Why I Shouldn't Read Non-Systematic Review Articles: Special Pleadings and Undercover Authors

I usually resist looking at non-systematic review articles in medical journals, but because the title interested me, and things seem to be getting slow this holiday season, prompted by an update email from the American Journal of Medicine, I looked at Ram CVS. Beta-blockers in hypertension. Am J Cardiol 2010: 106: 1819-1825. (Link here.)

The Ram Article in Praise of Vasodilating Beta-Blockers

The article focused on the results of meta-analyses:

Concerns have also been raised by meta-analyses in which β blockers were reported to have a suboptimal effect on reducing stroke risk and increasing the risk for new-onset diabetes compared with other antihypertensive agents.

The article discussed several meta-analyses in which beta-blockers, [a specific class of blood pressure lowering drugs] but mostly atenolol (mostly sold generically), usually combined with a diuretic, were compared with other antihypertensive drugs, usually including angiotensin converting enzyme inhibitors (ACEIs) and calcium channel blockers. But after discussing these comparative results, the author jumped to descriptions of another group of drugs which were not included in any of these comparative studies. This was the category of vasodilating beta-blockers, consisting of labetolol (mostly sold generically), carvedilol (Coreg, GlaxoSmithKline [GSK]), and nebivolol (Bystolic, Forest Laboratories. Based on physiologic studies of these drugs and trials in which they were compared with placebo, but not on studies which directly compared clinical outcomes of patients given these drugs or other kinds of antihypertensives, Dr Ram reached conclusions that they were a better alternative:

The review of the evidence provided herein confirms that there are valid reasons to question the utility of certain β blockers in treating hypertension. However, many of the perceptions about β blockers are derived from data obtained from studies of traditional agents or combinations of diuretics and β blockers. Evidence suggests, and the guidelines concur, that there are intrinsic differences among members of the β-blocker class. Indeed, the vasodilatory β-blockers, which have generally not been included in comparative meta-analyses, lower blood pressure to a similar degree as other antihypertensive drugs, may provide better central aortic pressure reductions than traditional β blockers, and are associated with neutral or favorable metabolic effects.

Special Pleading

Dr Ram's questioned the old-fashioned beta-blocker atenolol (perhaps only when added to a diuretic)  based on the results of meta-analyses which attempted to compare it to other drugs. Such meta-analyses could suggest that atentolol (again, perhaps only in combination with a diuretic) might be in some way less preferable than the other drugs to which it was compared. However, the meta-analyses did not address the vasodilating beta-blockers at all. Dr Ram concluded that they were preferable based on different kinds of and probably less definitive evidence. He did not seek to compare such studies done on the vasodilating beta-blockers to similar studies done on the conventional beta-blockers.  Thus it seems his conclusions were based on a double standard.

In the vocabulary of logical fallacies, this was an example of a special pleading:

Special Pleading is a fallacy in which a person applies standards, principles, rules, etc. to others while taking herself (or those she has a special interest in) to be exempt, without providing adequate justification for the exemption.

Here was more reason not to bother reading a narrative review articles to learn how to better practice clinical medicine.  They often are based on idiosyncratic, if not biased evidence used to support illogical arguments.

But having read so far, I wondered why the authors of this article were so happy to use a double standard as the basis of their arguments.

Undercover Author

Those paying attention may also now be wondering why I referred to the authors in plural, when the citation lists only one author. The clue is at the end of the article:

Acknowledgment

I would like to thank Tamalette Loh, ProEd Communications, Inc. (Beachwood, Ohio), for her editorial assistance and literature validation in the preparation of this report.

Sensitized as I have been to the many recent discussions of ghost-writing, I immediately wondered who Ms Loh is, and what sort of "editorial assistance and literature validation" she provided. So first I looked at what her company, ProEd Communications does, wondering if its business is to help syntactically challenged academics and professionals write better sentences and more organized papers.

The ProEd Communications web-site states:

ProEd Communications balances diverse perspectives—clinical, regulatory, marketing, and customer—to create compelling messaging to maximize a product's potential.

So it appears that ProEd Communications does not provide independent editorial services. Instead, it is a medical education and communications company (MECC) which works mainly to market its clients' products, and further, its clients are essentially only pharmaceutical companies:

Of the world's 50 largest pharmaceutical companies, ProEd has worked with 18 in the past 3 years and currently supports projects for 7 of the top 10 largest pharmaceutical companies, as ranked by MedAdNews (2008).

Furthermore, a few minutes on Google reveals that Ms Loh seems to specialize in papers on anti-hypertensives, particularly Coreg (carvedilol), one of the three drugs in the vasodilating beta-blocker group favored by Dr Ram. In fact, two other papers whose authors she assisted sounded hauntingly familiar.

Let me first display the quote above from the Ram paper:

Concerns have also been raised by meta-analyses in which β blockers were reported to have a suboptimal effect on reducing stroke risk and increasing the risk for new-onset diabetes compared with other antihypertensive agents.

Now see this quote from Frishman WH, Henderson LS, Lukas MA. Controlled-release carvedilol in the management of systemic hypertension and myocardial dysfucntion. Vasc Health Risk Management 2008; 4: 1387-1400.  (Link here):

However, concerns have been raised recently from hypertension meta-analyses regarding suboptimal outcomes with use of beta-blockers, specifically atenolol, compared with outcomes for other antihypertensive drug classes.

Also see this relatively similar quote from McGill JB. Optimal use of beta-blockers in high-risk hypertension: a guide to dosing equivalence. Vasc Health Risk Management 2010; 6: 363-372. (Link here):

Concerns about the use of β-blockers as first-line agents for hypertension have been raised because of a 2005 metaanalysis that found β-blockers do not significantly reduce
cardiovascular events, especially stroke, compared with other antihypertensive drug classes

Furthermore, read this discussion of Coreg by Ram:

Carvedilol is a nonselective β blocker with α1 receptor–blocking activity and no intrinsic sympathomimetic activity. Clinical data suggest that carvedilol reduces systemic vascular resistance in patients with hypertension.

Here is Frishman et al:

Carvedilol is a third-generation, vasodilatory beta-blocker that nonselectively blocks both the beta 1- and beta 2-adrenergic receptors.... vasodilatory beta-blockers can lower blood pressure by reducing systemic vascular resistance (SVR)

Both Frishman et al and McGill are very positive about Coreg.  Although the emphases of the three articles are different, they have organizational similarities.  Again, all three were written with the assistance of Ms Loh.

At the end of the Frishman article we again find:

The authors would like to thank Tamalette Loh, PhD, ProEd Communications, Inc.®, for her medical editorial assistance with this manuscript.

At the end of the McGill article we find:

Editorial assistance, specifically revisions to the final draft, was provided by Tamalette Loh, PhD, at ProEd Communications, Inc.®, whose services were also funded by GlaxoSmithKline. Dr Loh’s revisions were reviewed and approved by Dr McGill.

Note that now it seems that Ms Loh has a doctoral degree, of unclear kind. Note also that now it seems that GSK, the manufacturer of Coreg, funded Dr Loh's work on the McGill article.

Dr McGill further disclosed:

Dr McGill is a consultant for GlaxoSmithKline and a speaker for AstraZeneca and Forest Pharmaceuticals. Financial support for medical editorial assistance was provided by GlaxoSmithKline, Philadelphia, Pennsylvania.

Finally, in another article, about angiotensin converting enzyme blockers combined with diuretics to treat hypertension (Egras AM, Ram CVS. Reduced cardiovascular risk and healthcare expenditures with angiotensin receptor blocker/ hydrochlorthiazide. Am J Pharmacy Benefits 2010; 2: 127-135. Lin here. ), Dr Ram acknowledged:

Dr Ram is in the speakers’ bureau pool of Cogenix, ProCom, and Genesis, which manage medical education programs for Bristol-Myers Squibb, GlaxoSmithKline, and Novartis.

The series of articles above demonstrated a phenomenon I have not seen explored before. All articles were written with some sort of assistance from an employee of a MECC, perhaps partly funded by a company which marketed a drug which was the subject of all the articles. The assistance was openly acknowledged.  The three articles had some remarkable similarities not explained by an overlap among their listed authors.  This suggested that the ostensible editorial assistant they had in common was substantively involved in the content of the papers, that is, was truly an author. Her presence was not ghost-like. However, the substance of her contribution may have been downplayed.  So let's call her an "undercover author."  (If someone has a better term, please leave a comment to that effect.)

Summary

So the reasons I rarely read narrative review articles except to make teaching points about health care dysfunction are:
- They often are based on idiosyncratic, if not biased selections of data
- They may employ logical fallacies to make their points
- They may be written by people with conflicts of interest, that is, with financial arrangements with companies seeking to market products, particularly drugs and devices.

My conclusions for health care professionals are: be very skeptical of non-systematic review articles, look for evidence that they are parts of stealth marketing campaigns, and do not assume all conflicts of interest are disclosed and all authorship roles revealed.

My conclusions for journal editors are: strictly demand more complete disclosure of conflicts of interest, or risk losing the trust of your readers.

My conclusions in general: until we start to sweep away the pervasive web of conflicts of interest that is draped over medicine and health care, expect further discombobulation.

Post Title → Why I Shouldn't Read Non-Systematic Review Articles: Special Pleadings and Undercover Authors

Another Haunting Tale

Halloween is more than two months away, but the ghost stories just keep on coming. The latest version was reported by the Associated Press (with a hat tip to Prof Margaret Soltan on the University Diaries blog). To quickly summarize,

Drugmaker GlaxoSmithKline used a sophisticated ghostwriting program to promote its antidepressant Paxil, allowing doctors to take credit for medical journal articles mainly written by company consultants, according to court documents obtained by The Associated Press.

An internal company memo instructs salespeople to approach physicians and offer to help them write and publish articles about their positive experiences prescribing the drug.

Known as the CASPPER program, the paper explains how the company can help physicians with everything from 'developing a topic,' to 'submitting the manuscript for publication.'

The actual document is now available from the PharmaGossip blog here. Reviewing that document suggests that the CASPPER program was a bit different from other ghost-writing schemes (for example, see previous posts here.)

A typical ghost-writing scheme would entail ghost-writers employed by a medical education and communications company (MECC) drafting manuscripts of a scholarly-appearing review articles. The articles would be written to support the marketing of a product made by the (usually pharmaceutical) company which hired the MECC. Then, the MECC would recruit well-known medical academics as (guest) authors for the articles. The guest authors might make some minor revisions in the draft manuscripts, which would then be submitted to scholarly journals. The MECCs would handle the submission process, while maintaining the pretense that the articles were the work of the guest academic authors. The ultimate purpose of such schemes apparently would be to market the product in the guise of scholarly publication.

CASSPER, on the other hand, was meant to produce more modest articles, ostensibly written by practicing, rather than purely academic physicians. Review of the CASSPER document leads to some interesting conclusions about the project

- The project was purely a marketing project. "The objectives of CASSPER, from a publication standpoint, are to strengthen the product positioning and overcome competitive issues." The document clearly was written by marketers, and directed to pharmaceutical representatives ("drug reps.") It did not mention any involvement by GSK scientific or medical personnel. The closest it came to making a pretense about any scientific or clinical usefulness of the project was, "publication of such articles will benefit the sales force by expanding the database of published data to support PAXIL."

- It was as much about promoting closer relationships among pharmaceutical representatives ("drug reps") and doctors as about publishing articles. The project was to be implemented by drug reps, and "your participation will establish and/or strengthen your relationships with key physicians and thought leaders in the psychiatric field." The drug reps would handle, and presumably shape all communications between their physicians and the MECC.

- Articles were to arise from instigation by the drug reps, rather than from physicians' initiatives. For example, a scenario for recruiting authors began, "a physician tells you that he or she has had treatment success with PAXIL in certain indications or difficult-to-treat patient populations." Then, "ask the physician if any consideration has been given to publishing a case study based on this clinical experience."

- Although the document is somewhat ambiguous about the role of the putative author in the process, an extensive list of services available from the MECC (Complete Healthcare Communications [CHC] ) would have left little for the author to do. "The full range of editorial assistance that CASSPER can offer contributing physicians includes: developing a topic, coordinating the editorial review process, submitting to the target journal." The company's role would include "coordinating" manuscript preparation, which was defined as "development of an outline and first draft, editorial reviews, and revisions." The company would make available "published literature, available internal support, literature search results, and a database of journal submission criteria." Also, "the numerous details that CHC is prepared to coordinate ... [include] copy editing and proofreading, production of tables and graphics, preparation of the submission package, and follow-up."

So CASSPER seems to be a not really so friendly example of a newly recognized species of ghost-writing, targeted more at promoting relationships among drug reps and physicians than at producing ostensibly scholarly articles. Nonetheless, this example of the haunting of medicine is as fundamentally deceptive as previously described ghost-writing schemes. In the CASSPER project, physicians would be reduced to little more than ectoplasm, goaded by drug reps into token involvement in a writing process exclusively handled by the MECC, and mediated by the friendly appearing drug reps. I wonder whether physicians who participated escaped with any psychological independence from the drug reps who magically turned them into acclaimed "published authors?"

In any case, the disclosure of CASSPER, a ghost who was friendly only in appearance, adds more evidence about how deception and dishonesty now haunts our health care system. To achieve real health care reform, we will have to find a new group of ghost-busters. Who you gonnna call?

ADDENDUM (25 August, 2009) - See also comments by Dr Howard Brody in the Hooked: Ethics, Medicine and Pharma Blog.

Post Title → Another Haunting Tale

"Man's Best Hospital," Run by the Boss of a MECC (Medical Education and Communications Company)?

In January, 2009 we posted about how the CEO of Blue Cross Blue Shield (BCBS) of Massachusetts and of Partners HealthCare, made a secret oral agreement that BCBS would pay Partners at a higher rate than that given to other hospitals.

Why BCBS would want to pay so much to this one hospital system was never clear. Partners does include some extremely prestigious hospitals, including the Brigham and Womens Hospital, and the Massachusetts General Hospital, ("Man's Best Hospital" in the House of God), but there are some other very prestigious teaching hospitals in Boston that were not blessed by BCBS' largess.

We speculated about one possible cause: the leadership of the two organizations may have felt they had more in common with each other than with the constituencies of their own organizations. A few leaders of each organization had direct ties to the other. Many leaders of both organizations were simultaneously leaders of finance, the same sector that has brought us what is now called the Great Recession. Leadership of both organizations had conflicted loyalties. The organizations' CEOs at the time, and many members of their boards had divided loyalties and apparent conflicts of interest. For example, Jack Connors, the chair of the Partners HealthCare board, is also the Chairman Emeritus of marketing communications company Hill, Holliday, Connors, Cosmopoulos Inc, whose clients include pharmaceutical and pharmacy benefits manager CVS / Caremark, and is also a member of the board of directors of Covidien, a medical device company.

The Boston Globe just published a report that Mr Connors had even more intense conflicts that had not heretofore been made public.

He's chairman of New England's largest healthcare company, and that position atop Partners HealthCare has tested the limits of Jack Connors's considerable corporate dexterity.

Though he has no background in medicine, Connors has been Partners' chief overseer, champion, and its most public face for 13 years.

[One board member] is the cofounder and chairman emeritus of Partners' advertising firm. That would be Jack Connors. And that potential point of conflict has been disclosed....

But to the chagrin of some former board members, never brought up for board review was Connors's stake in a leading medical education firm whose sale in 2004 made Connors a very wealthy man.

Nor has the board notified public officials of Connors's ownership of a fledgling home healthcare firm that has directly solicited Partners' hospitals for business.

Connors and top Partners officials defended the decision not to publicly disclose Connors's potential conflicts, saying that because Partners did not directly contract with either of Connors's firms there were no conflicts to report. Connors also defended his right to be an entrepreneur in the healthcare business while also chairing Partners' board, and strongly denied ever using his position for personal or financial advantage.

The larger company, M/C Communications, grew to become the biggest commercial provider of continuing education to physicians in the decade between its inception in 1994 and when Connors sold it in 2004. It profited hugely from an exclusive commercial relationship it maintained with Harvard Medical School, whose faculty teach at seminars the company holds. Partners' signature institutions, Massachusetts General Hospital and Brigham and Women's Hospital, are major teaching affiliates of Harvard Medical School.

In addition, M/C Communications benefited financially from millions of dollars in sponsorship revenue paid it from major pharmaceutical firms eager to play to this professional audience.

Connors said he was under no obligation to disclose his ownership of M/C Communications to the Partners board. He said that while there is an 'affiliation' between Harvard Medical School and the two Partners hospitals, there is no formal contract between them.

Connors said he informed Partners executives of his ownership of M/C Communications, and that they determined it did not warrant disclosure to the full Partners board.

'There is no contract between Partners and Harvard,' Partners said in a statement to the Globe.

Connors made a name for himself as an executive with Hill, Holliday, Connors, Cosmopulos, the Boston advertising company that he helped found and guided throughout a long career. Less well known is that he made most of his fortune from M/C Communications, which he sold to Bain Capital for $450 million in 2004.

The sale was the largest of a private healthcare-related company in Massachusetts that year, according to TM Capital Corp., an investment banking company. Connors, who led an investor group that bought the firm outright for $13 million in 2000, made about $250 million from its sale.

After his 2004 windfall, he founded a company that helps elderly patients readjust to life at home after a hospitalization.

That company, Dovetail Health, has - Connors acknowledged - solicited business from hospitals owned by Partners. And Connors confirmed that after Dovetail executives failed to convince Blue Cross Blue Shield of Massachusetts to contract with the firm, he personally spoke to the giant insurer's president, Cleve L. Killingsworth, on Dovetail's behalf. Partners and Blue Cross Blue Shield regularly negotiate over $2.5 billion worth of medical business a year.

Connors acknowledged in an interview that it might have appeared 'inappropriate' to some for him to pitch Killingsworth. But he said the conversation stemmed from a shared belief that new ways must be found to reduce frequent return trips of elderly patients to the hospital. More recently, however, he said he does not believe his approach to Killingsworth was inappropriate.

So let's try to recap this.

While Jack Connors has been chairman of the board of Partners HealthCare, the largest and most prestigious hospital system in Massachusetts, he also ran an advertising agency that did business with Partners, and has been on the board of Covidien, a medical device company. Both of these relationships he disclosed to his fellow board members, although no one seemed troubled by them.

However, while a Partners board member, Connors was also the founder, and ultimately profited very handsomely from the sale of M/C Communications. M/C Communications apparently begat M/C Holding Corporation, which in turn owns M/C Communications and Pri-Med Institute LLC. M/C Communications now describes itself as " established in 1994 and has become a leading provider of medical education event management solutions for health care professionals and others around the globe." M/C Communications runs Pri-Med, which is described thus: "Pri-Med is a platform for science and medicine that includes meetings, resources, online, and new media tools designed to meet the information and education needs of today’s practicing physician." Pri-Med markets itself to industry, presumably the pharmaceutical, biotechnology, and device industry, "Sixty percent of doctors’ offices restrict rep access, making it more challenging than ever to get in front of your customers. But with Pri-Med, you get to meet clinicians in a professional environment where they seek you out. More than 66% of attendees say they come to Pri-Med events to meet you, industry representatives." So Connors' company was a medical education and communication company (MECC), which provided what appeared to be educational programs to physicians that in fact were also sold to the health care industry as marketing opportunities.

So Partners HealthCare, which includes two of the world's most prestigious teaching hospitals, has been run by the boss of a MECC? Say it ain't so.

Not only did Connors own a company that had an exclusive contractual relationship (as described above) with the Harvard faculty who staff the main Partners HealthCare hospitals, that company was engaged in marketing the products of sponsoring drug and device companies disguised as education. Finally, Connors denied that this presented any kind of conflict of interest, because Partners HealthCare has no explicit contract, just an "affiliation" with Harvard Medical School.

Finally, just to ice the cake, Connors' latest venture is a home health care company that did business with Partners, and tried to do business with BCBS, spearheaded by Connors' direct conversations with the BCBS CEO.

Jack Connors thus seems to have just become the latest poster boy for leaders of health care organizations who put their personal financial interests ahead of their responsibilities to those organizations, and function as a power elite whose collective interests trump those of the constituents of the organizations they run.

Quoting from BoardSource, the main duties of the leader of any US not-for-profit are:

Duty of Care

The duty of care describes the level of competence that is expected of a board member, and is commonly expressed as the duty of 'care that an ordinarily prudent person would exercise in a like position and under similar circumstances.' This means that a board member owes the duty to exercise reasonable care when he or she makes a decision as a steward of the organization.

Duty of Loyalty

The duty of loyalty is a standard of faithfulness; a board member must give undivided allegiance when making decisions affecting the organization. This means that a board member can never use information obtained as a member for personal gain, but must act in the best interests of the organization.

Duty of Obedience

The duty of obedience requires board members to be faithful to the organization's mission. They are not permitted to act in a way that is inconsistent with the central goals of the organization. A basis for this rule lies in the public's trust that the organization will manage donated funds to fulfill the organization's mission.

By leading companies that did direct business with Partners and its staff, and failing to disclose that he was doing so to his fellow Partners board members, Connors appeared to have violated the Duty of Loyalty.

By running a MECC that helps drug and device companies market to physicians in the guise of education, using faculty from the academic teaching hospitals that he lead, Connors seems to have mocked the mission of the academic hospitals within Partners, and thus appeared to violate the Duty of Obedience.

This episode certainly does suggest that health care, and the organizations involved in this case, are lead by an "old-boy network," as one person interviewed for the Globe article suggested. More than just an old-boy network, they seem to be lead by chummy members of the power elite whose collective personal interests supersede the missions of the organizations they are supposed to steward. When this happens, is it any surprise that health care becomes less accessible, more expensive, and of lower quality?

Yet challenging the power elite that are increasingly revealed as controlling much of health care seems to be something that one cannot talk about when discussing health care reform. However, failing to address this problem will likely doom any effort, no matter how well intentioned, to improve health care.

Hat tip to and see comments by Alison Bass on the Alison Bass Blog.

ADDENDUM (3 June, 2009) - See also comments by Dr Daniel Carlat on the Carlat Psychiatry Blog.

Post Title → "Man's Best Hospital," Run by the Boss of a MECC (Medical Education and Communications Company)?

BLOGSCAN - An Example of Spinning Clinical Research Results

On the Clinical Psychology and Psychiatry blog, the anonymous blogger did a great job analyzing an article supported by pharmaceutical companies, and authored by in part pharmaceutical company employees, with the assistance of a medical education and communications company (MECC). The article ignored data about outcomes which were unfavorable to the companies' product, and dubbed a drug "well tolerated" even though a number of uncomfortable symptoms occurred two to four times as often on the drug as on placebo. This is a reminder of how often these days clinical research studies are spun in favor of the vested interests of their commercial sponsors.

Post Title → BLOGSCAN - An Example of Spinning Clinical Research Results

Paying More for Worse Outcomes - the Wyeth/ DesignWrite/ University of Wisconsin Hormone Replacement Therapy Course as Microcosm

The Milwaukee Journal-Sentinel just published a remarkable investigative report about continuing medical education courses provided (after a fashion) by the University of Wisconsin. Here are the main points,

The course was created by a medical education and communications company (MECC), paid for by Wyeth

The course material was developed largely by DesignWrite, a New Jersey-based firm paid by Wyeth.

The company is being investigated along with Wyeth by a U.S. senator looking into the practice of ghostwriting in scientific articles as a way to market hormone therapy drugs.

Together, Wyeth, DesignWrite and UW formed the Council on Hormone Education - the name of the educational organization stamped on course material for the class.

Thirty-four of the 40 council member physicians have financial ties to Wyeth, including the course director, Julie Fagan, a UW doctor and associate professor of medicine.

The course put hormone replacement therapy (HRT) for post-menopausal women in a very favorable light, at a time when results from a prominent randomized controlled trial sponsored by the Womens Health Initiative (WHI) had just become available, suggesting that HRT does more harm than good:

Rigorous studies involving thousands of women showed that hormone therapy increases the risk of heart disease, stroke, breast cancer, blood clots and dementia. They also showed quality-of-life benefits are short-lived.

In May 2002, a major clinical trial that was part of the Women's Health Initiative was suspended because medical investigators were worried they were subjecting women to too much risk.

In the fall of 2002, just months after the health initiative was stopped, the Council on Hormone Education launched its first UW hormone therapy medical education course.

'There were millions of women impacted by that information, and physicians and women really needed to have that information,' said Doug Petkus, spokesman for Wyeth. 'We felt we were providing a service to them by helping them . . . understand the significance.'

Over the next several years, Wyeth poured $12 million into the course.

According to the first newsletter published by the Council on Hormone Education, the goal of the course was 'to develop and disseminate balanced, accurate, timely and consistent information about hormone therapy' so doctors could "better serve women."

Other newsletters, which included patient handouts and multiple-choice exams in the back for physicians, urged doctors to consider the bonuses of hormone therapy.

For instance, in a newsletter titled 'Menopause and Quality of Life,' Wyeth-funded researcher JoAnn Pinkerton wrote: 'Undesirable skin changes associated with aging can have a deleterious impact on both physical and mental health. These changes include lines, wrinkles and dryness that affect Quality of Life.'

'American women attach to youthful, attractive skin,' she wrote, explaining that the age-induced changes are in large part the result of estrogen loss. There is no scientific consensus that estrogen supplements will reverse the aging process in skin.

The University of Virginia Health System doctor also suggested that depression, insomnia and mood issues could be the result of estrogen and other hormone imbalances.

Her conclusion: 'Hormone therapy treats menopausal symptoms more effectively than any other single agent.' And a physician must weigh those benefits against a woman's risk for 'coronary heart disease, deep vein thrombosis, pulmonary embolism, stroke, breast cancer, and gall bladder problems, which hormone therapy may be associated with.'

Fagan, the UW course director, defended the program, saying nothing in the course material was scientifically inaccurate. However, she said the material was presented in a 'more positive light' than she would have preferred.

Some experts who reviewed the material thought that the "positive light" it placed on hormone replacement was very bright.

The Journal Sentinel asked several doctors, including Jacques Rossouw, chief of the Women's Health Initiative branch of the National Institutes of Health, to review course material. The initiative is the largest clinical trial of hormone therapy drugs.

He said the views expressed in the course are not those of the general scientific community and are not suitable for a university medical education course.

'There is a history of this kind of thing from Wyeth,' Rossouw said. 'The materials regurgitate lines that I have heard and read many times, and I have come to believe (though I do not know) that this is part of an overall marketing strategy to the profession. It is not good science because it fails to strive for any kind of balance.'

Raymond Gibbons, a professor of medicine at the Mayo Clinic and former president of the American Heart Association, said he also found material relating to heart disease one-sided.

He noted that the materials inappropriately gave observational data equal weight to rigorously done, randomized clinical trials.

'It's a lot of post hoc analysis,' he said. 'I don't see the other side of the argument.'

This is the second time that the University of Wisconsin medical school has received media attention for the cozy relationships with industry enjoyed by the school and its faculty members. We posted about some University of Wisconsin faculty's lucrative industry relationships, which they often did not fully disclose.

This, of course, is another story about how the web of conflicts of interest that now so enmesh academic medicine can enable stealth marketing, the disguising of marketing of commercial health care goods or services as medical education.

But because of the timing and subject matter of this course, this case has become a microcosm of much of what has gone wrong with US (and global) health care. Note this progression:

- Wyeth paid DesignWrite to design the course, which then paid the University of Wisconsin and its faculty to produce it. Thus considerable money flowed to the MECC and its employees, and to the university and its faculty. Ultimately, this came out of the pockets of patients or the public, adding to health care costs.
- The course they produced was viewed by numerous physicians. It is likely at least some were influenced by it to prescribe long-term HRT.
- Yet there is now (and there was in 2002) reason to believe that long-term HRT does more harm than good. A review in 2002 (see this link for summary, and links to the review) suggested that it produces increased risks of breast cancer, stroke, and pulmonary embolism which outweigh decreses in colorectal cancer and fracture. The WHI trial in JAMA had similar results (link here.)
- Therefore, more patients prescribed HRT by these physicians may have been harmed by it than were helped. Thus, the course not only added to health care costs, but likely worsened health care outcomes.

So in this case, deceptive practices presumably condoned by the leadership of a drug company, by the leadership of an academic medical institution, and by particular medical faculty, all of whom may have benefited personally by money spent to conduct these practices, likely did patients no good, and possibly did them serious harm. Deceptive practices and conflicts of interest resulted in increased health care costs and probably worse health care outcomes.

This suggests, as we have said before, that bad leadership of health care organizations causes these organizations to employ ethically questionable tactics, and these tactics in turn can systemically increase costs and worsen outcomes.

But up to now, there has been little public discussion of bad leadership and governance of health care organizations, the unethical tactics that bad leaders may employ, and how these tactics threaten physicians' professional values, and lead to bad outcomes for patients and society. Up to now, those interested in health care policy and health systems research have ignored these issues, which appear to be the herd of elephants in the health care living room.

But maybe if we improved the leadership and governance of health care organizations, and prevented the unethical practices they may employ, we could improve patient outcomes while actually controlling costs, improving access, and improving professional morale.

Of course, doing so would threaten many vested interests and fat wallets.

See also Dr Daniel Carlat's comments on the Carlat Psychiatry Blog, and Margaret Soltan's comments on University Diaries. Hat tip to PharmaGossip and the Schwitzer Health News blog.

Post Title → Paying More for Worse Outcomes - the Wyeth/ DesignWrite/ University of Wisconsin Hormone Replacement Therapy Course as Microcosm

BLOGSCAN - An Industry Sponsored "Scholarly" CME Journal?

On the Carlat Psychiatry Blog, Dr Daniel Carlat discussed a new apparently scholarly peer-reviewed journal devoted to studies of continuing medical education. However, the journal seems to be funded by a group of pharmaceutical companies, published by a medical education and communications company (MECC), and edited by the Vice President of a for-profit medical education assessment company. A majority of the editorial board appear to work for the pharmaceutical industry, MECCs, and related businesses.

Post Title → BLOGSCAN - An Industry Sponsored "Scholarly" CME Journal?

BLOGSCAN - Who Actually Organizes Medical Conferences and Continuing Medical Education?

On the Carlat Psychiatry Blog, Dr Daniel Carlat delved more into the role of medical education and communication companies (MECCs) in medical education. He found a MECC prospectus for a psychiatry conference ostensibly presented by a very prestigious medical school. In it, the MECC solicited "independently supported symposia," and offered to prepare for such symposia "enduring materials," which appear to be polished monographs, which can be read for CME credit. The charge to the sponsor for preparing such an article was a cool $103,000. Funny, I used to think that doctors and medical academics put together medical conferences and continuing medical education. But look through the section on "partner responsibilities" in the MECC's prospectus, and see how little there is for the prestigious academic institution to do, and how much is actually done by the MECC. How naive I was.

Post Title → BLOGSCAN - Who Actually Organizes Medical Conferences and Continuing Medical Education?

BLOGSCAN - On the Physician Payment Sunshine Act and CME Put on by MECCs

On the Carlat Psychiatry Blog, Dr Daniel Carlat discussed the Physician Payment Sunshine Act. This proposed legislation would mandate disclosure by drug companies of all payments over $500 made to physicians for speaking, consulting, travel, etc. Dr Carlat, however, noted an important loophole. The legislation would not cover payments made to medical education and communication companies (MECCs) to put on continuing medical education (CME) activities. Pharmaceutical, biotechnology and device companies often sponsor CME produced by MECCs. Such CME, even though it may be accredited, may be done more for marketing than educational purposes. But payments to physicians by MECCs made with money supplied by industry would not need to be disclosed according to the present form of the bill. Dr Carlat fears that the legislation, in its present form, may have the unintended consequence of promoting even more industry-sponsored (and industry-friendly) by MECC provided CME.

Post Title → BLOGSCAN - On the Physician Payment Sunshine Act and CME Put on by MECCs

BLOGSCAN - CME Talks by "Hired Gun, MD"

On the Carlat Psychiatry Blog, Dr Daniel Carlat recounted the career of a "hired gun, MD" who earned an estimated $3 million total from honoraria giving pharma sponsored talks. Is this any way to provide continuing medical education? Would you trust a talk given by such a hired gun? Would you recognize a CME talk given by such a hired gun?

Post Title → BLOGSCAN - CME Talks by "Hired Gun, MD"

BLOGSCAN - Conflicts of Interest, CME, and MECCs

On the Carlat Psychiatry Blog, Dr Daniel Carlat reported an alternative take on the Macy Foundation report which called for the abolition of commercial funding of continuing medical education (CME). (See Dr Carlat's earlier post on this report here.)

In a seminar on medical ethics, Harvard University's Neurologist-in-Chief, Dr Martin Samuels, trashed the Macy report on the basis of, you guessed it, conflict of interest. He charged that one of the members of the conference that produced the Macy report was a top executive of UpToDate, a medical education and communication company (MECC) that makes its money by selling subscriptions, not from drug companies. Meanwhile, Dr Carlat also reported that Dr Samuels was praising yet another MECC, Pri-Med, for which he happens to direct a neurology course.

You can't tell the conflicts of interest without a scorecard. This story does seem to underline, in my humble opinion, the need to disclose all conflicts of interest, and the need to develop a structure for medical education (undergraduate, graduate, and continuing) that somehow avoids conflicts due to relationships with any organization, drug company, managed care organization, MECC, for-profit, not-for-profit, whatever that have vested interests other than discovering and disseminating the truth in a spirit of free enquiry (that is, the fundamental educational mission.)

We physicians also ought to remember the oaths we once swore, and stop trying to figure out clever deals to make more money on the side.

Post Title → BLOGSCAN - Conflicts of Interest, CME, and MECCs

New DSM Task Force Members' Ties to Pharmaceutical Companies

The latest reminder of the pervasiveness of financial entanglements among physicians and medical researchers and health care corporations comes from a story in US News and World Report. The topic was how the American Psychiatric Association is attempting to make the development of the new edition of The Diagnostic and Statistical Manual of Mental Disorders the "most transparent" ever. The impetus behind the new transparency may have been criticism that the last edition was written by a group of authors heavily financially entangled with health care corporations (see post here, based on early reports of the results of this article: Cosgrove L, Krimsky S, Vijayaraghavan M et al. Financial ties between DSM-IV panel members and the pharmaceutical industry. Psychother Psychosom 2006; 75: 154-160, available here).

This time around, pledging to avoid even the appearance of conflicts, the APA has instituted screening procedures for the 27 members of its DSM task force, asking them for detailed financial information about stocks, honoraria, and consulting fees from drug interests.

Yet the summaries of the disclosure statements that were recently released to the public are remarkably spare [see them here]; they show only the existence of corporate connections, not their dollar amount or their duration. The result is a document that even an APA board member suggested is not very revealing. In a 2006 memo to the board obtained by U.S. News, William Carpenter wrote: 'Simple listing of all relationships is not very informative and does not identify potential conflicts that may need to be resolved.'

Critics say the limited information violates the spirit of disclosure. 'There is disclosure, and then there is disclosure,' says Daniel Carlat, a psychiatrist and former consultant to drug companies [and blogger on the Carlat Psychiatry Blog]. "There is a big difference between $500,000 and $500. It is one thing to disclose in a generic way, to say that a psychiatrist has had some consulting with a company, but that doesn't tell you a number of things.'

Furthermore, the disclosure appears incomplete in many ways. There were errors by the task force members.

Dilip Jeste, a professor of psychiatry at the University of California-San Diego, had consulting ties that did not appear on his disclosure form. Yet during the reporting year of 2003, he was a consultant to Pfizer and AstraZeneca and received honoraria from Pfizer, according to documents. Jeste called the error 'unintentional,' saying he had relied on memory. The APA said that Jeste would submit a new disclosure. APA President Carolyn Robinowitz said that task force nominees 'were on the honor system' and acknowledged that the association had made no effort to check their accuracy.

There were errors by the APA.

The APA itself erred in its public summary for Jan Fawcett, a professor of psychiatry at the University of New Mexico and chair of the DSM's mood disorders work group. The summary lists no directorships or corporate positions for Fawcett. But a 2005 sec filing shows that he was a member of the board of directors for Berman Health and Media, a company that is poised to 'exploit opportunities in the female sexual medicine industry.' [He has since resigned from the board.] The APA said that Fawcett had disclosed the connections in private filings but that its staffers accidentally omitted them from the public disclosure form.

It's funny that the errors always seem to be of omission, not commission.

Also, task force members who received funding from medical education and communication companies (MECCs), that were, in turn, funded by drug companies, did not disclose the latter funding.

David Kupfer, the task force chair, reported multiple consulting arrangements with communications companies that 'sponsored pharmaceutical meetings & editorial work.' His public form, however, does not reveal that income from two of these companies, Prescott Communications and Innovative Medical Education, came from work for Forrest Pharmaceuticals and Pfizer, respectively. The APA said Kupfer did not need to disclose the ties because he was not paid directly by drug companies.

The APA actually not only required disclosing conflicts of interests, it required that "members pledged to limit their aggregate income from pharmaceutical sources to $10,000 a year. If their income exceeded that amount, they were required to reduce it or sever ties." On the other hand, "critics say that loopholes weaken the policy. One is that task force members can undertake new financial arrangements after being appointed. Second, task force members are not asked to disclose 'unrestricted research grants,' which often go straight to one's department or institution."

Given that the reporting may have been incomplete, it is striking that 18 of 27 (two thirds of the) members of the Task Force reported financial ties to the pharmaceutical industry, and that many of these reported multiple kinds of ties, and/or ties to multiple companies. Given how influential the DSM is on the mental health practice, and given how expansions of definitions of mental illness provide new opportunities to develop costly treatments for them, it is disturbing that the group who will develop the new DSM has had such extensive past relationships with the pharmaceutical industry.

ADDENDUM (2 January, 2008) - See also coverage of this case in Integrity in Science Watch (2 January, 2008 issue when up), and PharmaLot.

Post Title → New DSM Task Force Members' Ties to Pharmaceutical Companies

What a Tangled Web We Weave - Among Risk Management Education, a Pharmaceutical Manufacturer, a MECC, and an Insurance Program Manager

We have often blogged about the tangled web of conflicts of interest that now spans health care. Here is a story about just how tangled that web may be.

Most of the strands were unearthed by Dr Daniel Carlat on the Carlat Psychiatry Blog. Dr Carlat published a series of posts about how Eli Lilly and Company funded a continuing medical education (CME) program which first seems to have been produced by a medical education and communication company (MECC), PV Updates. The purpose of the program was ostensibly to educate physicians about risk management. But Carlat thought that the idea was to make learners more comfortable about prescribing risky medications.

Perusal of the online slide show to which Carlat referred immediately suggests how knotty this web may be. The program has a copyright notice from "PV Update Publishing," but a Google search revealed no listing for this company, and the URL http://www.pvupdate.com/ yields an error message, albeit with the PVUpdates logo. But the slide show was also noted to be "developed by PRMS, Inc., and under the sponsorship of Eli Lilly and Company." Stay tuned for a moment...

Meanwhile, amazingly, a Lilly spokeswoman answered Carlat almost immediately, arguing he had misunderstood the intent to "to provide helpful, independent, non-product-specific information to psychiatrists to keep the risk of litigation in perspective and to understand what they can appropriately do to reduce that risk." The response begged the question of why Lilly would choose to spend its money on such an educational program, and who actually produced the program.

But here it gets more tangled. An article in the Indianapolis Star noted that Lilly "hired a medical education company, Professional Risk Management Services [PRMS]of Virginia, to help spread the message that psychiatrists can manage risk. The company recently mailed a 14-page brochure to psychiatrists across the U.S. with the message that the best way to avoid malpractice claims is to provide good care and document it carefully." Note that PRMS was listed as the "developer" of the slide show.

But the Indianapolis Star article did not clarify what PRMS does. PRMS is not a MECC. It is an "insurance program manager" which handles "underwriting, claims, and risk management," although in connection with its insurance business, it also provides CME. Thus, a psychiatrist protested to Carlat,

I am outraged that PRMS has accepted money from Lilly and has chosen to offer its authority and reputation toward this Lilly effort. PRMS is the American Psychiatric Association-endorsed entity which directs APA members to a selected malpractice insurance agency. PRMS is thus the agency many or most of us psychiatrists turn to for guidance and direction as to liability exposure and malpractice coverage. For PRMS to work for Eli Lilly is a glaring conflict of interest between their psychiatrist clients and a pharmaceutical corporation whose interests do not necessarily coincide with those of the psychiatrists with whom they have a professional relationship. This is analogous to the same law firm representing two individuals opposing one another in a law suit; in that situation we assume that there cannot be fair representation of either client, and we may imagine that the client with an attorney who has more clout in the law firm may well prevail in the action. How can we trust PRMS, or the APA for that matter, to provide us with the best liability support?

The threads among a pharmaceutical company, apparently a MECC, and an insurance program manager are certainly is hard to follow. So Carlat concluded,

Look, I get as annoyed by conspiracy theorists as the next guy. But the web of money and influence here is so murky and repugnant that it leaves me wondering what's going on.

Sometimes you are paranoid, and sometimes they are really out to get you.

It seems that many trusted medical or health care institutions are now connected to some favored health care corporation(s), and many physicians, academicians, and academic, government, and not-for-profit health care leaders have part time gigs for such companies. The complexity of such relationships sometimes defies understanding. Who can you trust? Who really is for patient care, education, or science?

We may have to expose every such tawdry conflict of interest before we can answer these questions. "Sunlight is the best disinfectant."

Post Title → What a Tangled Web We Weave - Among Risk Management Education, a Pharmaceutical Manufacturer, a MECC, and an Insurance Program Manager

BLOGSCAN - The Porous Firewall Between MECCs and Commercial CME

On the Carlat Psychiatry Blog, Dr Daniel Carlat argues how porous is the firewall between commercial medical education and communication companies (MECCs) and commercial continuing medical education (CME) providers.

Post Title → BLOGSCAN - The Porous Firewall Between MECCs and Commercial CME

Haunted Health Care: the Scope of Ghost Management

An important new article in PLoS Medicine expanded thinking about the involvement of pharmaceutical companies (and possibly other health care corporations) in the shaping of clinical research. [Sismondo S. Ghost management: how much of the medical literature is shaped behind the scenes by industry? PLoS Med 4(9): e286 doi:10.1371/journal.pmed.0040286]

Sismondo defined ghost management of medical research and publishing:

when pharmaceutical companies and their agents control or shape multiple steps in the research, analysis, writing, and publication of articles. Such articles are 'ghostly' because signs of their actual production are largely invisible—academic authors whose names appear at the tops of ghost-managed articles give corporate research a veneer of independence and credibility. They are 'managed' because those companies shape the eventual message conveyed by the article or by a suite of articles.

Sismondo thus went beyond the issue of ghost-writing, the contribution of unnamed authors who may be influenced, or hired, by pharmaceutical companies or other organizations with vested interests. (See recent post here.) He also went beyond the issue of how pharmaceutical companies and other research sponsors may attempt to influence the design and implementation of research studies, the analysis of their results, and/or how the results are reported. (See this post.)

As Sismondo noted,

It has been repeatedly and firmly established that pharmaceutical company funding strongly biases published results in favor of the company's products. Ghost management amplifies that bias, because when one set of commercial interests exerts influence at multiple stages of research, writing, and publication, it will shape the resulting article. In turn, bias affects medical opinion and practice, and ultimately, patients.

Sismondo also attempted to estimate the prevalence of ghost management. This would have been predicted to be a difficult task, because,

it is not in the interests of writers, authors, or sponsors and their agents to reveal ghost management processes; hence a number of the published accounts of ghost management have stemmed from legal proceedings and investigative journalism.

So he set out to review existing evidence and find some new evidence.

First he noted the article by Healey and Cattall, based on documents produced during legal proceedings, that explained how Pfizer Inc ghost managed publications of multiple articles on the drug sertraline [Zoloft], producing 85 manuscripts, and accounting for an important part of the literature on this one drug. (See previous post here.)

An important contribution by Sismondo was what he called his "supply-side analysis."

A survey in 2001 identified 182 MECCs in the United States, up from 153 in 1998. A number specialize in producing, placing, and tracking journal articles, known in the trade as 'publication planning' or 'strategic communication planning.' While these firms hide details of their work—from potential critics and competitors—they also energetically promote themselves and their services.

I spent six hours searching web pages for MECCs offering publication planning or similar or overlapping services to the pharmaceutical industry, and found 23 (list available from the author). This is not an estimate of the number of such firms, but indicates how common they are. There may be many more firms providing publication planning, including some not uncovered in this search, and some not advertising these services on the Internet.

In a primer on publication planning, the director of one MECC defines the activity as: 'gaining product adoption and usage through the systematic, planned dissemination of key messages and data to appropriate target audiences at the optimum time using the most effective communication channels'.

Complete Healthcare Communications (CHC) claims on its banner that it 'has honed the systems and skills needed to develop the intellectual heart of pharmaceutical marketing—the publication plan. The result for your product? A continuum of awareness, interest, and prescriber confidence.'

CHC includes among its clients Pfizer, Sanofi-Aventis, Ortho Biotech, Wyeth, Schering-Plough, Shire, AstraZeneca, and other pharmaceutical companies.

Other agencies offer very similar services. As described in an article by three of its managers, the Medical Knowledge Group starts publication planning with a phase of exploring 'key messages' and 'author/journal options' before designing any publications to incorporate those messages

Another MECC, Envision Pharma, says that 'data generated from clinical trials programs are the most powerful marketing tools available to a pharmaceutical company.' Envision will work from early on in the process to ensure 'consistent message dissemination,' will plan and track the 'data dissemination plan,' and will produce 'scientifically accurate, commercially focused abstracts, posters, and primary and secondary publications'

Several of the publication planning firms identified are owned by major publishing houses. For example, Excerpta Medica is 'an Elsevier business' and writes that its 'relationship with Elsevier allows… access to editors and editorial boards who provide professional advice and deep opinion leader networks.'

Wolters Kluwer Health draws attention to its publisher Lippincott Williams & Wilkins, with 'nearly 275 periodicals and 1,500 books in more than 100 disciplines,' and to Ovid and its other medical information providers, emphasizing the links it can make between its different arms

Vertical integration is attractive in the industry as a whole: at least three of the world's largest advertising agencies own not only MECCs, but also CROs.

Ghost management of medical journal publications is clearly a substantial business, employing thousands of marketers, writers, and managers. It is large enough that the industry has established the International Publication Planning Association.

The conclusion is that

Given the amount of data that pharmaceutical companies control, the number of publication planning agencies that openly advertise on the Internet, the number of medical writers, the existence of two associations for publication planners, and meetings organized and reports written for them, we can conclude that ghost management is common.

Why is it so important?

Articles in medical journals have real effects upon physician prescribing behavior, which is why pharmaceutical companies invest so much in their publication. Journal articles are heavily used in detailing, to validate claims and rebut worries. Even independent of detailers, responsible physicians and medical researchers search the literature to gather evidence about the best treatments. Published scientific articles are the sources of medical information with the highest authority. Systematic reviews and meta-analyses almost all start with the published literature—so even fully independent reviews are influenced by ghostly activities.

It is clear that ghost management is a major part of the production of pseudoevidence-based medicine.

Sismondo's article is an important contribution to our knowledge of how research on human beings is manipulated into marketing and propaganda, if not outright disinformation. Such practices break the trust of research subjects who thought they were participating to advance science and medical care. Such practices mock physicians who think they are trying to make decisions based on clinical science. Such practices can harm patients who are subjected to tests and treatments based on hype and manipulation rather than unbiased data.

Sismondo ended with some suggestions for alleviating the problem, but noted,

There are no straightforward solutions, short of large changes to the nature of medical publishing and/or research, changes that would effectively sequester pharmaceutical company funding from research and publishing....

We have now said frequently that there are many reasons to think about whether organizations who have a vested interest having clinical research produce particular results should be banned from funding or other involvement in research on human beings. The probably pervasive practice of ghost management is another strong reason to consider this seemingly extreme step.

In the absence of such a drastic prohibition, all I could suggest is a much strengthened and more comprehensive disclosure policy. Many would now agree that all clinical trials should be registered. Such registration should include details of any involvement of pharmaceutical, biotechnology, device and similar companies in the design and implementation of the research, and the analysis and reporting of its results. Any involvement by contract research organizations, for-profit institutional review boards, medical education and communication companies, and the like should be disclosed in trial registration.

Furthermore, there should be full disclosure of all involvement by any of these organizations accompanying any publication or presentation of study results, including publications in peer-reviewed journals, abstract presentations, etc.

Furthermore, the penalties for concealing involvement of any of these organizations should be severe, all the way up to considering failing to disclose as potential criminal fraud.

Allowing ghost management to continue victimizes people who volunteer to participate in research, mocks physicians who try to base their clinical decisions on the best available evidence, and hurts patients.

Hat tip to the Medical Humanities Blog, and one of our corps of Health Care Renewal scouts.

Post Title → Haunted Health Care: the Scope of Ghost Management

BLOGSCAN - To Get CME Credit, Read a "Ridiculous Text"

On the Carlat Psychiatry Blog, this post detailed the disdain for which a noted psychiatrist expressed for a ghost-written, medical education and communication company organized, pharmaceutical company sponsored CME publication which ostensibly was derived from a panel discussion in which that psychiatrist participated. His most pithy comments I will not print in this family-oriented blog ;-) Yet physicians can still get CME credit in part for reading what he called a “ridiculous text… parts of it were inaccurate, simplistic, and [contained] over-generalizations.”

Post Title → BLOGSCAN - To Get CME Credit, Read a "Ridiculous Text"

BLOGSCAN - New CME Policies Dissected

On the Carlat Psychiatry Blog, this post dissects the new rules for providing continuing medical education (CME). My favorite was the re-definition of "commercial interest" that still does not define a for-profit medical education and communication company (MECC) as "commercial."

Post Title → BLOGSCAN - New CME Policies Dissected

BLOGSCAN - the Faults of CME by MECC

On the Carlat Psychiatry Blog, this saltily titled post provides another good illustration of the faults of industry-funded, medical education and communications company (MECC) written continuing medical education (CME), in this case, pushing what would appear to be a particularly hazardous anti-depressant medication, a MAO inhibitor delivered by a patch.

Post Title → BLOGSCAN - the Faults of CME by MECC

BLOGSCAN - How MECCs Tweak CME in Favor of their Sponsor's Product

On the Carlat Psychiatry Blog is a post on the "tweaking" of CME published by a medical education and communication company (MECC) in favor of the produce produced by its commercial sponsor.

Post Title → BLOGSCAN - How MECCs Tweak CME in Favor of their Sponsor's Product

More Things That Go Bump in the Night

From ghoulies and ghosties
And long-leggedy beasties
And things that go bump in the night,
Good Lord, deliver us!

The Wall Street Journal just published an investigative report updating our knowledge about the ghost writing of medical articles. It includes some important new examples of the genre.

• The manuscript of an article in the American Journal of Kidney Diseases, whose first author was ostensibly Alex J Brown was posted on the web-site of medical writer Michael Anello as an example of his work. He had been commissioned by a medical communications company to write the paper on behalf of Abbott Laboratories, which makes Zemplar (paricalcitol), a Vitamin D analog. Anello was not listed as an author of the published article. (Brown AJ. Therapeutic uses of vitamin D analogues. Am J Kidney Dis. 2001 Nov;38(5 Suppl 5):S3-S19.) Brown claims he partially re-wrote Anello's draft, and was responsible for the final version of the article. Anello has since removed the article from his web-site.
• A medical writer paid by GlaxoSmithKline helped draft a manuscript on the safety of acetaminophen versus aspirin and other analgesics for patients with asthma. GSK makes a version of acetaminophen (Panadol) outside the US. The published article stated that the first author "performed the analysis and drafted the paper." (Jenkins C, Costello J, Hodge L. Systematic review of prevalence of aspirin induced asthma and its implications for clinical practice. BMJ 2004;328:434) The lead author said that the "structure of her work was 'suggested' by the company version but she and the other authors did their own analysis." She also denied knowing that the company paid the writer. GSK said the failure to disclose the role of the medical writer was "a lapse on the part of GSK." A rapid response was just (December 13, 2005) appended to the electronic version of the article, stating, "A medical writer assisted in sourcing the papers, summarising their content and reviewing drafts for this review of the literature, but declined to be included as an author. The authors reviewed all papers considered for the analyses. The scientific evaluation of the data and the clinical commentary contained in the review was provided by the authors. The authors have recently been made aware that, without their knowledge, the medical writer's costs had been met by GlaxoSmithKline, but are confident that the information presented in the review was accurate and reflected the authors' personal scientific opinions."

The Wall Street Journal article also recounts some cases that may be familiar to the readers of Health Care Renewal.

• There was the omission by someone at Merck, unbeknownst to the lead author, of pertinent data about adverse events afflicting patients treated with Vioxx from the manuscript of the VIGOR study sent to the New England Journal of Medicine. (See our post here.)
• How the manuscript of the Advantage trial of Vioxx was written in-house by Merck, not by its first author. (See our post here.)
• The "stealth marketing" campaign that included the authoring of multiple articles about Zoloft (sertaline) by a medical education company at Pfizer's behest. (See our post here.)
• The finished draft of a manuscript on the adverse effects of warfarin sent to Dr. Adriane Fugh-Berman by a medical communications company hired by AstraZeneca, which was starting to market a new competing drug, Exanta (ximelagatran). (See our posts here, here and here.)

Kudos to the Wall Street Journal and reporter Anna Wilde Matthews for reminding us that ghost-writing is an ongoing, unsolved problem. It would be fitting to conclude with a quote from the editorial in the Journal of General Internal Medicine that accompanied Dr Fugh-Berman's article noted just above.

Publishing biased literature is not simply "getting the message out" for the pharmaceutical client of the medical education company. It injects bias and untruth into the scientific dialogue in order to enhance corporate profits.
How much is sullying the medical literature worth in market share?

Protect us, indeed!

Post Title → More Things That Go Bump in the Night

"Pharma Goes to the Laundry"

And nobody is left feeling clean....
Thanks for Sue Pelletier's blog Capsules for discovering an article written in 2004 entitled "Pharma Goes to the Laundry." (Full citation: Elliott C. Pharma goes to the laundry: public relations and the business of medical education. Hastings Center Rep 2004; 34: 18-23.) The article suggested that pharmaceutical companies "launder" their marketing message through medical education and/or communication companies to produce medical education or scholarly articles that appear to be independent and unbiased, and that these practices are much more frequent than even I previously thought.
In particular, Elliott, in turn, pointed out a 2003 article by David Healy (Healy D, Cattell D. Interface between authorship, industry and science in the domain of therapeutics. Br J Psych 2003; 183: 22-27) which took advantage of documents released during litigation from a medical communications company (Current Medical Directions) used by Pfizer to market sertaline (Zoloft). Healy and Cattell compared Current Medical Directions' log of the "scholarly" articles it wrote and PubMed searches. The results suggested that the majority of articles on sertaline from 1998-2000 were ghost-written by Current Medical Directions. If this data is generalizable, then the majority of apparently independent, scholarly articles in the medical literature related to the use of pharmaceuticals may have been ghost-written. Yikes!
Elliott also summarized how Wyeth allegedly marketed Fen-Phen via a "medical education" campaign designed to convince physicians that obesity was causing a "public health crisis," a few strategically placed articles ghost-written by Excerpta Medica, and an additional $100 million campaign to minimize the adverse effects of the drug (all derived from the book Dispensing with the Truth, by Alicia Mundy).
Finally, Elliott suggested that bioethicists have not helped, because "we forfeited any credibility we may have had when we started taking pharma money ourselves." As examples, he juxtaposed Healy's data about how Pfizer supported ghost-written articles about sertaline with the company's support for the Pfizer Hall for Medical Humanities at New York University Medical School, the Pfizer Lectureship in Medical Humanities at Royal Free and University College Medical School (in the UK), and the Center for Bioethics at the University of Pennsylvania. (And he noted that Hasting Center Reports are funded by Merck.)
More yikes! Read it, and read Sue Pelletier's post here.

Post Title → "Pharma Goes to the Laundry"