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.