Researchers from Harvard University obtained a total of 41 whistleblower complaints against drug companies in the US that were filed between 1996 and 2010. They analyzed the "off-label" marketing schemes of the drug companies and the practices used by them to achieve their sales targets. They were designed to either to get doctors to prescribe drugs for diseases for which they were not approved, or to get them to push dosages to non-approved levels. These 41 complaints arising from 18 unique cases led to $7.9 billion in sales recoveries. And those were the companies that got caught. We're not talking about a minor issue. The article was published in the April issue of PLoS Medicine.
There were many examples cited in the study. Gabapentin - under the brand name Neurontin - was approved as a treatment for epilepsy, yet was also allegedly promoted as a treatment for patients with bipolar disorder as well as depression. That case was settled in 2004 for $430 million. You had Viagra approved for erectile dysfunction (obviously in men) but then allegedly marketed "off-label" as a drug to "restore and increase orgasmic sensations" and as a treatment for low libido in women. Another example is the widely prescribed antidepressant citalopram or Celexa -- approved as an antidepressant for adults - but then allegedly promoted to pediatricians as a treatment for depression in young people.
The study focused on how pharmaceutical companies were able to boost "off-label" prescribing of these and other products. First, they targeted doctors, dentists and other professionals with prescribing privileges. Regulations prohibited pharmaceutical sales representatives from starting a conversation about "off-label" uses with MDs. However, the same regulations permitted sales representatives to talk about "off-label" uses if they were asked. Thus, some companies taught salespeople to steer the conversation onto the subject of "off-label" uses. On the other hand, some reps would simply flout the law.
Drug makers might also pay for speeches given by leading doctors who promoted "off-label" uses. In some cases, drug companies used free samples to encourage "off-label" use. Nearly half the whistleblowers alleged that pharmaceutical industry promoted "off-label" use through the publication of journal articles that featured flimsy or weak evidence of efficacy. The articles were often ghostwritten in the name of a leading researcher with ties to the drug company. Sometimes, the company paid for actual research to encourage "off-label" use. The drug company might go so far as to teach the doctor how to get the patient's "off-label" drugs reimbursed through the patient's health coverage plan.
You'd have to be dreaming if you think the same sorts of things don't happen in Canada. Health Canada estimates that up to a third of all prescriptions written in this country are for "off-label" use. Health Canada does not monitor the off-label use of drugs despite the recommendation of several coroner's juries. Health Canada maintains that the rules about product monographs are pretty clear: if a drug should not be used under certain conditions, it must be noted. On occasion, Health Canada will post warnings or advisories about certain drugs that may be prescribed for uses other than what they were approved for. Health Canada has a policy that explains the distinction between advertising and non-promotional activities. It allows the drug company to report scientific studies about unapproved uses for the drug and also allows the company to issue press releases about those scientific studies. There are guidelines about what can be reported in the press release. For an up to date review of the situation in Canada, check out this article in the Canadian Medical Association Journal.
The public should be concerned because "off-label" prescribing of drugs can have serious consequences to your health. The prescribing of Vioxx for non-approved uses undoubtedly contributed to the number of deaths from cardiovascular disease. "Off-label" prescribing of antidepressants to children likely caused or contributed to an increase in suicide attempts and violent episodes in that age group.
More recently, prescribing atypical antipsychotic drugs to control violent behavior in seniors with dementia has been shown to double the risk of death, prompting this warning from Health Canada.. The latter example is disturbing because the practice of "off-label" prescribing has continued despite warnings from regulators on both sides of the border. That tells me the voluntary system of dealing with off-label prescribing is completely inadequate. We need a system with strong enforcement and stiff penalties.
The next time you receive a prescription from your doctor, it's fair game to ask if the prescription is for an "off-label" or non-approved use. If it is, then ask lots of questions.