with concern over conflicts involving committee members, a hot-button topic that regularly embroils the FDA (see this item earlier today). The FDA has long argued finding experts without financial conflicts is arduous, if not impossible, because many top-flight physicians and academics serve as industry consultants.
To answer the criticism, the FDA has these new rules: For starters, if an individual, his or her spouse, or minor child has potentially conflicting financial interests totaling more than $50,000, he or she would not be allowed to participate in that meeting.
Second, the guidance specifies four scenarios where a conflict is significant and FDA does not intend to issue a waiver, even if the potential personal conflict is below $50,000. (For example, if the advisor is the principal investigator of a clinical trial of a product about which the committee will be providing advice, the advisor will not be allowed to participate in that meeting.) Third, before a waiver is issued, the FDA will require a showing that the waiver is necessary to ensure the committee has “essential expertise.” Fourth, as now required by law, the FDA will limit the number of waivers granted.
[Our thought: $50,000 is still a lot of money. Disagree? Ask someone who thinks $4 for a gallon of gas is too much. We recognize there is no perfect situation, but the threshhold remains stubbornly high.]
kyoto27
FDA spokeswoman Susan Cruzan offers revealing insight into advisory panel meetings and FDA decision making in a recent Reuter’s article:
She said that “FDA’s standards for what constitutes a safe, effective drug have not changed. We haven’t raised the bar for drug approvals.”
And then goes on to say:
Agency officials make independent, final decisions after carefully weighing advisory panel recommendations, Cruzan said. Rulings “are based on factors beyond those addressed by the advisory committees,” she said.
My question:
If the advisory panels are not addressing the real issues or ‘factors’ that determine the outcome of a yes or no FDA vote, I don’t even want to ask why have the AC panels; but then doesn’t the FDA owe patients and Americans a listing of what those factors are? Are they emotional? Are they political? Are they ‘factors’ based on ‘winks & nods’ between agency chiefs or serious discussion and debate? C’mon Susan, what are those X-factors?
http://www.reuters.com/article/latestCrisis/idUSN01307940
atlex
Ed,
Whether or not $50K is a lot of money is undoubtedly subjective. However, I don’t think it means much in reality. As I read it, someone with >$50K in conflicts would be excluded. If they have <$50K, they would still need a waiver. That seems reasonable enough.
Did I read it correctly?
Atlex
Common Sense
I agree that $50,000 is way too high. A better level would be $10,000 in the previous year. At the rates these guys charge, that’s about 2 days or 4 talks. Anything more is excessive.
Ed Silverman
Hi Atlex,
Yes, you read it correctly. I was trying to make the point that the threshhold should be lowered. As you say, ‘a lot of money’ is a subjective notion, but given the problems with real or perceived conflicts, the agency should have been more stringent about financial holdings and chosen to enforce a stricter limit, in my view.
This kind of discussion could, I suppose, go on endlessly, but do we want someone holding $48,000 in stock in a company given a waiver to make a crucial decision? Of course, $48K may be a modest amount to some panel members and ‘a lot’ to others, not to mention the public at large. But it’s still real dollars and, presumably, the fewer real dollars attached to a panel member, the better. Otherwise, why have the rule in the first place?
I realize my remarks will invite some people to throw darts - or maybe not - but I don’t understand how $50,000 came to be deemed the appropriate cut-off point, even with a waiver. So if anyone disagrees with me, that’s fine. This issue has been on the table for months, ever since the FDA proposed the new rule and I’ve written before that $50K seemed too high. I’m happy to hear opposing views.
Cheers
ed
Seeks the Truth
Although I applaud the “new” regs, it’s clear that the FDA continues to stonewall any efforts to delineate it’s egregious sin against Dendrion. In fact, the FDA’s tough new measures probably came about when at least two AC Committee members reviewing Dendrion’s revolutionary vaccine Provenge, were found to have SIGNIFICANT conflicts of interest after they successfully led a fight to block Provenge approval.
Did I mention that one of the doctors, a prominent naysayer on the AC decision, was found to have >10 major conflicts of interest that were not mentioned on his FDA “waiver” that allowed him to sit on the committee? That “waiver” allowed him to pass judgement on what could be viewed as a very severe threat to the chemo-cartel that controls vast and lucrative areas of cancer treatment?
Tens of thousands of men with late stage and soon to be FATAL Prostate Cancer, might have benefitted from Provenge vaccine therapy that had been shown in clinical trials to have SIGNIFICANT survival advantages.
The same doctor, at the very time that he was sitting in judgement of Provenge, was the LEAD INVESTIGATOR in a prominent clinical trial for a COMPETITIVE PRODUCT for prostate cancer.
Why has the FDA NOT been able to admit that the COI’s played a LARGE part in an egregious wrong??
It’s one thing to “change your ways” after the fact, but in the case of Dendrion’s Provenge, the FDA is OBLIGATED to both admit that Dendrion was wronged and that FDA officials were duped along the way.
In my view, there has been a concerted effort to cover-up the process and protect the individuals who so blatantly served to protect their own interests.
When will the perpetrators who wronged Dendrion, Provenge and THOUSANDS of sick men with advanced PCa be identified and punished?
WHEN???????????????????
Tony F
Ed, as those familiar with the Provenge story know, the FDA already had rules in place to limit Conflict of Interests in Advisory Committee panel members conflicts.
Last year, Howard Isadore Scher of Sloan Kettering certified to the FDA he had but 3 (Three) Conflict of Interests in order to be able to sit in judgment at Provenge’s AC meeting.
However, internet research suggest good old Dr. Scher has at least 17 (Seventeen) COI at the time he “served” as a panel member.
1. NOVACEA: Grants & Research support;
… STUDY CHAIR of DN-101
… a DIRECT competitor to Provenge
… DN-101 failed its clinical trial
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 MYERSSQUIBB: 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. AMBRILIABIOPHARMA INC: Principal Investigator PCK3145, Phase I/II
16. MEDIVATION, INC: Principal Investigator MDV3100
17. PROQUEST INVESTMENTS,
… Board of Directors
… Advisor
… INVESTED in Novacea.
These alleged COI have been supplied to the FDA and the HHS investigative offices without resulting in any investigation at all.
So, even with the less-restrictive rules of last year and the tightening you noted today, what makes an average Joe or Jill American believe that the FDA, today, is any more careful about whom they invite and allow to serve on Advisory Committee panels?
Is this latest action just “window dressing” to placate the public’s outrage over the FDA’s past actions?
Time will tell…..
Ed Silverman
Hi Tony,
At the time of the Provenge advisory committee meeting, those rules were only proposed. Please see here….
http://www.pharmalot.com/2007/03/fda_will_limit_conflicts_of_in/
Now, the FDA is formalizing the proposals.
Regards
ed
LILLI
I believe any person with the FDA Advisary Board should not have any financial interst at all and neither a member of their family.
All Medications have serious side effects that doctors are not rpoeting or monitoring and covering up the serious problems prescription drugs can cause.
Promotional advertising has led the general public to believe that every new drug will be a cure. It is not really true. Instead of selling drugs why don’t we urge Congress to work towards preventative medicine. It is discouraging news from Oncology predications that Cancer Medications will outsell Blockbuster Statins by 2011. Why are they predicting patients will have cancer? Our health care system is not concerned with the health of the people, our system is more concerned to have people dependant on medications It started in the 1960’s with the promotion of
psychiatric medications and every one was taking antidepressants when not really needed.The power of greed is corrupt and has inflicted physical and emotional harm.
Atlex
Ed,
Assuming that in any way you buy the FDA argument that it would have a difficult time finding panelists if a complete ban was in place, where would you draw the line? $25K, $10K, $5K? I presume that the FDA picked a number that it thought was reasonable and that gave it some flexibility to use waivers. I assume the policy went through some sort of commentary period and the policy was finalized.
Atlex
Ed Silverman
Hi Atlex,
This gets back to my last comment, in which I agreed with you that ‘a lot’ is in the eye of the beholder. Something less than that may have been appropriate, if we’re going to entertain allowing such conflicts at all. So which number? I would say less than $10k - which is a lot less than $50k to the average person and, presumably, a much smaller number to a sought-after physician or academic with substantive holdings. And yes, the FDA had public comment for awhile last year. I still think the agency has a tin ear on this issue, though, for reasons stated previously.
Cheers
ed
atlex
Ed,
Why $10K? To some people that’s a lot of money. To others, it’s not. So why pick that number? I’ve yet to hear a compelling argument for any specific number. While I vehemently disagree with those who want to eliminate all panelists with even a hint of conflict, at least they have a cogent argument for their non-arbitrary number (ie, $0).
Your focus on what the “average person” thinks doesn’t work for in my mind for a couple of reasons. First, I don’t know of any data to support what the “average person” believes is enough to be considered a conflict. Second, even if there was data, relying on the “average person”, while wonderfully democratic, its not necessarily a good way to set public policy. The “average person” may not have a frame of reference for making his or her determination.
My concern is not being able to access the world’s most knowledgeable experts on a disease because they may have a couple of hundred shares of stock in their kid’s 529 account and receive $2500 a piece for 2 speaking engagements. At least the The $50K limit before an outright ban kicks in, gives the FDA some flexibility.
By the way, I don’t think the policy deals with other types of financial interests that can be conflicts? Suppose a panelist has no pharma holdings that are in conflict, but does receive consulting fees or has stock in health plans. Certainly, the approval of a new high cost drug could hurt profits at the health plan. Is that a conflict we should be concerned with? Supposed a panelist just lost out on a grant from the drug company involved in the review? Should that be noted at a COI or bias?
Atlex
Ed Silverman
Hi Atlex,
Unfortunately, I don’t have a lot of time today to spend on this right now. But I agree it’s all too arbitrary, for me as well. As I indicated earlier, I think, I don’t have a good answer as to why any one number should be set. But I continue to believe that $50k is still a lot, which is why zero is a tempting solutuion. Again, this is all imperfect. (To answer your other questions, yes, the health plan example could be considered a conflict and same for the panelist who lost the grant, but that’s not a financial holding, is it? So that becomes a slightly separate, if related discussion). When I have more time, I’ll stop back later.
Cheers
ed
M Helm, MD
If I were the King, I’d look at this differently. I think I would divided the responsibilities of the FDA into at least three broad categories - Human Health, Human Nutrition, and Animal Health and Nutrition. Then I would consider income and assets differently. First, I’d consider income - anyone who derived more than 2% of their individual or family income from any of the interests regulated in relevant area in any of the past five years would require review for a waiver. Anyone with more than 5% of their income would be ineligible for participation in any decision-making or advisory capacity. I would then look at assets, and make the same sort of determinations. However, I’m not the King, and I didn’t think about this more than five minutes.
It is obvioulsy difficult to set arbitrary cutoffs. Everyone’s perspective on “a lot” is different.
Deborah B
Thanks Ed, for this fascinating discussion. I want to start a pharma company at some point, and I’ve always been concerned about this COI problem. The problem of COI gets larger, and thornier, in direct proportion to the size of the market/patient population that the drug addresses. Its ubiquitous in this agency, and as in the example of Dr. Scher above, clearly subject to subjective interpretation.
I think the FDA needs to re-write the rules for who serves on these committees AGAIN. (Even given the “new rules” guidance.) Tony F is correct. Even a hint of conflict of interest only serves to intimate that we are all ultimately at some risk when we choose to use an FDA-approved drug. (ie: Was this drug approved because it was the best in treating my particular indication? or was it approved because a majority of committee members, all of whom have relationships with the applicant, said it should be?) Eliminating COI, in all it’s varieties, should be a top priority. And yes, I personally feel that $50K is too high a threshold.
Paul G
This policy means that the true experts in the field, i.e. those who do clinical trials, would not be able to give their opinion. So let’s ask the opinion of people who don’t do clinical trials, don;t do publications, don’t do CME.
I don’t think $50K is too high a threshold.
Laurie
“This policy means that the true experts in the field, i.e. those who do clinical trials, would not be able to give their opinion. So let’s ask the opinion of people who don’t do clinical trials, don;t do publications, don’t do CME.”
No, lets omit those who do the clinical trial as members of the advisory committee. Those that have a connection with the specific drug are free to testify in a public hearing, but they should NOT be in a decision making position that they will benefit from.
Those that do the clinical trials are well represented in the data….we need someone who looks at the drug information without bias.
Dan
The true experts will always be sought after by industry as consultants, trial sites, etc. These people are very sensitive to attacks on their credibility, so in my experience, they tend to go out of their way to NOT be biased toward the industry. Besides, do we really want input from those who have fewer credentials in the field? Isn’t it just as likely that those with no conflicts (and likely lesser expertise) could misinterpret data to claim something is more safe and effective than it really is? For most of the experts involved, $50,000 is not a lot of money, and unlikely to sway their expert opinion.
Adirondack
Listening to and speaking at the advisory committee hearings, I would wager that it is not so much the COI per dollar amount, but the morality and ethics of the members. Evil is not only banal, but often results from brutal insensitivity rather than devilish malice.
Surely, there much be another measure in addition to cash on hand to find members who are honest and learned.
Laurie
“. Besides, do we really want input from those who have fewer credentials in the field? ”
Credentials are completely different than those that will gain financially from a drugs approval or who have a bias towards approval. There are plenty of experts who can and would serve on an Advisory Committee. Advisory Committees typically interpret data, that does not require an intimate knowledge of a particular drug. They even have a “public member” with minimal experience.It’s about evaluting risk vs benefit, that doesn’t require a job/consulting contract with a specific manufacturer.
It requires an ability to look at date, listen to public testimony and make a decision based on that. Pretty cut and dried.
Dan
I beg to differ with Laurie; most of the time the decisions are NOT cut and dried. Interpreting data is NOT black or white. Many factors are involved, and decisions have to be made in the context of the inclusion/exclusion criteria, protocol design, statistical analysis plan, the actual data obtained, the ADRs (and opinions of whether they are related to the drug or to the underlying disease) and many more factors. The FDA asks these Advisory Committee members specific questions for consideration that requires more than just the ability to look at numbers and listen to the public. For that, I’d want the biggest experts in the field, and if some have some COI, than as long as it’s disclosed, then the FDA can weigh their input accordingly. To exclude them is to cut off some of the best advise available. Frankly, the public member is a waste of resources; they are there for political purposes…they add next to nothing to the consideration.