title: Expanded Access Programme: looking for a common definition.
abstract: Therapeutic use of an unauthorised drug (or of an authorised drug for an unauthorised indication) for patients with a life-threating disease is permitted outside a clinical trial as an Expanded Access Programme (EAP).The regulations regarding EAPs is not the same all over the world. For example, the recommendation of the European Medicines Agency (EMA) in EU countries also includes within EAPs patients who have been treated in a clinical trial and who wish to continue the treatment. Nevertheless, the patients treated in a clinical trial could have the option of continuing treatment for an extended period in an Open-label Extension study, aimed to generate long-term data on efficacy, safety, tolerability and administration.The aims of this paper - based on the difficulties and incoherence encountered by an Italian Ethic Committee (EC) during the authorisation process of EAPs - are: understanding the origin of this misclassification by analysing differences and similarities among USA, European and Italian regulations concerning EAPs; and showing difficulties in classifying international study protocols as a consequence of the lack of harmonisation of definitions.We performed a critical review of the current USA, European and Italian regulations and we analysed some practical cases by retrieving protocols from Clinicaltrials.gov and the Italian Clinical Trials Registry (OsSC) containing in the title the keywords 'Expanded Access Programme', "'Expanded Access', 'Open-label Extension study' or 'Early Access'.We observed that the Food and Drug Administration ( FDA) definition of EAP is very clear while the EMA definition is similar to that of an Open-label Extension study. This lack of a clear definition generates misclassification and it is possible to find an EAP with an efficacy or safety endpoint; or an EAP managed as a clinical trial; or an EAP classified in Clinical Trials Registries as a phase II, III or IV clinical trial.The internationalisation of the studies requires a harmonisation on a global level of legislation and definitions to eliminate misclassification of protocols. For this reason, the authors suggest that: a) the EMA definition should be harmonised with the FDA definition of EAPs, b) European regulation, even if optional, should be adopted in a compulsory way by national regulations. Moreover, separate registries for both EAPs and clinical trials should be organised.
authors.affiliation: Pharmaceutical Department, Azienda USL of Modena, Policlinico Hospital, Modena, Italy. a.iudicello@ausl.mo.it.
authors.forename: Antonella
authors.initials: A
authors.lastname: Iudicello
authors.affiliation: Pharmaceutical Department, Azienda USL of Bologna, Maggiore Hospital, Largo B. Nigrisoli 2, 40133, Bologna, Italy. l.alberghini@ausl.bologna.it.
authors.forename: Lucia
authors.initials: L
authors.lastname: Alberghini
authors.affiliation: Pharmaceutical Department, Azienda USL of Bologna, Maggiore Hospital, Largo B. Nigrisoli 2, 40133, Bologna, Italy. g.benini@ausl.bologna.it.
authors.forename: Giulia
authors.initials: G
authors.lastname: Benini
authors.affiliation: IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy. paola.mosconi@marionegri.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Mosconi
mesh_terms: D002986:Clinical Trials as Topic; D057176:Compassionate Use Trials; D005060:Europe; D006801:Humans; D007558:Italy; D056687:Off-Label Use; D014481:United States; D014486:United States Food and Drug Administration