Tuesday, October 28, 2008

Marketing Drugs for Unapproved Uses: A How-To Guide

The open access medical journal PLOS Medicine just published this fascinating article detailing how drug companies promote off-label uses of drugs.

Co-authored by Georgetown University's Adriane Fugh-Berman, M.D., and by Douglas Melnick, M.D., a former medical liaison for a major drug company (see his YouTube interview here), this article is notable because it provides insider information about the nasty little marketing techniques used to promote off-label indications.

In general, I am not against off-label uses of drugs. In psychiatry, many, if not most patients are taking something off-label, such as an SSRI for an unapproved indication or trazodone for insomnia. However, off-label uses should be promoted and discussed by physicians unaffiliated with drug companies. We don't need drug companies, drug reps, or industry-funded hired guns to educate us about off-label uses, because legitimate uses are published in peer-reviewed journals, which generate a buzz among physicians and a gradual rise in evidence-based off-label prescribing. We've seen many cases in which drugs, such as Neurontin, have been promoted by companies for unapproved conditions based on anecdotal data, only to find that they were completely ineffective once controlled data were published.

At any rate, this PLOS article describes a variety of methods used to market drugs off-label, including:

--The "decoy indication." "In development, drugs may be promising for several uses, and companies must choose one or two conditions on which to focus research. Ease of approval is the most important factor in this decision. If extensive off-label use is anticipated, a company may seek approval for just a narrow indication in order to speed a drug to market. In other words, a drug may be approved for this very narrow "decoy indication" while an extensive off-label campaign is not disclosed to drug regulators."

--Use of Key Opinion Leaders to skirt regulations. "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."

There are many more interesting tidbits in this article--but I'll stop here, because I don't want to spoil your fun!


Anonymous said...

The article mentions occasions where the manufacturer chooses not to seek a new indication for their drug and a publicly funded study for efficacy is done. So what happens in this situation? If the public study shows the drug to be safe and efficacious - does FDA approve the new indication? Is it added to the label? Is the manufacturer the only entity that can apply for a new indication? Or would it still be considered off-label? How does it work?

Sorry for all of the questions - I haven't come across a discussion of this aspect of off-label sales before.

Anonymous said...

Interesting, but not surprising. For example, currently the manufacturers of HPV vaccines are using KOLs to promote the vaccines for women in older age groups. In the U.S., Gardasil is the only approved HPV vaccine, and it is not approved for women over 26. See this Pharmalot post and Medscape article:



Merck also used a group of female state legislators called Women in Government to promote mandated HPV vaccination, but they had to back off from that. They are still promoting mandates in other countries.


Anonymous said...

I am always disappointed whenever drug companies settle off label use prosecutions, failing to counter-attack the government thugs as persons. To deter these unAmerican, unlawful restrictions on commercial speech.

The multiplicity of actions of most medications makes off label uses the single biggest, cheapest gold mine of drug benefits yet to be exploited. The cost of getting an additional FDA approval is unconscionable, has no more scientific validity than an ordinary study, and lends no additional safety to the public. It is government unfunded mandated, and useless government worker make work.

I would not settle. I would demand total e-discovery on every lawyer at the DOJ seeking to attack clinical care, searching for bias and improper motives. I would attack in the press every member of Congress doing so. They are insurance company running dogs, seeking to grow the obscene reserves of those government enabled predators. All whistleblowers in this matter get placed on a clinical care enemies list. All government workers prosecuting retaliation against whistleblowers get on the list.

Because of the government granted immunities and the lack of legal recourse against these enemies of clinical care, direct action patient groups self-help is morally and intellectually justified.