Off-label Prescriptions: how to Identify Them, Frame Them, Announce Them and Monitor Them in Practice?
Claire Le Jeunne1, Nathalie Billon2, Anne Dandon3 and participants of round table N° 3 of Giens XXVIII:
Driss Berdaï4, Yolande Adgibi5, Jean-François Bergmann6, Régis Bordet7, Anne Carpentier8, Emmanuelle Cohn9, Soizic Courcier10, Danièle Girault11, Sylvia Goni12, Pascale Jolliet13, François Liard14, Sonia Prot-Labarthe15, Tabassome Simon16, Christine Vernotte17 and Jérémie Westerloppe18†
1 Service de Médecine interne,
Assitance Publique – Hôpitaux de Paris, Hôtel Dieu, Paris, France
2 Laboratoire Sanofi, Paris, France
3 Haute Autorité de Santé, Saint-Denis la Plaine, France
4 Centre hospitalier de Bordeaux, Bordeaux, France
5 Orphandev, Centre hospitalier de Marseille, Marseille, France
6 Centre hospitalier Lariboisière, Paris, France
7 Pharmacologie, Faculté de Médecine, Lille, France
8 Les entreprises du médicament (LEEM), Paris, France
9 Haute Autorité de Santé, Saint-Denis la Plaine, France
10 Laboratoire GlaxoSmithKline, Marly-le-Roi, France
11 Laboratoire Novartis Pharma, Rueil-Malmaison, France
12 Laboratoire Lundbeck, Issy-les-Moulineaux, France
13 Centre hospitalier de Nantes, Nantes, France
14 Cabinet de Médecine générale, Saint-Épain, France
15 Pharmacie Hôpital Robert Debré, Paris, France
16 Centre hospitalier Saint Antoine, Paris, France
17 Laboratoire Lilly France, Suresnes, France
18 Laboratoire Celgene, Paris, France
Correspondence and offprints: Claire Le Jeunne,
Service de Médecine interne, Assistance Publique – Hôpitaux de Paris, Hôtel Dieu, 1 place
du Parvis de Notre Dame, 75004 Paris, France. E-mail:
Accepted: 7 May 2013
Following the Mediator crisis and the passage of the Health and Safety Law of December 2011, off-label prescriptions are a real concern shared by all those involved in healthcare system. Off-label, in the strictest sense of the term, is defined as all prescriptions that do not correspond to the summary of product characteristics (SPC), particularly those that fail to comply with the indications and dosage regimens defined by the marketing authorization (MA) for clear safety reasons. There are various rasons for off-label prescriptions, both conscious and unconscious. They are intended to respond to unmet medical needs, the needs of poorly studied populations or not studied at all in trials, but in relation to whom it is reasonable to extrapolate that MA would be given (common-sense prescriptions) and, additionally, to urgent public health needs (such as baclofen, pregnant women, and HIV drugs). All these prescriptions would deserve to be studied for a potential MA. However, there are off-label prescriptions that need to be restricted or even penalized in the case of compassionate prescriptions or unjustified prescriptions or prescriptions not based on any scientific grounds.
Off-label prescriptions are not easy to track down because if the prescriber has to write “off-label” on his prescription, then clearly, in practice, he will only do so in exceptional cases. Neither the pharmacists who dispense the drug nor the Social Security that reimburses it, have access to the diagnosis (or targeted indication). Thus, in order to identify the off-label prescription, we must be able to cross reference the available databases (such as pharmacovigilance database, medicalized information system program [programme de médicalisation des systèmes d'information, PMSI], hospital drug formularies, general sample of beneficiaries [échantillon généraliste de bénéficiaires, EGB] or national inter-regional Health Insurance Information System [système national d'informations inter-régions d'Assurance maladie, SNIIRAM], sales data, and data from market surveys). The shared computerized patient file may resolve this problem. The temporary use recommendation (TUR) proposed by the Drug Safety Law will only partially deal with this problem for recently marketed molecules.
This temporary and exceptional mechanism will authorize a recognized off-label prescription, which may be reimbursed and monitored for 3 years. These TURs will only concern a small portion of “off-label” drugs having yet a positive risk/benefit ratio (conditional MA) but this is far from matching with majority of off-label prescriptions. As such, and in order to improve the use of drugs, it is important to propose a control system for all “off-label” prescriptions with a dedicated committee: the “off-label” committee which would determine the frame of the “off-label” prescriptions.
Key words: MA / off-MA / conditonal MA / temporary treatment protocol / regulation / temporary use recommendations
© 2013 Société Française de Pharmacologie et de Thérapeutique