Off-Label Drug Use: The Good, The Bad, and the Inexcusably Ugly

My previous post about a medical indication suggests a follow-up about off-label drug use. A FDA-approved drug can be prescribed for treatment of an indication for which it has not been approved. This can lead to higher risk for both the physician and the patient, because a valid reason for using the drug that was proven in a clinical trial and approved by the FDA does not exist for off-label use. Any insurance coverage a person might have may not pay for off-label use of a drug.

There are examples in favor of using a drug off-label. The increase in hospital-acquired Clostridium difficile infections has led to questions about whether or not the bacteria is becoming resistant to standard antibiotic treatment with vancomycin. When the infection recurs after one or more courses of treatment with vancomycin, the patient is sometimes given vancomycin + metronidazole. This is an off-label use of metronidazole that works sometimes and has been adopted out of necessity. Medical professionals talking to each other, presenting at meetings and publishing case studies leads to this sort of off-label use. Last May the FDA approved a new antibiotic, fidaxomicin, marketed by Optimer Pharmaceuticals as Dificid. A clinical trial showed that Dificid prevented recurrences better than vancomycin, so the off-label use of metronidazole will likely decrease.

What is not permitted, but nevertheless occurs, is the promotion of off-label use by the manufacturer. A retrospective study of how the pharmaceutical industry promotes off-label use found that:

"Despite regulatory restrictions on off-label marketing, the practice appears to have flourished [6],[7]. In 2009, Pfizer paid US$2.3 billion to settle allegations that it marketed its drugs illegally to physicians—the largest federal health care fraud settlement in US history [8]. In 2010, at least six other manufacturers settled charges pertaining to off-label marketing, and more were under investigation [9]–[15]. The widely publicized litigation over the anti-inflammatory drug rofecoxib (Vioxx) also exposed marketing practices, such as seeding trials and ghost-writing of medical journal articles, that could promote off-label uses [16],[17]."

Pfizer's technique for off-label promotion in the instance mentioned above was reported by CNN Health. In the retrospective study published in PLoS Medicine, this procedure was still in use. "All of the complaints we analyzed detailed off-label promotion to prescribers; this was generally the centerpiece of the whistleblowers' complaints." If you take the time to read through the short collection of blogs and articles below, you will notice that the pharmaceutical companies involved are preying on and profiting from some of the most defenseless members of society - young people in jail and the elderly in nursing homes. This behavior is particularly reprehensible and loathsome.

New York Times - Duff Wilson: Side Effects May Include Lawsuits

Youth Today - report of a survey, reporter Ben Penn contributed:  Psych Meds in Jails

New York Times - Duff Wilson: Child’s Ordeal Shows Risks of Psychosis Drugs for Young

Health Beat - Maggie Mahar:  "Atypical" Antipsychotics Misused As "Chemical Restraints" For Youthful Offenders

Project on Government Oversight - Paul Thacker: Why Get Spooked by a Little Ol' Ghost? The Story of Pfizer, 16 Year-Old Dustin Yankus, and Whistleblower David Franklin

Also from POGO:
Frequently Asked Questions about Medical Ghostwriting 
 What is “off-label” promotion and how is ghostwriting involved?
....Companies cannot advertise their products to treat conditions “off label.” However, they regularly promote off-label use with ghostwritten studies that emphasize the benefits of the products.  For instance, sales of Neurontin climbed astronomically because the company seeded the scientific literature with ghostwritten studies that found Neurontin could treat a variety of diseases.