In the course of this past month I have been blogging about Eli Lilly and Zyprexa (olanzapine) and how the company marketing managed to make a silk purse out of this medication, which we now know to have been massively overhyped both as to its efficacy and its safety. We are now onto their tricks, and Lilly is being hit with record fines--just as Zyprexa is about to go off patent anyway and as Lilly is taking the $16 billion it made on the drug to the bank. A new article, generally very good, on the history of this debacle, called to my attention by a loyal ally of this blog, is:
http://www.rollingstone.com/politics/story/25569107/bitter_pill
Some great quotes-- after starting off talking about how medical investigators have to be wary of placebo effects among the subjects which could produce misleading results, the author goes on: "The story of how Zyprexa and other atypicals [newer drugs for psychosis] became a multibillion-dollar market suggests that the medical community — doctors, researchers, the institutions that back them — may be themselves prone to a placebo effect: the willed conviction that a new drug, presented as a breakthrough, must in fact be one, that a product sold as healing must in fact do good."
And: "[Allen] Jones, [an inspector for the PA inspector general's office turned Zyprexa whistle-blower] an outsider gazing in, thought he saw a basic quid pro quo, a corrupt transaction between two parties that stood to benefit. But it is possible that he missed a more complex and fundamental truth: that the system of developing and marketing drugs is so broken that it can coax corruption out of well-meaning doctors who think they are doing good. Every incremental permission that the atypical makers allowed themselves, and the regulators allowed them — structuring their studies in the most advantageous ways, omitting studies unhelpful to their cause, publicizing only the most supportive data — helped shift the medical perception of the atypicals. The companies didn't need to pay off doctors. They just needed to put the grant money out there and wait for the true believers...to walk through the door."
Indeed if I had one criticism of this otherwise insightful article by Ben Wallace-Wells, it is his readiness to excuse physicians as being subject to a "placebo effect" rather than a "basic quid pro quo." As this blog has documented numerous times, there is sadly enough evidence of the latter to balance out the undoubted occurrence of the former.
Wallace-Wells ends his article with a plea for a return to the older days of psychiatry--when psychiatrists actually spent time with their patients, talked with them, got involved with the events in their lives, and monitored them carefully enough so that no drug side effect was likely to get out of control. He makes a good case that since those days, we have decided that it was too expensive for psychiatrists to spend that sort of time with patients with diseases such as schizophrenia. Let the lower-paid psychologists and social workers hold the patients' hands and let the MD simply show up once a month and write the prescriptions. Unfortunately, that assumes that the newer antipsychotics are rifle bullets that worked directly on the causes of schizophrenia, when based on what we now know they are much more like shotgun shells, if they hit the target at all. Wallace-Wells also cites a WHO study that hints that patients with schizophrenia in other parts of the world, where treatment is short on medications but long on social support, actually do better than in the US.
Friday, January 30, 2009
Tuesday, January 27, 2009
Compassion or Conflict of Interest? New Medicare Cancer Coverage Rules
Check out these sources on the recent Medicare rules change for coverage of cancer drugs:
http://online.wsj.com/article/SB123302745342318667.html
http://blogs.wsj.com/health/2009/01/27/cosy-world-of-cancer-drug-compendia-draws-questions/#more-5055
http://www.nytimes.com/2009/01/27/health/27cancer.html?_r=2&pagewanted=1&hp
Basics: Medicare has relied in the past on a single drug compendium as its authority for choosing which cancer chemotherapy drugs are covered. Critics have charged that this is wrong because some promising new drugs are excluded and patients who have exhausted all other hope are unable to get coverage for these reasonable drugs. The new rule allows many more drugs to be covered by expanding to four the number of compendia that might be viewed as authoritative. Clinical oncologists (who at least until recently earned a percentage commission as it were on chemo drugs that they administer) praise this move.
Problem: this seems less a boon for desperate patients than a boondoggle designed to help out the drug companies. The new compendia that have been added to the list include those that are compiled by people who have serious conflicts of interest with the drug industry, and even a compendium that for all intents and purposes is written by the drug companies. (One outfit that essentially sells itself to the drug industry in return for listing their products in its compendium has the nerve to call itself the "Foundation for Evidence-Based Medicine.")
As a sign that this is intended for the oncologists' and drug makers' incomes rather than real patient benefit, it seems significant that representatives of the patient advocacy groups interviewed for these press accounts generally were skeptical about the new rules.
If the Obama Administration is serious about holding down health care costs while maintaining quality care, this is one rule they will have to tackle.
http://online.wsj.com/article/SB123302745342318667.html
http://blogs.wsj.com/health/2009/01/27/cosy-world-of-cancer-drug-compendia-draws-questions/#more-5055
http://www.nytimes.com/2009/01/27/health/27cancer.html?_r=2&pagewanted=1&hp
Basics: Medicare has relied in the past on a single drug compendium as its authority for choosing which cancer chemotherapy drugs are covered. Critics have charged that this is wrong because some promising new drugs are excluded and patients who have exhausted all other hope are unable to get coverage for these reasonable drugs. The new rule allows many more drugs to be covered by expanding to four the number of compendia that might be viewed as authoritative. Clinical oncologists (who at least until recently earned a percentage commission as it were on chemo drugs that they administer) praise this move.
Problem: this seems less a boon for desperate patients than a boondoggle designed to help out the drug companies. The new compendia that have been added to the list include those that are compiled by people who have serious conflicts of interest with the drug industry, and even a compendium that for all intents and purposes is written by the drug companies. (One outfit that essentially sells itself to the drug industry in return for listing their products in its compendium has the nerve to call itself the "Foundation for Evidence-Based Medicine.")
As a sign that this is intended for the oncologists' and drug makers' incomes rather than real patient benefit, it seems significant that representatives of the patient advocacy groups interviewed for these press accounts generally were skeptical about the new rules.
If the Obama Administration is serious about holding down health care costs while maintaining quality care, this is one rule they will have to tackle.
Monday, January 26, 2009
The Outsourcing of Drug Supply: Market Failure
I would have thought that this article by Gardiner Harris would have stirred up more of a fuss:
http://www.nytimes.com/2009/01/20/health/policy/20drug.html?_r=1
It contains this interesting quote from one of India's top generic drug manufacturers: “If tomorrow China stopped supplying pharmaceutical ingredients, the worldwide pharmaceutical industry would collapse.” The article adds that if America were to decide tomorrow that it is a top national priority to be able to make our own supply of penicillin, it would take at least two years before the first fermentation apparatus could come on line.
The fact that the rest of the world has become totally dependent on China for the ingredients needed to make almost all drugs represents a smart business move by Chinese leaders over the past two decades. It also represents the irony that the reason it costs so much more to make drugs in the US and Europe--making outsourcing financially attractive--is because plants in those nations are so thoroughly regulated and inspected.
A part of the reason Harris's article comes as news is that the pharmaceutical industry has always treated its supply sources as part of its web of business secrets, and has generally been very unwilling to come clean on just where it gets its materials.
As my wife astutely commented when I mentioned this article to her, it shows how much of a joke it has been that people are worried about Americans buying drugs from Canada, where supposedly quality might be a problem and we could end up with counterfeit drugs. Given that both America and Canada in the end get all their drugs from China anyway...
Jokes aside, and not to engage in anti-Chinese sentiment (I gave some lectures in Beijing in December and people treated me very nicely and fed me excellent food), but let's for a minute make the assumption that it is not good public policy for us to be completely dependent on one other nation for our pharmaceutical supply. It then seems to follow that just in case there is a person, in these post-subprime-mortgage-financial-meltdown days, who honestly still believes that the "free market" is ideally self-regulating and always produces the maximum good for humanity when left alone, that we seem to have yet another example of "market failure," with which the road of the drug industry in recent years has been thickly strewn.
http://www.nytimes.com/2009/01/20/health/policy/20drug.html?_r=1
It contains this interesting quote from one of India's top generic drug manufacturers: “If tomorrow China stopped supplying pharmaceutical ingredients, the worldwide pharmaceutical industry would collapse.” The article adds that if America were to decide tomorrow that it is a top national priority to be able to make our own supply of penicillin, it would take at least two years before the first fermentation apparatus could come on line.
The fact that the rest of the world has become totally dependent on China for the ingredients needed to make almost all drugs represents a smart business move by Chinese leaders over the past two decades. It also represents the irony that the reason it costs so much more to make drugs in the US and Europe--making outsourcing financially attractive--is because plants in those nations are so thoroughly regulated and inspected.
A part of the reason Harris's article comes as news is that the pharmaceutical industry has always treated its supply sources as part of its web of business secrets, and has generally been very unwilling to come clean on just where it gets its materials.
As my wife astutely commented when I mentioned this article to her, it shows how much of a joke it has been that people are worried about Americans buying drugs from Canada, where supposedly quality might be a problem and we could end up with counterfeit drugs. Given that both America and Canada in the end get all their drugs from China anyway...
Jokes aside, and not to engage in anti-Chinese sentiment (I gave some lectures in Beijing in December and people treated me very nicely and fed me excellent food), but let's for a minute make the assumption that it is not good public policy for us to be completely dependent on one other nation for our pharmaceutical supply. It then seems to follow that just in case there is a person, in these post-subprime-mortgage-financial-meltdown days, who honestly still believes that the "free market" is ideally self-regulating and always produces the maximum good for humanity when left alone, that we seem to have yet another example of "market failure," with which the road of the drug industry in recent years has been thickly strewn.
Is Device Industry Shaping Up?
According to Barry Meier in the New York Times--
http://www.nytimes.com/2009/01/24/business/24device.html?ref=health
--the medical device industry has started to get the message that they have an ethics problem on their hands and need to clean up their act.
Admittedly the message might be hard to miss, when the nation's biggest manufacturers of surgical-implant hip and knee prostheses are all under Justice Dept. monitoring and ordered to post on the Internet how much they are paying each physician with whom they consult or contract. Nonetheless, if Meier's story is to be believed, the industry is taking a hard look at itself and actually changing its practices--at least in the direction of greater disclosure and transparency.
Meier reports that the Justice Dept. investigations showed that the majority of financial contacts between the makers and the docs were on the up and up. An example, apparently, from the article, was an orthopedist in Kingston, PA, who had previously given courses in which he trained his peers how to use the implants manufactured by Zimmer Holdings. In 2007, Zimmer abruptly called him and cancelled his next set of scheduled training workshops. Only recently did they call him back and start to reschedule him. In other cases, consulting fees are apparently paid for legitimate consulting that leads to new product development or old product improvement.
Nonetheless, Justice found enough evidence of illegitimate payments--basically bribes for using large volumes of a company's product exclusively--that the firms caved in and did not oppose the settlement. Perhaps today, the legitimate contacts will continue and the others will start to go by the boards. (Comments welcome from those who have any insider experience, which I certainly do not!)
http://www.nytimes.com/2009/01/24/business/24device.html?ref=health
--the medical device industry has started to get the message that they have an ethics problem on their hands and need to clean up their act.
Admittedly the message might be hard to miss, when the nation's biggest manufacturers of surgical-implant hip and knee prostheses are all under Justice Dept. monitoring and ordered to post on the Internet how much they are paying each physician with whom they consult or contract. Nonetheless, if Meier's story is to be believed, the industry is taking a hard look at itself and actually changing its practices--at least in the direction of greater disclosure and transparency.
Meier reports that the Justice Dept. investigations showed that the majority of financial contacts between the makers and the docs were on the up and up. An example, apparently, from the article, was an orthopedist in Kingston, PA, who had previously given courses in which he trained his peers how to use the implants manufactured by Zimmer Holdings. In 2007, Zimmer abruptly called him and cancelled his next set of scheduled training workshops. Only recently did they call him back and start to reschedule him. In other cases, consulting fees are apparently paid for legitimate consulting that leads to new product development or old product improvement.
Nonetheless, Justice found enough evidence of illegitimate payments--basically bribes for using large volumes of a company's product exclusively--that the firms caved in and did not oppose the settlement. Perhaps today, the legitimate contacts will continue and the others will start to go by the boards. (Comments welcome from those who have any insider experience, which I certainly do not!)
Protecting Prescription Privacy from Industry Marketing
So much recent legislative attention has been focused on sunshine biils, requiring disclosure of physician payments from the drug companies, that other issues may have been forgotten. An article from Seattle--
http://seattlepi.nwsource.com/local/397259_pharmacyprivacy24.html
--shows us that in Washington State, legislators are attempting to close a loophole in the HIPAA privacy law, that has been exploited by both drug companies and pharmacy benefits managers.
The loophole arose because the Bush administration added language stating that HIPAA could be extended to cover communications among physicians and pharmacists and their "business associates" so long as the communication had something to do with "patient care."
The result is that a patient whose prescription is about to run out may receive a letter saying one of two things. If it's the drug company footing the bill, the letter reminds the patient that they should get a refill, and then launches into a marketing pitch for a newer, more expensive medication for the same problem.
If it's the PBM, the pitch goes in the other direction--after the obligatory reminder to get the refill (that makes it "patient care"), the pitch becomes switching to a cheaper generic drug.
The scam is that most patients assume that their prescription information is private, and so they figure that the letter must have come either from their physician's office or from their pharmacy. They may not realize that the letter lacks this authority and did not come from anyone personally familiar with their medical or medication history.
HIPAA fortunately allows individual states to pass more stringent privacy requirements, so the bill in Washington is designed to close the loophole for that state's residents.
My own view of this is that I am completely unsympathetic to marketing to patients to get them to buy more expensive drugs. I must admit to having a lot more sympathy with an effort to get more docs to prescribe generic drugs when they are medically equivalent. But this ought not be done by ads directed to the patient. Instead, the doc can get reminder letters from the insurer urging a generic switch; and the pharmacy plan can give the patients a price break on generics that will incentivize them to ask their docs whether a generic would work.
http://seattlepi.nwsource.com/local/397259_pharmacyprivacy24.html
--shows us that in Washington State, legislators are attempting to close a loophole in the HIPAA privacy law, that has been exploited by both drug companies and pharmacy benefits managers.
The loophole arose because the Bush administration added language stating that HIPAA could be extended to cover communications among physicians and pharmacists and their "business associates" so long as the communication had something to do with "patient care."
The result is that a patient whose prescription is about to run out may receive a letter saying one of two things. If it's the drug company footing the bill, the letter reminds the patient that they should get a refill, and then launches into a marketing pitch for a newer, more expensive medication for the same problem.
If it's the PBM, the pitch goes in the other direction--after the obligatory reminder to get the refill (that makes it "patient care"), the pitch becomes switching to a cheaper generic drug.
The scam is that most patients assume that their prescription information is private, and so they figure that the letter must have come either from their physician's office or from their pharmacy. They may not realize that the letter lacks this authority and did not come from anyone personally familiar with their medical or medication history.
HIPAA fortunately allows individual states to pass more stringent privacy requirements, so the bill in Washington is designed to close the loophole for that state's residents.
My own view of this is that I am completely unsympathetic to marketing to patients to get them to buy more expensive drugs. I must admit to having a lot more sympathy with an effort to get more docs to prescribe generic drugs when they are medically equivalent. But this ought not be done by ads directed to the patient. Instead, the doc can get reminder letters from the insurer urging a generic switch; and the pharmacy plan can give the patients a price break on generics that will incentivize them to ask their docs whether a generic would work.
Change in Washington and Elsewhere--Latest News
Several news items in the last 24 hours' worth of e-mail. Our friends at Integrity in Science Watch report on the reintroduction by Sens. Grassley and Kohl of their Physician Payment Sunshine Act in Congress, and mention in passing that several more academic medical centers appear to be moving in the direction of ordering fuller disclosure of faculty members' payments from the drug and device makers: Harvard joins Cleveland Clinic and Duke in pursuing more sunshine, as does a major health provider in Minnesota, Park Nicolett.
My recent mailing from the American Academy of Family Physicians urges me to write my congressman to support the Obama economic stimulus package, in part because it contains a number of health care investments friendly toward primary care-- one of which is said to be increasing the amount of research the Feds can conduct comparing drugs head to head to determine which is more effective.
My recent mailing from the American Academy of Family Physicians urges me to write my congressman to support the Obama economic stimulus package, in part because it contains a number of health care investments friendly toward primary care-- one of which is said to be increasing the amount of research the Feds can conduct comparing drugs head to head to determine which is more effective.
Friday, January 23, 2009
Lilly Fine for Zyprexa Off Label Marketing: $1.4B
When it came to fines paid for illegal marketing practices, the big drug companies had for some time been stuck in the mere hundreds of millions. Give Eli Lilly credit--they stole the lead with total fines of $1.4 billion for Zyprexa (olanzapine) marketing.
Specifically, the company tried to push its second-generation anti-psychotic drug well beyond its FDA-approved uses for schizophrenia and bipolar disorder. Perhaps the most extreme use detailed in these recent charges was a campaign to get docs to use Zyprexa as a--get this--sleeping pill, since sedation is a common side effect. Lilly reps were schooled in a "5 at 5" campaign, by which docs working in nursing homes were urged to prescribe a 5 milligram dose of the drug at 5 pm to assure a good night's sleep. This occurred well after Lilly knew of the drug's serious side effects, particularly obesity and an increased incidence of Type II diabetes. The settlement also cites Lilly's efforts to assure that the drug was heavily marketed to primary care physicians, despite the fact that relatively few primary care docs would be treating the major indications for which the drug was labelled.
As I alluded to in a previous post (http://brodyhooked.blogspot.com/2009/01/are-second-generation-antipsychotic.html), the basic problem here seems to have been the aggressive marketing of all the so-called "second generation" or "atypical" antipsychotics as extremely safe, free of the horrible side effects of tardive dyskinesia and the zombie-like state often seen with high-dose, continued use of the older antisychotics. There seems to be a two-step process. First you convince the medical community that a drug is extraordinarily free of side effects. Then you engage in "indication creep"-- since the drug is so safe, why not try it for patients who are less and less sick, or for patients who suffer from conditions less and less closely related to the major indications for the drug. In the case of Zyprexa, the creep was away from major psychosis and toward milder and milder mental health problems in the elderly, including depression, sleep disorders, and problem behavior such as wandering associated with dementia. In the case of the serotonin antidepressants, the creep took the form of prescribing antidepressants only in severe depression, to prescribing the drugs for any patients who had a bad hair day. Finally the research is done, very late in the day, revealing that the supposed absence of side effects was actually mythical (along with the mythical reports of the drugs' real efficacy), the creation of flawed research and aggressive marketing rather than pharmaceutical science.
Kmietowicz Z. Eli Lilly pays record $1.4bn for promoting off-label use of olanzapine. BMJ 2009, 338:b217. (Subscription required)
Specifically, the company tried to push its second-generation anti-psychotic drug well beyond its FDA-approved uses for schizophrenia and bipolar disorder. Perhaps the most extreme use detailed in these recent charges was a campaign to get docs to use Zyprexa as a--get this--sleeping pill, since sedation is a common side effect. Lilly reps were schooled in a "5 at 5" campaign, by which docs working in nursing homes were urged to prescribe a 5 milligram dose of the drug at 5 pm to assure a good night's sleep. This occurred well after Lilly knew of the drug's serious side effects, particularly obesity and an increased incidence of Type II diabetes. The settlement also cites Lilly's efforts to assure that the drug was heavily marketed to primary care physicians, despite the fact that relatively few primary care docs would be treating the major indications for which the drug was labelled.
As I alluded to in a previous post (http://brodyhooked.blogspot.com/2009/01/are-second-generation-antipsychotic.html), the basic problem here seems to have been the aggressive marketing of all the so-called "second generation" or "atypical" antipsychotics as extremely safe, free of the horrible side effects of tardive dyskinesia and the zombie-like state often seen with high-dose, continued use of the older antisychotics. There seems to be a two-step process. First you convince the medical community that a drug is extraordinarily free of side effects. Then you engage in "indication creep"-- since the drug is so safe, why not try it for patients who are less and less sick, or for patients who suffer from conditions less and less closely related to the major indications for the drug. In the case of Zyprexa, the creep was away from major psychosis and toward milder and milder mental health problems in the elderly, including depression, sleep disorders, and problem behavior such as wandering associated with dementia. In the case of the serotonin antidepressants, the creep took the form of prescribing antidepressants only in severe depression, to prescribing the drugs for any patients who had a bad hair day. Finally the research is done, very late in the day, revealing that the supposed absence of side effects was actually mythical (along with the mythical reports of the drugs' real efficacy), the creation of flawed research and aggressive marketing rather than pharmaceutical science.
Kmietowicz Z. Eli Lilly pays record $1.4bn for promoting off-label use of olanzapine. BMJ 2009, 338:b217. (Subscription required)
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