Latest Drugwonks' Blog
Here's Alan Greenspan on the economic models used by the Fed and the banking community that "justified" the deep exposure of some financial institutions in subprime mortgage instruments:
"The models used by the finance industry to determine risk and measure economic strength are too simple to fully account for human responses. We cannot hope to anticipate the specifics of future crises with any degree of confidence."
http://money.cnn.com/2008/03/17/news/economy/greenspan/index.htm?postversion=2008031707
Translation: the rational models of utility and discounting activities are outdated because they fail to capture rapid and wide variations in response to risk and uncertainty.
Similarly, comparative effectiveness research, complete with QALYs and the assumption that standardizing care will lead to lower costs and optimal health are essentially ersatz consumer welfare models based again on the "rational actor" view of economics. There is more variability in healthcare because valuations and value do not correspond to particular price but rather to individual perceptions of risk and uncertainty that are part and parcel of the effort to treat and prevent disease. The simple models developed to predict and shape human responses in the healthcare system will anticipate changes or outcomes with any accuracy. Nor have they.
We have come a long way from when the RAND experiment was conducted.
"The models used by the finance industry to determine risk and measure economic strength are too simple to fully account for human responses. We cannot hope to anticipate the specifics of future crises with any degree of confidence."
http://money.cnn.com/2008/03/17/news/economy/greenspan/index.htm?postversion=2008031707
Translation: the rational models of utility and discounting activities are outdated because they fail to capture rapid and wide variations in response to risk and uncertainty.
Similarly, comparative effectiveness research, complete with QALYs and the assumption that standardizing care will lead to lower costs and optimal health are essentially ersatz consumer welfare models based again on the "rational actor" view of economics. There is more variability in healthcare because valuations and value do not correspond to particular price but rather to individual perceptions of risk and uncertainty that are part and parcel of the effort to treat and prevent disease. The simple models developed to predict and shape human responses in the healthcare system will anticipate changes or outcomes with any accuracy. Nor have they.
We have come a long way from when the RAND experiment was conducted.
A post on the wsj.com healthblog by Heather Won Tesoriero claims
"Late last night, a pair of congressmen introduced a bill aimed at creating a pathway for approval of generic biotech drugs.
Finally, you say. But, wait, there’s a catch, and it’s a big one. The legislation would also give brand-name biotech drugs an extra 14 1/2 years of patent protection. (Read a summary of the bill, or the complete text.) That almost defeats the purpose of establishing a route to market for generic biotech drugs, advocates for them say. "
Well I read the summary and the text and it sounds like someone is buying the generic trade group's spin on the patent protection. No one is getting 15 years of additional patent protection. Rather, it gives companies going forward 12 years of data exclusivity and 2.5 years of patent life that of course begins well before a biologic enters clinical trials. The wailing is part of a larger strategy by the generic trade group to argue for the right to challenge biologic patents early and get market exclusivity as generic firms receive if they do make a successful challenge. Wailing as in: "Waah! Innovators get solid patent protection so I can't start copying their products from day one...waah!!
I am sure the anti-capitalists who attack pharma and BIO will go wild...
http://blogs.wsj.com/health/2008/03/14/want-generic-biotech-you-might-wait-14-more-years/?mod=googlenews_wsj
"Late last night, a pair of congressmen introduced a bill aimed at creating a pathway for approval of generic biotech drugs.
Finally, you say. But, wait, there’s a catch, and it’s a big one. The legislation would also give brand-name biotech drugs an extra 14 1/2 years of patent protection. (Read a summary of the bill, or the complete text.) That almost defeats the purpose of establishing a route to market for generic biotech drugs, advocates for them say. "
Well I read the summary and the text and it sounds like someone is buying the generic trade group's spin on the patent protection. No one is getting 15 years of additional patent protection. Rather, it gives companies going forward 12 years of data exclusivity and 2.5 years of patent life that of course begins well before a biologic enters clinical trials. The wailing is part of a larger strategy by the generic trade group to argue for the right to challenge biologic patents early and get market exclusivity as generic firms receive if they do make a successful challenge. Wailing as in: "Waah! Innovators get solid patent protection so I can't start copying their products from day one...waah!!
I am sure the anti-capitalists who attack pharma and BIO will go wild...
http://blogs.wsj.com/health/2008/03/14/want-generic-biotech-you-might-wait-14-more-years/?mod=googlenews_wsj
Those who think a comparative effectiveness institute will generate super savings by imposing standardization on clinical practice should read Benjamin Brewer's latest blog in the WSJ entitled "Uncertainty is My Co-Pilot"
http://online.wsj.com/article/SB120527311006228441.html?mod=djempersonal
http://online.wsj.com/article/SB120527311006228441.html?mod=djempersonal
Two articles in the NY Times -- one about the discussion of off-label uses for Zyprexa and another accusing drug companies of launching meds at a higher dose than necessary -- are devoid of scientific context.
The failure to report on off-label uses without describing the process of arriving at them and the fact that most are the product of trying to solve a clinical problem is a consistent and glaring gap in reporting. And burying the science only empowers trial attorneys and federal prosecutors who are constantly prodded by Senator Grassley to use the threat of prosecution to shake down drug companies for settlement fees.
With respect to the allegation that Avastin, Herceptin, Cerazyme, etc., are overdosed on purpose is completely without merit. Dosing is -- by the nature of clinical trials -- one size fits all. Achieving an appropriate dose in the real world goes on all the time and hitting the right dose -- as the warfarin genetic labeling effort suggests -- is a matter of genetic variation and other factors that cannot be integrated into drug development. And consider this: in some instances changing the timing and dosing of certain drugs can be regarded as off-label use and therefore subject to prosecution and tort lawyer litigation.
When Avastin was being developed it's initial "failure" in early trials was -- according to Judah Folkman who pioneered angiogenesis drugs -- linked directly to the fact that the FDA wanted every patient to get the same dose even though he believed varying dosing to a number of criteria -- would have led to better and more precise outcomes.
Many drugs don't work in most people at the marketed dose. The failure of HMOs not to provide coverage of the most expensive and innovative medicines should have nothing to do with dosing. The right dose for the right patient at the right time for the best outcome is the goal of any doctor. The Critical Path leading to personalized medicine or tailored treatments reflects the commitment of companies and the FDA to move away from the one-size fits all approach.
The media continues to ignore the underlying science shaping medicine and it leads to the arrogant notion that prosecutors and policy analysts can strip doctors of their discretion about how to prescribe and use medicines to advance the health of their patients.
http://www.nytimes.com/2008/03/16/business/16gaucher.html?pagewanted=1&_r=1&ref=todayspaper
http://www.nytimes.com/2008/03/15/business/15drug.html?scp=1&sq=berenson&st=nyt
The failure to report on off-label uses without describing the process of arriving at them and the fact that most are the product of trying to solve a clinical problem is a consistent and glaring gap in reporting. And burying the science only empowers trial attorneys and federal prosecutors who are constantly prodded by Senator Grassley to use the threat of prosecution to shake down drug companies for settlement fees.
With respect to the allegation that Avastin, Herceptin, Cerazyme, etc., are overdosed on purpose is completely without merit. Dosing is -- by the nature of clinical trials -- one size fits all. Achieving an appropriate dose in the real world goes on all the time and hitting the right dose -- as the warfarin genetic labeling effort suggests -- is a matter of genetic variation and other factors that cannot be integrated into drug development. And consider this: in some instances changing the timing and dosing of certain drugs can be regarded as off-label use and therefore subject to prosecution and tort lawyer litigation.
When Avastin was being developed it's initial "failure" in early trials was -- according to Judah Folkman who pioneered angiogenesis drugs -- linked directly to the fact that the FDA wanted every patient to get the same dose even though he believed varying dosing to a number of criteria -- would have led to better and more precise outcomes.
Many drugs don't work in most people at the marketed dose. The failure of HMOs not to provide coverage of the most expensive and innovative medicines should have nothing to do with dosing. The right dose for the right patient at the right time for the best outcome is the goal of any doctor. The Critical Path leading to personalized medicine or tailored treatments reflects the commitment of companies and the FDA to move away from the one-size fits all approach.
The media continues to ignore the underlying science shaping medicine and it leads to the arrogant notion that prosecutors and policy analysts can strip doctors of their discretion about how to prescribe and use medicines to advance the health of their patients.
http://www.nytimes.com/2008/03/16/business/16gaucher.html?pagewanted=1&_r=1&ref=todayspaper
http://www.nytimes.com/2008/03/15/business/15drug.html?scp=1&sq=berenson&st=nyt
Last August I commented on the Lou Dobbs program that it was unlikely that Congress would take FDA reform seriously “until there were dead bodies.â€
Unfortunately, I was right.
On Friday, in the shadows of tainted Heparin, the Senate passed a budget resolution to give the F.D.A. an additional $375 million, a 20 percent increase over this year.
Some representative quotes on this issue from an article by Gardiner Harris in today’s edition of the New York Times:
“Congress has a responsibility to close the glaring gaps in food and drug safety that have begun to overwhelm the F.D.A.,†Senator Edward M. Kennedy, Democrat of Massachusetts.
“F.D.A. needs a serious infusion of resources and strong leadership dedicated to reforming the agency,†said Representative Henry A. Waxman, Democrat of California.
And, of course, everyone’s favorite FDA expert, Representative Rosa DeLauro, Democrat of Connecticut, “I don’t want to throw money at an agency that doesn’t have the infrastructure to carry out its mission.â€
Some top agency officials are simply “incompetent,†she added, and real change can occur only with a new administration.
Really, a new administration? Note to Representative DeLauro – the head of every center at the FDA is a career government employee. At the FDA, an agency of roughly 10,000, there are fewer than 10 “political†appointees. Does Ms. DeLauro, the chair of the House appropriations subcommittee with authority over the agency, believe that Dr. Janet Woodcock is “incompetent?†What about CBER’s Dr. Jesse Goodman – widely considered one of the finest scientists in government?
And then, of course, there’s the usual ranting from our favorite Sheep in Wolfe’s Clothing.
Here’s a link to the complete article:
http://www.nytimes.com/2008/03/17/health/policy/17fda.html?scp=2&sq=gardiner+harris&st=nyt
Alas, the title of the article says it all –“Tainted Drugs Put Focus on the F.D.A.â€
And it isn’t even a done deal.
Unfortunately, I was right.
On Friday, in the shadows of tainted Heparin, the Senate passed a budget resolution to give the F.D.A. an additional $375 million, a 20 percent increase over this year.
Some representative quotes on this issue from an article by Gardiner Harris in today’s edition of the New York Times:
“Congress has a responsibility to close the glaring gaps in food and drug safety that have begun to overwhelm the F.D.A.,†Senator Edward M. Kennedy, Democrat of Massachusetts.
“F.D.A. needs a serious infusion of resources and strong leadership dedicated to reforming the agency,†said Representative Henry A. Waxman, Democrat of California.
And, of course, everyone’s favorite FDA expert, Representative Rosa DeLauro, Democrat of Connecticut, “I don’t want to throw money at an agency that doesn’t have the infrastructure to carry out its mission.â€
Some top agency officials are simply “incompetent,†she added, and real change can occur only with a new administration.
Really, a new administration? Note to Representative DeLauro – the head of every center at the FDA is a career government employee. At the FDA, an agency of roughly 10,000, there are fewer than 10 “political†appointees. Does Ms. DeLauro, the chair of the House appropriations subcommittee with authority over the agency, believe that Dr. Janet Woodcock is “incompetent?†What about CBER’s Dr. Jesse Goodman – widely considered one of the finest scientists in government?
And then, of course, there’s the usual ranting from our favorite Sheep in Wolfe’s Clothing.
Here’s a link to the complete article:
http://www.nytimes.com/2008/03/17/health/policy/17fda.html?scp=2&sq=gardiner+harris&st=nyt
Alas, the title of the article says it all –“Tainted Drugs Put Focus on the F.D.A.â€
And it isn’t even a done deal.
Here's a link to a a video that shows how atherosclerosis happens. This arterial tour gives you a graphic view of how unhealthy habit and genes can conspire to clog the major routes that supply blood to the heart and back again. No butter with your popcorn when watching this movie. Steve Nissen makes a cameo appearance as an avenging LDL molecule..(Not really.)
Read Full Story
Read Full Story
The Center for Medicine in the Public Interest (the think tank home of drugwonks.com) is part of a transatlantic public policy institute consortium on the future of healthcare technology assessment (HTA). One of the member organizations, the German Institut fur Unternehmerische Freiheit (the Institute for Free Enterprise) held a seminar in Berlin yesterday entitled, "Cost Pressures on the German Health System -- Is Health Technology Assessment the Solution?"
One of the speakers was Dr. Christian Behles, Director and Professor of Drug Regulatory Affairs at the University of Bonn and an advisor to the German government.
Professor Behles pointed out that while IQWiG casts a suspicious eye on industry-designed pharmaco-economic studies, they use industry-sponsored RCTS as the basis of their comparative effectiveness findings.
He also noted that these RCTS were not designed to be used for head-to-head comparisons -- further reinforcing the recent comments made by NICE's Sir Michael Rawlings in front of the British House of Commons that HTA "is not based on empirical research."
In other words, IQWiG embraces industry-sponsored RCT data that was not designed to be used comparatively, while rejecting industry-sponsored data that was specifically designed to show the value of a new innovative medicine.
When is an industry study not an industry study? It seems that, for IQWiG, the answer is "when it's convenient."
It's interesting to note that the title of Professor Behles' presentation was, "HTA and Political Interference -- the Case of Germany's IQWiG."
One of the speakers was Dr. Christian Behles, Director and Professor of Drug Regulatory Affairs at the University of Bonn and an advisor to the German government.
Professor Behles pointed out that while IQWiG casts a suspicious eye on industry-designed pharmaco-economic studies, they use industry-sponsored RCTS as the basis of their comparative effectiveness findings.
He also noted that these RCTS were not designed to be used for head-to-head comparisons -- further reinforcing the recent comments made by NICE's Sir Michael Rawlings in front of the British House of Commons that HTA "is not based on empirical research."
In other words, IQWiG embraces industry-sponsored RCT data that was not designed to be used comparatively, while rejecting industry-sponsored data that was specifically designed to show the value of a new innovative medicine.
When is an industry study not an industry study? It seems that, for IQWiG, the answer is "when it's convenient."
It's interesting to note that the title of Professor Behles' presentation was, "HTA and Political Interference -- the Case of Germany's IQWiG."
The best part of the ODAC meeting was when the committee as a whole dismissed Richard Padzur question -- designed to prop up an increasingly suspect coverage decision by CM -- asking to slap a one-size fits all dosing limit on ESAs. To quote one panelists: "This is silliness." Other comments could be characterized as dismissive.
In general the panel appeared perturbed that the FDA essentially did not provide it with either an objective or complete picture of the overall risks and benefits of ESA use in chemotherapy. The same goes with Padzur's lame attempt to misconstrue his negative opinion of the nature of quality of life data because most of it is observational study as the final word on the subject. He fooled the media who failed to look deeply into the data but not practicing oncologists on the panel.
Of course the media had all but predicted the demise of ESAs and is treating the ODAC decision as some sort of upset. Read the CNN.com piece below. You can just feel the shock and disappointment....Ultimately companies and doctors will have to work together to come up with more patient-centric data on who the drugs work for. If they had done this in the first place, the generalized concerns about safety could have been mitigated. Let's hope they do so going forward.
The committee did the right thing by swatting away Padzur's thinly veiled attemtp to manipulate them into affirming CMS' wrongheaded coverage decision. It did the right thing by giving doctors flexibility and recommending limiting use in areas where no benefit seems to exist.
http://money.cnn.com/2008/03/13/news/companies/amgen/?postversion=2008031316
In general the panel appeared perturbed that the FDA essentially did not provide it with either an objective or complete picture of the overall risks and benefits of ESA use in chemotherapy. The same goes with Padzur's lame attempt to misconstrue his negative opinion of the nature of quality of life data because most of it is observational study as the final word on the subject. He fooled the media who failed to look deeply into the data but not practicing oncologists on the panel.
Of course the media had all but predicted the demise of ESAs and is treating the ODAC decision as some sort of upset. Read the CNN.com piece below. You can just feel the shock and disappointment....Ultimately companies and doctors will have to work together to come up with more patient-centric data on who the drugs work for. If they had done this in the first place, the generalized concerns about safety could have been mitigated. Let's hope they do so going forward.
The committee did the right thing by swatting away Padzur's thinly veiled attemtp to manipulate them into affirming CMS' wrongheaded coverage decision. It did the right thing by giving doctors flexibility and recommending limiting use in areas where no benefit seems to exist.
http://money.cnn.com/2008/03/13/news/companies/amgen/?postversion=2008031316
The committee voted against restricting the use of ESAs to small cell lung cancer.
Question 2--Should FDA require that product labeling be modified? Please address each of four potential approaches to mitigating risks through revised labeling separately.
a. To date, only clinical trials in small cell lung cancer have reasonably excluded an increased risk for death among patients receiving ESAs. Trials have demonstrated an increased risk of death and/or tumor promotion in head/neck, non-small cell lung cancer, breast (neoadjuvant and metastatic settings), lymphoid malignancies, and cervical cancers. Tumor types, other than those listed above, have not been adequately studied. Should the current indication be modified to restrict use only to patients with small cell lung cancer?
Vote: YES-- 6 NO-- 8
Question 2--Should FDA require that product labeling be modified? Please address the following potential approaches to mitigating risks through revised labeling.
b. Vote: The PREPARE trial demonstrated decreased relapse-free and overall survival in breast cancer patients receiving neoadjuvant chemotherapy. The risk/benefit assessment is different for patients receiving neoadjuvant and adjuvant chemotherapies than for patients with metastatic or incurable cancers. Should the current indication be modified to include a statement that ESA use is not indicated for patients receiving potentially curative treatments?
Vote: YES--11 NO--2
The current indication should be modified to say that it should not be used in the adjuvant setting.
c. Vote: Although increased tumor promotion and/or decreased survival have been demonstrated in several tumor types, adverse findings have been duplicated in two malignancies-breast cancer and head and neck cancer Should the current indication be modified to include a statement that ESA use is not indicated for patients with breast and/or head & neck cancers? (If yes, please specify breast and/or head & neck cancer).
Vote: YES--9 NO--5
Modified to say that ESA use not indicated for metastatic breast and head and neck cancers.
Question 2--Should FDA require that product labeling be modified? Please address each of four potential approaches to mitigating risks through revised labeling separately.
a. To date, only clinical trials in small cell lung cancer have reasonably excluded an increased risk for death among patients receiving ESAs. Trials have demonstrated an increased risk of death and/or tumor promotion in head/neck, non-small cell lung cancer, breast (neoadjuvant and metastatic settings), lymphoid malignancies, and cervical cancers. Tumor types, other than those listed above, have not been adequately studied. Should the current indication be modified to restrict use only to patients with small cell lung cancer?
Vote: YES-- 6 NO-- 8
Question 2--Should FDA require that product labeling be modified? Please address the following potential approaches to mitigating risks through revised labeling.
b. Vote: The PREPARE trial demonstrated decreased relapse-free and overall survival in breast cancer patients receiving neoadjuvant chemotherapy. The risk/benefit assessment is different for patients receiving neoadjuvant and adjuvant chemotherapies than for patients with metastatic or incurable cancers. Should the current indication be modified to include a statement that ESA use is not indicated for patients receiving potentially curative treatments?
Vote: YES--11 NO--2
The current indication should be modified to say that it should not be used in the adjuvant setting.
c. Vote: Although increased tumor promotion and/or decreased survival have been demonstrated in several tumor types, adverse findings have been duplicated in two malignancies-breast cancer and head and neck cancer Should the current indication be modified to include a statement that ESA use is not indicated for patients with breast and/or head & neck cancers? (If yes, please specify breast and/or head & neck cancer).
Vote: YES--9 NO--5
Modified to say that ESA use not indicated for metastatic breast and head and neck cancers.
http://www.bmj.com/cgi/content/full/327/7429/1459?eaf
Hazardous journey
Parachute use to prevent death and major trauma related to gravitational challenge: systematic review of randomised controlled trials
Gordon C S Smith, professor1, Jill P Pell, consultant2
1 Department of Obstetrics and Gynaecology, Cambridge University, Cambridge CB2 2QQ, 2 Department of Public Health, Greater Glasgow NHS Board, Glasgow G3 8YU
Correspondence to: G C S Smith gcss2@cam.ac.uk
Abstract
Objectives To determine whether parachutes are effective in preventing major trauma related to gravitational challenge.
Design Systematic review of randomised controlled trials.
Data sources: Medline, Web of Science, Embase, and the Cochrane Library databases; appropriate internet sites and citation lists.
Study selection: Studies showing the effects of using a parachute during free fall.
Main outcome measure Death or major trauma, defined as an injury severity score > 15.
Results We were unable to identify any randomised controlled trials of parachute intervention.
Conclusions As with many interventions intended to prevent ill health, the effectiveness of parachutes has not been subjected to rigorous evaluation by using randomised controlled trials. Advocates of evidence based medicine have criticised the adoption of interventions evaluated by using only observational data. We think that everyone might benefit if the most radical protagonists of evidence based medicine organised and participated in a double blind, randomised, placebo controlled, crossover trial of the parachute.
I am sure CBO's Peter Orzag, who has been pushing comparative effectiveness as a way to reduce costs by denying access to new technology will be the first to volunteer....
Hazardous journey
Parachute use to prevent death and major trauma related to gravitational challenge: systematic review of randomised controlled trials
Gordon C S Smith, professor1, Jill P Pell, consultant2
1 Department of Obstetrics and Gynaecology, Cambridge University, Cambridge CB2 2QQ, 2 Department of Public Health, Greater Glasgow NHS Board, Glasgow G3 8YU
Correspondence to: G C S Smith gcss2@cam.ac.uk
Abstract
Objectives To determine whether parachutes are effective in preventing major trauma related to gravitational challenge.
Design Systematic review of randomised controlled trials.
Data sources: Medline, Web of Science, Embase, and the Cochrane Library databases; appropriate internet sites and citation lists.
Study selection: Studies showing the effects of using a parachute during free fall.
Main outcome measure Death or major trauma, defined as an injury severity score > 15.
Results We were unable to identify any randomised controlled trials of parachute intervention.
Conclusions As with many interventions intended to prevent ill health, the effectiveness of parachutes has not been subjected to rigorous evaluation by using randomised controlled trials. Advocates of evidence based medicine have criticised the adoption of interventions evaluated by using only observational data. We think that everyone might benefit if the most radical protagonists of evidence based medicine organised and participated in a double blind, randomised, placebo controlled, crossover trial of the parachute.
I am sure CBO's Peter Orzag, who has been pushing comparative effectiveness as a way to reduce costs by denying access to new technology will be the first to volunteer....
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.
