I have occasionally posted about the controversy aroused by the American Psychiatric Association's (APA)forthcoming DSM-V classification of mental illnesses, for example:
http://brodyhooked.blogspot.com/2009/07/more-on-psychiatrys-dsm-v-mess.html
http://brodyhooked.blogspot.com/2009/06/will-psychiatrys-dsm-v-be-huge-growth.html
http://brodyhooked.blogspot.com/2012/01/from-health-care-renewal-egregious.html
I will now offer a further comment based on two posts, first, Dr. Bernard Carroll over on Health Care Renewal:
http://hcrenewal.blogspot.com/2012/11/does-american-psychiatry-matter.html
--who in turn cites the 1 Boring Old Man blog run by a retired psychiatrist:
http://1boringoldman.com/index.php/2012/11/02/cest-la-vie/
The short form of these two posts is that the APA has antagonized so many folks with the way they have mishandled the DSM-V business that they risk making both DSM-V and themselves irrelevant to mental health, and that smart people will ignore DSM-V and turn elsewhere for classifications of mental illness.
What follows is my attempt to synthesize some important ideas from these two recent posts, and I'll use the excuse that even though I am not a psychiatrist, the other two bloggers are, and so I am simply trying to pass along what they have said.
1 Boring Old Man recalls what it was like to practice psychiatry in the 1970s and 1980s. He recalls that a thousand flowers bloomed. There were many disparate, incompatible theories and schools of psychiatry--and that was good. Psychiatrists read Freud and benefited from the reading, but very few were the cardboard-caricarture Freudians that now are derided and are trotted out as the excuse as to why psychiatry had to reform itself. When the DSM-III (the first modern version) came out, most psychiatrists realized why it had been created, and basically supported the idea that some sort of standard diagnostic approach was necessary; but hardly anyone found it clinically useful. The eclectic mix of disparate schools and theories was confusing to the statisticians and epidemiologists, but a rich mine ideas for the psychiatrist who had to confront a wide variety of symptoms in a wide variety of people. The eclectic mix gave them the freedom to do what worked best under any given circumstance.
This state of affairs, these psychiatrists say, has evolved from toolbox to straitjacket as the new DSM-V seems a further attempt to impose a rigid orthodoxy on the field that stresses brain biology and drug treatment--so much so that many are now saying they'll have none of it and the APA can go take a hike.
Okay, now I'll add my own ideas. When eclecticism is working for a field, and people decide to throw out the eclecticism and replace it with something clinically much less helpful, that's bad. What this blog is mostly concerned about is the impact of industry-driven commercialization on medicine. So the next question is, how much of this bad stuff can be traced to drug industry influence.
In a previous post:
http://brodyhooked.blogspot.com/2010/05/whitakers-anatomy-of-epidemic.html
--I recounted journalist Robert Whitaker's history of the APA (in his Anatomy of an Epidemic) giving the specific dates (between 1974 and 1980) when the APA decided they had major problems on their hands, that those problems could be solved by a big influx of Pharma dollars, and that their policies therefore should shift to make APA an extremely Pharma-friendly venue. The above-listed posts further document how the new DSM-V appears to be an even bolder move toward allowing the Pharma fox to guard the psychiatric-diagnosis henhouse, in ways that maximize industry profits and the drugging of patients with even mild symptoms.
So does this shift in the DSM, that results in a further flight from clinical utility, have something to do with Pharma influence? Yes.
Wednesday, November 7, 2012
Monday, November 5, 2012
Let's Do It Again: Latest Federal Settlement (Boehringer Ingelheim)
We are back to our standard form, to report the latest incident of a drug firm settling with the Feds over alleged lawbreaking:
Drug company: Boehringer Ingelheim
Drugs involved: Combivent (ipratropium/albuterol), Micardis (telmisartan), Aggrenox (aspirin/dipyridamole)
Amount of settlement: $95M
Settlement equals what percentage of one year's sales of the drug?: I could quickly locate annual US sales figures only for two of the drugs in 2010, Micardis and Combivent; the settlement amount is 4% of that combined figure.
Did the company admit wrongdoing? Yes/No: Of course not
Link to detailed news coverage:
http://www.washingtonpost.com/business/pharmaceutical-company-to-pay-95m-to-settle-allegations-of-improper-promotion/2012/10/25/ef595032-1ee1-11e2-8817-41b9a7aaabc7_story.html
http://articles.courant.com/2012-10-26/business/hc-boehringer-ingelheim-fraud-20121026_1_hypertension-drug-civil-settlement-risk-of-heart-attacks
This is such small potatoes in the balance sheet of a big drug firm, less than $100M, that it's hardly worth even mentioning, except that the Feds claimed that besides evidence for off-label promotion which amounted to lying about the drug's effectiveness, the company also engaged in paying kickbacks to docs for prescribing the drugs. Not surprising to any regular readers of this blog, the kickbacks consisted of payment for serving on advisory boards, speaker panels, speakers' training programs, and consultancies.
The company, in denying any wrongdoing, commented that industry standards had recently changed, that the company was cooperating fully, and that they had entered into a supposed integrity agreement. Given the frequency with which other drug companies in the past have entered into such agreements and then repeatedly re-violated, one can be forgiven for skepticism that this amounts to any significant deterrent.
Hat tip to our Health Care Renewal friends for tipping us off:
http://hcrenewal.blogspot.com/2012/10/just-another-day-at-office-boehringer.html
Drug company: Boehringer Ingelheim
Drugs involved: Combivent (ipratropium/albuterol), Micardis (telmisartan), Aggrenox (aspirin/dipyridamole)
Amount of settlement: $95M
Settlement equals what percentage of one year's sales of the drug?: I could quickly locate annual US sales figures only for two of the drugs in 2010, Micardis and Combivent; the settlement amount is 4% of that combined figure.
Did the company admit wrongdoing? Yes/No: Of course not
Link to detailed news coverage:
http://www.washingtonpost.com/business/pharmaceutical-company-to-pay-95m-to-settle-allegations-of-improper-promotion/2012/10/25/ef595032-1ee1-11e2-8817-41b9a7aaabc7_story.html
http://articles.courant.com/2012-10-26/business/hc-boehringer-ingelheim-fraud-20121026_1_hypertension-drug-civil-settlement-risk-of-heart-attacks
This is such small potatoes in the balance sheet of a big drug firm, less than $100M, that it's hardly worth even mentioning, except that the Feds claimed that besides evidence for off-label promotion which amounted to lying about the drug's effectiveness, the company also engaged in paying kickbacks to docs for prescribing the drugs. Not surprising to any regular readers of this blog, the kickbacks consisted of payment for serving on advisory boards, speaker panels, speakers' training programs, and consultancies.
The company, in denying any wrongdoing, commented that industry standards had recently changed, that the company was cooperating fully, and that they had entered into a supposed integrity agreement. Given the frequency with which other drug companies in the past have entered into such agreements and then repeatedly re-violated, one can be forgiven for skepticism that this amounts to any significant deterrent.
Hat tip to our Health Care Renewal friends for tipping us off:
http://hcrenewal.blogspot.com/2012/10/just-another-day-at-office-boehringer.html
Saturday, November 3, 2012
Roses (and Thorns) by Any Other Name: ACRE's New "Guidelines"
I have blogged at length about the Association of Clinical Researchers and Educators (ACRE), the primary outlet for pharmapologist sentiments, for example:
http://brodyhooked.blogspot.com/2012/01/another-planet-heard-from-sunshine-law.html
http://brodyhooked.blogspot.com/2010/04/encounters-with-dr-tom-stossel.html
http://brodyhooked.blogspot.com/2010/02/another-county-heard-from-acre.html
ACRE has now come out with what seems alternatively to be called either a "statement" or "guidelines" on "relationships between physicians and industry":
http://www.policymed.com/2012/11/association-of-clinical-researchers-and-educators-releases-statement-on-relationships-between-physicians-and-industry.html
(Side note: I looked for this statement first on ACRE's own website and found that their latest posted news release was dated mid-2011, so I'm not sure what's up with them, but for all I can tell this statement is legit.)
If you want to cut to the chase and read the statement directly, not the summary of it in the press release, you can go to:
http://aace.metapress.com/content/k12021244705x03w/fulltext.pdf
The summary says that this is to be published in the journal Endocrine Practice, which is not exactly a high-impact journal, but leave that aside. Corresponding author is Dr. Michael A. Weber of SUNY-Downstate, with our old friends Drs. Tom Stossel, Avi Markowitz, and philosopher Lance Stell among the writing committee.
OK, so why should a pharmascold blog like this one devote (virtual) ink to anything coming out of ACRE? I decided it might be instructive to see what happens when this organization attempts to be positive and actually issue a set of practical guidelines. Think of an analogy with the Romney campaign. Romney had it easy early on when all he had to do was attack "Obamacare." Then things got tougher when unkind folks asked him what his own health plan consisted of. When forced to come up with concrete policy proposals, Romney suddenly discovered that he actually agreed with some parts of the Affordable Care Act. So one might ask whether any similar "aha" moments might emerge from ACRE's recent efforts.
Let's quickly review ACRE's track record. Perhaps guided by in-house philosopher Stell, ACRE has never been content to quibble about the details of the ethics of the Pharma-medicine relationship. They have always gone for the jugular, attacking the core assumptions of the pharmascold position (if I may caricature it that way for brevity).
What are those assumptions? Folks like me always start with a collection of ideas:
So, having trashed all the more usual ethical assumptions on which one could base guidelines for physician-industry interactions, and which in fact were relied on by folks like the IOM, NIH, and AAMC in their proposed guidelines, what can ACRE come up with?
Their summary statement seems to be: "While there may be strengths and weaknesses to [current] approaches [to regulate these relationships], the best course is a middle road: one that values transparency of such relationships, but does not harm patients or slow innovation in the process."
They then begin their statement with a substatement: "The vast majority of collaborations between physicians and industry has added considerably to improved patient care. Moreover, these collaborations have been conducted with integrity and commitment. Critics of these collaborations have raised concerns, largely speculative and theoretical, that have created complicated and counterproductive regulations and rules regarding these relationships."
This sounds like the old ACRE, trashing the pharmascold position as based solely on theoretical concerns when everyone knows that in the real world, nothing but benefits flow from the exchange of cash between docs and industry. And in fact, a good deal of the verbiage in the actual statement consists of a long list of all the advantages to science and patient care provided by industry and strong relationships between medicine and industry. But wait...
Here are some comments culled from the summary review, which reflect the language in the statement itself:
On medical societies: "Accordingly, ACRE recommended that leaders of medical societies have a strong obligation to create internal operational procedures ... to ensure corporate support does not create inappropriate endorsements of industry products. ... societies should be proactive in protecting themselves and their corporate supporters against the appearance of inappropriate endorsements."
On CME: "Faculty should create their own talks"
On publishing: "Cannot prevent or delay publication of unfavorable results... Begin before outlines of article or any drafts are written ... 'ghostwriting' should be avoided and the use of external writing agencies or 'editorial assistance' should be undertaken with great care..."
On travel expenses for meeting attendance: "Travel support to attend a meeting as a member of the audience, not the faculty, should be declined...Acceptance of travel support must not be linked in any way to prescribing performance or other support of the sponsor’s products"
On consulting/advising: "Avoid giving the impression of primarily defending industry interests"
Comments:
http://brodyhooked.blogspot.com/2012/01/another-planet-heard-from-sunshine-law.html
http://brodyhooked.blogspot.com/2010/04/encounters-with-dr-tom-stossel.html
http://brodyhooked.blogspot.com/2010/02/another-county-heard-from-acre.html
ACRE has now come out with what seems alternatively to be called either a "statement" or "guidelines" on "relationships between physicians and industry":
http://www.policymed.com/2012/11/association-of-clinical-researchers-and-educators-releases-statement-on-relationships-between-physicians-and-industry.html
(Side note: I looked for this statement first on ACRE's own website and found that their latest posted news release was dated mid-2011, so I'm not sure what's up with them, but for all I can tell this statement is legit.)
If you want to cut to the chase and read the statement directly, not the summary of it in the press release, you can go to:
http://aace.metapress.com/content/k12021244705x03w/fulltext.pdf
The summary says that this is to be published in the journal Endocrine Practice, which is not exactly a high-impact journal, but leave that aside. Corresponding author is Dr. Michael A. Weber of SUNY-Downstate, with our old friends Drs. Tom Stossel, Avi Markowitz, and philosopher Lance Stell among the writing committee.
OK, so why should a pharmascold blog like this one devote (virtual) ink to anything coming out of ACRE? I decided it might be instructive to see what happens when this organization attempts to be positive and actually issue a set of practical guidelines. Think of an analogy with the Romney campaign. Romney had it easy early on when all he had to do was attack "Obamacare." Then things got tougher when unkind folks asked him what his own health plan consisted of. When forced to come up with concrete policy proposals, Romney suddenly discovered that he actually agreed with some parts of the Affordable Care Act. So one might ask whether any similar "aha" moments might emerge from ACRE's recent efforts.
Let's quickly review ACRE's track record. Perhaps guided by in-house philosopher Stell, ACRE has never been content to quibble about the details of the ethics of the Pharma-medicine relationship. They have always gone for the jugular, attacking the core assumptions of the pharmascold position (if I may caricature it that way for brevity).
What are those assumptions? Folks like me always start with a collection of ideas:
- Conflict of interest
- Professionalism
- Trust (alleging that conflicts threaten patient and public trust in medicine)
So, having trashed all the more usual ethical assumptions on which one could base guidelines for physician-industry interactions, and which in fact were relied on by folks like the IOM, NIH, and AAMC in their proposed guidelines, what can ACRE come up with?
Their summary statement seems to be: "While there may be strengths and weaknesses to [current] approaches [to regulate these relationships], the best course is a middle road: one that values transparency of such relationships, but does not harm patients or slow innovation in the process."
They then begin their statement with a substatement: "The vast majority of collaborations between physicians and industry has added considerably to improved patient care. Moreover, these collaborations have been conducted with integrity and commitment. Critics of these collaborations have raised concerns, largely speculative and theoretical, that have created complicated and counterproductive regulations and rules regarding these relationships."
This sounds like the old ACRE, trashing the pharmascold position as based solely on theoretical concerns when everyone knows that in the real world, nothing but benefits flow from the exchange of cash between docs and industry. And in fact, a good deal of the verbiage in the actual statement consists of a long list of all the advantages to science and patient care provided by industry and strong relationships between medicine and industry. But wait...
Here are some comments culled from the summary review, which reflect the language in the statement itself:
On medical societies: "Accordingly, ACRE recommended that leaders of medical societies have a strong obligation to create internal operational procedures ... to ensure corporate support does not create inappropriate endorsements of industry products. ... societies should be proactive in protecting themselves and their corporate supporters against the appearance of inappropriate endorsements."
On CME: "Faculty should create their own talks"
On publishing: "Cannot prevent or delay publication of unfavorable results... Begin before outlines of article or any drafts are written ... 'ghostwriting' should be avoided and the use of external writing agencies or 'editorial assistance' should be undertaken with great care..."
On consulting/advising: "Avoid giving the impression of primarily defending industry interests"
Comments:
- As I noted, ACRE's past publications have ruthlessly trashed the ideas of COI, professionalism, and concern about public trust. But their new statement/guidelines offers no alternative set of principles on which ethical conclusions might be based. And many observers would note that the above-quoted recommendations make no sense at all unless one implicitly assumes concerns about COI, professionalism, and breaches of trust.
- Put another way, whenever the principal actors in ACRE have allowed us to peek behind the curtain to see what basic philosophy motivates them, we see some version of economism, or a faith that the unregulated free market will solve all human problems (see http://brodyhooked.blogspot.com/2011/11/shameless-commerce-division-new-book.html). This proposed set of guidelines is inconsistent with that philosophy. If the market did not want ghostwriting to exist, it would not be so profitable and hence so commonplace. So the guidelines represent a tacit admission that the marketplace cannot solve all these problems on its own, and that the unregulated marketplace indeed creates problems for medicine.
- ACRE's champions have always insisted that pharmascolds have blown a very few anecdotes way out of proportion, to claim that problems at the Pharma-medicine interface are serious and widespread. But if you look at what this blog has repeatedly documented, and then look at what ACRE's guidelines call for, you see that behavior that their own guidelines criticize occurs commonly. So these guidelines represent a tacit admission by ACRE that their past dismissal of these problems is ill-founded.
Monday, October 29, 2012
When the Marketing Tail Wags the Research Dog: More on Medtronic and InFuse
I have posted a number of times on the case of Medtronic, its payments (bribes) to spine surgeons, and its product BMP-2 or InFuse:
http://brodyhooked.blogspot.com/2011/06/taking-professionalism-seriously.html
http://brodyhooked.blogspot.com/2010/12/in-defense-of-paranoia-suspecting.html
http://brodyhooked.blogspot.com/2011/08/in-praise-of-good-corporate-behavior.html
Our good friends at Health Care Renewal now inform us that the staff of the Senate Finance Committee has issued a report on this whole episode:
http://hcrenewal.blogspot.com/2012/10/marketers-systemic-influence-over.html
The Senate staff report itself can be found at:
http://www.finance.senate.gov/imo/media/doc/Medtronic_Report1.pdf
I'd caution you that the entire report is over 2300 pages, of which 22 pages is the report itself and the rest is "exhibits." (More on that later.) I am not sufficiently dedicated to have read all 2300 pages so what follows is based on the HCRenewal summary plus the first 22 pages of the Report proper.
The committee, no doubt at the urging of Sen. Grassley of Iowa, demanded internal documents from Medtronic regarding its clinical trials of InFuse, which is a biological product that makes bone grow. The basic idea is that when a surgeon wants to do a spinal fusion, in which two vertebrae are more or less glued together to stabilize the back, you can do it in two ways. You can take a graft of bone from the patient's hip and use that to bridge the two vertebrae; or you can use InFuse, put into a special metal cage made for the purpose, and it causes bone to grow in the same area and fuses the vertebrae. The problem is when InFuse makes bone grow where you don't want it, or escapes from its cage, or causes a variety of untoward reactions. The earlier posts describe the problems with InFuse, Medtronic's initial efforts to hide the problems, and the exhorbitant sum it paid to spine surgeons who did its bidding; the later posts show how Medtronic has changed its tune and promised a full and neutral investigation.
Now enter the Senate Finance Committee. They plowed through all those documents and concluded that Medtronic exerted an undue influence over the clinical studies and the way they were reported in scientific journals. I'll focus here on one specific anecdote included in the report, that probably add the most to what we have long known about how Pharma allows its marketing apparatus to control the scientific branch.
One study compared the use of InFuse with the standard hip bone graft method. The authors of the study first reported, "12 months after surgery, the patients [sic] graft-site pain had resolved...and no patients complained about the graft-site appearance." Medtronic employee Neil Beals, assigned to manage marketing programs and initiatives for biologic products like InFuse, inserted a comment in the draft: "ALTHOUGH THE PATIENTS DID NOT COMPLAIN ABOUT THE APPEARANCE DIDN'T SOME STILL EXPERIENCE PAIN AT THE DONOR SITE? SEEMS LIKE RESIDUAL EFFECTS OF DONOR SITE SHOULD BE NOTED." The supposedly "scientific" authors then dutifully inserted a sentence: "...even at the 24-month follow-up assessment, some patients continued to experience residual pain at the donor site, and rated the appearance of the site as only fair."
This seems quite a blatant example--the clinician-scientists report that pain and appearance of the donor site are not a problem. The marketing dude back at the company, who probably never laid eyes on a single patient, says, that can't be right, we'll never sell a lot of product that way. So the scientists meekly buckle under and change their report to make it come out like the marketing guy wanted. When you read further that one of the authors of this study was paid $22M in so-called consulting fees by Medtronic between 1997 and 2010, you might hazard a guess as to why the authors were so malleable.
Now let me switch-hit and say a word for the other team. If indeed the Senate Finance staff plowed through 2300 pages of documents, and the worst dirt they could find against Medtronic was the few anecdotes in the brief report, then maybe things were not all that bad. (Except, if you read my previous posts, they were.) But as I say I am not just now about to read all 2300 pages for myself, so we'll just have to leave it there.
http://brodyhooked.blogspot.com/2011/06/taking-professionalism-seriously.html
http://brodyhooked.blogspot.com/2010/12/in-defense-of-paranoia-suspecting.html
http://brodyhooked.blogspot.com/2011/08/in-praise-of-good-corporate-behavior.html
Our good friends at Health Care Renewal now inform us that the staff of the Senate Finance Committee has issued a report on this whole episode:
http://hcrenewal.blogspot.com/2012/10/marketers-systemic-influence-over.html
The Senate staff report itself can be found at:
http://www.finance.senate.gov/imo/media/doc/Medtronic_Report1.pdf
I'd caution you that the entire report is over 2300 pages, of which 22 pages is the report itself and the rest is "exhibits." (More on that later.) I am not sufficiently dedicated to have read all 2300 pages so what follows is based on the HCRenewal summary plus the first 22 pages of the Report proper.
The committee, no doubt at the urging of Sen. Grassley of Iowa, demanded internal documents from Medtronic regarding its clinical trials of InFuse, which is a biological product that makes bone grow. The basic idea is that when a surgeon wants to do a spinal fusion, in which two vertebrae are more or less glued together to stabilize the back, you can do it in two ways. You can take a graft of bone from the patient's hip and use that to bridge the two vertebrae; or you can use InFuse, put into a special metal cage made for the purpose, and it causes bone to grow in the same area and fuses the vertebrae. The problem is when InFuse makes bone grow where you don't want it, or escapes from its cage, or causes a variety of untoward reactions. The earlier posts describe the problems with InFuse, Medtronic's initial efforts to hide the problems, and the exhorbitant sum it paid to spine surgeons who did its bidding; the later posts show how Medtronic has changed its tune and promised a full and neutral investigation.
Now enter the Senate Finance Committee. They plowed through all those documents and concluded that Medtronic exerted an undue influence over the clinical studies and the way they were reported in scientific journals. I'll focus here on one specific anecdote included in the report, that probably add the most to what we have long known about how Pharma allows its marketing apparatus to control the scientific branch.
One study compared the use of InFuse with the standard hip bone graft method. The authors of the study first reported, "12 months after surgery, the patients [sic] graft-site pain had resolved...and no patients complained about the graft-site appearance." Medtronic employee Neil Beals, assigned to manage marketing programs and initiatives for biologic products like InFuse, inserted a comment in the draft: "ALTHOUGH THE PATIENTS DID NOT COMPLAIN ABOUT THE APPEARANCE DIDN'T SOME STILL EXPERIENCE PAIN AT THE DONOR SITE? SEEMS LIKE RESIDUAL EFFECTS OF DONOR SITE SHOULD BE NOTED." The supposedly "scientific" authors then dutifully inserted a sentence: "...even at the 24-month follow-up assessment, some patients continued to experience residual pain at the donor site, and rated the appearance of the site as only fair."
This seems quite a blatant example--the clinician-scientists report that pain and appearance of the donor site are not a problem. The marketing dude back at the company, who probably never laid eyes on a single patient, says, that can't be right, we'll never sell a lot of product that way. So the scientists meekly buckle under and change their report to make it come out like the marketing guy wanted. When you read further that one of the authors of this study was paid $22M in so-called consulting fees by Medtronic between 1997 and 2010, you might hazard a guess as to why the authors were so malleable.
Now let me switch-hit and say a word for the other team. If indeed the Senate Finance staff plowed through 2300 pages of documents, and the worst dirt they could find against Medtronic was the few anecdotes in the brief report, then maybe things were not all that bad. (Except, if you read my previous posts, they were.) But as I say I am not just now about to read all 2300 pages for myself, so we'll just have to leave it there.
Thursday, October 25, 2012
Against Capitalism?
One of my most faithful pen-pals (if such a term can be applied to people who send me e-mails) shipped over this link:
http://dissidentvoice.org/2012/10/bad-pharma-bad-journalism/
Briefly, this blog post recounts the history of an exchange between Dr. Ben Goldacre, a British physician/journalist and author of a new book called Bad Pharma, and a dissident economist, Harry Shutt. Goldacre's book appears based on what I've heard so far to be same ol', same ol' for readers of this blog--he nails the drug industry and its medical hangers-on for their addiction to profits over science and health. Shutt's criticism was that all Goldacre calls for is improved regulation of the industry. How, he asked, can you assume that's any sort of adequate measure, when you've just compiled this huge body of evidence that the industry snaps its fingers at all the regulation previously put in place? Goldacre first sent a wimpy reply back, then ceased to respond at all as Shutt pressed him further.
This exchange points out a basic feature of my book HOOKED as well as of this blog. I'm guilty as Goldacre is charged. I have clung to the position that I accept that we live in a capitalist society and that the drug industry is going to continue to be run as a for-profit endeavor. I have called for a lot of changes in how the industry, medicine, and government all do business, but have not called for nationalization of the industry or making it a public utility.
I may be accused of similar wimpiness in my recent book, The Golden Calf (see http://brodyhooked.blogspot.com/2011/11/shameless-commerce-division-new-book.html). I there attack economism, the belief in an unregulated free market as the solution to all human social problems. But to the extent that I offer a vision for an improved future, it's largely a return to the capitalism of the 1950s where the power of government and organized labor helped balance out the excesses of big business, and not the overthrow of capitalism.
I cannot honestly report that I have a deep philosophical commitment to capitalism, though I am persuaded by authors such as economist-philosopher Amartya Sen that basic respect for human rights and human liberty has to include respect for rights to participate in fair markets. My overall goal has been strategic rather than philosophical. I am trying to get the attention of readers, most especially my fellow physicians and health professionals. If the position from which I started is anti-capitalist, I could expect that hardly any of them would read beyond the first sentence. If I stay under the capitalist big tent and specifically detail the problems with medicine and Pharma, maybe at least a few more of them will pay attention.
Is that a coherent and responsible position to take? The beauty of a blog is that y'all get to decide.
http://dissidentvoice.org/2012/10/bad-pharma-bad-journalism/
Briefly, this blog post recounts the history of an exchange between Dr. Ben Goldacre, a British physician/journalist and author of a new book called Bad Pharma, and a dissident economist, Harry Shutt. Goldacre's book appears based on what I've heard so far to be same ol', same ol' for readers of this blog--he nails the drug industry and its medical hangers-on for their addiction to profits over science and health. Shutt's criticism was that all Goldacre calls for is improved regulation of the industry. How, he asked, can you assume that's any sort of adequate measure, when you've just compiled this huge body of evidence that the industry snaps its fingers at all the regulation previously put in place? Goldacre first sent a wimpy reply back, then ceased to respond at all as Shutt pressed him further.
This exchange points out a basic feature of my book HOOKED as well as of this blog. I'm guilty as Goldacre is charged. I have clung to the position that I accept that we live in a capitalist society and that the drug industry is going to continue to be run as a for-profit endeavor. I have called for a lot of changes in how the industry, medicine, and government all do business, but have not called for nationalization of the industry or making it a public utility.
I may be accused of similar wimpiness in my recent book, The Golden Calf (see http://brodyhooked.blogspot.com/2011/11/shameless-commerce-division-new-book.html). I there attack economism, the belief in an unregulated free market as the solution to all human social problems. But to the extent that I offer a vision for an improved future, it's largely a return to the capitalism of the 1950s where the power of government and organized labor helped balance out the excesses of big business, and not the overthrow of capitalism.
I cannot honestly report that I have a deep philosophical commitment to capitalism, though I am persuaded by authors such as economist-philosopher Amartya Sen that basic respect for human rights and human liberty has to include respect for rights to participate in fair markets. My overall goal has been strategic rather than philosophical. I am trying to get the attention of readers, most especially my fellow physicians and health professionals. If the position from which I started is anti-capitalist, I could expect that hardly any of them would read beyond the first sentence. If I stay under the capitalist big tent and specifically detail the problems with medicine and Pharma, maybe at least a few more of them will pay attention.
Is that a coherent and responsible position to take? The beauty of a blog is that y'all get to decide.
Wednesday, October 24, 2012
Yet More from the Belly of the Beast: Pfizer's Campaign to Market Neurontin Off-Label
Thanks as so often to Dr. Roy Poses over at Health Care Renewal--
http://hcrenewal.blogspot.com/2012/10/when-clinical-trials-are-meant-for.html
--we are alerted to the recent publication by S. Swaroop Vedula and colleagues:
http://www.trialsjournal.com/content/13/1/136
These authors were part of the team that testified in lawsuits brought against Pfizer related to the drug Neurontin (gabapentin). As a result they had access to a trove of internal e-mails and documents. Here they report their analysis of these documents, from two separate legal actions in 2004 and 2008, providing a longitudinal account of how the company approached publication of clinical trial data on gabapentin for off-label uses. (The drug was approved by the FDA for two relatively narrow indications, epilepsy and post-herpetic neuralgia;and the company wanted to extend sales by showing that it worked also for migraine, bipolar disorders, neuropathic pain, and nociceptive pain.)
First the authors documented: "For each of the four off-label indications we included in our study, a document titled ‘marketing assessment,’ designed to examine the financial impact of seeking FDA approval for a new indication versus other methods of increasing sales for the indication, preceded clinical trials sponsored by Pfizer ..." That is, before the company or independent academic scientists had a go at designing and conducting a clinical trial, the marketing people already had their innings and decided on the overall strategy. In this instance, the key decision was not to try to gather data that would allow an aplication to the FDA to expand the approved indications for Neurontin, but to find data that would support off-label prescribing for that usage. And that key decision was made not based on the scientific results of clinical trials, but before the clinical trials were even begun. A critical difference is that if the company had approached the FDA, they would have been legally required to hand over all study results, both favoring the drug and not; while by going the off-label route, they could cherry-pick what they published, as we'll come to. (Reminder: a company cannot legally market a drug for off-label use directly, but its physician "key opinion leaders" are free to recommend off-label use so long as it seems to be at arm's length from the company. Today, drug reps can also hand out trial report reprints that support off-label use, hence the need to publish trials that are favorable.)
The other main reason, besides more control over publication, was that the patent on Neurontin was about the expire and it made no business sense for the company to expand its use just as the drug was about to go generic. In one instance, the decision as to publication of negative results seems to have been driven by the form's "evergreening" strategy, which was to roll out the "new" drug pregabalin as a me-too drug to replace gabapentin as their expensive, heavily-marketed brand-name drug. As pregabalin was about to be launched, the company may have wanted negative trials published about Neurontin, so as to lay the groundwork for later being able to claim that pregabalin was really head and shoulders better than its predecessor.
The next major finding from the authors was, "According to the internal company documents, 'affiliate-driven manuscripts' were written for Pfizer ... by [Medical Action Communications, a medical communication company] and sent to the authors for approval. Each article was coordinated by a manuscript team, consisting of representatives from the medical and marketing divisions of the company." This suggests that ghostwriting--having paid writers spin the research papers the way the company wanted them, and only then letting the scientific "authors" see the drafts of the papers--was simply standard operating procedure within the company. The entire process showed that Pfizer, and especially its marketing division, kept everyone involved in the publication of a paper on a short leash.
Finally, the authors demonstrated that the journals in which papers were published, and the timing of publication, were also chosen for maximum marketing impact--for instance, with positive results published in high-impact journals and published quickly, and with negative results showing up in low-circulation journals years later.
As the authors summarize: "In this study we also observed that publication occurred in journals with higher or lower circulations related to statistical significance of findings; delay in publishing statistically non-significant findings; tailoring of publication content to reflect key marketing messages; adding spin to scientific publications such that conclusions favoring gabapentin were emphasized and conclusions that did not favor gabapentin were explained away; and indicators of ghost authorship. Each form of bias, and spin, on its own, could be seen as a relatively minor issue. The value of our findings is in the overall picture that emerges from what appears to be the simultaneous use of many forms of reporting bias and spin, all within the context of a pharmaceutical company’s publication strategy, implemented for marketing purposes."
So-- it's all about the marketing, and not about the science. No big surprise here, but further documentation of what we've had reason to believe from all previous reports of this type.
Now, I sort of hate to keep beating up on editor Jeffrey Drazen of the New England Journal:
http://brodyhooked.blogspot.com/2012/09/nejm-overly-defensive-or-just-naive.html
--who as previously reported said we should not judge articles based on who sponsored the research but on the quality as depicted in the published paper. What Dr. Vedula and colleagues show us is that if a paper that's positive about a new drug shows up in Dr. Drazen's high-impact journal, we can be reasonably sure that there are 3-4 other studies with much less impressive, or even negative results, which are kept aside to be not published at all, or else published in much-lower-circulation journals many years later--or at least that's the standard business plan within the industry. And of course there's no way on this green earth that even the most fastidious reader of NEJM could ever know that. So much for being able to read a paper in the journal and then draw your own conclusions.
http://hcrenewal.blogspot.com/2012/10/when-clinical-trials-are-meant-for.html
--we are alerted to the recent publication by S. Swaroop Vedula and colleagues:
http://www.trialsjournal.com/content/13/1/136
These authors were part of the team that testified in lawsuits brought against Pfizer related to the drug Neurontin (gabapentin). As a result they had access to a trove of internal e-mails and documents. Here they report their analysis of these documents, from two separate legal actions in 2004 and 2008, providing a longitudinal account of how the company approached publication of clinical trial data on gabapentin for off-label uses. (The drug was approved by the FDA for two relatively narrow indications, epilepsy and post-herpetic neuralgia;and the company wanted to extend sales by showing that it worked also for migraine, bipolar disorders, neuropathic pain, and nociceptive pain.)
First the authors documented: "For each of the four off-label indications we included in our study, a document titled ‘marketing assessment,’ designed to examine the financial impact of seeking FDA approval for a new indication versus other methods of increasing sales for the indication, preceded clinical trials sponsored by Pfizer ..." That is, before the company or independent academic scientists had a go at designing and conducting a clinical trial, the marketing people already had their innings and decided on the overall strategy. In this instance, the key decision was not to try to gather data that would allow an aplication to the FDA to expand the approved indications for Neurontin, but to find data that would support off-label prescribing for that usage. And that key decision was made not based on the scientific results of clinical trials, but before the clinical trials were even begun. A critical difference is that if the company had approached the FDA, they would have been legally required to hand over all study results, both favoring the drug and not; while by going the off-label route, they could cherry-pick what they published, as we'll come to. (Reminder: a company cannot legally market a drug for off-label use directly, but its physician "key opinion leaders" are free to recommend off-label use so long as it seems to be at arm's length from the company. Today, drug reps can also hand out trial report reprints that support off-label use, hence the need to publish trials that are favorable.)
The other main reason, besides more control over publication, was that the patent on Neurontin was about the expire and it made no business sense for the company to expand its use just as the drug was about to go generic. In one instance, the decision as to publication of negative results seems to have been driven by the form's "evergreening" strategy, which was to roll out the "new" drug pregabalin as a me-too drug to replace gabapentin as their expensive, heavily-marketed brand-name drug. As pregabalin was about to be launched, the company may have wanted negative trials published about Neurontin, so as to lay the groundwork for later being able to claim that pregabalin was really head and shoulders better than its predecessor.
The next major finding from the authors was, "According to the internal company documents, 'affiliate-driven manuscripts' were written for Pfizer ... by [Medical Action Communications, a medical communication company] and sent to the authors for approval. Each article was coordinated by a manuscript team, consisting of representatives from the medical and marketing divisions of the company." This suggests that ghostwriting--having paid writers spin the research papers the way the company wanted them, and only then letting the scientific "authors" see the drafts of the papers--was simply standard operating procedure within the company. The entire process showed that Pfizer, and especially its marketing division, kept everyone involved in the publication of a paper on a short leash.
Finally, the authors demonstrated that the journals in which papers were published, and the timing of publication, were also chosen for maximum marketing impact--for instance, with positive results published in high-impact journals and published quickly, and with negative results showing up in low-circulation journals years later.
As the authors summarize: "In this study we also observed that publication occurred in journals with higher or lower circulations related to statistical significance of findings; delay in publishing statistically non-significant findings; tailoring of publication content to reflect key marketing messages; adding spin to scientific publications such that conclusions favoring gabapentin were emphasized and conclusions that did not favor gabapentin were explained away; and indicators of ghost authorship. Each form of bias, and spin, on its own, could be seen as a relatively minor issue. The value of our findings is in the overall picture that emerges from what appears to be the simultaneous use of many forms of reporting bias and spin, all within the context of a pharmaceutical company’s publication strategy, implemented for marketing purposes."
So-- it's all about the marketing, and not about the science. No big surprise here, but further documentation of what we've had reason to believe from all previous reports of this type.
Now, I sort of hate to keep beating up on editor Jeffrey Drazen of the New England Journal:
http://brodyhooked.blogspot.com/2012/09/nejm-overly-defensive-or-just-naive.html
--who as previously reported said we should not judge articles based on who sponsored the research but on the quality as depicted in the published paper. What Dr. Vedula and colleagues show us is that if a paper that's positive about a new drug shows up in Dr. Drazen's high-impact journal, we can be reasonably sure that there are 3-4 other studies with much less impressive, or even negative results, which are kept aside to be not published at all, or else published in much-lower-circulation journals many years later--or at least that's the standard business plan within the industry. And of course there's no way on this green earth that even the most fastidious reader of NEJM could ever know that. So much for being able to read a paper in the journal and then draw your own conclusions.
Friday, October 12, 2012
More on Sponsorship of Studies in Medical Journals
In my last post: http://brodyhooked.blogspot.com/2012/09/nejm-overly-defensive-or-just-naive.html
--I took off after an editorial in the New England Journal defending industry sponsorship of trials, saying that you should decide whether a trial is trustworthy based on reading its methods, not based on who sponsored it. My rebuttal is that many of the features that make results untrustworthy simply cannot be gleaned from reading the published report in the journal.
Here's the other side of the coin--things that make results untrustworthy that the alert reader can spot.
Again tipping my hat to Rick Bukata and Jerry Hoffman's Primary Care Medical Abstracts, I come across a study by Drs. Michael Hochman of UCLA and Danny McCormick of Harvard:
http://www.springerlink.com/content/8h66774155415128/
These guys looked at several ways of reporting results that overestimate benefits:
Drs. Hochman and McCormick then compared how likely it was that a study would report results in these ways, based on who sponsored the study. They found significant differences in two categories. Exclusively industry-sponsored studies were more likely than studies with at least some non-commercial support to report surrogate endpoints (45% vs. 29%) and disease-specific mortality (27% vs. 16%).
Now, if you wanted to defend the NEJM editorial position, you could say that readers of studies can readily see how the data are reported according to these criteria and can be wary of any study, regardless who funds it, that reports data in the less desirable way. But let's give the last word to Drs. Hochman and McCormick, in their final recommendations: "These findings highlight the need for educational efforts to ensure that readers understand the complexities of these endpoints and of relative risk reporting. ... In addition, Institutional Scientific Review Committees and regulatory agencies (e.g. the FDA) must closely examine the endpoints used in clinical trials and discourage the inappropriate use of surrogate and composite endpoints, and endpoints involving disease-specific mortality. Finally, medical journals may consider instituting editorial policies mandating the reporting of results in absolute numbers."
In other words, rather than asking readers to sift through whether the results are reported in a useful and valid fashion, medical journals like NEJM could simply refuse to publish papers that don't adhere to the highest standards. Of course, if they did, they might lose revenue as drug companies would not buy so many expensive reprints of papers that are really useful for marketing drugs--which may be one of the roots of the problem.
--I took off after an editorial in the New England Journal defending industry sponsorship of trials, saying that you should decide whether a trial is trustworthy based on reading its methods, not based on who sponsored it. My rebuttal is that many of the features that make results untrustworthy simply cannot be gleaned from reading the published report in the journal.
Here's the other side of the coin--things that make results untrustworthy that the alert reader can spot.
Again tipping my hat to Rick Bukata and Jerry Hoffman's Primary Care Medical Abstracts, I come across a study by Drs. Michael Hochman of UCLA and Danny McCormick of Harvard:
http://www.springerlink.com/content/8h66774155415128/
These guys looked at several ways of reporting results that overestimate benefits:
- Reporting relative vs. absolute risks
- Reporting surrogate endpoints rather than significant changes in health
- Reporting composite endpoints instead of reporting each endpoint of interest separately
- Reporting only disease-specific mortality instead of all-cause mortality
Drs. Hochman and McCormick then compared how likely it was that a study would report results in these ways, based on who sponsored the study. They found significant differences in two categories. Exclusively industry-sponsored studies were more likely than studies with at least some non-commercial support to report surrogate endpoints (45% vs. 29%) and disease-specific mortality (27% vs. 16%).
Now, if you wanted to defend the NEJM editorial position, you could say that readers of studies can readily see how the data are reported according to these criteria and can be wary of any study, regardless who funds it, that reports data in the less desirable way. But let's give the last word to Drs. Hochman and McCormick, in their final recommendations: "These findings highlight the need for educational efforts to ensure that readers understand the complexities of these endpoints and of relative risk reporting. ... In addition, Institutional Scientific Review Committees and regulatory agencies (e.g. the FDA) must closely examine the endpoints used in clinical trials and discourage the inappropriate use of surrogate and composite endpoints, and endpoints involving disease-specific mortality. Finally, medical journals may consider instituting editorial policies mandating the reporting of results in absolute numbers."
In other words, rather than asking readers to sift through whether the results are reported in a useful and valid fashion, medical journals like NEJM could simply refuse to publish papers that don't adhere to the highest standards. Of course, if they did, they might lose revenue as drug companies would not buy so many expensive reprints of papers that are really useful for marketing drugs--which may be one of the roots of the problem.
Subscribe to:
Posts (Atom)