A conversation has been going on recently on the Healthy Skepticism list-serv about how hard or how easy it is for physicians to stay up to date on new drugs and therapeutics without relying on sources that are controlled or heavily influenced by the pharmaceutical and device industries and their marketing juggernauts. Dr. Mark McConnell, who practices internal medicine in LaCrosse, WI, offered a set of highly practical tips that seemed too good not to share with all readers. He's given me permission to reproduce his how-to list, to which I have just a couple of additional suggestions.
Dr. McConnell states that by adhering to his program the necessary investment of time needed to stay reasonably informed and up to date is about 5-10 hours per month. (Like anything else, I'll add, when you just begin to start using any of these sources, it will take a bit longer; once you become used to how each works and where to locate the information you need, your time will shrink.) Dr. McConnell notes that he does not have a specific set-aside budget for CME and so he uses his own funds for these programs and sources.
His core resources:
Oakstone's Practical Reviews in internal medicine
$400/year
http://www.cmeonly.com/ME2/Audiences/dirmod.asp?sid=169BFEB1B46447C79F7F4D0B70D0253B&nm=Product+Catalog&type=Commerce&mod=GenComJournals&mid=63594F04C705480CA3E0A9BAAEE18D0E&AudId=920904C7329349CDA12AB2FB770606B1&tier=3&id=908141712AE34A799974F093EB52E0E6
InfoPOEMs from Essential Evidence Plus
$79/year
http://www.essentialevidenceplus.com/index.cfm
Therapeutic Initiatives Drug Therapy review course
$1000/year
http://www.ti.ubc.ca/node/14
Prescriber's Letter
$88/year
http://www.prescribersletter.com/(S(izxxzx45ukr2sobec3nt2sym))/home.aspx?cs=&s=PRL
I just have two additional resources to comment on. One is a service that provides a monthly CD with an audio presentation and evidence-based discussion of 40 recent articles pertinent to primary care, along with a database that allows you to store all 40 abstracts each month on your computer and later search them--Primary Care Medical Abstracts, http://www.ccme.org/PCMA/index-frame.html, $279/year. Rick Bukatra and Jerry Hoffman present, discuss, and argue about the abstracts in a manner somewhat reminiscent of "Car Talk" on NPR.
Second, I have been a long-time satisfied subscriber of The Medical Letter, http://www.medicalletter.org/, $98/year. This is supposed to be the Granddaddy of all U.S. non-commercially-sponsored publications on therapeutics, having been founded in 1959. The Medical Letter was being criticized on the HS list for not being truly independent and for allowing companies to review its assessments of their drugs. All I can say in defense of my longstanding use of this source (when I was in practice, which I am not currently) is that the publication hardly ever endorses a new drug, and most often says that a new drug is really no better than an older drug. The few times I have mentioned this publication to a drug rep, he has pooh-poohed it vigorously and given me numerous reasons why I should pay no attention. So if the drug companies are allowed to see the reviews, it does not appear that they have much influence over what is eventually published. I'd appreciate more discussion of this in the Comments.
None of the above sources accept ads from industry.
Monday, March 8, 2010
Tuesday, February 23, 2010
Internal Medicine Residencies and Pharma Money: We Don't Like It but We Take It
Duff Wilson in the New York Times:
http://www.nytimes.com/2010/02/23/business/23docs.html
--offered a handy synopsis of a paper by Dr. Laura L. Loertscher and colleagues (subscription required to access). The Association of Program Directors in Internal Medicine (residency program directors) conducted a survey of their members. A little more than half, 55.9% reported receiving some form of money from the pharmaceutical industry; the most common item funded was food for lunch conferences (90%). A wide majority (72.0%) of the directors disapproved of taking these funds, but were swayed especially by the popularity of these benes among the residents (40%), as well as by a general sense of the lack of alternative funding sources. The authors remarked that overall this represents an improvement over a 1990 survey that showed 88.6% of residencies taking money.
The surveyers next tried to correlate one measure of a residency's quality, the percentage of residents who pass the Board exam, with taking Pharma money, and found a direct inverse correlation--the worse the residency, the more likely it was to accept Pharma money. (One has to wonder whether if this word gets around, "drug lunches" will still be such a popular item among the residents.)
Wilson's article in the Times noted that the Accreditation Council for Graduate Medical Education has the authority to end this practice instantly by fiat. The authors, like good internists, did not make such a suggestion, but rather called for more research.
Loertscher LL, Halvorsen AJ, Beasley BW, et al. Pharmaceutical industry support and residency education: a survey of internal medicine program directors. Archives of Internal Medicine 170:356-62, Feb. 22, 2010.
http://www.nytimes.com/2010/02/23/business/23docs.html
--offered a handy synopsis of a paper by Dr. Laura L. Loertscher and colleagues (subscription required to access). The Association of Program Directors in Internal Medicine (residency program directors) conducted a survey of their members. A little more than half, 55.9% reported receiving some form of money from the pharmaceutical industry; the most common item funded was food for lunch conferences (90%). A wide majority (72.0%) of the directors disapproved of taking these funds, but were swayed especially by the popularity of these benes among the residents (40%), as well as by a general sense of the lack of alternative funding sources. The authors remarked that overall this represents an improvement over a 1990 survey that showed 88.6% of residencies taking money.
The surveyers next tried to correlate one measure of a residency's quality, the percentage of residents who pass the Board exam, with taking Pharma money, and found a direct inverse correlation--the worse the residency, the more likely it was to accept Pharma money. (One has to wonder whether if this word gets around, "drug lunches" will still be such a popular item among the residents.)
Wilson's article in the Times noted that the Accreditation Council for Graduate Medical Education has the authority to end this practice instantly by fiat. The authors, like good internists, did not make such a suggestion, but rather called for more research.
Loertscher LL, Halvorsen AJ, Beasley BW, et al. Pharmaceutical industry support and residency education: a survey of internal medicine program directors. Archives of Internal Medicine 170:356-62, Feb. 22, 2010.
NPR: More Details on the Obama-PhRMA Back Room Deal
A while back we noted the possible connection between Billy Tauzin's departure as president of PhRMA and the deal the lobbying organization made with the Obama White House over health reform legislation:
http://brodyhooked.blogspot.com/2010/02/departure-of-two-million-dollar-man.html
Anyone wanting more details about this deal should check out the NPR Fresh Air story:
http://www.npr.org/templates/story/story.php?storyId=123889454&ft=1&f=1027
(Note: The NPR link has additional links to source materials)
Paul Blumenthal, a writer for a nonprofit open-government group, documented a series of meetings between Tauzin and major drug company CEOs, on one side, and Obama chief of staff Rahm Emanuel and his deputy Jim Messina on the other. They cut a deal with the following features:
The deal became public knowledge in the late summer when Tauzin started to fear that Obama might be pulling back, and leaked the deal to the press. That led the White House to admit the deal two days later. Blumenthal reconstructed who came to the meetings from the White House visitors log which the Obama administration, for the first time, has made public.
Blumenthal offered as his take on Tauzin's resignation that PhRMA was upset because it spent the $150M on ads and has no bill to show for it. He added that at present, PhRMA stands to make out like bandits if some type of health reform similar to the Senate bill becomes law. Millions more Americans will be insured and able to afford to buy their products, and to pay top dollar for the privilege. As we noted in a previous post, the drug firms have already jacked up their prices of brand-name drugs to the tune of a $100B increase over the next decade, effectively cancelling out the promised $80B price savings.
http://brodyhooked.blogspot.com/2010/02/big-pharmas-sacrifice-for-health-reform.html
Bottom line-- if you're a political cynic and expect health reform to be done according to the age-old Washington formula, you're not surprised to see this particular brand of sausage being made. You can defend your cynicism by noting that at this point, health reform has come closer to passage under Obama's watch than it has in the past century, so he must be doing something right. If you were hoping that Obama would, as promised, change the way Washington does business, you have to be somewhat disappointed.
http://brodyhooked.blogspot.com/2010/02/departure-of-two-million-dollar-man.html
Anyone wanting more details about this deal should check out the NPR Fresh Air story:
http://www.npr.org/templates/story/story.php?storyId=123889454&ft=1&f=1027
(Note: The NPR link has additional links to source materials)
Paul Blumenthal, a writer for a nonprofit open-government group, documented a series of meetings between Tauzin and major drug company CEOs, on one side, and Obama chief of staff Rahm Emanuel and his deputy Jim Messina on the other. They cut a deal with the following features:
- PhRMA would pay for $150 million in ads favoring health reform (the ads appeared as sponsored by a coalition of organizations and PhRMA funding was not clearly labeled).
- PhRMA would agree to back Obama's efforts overall, and also to forgo $80B in potential profits over the next decade to support reform.
- Obama would eliminate from any final bill the cost-cutting measures PhRMA most feared-- allowing reimportations of cheaper drugs from canada, and using government mass purchasing power to negituiate lower prices.
- The deal would be made around the draft bill being prepared by Max Baucus's Senate Finance Committee; the House committees and other Senate committees working on reform legislation were cut out.
The deal became public knowledge in the late summer when Tauzin started to fear that Obama might be pulling back, and leaked the deal to the press. That led the White House to admit the deal two days later. Blumenthal reconstructed who came to the meetings from the White House visitors log which the Obama administration, for the first time, has made public.
Blumenthal offered as his take on Tauzin's resignation that PhRMA was upset because it spent the $150M on ads and has no bill to show for it. He added that at present, PhRMA stands to make out like bandits if some type of health reform similar to the Senate bill becomes law. Millions more Americans will be insured and able to afford to buy their products, and to pay top dollar for the privilege. As we noted in a previous post, the drug firms have already jacked up their prices of brand-name drugs to the tune of a $100B increase over the next decade, effectively cancelling out the promised $80B price savings.
http://brodyhooked.blogspot.com/2010/02/big-pharmas-sacrifice-for-health-reform.html
Bottom line-- if you're a political cynic and expect health reform to be done according to the age-old Washington formula, you're not surprised to see this particular brand of sausage being made. You can defend your cynicism by noting that at this point, health reform has come closer to passage under Obama's watch than it has in the past century, so he must be doing something right. If you were hoping that Obama would, as promised, change the way Washington does business, you have to be somewhat disappointed.
The Secret Avandia Tapes: Comedy or Smoking Gun?
Gardiner Harris broke this story yesterday in the New York Times:
http://www.nytimes.com/2010/02/23/health/23niss.html
My own opinion is that this is more of a bit of Pharmagossip than anything really substantive that moves forward our understanding of the ethical issues at the medicine/Pharma interface; but who can withstand the attraction of a really juicy bit of gossip?
According to the timeline provided by Cleveland Clinic cardiologist Dr. Steve Nissen in the last post, it's now May 10, 2007. On May 1, Nissen and his colleagues submitted a manuscript of a meta-analysis showing excess cardiac risks with the diabetes drug Avandia (rosiglitazone) to the New England Journal of Medicine. On May 17, highlighting the public health importance of the findings, NEJM will publish the paper on line. I gather from the story that Nissen knew by May 10 that NEJM was about to accept the paper if they had not already formally accepted. What Nissen did not know on May 10 was that an NEJM reviewer, Dr. Steven M. Haffner of the University of Texas-San Antonio medical center, had faxed a copy of the manuscript to GlaxoSmithKline, with whom he had a financial relationship (in violation of all the rules of journal publishing and academic peer review--see previous post).
On May 10, four executives from GlaxoSmithKline, the manufacturers of Avandia, met with Nissen in his office. Presumably Nissen knew that they knew that a paper had been submitted to NEJM. Nissen did not know that they knew the paper's exact contents. Nissen knew that they would not like the conclusions of the paper. Nissen did not know that GSK had internally crunched the numbers and that their own statisticians agreed that Nissen et al. had got the numbers right.
Now, add to the who-didn't-know-what that Nissen decided to tape the meeting without telling the GSK execs--which is legal in Ohio, we are told. Harris says that Nissen "fear[ed] he would face pressure and criticism from executives" and therefore decided to record the meeting. I don't know if Nissen had read John Le Carre's novel, The Constant Gardener, or had seen the movie, but if so, he might have feared further that if GSK had its way, he'd soon be sleeping with the fishes. For whatever reason he decided on the recording gambit.
GSK told the Times they were "disturbed" to learn that the meeting had been recorded without their knowledge. GSK did not indicate that they were disturbed that their lackey had violated all the rules of journal peer review by sending them a fax of Nissen's paper.
So, with all this high drama, what do we now know from the tape? Well, not all that much, but a few nuggets.
First, GSK tried to buy off Nissen from publishing his paper by promising that important new data would be available very soon, and hinting that Nissen might look stupid if he published his own, incomplete data before awaiting the new, definitive study. (Again, no hint that they had already internally confirmed the correctness of Nissen's numbers.) Specifically, on June 6, 2007, GSK published an interim analysis of another trial called RECORD. GSK's chief medical officer, Dr. Ronald L. Krall, is captured on the tape playing a "what if" game with Nissen. Nissen's group had calculated that the hazard ratio for excess heart disease due to Avandia was 1.64. "Let's suppose," said Krall, "RECORD was done tomorrow and the hazard ratio was 1.12."
The lesson here is that when RECORD was later published, the hazard ratio was 1.11. Krall would not have known this fact on May 10 if the study protocol had been followed correctly; as of that date the study would still have been blinded. So the tape suggests that GSK was playing fast and loose with the study methodology, looking for ways to cover its rear end with the disclosure of Avandia's risks imminent.
Krall's next "what if" move was--"Suppose we did [a] patient-level analysis and it looked very different from what you have?" Nissen shot back that he agreed that a patient-level analysis, returning to the actual raw data, would be superior in reliability to his meta-analysis that relied only on grouped study data. But he also had enough confidence in his meta-analysis numbers to claim that it was not mathematically possible that the patient-level data could deviate from his calculations by a significant degree--certainly not enough to remove evidence of a serious risk. In any event, if GSK ever actually ran the patient-level data and were not simply bluffing, those data have never been made public.
http://www.nytimes.com/2010/02/23/health/23niss.html
My own opinion is that this is more of a bit of Pharmagossip than anything really substantive that moves forward our understanding of the ethical issues at the medicine/Pharma interface; but who can withstand the attraction of a really juicy bit of gossip?
According to the timeline provided by Cleveland Clinic cardiologist Dr. Steve Nissen in the last post, it's now May 10, 2007. On May 1, Nissen and his colleagues submitted a manuscript of a meta-analysis showing excess cardiac risks with the diabetes drug Avandia (rosiglitazone) to the New England Journal of Medicine. On May 17, highlighting the public health importance of the findings, NEJM will publish the paper on line. I gather from the story that Nissen knew by May 10 that NEJM was about to accept the paper if they had not already formally accepted. What Nissen did not know on May 10 was that an NEJM reviewer, Dr. Steven M. Haffner of the University of Texas-San Antonio medical center, had faxed a copy of the manuscript to GlaxoSmithKline, with whom he had a financial relationship (in violation of all the rules of journal publishing and academic peer review--see previous post).
On May 10, four executives from GlaxoSmithKline, the manufacturers of Avandia, met with Nissen in his office. Presumably Nissen knew that they knew that a paper had been submitted to NEJM. Nissen did not know that they knew the paper's exact contents. Nissen knew that they would not like the conclusions of the paper. Nissen did not know that GSK had internally crunched the numbers and that their own statisticians agreed that Nissen et al. had got the numbers right.
Now, add to the who-didn't-know-what that Nissen decided to tape the meeting without telling the GSK execs--which is legal in Ohio, we are told. Harris says that Nissen "fear[ed] he would face pressure and criticism from executives" and therefore decided to record the meeting. I don't know if Nissen had read John Le Carre's novel, The Constant Gardener, or had seen the movie, but if so, he might have feared further that if GSK had its way, he'd soon be sleeping with the fishes. For whatever reason he decided on the recording gambit.
GSK told the Times they were "disturbed" to learn that the meeting had been recorded without their knowledge. GSK did not indicate that they were disturbed that their lackey had violated all the rules of journal peer review by sending them a fax of Nissen's paper.
So, with all this high drama, what do we now know from the tape? Well, not all that much, but a few nuggets.
First, GSK tried to buy off Nissen from publishing his paper by promising that important new data would be available very soon, and hinting that Nissen might look stupid if he published his own, incomplete data before awaiting the new, definitive study. (Again, no hint that they had already internally confirmed the correctness of Nissen's numbers.) Specifically, on June 6, 2007, GSK published an interim analysis of another trial called RECORD. GSK's chief medical officer, Dr. Ronald L. Krall, is captured on the tape playing a "what if" game with Nissen. Nissen's group had calculated that the hazard ratio for excess heart disease due to Avandia was 1.64. "Let's suppose," said Krall, "RECORD was done tomorrow and the hazard ratio was 1.12."
The lesson here is that when RECORD was later published, the hazard ratio was 1.11. Krall would not have known this fact on May 10 if the study protocol had been followed correctly; as of that date the study would still have been blinded. So the tape suggests that GSK was playing fast and loose with the study methodology, looking for ways to cover its rear end with the disclosure of Avandia's risks imminent.
Krall's next "what if" move was--"Suppose we did [a] patient-level analysis and it looked very different from what you have?" Nissen shot back that he agreed that a patient-level analysis, returning to the actual raw data, would be superior in reliability to his meta-analysis that relied only on grouped study data. But he also had enough confidence in his meta-analysis numbers to claim that it was not mathematically possible that the patient-level data could deviate from his calculations by a significant degree--certainly not enough to remove evidence of a serious risk. In any event, if GSK ever actually ran the patient-level data and were not simply bluffing, those data have never been made public.
Sunday, February 21, 2010
The Avandia Story: Failures of Regulation and Professionalism
Rosiglitazone (Avandia) is back in the news. First I opened my newspaper this morning to read the following article:
http://hosted.ap.org/dynamic/stories/U/US_MED_DIABETES_DRUG?SITE=CTWAT&SECTION=HOME&TEMPLATE=DEFAULT
Next, faithful reader Marilyn Mann kindly alerted me to a new editorial on rosiglitazone by Steve Nissen of the Cleveland Clinic, author of the meta-analysis that revealed the serious cardiovascular risks associated with the drug (citation below). Finally, through that article's citations, I was alerted to a New York Times article I had originally missed:
http://www.nytimes.com/2008/01/31/business/31censure.html?_r=1
Let's do a quick recap of the story Nissen tells. Early on there were reasons to be concerned that rosiglitazone's blood-sugar-lowering effects might come at the cost of cardiovascular risk, especially increased risk of congestive heart failure. This was important news because there are many other drugs available for management of diabetes, and one of the main reasons doctors want to control Type 2 diabetes is to reduce, not increase, heart risks. (More on that at the end.)
The FDA, meanwhile, was mostly focused on the first drug in that class to be aproved for diabetes, troglitazone (which I discuss at length in HOOKED). That drug (Rezulin) was causing big concern because of recently revealed risks of liver damage, in some cases so bad as to require liver transplant. The FDA wanted to get troglitazone off the market but feared reaction of the diabetes treatment community if it removed the only drug in this promising new class. Problem solved-- in 1999 the FDA quickly approved rosiglitazone plus another cousin, pioglitazone, both known to be relatively free of the liver problem; then later took troglitazone off the market. Trouble was the FDA was in such a rush that the heart risks of rosiglitazone (not shared, it seems, by pio-, thank goodness) got short shrift.
One prominent endocrinologist, Dr. John Buse, started to talk about the increased heart risks associated with the new drug. A delegation from the manufacturer paid him a visit. The upshot was that he ended up signing a contract essentially gagging him from commenting unfavorably on rosiglitazone. (Earlier post on the ins and outs of the Buse case at: http://brodyhooked.blogspot.com/2007/11/intimidation-of-dr-john-buse-some.html)
By October, 2006, GlaxoSmithKline had pretty good evidence from a large trial that there was a significant increased heart-failure risk with its drug, then selling in excess of $3B annually. The company shared the evidence with the FDA. Neither notified the medical profession or the general public. (Hence, the recent report from the US Senate reported by the AP, of how long the company knew the risks before revealing them.)
Nissen and his team conducted their independent meta-analysis and submitted it for publication in May 2007. As soon as he received a copy of the manuscript from the New England Journal of Medicine for his confidential review, Dr. Steven M. Haffner of the University of Texas-San Antonio medical center faxed a copy of it to GlaxoSmithKline, with whom he had a financial relationship, in violation of all the rules of journal publishing and academic peer review. However, GSK had already (as noted) been alerted to the risks of Avandia and merely noted that the figures calculated in Nissen's meta-analysis matched closely its own internal figures. The advance leak of the NEJM paper did however give GSK time to rush the publication of another study as a partial response to the unfavorable publicity. Eventually Avandia sales plummeted. (The Times reported in 2008 that UT-San Antonio was dealing internally with the Haffner accusations, as was NEJM. If any action was taken against him, a quick Google search reveals no sign of same.)
Nissen in his editorial provides a handy time line of all these events and lists the various failures of both government regulation and professionalism. I would add to his list the continued miseducation of both the physicians and the general public that the "answer" to Type 2 diabetes is better glucose control. (If you don't think this is the general impression, watch all the ads on daytime TV for glucose monitors, paid for by Medicare despite repeated evidence that home monitoring of Type 2 diabetes not treated with insulin does nothing to improve patient outcomes.) Starting with the massive UKPDS trial many years ago, several large studies have shown that unfortunately, tighter control of blood glucose does nothing to prevent the major complications of Type 2 diabetes, which are heart attack, stroke, and vascular conditions such as those leading to amputation of limbs. By contrast, aggressive attention to other cardiovascular risk factors, such as controlling blood pressure, and at least one drug, an old generic, metformin, can reduce the cardiovascular risk significantly.
So, if the scientific evidence says forget about close monitoring and tight control of blood sugar in Type 2 diabetes, why are both physicians and patients still so fixated on blood sugar? Well, if GSK is busy marketing a drug that lowers blood sugar, but that just so happens actually to increase cardiovascular risk, you'd expect a marketing campaign that says a lot about the importance of lowering blood sugar and keeps mum about real strategies for reducing cardiovascular risk. The fact that rosiglitazone once sold $3.3B worth of drug is good evidence of the resulting miscommunication--the glitazone drugs were never supposed to be first-line drugs for diabetes even under the best of circumstances, and if that much was sold, it could only be because what truly works for diabetes was completely distorted in the minds of most physicians.
I don't mean to say that it's solely on GSK's head that docs are bonkers about what really works for Type 2 diabetes. Clearly we all want to believe that diabetes = sugar--isn't that what all of us learned on our mother's knees?--and we don't want to believe evidence to the contrary no matter how high it piles up. However, it's one thing when this bias works all by itself, and quite another when millions of marketing dollars are spent to further convince us that what is untrue is true, thereby reinforcing the bias in spades. Even if we aggressively started today we will be years reversing this massive misinformation campaign.
Nissen SE. The rise and fall of rosiglitazone [editorial]. European Heart Journal, published online Feb. 12, 2010; doi 10.1093/eurheartj/ehq016.
NOTE ADDED 3/1/10: The original version of this post contained a typo that distorted the meaning; that typo has now been corrected. Sorry!
http://hosted.ap.org/dynamic/stories/U/US_MED_DIABETES_DRUG?SITE=CTWAT&SECTION=HOME&TEMPLATE=DEFAULT
Next, faithful reader Marilyn Mann kindly alerted me to a new editorial on rosiglitazone by Steve Nissen of the Cleveland Clinic, author of the meta-analysis that revealed the serious cardiovascular risks associated with the drug (citation below). Finally, through that article's citations, I was alerted to a New York Times article I had originally missed:
http://www.nytimes.com/2008/01/31/business/31censure.html?_r=1
Let's do a quick recap of the story Nissen tells. Early on there were reasons to be concerned that rosiglitazone's blood-sugar-lowering effects might come at the cost of cardiovascular risk, especially increased risk of congestive heart failure. This was important news because there are many other drugs available for management of diabetes, and one of the main reasons doctors want to control Type 2 diabetes is to reduce, not increase, heart risks. (More on that at the end.)
The FDA, meanwhile, was mostly focused on the first drug in that class to be aproved for diabetes, troglitazone (which I discuss at length in HOOKED). That drug (Rezulin) was causing big concern because of recently revealed risks of liver damage, in some cases so bad as to require liver transplant. The FDA wanted to get troglitazone off the market but feared reaction of the diabetes treatment community if it removed the only drug in this promising new class. Problem solved-- in 1999 the FDA quickly approved rosiglitazone plus another cousin, pioglitazone, both known to be relatively free of the liver problem; then later took troglitazone off the market. Trouble was the FDA was in such a rush that the heart risks of rosiglitazone (not shared, it seems, by pio-, thank goodness) got short shrift.
One prominent endocrinologist, Dr. John Buse, started to talk about the increased heart risks associated with the new drug. A delegation from the manufacturer paid him a visit. The upshot was that he ended up signing a contract essentially gagging him from commenting unfavorably on rosiglitazone. (Earlier post on the ins and outs of the Buse case at: http://brodyhooked.blogspot.com/2007/11/intimidation-of-dr-john-buse-some.html)
By October, 2006, GlaxoSmithKline had pretty good evidence from a large trial that there was a significant increased heart-failure risk with its drug, then selling in excess of $3B annually. The company shared the evidence with the FDA. Neither notified the medical profession or the general public. (Hence, the recent report from the US Senate reported by the AP, of how long the company knew the risks before revealing them.)
Nissen and his team conducted their independent meta-analysis and submitted it for publication in May 2007. As soon as he received a copy of the manuscript from the New England Journal of Medicine for his confidential review, Dr. Steven M. Haffner of the University of Texas-San Antonio medical center faxed a copy of it to GlaxoSmithKline, with whom he had a financial relationship, in violation of all the rules of journal publishing and academic peer review. However, GSK had already (as noted) been alerted to the risks of Avandia and merely noted that the figures calculated in Nissen's meta-analysis matched closely its own internal figures. The advance leak of the NEJM paper did however give GSK time to rush the publication of another study as a partial response to the unfavorable publicity. Eventually Avandia sales plummeted. (The Times reported in 2008 that UT-San Antonio was dealing internally with the Haffner accusations, as was NEJM. If any action was taken against him, a quick Google search reveals no sign of same.)
Nissen in his editorial provides a handy time line of all these events and lists the various failures of both government regulation and professionalism. I would add to his list the continued miseducation of both the physicians and the general public that the "answer" to Type 2 diabetes is better glucose control. (If you don't think this is the general impression, watch all the ads on daytime TV for glucose monitors, paid for by Medicare despite repeated evidence that home monitoring of Type 2 diabetes not treated with insulin does nothing to improve patient outcomes.) Starting with the massive UKPDS trial many years ago, several large studies have shown that unfortunately, tighter control of blood glucose does nothing to prevent the major complications of Type 2 diabetes, which are heart attack, stroke, and vascular conditions such as those leading to amputation of limbs. By contrast, aggressive attention to other cardiovascular risk factors, such as controlling blood pressure, and at least one drug, an old generic, metformin, can reduce the cardiovascular risk significantly.
So, if the scientific evidence says forget about close monitoring and tight control of blood sugar in Type 2 diabetes, why are both physicians and patients still so fixated on blood sugar? Well, if GSK is busy marketing a drug that lowers blood sugar, but that just so happens actually to increase cardiovascular risk, you'd expect a marketing campaign that says a lot about the importance of lowering blood sugar and keeps mum about real strategies for reducing cardiovascular risk. The fact that rosiglitazone once sold $3.3B worth of drug is good evidence of the resulting miscommunication--the glitazone drugs were never supposed to be first-line drugs for diabetes even under the best of circumstances, and if that much was sold, it could only be because what truly works for diabetes was completely distorted in the minds of most physicians.
I don't mean to say that it's solely on GSK's head that docs are bonkers about what really works for Type 2 diabetes. Clearly we all want to believe that diabetes = sugar--isn't that what all of us learned on our mother's knees?--and we don't want to believe evidence to the contrary no matter how high it piles up. However, it's one thing when this bias works all by itself, and quite another when millions of marketing dollars are spent to further convince us that what is untrue is true, thereby reinforcing the bias in spades. Even if we aggressively started today we will be years reversing this massive misinformation campaign.
Nissen SE. The rise and fall of rosiglitazone [editorial]. European Heart Journal, published online Feb. 12, 2010; doi 10.1093/eurheartj/ehq016.
NOTE ADDED 3/1/10: The original version of this post contained a typo that distorted the meaning; that typo has now been corrected. Sorry!
Friday, February 19, 2010
Latest from the Bonkers Institute: Why Didn't Pharma Marketers Think of This?
Those wishing a chuckle should check out the recent report from the Bonkers Institute for Nearly Genuine Research:
http://www.bonkersinstitute.org/asymptomatic.html
http://www.bonkersinstitute.org/asymptomatic.html
Saturday, February 13, 2010
Departure of the Two Million Dollar Man--A Blow to Reform?
On a speaking trip to LA, I belatedly opened yesterday's edition of the Los Angeles Times to encounter Tom Hamburger's detailed reporting on Billy Tauzin's announced resignation as head of PhRMA (Sorry, my recalcitrant laptop refuses to copy/paste the URL for the story--go to www.latimes.com and search on "Tauzin").
Billy Tauzin, former congressman from Louisiana, is best known to us pharmascolds for his appearance in Michael Moore's Sicko, shamelessly mugging for the camera while holding the outsized cardboard check for $2 million as he celebrated being hired by PhRMA as their CEO, immediately after he had successfully pushed Medicare Part D through Congress with multiple provisions handcrafted to suit the desires of the drug industry. With that background, it seems odd to read Hamburger's account of how Tauzin's departure may present a serious problem for advancement of health reform.
Here's how Hamburger totes the balance sheet on Tauzin's negotations to date with the Obama White House. Tauzin gave up: a promise of a total of $80B in the next decade in drug industry profits, and a promise to launch a series of ads supporting health reform. Tauzin got: promises that the White House would oppose legislation to use government mass purchasing power to negotiate down drug prices, and legislation allowing the reimportation of cheaper drugs from Canada and elsewhere. Add to that the information presented in the most recent previous post, that in the runup to this year, the drug industry actually managed to raise its prices by an amount that promises a $100B increase over the next decade, and you see that the promised $80B savings has already been wiped out. The negotiating score seems to be Tauzin and PhRMA 100, White House 0. (No wonder that Hamburger reports that the PhRMA board was in favor of retaining Tauzin and that his resignation was for purely personal reasons.)
Yet there is no joy in Mudville, apparently. Other business interests, notably the US Chamber of Commerce, want to continue to oppose health reform tooth and nail and were livid when PhRMA broke ranks with a uniform business front. The GOP, which used to count on getting almost all of PhRMA's campaign contributions until PhRMAS responded to recent Democratic gains by splitting their lobbying largesse more or less 50-50, has threatened retaliation if they win big this fall as they hope to.
Lessons for us folks who make less than $2M annually? I offer two. First: If we want health reform we are going to have to really pitch in, work hard, and take off the gloves. The simple matter is that health care is becoming completely unaffordable in the US because of money that flows into the pockets of many corporate interests. They have shown us that they are not going to go quietly--they will fight with everything they have to keep that gravy train. Good sense, rational arguments, and evidence count as nothing against that entrenched lobbying power.
Second: Those corporate interests would like nothing more than to be joined by yet another corporate interest--physicians. Many US physicians are falling into line, refusing to look at any cost saving that would cut into their already bloated incomes, and lobbying hard to make the government leave their pet profit lines alone. This is an abject failure of medical professionalism and medical leadership. The remaining medical specialties must loudly denounce that behavior. The days of doctors always being polite to other doctors in public, and never pointing fingers no matter how egregious the behavior, must end.
Billy Tauzin, former congressman from Louisiana, is best known to us pharmascolds for his appearance in Michael Moore's Sicko, shamelessly mugging for the camera while holding the outsized cardboard check for $2 million as he celebrated being hired by PhRMA as their CEO, immediately after he had successfully pushed Medicare Part D through Congress with multiple provisions handcrafted to suit the desires of the drug industry. With that background, it seems odd to read Hamburger's account of how Tauzin's departure may present a serious problem for advancement of health reform.
Here's how Hamburger totes the balance sheet on Tauzin's negotations to date with the Obama White House. Tauzin gave up: a promise of a total of $80B in the next decade in drug industry profits, and a promise to launch a series of ads supporting health reform. Tauzin got: promises that the White House would oppose legislation to use government mass purchasing power to negotiate down drug prices, and legislation allowing the reimportation of cheaper drugs from Canada and elsewhere. Add to that the information presented in the most recent previous post, that in the runup to this year, the drug industry actually managed to raise its prices by an amount that promises a $100B increase over the next decade, and you see that the promised $80B savings has already been wiped out. The negotiating score seems to be Tauzin and PhRMA 100, White House 0. (No wonder that Hamburger reports that the PhRMA board was in favor of retaining Tauzin and that his resignation was for purely personal reasons.)
Yet there is no joy in Mudville, apparently. Other business interests, notably the US Chamber of Commerce, want to continue to oppose health reform tooth and nail and were livid when PhRMA broke ranks with a uniform business front. The GOP, which used to count on getting almost all of PhRMA's campaign contributions until PhRMAS responded to recent Democratic gains by splitting their lobbying largesse more or less 50-50, has threatened retaliation if they win big this fall as they hope to.
Lessons for us folks who make less than $2M annually? I offer two. First: If we want health reform we are going to have to really pitch in, work hard, and take off the gloves. The simple matter is that health care is becoming completely unaffordable in the US because of money that flows into the pockets of many corporate interests. They have shown us that they are not going to go quietly--they will fight with everything they have to keep that gravy train. Good sense, rational arguments, and evidence count as nothing against that entrenched lobbying power.
Second: Those corporate interests would like nothing more than to be joined by yet another corporate interest--physicians. Many US physicians are falling into line, refusing to look at any cost saving that would cut into their already bloated incomes, and lobbying hard to make the government leave their pet profit lines alone. This is an abject failure of medical professionalism and medical leadership. The remaining medical specialties must loudly denounce that behavior. The days of doctors always being polite to other doctors in public, and never pointing fingers no matter how egregious the behavior, must end.
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