Latest Drugwonks' Blog
An excellent commentary from today's edition of the Wall Street Journal ...
Drug Crazy
By RICHARD A. EPSTEIN
In an industry advisory last week, the U.S. Food and Drug Administration announced tough new conflict-of-interest rules against doctors who sit on its advisory committees, which recommend whether the FDA should allow pharmaceutical companies to market their new products. The agency's rationale is that greater transparency is necessary to remove any taint that might undermine the public's confidence in the approval process.
The new rules categorically bar any individual from sitting on any committee to evaluate a drug up for approval when that individual has a financial interest exceeding $50,000. The $50,000 figure includes stock ownership, related research and consulting arrangements. Unfortunately, this measure sweeps too widely by lumping together experts who do clinical trials with those who have a direct economic stake in the success of a drug. The precise measurement of that stake mysteriously turns on the extent that the drug has a "potential for gain or loss" to the committee members or their families. Persons whose financial stakes are less than $50,000 may be allowed to meet with these committees, but not to vote.
The main justification for this new regime is the widespread perception that drug and device makers have "hijacked" the FDA process, allowing dangerous drugs to slip into the market. The most conspicuous illustration involves the various COX-2 inhibitors such as Vioxx and Bextra, when at least 10 members of the FDA advisory panel who voted to leave these drugs on the market had some ties to their respective manufacturers, Merck and Pfizer.
It is here that the difficulties begin. The common perception is that the FDA acted too late in removing these drugs from the marketplace, and indeed should never have approved them at all. That perception rests on a crucial tradeoff: how much of an increased risk of heart attack should people be allowed to run in order to mitigate the ravages of arthritis and other degenerative diseases. One common, but cavalier, notion is that people should learn to cope with pain to stave off the greater potential harm of a heart attack. The evidence on the ground suggests another story.
"Suffering boomers want to fill Vioxx void" is a headline in last Friday's Chicago Tribune. The gist of the story: Baby boomers and others have returned to Pfizer's Celebrex, which reported an 18% increase in sales notwithstanding the FDA's stringent black box warning. Similarly, many individuals stashed away their Vioxx for a rainy day after it was recalled by Merck. These individuals understand the risk they're running, but trust their physicians to minimize its impact.
This evidence should put the FDA's zeal in a new light. Just how do these advisory committees "protect" informed product users by limiting their choices for dealing with crippling chronic conditions?
The FDA's major problem is not laxity, but zealotry. Its current get-tough view on conflict of interest only aggravates the fundamental flaw in its institutional design. Transfixed on the harms drugs can cause, the FDA remains largely oblivious to the harms they can prevent. Any delay in the use of a successful drug is costly: The delay matters little to the FDA, but a great deal to the thousands who plea for compassionate exemptions to try a drug that has not met with FDA approval. Nor is the FDA sensitive, as individual physicians surely are, to the simple fact that a drug which cannot be tolerated by one person works wonders in another.
The current get-tough policy on conflicts of interest only magnifies these costly FDA biases. The agency rules cut out the persons who know most about the drugs, and who could well counter unsound objections by critical committee members. But keeping these experts off the committees also skews the deliberative process in a more subtle and powerful way.
Anyone who consults for drug companies is likely to come with the presumption that new drugs may well fill important therapeutic voids. Once these individuals, as a class, are kept off advisory committees, the remaining drug experts are more likely to have the populist views held by the likes of a Marcia Angell or Sidney Wolfe, who suspiciously view most new drugs as insignificant advances over prior treatments. I tremble at the thought that these "untainted" experts will markedly slow down the FDA approval process. This would be bad news for the tens of millions who suffer from arthritis, and the countless individuals who suffer from other conditions. Nor would a the change go unnoticed by drug manufacturers or venture capitalists.
Right now, we all have a simple expedient to protect ourselves against dangerous drugs that make it to the market: Don't take them. But we have no protection at all when the FDA denies us that choice in the first place. Right now the pace of drug approval is too slow. We don't need the FDA to slow it up still further.
Drug Crazy
By RICHARD A. EPSTEIN
In an industry advisory last week, the U.S. Food and Drug Administration announced tough new conflict-of-interest rules against doctors who sit on its advisory committees, which recommend whether the FDA should allow pharmaceutical companies to market their new products. The agency's rationale is that greater transparency is necessary to remove any taint that might undermine the public's confidence in the approval process.
The new rules categorically bar any individual from sitting on any committee to evaluate a drug up for approval when that individual has a financial interest exceeding $50,000. The $50,000 figure includes stock ownership, related research and consulting arrangements. Unfortunately, this measure sweeps too widely by lumping together experts who do clinical trials with those who have a direct economic stake in the success of a drug. The precise measurement of that stake mysteriously turns on the extent that the drug has a "potential for gain or loss" to the committee members or their families. Persons whose financial stakes are less than $50,000 may be allowed to meet with these committees, but not to vote.
The main justification for this new regime is the widespread perception that drug and device makers have "hijacked" the FDA process, allowing dangerous drugs to slip into the market. The most conspicuous illustration involves the various COX-2 inhibitors such as Vioxx and Bextra, when at least 10 members of the FDA advisory panel who voted to leave these drugs on the market had some ties to their respective manufacturers, Merck and Pfizer.
It is here that the difficulties begin. The common perception is that the FDA acted too late in removing these drugs from the marketplace, and indeed should never have approved them at all. That perception rests on a crucial tradeoff: how much of an increased risk of heart attack should people be allowed to run in order to mitigate the ravages of arthritis and other degenerative diseases. One common, but cavalier, notion is that people should learn to cope with pain to stave off the greater potential harm of a heart attack. The evidence on the ground suggests another story.
"Suffering boomers want to fill Vioxx void" is a headline in last Friday's Chicago Tribune. The gist of the story: Baby boomers and others have returned to Pfizer's Celebrex, which reported an 18% increase in sales notwithstanding the FDA's stringent black box warning. Similarly, many individuals stashed away their Vioxx for a rainy day after it was recalled by Merck. These individuals understand the risk they're running, but trust their physicians to minimize its impact.
This evidence should put the FDA's zeal in a new light. Just how do these advisory committees "protect" informed product users by limiting their choices for dealing with crippling chronic conditions?
The FDA's major problem is not laxity, but zealotry. Its current get-tough view on conflict of interest only aggravates the fundamental flaw in its institutional design. Transfixed on the harms drugs can cause, the FDA remains largely oblivious to the harms they can prevent. Any delay in the use of a successful drug is costly: The delay matters little to the FDA, but a great deal to the thousands who plea for compassionate exemptions to try a drug that has not met with FDA approval. Nor is the FDA sensitive, as individual physicians surely are, to the simple fact that a drug which cannot be tolerated by one person works wonders in another.
The current get-tough policy on conflicts of interest only magnifies these costly FDA biases. The agency rules cut out the persons who know most about the drugs, and who could well counter unsound objections by critical committee members. But keeping these experts off the committees also skews the deliberative process in a more subtle and powerful way.
Anyone who consults for drug companies is likely to come with the presumption that new drugs may well fill important therapeutic voids. Once these individuals, as a class, are kept off advisory committees, the remaining drug experts are more likely to have the populist views held by the likes of a Marcia Angell or Sidney Wolfe, who suspiciously view most new drugs as insignificant advances over prior treatments. I tremble at the thought that these "untainted" experts will markedly slow down the FDA approval process. This would be bad news for the tens of millions who suffer from arthritis, and the countless individuals who suffer from other conditions. Nor would a the change go unnoticed by drug manufacturers or venture capitalists.
Right now, we all have a simple expedient to protect ourselves against dangerous drugs that make it to the market: Don't take them. But we have no protection at all when the FDA denies us that choice in the first place. Right now the pace of drug approval is too slow. We don't need the FDA to slow it up still further.
John Kamp weighs in on the Markey/Waxman bill:
Although I have considerable respect for Congressman Markey, I most of the marketing "improvements," in the new Markey Waxman bill are simply marketing restraints. What an irony that two of the most articulate speakers in the U. S. House of Representatives would use censorship to as a way to help patients learn about the safety aspects of medicine.
Take a careful look at a couple of the restrictions.
1. Clearly an across the board ban on DTC the first three years after a drug's approval would be a violation of the First Amendment. The Supreme Court has never approved censorship as a way to promote an informed population. Even more important, it would be a mistake. What if we have a new drug for bird flu about the time of an outbreak? Wouldn't we want the public to know in every possible way? Similarly, don't we want the public to know about any HPV virus drug that could save the life of hundreds of women? Ignorance is never preferable to education.
2. Mandatory review of the all DTC ads before airing is clearly the kind of "prior restraint" government censorship long banned by English common law and recognized by the Supreme Court as a violation of the First Amendment.
The Coalition for Healthcare Communication salutes companies for taking great care in their ads and following the PhRMA self-regulatory principles. We don't salute Congressmen who would make censorship FDA law. Congress should never force Congressman Markey submit his often pithy remarks to a censor before he is allowed to utter them, nor should Congress silence drug companies until some censor can pass judgment.
It's one thing for a speaker to hold his tongue, it's another for the government to tie it in knots.
Although I have considerable respect for Congressman Markey, I most of the marketing "improvements," in the new Markey Waxman bill are simply marketing restraints. What an irony that two of the most articulate speakers in the U. S. House of Representatives would use censorship to as a way to help patients learn about the safety aspects of medicine.
Take a careful look at a couple of the restrictions.
1. Clearly an across the board ban on DTC the first three years after a drug's approval would be a violation of the First Amendment. The Supreme Court has never approved censorship as a way to promote an informed population. Even more important, it would be a mistake. What if we have a new drug for bird flu about the time of an outbreak? Wouldn't we want the public to know in every possible way? Similarly, don't we want the public to know about any HPV virus drug that could save the life of hundreds of women? Ignorance is never preferable to education.
2. Mandatory review of the all DTC ads before airing is clearly the kind of "prior restraint" government censorship long banned by English common law and recognized by the Supreme Court as a violation of the First Amendment.
The Coalition for Healthcare Communication salutes companies for taking great care in their ads and following the PhRMA self-regulatory principles. We don't salute Congressmen who would make censorship FDA law. Congress should never force Congressman Markey submit his often pithy remarks to a censor before he is allowed to utter them, nor should Congress silence drug companies until some censor can pass judgment.
It's one thing for a speaker to hold his tongue, it's another for the government to tie it in knots.
Today's New York Times editorial page thinks that the FDA should be 100% funded by legislative appropriations. Here we go again.
First, a correction that you will not see in the Gray Lady:
The Times writes that PDUFA fees “help finance the approval process …â€
True, but not accurate. PDUFA fees finance the review process. A trivial, rhetorical difference? Certainly not.
So what’s the big deal where the money comes from? Two big reasons:
(1) Reality. Does anybody even remotely familiar with the funding history of the FDA really believe that Congress is going to fund the agency at anywhere near appropriate levels? Indeed, if history is any guide, the reverse would occur.
(2) Alacrity. With PDUFA fees come PDUFA dates. Is our short-term memory so bad that we have already forgotten the shameful days of the “drug-lag?†Yes, folks – it was real.
And to add to their revisionist view of pharmaceutical regulation, the New York Times agrees with many of the agency’s critics that, if only the FDA worked harder, they could replace “conflicted†advisory committee members with ones equally talented and more pure.
Malarkey.
Ladies and Gentlemen – mediocrity is not an option.
When legislators try to rewrite history we suffer the inevitable consequences.
First, a correction that you will not see in the Gray Lady:
The Times writes that PDUFA fees “help finance the approval process …â€
True, but not accurate. PDUFA fees finance the review process. A trivial, rhetorical difference? Certainly not.
So what’s the big deal where the money comes from? Two big reasons:
(1) Reality. Does anybody even remotely familiar with the funding history of the FDA really believe that Congress is going to fund the agency at anywhere near appropriate levels? Indeed, if history is any guide, the reverse would occur.
(2) Alacrity. With PDUFA fees come PDUFA dates. Is our short-term memory so bad that we have already forgotten the shameful days of the “drug-lag?†Yes, folks – it was real.
And to add to their revisionist view of pharmaceutical regulation, the New York Times agrees with many of the agency’s critics that, if only the FDA worked harder, they could replace “conflicted†advisory committee members with ones equally talented and more pure.
Malarkey.
Ladies and Gentlemen – mediocrity is not an option.
When legislators try to rewrite history we suffer the inevitable consequences.
The first post of our new CMPI fellow ... Marc Siegel MD
The spread of Elizabeth Edwards cancer may provoke the public to many reactions: sympathy, empathy, worry. Surely, we all hope that this unfortunate event won't be grounds for either political gain or loss. Surely, we all hope that any public discussion of cancer spread will be grounds for more cancer awareness and prevention and treatment advances.
It was just last week that I wrote an oped in the WSJ about the importance of diagnosing lung cancer before it escapes the lung. I pointed out the need for effective use of technologically advanced CT scanning for this to happen.
I mentioned breast cancer as an example of another cancer where early detection was important for reduced morbidity and lifestyle advantage, if not survival.
Of course breast cancer is generally not as aggressive and is somewhat more responsive to chemotherapy.
But what Mrs. Edwards case points out is just how treacherous the disease is, and just how expensive and emotionally costly treatments for advanced cancer are.
Metastases to the bone, as Mrs. Edwards has sustained, tend to be somewhat amenable to chemotherapy, so that if not a cure, at least this patient can hope for a long term remission and an effective and happy life.
I do not know the details of Edwards' case, or how it was diagnosed. As we all hope for the best outcome for this public figure, I can't help but hope that many other women have their cancer caught as early as possible, whether by mammogram, or breast exam, or by whatever MRI technology becomes more accessible and useful for breast screening. While we hope for the longest life possible for Mrs. Edwards and those like her who suffer from metastatic cancer, we also hope that expensive treatments for metastatic disease can be avoided as frequently as possible as the result of advances in techniques of early detection.
Marc Siegel MD
Dr. Siegel is a prolific writer, an Associate Professor of Medicine and a Fellow in the Master Scholars Society at New York University School of Medicine, a columnist for the Los Angeles Times, a frequent contributor to the Washington Post and Family Circle. He is a member of the board of contributors at USA Today. He appears frequently on CNN, the Fox News Channel, and the NBC Today Show.
Dr. Siegel's "False Alarm: The Truth About the Epidemic of Fear" has been named one of the "Top Science Books of the Year"
The spread of Elizabeth Edwards cancer may provoke the public to many reactions: sympathy, empathy, worry. Surely, we all hope that this unfortunate event won't be grounds for either political gain or loss. Surely, we all hope that any public discussion of cancer spread will be grounds for more cancer awareness and prevention and treatment advances.
It was just last week that I wrote an oped in the WSJ about the importance of diagnosing lung cancer before it escapes the lung. I pointed out the need for effective use of technologically advanced CT scanning for this to happen.
I mentioned breast cancer as an example of another cancer where early detection was important for reduced morbidity and lifestyle advantage, if not survival.
Of course breast cancer is generally not as aggressive and is somewhat more responsive to chemotherapy.
But what Mrs. Edwards case points out is just how treacherous the disease is, and just how expensive and emotionally costly treatments for advanced cancer are.
Metastases to the bone, as Mrs. Edwards has sustained, tend to be somewhat amenable to chemotherapy, so that if not a cure, at least this patient can hope for a long term remission and an effective and happy life.
I do not know the details of Edwards' case, or how it was diagnosed. As we all hope for the best outcome for this public figure, I can't help but hope that many other women have their cancer caught as early as possible, whether by mammogram, or breast exam, or by whatever MRI technology becomes more accessible and useful for breast screening. While we hope for the longest life possible for Mrs. Edwards and those like her who suffer from metastatic cancer, we also hope that expensive treatments for metastatic disease can be avoided as frequently as possible as the result of advances in techniques of early detection.
Marc Siegel MD
Dr. Siegel is a prolific writer, an Associate Professor of Medicine and a Fellow in the Master Scholars Society at New York University School of Medicine, a columnist for the Los Angeles Times, a frequent contributor to the Washington Post and Family Circle. He is a member of the board of contributors at USA Today. He appears frequently on CNN, the Fox News Channel, and the NBC Today Show.
Dr. Siegel's "False Alarm: The Truth About the Epidemic of Fear" has been named one of the "Top Science Books of the Year"
A taste of the stale debate about Medicare that took -- and will take place -- in Congress. I am so glad I have HBO...
Senator Jon Cornyn sponsored an amendment that would make high income Medicare beneficiaries to pay higher premiums for prescription drugs. It went down in flames.
Not before it got doused by with rhetorical kerosene by Democrat Sen. Sherrod Brown who claimed that Republicans "come to the floor of this chamber ... over and over, from every different direction they attack one of the single greatest programs that this government has ever done."
As opposed to shoving every senior into a VA or Canadian style drug program Senator?
How about enlisting seniors, doctors and others to save Medicare money by not using services and staying healthy? We have taken some steps in that direction but I fear that we are not going to get much traction with Democrats in control...
Senator Jon Cornyn sponsored an amendment that would make high income Medicare beneficiaries to pay higher premiums for prescription drugs. It went down in flames.
Not before it got doused by with rhetorical kerosene by Democrat Sen. Sherrod Brown who claimed that Republicans "come to the floor of this chamber ... over and over, from every different direction they attack one of the single greatest programs that this government has ever done."
As opposed to shoving every senior into a VA or Canadian style drug program Senator?
How about enlisting seniors, doctors and others to save Medicare money by not using services and staying healthy? We have taken some steps in that direction but I fear that we are not going to get much traction with Democrats in control...
Why is it that only some groups need to be transparent? In many of today's news reports on the FDA's new draft guidance on advisory committee conflict of interest some groups are deemed "consumer advocates" -- but no mention is made of their funding sources, while other organizations are quoted, but tagged "industry funded."
Why is this?
For example:
http://www.baltimoresun.com/news/nationworld/bal-te.fda22mar22,0,763576.story?coll=bal-home-headlines
A good story by a solid reporter -- but shouldn't there be transparency for all concerned?
Isn't that the point?
Why is this?
For example:
http://www.baltimoresun.com/news/nationworld/bal-te.fda22mar22,0,763576.story?coll=bal-home-headlines
A good story by a solid reporter -- but shouldn't there be transparency for all concerned?
Isn't that the point?
How about a $50K cap for anyone who has taken money a legal expert in a plaintiffs suit or as a consultant thereof or has received a cut from a personal injury or product liability suit. How about anyone who has received large grants from private foundations or government in excess of that amount?
My prediction: just as you saw an exodus of the best and brightest from the NIH as a result of a restrictive and hyper-reactive cap on consulting to crack down on the appearance of the appearance of a conflict, the same will happen with Advi Comms at the FDA. You will get mediocre, unmotivated or ideologically driven researchers populating committees and using the proceedings to promote their particular positions.
http://online.wsj.com/article/SB110980263395968693.html
My prediction: just as you saw an exodus of the best and brightest from the NIH as a result of a restrictive and hyper-reactive cap on consulting to crack down on the appearance of the appearance of a conflict, the same will happen with Advi Comms at the FDA. You will get mediocre, unmotivated or ideologically driven researchers populating committees and using the proceedings to promote their particular positions.
http://online.wsj.com/article/SB110980263395968693.html
Another smear job on another servant of the public health, Allen Collins, as head of the National Kidney Foundation as part of a INDEPENDENT group of experts developed guidelines to develop EPO levels to a point where people on dialysis lived longer and better lives.
Somehow that never got into the smear job Gardiner Harris did on him...
http://www.nytimes.com/2007/03/21/us/21drug.html?ei=5087%0A&em=&en=1b7a123ccba022cd&ex=1174622400&pagewanted=print
In case anyone is interested in a real contribution to the public health, here a link to the work undertaken by Dr. Collins
http://www.kidney.org/PROFESSIONALS/kdoqi/nkfAdvisory.cfm
Somehow that never got into the smear job Gardiner Harris did on him...
http://www.nytimes.com/2007/03/21/us/21drug.html?ei=5087%0A&em=&en=1b7a123ccba022cd&ex=1174622400&pagewanted=print
In case anyone is interested in a real contribution to the public health, here a link to the work undertaken by Dr. Collins
http://www.kidney.org/PROFESSIONALS/kdoqi/nkfAdvisory.cfm
Here is the link to the relevant documents:
http://www.fda.gov/bbs/topics/NEWS/2007/NEW01591.html
If you are conflicted (either existentially or actually), I grant you a waiver to view these materials.
http://www.fda.gov/bbs/topics/NEWS/2007/NEW01591.html
If you are conflicted (either existentially or actually), I grant you a waiver to view these materials.
I am currently listening to an FDA stakeholder call on a new draft guidance for FDA advisory committee conflict of interest.
Rather than "in" or "out," the agency is suggesting three options:
(1) If an adcomm member has "some" conflicts, they can sit on the committee and participate in the meeting -- but cannot vote.
The FDA did not define what "some" means.
(2) If an adcomm member receives more than $50,000 compensation from a firm in front of an adcomm, they may not sit on the panal, participate in the debate, or vote.
It isn't clear (at least to me) in what period of time this money can be accrued (i.e., $50,000 in a calendar year, or in 12 months prior to the meeting, etc.).
(3) If a panel member has the "appearance" of a conflict they may be recused.
No definition of what "appearance" means. Perhaps this will be clarified in the actual draft guidance.
More as more develops.
Rather than "in" or "out," the agency is suggesting three options:
(1) If an adcomm member has "some" conflicts, they can sit on the committee and participate in the meeting -- but cannot vote.
The FDA did not define what "some" means.
(2) If an adcomm member receives more than $50,000 compensation from a firm in front of an adcomm, they may not sit on the panal, participate in the debate, or vote.
It isn't clear (at least to me) in what period of time this money can be accrued (i.e., $50,000 in a calendar year, or in 12 months prior to the meeting, etc.).
(3) If a panel member has the "appearance" of a conflict they may be recused.
No definition of what "appearance" means. Perhaps this will be clarified in the actual draft guidance.
More as more develops.
Center for Medicine in the Public Interest is a nonprofit, non-partisan organization promoting innovative solutions that advance medical progress, reduce health disparities, extend life and make health care more affordable, preventive and patient-centered. CMPI also provides the public, policymakers and the media a reliable source of independent scientific analysis on issues ranging from personalized medicine, food and drug safety, health care reform and comparative effectiveness.
