Use of off-label medicines puts patient safety at risk

Concerns raised during the recent inquest into the tragic death of Bimbo Onanuga have again highlighted the potential difficulties arising from the use of off-label medicines.

Earlier this month, the Dublin Coroner's Court heard that Ms Onanuga was given an ulcer medication, misoprostol, to induce labour. In returning a verdict of medical misadventure, the coroner stated that the main risk factors were the deceased's pre-existing scar and the off-label use of misoprostol. The coroner signalled his intention to raise the concerns of Ms Onanuga's family regarding the use of this off-label drug with the Irish Medicines Board.

Looking at the broader picture, the use of medicines for purposes for which they are not authorised gives rise to fundamental issues of patient safety. For obvious reasons, prescription drugs are among the world’s most tightly regulated products. They are licensed for specific health issues after lengthy and robust clinical trials.

Off-label use occurs where a doctor prescribes an approved medicine for the treatment of a particular illness or for doses for which it is not licensed or authorised. Proper practice dictates that only where there is no available licensed alternative should off-label prescriptions be allowed. In addition, any therapeutic decision should be made with the patient’s consent. If a licensed alternative is available, the patient should be told so that he or she can make an informed decision.

However sometimes where a doctor has a choice between an unlicensed medicine and a licensed alternative, he or she may opt for the former, particularly if it is less expensive. That said, off-label use for budgetary reasons is not consistent with the jurisprudence of the European courts, which have consistently held that the protection of public health takes precedence over financial considerations. Notwithstanding this, recent years have seen a change in attitude by certain EU member states.

Just under a year ago, France adopted a law authorising the government to issue recommendations encouraging off-label use of a drug despite the existence of authorised alternatives, with a view to reducing its expenditure on social security. Previously, off-label use was only permitted in the absence of any authorised therapeutic alternative and provided that the patient was informed.

Moreover, certain Finnish and UK authorities promoted the unauthorised use of Avastin to treat age-related macular degeneration or AMD on cost grounds because Lucentis, the authorised medicine to treat AMD, was more expensive.

This shift in policy contrasts with the consequences faced by pharmaceutical manufacturers which are suspected or found to have wrongly promoted a drug for off-label use. These include investigations, litigation and heavy fines, not to mention the associated controversy and negative publicity. To take a recent example, a US court fined American biotechnology giant Amgen $762 million in December 2012 after it pleaded guilty to promoting the off-label use of Aranesp. As a result of cases such as this, manufacturers are best advised to take great care not to promote off-label use inappropriately.

Since the health concerns that arose during the BSE in British beef controversy, EU law has been clear that public health must outweigh financial considerations. In March 2012, as a result of enforcement proceedings brought by the European Commission, the European Court of Justice found that a Polish law permitting the sale of unauthorised medicines on cost grounds was illegal under EU law.

The court noted that exceptions to the rule that all prescribed medicines must be authorised should be read very narrowly. Doctors’ rights to prescribe off-label only arise following “an actual examination of his patients and on the basis of purely therapeutic considerations”, ie not for financial reasons. The court also noted that where an equivalent authorised medicine was available, there existed no special need for an unauthorised product.

The decision of certain public authorities to promote off-label medicines raises the question as to what would happen if the use of such drugs gave rise to patient safety concerns. Given the negative consequences for private companies which promote off-label medicines, it would be interesting to see whether these public authorities would face similar liability.

Given the overall economic backdrop, the pressure on public finances across Europe is unlikely to ease any time soon. Therefore, healthcare budgets will continue to come under scrutiny. That said, EU law prevents patient safety being undermined for financial reasons.

If national authorities continue to promote off-label use for budgetary reasons, we may again see the European Commission having to step in. This is only a fair outcome: since the private sector is rightly held to high standards of conduct when it comes to promoting off-label use; the public sector must be too.

Cormac Little is partner and head of EU and competition law at William Fry