Tuesday, October 28, 2008

How Pharmaceutical Companies Disguise Promotion of Off-Label Drug Uses

An article just published in PLoS Medicine [Fugh-Berman A, Melnick D. Off-label promotion, on-target sales. PLoS Med 2008; 5(10): e210 doi:10.1371/journal.pmed.0050210] just cataloged methods used by pharmaceutical companies to promote medications for "off-label" uses. These main points are worth reviewing:

Use of "Key Opinion Leaders" -

Off-label campaigns are launched outside of the sales force.

Nationally known, influential academic physicians help 'word-of-mouth' or 'buzz' marketing. These 'thought leaders' or 'key opinion leaders' (KOLs) support labeled marketing efforts as well, but they are considered crucial for the promotion of off-label uses. Industry-paid KOLs are never company employees. Rendering purportedly independent opinions, via articles and lectures, KOLs are able to elude laws against off-label promotion.

Note that this supports the notion, raised elsewhere, that "key opinion leaders" are paid mainly for marketing purposes, and chosen for their sympathy to marketing objectives. Many KOLs, however, themselves assert that they are paid because of their expertise and brilliance. This suggests that deception is at the root of the concept of "key opinion leader."

"Publication Strategies" to Generate Influential Publications Whose Industry Origins are Disguised -

The 'publication' strategy ... stimulates off-label prescribing by using research 'to disseminate the information as widely as possible through the world's medical literature'. Clinical studies provide key references for the industry-produced reviews and commentaries, signed by KOLs, used for promoting off-label sales. Case studies about off-label uses may be solicited; physicians may be paid for combing patient medical records for cases that help industry goals. A physician—or a medical writer—will write up the case or case series, which may be submitted for publication or presented as a meeting abstract. Industry-sponsored reprints may be included in continuing medical education (CME) activities sponsored by medical education companies (MECs), often distributed by direct mail.

Note again that KOLs are intrinsic to the "publication strategy." The existence of this strategy suggests that physicians need to be extremely skeptical of even apparently academic publications in scholarly journals.

Leveraging Abstracts and Meeting Presentations -

Posters and abstracts presented at medical meetings create buzz, especially if a press release garners media attention. Meeting abstracts and posters are considered cutting-edge, but the information is almost always incomplete and usually lacks peer review.

Abstracts or posters may be 'published' in conference proceedings, medical journals, 'throwaway' journals, or industry-sponsored medical journal supplements. These industry-generated, non-peer-reviewed, covert promotional pieces are now citable items that are provided to physicians by a company's medical affairs office to support off-label use, and can be referenced in peer-reviewed articles, ads, and other marketing materials.

This strategy and the one above remind physicians not to assume anything about the origins of what they read. Much of the information placed before physicians for apparently educational purposes may really be meant to market products. Also note that compilations of presented abstracts usually provide not even rudimentary information about authors' financial relationships or conflicts of interest.

Bleed-Through from Unaccredited "Drug Talks" to Accredited Continuing Medical Education -

MECs know that accredited CME programs funded by unrestricted grants must favor marketing messages. The easiest way to accomplish this goal is to use company speakers trained for unaccredited (non-CME) promotional presentations.

Physician-speakers are trained in presenting unaccredited talks, sometimes called 'dinner talks' or 'lunch-and-learns.' This training, using company slides, often occurs at resorts. Some speakers are genuinely unaware of the marketing messages they are responsible for disseminating. For example, messages that a certain disease is underdiagnosed, undertreated, or more serious than commonly believed can bolster a company's marketing goals even if drugs are never mentioned.

Physicians trained in unaccredited talks may present the same talk at a CME event. Most industry-paid physicians believe that they maintain intellectual independence. Presenting different statements in different settings would create cognitive dissonance. Psychologically, it is easier to believe that what one is saying is scientific and accurate, and thus to say the same thing at accredited and unaccredited programs.

This strategy is striking in its ingeniousness, but also its audacity. Again, it challenges the assertion, which I have heard often from KOLs, that they cannot possibly have been influenced by what they were paid, or who they were paid by to give their talks.

Using Obligations Generated by "Unrestricted Educational Grants" -

'Unrestricted' grants provided to departments at academic medical centers for grand rounds and lunch conferences depend on a sense of obligation rather than a quid pro quo. When lists of recommended speakers are supplied to organizers, it is unstated, but nonetheless understood, that company-paid speakers will be included in the lecture series.

Of course, many medical schools, hospitals and academic medical centers, and physicians' societies deny that "unrestricted educational grants" could possible affect the content or direction of their educational offering. Again, physicians must maintain extreme skepticism, asking "who benefits" about every lecture or presentation they attend, and about every article they read.

Use of Compendia and Drug Indices-

Compendia are compilations of drug information that include both on-label and off-label uses. Medicare, Medicaid, and many other insurers will cover off-label uses of reimbursable drugs included in major compendia, including the American Hospital Formulary Service–Drug Information (American Society of Health-System Pharmacists), the US Pharmacopoeia–Drug Information (Micromedex, a division of the Thomson Publishing Company), and DRUGDEX. Pharmaceutical companies strive to establish good relationships with compendia staff, and may assign an employee as the designated compendia contact. The pharmacists who write compendia listings are very busy, and are usually delighted to receive organized packets of scientific articles, abstracts, and contact information. Using company-provided articles (which always contain marketing messages) saves time; all of the company's assertions for off-label use may be transferred intact to the final product. Companies celebrate new compendia listings because expanded insurance coverage ensures more sales.

Drug information listings, similar to compendia, usually solicit company input and review. Although companies do not pay for listings, they may offer to buy hundreds or thousands of reprints for sales staff. In any case, it makes sense to contribute to entries that show company data in the best light.

Dr Fugh-Berman continues to raise disturbing points about how medical education and publishing has become entwined with industry. Physicians who read and view uncritically, and who place their trust in seemingly authoritative figures, risk being seduced by those more interested in selling products than in making sure each patient gets the most beneficial and least harmful management.

See also comments on the Carlat Psychiatry Blog.


InformaticsMD said...

As former Director of The Merck Index of Chemicals, Drugs and Biologicals, 13th edition, I can honestly say that to my knowledge there were no attempts at manipulation of the content of the Index, which is considered an authoritative source of information in medicinal chemistry.

If I had been approached to modify or alter its content over the decisions of its small cadre of editors and writers (who were extremely good researchers of the biomedical literature, broadly construed, in their own right, with great pride in the integrity of The Index which dated to the late 1800's), I would have told such party(s) to go take a hike.

Actually, I would have been a bit ruder than that.

The largest problem with The Index, paradoxically, was in ensuring the non-scientist computer department leaders we reported to understood its value (it was nonprofit but somewhat costly to research and produce) to the company's scientific reputation and goodwill.

Hopefully The Index remains untainted.

-- SS

Anonymous said...

During the early and mid 1970s psychology played a major role in mot business programs. Nature versus nurture was a big topic. Supervision courses dealt with motivation and supervisors were to be measured on how well their group performed not on the supervisors ability to eliminate competition. The whole vetting process to promotion dealt with building concessus, not on force of will, or self promotion.

Sales and sales management courses dealt with how to transfer these concepts to a larger group. Everybody is doing it and presenting an idea as fact were two tools to be used to accomplish this goal.

In my early contacts with the pharma business model I learned that the nature of the business leads to a very long view. Drug companies deal with years of research and then years of product cycle.

Pharma is all about measurement. In the early 70's they measure sales and performance of drugs and reps weekly. They were early adopters of statistical business models.

Pharma, while completive, presents a united front and message: "Drugs are good."

Against this back drop it is not hard to imagine the current marketing practices mentioned. In any industry, automotive comes to mind, management will continue to produce product in the same manner as long as profits continue. Only when faced with government regulation, or a change in market forces, will management change. Only now are we seeing the car companies promoting small cars.

Given the long time line, along with the profit profile of pharma for the last 20 years, it is not hard to conceive of the continued manipulation of data and information flow.

What struck me about the Oct. 22 WSJ article Drug Makers Cut Expenses was the lack of concern for the loss of corporate culture. The lack of concern for the loss of talented research personnel. The lack of concern for the loss of scientific data regarding future products.

Pharma has proven time and time again it is a marketing entity, and the drugs are only incidental to this function. The bottom line is you sell product at any cost and fines and lost careers are just a cost of doing business.

Steve Lucas

Anonymous said...

I would also recommend from Junkfood Science:


This excellent piece on obesity and childhood type 2 diabetes shows how a plausible sounding medical standard can be based on essentially no facts.

Steve Lucas

InformaticsMD said...

Pharma has proven time and time again it is a marketing entity, and the drugs are only incidental to this function. The bottom line is you sell product at any cost and fines and lost careers are just a cost of doing business.

This worked for awhile, but as an old merchant once told me:

"If you want to make a sale, you have to have the merchandise", and "you can't do business from an empty wagon."

Anonymous said...


You are right. In some of my most basic business classes we were taught not to gut your R&D department. One of the sadder concepts I have heard is pharma now wants to bring some of the billions back from overseas tax free. I am sure they will not rehire staff, bring new product to market, or just improve the science.

The money will bolster profits which will lead to higher executive bonuses. No increase or special dividends for the shareholders.

Steve Lucas