Off-label use of drugs - why the concern

All modern pharmaceuticals are subject to rigorous testing before they are allowed to enter the market place. Pharmaceutical companies are required to show good evidence of efficacy and safety for the dosages used and for the specific clinical conditions they are meant to treat. Consequently, when they are finally licensed into the market place, they carry a product label listing the specific disease indications for which claims have been validated.

Off-label use of the drug occurs when drugs are used for indications that have not been tested for. Hence the implications are that there is really no evidence other than anecdotal ones, that using these drugs in off-label situations will be effective and safe.

Off-label drug use is not illegal, but the US FDA prohibits the promotion of off-label use. The reason for this relate to the concern that pharmaceutical companies tend to gain market access by initially testing their drugs in a very narrow and specific way and can therefore show that the drugs are sfae and efficacious. Once the drugs are licensed, a host of off-label uses are then directly or indirectly promoted. For many drugs, the off-label uses may be even more lucrative than the labelled uses. In this Canadian report, approximately 25% of all prescriptions may be off-label prescriptions. This number is however decptive as the actual figure may be higher in different clinical situations. It is particularly prevalent in paediatrics, oncology and psychiatry. It is particularly problematic for expensive prescribed drugs.

In recent times, some major players have been caught. In Jan 2009, Lilly had to pay out US$1.4Bn for promoting off-label use of their drug Zyprexa. In 2004, Pfizer itself pleaded guilty and had to pay out US$430million for promoting their drug Neurontin. I imagine these are but the tips of the iceberg in the pharmaceutical industry given the attractiveness of the off-label market.

But what, you may ask, is the problem with off-label use?

Well, the main problem is that every medicine we use have been licensed only for very specific conditions for which they have been extensively tested for safety and efficacy. This evidence is vitally important for the protection of the patient consumer. Off-label use of drugs imply that drugs can be marketed for conditions for which there is no evidence of safety or efficacy. If this level of ambiguity is acceptable for medical therapeutics, then why bother with drug licensing in the first place? Surely the patient-consumer has to be treated with more respect and consideration.

Doctors have a legally sanctioned ability to use drugs according to their clinical judgement, and in an off-label situation, but this practice should be covered by the SMC guidelines which make it clearly unethical if the doctor provides unproven therapies, other than part of a clinical research protocol.