title: Methodological issues in the choice among different drugs approved for the same therapeutic indication: a position paper by the Italian Association of Medical Oncology (AIOM).
abstract: In oncology, as in other clinical fields, different treatments are often approved for the same therapeutic indication. In many cases, no direct comparisons are available to inform the choice in clinical practice. In 2015, the Italian Association of Medical Oncology (AIOM) instructed a working group, including both clinicians and methodologists, to discuss the issue of the best choice among different treatments available for the same indication. The working group discussed 3 different scenarios: (1) biosimilar drugs; (2) different drugs with same mechanism of action; (3) different drugs with different mechanism of action. For each scenario, methodological issues were discussed, along with the priority for investment of resources in the conduct of clinical trials testing direct comparison. As for biosimilar drugs, the panel recommended that, following comparability exercise and approval by regulatory agencies, they should be widely used, considered that their use allows financial savings. As for different drugs (with either the same or a different mechanism of action), the panel agreed that indirect comparisons and network meta-analyses are associated with relevant risk of bias and imprecision, and direct comparisons should be encouraged. The priority of these direct comparisons should be higher when the potential differences in efficacy and/or toxicity are clinically relevant. The choice of the study design (superiority vs non-inferiority) depends on the toxicity profiles and also on the presumed difference in efficacy. Scientific societies should put pressure on public bodies to identify all the administrative and financial mechanisms useful to facilitate the conduct of trials testing direct comparisons, when needed. Decision about therapeutic equivalence can have important consequences on innovation: the availability of drugs characterised by the same effectiveness, but at a lower cost, could enable non-negligible savings of economic resources that could be used to guarantee access to innovative, high-cost drugs.
authors.affiliation: Division of Medical Oncology, Mauriziano Hospital, Oncology Department, University of Turin, Torino, Italy. Electronic address: massimo.dimaio@unito.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Maio
authors.affiliation: Department of Epidemiology, Biostatistics and Clinical Trials, IRCCS AOU San Martino, IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bruzzi
authors.affiliation: Clinical Trials Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori -Fondazione Giovanni Pascale IRCCS, Napoli, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Perrone
authors.affiliation: Laboratory of Methodology for Clinical Research, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
authors.forename: Valter
authors.initials: V
authors.lastname: Torri
authors.affiliation: Investigative Clinical Oncology, Fondazione del Piemonte per l'Oncologia (FPO), Candiolo Cancer Institute (IRCCS), Candiolo (TO), Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Montemurro
authors.affiliation: Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Tiseo
authors.affiliation: Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, Pisa, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Vasile
keywords: Biosimilars; Sustainability; Therapeutic equivalence; Value