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Our friends at the C-Path Institute have blazed that trail of personalized drug safety. Go to the C-Path website..it is full of initiatives and partnerships with the FDA. Ditto the folks at BG Medicine who have a CRADA with the FDA on a liver tox biomarker. Then there is the work of Dr. Ruano (that I have benefitted from directly -- put that in there because I know my critics just hate when I use personal examples ) with regard to side effects from statins at Genomas.
As Ray Woosley of C-Path asks about Personalized Medicine. When? Why Not Now?
http://www.cpath-institute.org
http://www.bgmedicine.com
http://www.genomas.net
As Ray Woosley of C-Path asks about Personalized Medicine. When? Why Not Now?
http://www.cpath-institute.org
http://www.bgmedicine.com
http://www.genomas.net
From today's edition of the Wall Street Journal ...
Consortium to Study Genetics, Drug Safety
By JENNIFER CORBETT DOOREN
WASHINGTON -- A group of seven pharmaceutical companies and academic institutions today will announce an alliance designed to look for genetic links to safety problems associated with medicines.
The group, known as the International Serious Adverse Events Consortium, will launch two studies to look for genetic markers that researchers hope will predict which people are at risk for serious drug-related adverse events.
The first study, with results tentatively slated for release about a year from now, will look at whether variations in a person's DNA are responsible for the development of a rare drug-related skin condition known as Stevens-Johnson Syndrome. Stevens-Johnson is typically marked by a painful, blistering skin rash that causes the top layer of the skin to die. It can be fatal if a person is exposed to the drug that initially caused Stevens-Johnson again.
The second study will look at genetic variations behind serious drug-induced liver injury. Arthur Holden, a former Baxter International Inc. executive who is chairman of the consortium, said he hoped results from that study would be available in two years.
"Everyone's talking about drug safety, and this is what we need to do to improve drug safety," Mr. Holden said in an interview. The seven companies, Abbott Laboratories, GlaxoSmithKline PLC, Johnson & Johnson, Pfizer Inc., Roche Holding AG, Sanofi-Aventis SA and Wyeth are providing "millions" of dollars for the research effort, he said.
The consortium will collect and combine already existing data on serious liver side effects, tissue samples housed in two Britain-based academic institutions, and information and DNA samples from at least one pharmaceutical firm on Stevens-Johnson Syndrome and a related skin condition known as toxic epidermal necrolysis. The DNA from the individuals with side effects will be compared with DNA from "control" subjects who didn't have drug side effects to see if there are genetic variations among the two groups.
Mr. Holden said that if the first two studies are successful, the consortium would then move to other serious side effects like heart trouble and kidney damage that are linked to several different types of drugs as well as drugs in the same class.
The data from the consortium will be made public and could be used by government regulators such as the Food and Drug Administration.
Janet Woodcock, the FDA's chief medical officer, will work with the consortium, although the agency isn't formally a member. "We want this kind of information," she said of the genetic studies, so the agency can find ways to prevent drug side effects or to better manage them. Dr. Woodcock said it is possible that FDA regulations and guidelines on drug development and approval could change if the studies yield clear results.
Many serious drug side effects, such as an increased risk for heart attacks and strokes seen with Merck & Co.'s withdrawn painkiller Vioxx, don't become apparent until after drugs hit the market and thousands or millions more people are exposed. Most clinical studies used to gain approval for a drug involve several hundred to a few thousand patients.
Already, the FDA is highlighting genetic information to help doctors and patients manage drug side effects. Last month alone, the agency said as many as one-third of people on the blood-thinning drug warfarin metabolize the drug differently than expected and warned that breast-feeding women on painkillers with codeine could expose the infant to too much codeine if they are "ultra-rapid" metabolizers of the drug. However, the FDA stopped short of recommending that patients undergo genetic testing to see how they might process the drugs
Consortium to Study Genetics, Drug Safety
By JENNIFER CORBETT DOOREN
WASHINGTON -- A group of seven pharmaceutical companies and academic institutions today will announce an alliance designed to look for genetic links to safety problems associated with medicines.
The group, known as the International Serious Adverse Events Consortium, will launch two studies to look for genetic markers that researchers hope will predict which people are at risk for serious drug-related adverse events.
The first study, with results tentatively slated for release about a year from now, will look at whether variations in a person's DNA are responsible for the development of a rare drug-related skin condition known as Stevens-Johnson Syndrome. Stevens-Johnson is typically marked by a painful, blistering skin rash that causes the top layer of the skin to die. It can be fatal if a person is exposed to the drug that initially caused Stevens-Johnson again.
The second study will look at genetic variations behind serious drug-induced liver injury. Arthur Holden, a former Baxter International Inc. executive who is chairman of the consortium, said he hoped results from that study would be available in two years.
"Everyone's talking about drug safety, and this is what we need to do to improve drug safety," Mr. Holden said in an interview. The seven companies, Abbott Laboratories, GlaxoSmithKline PLC, Johnson & Johnson, Pfizer Inc., Roche Holding AG, Sanofi-Aventis SA and Wyeth are providing "millions" of dollars for the research effort, he said.
The consortium will collect and combine already existing data on serious liver side effects, tissue samples housed in two Britain-based academic institutions, and information and DNA samples from at least one pharmaceutical firm on Stevens-Johnson Syndrome and a related skin condition known as toxic epidermal necrolysis. The DNA from the individuals with side effects will be compared with DNA from "control" subjects who didn't have drug side effects to see if there are genetic variations among the two groups.
Mr. Holden said that if the first two studies are successful, the consortium would then move to other serious side effects like heart trouble and kidney damage that are linked to several different types of drugs as well as drugs in the same class.
The data from the consortium will be made public and could be used by government regulators such as the Food and Drug Administration.
Janet Woodcock, the FDA's chief medical officer, will work with the consortium, although the agency isn't formally a member. "We want this kind of information," she said of the genetic studies, so the agency can find ways to prevent drug side effects or to better manage them. Dr. Woodcock said it is possible that FDA regulations and guidelines on drug development and approval could change if the studies yield clear results.
Many serious drug side effects, such as an increased risk for heart attacks and strokes seen with Merck & Co.'s withdrawn painkiller Vioxx, don't become apparent until after drugs hit the market and thousands or millions more people are exposed. Most clinical studies used to gain approval for a drug involve several hundred to a few thousand patients.
Already, the FDA is highlighting genetic information to help doctors and patients manage drug side effects. Last month alone, the agency said as many as one-third of people on the blood-thinning drug warfarin metabolize the drug differently than expected and warned that breast-feeding women on painkillers with codeine could expose the infant to too much codeine if they are "ultra-rapid" metabolizers of the drug. However, the FDA stopped short of recommending that patients undergo genetic testing to see how they might process the drugs
I forgot to mention (because it's beaten into the mainstream mindset that only free market thinkers can be "conflicted")) that the comparative effectiveness crowd has some conflicts of their own, starting with the fact that they are funded by insurance companies. But I guess taking money from organizations that switch people from one molocule to another without telling patients is okay for bloggers like Health Care Renewal. The science linking statin response to genetic mutation is pretty compelling -- but maybe HCR wants to challenge the science in this area too?
Then there is the trial attorney/Soros/Avorn connection that is never disclosed. Drugwonks posted on that previously.
http://drugwonks.com/2007/02/iom_safety_committee_conflicted_and_confused.html
Then there is the trial attorney/Soros/Avorn connection that is never disclosed. Drugwonks posted on that previously.
http://drugwonks.com/2007/02/iom_safety_committee_conflicted_and_confused.html
“If you want to save money and save lives, the "switching" we need in the United States is a one from a focus on acute care to one on chronic care.â€
So begins a new op-ed in The Journal of Life Sciences.
The complete article can be found at:
http://www.tjols.com/article-289.html
To cut healthcare costs, we need to focus on early treatment of chronic conditions, rather than force patients to switch to generic alternatives that may not be equivalent to the medicines they are using.
The repercussions of choosing short-term thinking over long-term results, of short-term cost-based choices over patient-based care, of “me-too†medicines over the right medicine for the right patient at the right time—are pernicious to both the public purse as well as the public health.
So begins a new op-ed in The Journal of Life Sciences.
The complete article can be found at:
http://www.tjols.com/article-289.html
To cut healthcare costs, we need to focus on early treatment of chronic conditions, rather than force patients to switch to generic alternatives that may not be equivalent to the medicines they are using.
The repercussions of choosing short-term thinking over long-term results, of short-term cost-based choices over patient-based care, of “me-too†medicines over the right medicine for the right patient at the right time—are pernicious to both the public purse as well as the public health.
Here's a weak effort to discredit my argument through misdirection and personal attacks. Only my kids can do that with any success.
http://hcrenewal.blogspot.com/2007/09/over-top-denunciation-of-comparative.html
I have posted my response below in case HCR doesn't see fit to publish it.
If you are going to attack me you had better have your facts right. Not even close.
1. You treat congestive heart failure with anti-hypertension drugs. Ask any doctor.
2. At the risk of being deliberately misconstrued again, I will refer you to the A-HeFT study and it's design which included BiDIl with OTHER anti-hypertensives to prolong survival from congestive heart failure.
3. As for the ALLHAT study, nice of you to ignore step 1. Let me quote Dr. Michael Weber who was an investigator in ALLHAT on the design of the study and it's impact on blacks..."it was poorly designed, the interpretations were disingenuous, it violated appropriate scientific reporting, and most frightening, it did something that was so unethical that if a pharmaceutical company had done it or any of us as individual academics had done it, we would not only be thrown out of our jobs, we would be pilloried and maybe even be facing criminal charges: And one thing that did show up in favor of diuretics, the fact that they cause fewer strokes than one of the other drug classes, was driven entirely by a 40% excess stroke rate in black patients that was predictable before the study began. "
Like I said Avorn attacked BiDil for being a lousy study but peddles his academic detailing plan and uses ALLHAT as a dispensing model.
You can try to sling mud about the fact that CMPI accepts grant from drug companies -- and we do so proudly because they actually invent things that help people -- but get your freakin facts right. If you don't know that hypertension drugs are used to treat heart failure don't talk about them. And I know a lot more about the ALLHAT situation then you ever will. What's nonsense is you trying apologize for a movement that places the cost of drugs over the quality of human life. As for the rest of the post, I am still waiting to see evidence that people are less interesting in hating drug companies than in helping people live. Most of the post are biased in that they believe drugs are part of the apparatus by which corporate capitalism maintains inequalities that harm society and the health care system. Keep drugs off the market and strike a blow for economic justice and health equity. If people die in the process so what? The end justifies the means. That is what drives the comparative effectiveness movement.
http://hcrenewal.blogspot.com/2007/09/over-top-denunciation-of-comparative.html
I have posted my response below in case HCR doesn't see fit to publish it.
If you are going to attack me you had better have your facts right. Not even close.
1. You treat congestive heart failure with anti-hypertension drugs. Ask any doctor.
2. At the risk of being deliberately misconstrued again, I will refer you to the A-HeFT study and it's design which included BiDIl with OTHER anti-hypertensives to prolong survival from congestive heart failure.
3. As for the ALLHAT study, nice of you to ignore step 1. Let me quote Dr. Michael Weber who was an investigator in ALLHAT on the design of the study and it's impact on blacks..."it was poorly designed, the interpretations were disingenuous, it violated appropriate scientific reporting, and most frightening, it did something that was so unethical that if a pharmaceutical company had done it or any of us as individual academics had done it, we would not only be thrown out of our jobs, we would be pilloried and maybe even be facing criminal charges: And one thing that did show up in favor of diuretics, the fact that they cause fewer strokes than one of the other drug classes, was driven entirely by a 40% excess stroke rate in black patients that was predictable before the study began. "
Like I said Avorn attacked BiDil for being a lousy study but peddles his academic detailing plan and uses ALLHAT as a dispensing model.
You can try to sling mud about the fact that CMPI accepts grant from drug companies -- and we do so proudly because they actually invent things that help people -- but get your freakin facts right. If you don't know that hypertension drugs are used to treat heart failure don't talk about them. And I know a lot more about the ALLHAT situation then you ever will. What's nonsense is you trying apologize for a movement that places the cost of drugs over the quality of human life. As for the rest of the post, I am still waiting to see evidence that people are less interesting in hating drug companies than in helping people live. Most of the post are biased in that they believe drugs are part of the apparatus by which corporate capitalism maintains inequalities that harm society and the health care system. Keep drugs off the market and strike a blow for economic justice and health equity. If people die in the process so what? The end justifies the means. That is what drives the comparative effectiveness movement.
Let's restrict access out of cost considerations and use safety as the excuse!!!
http://www.telegraph.co.uk/news/main.jhtml?xml=/news/2007/09/19/ncancer219.xml
http://www.telegraph.co.uk/news/main.jhtml?xml=/news/2007/09/19/ncancer219.xml
PRINCIPLES FOR REAUTHORIZATION OF sCHIP
From the Health Policy Consensus Group
* The primary focus of the State Children’s Health Insurance Program should be to cover children in families with incomes at or below 200 percent of poverty. States that wish to expand sCHIP to cover children and adults in higher-income families are free to do so with their own state funds.
For those above 200 percent of poverty, the appropriate federal mechanism for support is through a combination of tax reform and direct financial subsidies to help families purchase the private health insurance of their choice.
* The program’s subsidies should be re-structured to encourage the purchase of private health insurance. sCHIP subsidies could be used to allow parents to purchase the health coverage that they believe is best for their children, including adding them to policies that may be offered at their workplaces. Research shows that children and their parents benefit if the whole family is covered.
* The federal-state matching ratio for sCHIP funding should be changed to eliminate the distortions that exist in today’s system. States receive a higher federal matching rate for covering sCHIP recipients (which today include many adults) than they receive for covering children eligible for Medicaid, even though these Medicaid children are in families with lower incomes. Congress should focus on fixing the perverse incentives that reward states at a higher level for enrolling higher-income sCHIP children over poorer Medicaid children. The current funding formulas also mean more federal sCHIP dollars will go to wealthier states that can afford to expand the program than to poorer states that do not have sufficient state funds to expand their programs.
* sCHIP must not be turned into another entitlement program modeled after Medicaid, with unlimited federal funds matching state spending on benefits. That would add to the taxpayers’ already-overwhelming burden of tens of trillions of dollars in unfunded entitlement liabilities. It also would encourage states to use accounting tricks to inappropriately increase federal payments, as they have done for years in the Medicaid program. sCHIP must remain as a capped funding program to the states, and Congress must require states to live within their allocations.
Here is the complete Consensus Group statement:
Download file
Two-thirds of uninsured children are eligible for either sCHIP or Medicaid under current law, including many children under 200 percent of poverty who are not yet enrolled. Expanding sCHIP to children in higher-income families would mean shifting the focus away from these children who most need help and would grow the program into a middle-class entitlement that goes far beyond its current mission of helping near-poor children. Reauthorization of sCHIP should concentrate on reducing the number of near-poor children who are eligible for coverage.
From the Health Policy Consensus Group
* The primary focus of the State Children’s Health Insurance Program should be to cover children in families with incomes at or below 200 percent of poverty. States that wish to expand sCHIP to cover children and adults in higher-income families are free to do so with their own state funds.
For those above 200 percent of poverty, the appropriate federal mechanism for support is through a combination of tax reform and direct financial subsidies to help families purchase the private health insurance of their choice.
* The program’s subsidies should be re-structured to encourage the purchase of private health insurance. sCHIP subsidies could be used to allow parents to purchase the health coverage that they believe is best for their children, including adding them to policies that may be offered at their workplaces. Research shows that children and their parents benefit if the whole family is covered.
* The federal-state matching ratio for sCHIP funding should be changed to eliminate the distortions that exist in today’s system. States receive a higher federal matching rate for covering sCHIP recipients (which today include many adults) than they receive for covering children eligible for Medicaid, even though these Medicaid children are in families with lower incomes. Congress should focus on fixing the perverse incentives that reward states at a higher level for enrolling higher-income sCHIP children over poorer Medicaid children. The current funding formulas also mean more federal sCHIP dollars will go to wealthier states that can afford to expand the program than to poorer states that do not have sufficient state funds to expand their programs.
* sCHIP must not be turned into another entitlement program modeled after Medicaid, with unlimited federal funds matching state spending on benefits. That would add to the taxpayers’ already-overwhelming burden of tens of trillions of dollars in unfunded entitlement liabilities. It also would encourage states to use accounting tricks to inappropriately increase federal payments, as they have done for years in the Medicaid program. sCHIP must remain as a capped funding program to the states, and Congress must require states to live within their allocations.
Here is the complete Consensus Group statement:
Download file
Two-thirds of uninsured children are eligible for either sCHIP or Medicaid under current law, including many children under 200 percent of poverty who are not yet enrolled. Expanding sCHIP to children in higher-income families would mean shifting the focus away from these children who most need help and would grow the program into a middle-class entitlement that goes far beyond its current mission of helping near-poor children. Reauthorization of sCHIP should concentrate on reducing the number of near-poor children who are eligible for coverage.
Additional thoughts on warfarin, genetic testing and personalized medicine courtesy of Dr Caroline Wright of the Foundation for Genomics and Population Health (a charitable company registered in England and Wales) …
“Just a month after the label for the blood-thinning drug warfarin was updated to explain that genetic variation in specific genes influences how patients respond to the drug (see previous news article), the US Food and Drug Agency (FDA) has approved the first genetic test for warfarin sensitivity.
Warfarin is the most widely used anti-coagulant medication in the world, prescribed to over 2 million people a year to prevent blood clots, heart attacks and strokes. Patients can display markedly different responses to the drug, so doses vary enormously between individuals. Achieving the correct dose is critical, as patients who receive too high a dose are at risk of severe bleeding, whilst those who receive too low a dose may remain at risk of life-threatening blood clots.
The Nanosphere Verigene Metabolism Nucleic Acids Test detects particular variations in two genes, CYP2C9 and VKORC1, which are involved in the metabolism and mechanism of action of warfarin respectively. Specific variants of these genes are identified from a patient sample by hybridization to sequence specific probes (oligonucleotides) attached to a microarray. These are subsequently detected using the Verigene System which measures light scattering from gold nanospheres tethered to another complementary oligonucleotide. Depending upon the genotype, patients can then divided into slow, fast or normal warfarin metabolisers and their doses adjusted accordingly.
FDA states that it cleared the test based on a broad range of published literature together with the results of a study, conducted by the manufacturer, on hundreds of DNA samples. ‘In a three site study, the test was accurate in all cases where the test yielded a result, although 8% of the tests could not identify which genetic variants were present.’ Although the Nanosphere test is not intended as a stand-alone tool to determine optimum drug dosage but to be used alongside clinical evaluation and other tools to determine the best treatment for patients, this approval underlines the FDA’s ongoing commitment to personalised medicineâ€
Remember – PDUFA page 182. Working together we can accomplish great things for the public health.
“Just a month after the label for the blood-thinning drug warfarin was updated to explain that genetic variation in specific genes influences how patients respond to the drug (see previous news article), the US Food and Drug Agency (FDA) has approved the first genetic test for warfarin sensitivity.
Warfarin is the most widely used anti-coagulant medication in the world, prescribed to over 2 million people a year to prevent blood clots, heart attacks and strokes. Patients can display markedly different responses to the drug, so doses vary enormously between individuals. Achieving the correct dose is critical, as patients who receive too high a dose are at risk of severe bleeding, whilst those who receive too low a dose may remain at risk of life-threatening blood clots.
The Nanosphere Verigene Metabolism Nucleic Acids Test detects particular variations in two genes, CYP2C9 and VKORC1, which are involved in the metabolism and mechanism of action of warfarin respectively. Specific variants of these genes are identified from a patient sample by hybridization to sequence specific probes (oligonucleotides) attached to a microarray. These are subsequently detected using the Verigene System which measures light scattering from gold nanospheres tethered to another complementary oligonucleotide. Depending upon the genotype, patients can then divided into slow, fast or normal warfarin metabolisers and their doses adjusted accordingly.
FDA states that it cleared the test based on a broad range of published literature together with the results of a study, conducted by the manufacturer, on hundreds of DNA samples. ‘In a three site study, the test was accurate in all cases where the test yielded a result, although 8% of the tests could not identify which genetic variants were present.’ Although the Nanosphere test is not intended as a stand-alone tool to determine optimum drug dosage but to be used alongside clinical evaluation and other tools to determine the best treatment for patients, this approval underlines the FDA’s ongoing commitment to personalised medicineâ€
Remember – PDUFA page 182. Working together we can accomplish great things for the public health.
Alison Bass (a former Boston Globe reporter with a long hate the industry bias) is the latest apologist for the increase in suicides as a result of the fearmongering over SSRIs. In an editorial called "Suicide Rates as a PR Tool" she attributes better mental health care and gun control (!) Really? So how are kids killing themselves now in the wake of better mental health care and stricter gun controls if SSRIs have nothing to do with it. The idiocy of zealot courtesy of another anti-medication fanatic, Univ of Maryland researcher Julie Zito.
Oh, Bass is the author of a forthcoming book entitled, "Side Effects: A Best-selling Drug on Trial." How about fearmongering and demeaning those who have struggled to combat suicide as a PR tool. Where does a suicide denier stack up next to a Holocaust denier.
http://www.boston.com/news/globe/editorial_opinion/
Others like Alex (I stole the documents) Berenson dismiss the number of suicides as so small as to really merit concern. Funny, when Steve (I want to cause people's hands to tremble a little bit before they write that prescription," )Nissen and Curt Furberg were foaming at the mouth about 25 'unexplained' heart attacks among kids taking ADHD drugs over a ten year period that was enough to demand a black box an entire class of drugs and for the NY Times to run story after story validating as opposed to questioning the concerns.
http://www.nytimes.com/2006/02/10/health/policy/10drug.html
http://www.nytimes.com/2006/02/21/health/21psyc.html?fta=y
Keep it coming. Every time these whack jobs and their apologists take a run at the work of Robert Gibbons -- which has been verified by Greg Simon at Group of Health Puget Sound and J. John Mann and many others -- the most extreme and dangerous they appear.
Oh, Bass is the author of a forthcoming book entitled, "Side Effects: A Best-selling Drug on Trial." How about fearmongering and demeaning those who have struggled to combat suicide as a PR tool. Where does a suicide denier stack up next to a Holocaust denier.
http://www.boston.com/news/globe/editorial_opinion/
Others like Alex (I stole the documents) Berenson dismiss the number of suicides as so small as to really merit concern. Funny, when Steve (I want to cause people's hands to tremble a little bit before they write that prescription," )Nissen and Curt Furberg were foaming at the mouth about 25 'unexplained' heart attacks among kids taking ADHD drugs over a ten year period that was enough to demand a black box an entire class of drugs and for the NY Times to run story after story validating as opposed to questioning the concerns.
http://www.nytimes.com/2006/02/10/health/policy/10drug.html
http://www.nytimes.com/2006/02/21/health/21psyc.html?fta=y
Keep it coming. Every time these whack jobs and their apologists take a run at the work of Robert Gibbons -- which has been verified by Greg Simon at Group of Health Puget Sound and J. John Mann and many others -- the most extreme and dangerous they appear.
In PDUFA, that is. Page 182. That's where the language creating the Reagan/Udall Foundation begins. And if you want to talk about real FDA reform -- its really the most important part of the whole package.
But what's been written about it can be summed up in two words -- almost nothing.
All the more reason to watch this space.
But what's been written about it can be summed up in two words -- almost nothing.
All the more reason to watch this space.
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.
