Latest Drugwonks' Blog
I have decided to pull together the best of the blog commentary on Nissen's Avandia study:
From the Angry Pharmacist
http://www.theangrypharmacist.com/archives/2007/05/avandia_oh_why.html
From Respectful Insolence..
http://scienceblogs.com/insolence/2007/05/well_well_well_what_have_we_here_about_t_1.php
Kevin MD (who cites Medpage who cites but does not attribute my comparison of the WHI to Avandia risk)
http://www.kevinmd.com/blog/2007/05/avandia-and-heart-attacks.html
Dr. Kevin links to Nissen -- one day after making his Avandia > 9-11 tragedy with this ask and answer with Newsweek:
"Is there a case for prescribing Avandia? Are there some patients for whom the benefits outweigh the risks?
Again, I don’t think I want to go there. It’s important for me as a physician-scientist to put the data out there in a very neutral fashion, and not cast judgment about what people ought to do. We’re going to let everybody read our paper and make up their own minds. Obviously the FDA read our paper because they just issued a safety alert."
What a creep.
http://www.msnbc.msn.com/id/18789572/site/newsweek/
From the Angry Pharmacist
http://www.theangrypharmacist.com/archives/2007/05/avandia_oh_why.html
From Respectful Insolence..
http://scienceblogs.com/insolence/2007/05/well_well_well_what_have_we_here_about_t_1.php
Kevin MD (who cites Medpage who cites but does not attribute my comparison of the WHI to Avandia risk)
http://www.kevinmd.com/blog/2007/05/avandia-and-heart-attacks.html
Dr. Kevin links to Nissen -- one day after making his Avandia > 9-11 tragedy with this ask and answer with Newsweek:
"Is there a case for prescribing Avandia? Are there some patients for whom the benefits outweigh the risks?
Again, I don’t think I want to go there. It’s important for me as a physician-scientist to put the data out there in a very neutral fashion, and not cast judgment about what people ought to do. We’re going to let everybody read our paper and make up their own minds. Obviously the FDA read our paper because they just issued a safety alert."
What a creep.
http://www.msnbc.msn.com/id/18789572/site/newsweek/
Yes, Steve Nissen has sleepless nights about drug safety, particularly about the misuse of surrogate endpoints to approve drugs (which is why he has developed IVUS to develop a surrogate endpoint for drug approval).
And he compares Avandia's risk of death to that of 9-11 (though even his own meta-analysis did not estimate increased number of deaths only risk of having a heart attack sooner and not death).
He tells Diedtra Henderson of the Boston Globe he doesn't want to be FDA commissioner but tells the NYT he won't rule it out.
He uses the "I give all my money to charity" line but there is nothing about the fact the charities are his own research organizations and the Steven E Nissen Healthy Heart fund that doled out gym memberships and travel money to people at the ACC.
He is described as an "informal advisor to Congress" on drug safety. How about someone who coordinated with Congress to preempt the FDA's own analysis of Avandia in order stoke support for alternative FDA reform proposals. Who was working with Congressman Waxman and the NEJM to release his paper, supposedly told a Glaxo rep he was going to "destroy Avandia" but had the chutzpah to claim to the media he offered Glaxo the chance to co-author a paper.
Nissen's behavior with respect to Avandia and the increasing criticism that has been leveled at his "study" (if all the short term data showed a 40 percent increased risk, why is there no hint of it in long term studies like RECORD) were all neglected in the NYT study.
I predict that when all is said and done Nissen will be revealed as the Michael Nifong of medical research.
http://www.nytimes.com/2007/07/22/business/22nissen.html
And he compares Avandia's risk of death to that of 9-11 (though even his own meta-analysis did not estimate increased number of deaths only risk of having a heart attack sooner and not death).
He tells Diedtra Henderson of the Boston Globe he doesn't want to be FDA commissioner but tells the NYT he won't rule it out.
He uses the "I give all my money to charity" line but there is nothing about the fact the charities are his own research organizations and the Steven E Nissen Healthy Heart fund that doled out gym memberships and travel money to people at the ACC.
He is described as an "informal advisor to Congress" on drug safety. How about someone who coordinated with Congress to preempt the FDA's own analysis of Avandia in order stoke support for alternative FDA reform proposals. Who was working with Congressman Waxman and the NEJM to release his paper, supposedly told a Glaxo rep he was going to "destroy Avandia" but had the chutzpah to claim to the media he offered Glaxo the chance to co-author a paper.
Nissen's behavior with respect to Avandia and the increasing criticism that has been leveled at his "study" (if all the short term data showed a 40 percent increased risk, why is there no hint of it in long term studies like RECORD) were all neglected in the NYT study.
I predict that when all is said and done Nissen will be revealed as the Michael Nifong of medical research.
http://www.nytimes.com/2007/07/22/business/22nissen.html
Last week I had the opportunity to speak to a roundtable of Turkish journalists on how the second largest nation in Europe can help to reinvent and reinvigorate its health care system.
We talked about why getting new drugs to market in a timely manner is in the best interest of the public health. We talked about how government-run health care systemts often make the mistake of focusing on cost-based rather than patient-centric care. We talked about the dangers of counterfeiting. We talked about the need to develop better "evidence" for the era of personalized medicine. We talked about the urgent need to design a health care system that stresses prevention and chronic care.
In short, it sounded very much like the health care debate in Europe and the United States.
Except there's one enormous difference -- Turkey, demographically speaking, is a young nation. And that's a terrific opportunity. Rather than focusing on the health care needs of a fast-aging population (as is the case in the US and the EU), Turkey has the chance to "start young and stay healthy" -- avoiding many of the "chronic" problems we now face (diabetes, hypertension, high cholesterol, obesity, etc.)
Turkey has the chance to avoid these health care anchors and show us all how to do it right.
We talked about why getting new drugs to market in a timely manner is in the best interest of the public health. We talked about how government-run health care systemts often make the mistake of focusing on cost-based rather than patient-centric care. We talked about the dangers of counterfeiting. We talked about the need to develop better "evidence" for the era of personalized medicine. We talked about the urgent need to design a health care system that stresses prevention and chronic care.
In short, it sounded very much like the health care debate in Europe and the United States.
Except there's one enormous difference -- Turkey, demographically speaking, is a young nation. And that's a terrific opportunity. Rather than focusing on the health care needs of a fast-aging population (as is the case in the US and the EU), Turkey has the chance to "start young and stay healthy" -- avoiding many of the "chronic" problems we now face (diabetes, hypertension, high cholesterol, obesity, etc.)
Turkey has the chance to avoid these health care anchors and show us all how to do it right.
Take a look at who is board leader in conflict cash for the upcoming Avandia Adcomm.
Steve Nissen is pocketing nearly $1 million in study money from companies that are directly competing AGAINST Avandia. The rest of the folks have stock and speaking fees less than $10K per. In fact, St. Steven the Pure has racked up more conflict cash than the rest of the exemption seeking members combined..
And the media? Why, nary a word on the conflict back when or now even as Steve spins them feverishly in the lead up to Adcomm.
http://www.fda.gov/ohrms/dockets/ac/07/waivers/2007-4308w1-00-index.htm
Steve Nissen is pocketing nearly $1 million in study money from companies that are directly competing AGAINST Avandia. The rest of the folks have stock and speaking fees less than $10K per. In fact, St. Steven the Pure has racked up more conflict cash than the rest of the exemption seeking members combined..
And the media? Why, nary a word on the conflict back when or now even as Steve spins them feverishly in the lead up to Adcomm.
http://www.fda.gov/ohrms/dockets/ac/07/waivers/2007-4308w1-00-index.htm
CMPI held an event yesterday (as noted in my previous post) on Capitol Hill where it released a report entitled “The Effect of Chemotherapy
Innovation on Cancer Survival, 1991-2003: State Level Evidence from the SEERMedicare
Linked Database.†The report written by Dr. Frank R. Lichtenberg of Columbia University and the National Bureau of Economic Research in conjunction with the Center for Medicine in the Public Interest proves that using new cancer therapies is an effective way of lengthening the lives of cancer patients.
But it was more than your usual DC get out the report event. It was time to both celebrate what medical progress can provide and reassert the dying proposition that public policy should focus on what value medicines can add to people lives instead of what money can be squeezed from the lives of patients.
Michael Katz, VP of the International Myeloma Foundation http://www.myeloma.org/ spoke of not being a statistic because as a 17 year survivor of multiple myeloma, he should have been dead and not seen his three children grow and graduate college.
Congressman Mike Ferguson spoke of the joy he felt in hearing Michael's story and of the fact that his mom, who also had multiple myeloma, lived long enough to see her grandchildren. He spoke of the pride and joy he felt knowing that Celgene, the company that has developed a pill replacing blood transfusions for MM, is in his district.
Press events are usually canned activities but because of the people and passion that everyone brought, it was much more. I didn't know when we invited Mike that our event fell on the fourth anniversary of his mom's death. But it only reinforced our sense that CMPI's mission is, in Mike's words, to promote medical progress that saves and extends lives.
Thanks to everyone who made this possible.
Innovation on Cancer Survival, 1991-2003: State Level Evidence from the SEERMedicare
Linked Database.†The report written by Dr. Frank R. Lichtenberg of Columbia University and the National Bureau of Economic Research in conjunction with the Center for Medicine in the Public Interest proves that using new cancer therapies is an effective way of lengthening the lives of cancer patients.
But it was more than your usual DC get out the report event. It was time to both celebrate what medical progress can provide and reassert the dying proposition that public policy should focus on what value medicines can add to people lives instead of what money can be squeezed from the lives of patients.
Michael Katz, VP of the International Myeloma Foundation http://www.myeloma.org/ spoke of not being a statistic because as a 17 year survivor of multiple myeloma, he should have been dead and not seen his three children grow and graduate college.
Congressman Mike Ferguson spoke of the joy he felt in hearing Michael's story and of the fact that his mom, who also had multiple myeloma, lived long enough to see her grandchildren. He spoke of the pride and joy he felt knowing that Celgene, the company that has developed a pill replacing blood transfusions for MM, is in his district.
Press events are usually canned activities but because of the people and passion that everyone brought, it was much more. I didn't know when we invited Mike that our event fell on the fourth anniversary of his mom's death. But it only reinforced our sense that CMPI's mission is, in Mike's words, to promote medical progress that saves and extends lives.
Thanks to everyone who made this possible.
Berenson, not Rodriguez... With his latest piece describing how reimbursement factors create variations in oncology practice that appear delay access to new and in some individual cases, better, cancer drugs. (He calls them market forces, but why quibble.)
This should be a cautionary tale to those in the comparative effectiveness cult: a reimbursement code is as good as a death sentence to thousands of cancer patients if it creates practice variations that delay access to drugs that work for particular groups of patients.
For even more evidence of that, CMPI released study yesterday by Professor Frank Lichtenberg of Columbia University showing a direct association between access to new cancer drugs and increases in life expectancy and survival from cancer between the years 1991-2003. And for those who bleat that we need comparative effectiveness to turn each patient into a cost center consider that Dr. L found that each additional year of cancer free life cost $4300, a fraction of what other economists pegged the value of that achievement: $250k.
You can find the Lichtenberg study later at http://www.cmpi.org
The Berenson piece is here: http://www.nytimes.com/2007/07/14/health/14lymphoma.html?_r=1&oref=slogin
This should be a cautionary tale to those in the comparative effectiveness cult: a reimbursement code is as good as a death sentence to thousands of cancer patients if it creates practice variations that delay access to drugs that work for particular groups of patients.
For even more evidence of that, CMPI released study yesterday by Professor Frank Lichtenberg of Columbia University showing a direct association between access to new cancer drugs and increases in life expectancy and survival from cancer between the years 1991-2003. And for those who bleat that we need comparative effectiveness to turn each patient into a cost center consider that Dr. L found that each additional year of cancer free life cost $4300, a fraction of what other economists pegged the value of that achievement: $250k.
You can find the Lichtenberg study later at http://www.cmpi.org
The Berenson piece is here: http://www.nytimes.com/2007/07/14/health/14lymphoma.html?_r=1&oref=slogin
"Older, cheaper diabetes drugs are as safe and effective as newer ones, concludes an analysis that is good news for diabetics and may further hurt sales of Avandia, a blockbuster pill recently tied to heart problems.
The clear winner: metformin, sold as Glucophage and generically for about $100 a year. It works as well as other diabetes pills but does not cause weight gain or too-low blood sugar, the analysis found. It also lowers LDL or bad cholesterol."
http://news.yahoo.com/s/ap/20070716/ap_on_he_me/diabetes_drugs;_ylt=AjRpOmAY4PhCXhkEvojSg37VJRIF
I guess AP was just reading the press release and not the report or even the exec summary which carried these important tidbits:
The study only focused on monotherapy while the trend in diabetes care is towards combination therapy to maintain glycemic control, blood pressure, cholesterol. Hence, Avandia or Actos will be used in combination with Glucphage or insulin, not one or the other.
The study ignored many important clinical endpoints for which combination therapies are used, hyperinsulinaemia, for instance or fat build up.
The study acknowledges that combo therapy works better than monotherapy.
It also acknowledges that the supposed superiority of weight loss associated with metformin could be due to removing a prior drug used in head to head comparision trials so that the weight loss is an artifact of an experiment not the medicine. Oh.
So why did the authors not make these caveats in their statements to the media and so eager to push metformin as the....cheapest and best? Here is what the authors siad in their article in the Annals of Internal Medicine: Drugs like metformin "lower cost, longer use in practice and more intensive scrutiny in long-term trials" But the trend is towards combination therapy. Do I detect a bias, a falling into line with a ideological bent beyond what the data suggest? Is this ALLHAT and CATIE redux?
http://www.annals.org/cgi/content/full/0000605-200709180-00178v1
The clear winner: metformin, sold as Glucophage and generically for about $100 a year. It works as well as other diabetes pills but does not cause weight gain or too-low blood sugar, the analysis found. It also lowers LDL or bad cholesterol."
http://news.yahoo.com/s/ap/20070716/ap_on_he_me/diabetes_drugs;_ylt=AjRpOmAY4PhCXhkEvojSg37VJRIF
I guess AP was just reading the press release and not the report or even the exec summary which carried these important tidbits:
The study only focused on monotherapy while the trend in diabetes care is towards combination therapy to maintain glycemic control, blood pressure, cholesterol. Hence, Avandia or Actos will be used in combination with Glucphage or insulin, not one or the other.
The study ignored many important clinical endpoints for which combination therapies are used, hyperinsulinaemia, for instance or fat build up.
The study acknowledges that combo therapy works better than monotherapy.
It also acknowledges that the supposed superiority of weight loss associated with metformin could be due to removing a prior drug used in head to head comparision trials so that the weight loss is an artifact of an experiment not the medicine. Oh.
So why did the authors not make these caveats in their statements to the media and so eager to push metformin as the....cheapest and best? Here is what the authors siad in their article in the Annals of Internal Medicine: Drugs like metformin "lower cost, longer use in practice and more intensive scrutiny in long-term trials" But the trend is towards combination therapy. Do I detect a bias, a falling into line with a ideological bent beyond what the data suggest? Is this ALLHAT and CATIE redux?
http://www.annals.org/cgi/content/full/0000605-200709180-00178v1
To see what happens when too many people toady up to for too long and what being imperious does to one's brain cells and personality, read Arnold Relman's screed against Richard Epstein's book "Overdose: How Excessive Government Regulation Stifles Pharmaceuetical Innovation."
To be fair, Epstein lays into Relman in his book, so Arnie is entitled to hit back. But the review is long, boring and short on detail. He never rebuts Epstein's claim. Rather he just screams that Big Pharma buys and sells the FDA and every other major political institution. Well if that's the case, why do so many of their drugs fail to make past FDA reviewers? If the marketing is so successful why not crank out one me too after another and just ram them down the throats of stupid docs and consumers? Why invest in innovation at all? Then the problem of government regulation disappears.
Relman is so obsessed with his droning that he does not realize he has no point. That is the biomarker of a zealot or some other condition.
http://www.tnr.com/doc.mhtml?i=20070723&s=relman072307
To be fair, Epstein lays into Relman in his book, so Arnie is entitled to hit back. But the review is long, boring and short on detail. He never rebuts Epstein's claim. Rather he just screams that Big Pharma buys and sells the FDA and every other major political institution. Well if that's the case, why do so many of their drugs fail to make past FDA reviewers? If the marketing is so successful why not crank out one me too after another and just ram them down the throats of stupid docs and consumers? Why invest in innovation at all? Then the problem of government regulation disappears.
Relman is so obsessed with his droning that he does not realize he has no point. That is the biomarker of a zealot or some other condition.
http://www.tnr.com/doc.mhtml?i=20070723&s=relman072307
Avandia raises good cholesterol and (however it raises bad )while controlling diabetes..how about that? To quote the study... "Pioglitazone and rosiglitazone cause a small but significant increase in high-density lipoprotein, often called "good cholesterol" because it promotes the breakdown and removal of cholesterol from the body." This has been Nissen's holy grail...it must kill him to see it reported in a drug he tried to destroy while others he has worked on have tanked...
And the study which looks at all forms a drugs to control Type 2 diabetes, many of which are used in tandem, is a kick in a teeth to Nissen's sloppy and skewed handling of the data and Furberg's hysterical handling of the results thereof. Now that they two have been added to Adcomm, let's see if they behave responsibly before, during and after the meeting instead of trying to inflame passion. My guess is, on the heels of the AHQR study and a recent microvascular study by Eric Topol and colleagues showing a protective effect impact from Avandia in certain patients with metabolic disorders undergoing revascularization, the black box warning will be mild and some primary care docs might even begin to prescribe again, though not to patients at risk for CHF.
Now let's see how the media covers this study and its rebuke to Nissen.
http://www.ahcpr.gov/news/press/pr2007/effdiabpr.htm
Seel also "Peroxisome proliferator-activated receptor gamma agonists for the Prevention of Adverse events following percutaneous coronary Revascularization--results of the PPAR study."
Am Heart J. 2007 Jul;154(1):137-43.
And the study which looks at all forms a drugs to control Type 2 diabetes, many of which are used in tandem, is a kick in a teeth to Nissen's sloppy and skewed handling of the data and Furberg's hysterical handling of the results thereof. Now that they two have been added to Adcomm, let's see if they behave responsibly before, during and after the meeting instead of trying to inflame passion. My guess is, on the heels of the AHQR study and a recent microvascular study by Eric Topol and colleagues showing a protective effect impact from Avandia in certain patients with metabolic disorders undergoing revascularization, the black box warning will be mild and some primary care docs might even begin to prescribe again, though not to patients at risk for CHF.
Now let's see how the media covers this study and its rebuke to Nissen.
http://www.ahcpr.gov/news/press/pr2007/effdiabpr.htm
Seel also "Peroxisome proliferator-activated receptor gamma agonists for the Prevention of Adverse events following percutaneous coronary Revascularization--results of the PPAR study."
Am Heart J. 2007 Jul;154(1):137-43.
When is a serious side effect not a serious side effect?
When the people who are at risk or talk about it receive support from drug companies.
At least that's what the WSJ implies in it's article about people with epilepsy who suffer seizures when they are switched -- without their consent -- to a generic version of an anti-convulsant to save a few bucks.
PILL PUSH
Industry Fights Switch
To Generics for Epilepsy
Big Drug Makers Help
Patient Groups Lobby;
More Attention to States
By SARAH RUBENSTEIN
In state legislatures across the country, the Epilepsy Foundation has been campaigning for bills that would make it harder for pharmacists to switch patients to inexpensive generic epilepsy pills. The effort is getting behind-the-scenes support from drug companies -- a sign of how the industry, long a potent lobbying force in Washington, is increasingly looking to states to achieve its goals.
http://online.wsj.com/article/SB118426152232264867-search.html?KEYWORDS=epilepsy&COLLECTION=wsjie/6month
I will get to the science behind this issue -- and there is science, though you wouldn't know it from reading the piece -- in a second. But consider this:
The WSJ piece depicts the epilepsy drug switch-side effect issue as anecdot dotted campaign led by Big Pharma to keep their drugs on formulary. Yet Steve Nissen receives money from drug companies and did a slap dash study about heart attack risk of Avandia and that was front page news. He had to pool studies of widely varying quality and size (basically pooling anecdotal information) and he was hailed by the media as a whistleblower.
Now AP reports that the FDA is getting anecdotal reports of heart attacks from Avandia users (no surprise since diabetics are 2x likely to have heart problems than others) and claims that this is evidence of Avandia's dangers previously being under-reported. "Only five heart attacks were reported in the 35 days before the study, compared with 90 in the same period afterward. Heart-related hospitalizations went from 11 to 126. The reports involve rosiglitazone, sold as Avandia and Avandamet."
http://news.yahoo.com/s/ap/20070713/ap_on_he_me/diabetes_drug_risks_8
Now to the evidence of drug switching triggering seizures. Anti-convulsants have very narrow therapeutic windows. So switching, whether from one brand to another or from a brand to a cheaper older med can cause problems. That is fact.
Here is one study "Compulsory generic switching of antiepileptic drugs: high switchback rates to branded compounds compared with other drug classes." Epilepsia. 2007 Mar;48(3):464-9. The study found: These results reflect poor acceptance of switching AEDs (anti-epileptic drugs) to generic compounds. They may also indicate increased toxicity and/or loss of seizure control associated with generic AED use."
So what did we learn class?
Take adverse reports after hysterical reporting of a sloppy and politically motivated meta analysis on Avandia seriously. Why? Not generated by Big Pharma.
Ignore the reports of seizures associated with compulsory drug switching to generic anti convulsants. Why? Obviously generated by Big Pharma.
And what about the scientific basis behind the seizures? Too bad. If someone is supported by Big Pharma, then they obviously deserve to get seizures anyway.
When the people who are at risk or talk about it receive support from drug companies.
At least that's what the WSJ implies in it's article about people with epilepsy who suffer seizures when they are switched -- without their consent -- to a generic version of an anti-convulsant to save a few bucks.
PILL PUSH
Industry Fights Switch
To Generics for Epilepsy
Big Drug Makers Help
Patient Groups Lobby;
More Attention to States
By SARAH RUBENSTEIN
In state legislatures across the country, the Epilepsy Foundation has been campaigning for bills that would make it harder for pharmacists to switch patients to inexpensive generic epilepsy pills. The effort is getting behind-the-scenes support from drug companies -- a sign of how the industry, long a potent lobbying force in Washington, is increasingly looking to states to achieve its goals.
http://online.wsj.com/article/SB118426152232264867-search.html?KEYWORDS=epilepsy&COLLECTION=wsjie/6month
I will get to the science behind this issue -- and there is science, though you wouldn't know it from reading the piece -- in a second. But consider this:
The WSJ piece depicts the epilepsy drug switch-side effect issue as anecdot dotted campaign led by Big Pharma to keep their drugs on formulary. Yet Steve Nissen receives money from drug companies and did a slap dash study about heart attack risk of Avandia and that was front page news. He had to pool studies of widely varying quality and size (basically pooling anecdotal information) and he was hailed by the media as a whistleblower.
Now AP reports that the FDA is getting anecdotal reports of heart attacks from Avandia users (no surprise since diabetics are 2x likely to have heart problems than others) and claims that this is evidence of Avandia's dangers previously being under-reported. "Only five heart attacks were reported in the 35 days before the study, compared with 90 in the same period afterward. Heart-related hospitalizations went from 11 to 126. The reports involve rosiglitazone, sold as Avandia and Avandamet."
http://news.yahoo.com/s/ap/20070713/ap_on_he_me/diabetes_drug_risks_8
Now to the evidence of drug switching triggering seizures. Anti-convulsants have very narrow therapeutic windows. So switching, whether from one brand to another or from a brand to a cheaper older med can cause problems. That is fact.
Here is one study "Compulsory generic switching of antiepileptic drugs: high switchback rates to branded compounds compared with other drug classes." Epilepsia. 2007 Mar;48(3):464-9. The study found: These results reflect poor acceptance of switching AEDs (anti-epileptic drugs) to generic compounds. They may also indicate increased toxicity and/or loss of seizure control associated with generic AED use."
So what did we learn class?
Take adverse reports after hysterical reporting of a sloppy and politically motivated meta analysis on Avandia seriously. Why? Not generated by Big Pharma.
Ignore the reports of seizures associated with compulsory drug switching to generic anti convulsants. Why? Obviously generated by Big Pharma.
And what about the scientific basis behind the seizures? Too bad. If someone is supported by Big Pharma, then they obviously deserve to get seizures anyway.
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.
