Latest Drugwonks' Blog
You know it's a slow news cycle when various media outlets stumble over themselves to report what every endo has known for years: long term use of Avandia in women with low bone density can contribute to bone thinning. Easily mitigated by treatment with an osteoporosis drug. Duh. And the Nature Medicine article simply identified the specific receptor the PPAR pathway targeted that caused the degeneration in mice, it did not discover the mechanism of degeneration. That was discovered a long time ago. Not one article suggested that there was a benefit to continuing Avandia or put the bone loss risk in context with blindness, kidney loss, amputation as a result of diabetes.
Here are some sources in case journalists are interested in reading....
Rosiglitazone causes bone loss in mice by suppressing osteoblast differentiation and bone formation.
[Endocrinology. 2005]
Aging increases stromal/osteoblastic cell-induced osteoclastogenesis and alters the osteoclast precursor pool in the mouse.
[J Bone Miner Res. 2005]
Surface-specific effects of a PPARgamma agonist, darglitazone, on bone in mice.
[Bone. 2006]
Netoglitazone is a PPAR-gamma ligand with selective effects on bone and fat.
[Bone. 2006]
Rosiglitazone impacts negatively on bone by promoting osteoblast/osteocyte apoptosis.
[J Endocrinol. 2004]
Here are some sources in case journalists are interested in reading....
Rosiglitazone causes bone loss in mice by suppressing osteoblast differentiation and bone formation.
[Endocrinology. 2005]
Aging increases stromal/osteoblastic cell-induced osteoclastogenesis and alters the osteoclast precursor pool in the mouse.
[J Bone Miner Res. 2005]
Surface-specific effects of a PPARgamma agonist, darglitazone, on bone in mice.
[Bone. 2006]
Netoglitazone is a PPAR-gamma ligand with selective effects on bone and fat.
[Bone. 2006]
Rosiglitazone impacts negatively on bone by promoting osteoblast/osteocyte apoptosis.
[J Endocrinol. 2004]
Today CMPI helped with the formal launch of IGuard.org, the first personalized drug safety tool developed for consumers and created by consumers that will tell, in real time, what drugs are working best for what people. iGuard provides patients with free medication safety checks, personalized safety alerts and updates, and the opportunity to share medication experiences with others. And, by monitoring outcomes across its user community, iGuard can help the FDA and other researchers identify problems faster than ever. Who will benefit from iGuard. Consumers who want to learn more about how the medicines, vitamins and supplements they are taking or plan to take will affect them as individuals. Drug companies should want to get involved to learn sooner rather than later about the consumer's experience with a drug, including how they are benefitting, drug-drug interactions, drug-disease interactions, as well as companies who want to communicate with consumers about ways to improve their experience with a medicine. It's a much better way to communicate with customers than through meta-analysis conducted by Steve Nissen.
IGuard is a free service to anyone who signs up and use of information for research purposes is confidential and voluntary.
Registration is free online at www.iGuard.org.
IGuard is a free service to anyone who signs up and use of information for research purposes is confidential and voluntary.
Registration is free online at www.iGuard.org.
Jamie Love thinks he has Big Pharma in zugzwang. (That's a chess term referring to a position where one player is reduced to utter helplessness -- but must continue to play even though every additional move makes his position worse.)
Here’s what he has to say this week in Fortune Magazine about his plan to replace pharmaceutical patents with “prizes†…
"It's either going to be price controls or prizes.â€
Not so. And even though he's King of the Big Lie -- say it enough times and maybe people will begin to think it’s true -- it just isn't so. There are many alternatives that are, well, sane ones.
But as the article (authored by John Simons) concludes …
“Clearly, if industry wants to avoid this (Jamie Love's) scenario, they had better start fashioning some new ideas of their own.â€
How about a more robust discussion of a patient-centric Critical Path program for Comparative Effectiveness?
Here’s the rest of the story from Fortune:
http://money.cnn.com/2007/11/28/magazines/fortune/simons_patent.fortune/index.htm
Next up on this front is just how far Senator Bernie Sanders' Prizes vs. Patents bill gets in the Senate.
Here’s what he has to say this week in Fortune Magazine about his plan to replace pharmaceutical patents with “prizes†…
"It's either going to be price controls or prizes.â€
Not so. And even though he's King of the Big Lie -- say it enough times and maybe people will begin to think it’s true -- it just isn't so. There are many alternatives that are, well, sane ones.
But as the article (authored by John Simons) concludes …
“Clearly, if industry wants to avoid this (Jamie Love's) scenario, they had better start fashioning some new ideas of their own.â€
How about a more robust discussion of a patient-centric Critical Path program for Comparative Effectiveness?
Here’s the rest of the story from Fortune:
http://money.cnn.com/2007/11/28/magazines/fortune/simons_patent.fortune/index.htm
Next up on this front is just how far Senator Bernie Sanders' Prizes vs. Patents bill gets in the Senate.
When is off-label promotion not off-label promotion? Well, as with so much in the world of FDA regulations -- it depends.
In this case it depends on the FDA's decision to relace ambiguity with a draft guidance on the matter. But the question remains, is this even within the agency's jurisdiction?
Of course, we can always depend on Henry Waxman (America's Oversighter-in-Chief) for a fair and balanced comment. Here's one sentence from his 11 page letter to the FDA on the leaked draft of the draft guidance:
"It would open the door to abusive marketing practices that will jeopardize safety, undermine public health, and lead to an increase in unapproved uses of powerful drugs."
But Henry, what do you really think?
At the end of the day, shouldn't physicians have free and unfettered access to publicly available, peer-reviewed scientific information?
Oh yes, and then there's that First Amendment thing.
In this case it depends on the FDA's decision to relace ambiguity with a draft guidance on the matter. But the question remains, is this even within the agency's jurisdiction?
Of course, we can always depend on Henry Waxman (America's Oversighter-in-Chief) for a fair and balanced comment. Here's one sentence from his 11 page letter to the FDA on the leaked draft of the draft guidance:
"It would open the door to abusive marketing practices that will jeopardize safety, undermine public health, and lead to an increase in unapproved uses of powerful drugs."
But Henry, what do you really think?
At the end of the day, shouldn't physicians have free and unfettered access to publicly available, peer-reviewed scientific information?
Oh yes, and then there's that First Amendment thing.
But Ralph -- what have you done lately?
Many congrats.
Ralph Snyderman, M.D., Chancellor Emeritus at Duke University and Founder and Chairman of Prevents, Inc., receives the 2007 Leadership in Personalized Medicine Award today from the Personalized Medicine Coalition (PMC) for his efforts in advancing predictive and targeted therapies on a national scale.
The annual PMC award recognizes the contributions of a visionary individual whose actions in science, business, or policy have advanced the frontier of personalized medicine.
Many congrats.
Ralph Snyderman, M.D., Chancellor Emeritus at Duke University and Founder and Chairman of Prevents, Inc., receives the 2007 Leadership in Personalized Medicine Award today from the Personalized Medicine Coalition (PMC) for his efforts in advancing predictive and targeted therapies on a national scale.
The annual PMC award recognizes the contributions of a visionary individual whose actions in science, business, or policy have advanced the frontier of personalized medicine.
PRESS ADVISORY: Science Board to the Food and Drug Administration
Date and Time: Monday, December 3, from 8:00 a.m. to 5:30 p.m.
Location: Washington DC North/Gaithersburg Hilton, 620 Perry Pkwy., Gaithersburg, MD 20877, Salons A, B, and C
Key item: Presentation of the report FDA Science and Mission at Risk
12:30 p.m. Report of the Subcommittee on Science and Technology, Gail Cassell, PhD, D.Sc. (hon), Subcommittee Chair
2:00 p.m. Science Board Q&A and Discussion of the Subcommittee Report
PRESS ADVISORY: Media conference call with Dr. Cassell and other authors of: FDA Science and Mission at Risk
Date and Time: Tuesday, December 4, at 10 a.m.
Call-in number: 1-888-622-5357; Participant: 453189#
Date and Time: Monday, December 3, from 8:00 a.m. to 5:30 p.m.
Location: Washington DC North/Gaithersburg Hilton, 620 Perry Pkwy., Gaithersburg, MD 20877, Salons A, B, and C
Key item: Presentation of the report FDA Science and Mission at Risk
12:30 p.m. Report of the Subcommittee on Science and Technology, Gail Cassell, PhD, D.Sc. (hon), Subcommittee Chair
2:00 p.m. Science Board Q&A and Discussion of the Subcommittee Report
PRESS ADVISORY: Media conference call with Dr. Cassell and other authors of: FDA Science and Mission at Risk
Date and Time: Tuesday, December 4, at 10 a.m.
Call-in number: 1-888-622-5357; Participant: 453189#
A subcommittee of the FDA’s Science Board (headed by the talented Dr. Gail Cassell of Eli Lilly & Company) says the agency suffers from a "plethora of inadequacies," including an "appallingly low'' rate of food inspections and a lack of scientists who understand new technologies.
According to a new report issued by the subcommittee, the FDA needs more money, better computer systems, and should be restructured to include a scientific leader.
"Without a substantial increase in resources, the agency is powerless to improve its performance, will fall further behind, and will be unable to meet either the mandates of Congress or the expectations of the American public. This will damage not only the health of the population of the U.S., but also the health of our economy.''
The report describes rapidly developing advances in areas such as genomics, wireless health-care devices and nanotechnology, and says the FDA can't adequately monitor products because it can't keep up with the science. The FDA suffers `"serious scientific deficiencies,'' the report concluded. The subcommittee consulted more than 25 specialists in industry, academics and government
The report blames Congress for requiring the FDA to take on more responsibilities without providing enough funding to hire staff.
Each American pays about 1 1/2 cents a day to fund the FDA, and an increase to 3 cents a day wouldn't "be a great price to pay for the assurance that our food and drug supply is, indeed, the best and safest in the world,'' according to the report.
And that shouldn't be a problem – after all, everybody else seems to want to give the FDA their two cents worth.
According to a new report issued by the subcommittee, the FDA needs more money, better computer systems, and should be restructured to include a scientific leader.
"Without a substantial increase in resources, the agency is powerless to improve its performance, will fall further behind, and will be unable to meet either the mandates of Congress or the expectations of the American public. This will damage not only the health of the population of the U.S., but also the health of our economy.''
The report describes rapidly developing advances in areas such as genomics, wireless health-care devices and nanotechnology, and says the FDA can't adequately monitor products because it can't keep up with the science. The FDA suffers `"serious scientific deficiencies,'' the report concluded. The subcommittee consulted more than 25 specialists in industry, academics and government
The report blames Congress for requiring the FDA to take on more responsibilities without providing enough funding to hire staff.
Each American pays about 1 1/2 cents a day to fund the FDA, and an increase to 3 cents a day wouldn't "be a great price to pay for the assurance that our food and drug supply is, indeed, the best and safest in the world,'' according to the report.
And that shouldn't be a problem – after all, everybody else seems to want to give the FDA their two cents worth.
Mark McClellan (“the hardest working man in American health care") told a gaggle of biotech executives at Lazard Capital Markets' 4th annual health care conference that a new bill passed by Congress will create a vast new database of drug patients by 2012.
McClellan said major health care organizations such as eHealth Initiative, Partners Healthcare and Kaiser Permanente will coordinate with insurers like Wellpoint, Inc.and Unitedhealth Group to gather and collate the data from patients. This initiative is part of the FDA Amendment Act of 2007.
"Most of the evidence on your products will be coming from sources other than you," said McClellan, who sees the information as being more complete and more objective.
If all members of the American health care system can work together and following the same rules (in how they define adverse events and how they use the data) “you've got tens of millions (of people) in the database," said McClellan.
McClellan said major health care organizations such as eHealth Initiative, Partners Healthcare and Kaiser Permanente will coordinate with insurers like Wellpoint, Inc.and Unitedhealth Group to gather and collate the data from patients. This initiative is part of the FDA Amendment Act of 2007.
"Most of the evidence on your products will be coming from sources other than you," said McClellan, who sees the information as being more complete and more objective.
If all members of the American health care system can work together and following the same rules (in how they define adverse events and how they use the data) “you've got tens of millions (of people) in the database," said McClellan.
As any medical scientist will tell you, there are few "Eureka!" moments in health research. Progress comes step-by-step, one incremental innovation at a time. Companies more often profit by improving existing chemicals and making processes more efficient than by revolutionizing the whole field with new products. And even the smallest innovations are made only after large amounts of very expensive research.
How distressing, then, that the U.S. Senate has taken up a bill that would pretty much decimate patents as we know them. The Patent Reform Act of 2007, a version of which has already passed the House, would require every patent application to be published on the Internet only 18 months after filing.
Considering the years of research underlying most medical innovations, it is madness to require pharmaceutical companies to reveal their secrets so early. It seems even more unfair when you consider that it often takes in excess of 36 months after filing a patent to actually have it approved. This means that competitors and criminals will have a window of at least 18 months to replicate new drugs and medical research.
Here’s the rest of the story …
http://www.spectator.org/dsp_article.asp?art_id=12332
Our strong patent law is a major reason why many pharmaceutical companies are still based here, instead of, say, Canada, where laws are weaker. If the Senate passes the Patent Reform Act of 2007, some companies might pack up and leave. Or, more worryingly, they might simply halt research on what could be tomorrow's life-saving cures.
How distressing, then, that the U.S. Senate has taken up a bill that would pretty much decimate patents as we know them. The Patent Reform Act of 2007, a version of which has already passed the House, would require every patent application to be published on the Internet only 18 months after filing.
Considering the years of research underlying most medical innovations, it is madness to require pharmaceutical companies to reveal their secrets so early. It seems even more unfair when you consider that it often takes in excess of 36 months after filing a patent to actually have it approved. This means that competitors and criminals will have a window of at least 18 months to replicate new drugs and medical research.
Here’s the rest of the story …
http://www.spectator.org/dsp_article.asp?art_id=12332
Our strong patent law is a major reason why many pharmaceutical companies are still based here, instead of, say, Canada, where laws are weaker. If the Senate passes the Patent Reform Act of 2007, some companies might pack up and leave. Or, more worryingly, they might simply halt research on what could be tomorrow's life-saving cures.
From today's edition of the Wall Street Journal ...
The Media on Drugs
By SIDNEY TAUREL
When it comes to describing the benefits and risks of prescription drugs, the hyper-competitive, around-the-clock media is rarely at its best. Call the following a case study in the challenge of doing right by doctors and patients -- in spite of the need to feed the media beast with copy.
Our story starts Oct. 24, when several media outlets reported that Eli Lilly and Company had halted two clinical trials for the drug prasugrel -- a possible new therapy for heart-attack patients that Lilly is developing with Daiichi Sankyo. The speculation that followed these reports was that the drug must have failed its initial trials. Within a few days the market capitalization of Eli Lilly fell by about $6 billion.
This speculation was unfounded and, incidentally, false. In early November, the academic TIMI Study Group announced the results of a massive clinical trial showing that prasugrel produced significant improvements in patient outcomes compared with current treatments.
Specifically, the trial, known as TRITON, showed that prasugrel produced a 19% reduction in relative risk for cardiovascular death, nonfatal heart attack, or nonfatal stroke when compared with the drug clopidogrel -- today's standard of care -- and had a favorable benefit-risk profile in a large majority of patients.
Statistical data can be interpreted in different ways. Some experts will reach more nuanced or skeptical conclusions about TRITON. But a Duke University cardiologist told this newspaper, after seeing the trial's results, "If you can't get a drug on the market with that kind of data, we should stop developing drugs."
So what happened in those days after Oct. 24? Lilly's goal was to turn over our prasugrel findings to doctors in a manner that left no doubt as to their scientific rigor and completeness. This meant publishing the findings in a highly respected journal and discussing them directly with top cardiologists, ahead of mass-media reporting. We decided to present these findings to the New England Journal of Medicine (NEJM) and the Annual Scientific Sessions of the American Heart Association (AHA) on Nov. 4.
NEJM and AHA asked for promises from Lilly and its partners, and we agreed, not to disclose any of the results of TRITON prior to Nov. 4. Such guarantees of exclusivity are not only common, but also appropriate, in focusing expert attention on important research. A definitive source and a "zero hour" of first-hand disclosure for complex scientific data help to limit misinformation.
Doctors and scientists at Lilly and Daiichi Sankyo, of course, had begun to analyze the results of TRITON in the weeks leading up to the AHA meeting. In addition to showing strong efficacy, the data also showed that in three small subgroups of patients, the drug at its current dosage raised the risk of major bleeding relative to its effect on preventing heart attacks.
Lilly had two small clinical trials of prasugrel underway for different research purposes, and we had received no reports of safety concerns from them. But when we saw the TRITON results, we put patients first. Based on the small chance that patients in the three identified subgroups might be given prasugrel and experience serious bleeding, we advised our researchers to suspend the two trials pending a review.
Enter the beast. Ten days before our "zero hour," word leaked out, causing us to confirm that the two prasugrel trials had been suspended, although our promises to NEJM and AHA prevented us from explaining why. The media entered a feeding frenzy, catered by commentators on Wall Street and elsewhere who speculated that prasugrel posed broad risks and had probably failed its major trial. Our stock began its trip south and, more seriously, some doctors and patients were left with false impressions.
Unveiling the data at AHA brought some relief. Still swimming against the tide of rumor, a few stories distorted the TRITON results, but most were balanced. In the end, the Food and Drug Administration will not rely on media reports to reach approval decisions. Lilly is confident that prasugrel will be given a chance to help patients on a large scale.
There are a few lessons here that need to be learned. For the pharmaceutical industry: Preserving the integrity of scientific data and protecting the safety of patients are always the right choices. Stock prices recover but trust is much harder to regain. Trust hinges on our openness in sharing everything we know about who should use our products -- along with when, how and at what dose -- and who should not.
For the media, if I may be so bold: Don't trade in leaks and rumors where scientific data are concerned. Damage to public understanding is hard to repair after it's been done. Wait for real numbers, and take the time to explain statistics and benefit-risk analysis, which cannot be conveyed in sound bites alone. And for would-be pundits: If you have not had firsthand exposure to the scientific results or specialized knowledge under discussion, then qualify your comments if you must make them at all.
We all have a stake in taming this beast -- not for the sake of any company or individual discovery, but for the sake of those who ultimately rely on accurate information for the care of patients.
Mr. Taurel is chairman and CEO of Eli Lilly and Company.
The Media on Drugs
By SIDNEY TAUREL
When it comes to describing the benefits and risks of prescription drugs, the hyper-competitive, around-the-clock media is rarely at its best. Call the following a case study in the challenge of doing right by doctors and patients -- in spite of the need to feed the media beast with copy.
Our story starts Oct. 24, when several media outlets reported that Eli Lilly and Company had halted two clinical trials for the drug prasugrel -- a possible new therapy for heart-attack patients that Lilly is developing with Daiichi Sankyo. The speculation that followed these reports was that the drug must have failed its initial trials. Within a few days the market capitalization of Eli Lilly fell by about $6 billion.
This speculation was unfounded and, incidentally, false. In early November, the academic TIMI Study Group announced the results of a massive clinical trial showing that prasugrel produced significant improvements in patient outcomes compared with current treatments.
Specifically, the trial, known as TRITON, showed that prasugrel produced a 19% reduction in relative risk for cardiovascular death, nonfatal heart attack, or nonfatal stroke when compared with the drug clopidogrel -- today's standard of care -- and had a favorable benefit-risk profile in a large majority of patients.
Statistical data can be interpreted in different ways. Some experts will reach more nuanced or skeptical conclusions about TRITON. But a Duke University cardiologist told this newspaper, after seeing the trial's results, "If you can't get a drug on the market with that kind of data, we should stop developing drugs."
So what happened in those days after Oct. 24? Lilly's goal was to turn over our prasugrel findings to doctors in a manner that left no doubt as to their scientific rigor and completeness. This meant publishing the findings in a highly respected journal and discussing them directly with top cardiologists, ahead of mass-media reporting. We decided to present these findings to the New England Journal of Medicine (NEJM) and the Annual Scientific Sessions of the American Heart Association (AHA) on Nov. 4.
NEJM and AHA asked for promises from Lilly and its partners, and we agreed, not to disclose any of the results of TRITON prior to Nov. 4. Such guarantees of exclusivity are not only common, but also appropriate, in focusing expert attention on important research. A definitive source and a "zero hour" of first-hand disclosure for complex scientific data help to limit misinformation.
Doctors and scientists at Lilly and Daiichi Sankyo, of course, had begun to analyze the results of TRITON in the weeks leading up to the AHA meeting. In addition to showing strong efficacy, the data also showed that in three small subgroups of patients, the drug at its current dosage raised the risk of major bleeding relative to its effect on preventing heart attacks.
Lilly had two small clinical trials of prasugrel underway for different research purposes, and we had received no reports of safety concerns from them. But when we saw the TRITON results, we put patients first. Based on the small chance that patients in the three identified subgroups might be given prasugrel and experience serious bleeding, we advised our researchers to suspend the two trials pending a review.
Enter the beast. Ten days before our "zero hour," word leaked out, causing us to confirm that the two prasugrel trials had been suspended, although our promises to NEJM and AHA prevented us from explaining why. The media entered a feeding frenzy, catered by commentators on Wall Street and elsewhere who speculated that prasugrel posed broad risks and had probably failed its major trial. Our stock began its trip south and, more seriously, some doctors and patients were left with false impressions.
Unveiling the data at AHA brought some relief. Still swimming against the tide of rumor, a few stories distorted the TRITON results, but most were balanced. In the end, the Food and Drug Administration will not rely on media reports to reach approval decisions. Lilly is confident that prasugrel will be given a chance to help patients on a large scale.
There are a few lessons here that need to be learned. For the pharmaceutical industry: Preserving the integrity of scientific data and protecting the safety of patients are always the right choices. Stock prices recover but trust is much harder to regain. Trust hinges on our openness in sharing everything we know about who should use our products -- along with when, how and at what dose -- and who should not.
For the media, if I may be so bold: Don't trade in leaks and rumors where scientific data are concerned. Damage to public understanding is hard to repair after it's been done. Wait for real numbers, and take the time to explain statistics and benefit-risk analysis, which cannot be conveyed in sound bites alone. And for would-be pundits: If you have not had firsthand exposure to the scientific results or specialized knowledge under discussion, then qualify your comments if you must make them at all.
We all have a stake in taming this beast -- not for the sake of any company or individual discovery, but for the sake of those who ultimately rely on accurate information for the care of patients.
Mr. Taurel is chairman and CEO of Eli Lilly and Company.
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.
