Latest Drugwonks' Blog
Who do you trust? The New York Times editorial page or the consensus statement of the American College of Cardiology which said with regard to Vytorin:
"The study involved 720 patients with heterozygous familial hypercholesterolemia and showed no significant difference in the primary endpoint between patients treated with ezetimibe and simvastatin versus patients treated with simvastatin alone over a two-year period. The study was designed to prove that Vytorin could slow the growth of plaque in carotid arteries supplying the brain more than simvastatin alone. Media reports indicate that the results of the trial show no benefit from the combination of ezetimibe (Zetia) and simvastatin (sold together as Vytorin) over simvastatin alone.
The American College of Cardiology recommends that major clinical decisions not be made on the basis of the ENHANCE study alone."
According to the American College of Cardiology (ACC), this study deserves serious thought and follow-up. The overall incidence rates of cardiac events were nearly identical between both treatment groups, and both medicines were generally well tolerated. There should no be reason for patients to panic. The difference in IMT changes between the simvastatin group and the Vytorin group was 0.006 mm vs. 0.011 mm.
Health care professionals should speak to their concerned patients using this drug. The ACC is also releasing a public statement explaining that this is not an urgent situation and patients should never stop taking any prescribed medications without first discussing the issue with their health care professional. Further research will be needed in this area to provide conclusive evidence about which lipid lowering strategy is preferred (statin alone vs. statin plus ezetimibe).
Furthermore, the ACC notes that this trial is an imaging study and not a clinical-outcome study. Conclusions should not be made until the three large clinical-outcome trials are presented within the next two to three years. The ACC recommends that Zetia remain a reasonable option for patients who are currently on a high dose statin but have not reached their goal. The ACC also notes that Zetia is a reasonable option for patients who cannot tolerate statins or can only tolerate a low dose statin.
On the subject of endpoints and markers. The Critical Path is not about using surrogate endpoints. Anyone who has listened to Dr. Woodcock more than once knows it is about finding and qualifying biomarkers -- molecular and imaging -- that predict disease progression and outcome as well as response to treatment -- as well as developing novel statistical ways that can be deployed across divisions and technologies to advance understanding of technology impact on disease.
The issue in the ENHANCE study was whether or not imaging studies were accurate measures of disease progression in this small population. Nothing more or less. In this regard, development of better standards and predictive imaging studies will help advance their use in clinical trials. Also let's remember that Dr. Nissen, who has trashed the results might be a bit biased since his own imaging studies demonstrated a regression of atherosclerosis by reducing LDL levels with another drug, something the NY Times failed to point out. And let's remember Dr. Nissen also tossed out imaging studies in another clinical trial looking at plaque regression because they were unreadable, so he just looked at the results of the readable ones.
At the risk of repeating myself again and again -- here's a link to the story we repeated when the MSM was looking for a Vytorin coverup months ago.
http://www.thestreet.com/pf/comment/adamfeuerstein/10195643.html
The problem with the Atherogenic drug that Nissen worked on was the same one -- more or less -- the scientists running the ENHANCE study struggled with. Namely, the statistical correlation was hard to measure because of the unwieldy nature of the biomarker. In each study, patients taking the drug did better than patients taking a placebo on most endpoints, just not on the endpoint most difficult to measure. But unlike the Nissen re-analysis, ENHANCE did not do an interim analysis with fewer patients to produce a benefit. The debate was whether or not to chuck the analysis altogether because of questions about the reliability of the biomarker.
Which is what the Critical Path is all about.
No need to panic or disregard your doctor in favor of the medical advice dispensed by the fearmongers and Pharm-haters on the NY Times editorial page.
"The study involved 720 patients with heterozygous familial hypercholesterolemia and showed no significant difference in the primary endpoint between patients treated with ezetimibe and simvastatin versus patients treated with simvastatin alone over a two-year period. The study was designed to prove that Vytorin could slow the growth of plaque in carotid arteries supplying the brain more than simvastatin alone. Media reports indicate that the results of the trial show no benefit from the combination of ezetimibe (Zetia) and simvastatin (sold together as Vytorin) over simvastatin alone.
The American College of Cardiology recommends that major clinical decisions not be made on the basis of the ENHANCE study alone."
According to the American College of Cardiology (ACC), this study deserves serious thought and follow-up. The overall incidence rates of cardiac events were nearly identical between both treatment groups, and both medicines were generally well tolerated. There should no be reason for patients to panic. The difference in IMT changes between the simvastatin group and the Vytorin group was 0.006 mm vs. 0.011 mm.
Health care professionals should speak to their concerned patients using this drug. The ACC is also releasing a public statement explaining that this is not an urgent situation and patients should never stop taking any prescribed medications without first discussing the issue with their health care professional. Further research will be needed in this area to provide conclusive evidence about which lipid lowering strategy is preferred (statin alone vs. statin plus ezetimibe).
Furthermore, the ACC notes that this trial is an imaging study and not a clinical-outcome study. Conclusions should not be made until the three large clinical-outcome trials are presented within the next two to three years. The ACC recommends that Zetia remain a reasonable option for patients who are currently on a high dose statin but have not reached their goal. The ACC also notes that Zetia is a reasonable option for patients who cannot tolerate statins or can only tolerate a low dose statin.
On the subject of endpoints and markers. The Critical Path is not about using surrogate endpoints. Anyone who has listened to Dr. Woodcock more than once knows it is about finding and qualifying biomarkers -- molecular and imaging -- that predict disease progression and outcome as well as response to treatment -- as well as developing novel statistical ways that can be deployed across divisions and technologies to advance understanding of technology impact on disease.
The issue in the ENHANCE study was whether or not imaging studies were accurate measures of disease progression in this small population. Nothing more or less. In this regard, development of better standards and predictive imaging studies will help advance their use in clinical trials. Also let's remember that Dr. Nissen, who has trashed the results might be a bit biased since his own imaging studies demonstrated a regression of atherosclerosis by reducing LDL levels with another drug, something the NY Times failed to point out. And let's remember Dr. Nissen also tossed out imaging studies in another clinical trial looking at plaque regression because they were unreadable, so he just looked at the results of the readable ones.
At the risk of repeating myself again and again -- here's a link to the story we repeated when the MSM was looking for a Vytorin coverup months ago.
http://www.thestreet.com/pf/comment/adamfeuerstein/10195643.html
The problem with the Atherogenic drug that Nissen worked on was the same one -- more or less -- the scientists running the ENHANCE study struggled with. Namely, the statistical correlation was hard to measure because of the unwieldy nature of the biomarker. In each study, patients taking the drug did better than patients taking a placebo on most endpoints, just not on the endpoint most difficult to measure. But unlike the Nissen re-analysis, ENHANCE did not do an interim analysis with fewer patients to produce a benefit. The debate was whether or not to chuck the analysis altogether because of questions about the reliability of the biomarker.
Which is what the Critical Path is all about.
No need to panic or disregard your doctor in favor of the medical advice dispensed by the fearmongers and Pharm-haters on the NY Times editorial page.
As Mark Twain -- an author of choice here at drugwonks -- once said: "Presume you were an idiot. Then presume you were a member of Congress. But I repeat myself."
Can any be so stupid and petty as to quibble about having the inventor of the artificial heart promoting as important a drug as Lipitor?
Apparently Bart Stupak and John Dingell think it rises to a high enough crime to demand a congressional investigation. And Katie Watson of the Medical Humanities and Bioethics Program at Northwestern University agrees: "To have a celebrity physician associated with cardiac health telling me I need Lipitor and when it costs significantly more than a generic alternative that might be appropriate for me— that's a physician motivated by a paycheck, not by patient health."
Let it be noted that Ms. Watson is famous for her lecture "Playing Doctor: Improvisational Theater & the Medical Encounter" which was presented at the Searle Seminar Room in the Medical Humanites and Bioethics building. That's Searle, as in the drug company, better known as Pharmacia which is now part of...you guessed it...Pfizer.
But I digress. So apparently it is unethical to have a famous doctor who does not practice medicine promoting a brand drug that works. It is ethical to have someone playing doctor promote a generic drug that doesn't? Or how about a Nobel Prize Winner who is no longer licensed promoting a new drug? And how does Ms. Watson know if the Nobel Prize winner is motivated by a paycheck and not patient health? Is it wrong to accept a paycheck in the process of advancing patient care by being a spokesperson.
Back to Ms. Watson. " Katie is also the author of the screenplay Sperm Daddy, and a contributor to the TimeOut Chicago humor back page and the WBEZ news magazine 848." I wonder if she is motivated by a paycheck or patient health?
http://www.sirensimprov.com/katie.html
Can any be so stupid and petty as to quibble about having the inventor of the artificial heart promoting as important a drug as Lipitor?
Apparently Bart Stupak and John Dingell think it rises to a high enough crime to demand a congressional investigation. And Katie Watson of the Medical Humanities and Bioethics Program at Northwestern University agrees: "To have a celebrity physician associated with cardiac health telling me I need Lipitor and when it costs significantly more than a generic alternative that might be appropriate for me— that's a physician motivated by a paycheck, not by patient health."
Let it be noted that Ms. Watson is famous for her lecture "Playing Doctor: Improvisational Theater & the Medical Encounter" which was presented at the Searle Seminar Room in the Medical Humanites and Bioethics building. That's Searle, as in the drug company, better known as Pharmacia which is now part of...you guessed it...Pfizer.
But I digress. So apparently it is unethical to have a famous doctor who does not practice medicine promoting a brand drug that works. It is ethical to have someone playing doctor promote a generic drug that doesn't? Or how about a Nobel Prize Winner who is no longer licensed promoting a new drug? And how does Ms. Watson know if the Nobel Prize winner is motivated by a paycheck and not patient health? Is it wrong to accept a paycheck in the process of advancing patient care by being a spokesperson.
Back to Ms. Watson. " Katie is also the author of the screenplay Sperm Daddy, and a contributor to the TimeOut Chicago humor back page and the WBEZ news magazine 848." I wonder if she is motivated by a paycheck or patient health?
http://www.sirensimprov.com/katie.html
Have a look at today’s New York Times house editorial, “Cholesterol Drug Bombs.â€
http://www.nytimes.com/2008/01/16/opinion/16wed2.html?_r=1&ref=opinion&oref=slogin
There are a number of issues going on here, but pay particular attention to these two paragraphs:
“There are reasons to be cautious about interpreting these results. The number of patients was relatively small. And many of them may have used different drug treatments for years before entering the trial, possibly diminishing the effectiveness of adding Zetia …
The findings also raise doubts about the current belief that lowering cholesterol is the key to cardiovascular health. The study showed that Vytorin reduced bad cholesterol significantly more than Zocor alone. The problem was that it failed to reduce the formation of plaque.â€
Here’s what well-respected cardiologist (and CMPI board chairman) Dr. Michael Weber has to say:
“The study with Vytorin looked only at surrogate endpoints, not morbidity and mortality. The ongoing clinical outcomes trials will answer the questions definitively. We must hope that the alarmist comments by certain opinion leaders quoted in the lay press will not compromise the integrity of these critical studies by intimidating the patients who have been enrolled. We should not forget that many people simply cannot use statins in full doses due to side effects, so properly studying Zetia and Vytorin is absolutely vital.â€
As to whether or not clinical data was withheld (or as the Times writes, “cynically" sat on) is another issue altogether and cannot be allowed to muddy the far more important clinical questions.
http://www.nytimes.com/2008/01/16/opinion/16wed2.html?_r=1&ref=opinion&oref=slogin
There are a number of issues going on here, but pay particular attention to these two paragraphs:
“There are reasons to be cautious about interpreting these results. The number of patients was relatively small. And many of them may have used different drug treatments for years before entering the trial, possibly diminishing the effectiveness of adding Zetia …
The findings also raise doubts about the current belief that lowering cholesterol is the key to cardiovascular health. The study showed that Vytorin reduced bad cholesterol significantly more than Zocor alone. The problem was that it failed to reduce the formation of plaque.â€
Here’s what well-respected cardiologist (and CMPI board chairman) Dr. Michael Weber has to say:
“The study with Vytorin looked only at surrogate endpoints, not morbidity and mortality. The ongoing clinical outcomes trials will answer the questions definitively. We must hope that the alarmist comments by certain opinion leaders quoted in the lay press will not compromise the integrity of these critical studies by intimidating the patients who have been enrolled. We should not forget that many people simply cannot use statins in full doses due to side effects, so properly studying Zetia and Vytorin is absolutely vital.â€
As to whether or not clinical data was withheld (or as the Times writes, “cynically" sat on) is another issue altogether and cannot be allowed to muddy the far more important clinical questions.
Representative Rosa DeLauro has introduced the Cloned Food Labeling Act, which would require the FDA and the Department of Agriculture (USDA) to mandate that all food derived from cloned animals be labeled.
She’s not happy with the FDA’s stance on the safety of food:
“The studies on which the FDA is basing its assessment include very little information on the specific question of whether food from cloned animals is safe."
But, according to the FDA, the agency has "studies that show that the meat and milk from cattle clones and their offspring are as safe as that from conventionally bred animals."
The agency has been studying this issue in great detail for a very long period of time. In fact, many of the world's leading experts on this issue work at the FDA's Center for Veterinary Medicine. During my tenure at the FDA (which ended in 2004), this issue was already being deeply investigated and intensely debated.
Representative DeLauro, rather than shooting from the hip, should call the FDA and ask for a briefing.
She’s not happy with the FDA’s stance on the safety of food:
“The studies on which the FDA is basing its assessment include very little information on the specific question of whether food from cloned animals is safe."
But, according to the FDA, the agency has "studies that show that the meat and milk from cattle clones and their offspring are as safe as that from conventionally bred animals."
The agency has been studying this issue in great detail for a very long period of time. In fact, many of the world's leading experts on this issue work at the FDA's Center for Veterinary Medicine. During my tenure at the FDA (which ended in 2004), this issue was already being deeply investigated and intensely debated.
Representative DeLauro, rather than shooting from the hip, should call the FDA and ask for a briefing.
How can we trust that the drugs will be safe or effective? Since Gates Foundation President Yamada is under investigation by Senator Grassley and Cong. DeLauro for his role in talking to Dr. John Buse about Avandia nearly a decade ago, obviously any money he doles out while at Gates must be considered tainted and therefore the results of any studies cannot be trusted. And if the orphan drug for sleeping sickness uses Critical Path steps developed by the Reagan Udall Foundation how do we know they actually are not steps that weaken standards of safety and efficacy to simply line the pockets of the company that the Gates Foundation gave the grant to? We all know that's what the Critical Path is all about: watering down standards so that foundations can give grants to companies who in turn can develop at cost an orphan drug that is neither safe or effective because it uses biomarkers.
http://www.nytimes.com/2008/01/08/health/research/08slee.html?_r=1&ref=health&oref=slogin
http://www.nytimes.com/2008/01/08/health/research/08slee.html?_r=1&ref=health&oref=slogin
I took Senator Grassley to task for suggesting that unhappy reviewers and other malcontents air the grievances and differences with FDA division decisions at AdComm meetings a while back. Now from the other side, people and companies who complain about the lack of consistent or guidance from the FDA regarding the reason for holding up an approval also want transparency.
Transparency is the refuge of those who, short of being able to control the outcome, want to at least try to control perception. The FDA needs less transparency and more consistency based on better science. And it needs leadership regarding the question of "Whose life and health care decision is it anyway?" The Critical Path is designed to help shift that decisionmaking to doctors and individuals.
What I'd like to know is, where do the presidential candidates stand on The Critical Path? Do they care? Or are they more interested in making sure there are cheap knock offs of old drugs and faster FDA inspections for UPS shipments of medicines ordered online?
http://www.fool.com/investing/high-growth/2008/01/14/score-one-for-dendreon-and-disclosure.aspx
Transparency is the refuge of those who, short of being able to control the outcome, want to at least try to control perception. The FDA needs less transparency and more consistency based on better science. And it needs leadership regarding the question of "Whose life and health care decision is it anyway?" The Critical Path is designed to help shift that decisionmaking to doctors and individuals.
What I'd like to know is, where do the presidential candidates stand on The Critical Path? Do they care? Or are they more interested in making sure there are cheap knock offs of old drugs and faster FDA inspections for UPS shipments of medicines ordered online?
http://www.fool.com/investing/high-growth/2008/01/14/score-one-for-dendreon-and-disclosure.aspx
While lots of folks are making much ado about whether or not to readjust the athero endpoint of the Vytorin study because of hard to read ultrasounds (remember Steve Nissen and Atherogenics?) the the results of the study demonstrate, once again, just how hard it is to use statins to get reversal of plaque. We need better drugs. Good article from cnn.com on what the study shows and don't. Ignore the Congressional witchhunt threats and the whining of the "Kill Pharma Even If People Die" bloggers...
http://money.cnn.com/news/newsfeeds/articles/djf500/200801141513DOWJONESDJONLINE000640_FORTUNE5.htm
http://money.cnn.com/news/newsfeeds/articles/djf500/200801141513DOWJONESDJONLINE000640_FORTUNE5.htm
My book review of Embryo: A Defense of Human Life...
http://www.nypost.com/seven/01132008/postopinion/postopbooks/the_born_identity_433669.htm
http://www.nypost.com/seven/01132008/postopinion/postopbooks/the_born_identity_433669.htm
Here are two of the qualities Leon Wieseltier in The New Republic like about about John McCain that make him a nearly ideal presidential candidate. "anxiety over the environment and contempt for pharmaceutical companies."
Contempt for pharmaceutical companies? And how does that translate into good public policy? Pushing for drug reimportation? Patent seizures?
I think there is a bit of projection on Leon's part but what prompts this hatred? What did drug company's do wrong that deserves contempt? I know this will tick off the whack jobs that equate anything that is sponsored by drug companies as a pollutant or a criminal activity, but I really would like to know.
Contempt for pharmaceutical companies? And how does that translate into good public policy? Pushing for drug reimportation? Patent seizures?
I think there is a bit of projection on Leon's part but what prompts this hatred? What did drug company's do wrong that deserves contempt? I know this will tick off the whack jobs that equate anything that is sponsored by drug companies as a pollutant or a criminal activity, but I really would like to know.
The U.S. Supreme Court has, without comment, opted not to accept an appeal of Abigail Alliance v. von Eschenbach. This means the federal appeals court ruling that patients do not have a constitutional right to experimental drugs stands.
This is a tough, emotional issue and, with such heated rhetoric on both sides, it's easy to lose sight of the fact that everyone wants the same thing -- expanded access to drugs under clinical investigation.
That's precisely why, when I was at the FDA, we stopped calling clinical trials "compassionate use." It sounded too paternalistic. Allowing desperately ill patients into clinical trial programs shouldn't be an act of noblesse oblige it should be an act of civil society.
The question is, how to do so with greater alacrity and responsible, robust oversight.
When it comes to pharmaceutical safety, pure libertarianism isn't in the best interests of the public health. Expanded access to experimental drugs simply can't and shouldn't morph into total, unfettered access.
That doesn't mean the status quo is working. What it means is that the FDA needs to figure out a way to dramatically broaden and facilitate expanded access to experimental drugs under its review. And the Abigail Alliance and its supporters need to keep up the pressure to reform the current system.
We believe this is best done in a spirit of collegiality rather than a confrontational courtroom or in Congress.
And we believe the time for all parties to sit down for serious discussions is immediately. Lives hang in the balance.
This is a tough, emotional issue and, with such heated rhetoric on both sides, it's easy to lose sight of the fact that everyone wants the same thing -- expanded access to drugs under clinical investigation.
That's precisely why, when I was at the FDA, we stopped calling clinical trials "compassionate use." It sounded too paternalistic. Allowing desperately ill patients into clinical trial programs shouldn't be an act of noblesse oblige it should be an act of civil society.
The question is, how to do so with greater alacrity and responsible, robust oversight.
When it comes to pharmaceutical safety, pure libertarianism isn't in the best interests of the public health. Expanded access to experimental drugs simply can't and shouldn't morph into total, unfettered access.
That doesn't mean the status quo is working. What it means is that the FDA needs to figure out a way to dramatically broaden and facilitate expanded access to experimental drugs under its review. And the Abigail Alliance and its supporters need to keep up the pressure to reform the current system.
We believe this is best done in a spirit of collegiality rather than a confrontational courtroom or in Congress.
And we believe the time for all parties to sit down for serious discussions is immediately. Lives hang in the balance.
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.
