Key Opinion Leader Services Companies: the Creation of Useful Idiots and Usefully Idiotic Organizations

In researching the conflicts of interest of the University of California "36," I stumbled upon a fascinating corner of the pharmaceutical/ biotechnology/ medical device marketing universe, the companies that find and manage key opinion leaders (KOLs), also known as "thought leaders."  Reviewing their own marketing materials reveals how KOLs truly are health care corporate marketing's useful idiots.

I found three companies which seem entirely devoted to the adoption, care and feeding of KOLs, plus numerous companies, including some medical education and communication companies (MECCs) that provide KOL-related products and services.  I will first describe the companies briefly, then draw upon their marketing materials to underline what KOLs are really about.

Leadership in Medicine Inc

This is the company I found first, because one of its directors is a member of the UC 36, the group of top university leaders who threatened to sue the university to increase their already generous pensions.

Leadership in Medicine Inc's web-site describes its reason for being thus:

IF YOU NEED TO KNOW who are the most prominent, admired, and influential actors in healthcare, how they are interconnected, and why, you need our expertise.

Given how vastly complex are the relationships among providers, researchers, and other significant actors in healthcare, it is vital to focus on key opinion leaders (KOLs) at local, regional, and global levels, and to understand the ties among them.

Its clients are:

Over 80 client companies
* All of the top 15 largest pharmaceuticals
* 8 of the 10 largest biotechs
* 5 of the 10 largest medical device companies

A graphic on its "experience" page listed the following companies: Baxter, Wyeth, Lilly, Roche, Gilead, GlaxoSmithKline, Pfizer, Abbott Laboratories, Genzyme, Bristol-Myers-Squibb, Medtronic, Johnson and Johnson, Genentech, and Covidien.

KOL LLC

Company description:

As our name implies, we are a company devoted to providing Key Opinion Leader software and Key Opinion Leader Management services for pharmaceutical, biotechnology and device companies.

The company's graphic client list included: Cephalon, Scios, Novartis, Schering-Plough King Pharmaceuticals, Pfizer, Genentech, Reliant Pharmaceuticals, McNeil (division of Johnson and Johnson, Jazz Pharmaceuticals, Endo Pharmaceuticals, Cytogen, Health Products Research, Shire, Reckitt Benckiser, Protein Design Labs, and Odyssey Pharmaceuticals.

Thought Leader Select

The relevant parts of the company description:

Thought Leader Select is a Chapel Hill, NC-based private research and consulting firm serving the biopharmaceutical and healthcare industries.

and

We serve these industries and the medical community at large by assessing medical experts (known as 'thought leaders' and 'key opinion leaders')....

Perusal of the materials used by these companies, and other companies which market KOL or thought leader related services makes the nature of the relationship between KOLs and commercial health care firms, and the purpose of employing KOLs clear.

KOLs are Employed by Marketing Departments to do Marketing

The best example comes from a description of a KOL information technology application sold by Nagarro:

A web-based application was developed by Nagarro to help the marketing department of a global pharmaceutical company exploit Key Opinion Leader (KOL) information in order to promote products and remain ahead of its competition.

Problem Description

In today s fast-paced competitive environment, pharmaceutical companies cannot solely rely on superior products to succeed. Well organized marketing departments help sales departments reach goals and give companies an edge over competition, but without access to valuable resources, like KOLs, they are ineffective. KOLs influence the medical community and ultimately the end users of pharmaceutical products.

Pharmaceutical companies that are able to identify and work with KOLs will be better positioned to compete....

Benefits

[include]
Creation of market intelligence from highly specialized and customizable reports containing previously unavailable aggregate data....

Ability to group KOLs by product knowledge and associations in order to better promote products

Ability to maximize ROI from KOL related events

Enhanced sales and marketing productivity through streamlining of complex multi-source information

That makes it crystal clear that marketers use KOLs to market, to sell products. While at times KOLs might actually be used to advise health care corporations about clinical or scientific issues, that is hardly their major point. KOLs are almost always hired to market by marketing departments.

In case someone might argue that this is only one example, let us look at materials from the other companies.

KOL LLC described the usefulness of KOLs thus:

Everyone recognizes the value of opinion leaders (OL), or thought leaders. While national level OLs may not write many prescriptions they influence thousands of prescribers and hence prescriptions through their research, lectures, publications and their participation on advisory boards, committees, editorial boards, professional societies and guidelines/consensus document development. Regional level OLs are often involved in state societies or legislative initiatives in addition to their speaking and publications. While local level OLs may not publish, they provide advice to local colleagues and may speak at grand rounds. And who are the ‘rising stars’ in your therapeutic area?

It is imperative that you know the OLs in your market at a national, regional and local influence level as well as those ‘rising stars’.

This is a bit more indirect, but it is clear that the goal is to "influence prescribers" to prescribe, not provide scientific or clinical advice to the company.

Leadership in Medicine Inc's materials also continually emphasized the point of KOLs is to influence, for example, they boasted of pioneering analyses "to assess paths of influence in healthcare," developed a particular tool called "Centrality Ranking" to "provide fine-grained ratings of KOLs' influence," and claimed to "have identified, profiled, and mapped the influence of tens of thousands of individual KOLs...." The clear implication is that KOLs' influence is the central consideration, and what else is this influence good for other than to sell products, and perhaps advocate for corporations in general?

When KOLs are Involved, Many Activities that Appear to be Educational or Scientific Really Are For Marketing

Strikingly, KOL LLC claimed its role in guideline development:

Guidelines produced by national societies are optimal, but often can be a slow, painful and expensive process to develop. KOL, L.L.C. can provide a faster alternative. We have experience convening a panel of experts in a therapeutic area. We serve a project management role to ensure the timelines and deliverables are met. We have access to a medical writing team of 25 healthcare professionals who can write the initial drafts, as our experience tells us it is easier for experts to edit, than to write from scratch.

There has been growing realization that guidelines may be biased by commercial sponsorship and by the participation by individuals with conflicts of interest. The KOL LLC marketing materials suggest, however, that guidelines have become purpose-built marketing vehicles through the participation of selected KOLs with allegiances to drug, device and biotechnology companies. As an aside, note that guideline-development services includes the participation of a team of ghost-writers who will write the first drafts, a function that naive academics might have thought should be that of clinical and scientific experts.

For another example, KOL LLC asserted it could manage "investigator meetings," :

We’ll help you better plan to maximize the communication of the trial results through targeted abstracts, posters, publications and lectures.

so

Due to the time constraints placed on Clinical Research Departments, many times ‘research mills’ are selected as the trial sites. This is fine, but who is going to publish the results and stand up and present the results at national, regional and local meetings. We can provide you advice and counsel about how to involve your KOLs effectively, while maintaining your aggressive timelines.

The goal of KOL management here is for the company to control how the research is disseminated. Note also the cynical view of "research mills," which likely refers to contract research organizations. Do we really think that CROs are used by commercial firms because they do better research?

Key Leading Organizations

A bonus from reading through the offerings on KOL management was to discover another related business that has not been subject of polite conversation before. Leadership in Medicine Inc put it this way:

Equally essential is recognizing the roles played by key leading organizations (KLOs) such as medical institutions, payers, professional organizations, patient groups, government entities, and journals in structuring KOL activities and relationships, since those are the stages on which KOLs perform.

Key Leading Organizations (KLOs) apparently include influential organizations, e.g., academic medical institutions, medical societies, and patient advocacy groups that can be deliberately turned into organizations of useful idiots for marketing purposes. Note that we and others have discussed how institutional conflicts of interest and conflicts of interest affecting leaders of of such organizations can lead to bias in favor of commercial interests. But what Leadership in Medicine Inc has written suggests that such organizations can be deliberately taken over to function as industry's fellow travelers.

Similarly, Thought Leader Select advertised services to manage organizations to support "thought leadership":

Through Centers, all of our research and assessment skills culminate in our evaluation of universities, influential clinics, and research foundations for a holistic approach to thought leadership in the medical community. With centers of excellence assessments we take a drill-down approach, starting at the academic medical centers, then moving into affiliated hospitals and clinics....

Summary

Industry spokespeople and key opinion leaders tout themselves as clinical, educational, and/or scientific experts chosen for their expertise to advance medicine, science and public health.  There are documented instances (e.g., see posts here and here) in which defectors from marketing departments of commercial health care corporations described KOLs as salespeople who could be more influential hidden within their professional or academic cloaks.  Even some physicians paid to be speakers on behalf of pharmaceutical corporations have acknowledged their role as salespeople in fancy dress (see post here).  There are cases of documents revealed by discovery in legal actions that show how companies planned organized stealth marketing efforts for drugs that included activities by KOLs (e.g., see post here about marketing of Lexapro, and here about Neurontin).

However, the marketing materials used by KOL service companies (for lack of a better name) show that KOLs are largely meant to be stealth marketers, and hired for that purpose, that KOLs participate as marketers in the sorts of activities that to the naive appear to be educational or scientific, and that marketers try to recruit whole organizations, such as medical schools, research organizations, medical societies, and patient advocacy groups as disguised sales organizations.

This goes beyond the problem of bias of physicians, or individual health professionals due to their financial relationships.  It goes beyond the problem of bias of organizations due to their sources of financial support or the financial relationships of their leaders.  It looks like there has been a massive campaign by health care corporate marketers to make useful idiots out of possibly a majority of medical academics and academic, professional, and supposedly patient-centered organizations.  This appears to be a massive, cynical effort to hollow out our once respected health care institutions and professionals in the service of marketing.

A final word to any individuals reading this who are paid by corporate marketers to be KOLs.  If you think that you are paid for educational or scientific purposes, you likely have been made into a chump.  The people who did this to you were likely not acting in your best interests, or those of society, but to cynically market their product and increase their own earnings.  If you doubt this, look at the materials cited above.  You really don't want to continue being chumps, do you?

Post Title → Key Opinion Leader Services Companies: the Creation of Useful Idiots and Usefully Idiotic Organizations

BLOGSCAN - This Book is Haunted

We have posted quite a bit about ghost-written articles, that is, ostensibly scholarly articles appearing in medical and health care journals with apparently prominent authors that were really written mainly by medical writers hired by companies to market particular products, usually drugs.  Now we hear of a case of a ghost-written book.  Our fellow bloggers have covered this well.  See posts here and here by Professor Margaret Soltan in University Diaries, and here on Inside Higher Ed; here by Dr Daniel Carlat on the Carlat Psychiatry Blog; here by Dr Howard Brody on the Hooked: Ethics, Medicine and Pharma blog; and here by Alison Bass on the Alison Bass blog.  Ghost writing is often an important component of stealth marketing schemes, and serves not only to deceptively market products, but to deceptively increase the influence and prestige of the "key opinion leaders" who enable the practice.  Be skeptical about the medical literature, and particularly skeptical by any academic who seems to have written more articles than would be humanly possible.

ADDENDUM (2 December, 2010) - As suggested by the comment below, see also posts here and  here on the 1BoringOld Man blog.  Also see an additional post by Dr Howard Brody on the Hooked: Ethics, Medicine and Pharma blog.

Post Title → BLOGSCAN - This Book is Haunted

Merck Settles Another Vioxx Case

All the shenanigans that went on in the course of Merck's marketing of the now withdrawn Cox-2 inhibitor non-steroidal anti-inflammatory drug Vioxx have provided grist for the Health Care Renewal mill since 2005.  For example, see these posts:

- here about ghost-writing of a Vioxx research publication;
- here, and here about allegations that Merck executives tried to intimidate Vioxx critics;
- here about how advocates of an extreme laissez faire approach to regulation of health care corporations used illogical arguments about the Vioxx case;
- here about how an apparently major clinical trial of Vioxx turned out to be a "seeding trial," that is, a study really meant to recruit supposed physician-researchers as prescribers; and
- here about how one once prominent Vioxx researcher pleaded guilty to fraud in connection with his research on other drugs. 

Thus, the Vioxx case provides a good lesson about some of the tactics used to deceptively and unethically promote health care products (pharmaceuticals in this case).

Merck just announced just the latest settlement of Vioxx related legal actions, as reported by Business Week:

Merck & Co. agreed to settle shareholder lawsuits over the withdrawn Vioxx painkiller by strengthening its drug-safety procedures, appointing a new chief medical officer and paying $12.2 million in legal fees.

Merck would appoint one committee to address risks that require immediate action and another to monitor the safety of drugs, the company said in a regulatory filing. Merck would also amend its code of conduct to promote scientific and academic integrity as well 'honest communication' with doctors.

'In all research endeavors that are sponsored by Merck, we will refrain from attempting to influence inappropriately the results and conclusions of such research,' according to the amended code. 'We strive for all communications with the medical community to be accurate, truthful and consistent with labeling.'

Also,

The company will be required to make corporate governance changes and “supplement existing policies and procedures,” ... [a Merck spokesperson] said.

Merck would submit results of clinical trials to a public registry, with its compliance overseen by an independent third party.

The chief medical officer will have an 'executive voice' on product safety issues independent of Merck Research Laboratories.

Note that this settlement is only of one type of lawsuit, as described in a Wall Street Journal article,

The pact, which is pending final court approval, would resolve state and federal shareholder 'derivative' complaints (which are brought by shareholders on behalf of a company) alleging that current and former Merck officers and directors breached their fiduciary duties in handling Vioxx.

Merck had already settled thousands of lawsuits,

Since the Vioxx controversy erupted, about 27,000 personal-injury lawsuits have been filed, the company says. Merck has been challenging all of the cases and settled many of them. Most notably, it agreed to a pay $4.85 billion to settle personal-injury claims of more than 40,000 people. In another settlement, the company will pay $80 million to resolve 190 claims filed by drug-benefit plans seeking to recover costs of paying for Vioxx use.

Merck has lots of other legal actions to go through,

The Vioxx litigation remains far from over. The U.S. Supreme Court is weighing a separate shareholder case, seeking billions of dollars in damages from the company. Merck disclosed last year the U.S. Attorney's office in Boston was conducting a grand-jury investigation of Merck's handling of Vioxx. The claims of some 310 plaintiff groups are outstanding in courts in the U.S., according to the securities filing. There are also cases overseas, including Australia and Turkey.

So the parade of legal actions and settlements thereof continues.  We believe that the scope of this parade provides some sort of index of bad behavior by the health care organizations needing to make such settlements.  Most of these legal results are reported on in the business media, and rarely appear in any medical, health care research, or health policy journals.  I submit that were health care professionals, health care researchers, and health policy makers more systematically aware of these cases, they might realize that unethical and sometimes illegal behavior, often generated by bad leadership unrestrained by poor organizational governance, is a major cause of the current, seemingly intractable health care crisis.

One notable attribute of the current Vioxx settlement is that it does mandate some changes in Merck's governance and leadership meant to prevent future cases similar to this one.  These include developing leadership structures and changing the company's code of conduct to emphasize the need for "truthful" communication, and the need to refrain from "inappropriately" influencing research. 

On Health Care Renewal we have discussed numerous examples of deceptive practices by health care organizations, often affecting marketing, and of manipulation and suppression of research.  It is a small step forward for one company to commit to honest communications and to not manipulate research.  A better code of conduct may at least be a start towards an organizational ethics policy, which in turn may have the potential to actually improve behavior. 

On the other hand, typical settlements that involve only monetary damages paid by the organization seem to have little deterrent effect on future bad behavior. Usually, the companies involved only need to pay fines, and no individual who performed, directed or approved unethical or illegal acts suffers any negative consequences. I submit once again that such fines are viewed merely as costs of doing business by the affected companies, and do not deter future bad behavior. Until the people who approve, direct, and perform unethical or illegal acts pay some penalties, expect such acts to continue, at best deterred only slightly by written policies that condemn them. I again suggest that to truly reform health care, we need rigorous regulation of health care organizations that has the power to deter unethical behavior that may risk patients' health

Post Title → Merck Settles Another Vioxx Case

British Medical Journal Interviews Dr Aubrey Blumsohn

About a year after we started Health Care Renewal, in late 2005, we wrote multiple posts about the complex and unfortunate case of Dr Aubrey Blumsohn's attempts to keep a research project honest.  Our most recent summary of the case was here.  The case involved suppression and manipulation of research, ghost-writing, institutional conflicts of interest, and attempts to silence a whistle blower. It provides lessons about the downsides of letting commercial firms sponsor and hence control human research designed to evaluate the products or services they sell; and of academic medicine becoming dependent on research money from such firms for such research.

The case was just re-capped in some detail on the occaision of an interview of Dr Blumsohn published in the British Medical Journal, just available on-line yesterday.  [Cyer C. Aubrey Blumsohn: academic who took on industry.  Brit Med J 2009; 339:b5293.  Link here.]  Dr Blumsohn's final words in the interview were:

It’s hard to encourage anyone to speak out about poor practice in the current environment. This case sums up what has gone wrong with systems set in place to ensure safety and integrity in scientific medicine. It would help if regulators put as much effort into responding to serious critics and whistleblowers as they do producing glossy brochures and yet more guidance.

My hat is off to Dr Blumsohn for his determination to pursue this case, and to the British Medical Journal for getting it into the "main-stream" health care literature.

Hat-tip to PharmaGossip.

Post Title → British Medical Journal Interviews Dr Aubrey Blumsohn

How Industry Views the Research It Sponsors

We have posted frequently about threats to the integrity of the clinical evidence-based, and to the practice of evidence-based medicine.  In particular, we have discussed how research may be manipulated in favor of vested interests, or suppressed when the results do not favor such interests.

Last week, the British Medical Journal electronically published a set of guidelines for how industry sponsored clinical research ought to be published, sponsored by the International Society for Medical Publication Professionals.  The authors came from pharmaceutical companies (Johnson & Johnson, AstraZeneca, Pfizer and Cephalon), medical device companies (LifeScan), and medical publishing and medical education and communication companies (John Wiley & Sons, Excerpta Medica, Field Advantage Medical Communications, PharmaWrite, and Knowledgepoint 360 Group).  [Graf C, Battisti WP, Bruce-Winkler V et al. Good publication practice for communicating company sponsored medical research: the GPP2 guidelines.  Brit Med J 2009; 339:b4430.  Link here.]

These guidelines are remarkable for the questions they raise about how people from industry view clinical research and how it should be reported in medical journals. 

Who's in Charge?

Nowhere does the article acknowledge that any one person has overall responsibility for a research project.  Clinical research projects funded by the US National Institutes of Health, Agency for Healthcare Quality and Research, and other federal agencies must have "principal investigators," who are the people who take overall scientific responsibility for the project.  The Graf et al article does not use this or an equivalent term.   There is no sense that they expect anyone to be in completely in charge of industry sponsored research. 

Particularly confusing is the following passage:

Before writing begins one author (a lead author, who may also be guarantor) should take the lead for writing and managing each publication or presentation. One author (identified as guarantor) should take overall responsibility for the integrity of a study and its report.

Here are some questions it raises.  If the guarantor could be chosen only when writing a paper is contemplated, which presumably could be years after the study that the paper would report was designed and implemented, who then would have been responsible for study "integrity" before the guarantor was chosen? Who would chose the guarantor for a particular paper? If a study generates more than one paper, could they each have a guarantor, and then how could they share responsibility for study "integrity?"  If the guarantor and lead author of a paper are different people, how would they share responsibilities, what would happen if they were not to agree, and who would be finally accountable?

So the guidelines seem to completely diffuse accountability for research projects, and the reports written about them.

Who is an Author?

In my experience with US federally and foundation funded research, research papers are written by the investigators, the people who actually did the research project.  However, in the guidelines by Graf et al, the concept of authorship is also ambiguous.  They suggest that "recognised criteria should be used to determine which of the contributors to an article should be identified as authors."  This is already confusing, since how could one be a "contributor" to an article without authoring it?  A later discussion of "contributors" as "investigators, sponsor employees, and individuals contracted by the sponsor" was not very helpful.  Why should a "sponsor employee" who was not an "investigator" be a "contributor" or an "author," whatever the distinction is between them? 

So the guidelines blur distinctions among people who do research, and people employed by companies that may have vested interests in the research favoring their products or services.

What do Professional Medical Writers Do?

There has been considerable recent controversy, not directly acknowledged by Graf et al, about the role of professional medical writers in the reporting of research and the writing of ostensibly scholarly medical publications, particularly in cases where the writers were paid by and reported to corporate sponsors, but were not recognized as such in the publications they wrote (a type of ghost-writing).  The guidelines by Graf et al do not clearly explain what the roles of professional medical writers ought to be:

Professional medical writers must be directed by the lead author from the earliest possible stage (for example, when the outline is written), and all authors must be aware of the medical writer’s involvement. The medical writer should remain in frequent contact with the authors throughout development of the article or presentation. The authors must critically review and comment on the outline and drafts, approve the final version of the article or presentation before it is submitted to the journal or congress, approve changes made during the peer review process, and approve the final version before it is published or accepted for presentation.

Note that this would not prevent a professional medical writer from writing an initial outline, the first draft, and all subsequent drafts. including the final draft of a paper. (The role of an "author" above might be restricted to simply commenting on and accepting the outline and all drafts.) Thus, the "authors" could function as distant editors, and the professional writer would assume authorship, as most people would define it. (Merriam-Webster: "1. one that originates or creates 2. the writer of a literary work.")

Furthermore, while the professional writer could take one the role of authorship, the guidelines do not require him or her to publicly acknowledge this role:

Professional medical writers, depending on the contributions they make, may qualify for authorship. For example, if a medical writer contributed extensive literature searches and summarised the literature discovered, and by doing so helped define the scope of a review article, and if he or she is willing to 'take public responsibility for relevant portions of the content' then he or she may be in a position to meet the remaining ICMJE criteria for authorship.

Presumably, a professional writer could dodge authorship by simply being "unwilling" to take such public responsibility.

So the guidelines apparently condone nearly all functions commonly assumed to be those of an author to be performed by a professional writer paid directly by the sponsor, without the writer being listed as an author.  The guidelines thus appear to condone ghost-writing in its most pernicious form.

Who Owns and Analyzes the Data?

Cases in which various the implementation and analysis of clinical research seems to have been manipulated to favor vested interests have raised concerns about the integrity of the data collected in the course of a research project, and how it is analyzed.  This is what Graf et al say about the ownership and use of the data:

Sponsors have a responsibility to share the data and the analyses with the investigators who participated in the study. Sponsors must provide authors and other contributors (for example, members of a publication steering committee or professional medical writers) with full access to study data and should do so before the manuscript writing process begins or before the first external presentation of the data. Information provided to the authors should include study protocols, statistical analysis plans, statistical reports, data tables, clinical study reports, and results intended for posting on clinical trial results websites. Sufficient time should be allowed for authors and contributors to review and interpret the data provided and to seek further information if they wish (for example, access to raw data tables or the study database).

The guidelines by Graf et al suggest that the company that sponsors the research should own the data. The investigators who collected the data and implemented the research project should not. At best, the company should "share" summaries, analyses, or pieces of the data, but at best investigators could have only "sufficient time" to "seek ... access to raw data tables or the study database."

So the guidelines would allow corporate research sponsors to analyze the data from studies evaluating their own products and services as they see fit, and the scientists who implemented the study and collected the data could only ask for access to it. 

Summary

The guidelines by Graf et al seem based on a very strange conceptualization of clinical research. In their view, no individual may be responsible for a clinical research project. Research data is controlled by the company that paid for the project, not scientists who implemented the research and collected the data. Research papers may be written by anonymous professional writers while the scientists who did the research only need to review and approve what they have written.

So why should anyone give credence to industry sponsored research?

We have discussed numerous instances in which clinical research was manipulated in favor of vested interests, and when clinical research whose results did not favor vested interests was suppressed. In most cases, the vested interests were held by for-profit pharmaceutical, biotechnology or device anufacturers acting as research sponsors. The guidelines by Graf et al seem to have been cleverly written to to employ comforting platitudes while licensing manipulation and suppression.  They should inspire no confidence in the integrity of industry sponsored research.

Post Title → How Industry Views the Research It Sponsors

GHOSTING MATILDA

The fall season is upon us and the markets are filled with advertising for Halloween, so our thoughts naturally turn to the recent stories of ghostwriting in medical journals. Here is a lighthearted take on that topic. This parody began on Margaret Soltan’s blog a few days ago, and it has just kept growing.

GHOSTING MATILDA

Once a jolly bagman signed on to some articles.
Corporate ghosts even promised him a fee.
And he sang as he watched and waited till they were in print,
These will be grand right up there on my CV.

Ghosting Matilda, ghosting Matilda,
Who’ll come a-ghosting Matilda with me?
And he sang as he watched and waited till they were in print,
These will be grand right up there on my CV.

This month it’s Janssen, next it’s Bristol-Myers Squibb.
Wyeth and Lilly soon might want to talk to me.
Novartis might sign me up, also AstraZeneca ─
Soon I’ll be famous like that guy at Emory.

Ghosting Matilda, ghosting Matilda,
Who’ll come a-ghosting Matilda with me?
Novartis might sign me up, also AstraZeneca ─
Soon I’ll be famous like that guy at Emory.

Up came an editor, looking for the telltale signs.
Ghost writing’s hard to cover up, you see.
And he found them in the documents: metadata do not lie ─
Bagman just sold his name and passed these off on me.

Ghosting Matilda, ghosting Matilda,
Who’ll come a-ghosting Matilda with me?
And he found them in the documents: metadata do not lie ─
Bagman just sold his name and passed these off on me.

Up jumped the bagman, pointing fingers right and left,
You’ll never prove that I lied, said he.
I will say that underlings failed to send disclosure forms;
Let them be blamed instead, while I get off scot-free.

Ghosting Matilda, ghosting Matilda,
Who’ll come a-ghosting Matilda with me?
I will say that underlings failed to send disclosure forms;
Let them be blamed instead, while I get off scot-free.

Out! said the editor, you’re now persona non grata.
So, too, the Dean and the Provost agreed.
Bagman’s ghost may be heard now, sighing in the library ─
Could have been grand right up there on my CV.

Ghosting Matilda, ghosting Matilda,
Who’ll come a-ghosting Matilda with me?
Bagman’s ghost may be heard now, sighing in the library ─
Could have been grand right up there on my CV.

Post Title → GHOSTING MATILDA

The Reappearance of a Ghost of Seasons Past

About a year after we started Health Care Renewal, in late 2005, we wrote multiple posts about the complex and unfortunate case of Dr Aubrey Blumsohn's attempts to keep a research project honest. The early posts were here, here, here, and here. In this post, we summarized the case thus:

• Dr Aubrey Blumsohn, a senior lecturer at Sheffield University, and Professor Richard Eastell performed a research project on the effects of the drug risedronate (Actonel, made by Procter & Gamble Pharmaceuticals [P&G]) under a contract between P&G and the University.
• Although the research contract designated Blumsohn and Eastell as "Investigators" under whose direction the project would be carried out, Blumsohn was not given access to the original data collected by the project.
• Despite numerous requests, (like this one), P&G refused access to this data repeatedly.
  Blumsohn was concerned that he and Eastell could be accused of scientific fraud if they continued to make presentations and write articles and abstracts without access to the data which they were supposedly writing about.
• Blumsohn became suspicious that some of the analyses done by P&G could be misleading, especially related to a graph shown to him that omitted 40% of patient data.
• Blumsohn objected to P&G arranging for papers and abstracts to be written by a professional writer, but with Blumsohn listed as first author. Blumsohn was concerned that such ghost-written documents were mainly meant to convey "key messages" in support of P&G's commercial interests.
• Eastell warned Blumsohn not to aggravate P&G, because the company was providing a grant to the University which "is a good source of income."
• After repeated failed attempt to get the data, Blumsohn complained to numerous officials at Sheffield University, including Eastell, medical school Dean Tony Weetman, University Vice-Chancellor Robert Boucher, and the Head of the University's Department of Human Resources, Ms R Valerio.
• Still unable to get the data, he spoke with news reporters about his case. At this point, Sheffield suspended him, but then offered him a severance agreement if he signed a contract binding him not to make any detrimental or derogatory statements about the University and its leaders.

So the case involved suppression and manipulation of research, ghost-writing, institutional conflicts of interest, and attempts to silence a whistle blower. It provides lessons about the downsides of letting commercial firms sponsor and hence control human research designed to evaluate the products or services they sell; and of academic medicine becoming dependent on research money from such firms for such research. Although Health Care Renewal, being US based, most often writes about such issues in the US, this case is a reminder that they are global. (Note that we posted more about this case in 2006, here, here and here, but since then it has not gotten much public attention.)

Last weekend the (UK) Guardian returned to it:

The Guardian has learned that one of Britain's leading bone specialists is facing disciplinary action over accusations that he was involved in 'ghost writing'.

The General Medical Council will call Professor Richard Eastell in front of a fitness to practice committee. Eastell, a bone expert at Sheffield University, has admitted he allowed his name to go forward as first author of a study on an osteoporosis drug even though he did not have access to all the data on which the study's conclusions were based. An employee of Proctor and Gamble, the US company making Actonel, was the only author who had all the figures.

Experts believe the practice is widespread in Britain.

In a letter published in the Journal of Bone and Mineral Research, which carried the original study, he stated: 'In the original paper one of the authors, a statistician working for P&G, Ian Barton, had full access to all the data.' The authors had full access to all the analyses of the data that they requested, he said – but those analyses were carried out by the company.

The letter, published in 2007, also acknowledged flaws in the study. A later independent analysis of the data 'identified some errors and poor practice', he wrote. The study was designed to show the strengths of Actonel which was in fierce competition with a rival bone-strengthening drug called Fosamax, made by Merck.

Eastell's paper concerned a study carried out on behalf of Proctor and Gamble, comparing the bone density of women prescribed Actonel with others who were not. Only the company knew which women were on the drug and which were taking something else.

Eastell's colleague, Dr Aubrey Blumsohn, wanted the codes which would say which of the patients who suffered fractures had been on the drug. The company refused. Blumsohn took his concerns to Eastell, but in a conversation which Blumsohn says he taped , Eastell said he was concerned that persistent requests might damage the relationship they had with the company. Eastell is said to have told him: 'The only thing that we have to watch all the time is our relationship with P&G. Because … we have the big Sheffield Centre Grant [from P&G] which is a good source of income, we have got to really watch it.' .

So, after four years, this case has generated an official hearing of sorts. The hearing is obviously late, and seemingly will only be devoted to only one aspect of this case (ghost writing). However, at least our friends in the UK are doing something. I cannot recall a single case that resulted in any serious consideration of imposing negative consequences on anyone who was accused of suppressing research, manipulating research, endorsing ghost-writing, or intimidating a whistle-blower. In fact, many of the more troubling cases have never resulted in any sort of public discussion either at the institutions at which they occurred, or at any organization with relevant regulatory, or even just moral authority. So the GMC hearing is at least a step forward. Two cheers for the British GMC, and none for US universities, academic medical centers, professional societies, and government regulators.

(If anyone can remind me of a case in which there was a public discussion at the relevant institution, or some public consideration of the case by a regulatory agency, professional society, or some group with moral authority, please remind me of it, and I would be happy to post about it.)

Post Title → The Reappearance of a Ghost of Seasons Past

Wyeth, Ghostwriting, Dr. Joseph Camardo and a Big Liquor Store With a Little Grocery Department

Ghostwriting is a topic covered extensively at Healthcare Renewal, including at my post "Wyeth: Ghostwritten Papers Fake, But Accurate" here, Roy Poses' "Wyeth's Industrial Scale Ghost-Writing" here, and many others about Wyeth and other pharmas that can be viewed via this link: http://hcrenewal.blogspot.com/search/label/ghost writing.

A story in the Philadelphia Inquirer yesterday about Wyeth and ghostwriting brought to mind my medical school days at Boston University, in a metaphorical and rather negative way, regarding an oddity reflecting today's pharma industry.

In those years I lived next to Boston City Hospital on the top floor of a 29-story high rise at 35 Northampton Street, at that time one of the toughest and highest crime neighborhoods in the region if not the country (I was careful and lucky, and only got mugged at gunpoint once.) I had an excellent bird's-eye view of the urban decay in the area, reflective of ethical decay in the community.

35 Northampton St., next to Boston Medical Center (formerly Boston City Hospital)

Across the street from the high rise was an oddity - a very large liquor store named Blanchard's. Inside Blanchard's was a very small grocery department of all things. Have a snack with your booze! (I went in only twice; once to see what it was all about, and again during the Blizzard of '78 to get some needed food when all transit in the city was shut down and several feet of snow -- and neighborhood guns -- inhibited foot travel.)

The area has much improved in the past three decades, but according to Google street view the liquor store is still there:

In the 1970's "Liquor Land" was a large liquor store with a small grocery department named "Blanchard's." Click to enlarge.

Why does this odd store remind me of Wyeth, and more generally today's pharmaceutical industry?

Because that industry has turned from what used to be a biomedical research & development industry with decent ethics and a small marketing arm, to large marketing industry with poor ethics and a small R&D arm.

(Or, perhaps more accurately, a large marketing industry with poor ethics and a busywork section disguised to look like R&D. As a colleague noted in my post "Pfizer/Wyeth Merger And Sacrificing The Future: Laying Off Scientific Staff All Over The Place" here, a small fraction of prime scientist intellectual horsepower and time is actually spent on true R&D today, the rest wasted on feeding the bureaucratic corpulence that is the modern pharma research lab. He observed that "what we today call pharmaceutical R&D is in reality busywork disguised to look like R&D, in effect a well engineered, well managed, massively expensive failure.")

Here is what led to my "pharmas have become large marketing firms with a small R&D effort" metaphor. It was a story in the local newspaper on ghostwriting.

The glib quotes from Dr. Joseph Camardo, Wyeth's senior vice president of global medical affairs, on the practice of ghostwriting are simply stunning:

Philadelphia Inquirer

Ghosts in the medical machine

Was drug research infected by ghostwriters? With Paxil suit in court, a Chadds Ford firm says it was ethical.

Sun, Sep. 20, 2009

By Miriam Hill

Inquirer Staff Writer

When GlaxoSmithKline P.L.C. marketers looked for doctors to promote the antidepressant Paxil, they called the project CASPPER. The name was more than just an offbeat tribute to the friendly cartoon ghost. It was a wink and a nod to "ghostwriting," a questionable practice in which scientists put their names on research written by someone else, usually a writer paid by a drugmaker.

Ghostwriting critics say it disguises marketing material as scientific research.

Charges of ghostwriting have been lobbed against many companies in recent years, including Glaxo, Wyeth, AstraZeneca P.L.C., and Merck & Co. Inc., often arising in lawsuits from consumers claiming a drug hurt them.

... Documents released in connection with 8,000 lawsuits filed against Wyeth over Premarin and Prempro show that the company, which employs several thousand people in Collegeville, paid a medical-writing firm to produce articles from 1998 to 2005 that allegedly downplayed the risks of hormone treatment and emphasized benefits.

In 2002, researchers stopped a landmark federal study after finding that menopausal women who took certain hormones had an increased risk of breast cancer, heart disease, and stroke.

"Ghostwriting was used to sway physician opinions to favor hormone use as disease prevention long after that was a scientifically defensible position," Fugh-Berman [writer Adriane Fugh-Berman - ed.] said.

Joseph Camardo, Wyeth's senior vice president of global medical affairs, called Fugh-Berman's view "baseless." Medical opinion evolves, he said, and the papers in question reflected scientific understanding then. He also said the authors alone controlled the content and writing of the papers, though some did have outside help paid for by Wyeth.

"It's really being misrepresented as something we wrote and paid for that said what we thought it should say," Camardo said. "But the authors were not paid, and the authors had the final say."

... Studies on ghostwriting have suggested that anywhere from 8 percent to 75 percent of articles in medical journals may involve the practice.

Aside from the point I raised in my post "Has Ghostwriting Infected The Experts With Tainted Knowledge, Creating Vectors for Further Spread and Mutation of the Scientific Knowledge Base?" here regarding possible severe contamination of the literature and therefore of "expert knowledge" as it exists today, Camardo's response raises a cornucopia of questions.

Regarding "Medical opinion evolves, he said, and the papers in question reflected scientific understanding then":

• Whose scientific opinion do they reflect, exactly?
• Does Camardo believe these ghostwritten papers, usually written by party "A" but with authorship claimed by party "B" (usually prominent academic physicians often nurtured by the industry into the role of "key opinion leaders", KOL's) are objective?
• Does Camardo actually believe most of the content comes from party "B" rather than party "A" in these papers?
  
• Does Camardo understand that paying a MECC (Medical education & communications company) or other firm to write scientific papers puts the author(s) of those papers in a conflict of interest position relative to the paying sponsor, injurious to objectivity?
• Is Camardo that naive to believe a paid writer would "diss" the holder of his or her paycheck?

Regarding "the authors alone controlled the content and writing of the papers, though some did have outside help paid for by Wyeth":

• Which authors is he referring to?
  
• The ghostwriters?
• Wyeth scientists?
• Academics claiming authorship?
  
• Was the "outside help" from Wyeth "authors" to the ghosts, or from the ghosts to Wyeth "authors", or from Wyeth to the academics claiming authorship, or what?
• Can Camardo produce statistics on what % of article content on ghostwritten articles Wyeth sponsored were written by the ghost vs. written by Wyeth scientists and/or the claimed academic author? If not, why not? And if not, why should any intelligent person not assume the papers are, say, 99% the product of the hired guns?

Regarding "the authors were not paid, and the authors had the final say":

• Again, which author(s) is he referring to?
• In terms of the ghosts, I assume they were not working for the MECC's for free.
• In terms of the academics and KOL's claiming authorship, they (maybe!) were not paid in money, but instead in the valuable academic currency of a publication in a major biomedical journal.
  

To claim the KOL's were "not paid" is disingenuous. In fact, I find his entire argument disingenuous, a play on words, PR "spin" completely callous to the needs for scientific objectivity, the advancement of science, and ultimately to patient's lives.

This is marketing, with poor ethics, in the extreme.

Being somewhat familiar with authorship issues as former Director of Published Scientific Information Resources and The Merck Index (of Chemicals, Drugs & Biologicals), 13th ed. at Merck Research Labs, I further pointed out in my post "Wyeth: Ghostwritten Papers Fake, But Accurate" here, that:

... in addition to the violation of accepted practices of authorship, such as specified by NIH and the International Committee of Medical Journal Editors, among others, such lucky authors [i.e., those who claim authorship of ghostwritten papers] get to "count" such papers in their academic portfolios, presumably also in violation of their own institutional policies and guidelines for fair attribution and intellectual honesty, e.g., here [Harvard - ed.]

These industry practices and Camardo's position may be based on:

• Ignorance of accepted practices of authorship of the NIH, the International Committee of Medical Journal Editors, and most academic institutions, or perhaps:
  
• Cavalier dismissal of these practices for pecuniary reasons.

Is Camardo informed and upfront? Inept? Disingenuous and dishonest? That is up to the reader to decide.

In my aforementioned post "Wyeth: Fake but Accurate" I'd also noted Wyeth attorney Stephen Urbanczyk acknowledging that the ghostwritten articles were part of a marketing effort. But he said that they were also "fair, balanced, and scientific." More spin.

This raises the following observation. It is said that you can judge people by the company they keep. I also believe that:

You can judge companies by the people they keep.

This raises the following very serious questions:

• Is the presence of a senior vice president of global medical affairs and a lawyer with such views on ghostwriting representative of the senior executive leadership's views on dissemination of biomedical scientific information?
  
• Is their presence reflective of the views of Wyeth's Board of Directors?

If so, then the objectivity of any article about Wyeth drugs is called into question, and physicians and patients should utilize Wyeth drugs (and literature on them) with great caution.

-- SS

Addendum: this from the Medical Ethics blog:

Recently released court documents in a lawsuit against drug giant Wyeth, thanks to a court action by the New York Times and PLoS Medicine, are now searchable at a University of California, San Francisco web site.

The Wyeth documents are the latest made searchable at the Drug Industry Document Archive, or DIDA, which archives the documents from several high-profile cases.

... The documents were first made available last month on the PLoS web site, but were not searchable and difficult to sort through. The DIDA site now make it possible to search for documents by name, type or content.

Also see "Ghostwriting: Why they do it" at that blog.

-- SS

Post Title → Wyeth, Ghostwriting, Dr. Joseph Camardo and a Big Liquor Store With a Little Grocery Department

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

Sixth International Congress on Peer Review and Biomedical Publication

I just found out that the program of this year's Sixth International Congress on Peer Review and Biomedical Publication, to be held on September 10-12, 2009, in Vancouver, BC, Canada is likely to be of great interest to Health Care Renewal readers. The conference is held every four years on topics relevant to medical journal editors and reviewers, but previous conferences emphasized topics as impact factors, blinded review, open publishing, etc. This year, however, there will sessions on:

• Authorship and Contributorship - including 3 of 4 presentations on ghost-writing
• Data Sharing and Conflicts of Interest - including 4 of 5 presentations on conflicts of interest in research
• Publication Bias - including 3 of 3 presentations which appear to discuss research manipulation and suppression
• Rhetoric - including 3 of 3 presentations apparently about how articles reporting original research may exaggerate or distort the results

There will also be poster presentations on relevant topics. See this link for further information and registration information.

This conference program seems to have a higher concentration of Health Care Renewal relevant topics than any conference of which I am aware to date.

Post Title → Sixth International Congress on Peer Review and Biomedical Publication

Guest Blog - On the Need to Get Ethical

Guest blog by Dr William Tierney -

This is old news. I'm the Co-Editor-in-Chief of the Journal of General Internal Medicine, and in our June 2005 issues we reported in detail a case of medical ghostwriting that had the particular target of showing the hazards of the oral anticoagulant drug warfarin, supporting a drug company's new oral anticoagulant. This article was accompanied by an editorial by me any my Co-Editor and a position statement by the World Association of Medical Editors decrying such practices.

I am a practicing general internist who prescribes drugs regularly that help my patients. I want and need new drugs to be developed, and I believe that users of those drugs should pay for the necessary research and development through both drug pricing and funding of NIH. I am also a patient and similarly want there to be effective drugs to prolong my life and healthy living. But they should be described in an evidence-based manner, and the evidence must be unbiased. The drugs should be priced so the drug company recoups its costs and makes a profit. I have no problems with any of that. But when they try to enhance their profits through illegitimate means -- by essentially lying through advertisements masquerading as scientific articles sneaked into peer-reviewed journals -- then these drug companies are behaving unethically and need to be punished.

I also am a clinical epidemiologist, and as such I do research investigating the positive and adverse outcomes of drugs. I have worked with and been funded by drug companies to do this work, collaborating with company scientists. To a person, I have found them to be honest, careful, and caring people who truly want to positively impact people's lives. It is the marketing divisions of these drug companies that operate in an atmosphere of "anything goes that helps the bottom line."

My father was a purchasing agent for a factory that made automobile parts. We used to get "presents" every Christmas, tickets to Broadway, etc. from suppliers, blatant attempts to influence his decision-making. I can't say whether it ever did, but in the end he had to live with his decisions and so did the company for which he worked. But as a physician, I don't receive the benefits of the drugs I prescribe for my patients, nor do I pay the costs. I act as an agent of my patients, and as such I need to balance benefits, adverse effects, and costs of everything I order. If I have bad information, or if I succumb to company bribes in the form of honoraria, meals, or gifts, my patients pay the price both directly (through my ordering an expensive drug they might not need) and indirectly (through inflated drug prices in general).

It is time for the drug companies to get ethical. Cut out the ghostwriting. Cut out the bribes. Cut out the marketing to patients that inflate drug benefits and minimize their costs and risks. Charge prices that recoup their drug development costs and stop paying billions to "push" drugs on physicians and patients, adding those costs to their drug prices. And we physicians likewise need to get ethical, stop taking bribes, stop reading propaganda or listening to drug detailmen, and base our decisions solely on what is best for our patients, without ignoring costs. (Nobody benefits if we bankrupt our system -- but that's another story...)

We are seeing changes. Eli Lilly now lists all payments they make to physicians (honoraria for speaking, meals, trips, etc.). Many medical schools and large practice organizations have outlawed meals and gifts by drug companies. Journals are more vigilant for ghostwriting and other conflicts of interest among authors. We are seeing a change, and hopefully the abuses by Wyeth, DesignWrite, and other companies involved in ghostwriting will become a thing of our (sordid) past. We can only hope and maintain our diligence as caring health care providers.

Dr Tierney is Co-Editor-in-Chief, the Journal of General Internal Medicine, and Professor of Medicine, Indiana University School of Medicine. This was also posted as a comment here on the NY Times article about Wyeth's sponsoring of ghost-writing of articles on hormone replacement therapy. See our most recent post on this topic here.

Post Title → Guest Blog - On the Need to Get Ethical

Wyeth's Industrial Scale Ghost-Writing

MedInformaticsMD noted the impending release of documents about how Wyeth engineered ghost-writing of articles about hormone replacement therapy (HRT) here. Now the NY Times has had a chance to review the documents, with fascinating results.

The scope of the ghost-writing campaign was on an impressively industrial scale: 26 articles published over 7 years in 18 medical journals.

The details were ably covered by at least three other blogs. Dr Adriane Fugh-Berman, guest- (not ghost-) blogging on PharmaGossip discussed how the documents reached the public domain. Dr Daniel Carlat on the Carlat Psychiatry Blog, Prof Margaret Soltan on the University Diaries offered some choice comments -

By Dr Carlat

As with baseball players on steroids, when companies pour marketing money into ghostwriting campaigns, they change the rules of the academic game. The playing field is no longer level; the drug company's version of the truth gains the upper hand. Sometimes, their truth really is the truth, but sometimes it's a carefully crafted lie. Sorting it out is difficult even for physicians who specialize in the area being written about. It's essentially impossible for the average generalist physician, to say nothing of patients who did not have the advantage of attending medical school.

By Prof Soltan

This filthy practice incorporates just about everything people rightly revile about some precincts of academia: Plagiarism. Fakery. Arrogance. Laziness. Cynicism (Wyeth was promoting drugs that turned out to be dangerous.).

People make fun of postmodernists by talking about the Postmodern Generator, a program that automatically generates articles full of obscurantist rhetoric. But that’s only generating words. Ghosting whores among our medical faculties are generating real sickness.

These are hard acts to follow, so my comment is: ghost writing is also corrupt. Transparency International defines corruption as abuse of entrusted power for private gain. Medical academics are entrusted to discover and disseminate the truth. Practicing physicians, patients and the public entrust medical academics to provide honest, informed, unbiased information and opinions.

When academics allow marketing hacks to write supposed scholarly articles in their name, they abuse this entrusted power (and privately gain by padding their CV, and often by direct payment as "consultants.") Of course, as noted above, this sort of corruption deceives the public, patients, and physicians into thinking that drugs and devices are better and more valuable than they actually are, denying patients preferable treatments, increasing the risk of needless adverse effects, and driving up the costs of health care.

Those who are pushing for meaningful health care reform ought to put fighting health care corruption at the top of their agendas, starting with the blatant corruption of academic medicine and medical research of which ghost-writing is but one species.

Post Title → Wyeth's Industrial Scale Ghost-Writing

Wyeth: Ghostwritten Papers Fake, But Accurate

It looks like Wyeth has lost its battle to keep secret its practices regarding ghostwriting of scientific papers. The issue in question is whether ghostwriting contributed to excessive prescription of post-menopausal hormones and increased the incidence of breast cancer:

Posted on Sun, Jul. 26, 2009
Philadelphia Inquirer

Wyeth told to release documents on ghostwriting

Associated Press

LITTLE ROCK, Ark. - A federal judge has ordered the unsealing of thousands of pages of documents pertaining to the ghostwriting practices of Wyeth Pharmaceuticals, which is being sued over hormone-replacement drugs.

U.S. District Judge Bill Wilson ordered the papers unsealed Friday at the request of a medical journal and the New York Times. Plaintiffs' attorneys presented the papers earlier at trial to show that Wyeth routinely hired medical-writing firms to ghostwrite articles that appeared in seemingly objective medical journals but included only the name of a scientific researcher as the author.

Of course, in addition to the violation of accepted practices of authorship, such as specified by NIH and the International Committee of Medical Journal Editors, among others, such lucky authors get to "count" such papers in their academic portfolios, presumably also in violation of their own institutional policies and guidelines for fair attribution and intellectual honesty, e.g., here. Ghostwriting may also skew the tenure process, providing advantages to the unscrupulous academic over the ethical scientist or scholar. (One wonders about the true percentage of the massive number of papers claimed by some medical academics actually written by the putative first author.)

The ruling came in a case that involves about 8,000 lawsuits that have been combined before Wilson. The lawsuits focus on whether Wyeth hormone-therapy drugs Prempro and Premarin, used to treat symptoms of menopause, have caused breast cancer in some women.

The New Jersey drugmaker, which has major operations in the Philadelphia area, had already turned over the documents, which it says concern about 40 articles in medical journals and other publications, to Sen. Charles Grassley (R., Iowa).

How is evidence based medicine possible if just one drug company has sponsored ghostwritten articles in 40 medical journals and other publications? What is the "total mass" of questionable articles now infecting the literature?

Grassley sought them last year without a subpoena as part of a congressional investigation into drug-industry influence on doctors.

The documents were shown to jurors at trial but have otherwise been unavailable publicly.

Plaintiffs say ghostwriting is when a drug company conjures up the concept for an article that will counteract criticism of a drug or embellish its benefits, hires a professional writing company to draft a manuscript conveying the company's message, retains a physician to sign off as the author, and finds a publisher to unwittingly publish the work.

There are several layers of dishonesty in this activity, including foreknowledge of scientific deception through fraudulent misrepresentation of authorship by the pharma, dishonesty of the physician who "signs off" as first author, and misrepresentation by the pharma, the writing company and the physician about provenance of the article to scientific publishers.

Drug firms disseminate their ghostwritten articles to their sales representatives, who present the articles to physicians as independent proof that the companies' drugs are safe and effective.

Wyeth attorney Stephen Urbanczyk acknowledged that the articles were part of a marketing effort. But he said that they were also fair, balanced, and scientific.

What business does a lawyer have lecturing the public that the articles were a dishonest marketing effort masquerading as legitimate science, but were "fair and scientific?" How does he know? In addition, the "fake but accurate" excuse is getting quite shopworn. Hopefully, Sen. Grassley will approach ending this ghostwriting practice with vigor.

In fact, this raises another issue. I have written that management of pharma by those lacking biomedical bona fides is, by definition, mismanagement. This is a case in point. Wyeth's President, Board Chair and CEO Bernard Poussot lacks biomedical credentials. Harry Truman said "the buck stops here", but a in the case of scientific ghostwriting, CEO's such as Poussot cannot vouch firsthand for the accuracy and fairness of their company's science. He lacks the expertise. The buck does not stop at his desk; he is dependent on scientific underlings in such matters.

This affair is another instantiation of my belief that pharma is best led by those with relevant scientific expertise such as Merck under clinician-scientist Dr. Roy Vagelos. (It is perhaps not coincidental that Merck became a shadow of its former self under non-scientist Raymond Gilmartin.)

Wyeth, the world's No. 12 pharmaceutical company by sales, is being bought this fall by No. 1 drugmaker Pfizer.

How appropriate, as Pfizer is led by the former top lawyer for McDonald's and Boston Chicken, bringing to life my "If you've run McDonald's, you can run anything" metaphor. If a wise investor were to take a bearish position on a stock, this merged company would be an excellent candidate.

Finally, another ghostwriter of sorts recently died, Sandford Dody (1918-2009). Dody anonymously penned best selling autobiographies of actresses Bette Davis and Helen Hayes, among many other notables. Such ghostwriting is essentially victimless, as opposed to its counterpart in the scientific domain. However, Mr. Dody had an astute observation about the practice, even when there was no trail of diseased or dead bodies.

Per the WSJ article "A Ghostwriter Who Struggled to Accept Life in the Shadows":

... Mr. Dody, who died July 4 at the age of 90, found the work spiritually destructive. "After all," he wrote, "how does one become a ghost without dying a little?"

In the case of biomedical ghostwriting, the conspirators all "die a little" in purveying their intellectual dishonesty on a trusting public.

It's too bad some of that same public also dies, and not just a little, as wages of professorial ghostwriting sins.

The acknowledgements are where minor contributions and reviews get placed in an ethically-attributed scientific paper. Anyone who does not understand this, or rationalizes "honorary authorship" or similar workarounds to meaningful attribution does not belong in science.

Finally, scientific ghostwriting must stop. I also believe its conspirators should be excluded from receiving public money for research and excluded from the biomedical literature for a good, long period of time.

-- SS

Post Title → Wyeth: Ghostwritten Papers Fake, But Accurate

A Handbook for Ghost-Writing

We posted a number of times about questionable practices Eli Lilly used to market its atypical anti-psychotic drug Zyprexa (olanzapine). A post from 2007, with links backward, is here, and our most recent post is here. The company remains entangled in litigation over its marketing of this drug. That litigation has lead to the release of numerous internal documents that provide quite a view of Lilly's marketing practices. In particular, a Bloomberg news article discussed how the company used ghost-writers:

Ensuring that medical journal articles presented Zyprexa study results in a positive light was one way for Lilly to reach its sales goal, company officials said in its plan, according to the documents.

To do that, Lilly officials hired ghostwriters to prepare submissions to journals such as Progress in Neurology and Psychiatry, according to the unsealed documents.

The article then described how Lilly marketers set up a ghost-written article.

'The paper for the Progress in Neurology and Psychiatry supplement has been completed and sent to the journal for peer review,' Kerrie Mitchell, an employee of the public relations agency Cohn & Wolfe, wrote in a Feb. 23, 2001, e-mail to Michael Sale, a Lilly marketing official. The message was among the unsealed files.

'We ‘ghost’ wrote this article and then worked with author Dr. Haddad to work up the final copy,' Mitchell said in the e- mail. Eric Litchfield, a spokesman for Cohn & Wolfe, didn’t immediately return a call seeking comment.

Peter Haddad, a researcher at Greater Manchester West Mental Health NHS Foundation Trust in the U.K., was listed as the article’s lead author. Haddad didn’t respond to requests for comment.

The global Lilly team approved a draft of Haddad’s ghost- written paper in 2000, according to the unsealed documents.

Lilly marketers, rather than articles' putative authors, sometimes exerted pressure to get ghost-written articles published. For example,

Lilly officials e-mailed journal editors to complain about delays in publishing favorable Zyprexa articles, according to the unsealed documents.

In one instance, Lilly employees contacted the Journal of Clinical Epidemiology about delays of an article criticizing a previously published piece linking Zyprexa, as well as the class of atypical antipsychotics, to diabetes.

After Suraja Roychowdhury, Lilly’s senior scientific communications coordinator, wrote to the journal in November 2002, its editor, Andre Knottnerus, replied in an e-mail that it was 'a bit strange to be contacted via the Lilly product team. Dr. Buse and coauthors can contact us directly next time.'

Knottnerus was referring to the manuscript’s lead author, John Buse, a former president of the American Diabetes Association. A copy of the Nov. 22, 2002, e-mail was included in the unsealed documents.

Patrizia Cavazzoni, a Lilly staffer who co-wrote the article, e-mailed Buse on Jan. 9, 2003, seeking permission to send a separate e-mail asking to expedite publication. She also asked Buse if he would prefer 'to send it in your name?'

It isn’t clear from the e-mail chain whether the e-mail was sent by Buse or Cavazzoni.

Finally, Lilly developed a handbook for ghost-writers:

To ensure that ghostwritten Zyprexa articles met Lilly’s standards, company officials issued a guide to preparing them, according to the unsealed files.

The guide, 'Medical Press: Pre-Launch Feature Outline,' was undated. It’s unclear from the documents which teams in Lilly’s top 10 markets for the drug received it.

The primer provided a how-to for writing articles, such as instructing the author to use Zyprexa’s generic name, olanzapine, instead of its brand moniker, according to the documents. Scientists in medical research traditionally refer to a drug’s chemical name.

The guide also offered tips on how to find authors by identifying a 'key opinion leader' and providing them either an outline of the article or a finished copy. Authors could include a study investigator, an advisory board member or “Lilly-friendly” doctor, according to the documents.

A sample article laid out how a Lilly employee may find a doctor to ghostwrite a submission that would 'prepare the market' for the launch of an intramuscular injectable version of the drug. It also offered an outline for the contents of the article, beginning with background on another drug, droperidol, which had been withdrawn from several countries.

The article, with the suggested title 'Filling the Droperidol Gap,' noted that an anti-anxiety drug could be used, before going on to say, 'more advanced IM treatments may soon be available to provide a superior alternative.' The article explained that injectable Zyprexa had just received approval from the FDA, and recounted its clinical trial history.

'The anticipated forthcoming availability of atypical antipsychotics in an IM formulation could be a major step forward in the treatment of acute agitation associated with schizophrenia,' the sample article concluded.

We addressed ghost-writing frequently when we started Health Care Renewal, and have returned to the topic periodically (see these more recent links, from 2008, here and here). The most striking feature of this newest case is the use of a "ghost-writers' handbook" denoting how systematized the practice has become. With each new case, it becomes clearer how common the practice may be. Since the parties involved seem ashamed enough of the practice to try to keep it well hidden, it may be that ghost-writing is even more common than we now realize.

Nonetheless, while the practice may be common, and mutually advantageous for ghost-writers, the academics who front for them, and the marketers who hire them all, as we and others have said before, ghost-writing is dangerous to health. It deludes physicians and patients into thinking health care products are more beneficial and less risky than they really are. Ghost-writing also undermines science by shifting the agenda away from interesting and important questions to questions whose answers may mainly benefit vested interests. Finally, on a personal note, ghost-writing demoralizes honest academics who must run their own studies, write their own papers, and manage the logistics of paper submission in competition with fake authors backed by corporate money and corporate staff. Scientists and academics who allow and front for ghost-writers ought to be ashamed of themselves.

See also comments in the Clinical Psychology and Psychiatry blog, and discussion of some of the other recent revelations about Zyprexa marketing in the Hooked: Ethics, Medicine and Pharma blog.

ADDENDUM (14 June, 2009) - Also see comments by Prof Margaret Soltan on the University Diary blog on the "Stockholm Syndrome" as manifested by "key opinion leaders" in the pay of health care corporations.

ADDENDUM (15 June, 2009) - Furthermore, see comments by Dr Howard Brody in the Hooked: Ethics, Medicine and Pharma Blog.

Post Title → A Handbook for Ghost-Writing