Latest Drugwonks' Blog
I have a lot of respect for John McCain but I wonder about what Leon Wieseltier of the New Republic praised and referred to as his "contempt for drug companies."
His contempt is getting in the way of clear thinking and good policy. And at time when we will need all the high paying, green jobs we can get, McCain's stance on pharmaceutical innovation -- where most of those jobs will be created worldwide -- is downright regressive and is at odds with his claim to be a pro growth Republican. If there has been a Republican, nay a member of Congress, with more pronounced and persistent antipathy to the pharmaceutical or biotech industry than John McCain, I can't think of one with the exception of New York’s two senator’s Charles Schumer or Hillary Clinton.
If he took the same position on the auto or housing industry he has on pharmaceuticals and biotech, he would shove the nation into an instant depression.
His contempt has been on display throughout the campaign, most notably in the New Hampshire debate when he call them "the bad guys". Why? From the straight talk express we never seem to get a straight answer. Seems to be related to his belief that drug companies inflate drug costs at government expense and artificial monopolies.
If drug costs reflects value, fine," "But if there are ways to bring greater competition to our drug markets by safe re-importation of drugs, by faster introduction of generic drugs, or by any other means we should do so. If I'm elected President, we will."
McCain has said: Problems with costs are created when market forces are replaced by government regulated prices.."
Yet he has aggressively pushed importation of drugs from foreign countries where "market forces are replaced by government regulated prices." And his legislation would force drug companies to sell as much of their price controlled product that is made to foreign spec -- not US spec -- as distributors would order and then would force the FDA to approve it instantly as safe and effective for the US market. Imagine forcing car, timber, building product, and steel companies to do the same! Meanwhile, Canada is the transhipment point for drugs from Iran, Pakistan, China, Venezuela..all our friends. The ultimate destination. America. McCain has no problem with letting Canada's lax importation policy stand as a surrogate for our drug and homeland security.
What are the “other means?†McCain voted for price controls and government run drug formularies for Medicare, especially when an HMO wanted to save money and pass it on to the government. This approach is used at the VA to restrict access to newer drugs and has actually shortened the lives of veterans. If imposed on Medicare and Medicaid it would mean seniors and the poor would be the last to the get what newer medicines are developed, if any are left.
Meanwhile according to a study by the Milken Institute, the biotechnology industry generated more than 2.7 million jobs and $172 billion in real output in 2003. The average income of each “green: job? $60000 plus benefits. But leave it to McCain to be the sponsor of a bill this coming session of Congress that would give overseas generic drug firms an incentive to sue new biotech firms for their patents before they expire in order to create “competition.â€
His contempt is getting in the way of clear thinking and good policy. And at time when we will need all the high paying, green jobs we can get, McCain's stance on pharmaceutical innovation -- where most of those jobs will be created worldwide -- is downright regressive and is at odds with his claim to be a pro growth Republican. If there has been a Republican, nay a member of Congress, with more pronounced and persistent antipathy to the pharmaceutical or biotech industry than John McCain, I can't think of one with the exception of New York’s two senator’s Charles Schumer or Hillary Clinton.
If he took the same position on the auto or housing industry he has on pharmaceuticals and biotech, he would shove the nation into an instant depression.
His contempt has been on display throughout the campaign, most notably in the New Hampshire debate when he call them "the bad guys". Why? From the straight talk express we never seem to get a straight answer. Seems to be related to his belief that drug companies inflate drug costs at government expense and artificial monopolies.
If drug costs reflects value, fine," "But if there are ways to bring greater competition to our drug markets by safe re-importation of drugs, by faster introduction of generic drugs, or by any other means we should do so. If I'm elected President, we will."
McCain has said: Problems with costs are created when market forces are replaced by government regulated prices.."
Yet he has aggressively pushed importation of drugs from foreign countries where "market forces are replaced by government regulated prices." And his legislation would force drug companies to sell as much of their price controlled product that is made to foreign spec -- not US spec -- as distributors would order and then would force the FDA to approve it instantly as safe and effective for the US market. Imagine forcing car, timber, building product, and steel companies to do the same! Meanwhile, Canada is the transhipment point for drugs from Iran, Pakistan, China, Venezuela..all our friends. The ultimate destination. America. McCain has no problem with letting Canada's lax importation policy stand as a surrogate for our drug and homeland security.
What are the “other means?†McCain voted for price controls and government run drug formularies for Medicare, especially when an HMO wanted to save money and pass it on to the government. This approach is used at the VA to restrict access to newer drugs and has actually shortened the lives of veterans. If imposed on Medicare and Medicaid it would mean seniors and the poor would be the last to the get what newer medicines are developed, if any are left.
Meanwhile according to a study by the Milken Institute, the biotechnology industry generated more than 2.7 million jobs and $172 billion in real output in 2003. The average income of each “green: job? $60000 plus benefits. But leave it to McCain to be the sponsor of a bill this coming session of Congress that would give overseas generic drug firms an incentive to sue new biotech firms for their patents before they expire in order to create “competition.â€
Yesterday we commented on the New York Times neglecting to mention -- in a story about clinical trial transparency and Prozac (along with other drugs) that Eli Lilly & Co. posts its clinical trials on a public website.
Well, sins of omission are seldom fun.
Here's Lilly's response:
INDIANAPOLIS, Jan 18, 2008
"Eli Lilly and Company strongly objects to implications in a New York Times article published Thursday that the company has suppressed results of negative clinical trials.
The story, based on a separate article in The New England Journal of Medicine (NEJM), cited Prozac and Lilly as high-profile examples of how the industry purportedly suppresses negative clinical trial data. Not only was the Times' story inaccurate when it comes to Prozac -- the NEJM article didn't identify a single Prozac study as unpublished -- but it also likely created a strong false impression with readers that Lilly suppresses data.
Lilly is an industry leader in being transparent with our clinical trial data. We are committed to publicly disclosing medical research results -- whether favorable or unfavorable to a Lilly medicine -- in an accurate, objective and balanced manner in order for our customers to make more informed decisions about our products.
In December 2004, Lilly was widely recognized as the first pharmaceutical company to voluntarily launch a clinical trials registry, where we post the results of all Lilly sponsored registration clinical trials for all of our marketed products dating back to 1994, and all clinical trials for marketed products since December 2004.
In addition, the two Cymbalta studies listed in an appendix to the NEJM article as "unpublished" have, in fact, been published in peer-reviewed journals. The results of HMAT-A and HMAQ-B were published twice -- first in the Autumn 2002 issue of Psychopharmacology Bulletin, and again in the Primary Care Companion Journal of Clinical Psychiatry in 2003. In addition, these studies were presented at one or more medical congresses that require peer review of abstract submissions and they also have been available to the general public on LillyTrials.com since 2004.
The authors of the NEJM article decided not to count studies as "published" if the manuscript included data from two or more studies. While this methodology might be suitable for an academic discussion, it's clearly not the appropriate standard for determining whether a company has been transparent in disclosing its data.
We clearly have been transparent. The data is publicly available online; we've presented it to health care professionals at major medical meetings; and we published it -- more than once -- in peer-reviewed medical journals. And we remain committed to transparency. All of which we would have told The New York Times ... if only they had called and asked."
Has the New York Times changed its motto from "All the news that's fit to print" to "Don't ask, don't tell?"
Well, sins of omission are seldom fun.
Here's Lilly's response:
INDIANAPOLIS, Jan 18, 2008
"Eli Lilly and Company strongly objects to implications in a New York Times article published Thursday that the company has suppressed results of negative clinical trials.
The story, based on a separate article in The New England Journal of Medicine (NEJM), cited Prozac and Lilly as high-profile examples of how the industry purportedly suppresses negative clinical trial data. Not only was the Times' story inaccurate when it comes to Prozac -- the NEJM article didn't identify a single Prozac study as unpublished -- but it also likely created a strong false impression with readers that Lilly suppresses data.
Lilly is an industry leader in being transparent with our clinical trial data. We are committed to publicly disclosing medical research results -- whether favorable or unfavorable to a Lilly medicine -- in an accurate, objective and balanced manner in order for our customers to make more informed decisions about our products.
In December 2004, Lilly was widely recognized as the first pharmaceutical company to voluntarily launch a clinical trials registry, where we post the results of all Lilly sponsored registration clinical trials for all of our marketed products dating back to 1994, and all clinical trials for marketed products since December 2004.
In addition, the two Cymbalta studies listed in an appendix to the NEJM article as "unpublished" have, in fact, been published in peer-reviewed journals. The results of HMAT-A and HMAQ-B were published twice -- first in the Autumn 2002 issue of Psychopharmacology Bulletin, and again in the Primary Care Companion Journal of Clinical Psychiatry in 2003. In addition, these studies were presented at one or more medical congresses that require peer review of abstract submissions and they also have been available to the general public on LillyTrials.com since 2004.
The authors of the NEJM article decided not to count studies as "published" if the manuscript included data from two or more studies. While this methodology might be suitable for an academic discussion, it's clearly not the appropriate standard for determining whether a company has been transparent in disclosing its data.
We clearly have been transparent. The data is publicly available online; we've presented it to health care professionals at major medical meetings; and we published it -- more than once -- in peer-reviewed medical journals. And we remain committed to transparency. All of which we would have told The New York Times ... if only they had called and asked."
Has the New York Times changed its motto from "All the news that's fit to print" to "Don't ask, don't tell?"
The “authorized generics†debate has made it to the other side of the pond. The Financial Times reports that the EU Commission is concerned that the price of medicines is rising -- while innovation declines—and will investigate whether the pharmaceutical industry abuses patent rights to delay the introduction of low-cost generic alternatives.
The Financial Times writes, “The answer may be that collusion between companies keeps prices high. But the pricing of medicines in much of Europe is more government-controlled than in the US. Companies may profit from national pricing. In the UK, where there is a freer approach, competition is more intense and discounting heavy. Not enough deregulation may be the bigger problem.â€
Here is the complete Financial Times editorial:
http://www.ft.com/cms/s/0/75dbce42-c52c-11dc-811a-0000779fd2ac.html?nclick_check=1
For more discussion of the authorized generics issue, along with an economic analysis of the same, please see:
http://drugwonks.com/2007/05/rockys_racoon.html
The conclusion of the Financial Times editorial is spot on – and something we should take to heart on our side of the Atlantic as well – that we must be careful that “a consumer-first approach does not become a populist one.â€
And -- when you consider some of the health care rhetoric being bandied about by the Presidential candidates -- that’s a notion worthy of serious consideration.
The Financial Times writes, “The answer may be that collusion between companies keeps prices high. But the pricing of medicines in much of Europe is more government-controlled than in the US. Companies may profit from national pricing. In the UK, where there is a freer approach, competition is more intense and discounting heavy. Not enough deregulation may be the bigger problem.â€
Here is the complete Financial Times editorial:
http://www.ft.com/cms/s/0/75dbce42-c52c-11dc-811a-0000779fd2ac.html?nclick_check=1
For more discussion of the authorized generics issue, along with an economic analysis of the same, please see:
http://drugwonks.com/2007/05/rockys_racoon.html
The conclusion of the Financial Times editorial is spot on – and something we should take to heart on our side of the Atlantic as well – that we must be careful that “a consumer-first approach does not become a populist one.â€
And -- when you consider some of the health care rhetoric being bandied about by the Presidential candidates -- that’s a notion worthy of serious consideration.
A US study by the Banner Good Samaritan Medical Center in Phoenix, Arizona has found surgical residents performed better during simulated surgery after playing on the Wii for an hour beforehand.
"The whole point about surgery is to execute small, finely controlled movements with your hands, and that is exactly what you get playing Wii," Kanav Kahol, who conducted the study with colleague Marshall Smith, told New Scientist magazine.
Professor John Quin, executive director of surgical affairs at the Royal Australasian College of Surgeons, said the study was interesting and showed promise, but it was still not clear whether better performance in simulated surgery translated into better performance in surgery on a live patient.
"What it shows at the moment is only that if you repeatedly play video games you get better at playing video games," he said, adding the RACS was conducting a Federal Government-aided study to determine the effectiveness of simulated surgery.
Professor Quin said he hoped high-tech tools like the Wii and simulated surgery proved useful because "it's getting more and more difficult to train the full experience of the surgical operation".
The study found only those games requiring precise movements, like Marble Mania in which a player guides a marble through a 3D obstacle course using the Wii's motion-sensitive remote, are effective.
"You don't gain a lot from swinging an imaginary tennis racket," Kahol said.
Past research by other academics has similarly found video games requiring fine control can help build the skills surgeons need for operations like keyhole surgery.
Kahol and Smith are now reportedly designing Wii software to accurately simulate surgical procedures. For developing countries unable to provide expensive professional training systems, the Wii could be used as a cheap and effective training tool.
In conducting their study, the pair called on eight trainee doctors to play the Wii for an hour before performing virtual surgery using a tool called ProMIS. The training tool provides a 3D simulation of a patient's body and tracks the surgeon's movements while they are "operating".
Movement data was then processed using an algorithm and the surgeons were given scores. Those who played the Wii scored 48 per cent higher on tool control and performance than those who didn't.
"The whole point about surgery is to execute small, finely controlled movements with your hands, and that is exactly what you get playing Wii," Kanav Kahol, who conducted the study with colleague Marshall Smith, told New Scientist magazine.
Professor John Quin, executive director of surgical affairs at the Royal Australasian College of Surgeons, said the study was interesting and showed promise, but it was still not clear whether better performance in simulated surgery translated into better performance in surgery on a live patient.
"What it shows at the moment is only that if you repeatedly play video games you get better at playing video games," he said, adding the RACS was conducting a Federal Government-aided study to determine the effectiveness of simulated surgery.
Professor Quin said he hoped high-tech tools like the Wii and simulated surgery proved useful because "it's getting more and more difficult to train the full experience of the surgical operation".
The study found only those games requiring precise movements, like Marble Mania in which a player guides a marble through a 3D obstacle course using the Wii's motion-sensitive remote, are effective.
"You don't gain a lot from swinging an imaginary tennis racket," Kahol said.
Past research by other academics has similarly found video games requiring fine control can help build the skills surgeons need for operations like keyhole surgery.
Kahol and Smith are now reportedly designing Wii software to accurately simulate surgical procedures. For developing countries unable to provide expensive professional training systems, the Wii could be used as a cheap and effective training tool.
In conducting their study, the pair called on eight trainee doctors to play the Wii for an hour before performing virtual surgery using a tool called ProMIS. The training tool provides a 3D simulation of a patient's body and tracks the surgeon's movements while they are "operating".
Movement data was then processed using an algorithm and the surgeons were given scores. Those who played the Wii scored 48 per cent higher on tool control and performance than those who didn't.
A combination of common and minor variations in five regions of DNA can help predict a man’s risk of getting prostate cancer, researchers reported Wednesday.
According to today's New York Times:
"A company formed by researchers at Wake Forest University School of Medicine is expected to make the test available in a few months, said Karen Richardson, a Wake Forest spokeswoman. It should cost less than $300.
This is, some medical experts say, a first taste of what is expected to be a revolution in medical prognostication. The results, they agree, are clear. But the question is what happens next."
Here’s a link to the complete story:
http://www.nytimes.com/2008/01/17/health/17cancer.html?scp=1&sq=medical+test
According to today's New York Times:
"A company formed by researchers at Wake Forest University School of Medicine is expected to make the test available in a few months, said Karen Richardson, a Wake Forest spokeswoman. It should cost less than $300.
This is, some medical experts say, a first taste of what is expected to be a revolution in medical prognostication. The results, they agree, are clear. But the question is what happens next."
Here’s a link to the complete story:
http://www.nytimes.com/2008/01/17/health/17cancer.html?scp=1&sq=medical+test
Predictably USA Today pushes the panic button on Vytorin
http://www.usatoday.com/news/health/2008-01-16-cholesterol-main_N.htm
But many doctors express frustration. They say they're increasingly asked to prescribe drugs like Vytorin, Zetia and Crestor though the drugs have never have been successfully tested in long-term trials. In the world of billion-dollar medicines, these have a nickname — "me-too" drugs, because they're purportedly like other drugs that have been more extensively tested.
Cholesterol-lowering drugs aren't the only culprits. A number of blood-pressure-lowering ACE-inhibitor drugs are riding on the coattails of the blockbuster Captopril. Zetia and Vytorin are me-too drugs that stretch the limits of the category. Although they were approved on the same basis as statins — for their power to lower bad cholesterol — they aren't statins. They work by an entirely new mechanism that Merck and Schering-Plough promote heavily to doctors and on television, though it's not as well-tested as the statin approach.
Doctors who prescribe them, and patients who use them, take it on faith that the drugs will protect them from heart attacks and prolong their lives, says Yale University cardiologist Harlan Krumholz.
"This is huge," he says. "It's a story of whether or not the profession is going to turn and say, 'We're not going to say me-too drugs are the same unless they prove it.' "
Meanwhile none of the articles picked up on the real reason why most drugs don't work for most people: genetic variations. Nor did they link this story to another important scientific one about cholesterol reported last week.
7 New Cholesterol Genes Found
Genes May Make Good Targets for New Cholesterol Drugs, Experts Say
By Miranda Hitti
WebMD Medical News
Reviewed by Louise Chang, MD
Jan. 14, 2008 -- Scientists have discovered seven genes that affect levels of HDL ("good") cholesterol, LDL ("bad") cholesterol, and triglycerides (another type of blood fat).
Several of those genes "are potentially attractive drug targets" to lower heart disease risk, write the University of Michigan's Cristen Willer, PhD, and colleagues.
Two of the newly identified genes only affect HDL cholesterol, one only affects LDL cholesterol, three only affect triglycerides, and one affects LDL cholesterol and triglycerides.....
....Willer and colleagues also noticed that genes for high LDL cholesterol levels were associated with greater risk of coronary artery disease, which makes heart attacks more likely.
"Nearly all of the gene regions that we found to be involved in higher LDL levels were also involved in coronary artery disease risk," Willer states in a news release. "This is a remarkable result and suggests that new drug therapies that target the genes in these regions will also help prevent coronary artery disease and allow people to live longer and healthier lives."
One day, it may be possible to tailor cholesterol and triglyceride treatments to a patient's gene profile, the researchers note.
Meanwhile, your doctor can check your cholesterol and triglyceride levels and give you advice about how to improve those levels through diet, exercise, and medication, if needed."
Not one article or news account discussed this important factor. It's easier just to make people panic and pick up on the old "me-too" drug issue.
http://www.webmd.com/heart/news/20080114/7-new-cholesterol-genes-found
http://www.usatoday.com/news/health/2008-01-16-cholesterol-main_N.htm
But many doctors express frustration. They say they're increasingly asked to prescribe drugs like Vytorin, Zetia and Crestor though the drugs have never have been successfully tested in long-term trials. In the world of billion-dollar medicines, these have a nickname — "me-too" drugs, because they're purportedly like other drugs that have been more extensively tested.
Cholesterol-lowering drugs aren't the only culprits. A number of blood-pressure-lowering ACE-inhibitor drugs are riding on the coattails of the blockbuster Captopril. Zetia and Vytorin are me-too drugs that stretch the limits of the category. Although they were approved on the same basis as statins — for their power to lower bad cholesterol — they aren't statins. They work by an entirely new mechanism that Merck and Schering-Plough promote heavily to doctors and on television, though it's not as well-tested as the statin approach.
Doctors who prescribe them, and patients who use them, take it on faith that the drugs will protect them from heart attacks and prolong their lives, says Yale University cardiologist Harlan Krumholz.
"This is huge," he says. "It's a story of whether or not the profession is going to turn and say, 'We're not going to say me-too drugs are the same unless they prove it.' "
Meanwhile none of the articles picked up on the real reason why most drugs don't work for most people: genetic variations. Nor did they link this story to another important scientific one about cholesterol reported last week.
7 New Cholesterol Genes Found
Genes May Make Good Targets for New Cholesterol Drugs, Experts Say
By Miranda Hitti
WebMD Medical News
Reviewed by Louise Chang, MD
Jan. 14, 2008 -- Scientists have discovered seven genes that affect levels of HDL ("good") cholesterol, LDL ("bad") cholesterol, and triglycerides (another type of blood fat).
Several of those genes "are potentially attractive drug targets" to lower heart disease risk, write the University of Michigan's Cristen Willer, PhD, and colleagues.
Two of the newly identified genes only affect HDL cholesterol, one only affects LDL cholesterol, three only affect triglycerides, and one affects LDL cholesterol and triglycerides.....
....Willer and colleagues also noticed that genes for high LDL cholesterol levels were associated with greater risk of coronary artery disease, which makes heart attacks more likely.
"Nearly all of the gene regions that we found to be involved in higher LDL levels were also involved in coronary artery disease risk," Willer states in a news release. "This is a remarkable result and suggests that new drug therapies that target the genes in these regions will also help prevent coronary artery disease and allow people to live longer and healthier lives."
One day, it may be possible to tailor cholesterol and triglyceride treatments to a patient's gene profile, the researchers note.
Meanwhile, your doctor can check your cholesterol and triglyceride levels and give you advice about how to improve those levels through diet, exercise, and medication, if needed."
Not one article or news account discussed this important factor. It's easier just to make people panic and pick up on the old "me-too" drug issue.
http://www.webmd.com/heart/news/20080114/7-new-cholesterol-genes-found
912 word story in today's edition of the New York Times under the headline, "Antidepressant Studies Unpublished."
Here's the first paragraph:
"The makers of antidepressants like Prozac and Paxil never published the results of about a third of the drug trials that they conducted to win government approval, misleading doctors and consumers about the drugs’ true effectiveness, a new analysis has found."
And later on:
"The finding is likely to inflame a continuing debate about how drug trial data is reported."
Here's the full story:
http://www.nytimes.com/2008/01/17/health/17depress.html?_r=1&oref=slogin
912 words and not a single one speaking to the fact that Lilly (per Prozac) was the first Pharma company to put all of its clinical trials on a public website.
Is Google blocked at the Grey Lady?
Here's the first paragraph:
"The makers of antidepressants like Prozac and Paxil never published the results of about a third of the drug trials that they conducted to win government approval, misleading doctors and consumers about the drugs’ true effectiveness, a new analysis has found."
And later on:
"The finding is likely to inflame a continuing debate about how drug trial data is reported."
Here's the full story:
http://www.nytimes.com/2008/01/17/health/17depress.html?_r=1&oref=slogin
912 words and not a single one speaking to the fact that Lilly (per Prozac) was the first Pharma company to put all of its clinical trials on a public website.
Is Google blocked at the Grey Lady?
The increasingly insufferable Roy Poses pontificates again and again and again about how everyone who is a consultant to drug companies cannot be trusted. To point out how zealotry should not be confused with objectivity let us go through the following exercise using the deflation of the self-impressed Dr. Poses as an example, with pharmalot.com giving him the platform: " pretending a panel is independent, when potential or perceived conflicts may exist, is misleading. This only casts more doubt on the willingness of these two drugmakers to let the facts speak for themselves - and not spin or cloak info that should be fully vetted."
So by definition, any financial tie is a conflict or perceived conflict which transmutes into faulty or inaccurate data which cannot be trusted which in turn transforms into a drug that should not be taken. Which is why people should stop taking SSRIs, Avandia, Vytorin,
Now I guess that should also apply to Zocor, the forerunner of simvastatin, the generic version of Zocor, especially if we have a negative risk to benefit result of that drug right? This in keeping with the other Poses or Pharmalot principle that disclosure of all negative trial result are to the public good.
So here is a negative trial reported in JAMA in 2004 on Zocor
he myopathy rate of the 80-mg/d dose of simvastatin observed in the A to Z trial and the previously reported meta-analysis are not particularly surprising. For many years following its introduction, the maximum dose of simvastatin approved by the Food and Drug Administration (FDA) was 40 mg/d. However, in 1997 the manufacturer undertook a development program to study 2 higher doses of simvastatin (80 mg/d and 160 mg/d).8, 19-20 Although a favorable report appeared in the medical literature,20 development of the 160-mg/d dose was abandoned due to high muscle toxicity.8, 19 Although never reported in the scientific literature, the financial community was informed that the rate of muscle-related symptoms was 5.7% for the 160 mg/d dose.19 The dose of 80 mg/d of simvastatin was eventually approved, but in 2002, the FDA product label was modified to include warnings about concomitant medications than inhibit cytochrome P450 3A4, the major metabolic pathway for simvastatin elimination.21 This warning was provoked by cases of rhabdomyolysis when simvastatin was administered with 3A4 inhibitors.21"
It is important to reassure practicing physicians and patients that the unfavorable risk-benefit relationship observed in the A to Z trial does not in any way diminish the value of intensive statin treatment in secondary prevention, including ACS patients. There was a trend toward reduced events in the A to Z trial, a finding that supports the lower is better concept. The increased myopathy rate applies only to a specific dose of a single agent and should not tarnish this remarkable class of drugs.24 It must also be emphasized that simvastatin in doses of up to 40 mg/d has shown excellent safety and efficacy in a series of clinical trials. For now, though, the 80-mg/d dose of simvastatin should be used with caution, particularly because other effective agents are available. Finally, in an era when criticism of selective reporting of positive trial results is common,25 the A to Z investigators are to be commended for their prompt and thorough reporting of a critically important major trial that did not meet its original objectives."
Ok, so we know that high dose simvastatin, the same dose compared in the ENHANCE trial carries risks. But we are reassured that other agents are available and that the 80mg can be used with caution.
Now, the person who wrote that editorial on the A to Z study was a paid consultant to Merck.
Steve Nissen. Who was a consultant to Merck, Astra Zeneca, Pfizer, Sankyo, Sanofi, Eli Lilly, Takeda, Novo Nordisk, Atherogenics, Lipid Sciences, GlaxoSmithKline, Hoffman LaRoche, Kos, and Wyeth. Dr Nissen also has directed clinical trials in collaboration with Astra Zeneca, Pfizer, Sankyo, Eli Lilly, Takeda, Atherogenics, and Lipid Sciences.
The same person now trashing Vytorin.
Sorry to beat the same drug over and over again but the bloggers and MSM keep referring to the same sources as well. Their views are biased and dangerous. I trust the doctors and researchers drug companies pay as advisors ten times more than then the second guessers who would discourage patients from taking drugs because of a built in bias against perceived financial conflicts without even looking at street creds or expertise. That is prejudice, plain and simple. And at a fundamental level it suggests that anyone who consults for drug companies is a prostitute and endangers the public health.
That's not independence or objectivity. That's intellectual thuggery.
http://www.pharmalot.com/2008/01/that-secret-vytorin-panel-truly-independent/
http://forum.lowcarber.org/archive/index.php/t-206955.html
He claims the Vytorin results are doctored
So by definition, any financial tie is a conflict or perceived conflict which transmutes into faulty or inaccurate data which cannot be trusted which in turn transforms into a drug that should not be taken. Which is why people should stop taking SSRIs, Avandia, Vytorin,
Now I guess that should also apply to Zocor, the forerunner of simvastatin, the generic version of Zocor, especially if we have a negative risk to benefit result of that drug right? This in keeping with the other Poses or Pharmalot principle that disclosure of all negative trial result are to the public good.
So here is a negative trial reported in JAMA in 2004 on Zocor
he myopathy rate of the 80-mg/d dose of simvastatin observed in the A to Z trial and the previously reported meta-analysis are not particularly surprising. For many years following its introduction, the maximum dose of simvastatin approved by the Food and Drug Administration (FDA) was 40 mg/d. However, in 1997 the manufacturer undertook a development program to study 2 higher doses of simvastatin (80 mg/d and 160 mg/d).8, 19-20 Although a favorable report appeared in the medical literature,20 development of the 160-mg/d dose was abandoned due to high muscle toxicity.8, 19 Although never reported in the scientific literature, the financial community was informed that the rate of muscle-related symptoms was 5.7% for the 160 mg/d dose.19 The dose of 80 mg/d of simvastatin was eventually approved, but in 2002, the FDA product label was modified to include warnings about concomitant medications than inhibit cytochrome P450 3A4, the major metabolic pathway for simvastatin elimination.21 This warning was provoked by cases of rhabdomyolysis when simvastatin was administered with 3A4 inhibitors.21"
It is important to reassure practicing physicians and patients that the unfavorable risk-benefit relationship observed in the A to Z trial does not in any way diminish the value of intensive statin treatment in secondary prevention, including ACS patients. There was a trend toward reduced events in the A to Z trial, a finding that supports the lower is better concept. The increased myopathy rate applies only to a specific dose of a single agent and should not tarnish this remarkable class of drugs.24 It must also be emphasized that simvastatin in doses of up to 40 mg/d has shown excellent safety and efficacy in a series of clinical trials. For now, though, the 80-mg/d dose of simvastatin should be used with caution, particularly because other effective agents are available. Finally, in an era when criticism of selective reporting of positive trial results is common,25 the A to Z investigators are to be commended for their prompt and thorough reporting of a critically important major trial that did not meet its original objectives."
Ok, so we know that high dose simvastatin, the same dose compared in the ENHANCE trial carries risks. But we are reassured that other agents are available and that the 80mg can be used with caution.
Now, the person who wrote that editorial on the A to Z study was a paid consultant to Merck.
Steve Nissen. Who was a consultant to Merck, Astra Zeneca, Pfizer, Sankyo, Sanofi, Eli Lilly, Takeda, Novo Nordisk, Atherogenics, Lipid Sciences, GlaxoSmithKline, Hoffman LaRoche, Kos, and Wyeth. Dr Nissen also has directed clinical trials in collaboration with Astra Zeneca, Pfizer, Sankyo, Eli Lilly, Takeda, Atherogenics, and Lipid Sciences.
The same person now trashing Vytorin.
Sorry to beat the same drug over and over again but the bloggers and MSM keep referring to the same sources as well. Their views are biased and dangerous. I trust the doctors and researchers drug companies pay as advisors ten times more than then the second guessers who would discourage patients from taking drugs because of a built in bias against perceived financial conflicts without even looking at street creds or expertise. That is prejudice, plain and simple. And at a fundamental level it suggests that anyone who consults for drug companies is a prostitute and endangers the public health.
That's not independence or objectivity. That's intellectual thuggery.
http://www.pharmalot.com/2008/01/that-secret-vytorin-panel-truly-independent/
http://forum.lowcarber.org/archive/index.php/t-206955.html
He claims the Vytorin results are doctored
Here's Tom Cruise on Scientology's superiority...if this video doesn't make you believe in SSRIs -- or at least Jaegermeister -- nothing will.
http://gawker.com/5002269/the-cruise-indoctrination-video-scientology-tried-to-suppress
http://gawker.com/5002269/the-cruise-indoctrination-video-scientology-tried-to-suppress
From an editorial in the American Journal of Psychiatry.
Editorial
Demonstrating Drug Action
Carol A. Tamminga, M.D.
The questions that have arisen in the public and scientific literature lately about the use of SSRIs in children and adolescents are addressed for one of the currently available SSRIs by Wagner et al. The issue of whether it is effective to use SSRIs in childhood and adolescent depression has been repeatedly raised over the last years in the context of our field failing to produce clear efficacy answers in children. Depressed children are being treated with SSRIs in greater and greater numbers, without demonstrated efficacy in the age group. The difficulty of demonstrating efficacy with tricyclic antidepressants in children has fueled suspicions that there may exist an age-dependent resistance to treatment. The importance of this well-designed large study for therapeutic strategies in children and adolescents cannot be overstated. It is important that the methodology of this study is solid and the numbers adequate to test the efficacy question asked. The result that citalopram reduced depression more than placebo in this child and adolescent population provides a clear answer for physicians that will (in combination with results from additional studies) guide treatment decisions. It is especially gratifying to see an early onset of action at 1 week of treatment, suggesting an advantage that can be followed up in future studies. This study also set a high methodologic standard for psychiatric diagnosis in pediatric studies. It would be an understatement to say that more such studies are needed.
One would always wish for more in terms of information from drug trials in psychiatric diseases. A common physician complaint about these trials is that they fail to sufficiently inform clinical practice because of restricted entry criteria, fixed-dose design, and limited duration of treatment. It is true that initial registration trials have a goal of demonstrating superiority over placebo to become approved for the market. But this does not rule out additional Phase 4 studies done in large enough patient cohorts to fully inform pressing clinical issues. How do comorbid conditions alter drug response? What treatments are effective in medication nonresponders? What kinds of actions can be expected with long-term treatment? It will be important for industry to address these kinds of Phase 4 questions for clinical use as well as the registration trials.
One particular issue in our field makes informative clinical trials particularly difficult. This is that we do not know what exactly we are treating in terms of its biology. Psychiatric diagnoses are not based on molecular pathology (rather, phenomenology), and new drugs are not directed toward known, disease-related molecules (rather, toward hypotheses). Therefore, we may not be recruiting the correct patient populations for a particular treatment nor have a drug directed toward the disease pathophysiology. Moreover, we may not be measuring anywhere near the optimal outcome measures in our trials (e.g., consider the constraint of only measuring "fatigue" in the treatment of anemia, and not having a RBC count). Nonetheless, even though we do not yet have our molecular targets, we cannot give up on drug development. Indeed, we already have treatments for our diseases, and these may be better treatments than we deserve, based on the state of our knowledge. We need now to hone the treatments that we have and develop the valuable clinical trial methodologies to carry us into the future. Meanwhile, we need to translate the rich basic knowledge accumulating in neuroscience into advances for therapeutics.
http://ajp.psychiatryonline.org/cgi/content/full/161/6/943?etoc
Editorial
Demonstrating Drug Action
Carol A. Tamminga, M.D.
The questions that have arisen in the public and scientific literature lately about the use of SSRIs in children and adolescents are addressed for one of the currently available SSRIs by Wagner et al. The issue of whether it is effective to use SSRIs in childhood and adolescent depression has been repeatedly raised over the last years in the context of our field failing to produce clear efficacy answers in children. Depressed children are being treated with SSRIs in greater and greater numbers, without demonstrated efficacy in the age group. The difficulty of demonstrating efficacy with tricyclic antidepressants in children has fueled suspicions that there may exist an age-dependent resistance to treatment. The importance of this well-designed large study for therapeutic strategies in children and adolescents cannot be overstated. It is important that the methodology of this study is solid and the numbers adequate to test the efficacy question asked. The result that citalopram reduced depression more than placebo in this child and adolescent population provides a clear answer for physicians that will (in combination with results from additional studies) guide treatment decisions. It is especially gratifying to see an early onset of action at 1 week of treatment, suggesting an advantage that can be followed up in future studies. This study also set a high methodologic standard for psychiatric diagnosis in pediatric studies. It would be an understatement to say that more such studies are needed.
One would always wish for more in terms of information from drug trials in psychiatric diseases. A common physician complaint about these trials is that they fail to sufficiently inform clinical practice because of restricted entry criteria, fixed-dose design, and limited duration of treatment. It is true that initial registration trials have a goal of demonstrating superiority over placebo to become approved for the market. But this does not rule out additional Phase 4 studies done in large enough patient cohorts to fully inform pressing clinical issues. How do comorbid conditions alter drug response? What treatments are effective in medication nonresponders? What kinds of actions can be expected with long-term treatment? It will be important for industry to address these kinds of Phase 4 questions for clinical use as well as the registration trials.
One particular issue in our field makes informative clinical trials particularly difficult. This is that we do not know what exactly we are treating in terms of its biology. Psychiatric diagnoses are not based on molecular pathology (rather, phenomenology), and new drugs are not directed toward known, disease-related molecules (rather, toward hypotheses). Therefore, we may not be recruiting the correct patient populations for a particular treatment nor have a drug directed toward the disease pathophysiology. Moreover, we may not be measuring anywhere near the optimal outcome measures in our trials (e.g., consider the constraint of only measuring "fatigue" in the treatment of anemia, and not having a RBC count). Nonetheless, even though we do not yet have our molecular targets, we cannot give up on drug development. Indeed, we already have treatments for our diseases, and these may be better treatments than we deserve, based on the state of our knowledge. We need now to hone the treatments that we have and develop the valuable clinical trial methodologies to carry us into the future. Meanwhile, we need to translate the rich basic knowledge accumulating in neuroscience into advances for therapeutics.
http://ajp.psychiatryonline.org/cgi/content/full/161/6/943?etoc
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.
