Latest Drugwonks' Blog
Re Gardiner Harris' article about the safety reviewers at the FDA (notice he did not mentioned David Graham):
First of all, I think Harris raises one set of important questions. Unfortunately, the analysis is "old school", the idea that FDA has two cultures nonsense that came out of the clueless and conflicted IOM panel (full of folks who failed to disclosed their connections to trial attorneys, Soros, Chubb,)... And ironically he proves his point: you want safety and efficacy to be reviewed at the same time, especially as you develop tools to make drugs more targeted in terms of risk and benefit..
In the wake of Avandia, companies had better wake up and realize that if they do not get ahead of the curve, stop being defensive about drugs, pretend problems don't exist, stop asking questions because they are afraid of the answers, other people will ask and answer those questions anyway. These questions are going to come fast and furious and will not die down after PDUFA is passed and certainly not in a Democrat administration. So companies had better step up their investment in targeting which drugs work best in which people -- to make medicines safer and to respond to a growing movement to impose comparative effectiveness on Medicare.
But people are also interested in life saving medicines. Would Harris - or has Harris -- ever written about the FDA reviewer leaving because a drug that could extend life or help someone suffering from disease -- where was he on Provenge -- as if he or she were a lonely crusader?
Has he ever looked at the scientific evidence surrounding SSRIs or Ketek ), the drug Ketek replaced (in terms of it's side effect profile) or the impact running to Congress and the media has on public fears about drugs or the drug approval process. In other words, is such reporting responsible? We go back to the fact that fewer kids are using SSRIs and that has been associated with an increase in suicides.
Given that most, if not all, safety signals cannot be confirmed, except through biomarkers and post market surveillance or huge randomized trials, what is the consequence of what is Harris effort to carry water for the IOM-trial attorney wing of the drug safety movement..."no signal too small to scuttle a drug approval or require a randomized clinical trial to establish drug safety" . Everyone knows what this will mean to drug development: fewer drugs that -- because companies are forced to do one size fits all post market studies and can't do adaptive trials for approval -- will have fewer targeted drugs on the market. That means more targets for headline seeking pols and tort seeking trial attorneys. It creates a permanent state of fear at the FDA.
To my way of thinking, people like Johann-Lianng, Ross and Graham aren't leaving fast enough...Let them have their 15 minutes of fame griping to Gardiner. And let them be replaced with biologically-based reviewers who don't think it's a sin to work with industry to improve the risk benefit profile of medicines.
The question is, can the NY Times ever run a story on the FDA that covers the safety story from this angle?
http://www.nytimes.com/2007/06/11/washington/11fda.html?pagewanted=2&_r=1&adxnnl=0&adxnnlx=1181564577-4YOVzl9UTftu+7qzVNmnvg
First of all, I think Harris raises one set of important questions. Unfortunately, the analysis is "old school", the idea that FDA has two cultures nonsense that came out of the clueless and conflicted IOM panel (full of folks who failed to disclosed their connections to trial attorneys, Soros, Chubb,)... And ironically he proves his point: you want safety and efficacy to be reviewed at the same time, especially as you develop tools to make drugs more targeted in terms of risk and benefit..
In the wake of Avandia, companies had better wake up and realize that if they do not get ahead of the curve, stop being defensive about drugs, pretend problems don't exist, stop asking questions because they are afraid of the answers, other people will ask and answer those questions anyway. These questions are going to come fast and furious and will not die down after PDUFA is passed and certainly not in a Democrat administration. So companies had better step up their investment in targeting which drugs work best in which people -- to make medicines safer and to respond to a growing movement to impose comparative effectiveness on Medicare.
But people are also interested in life saving medicines. Would Harris - or has Harris -- ever written about the FDA reviewer leaving because a drug that could extend life or help someone suffering from disease -- where was he on Provenge -- as if he or she were a lonely crusader?
Has he ever looked at the scientific evidence surrounding SSRIs or Ketek ), the drug Ketek replaced (in terms of it's side effect profile) or the impact running to Congress and the media has on public fears about drugs or the drug approval process. In other words, is such reporting responsible? We go back to the fact that fewer kids are using SSRIs and that has been associated with an increase in suicides.
Given that most, if not all, safety signals cannot be confirmed, except through biomarkers and post market surveillance or huge randomized trials, what is the consequence of what is Harris effort to carry water for the IOM-trial attorney wing of the drug safety movement..."no signal too small to scuttle a drug approval or require a randomized clinical trial to establish drug safety" . Everyone knows what this will mean to drug development: fewer drugs that -- because companies are forced to do one size fits all post market studies and can't do adaptive trials for approval -- will have fewer targeted drugs on the market. That means more targets for headline seeking pols and tort seeking trial attorneys. It creates a permanent state of fear at the FDA.
To my way of thinking, people like Johann-Lianng, Ross and Graham aren't leaving fast enough...Let them have their 15 minutes of fame griping to Gardiner. And let them be replaced with biologically-based reviewers who don't think it's a sin to work with industry to improve the risk benefit profile of medicines.
The question is, can the NY Times ever run a story on the FDA that covers the safety story from this angle?
http://www.nytimes.com/2007/06/11/washington/11fda.html?pagewanted=2&_r=1&adxnnl=0&adxnnlx=1181564577-4YOVzl9UTftu+7qzVNmnvg
According the NY Post Paris Hilton was ". let go because she was on the verge on a nervous breakdown."
The problem? Inadequate access to appropriate preventive care.
"..Hilton repeatedly pressed a medical-alert button, making herself a major nuisance, inmates said.
The Post quotes a friend: "It's so cruel what has happened to her. She wasn't allowed to wax or use a moisturizer. Her skin is so dry right now!"
If we had universal health care, this would not be a problem..
The problem? Inadequate access to appropriate preventive care.
"..Hilton repeatedly pressed a medical-alert button, making herself a major nuisance, inmates said.
The Post quotes a friend: "It's so cruel what has happened to her. She wasn't allowed to wax or use a moisturizer. Her skin is so dry right now!"
If we had universal health care, this would not be a problem..
Lot of debate going on globally on the subject of compulsory licensing of pharmaceuticals.
Most of the chatter focuses on what's going on in Thailand and Brazil -- but what about Switzerland?
Switzerland? Well, actually to be more specific -- Geneva. And to be even more direct, the World Health Organization (WHO).
The issue at hand is, who's going to make the drugs whose patents have been stolen by Brasilia and Bangkok?
And who's going to certify that these pirated products are safe and effective, manufactured to the highest public health standards?
In many cases, that certification process is handled by the WHO. But, while the WHO does say who passes their GMP tests -- the organization does not say who fails.
According to the folks at WHO, such transparency would deter facilities from applying for certification. That's nonsense. All that allows is for facilities that have failed to gain WHO certification to claim that they have applied for that global imprimatur.
And that allows many substandard facilities to fake it so they can make it. The result -- counterfeit and substandard medications for the less developed world. Not acceptable. Kind of like claiming "patent pending." (But maybe talking about "patents" is a mixed metaphor considering the circumstances.)
(Could you imagine if the FDA only sent out public notification for medicines that the agency approved?)
The folks down in WHOville need to step up to the plate and embrace transparency in their pharmaceutical GMP certification process.
Most of the chatter focuses on what's going on in Thailand and Brazil -- but what about Switzerland?
Switzerland? Well, actually to be more specific -- Geneva. And to be even more direct, the World Health Organization (WHO).
The issue at hand is, who's going to make the drugs whose patents have been stolen by Brasilia and Bangkok?
And who's going to certify that these pirated products are safe and effective, manufactured to the highest public health standards?
In many cases, that certification process is handled by the WHO. But, while the WHO does say who passes their GMP tests -- the organization does not say who fails.
According to the folks at WHO, such transparency would deter facilities from applying for certification. That's nonsense. All that allows is for facilities that have failed to gain WHO certification to claim that they have applied for that global imprimatur.
And that allows many substandard facilities to fake it so they can make it. The result -- counterfeit and substandard medications for the less developed world. Not acceptable. Kind of like claiming "patent pending." (But maybe talking about "patents" is a mixed metaphor considering the circumstances.)
(Could you imagine if the FDA only sent out public notification for medicines that the agency approved?)
The folks down in WHOville need to step up to the plate and embrace transparency in their pharmaceutical GMP certification process.
here's my latest thoughts on the TB patient and what the limited significance of the case is versus the massive importance of TB itself.
This was my Oped in yesterday's Boston Globe.
Flying clear of tuberculosis
By Marc Siegel | June 6, 2007
FOLLOWING the news of Andrew Speaker's honeymoon escapade, where he flew unchecked while harboring a resistant tuberculosis bug, many of my patients have begun to ask me what their risks are of catching TB on a plane. The simple answer I give them is "extremely low." Big HEPA filters screen out more than 99 percent of viral and bacterial particles, including tuberculosis. The risk of Speaker infecting another passenger when he reportedly wasn't coughing, had no fever, and was receiving some treatment is probably less than 1 percent. The chance of an actual case of serious TB resulting from this exposure is even less than that, as there has not yet been a single case of active tuberculosis found to be the result of exposure on a plane.
Speaker suffers from the extensively drug resistant kind of tuberculosis, which is quite rare, with only 49 cases reported in the United States since 1993. TB itself is common, infecting one-third of the world's population, with more than 8 million people getting sick from it every year. Even with billions of airplane passengers every year, the plane is an unlikely place for TB transmission. There have been several small studies that have followed exposure to active TB on planes. From 1992 to 1994, the Centers for Disease Control and Prevention followed six passengers and a crew member who had TB in their sputum and exhibited active symptoms. Of the 2,600 contacts of these TB patients (two were deliberately flying without alerting the airline, the other five didn't know they had TB), only a few people showed subsequent transmission of TB and none got sick.
These patients were not only much sicker than Speaker, they were spewing TB in their sputum. The gold standard of transmissibility is the presence of the tuberculosis bacillus in the sputum or mucous of a patient. Speaker has been tested repeatedly, and his mucous is clear.
I have worked on the Chest Service of Bellevue Hospital where Speaker was briefly interned. It is routine practice for doctors there to remove masks and allow patients to roam the ward and even go home once their mucous tests negative. Speaker was no different. Isolation only became necessary once it was determined that his TB was so resistant that none of the standard treatments work for it. The fact that his brand of TB is so difficult to cure makes it that much more important to prevent spread even to a single person.
Speaker's case is a wakeup call for improved patient compliance. TB drug resistance is a growing problem, in part due to patients stopping their medicines partway through the treatment. It is often the same patients who don't take their medicines who also don't exercise the proper caution and put others at some risk. This is a good time for public health to employ more advanced genetic techniques to detect all drug resistance earlier and then restrict travel on an as-needed basis.
It is also a good time for public health officials to learn to communicate risk through facts rather than fear. Because of media dramatizations of rare killers, we tend to overpersonalize the dangers of the latest mystery bacteria or virus. Worldwide, tuberculosis itself is well worth being afraid of, but the numbers in the United States are much lower (14,000 cases per year). Americans fear it more now because of the hype, much as we once feared anthrax, smallpox, Mad Cow Disease, bird flu, and SARS. It is human nature to fear the unknown, but it is not good science.
Our civil rights should protect us from excess scrutiny every time we board a plane. But fear and distrust tend to erode these rights, which is why it is so important that we draw the right conclusions from the Speaker case.
Tuberculosis, a tiny hook-shaped airborne bacteria, is transmitted by deep coughing and prolonged exposure. Initial infections are generally very mild and TB goes on to cause significant disease in only 5 percent of cases, many of whom suffer from HIV or other chronic diseases.
More than 2 billion passengers fly on planes every year, but there has yet to be a documented case of someone getting sick with TB from an airplane exposure. Though TB kills close to 2 million people per year worldwide and cannot be trivialized, the more important lesson from Speaker is about public and media overreaction to remote risks.
This was my Oped in yesterday's Boston Globe.
Flying clear of tuberculosis
By Marc Siegel | June 6, 2007
FOLLOWING the news of Andrew Speaker's honeymoon escapade, where he flew unchecked while harboring a resistant tuberculosis bug, many of my patients have begun to ask me what their risks are of catching TB on a plane. The simple answer I give them is "extremely low." Big HEPA filters screen out more than 99 percent of viral and bacterial particles, including tuberculosis. The risk of Speaker infecting another passenger when he reportedly wasn't coughing, had no fever, and was receiving some treatment is probably less than 1 percent. The chance of an actual case of serious TB resulting from this exposure is even less than that, as there has not yet been a single case of active tuberculosis found to be the result of exposure on a plane.
Speaker suffers from the extensively drug resistant kind of tuberculosis, which is quite rare, with only 49 cases reported in the United States since 1993. TB itself is common, infecting one-third of the world's population, with more than 8 million people getting sick from it every year. Even with billions of airplane passengers every year, the plane is an unlikely place for TB transmission. There have been several small studies that have followed exposure to active TB on planes. From 1992 to 1994, the Centers for Disease Control and Prevention followed six passengers and a crew member who had TB in their sputum and exhibited active symptoms. Of the 2,600 contacts of these TB patients (two were deliberately flying without alerting the airline, the other five didn't know they had TB), only a few people showed subsequent transmission of TB and none got sick.
These patients were not only much sicker than Speaker, they were spewing TB in their sputum. The gold standard of transmissibility is the presence of the tuberculosis bacillus in the sputum or mucous of a patient. Speaker has been tested repeatedly, and his mucous is clear.
I have worked on the Chest Service of Bellevue Hospital where Speaker was briefly interned. It is routine practice for doctors there to remove masks and allow patients to roam the ward and even go home once their mucous tests negative. Speaker was no different. Isolation only became necessary once it was determined that his TB was so resistant that none of the standard treatments work for it. The fact that his brand of TB is so difficult to cure makes it that much more important to prevent spread even to a single person.
Speaker's case is a wakeup call for improved patient compliance. TB drug resistance is a growing problem, in part due to patients stopping their medicines partway through the treatment. It is often the same patients who don't take their medicines who also don't exercise the proper caution and put others at some risk. This is a good time for public health to employ more advanced genetic techniques to detect all drug resistance earlier and then restrict travel on an as-needed basis.
It is also a good time for public health officials to learn to communicate risk through facts rather than fear. Because of media dramatizations of rare killers, we tend to overpersonalize the dangers of the latest mystery bacteria or virus. Worldwide, tuberculosis itself is well worth being afraid of, but the numbers in the United States are much lower (14,000 cases per year). Americans fear it more now because of the hype, much as we once feared anthrax, smallpox, Mad Cow Disease, bird flu, and SARS. It is human nature to fear the unknown, but it is not good science.
Our civil rights should protect us from excess scrutiny every time we board a plane. But fear and distrust tend to erode these rights, which is why it is so important that we draw the right conclusions from the Speaker case.
Tuberculosis, a tiny hook-shaped airborne bacteria, is transmitted by deep coughing and prolonged exposure. Initial infections are generally very mild and TB goes on to cause significant disease in only 5 percent of cases, many of whom suffer from HIV or other chronic diseases.
More than 2 billion passengers fly on planes every year, but there has yet to be a documented case of someone getting sick with TB from an airplane exposure. Though TB kills close to 2 million people per year worldwide and cannot be trivialized, the more important lesson from Speaker is about public and media overreaction to remote risks.
In case you didn't see it in many press accounts, here's some of the exchanges between Steve Nissen and members of the House Oversight Committee
Patrick McHenry, R-N.C.: At what point did you begin your conversations
with
Chairman Waxman and his staff?
Steven Nissen: In February, I had looked at the DREAM and the ADOPT
study,
but I didn't have enough information actually to answer the question
scientifically. ...At the time, I was discussing with various
congressional
committees the pending legislation around the similar version of the
Kennedy/Enzi bill on the House side, and so I mentioned to them I had
concerns about the cardiovascular safety of Avandia. And I actually
requested their assistance in getting access to the data. I had
essentially
a scientific mystery: I didn't have the means to answer the question in
a
robust scientific way, and I really was looking for help.
McHenry: Did you provide your interim analysis to any member of the
Hill or
staff?
Nissen: There were no interim results. Basically what we had done was a
very
preliminary analysis - nothing formal...
McHenry: Did you provide a preliminary analysis?
Nissen: Yes.
McHenry: At what point did you have that and did you share it with Mr.
Waxman's staff?
Nissen: The same time - February.
McHenry: So they were aware you were going through the process?
Nissen: They were aware.
McHenry: Why didn't you discuss your preliminary analysis with the Food
and
Drug Administration?
Nissen: The Food and Drug Administration had all of these studies on
record.
When you do a study, you submit a study report to the FDA.
McHenry: But you were actually submitting to a medical journal a new
study.
...You proffer your work as original do you not?
Nissen: It is original.
McHenry: Then why didn't you share that study with the Food and Drug
Administration? After all, as members of Congress we have a regulatory
structure we put in place for drug safety. Why didn't you go to the
FDA?
Nissen: This is not how it's done.
McHenry: So, going to Capitol Hill for political purpose to get
publicity
during a hearing is actually the way it is done?
Nissen: With all due respect, sir, this is about patients, and it's not
about politics....
McHenry: If it is about patients, why would you not go to the regulator
who
has the authority and oversight of drug safety?
Nissen: This is about patients - not politics. I had a preliminary
result. I
was looking for assistance to complete the study. When it was
completed, I
did what any scientist would do. I sent that for peer review and for
publication.
McHenry: What peers do you have on the Oversight and Government Reform
staff
- the Democrat staff? Because you shared your findings with them. Is
that
what you consider peer review? Is that what you consider putting
patients
above politics?
Nissen: I did not give out my manuscript to this committee or anybody
else
until it was published.
McHenry: It seems very peculiar to me that if you are considering the
patients first that you not go to the regulator who is overseeing drug
safety, that you would go to Capitol Hill ... and we don't have any
authority to take a drug off the market like the FDA does.
Nissen: The regulatory agency had all of the data that I had and much,
much
more. ...It made no sense for me to take study-level data and submit it
to
the FDA when they already had the patient-level data. So I would not
have
given them anything they hadn't had for many, many months.
Elijah Cummings, D-Md.: I hate that we have to make these accusations
that
people [are] putting politics over the health of the American people.
That
bothers me. ...Dr. Buse and Dr. Psaty you've heard this line of
questioning.
You've heard what Dr. Nissen has said. Do you all have any issues with
the
professionalism that he has [exhibited] doing what he has done to get
this
information published?
John Buse, University of North Carolina: I have no issues at all, and I
think he did a nice job of organizing data and setting out that it was
imperfect but important for people hear about.
Patrick McHenry, R-N.C.: At what point did you begin your conversations
with
Chairman Waxman and his staff?
Steven Nissen: In February, I had looked at the DREAM and the ADOPT
study,
but I didn't have enough information actually to answer the question
scientifically. ...At the time, I was discussing with various
congressional
committees the pending legislation around the similar version of the
Kennedy/Enzi bill on the House side, and so I mentioned to them I had
concerns about the cardiovascular safety of Avandia. And I actually
requested their assistance in getting access to the data. I had
essentially
a scientific mystery: I didn't have the means to answer the question in
a
robust scientific way, and I really was looking for help.
McHenry: Did you provide your interim analysis to any member of the
Hill or
staff?
Nissen: There were no interim results. Basically what we had done was a
very
preliminary analysis - nothing formal...
McHenry: Did you provide a preliminary analysis?
Nissen: Yes.
McHenry: At what point did you have that and did you share it with Mr.
Waxman's staff?
Nissen: The same time - February.
McHenry: So they were aware you were going through the process?
Nissen: They were aware.
McHenry: Why didn't you discuss your preliminary analysis with the Food
and
Drug Administration?
Nissen: The Food and Drug Administration had all of these studies on
record.
When you do a study, you submit a study report to the FDA.
McHenry: But you were actually submitting to a medical journal a new
study.
...You proffer your work as original do you not?
Nissen: It is original.
McHenry: Then why didn't you share that study with the Food and Drug
Administration? After all, as members of Congress we have a regulatory
structure we put in place for drug safety. Why didn't you go to the
FDA?
Nissen: This is not how it's done.
McHenry: So, going to Capitol Hill for political purpose to get
publicity
during a hearing is actually the way it is done?
Nissen: With all due respect, sir, this is about patients, and it's not
about politics....
McHenry: If it is about patients, why would you not go to the regulator
who
has the authority and oversight of drug safety?
Nissen: This is about patients - not politics. I had a preliminary
result. I
was looking for assistance to complete the study. When it was
completed, I
did what any scientist would do. I sent that for peer review and for
publication.
McHenry: What peers do you have on the Oversight and Government Reform
staff
- the Democrat staff? Because you shared your findings with them. Is
that
what you consider peer review? Is that what you consider putting
patients
above politics?
Nissen: I did not give out my manuscript to this committee or anybody
else
until it was published.
McHenry: It seems very peculiar to me that if you are considering the
patients first that you not go to the regulator who is overseeing drug
safety, that you would go to Capitol Hill ... and we don't have any
authority to take a drug off the market like the FDA does.
Nissen: The regulatory agency had all of the data that I had and much,
much
more. ...It made no sense for me to take study-level data and submit it
to
the FDA when they already had the patient-level data. So I would not
have
given them anything they hadn't had for many, many months.
Elijah Cummings, D-Md.: I hate that we have to make these accusations
that
people [are] putting politics over the health of the American people.
That
bothers me. ...Dr. Buse and Dr. Psaty you've heard this line of
questioning.
You've heard what Dr. Nissen has said. Do you all have any issues with
the
professionalism that he has [exhibited] doing what he has done to get
this
information published?
John Buse, University of North Carolina: I have no issues at all, and I
think he did a nice job of organizing data and setting out that it was
imperfect but important for people hear about.
SO many things of interest from yesterday's House Oversight hearing, but by far the most memorable one was Dr. Steven Nissen answering a direct question with a direct answer.
The question was "Would you tell doctors to stop prescribing Avandia." And his answer was "No."
Indeed, the good doctor made the point that prescribing decisions should be made by a doctor in consultation with his patient and based on the available information.
We agree. It was a considered and measured response -- and under oath.
And we were surprised -- considering that it came from the same guy who a few evenings earlier on Nightline compared Avandia to "9-11."
We don't agree about that. It was a response considered and measured to maximize media coverage.
The take-away here is that there's too much hyperbole and hysteria out there right now -- and none of it's beneficial to anything other than politics. Scaring patients and physicians makes nothing safer. (Unfortunatly, it makes for terrific headlines.)
When it comes to advancing the public health, better to rely on 4-1-1 than 9-11.
The question was "Would you tell doctors to stop prescribing Avandia." And his answer was "No."
Indeed, the good doctor made the point that prescribing decisions should be made by a doctor in consultation with his patient and based on the available information.
We agree. It was a considered and measured response -- and under oath.
And we were surprised -- considering that it came from the same guy who a few evenings earlier on Nightline compared Avandia to "9-11."
We don't agree about that. It was a response considered and measured to maximize media coverage.
The take-away here is that there's too much hyperbole and hysteria out there right now -- and none of it's beneficial to anything other than politics. Scaring patients and physicians makes nothing safer. (Unfortunatly, it makes for terrific headlines.)
When it comes to advancing the public health, better to rely on 4-1-1 than 9-11.
China said late Tuesday that it was overhauling its food and drug safety regulations and would introduce nationwide inspections.
According to the New York Times, “The announcement, from the State Council, the nation’s highest administrative body, is the strongest signal yet that Beijing is moving to crack down on the sale of dangerous food and medicine and trying to calm fears that some of its exports pose health problems.
The government said in its announcement that it planned by 2010 to place new controls on food and drug imports and exports and to step up random testing on medicines. It also said that it would have information on inspections of 90 percent of all food products, although it was unclear how that would work.
Food and drug safety experts have complained for years about a flawed system that has led to food scares or mass poisonings tied to counterfeit or substandard medicines on the market.â€
Here’s a link to the complete article:
http://www.nytimes.com/2007/06/07/business/worldbusiness/07safety.html?hp
If our political leaders are truly concerned about drug safety (as so many are and as many others claim to be) we should hold China’s feet to the fire and make sure these reforms (which sound good) are implemented – and with alacrity.
According to the New York Times, “The announcement, from the State Council, the nation’s highest administrative body, is the strongest signal yet that Beijing is moving to crack down on the sale of dangerous food and medicine and trying to calm fears that some of its exports pose health problems.
The government said in its announcement that it planned by 2010 to place new controls on food and drug imports and exports and to step up random testing on medicines. It also said that it would have information on inspections of 90 percent of all food products, although it was unclear how that would work.
Food and drug safety experts have complained for years about a flawed system that has led to food scares or mass poisonings tied to counterfeit or substandard medicines on the market.â€
Here’s a link to the complete article:
http://www.nytimes.com/2007/06/07/business/worldbusiness/07safety.html?hp
If our political leaders are truly concerned about drug safety (as so many are and as many others claim to be) we should hold China’s feet to the fire and make sure these reforms (which sound good) are implemented – and with alacrity.
Here's Rita Rubin about the chain of events leading up to the black box warning about congestive heart failure and PPARs at the FDA:
"Grassley, whose office released the letter Wednesday, asked von Eschenbach to respond to allegations that Johann-Liang had been reprimanded for agreeing with her staff's recommendation that Avandia needed a black-box warning about congestive heart failure and stronger warnings about macular edema, a serious eye condition."
Let's be clear about who Johann-Liang is and her history. She is the same person who was selectively leaking stuff to Grassley on Ketek and recommended pulling the drug altogether. Her actions and dalliance with Grassley's staff have led delays and increased costs in antibiotic research. Her demand for a black box was in advance of both the Glaxo meta analysis, the DREAM results and the RECORD study. And both Takeda and Actos had previously sent out letters to prescribers warning about the elevated risks of their drugs to patients with a history of heart failure.
"The FDA, which had received data from Glaxo last August suggesting a 30% increased risk of heart attacks in Avandia users, did not alert patients and doctors about that possibility until Steven Nissen, chair of cardiovascular medicine at the Cleveland Clinic, reported a similar finding, posted May 21 on The New England Journal of Medicine's website."
The facts are that the FDA had been working on this issue well in advance of the NIssen article -- as Nissen himself admitted in his testimony. Nissen's article was timed to pre-empt a pending FDA decision.
Rita again: " Glaxo should have begun enrolling high-risk diabetes patients in a large, long-term study when Avandia was approved in 1999. By now, Nissen said, the results would be in."
In fact, Glaxo did begin enrolling "high-risk diabetes patients in large long term study when Avandia was approved in 1999." It was called the DREAM study. It looked at heart problems as a secondary endpoint and was expected to have it's data blended with other studies looking at heart safety since the sample size alone was considered to be underpowered to determine RARE risks.
That's how safety signals are validated today in the absence of new IT and genomic tools. We could do it faster, better, more personalized and predictive.
Which is why Andy Von E kept on calling for more resources, not more authority to improve post market surveillance.
That's the rest of the story.
"Grassley, whose office released the letter Wednesday, asked von Eschenbach to respond to allegations that Johann-Liang had been reprimanded for agreeing with her staff's recommendation that Avandia needed a black-box warning about congestive heart failure and stronger warnings about macular edema, a serious eye condition."
Let's be clear about who Johann-Liang is and her history. She is the same person who was selectively leaking stuff to Grassley on Ketek and recommended pulling the drug altogether. Her actions and dalliance with Grassley's staff have led delays and increased costs in antibiotic research. Her demand for a black box was in advance of both the Glaxo meta analysis, the DREAM results and the RECORD study. And both Takeda and Actos had previously sent out letters to prescribers warning about the elevated risks of their drugs to patients with a history of heart failure.
"The FDA, which had received data from Glaxo last August suggesting a 30% increased risk of heart attacks in Avandia users, did not alert patients and doctors about that possibility until Steven Nissen, chair of cardiovascular medicine at the Cleveland Clinic, reported a similar finding, posted May 21 on The New England Journal of Medicine's website."
The facts are that the FDA had been working on this issue well in advance of the NIssen article -- as Nissen himself admitted in his testimony. Nissen's article was timed to pre-empt a pending FDA decision.
Rita again: " Glaxo should have begun enrolling high-risk diabetes patients in a large, long-term study when Avandia was approved in 1999. By now, Nissen said, the results would be in."
In fact, Glaxo did begin enrolling "high-risk diabetes patients in large long term study when Avandia was approved in 1999." It was called the DREAM study. It looked at heart problems as a secondary endpoint and was expected to have it's data blended with other studies looking at heart safety since the sample size alone was considered to be underpowered to determine RARE risks.
That's how safety signals are validated today in the absence of new IT and genomic tools. We could do it faster, better, more personalized and predictive.
Which is why Andy Von E kept on calling for more resources, not more authority to improve post market surveillance.
That's the rest of the story.
From the Food and Drug Letter...
Senate Passes PDUFA Reauthorization Bill
The Senate passed a bill to reauthorize the Prescription Drug User Fee Act (PDUFA) after adding an amendment to increase penalties for noncompliant drugmakers and narrowly rejecting two amendments that would have augmented other safety regulations in the bill.
We will see if certain senators have the stomach for their own show trial after Dr. Nissen's embarassing performance today.
Senate Passes PDUFA Reauthorization Bill
The Senate passed a bill to reauthorize the Prescription Drug User Fee Act (PDUFA) after adding an amendment to increase penalties for noncompliant drugmakers and narrowly rejecting two amendments that would have augmented other safety regulations in the bill.
We will see if certain senators have the stomach for their own show trial after Dr. Nissen's embarassing performance today.
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