1. The evidence base of the drug’s efficacy, or more importantly its safety, may not be adequate. This is a particular problem in paediatrics were you have to extrapolate data from adults to children.
2. Pharma themselves are not keen on off-license prescribing; they can’t be involved in any decision making. It is illegal to promote off-license prescribing; you just have to look at the size of recent fines handed out to Pharma by the FDA.
3. Our General Medical Council guidelines are very clear and discourage off-label prescribing
When prescribing a medicine for use outside the terms of its licence you must:
a. Be satisfied that it would better serve the patient’s needs than an appropriately licensed alternative
b. Be satisfied that there is a sufficient evidence base and/or experience of using the medicine to demonstrate its safety and efficacy. The manufacturer’s information may be of limited help in which case the necessary information must be sought from other sources
c. Take responsibility for prescribing the medicine and for overseeing the patient’s care, monitoring and any follow up treatment, or arrange for another doctor to do so (see also paragraphs 25-27 on prescribing for hospital outpatients)
d. Make a clear, accurate and legible record of all medicines prescribed and, where you are not following common practice, your reasons for prescribing the medicine.
4. It is also “technically illegal” in the EU for widespread off-label prescribing within a healthcare system; you simply need to read the legal implications for NHS Trusts in England allowing their ophthalmologists to use Avastin off-license, instead of the licensed Lucentis, for age-related macular degeneration. Another recent example is that of 3,4-diaminopyridine or 3,4-DAP that is used in neurology for a rare disease that causes muscle weakness called Lambert-Eaton Myasthenic syndrome. This drug was used for decades off-license at very little cost to the NHS (~£800-£1,000 per patient per year). However, once a trial was done and the drug licensed under the EU orphan-disease legislation the cost went up to between £40,000 and £70,000 per patient per year. Once a licensed drug was made available it became “illegal” to prescribe the off-license version. This issue could have arisen with the two formulations of Alemtuzumab, Campath and Lemtrada, which has been avoided by the withdrawal of Campath from the market by Genzyme. The reason for this EU legislation is to protect the incentives that has been created for Pharma to invest in R&D and recoup their investments.
If you are interested in these issue I suggest you read the open letter by British Neurologists to the Minister of Health that was published in the BMJ:
“At a personal level I am very concerned about this issue as it prevents clinicians testing licensed drugs for other indications. For example, cladribine, rituximab and alemtuzumab all emerged by some pioneering clinician who was prepared to take the risk of testing the drug in MS and the MSers who were prepared to take undefined risks. This kind of legal mindset, if taken literally, will inhibit innovation. It also makes it impossible for me as a clinician and opinion leader to recommend off-license use of a drug in MS. I hope you understand?”
Other relevant posts on this blog in relation this issue: