title: Assessment of benefits and risks in development of targeted therapies for cancer--The view of regulatory authorities.
abstract: Drug licensing and approval decisions involve the balancing of benefits against the risks (harms) in the presence of uncertainty. Typically, the benefits are estimated from primary efficacy endpoints from confirmatory (phase III) clinical trials although exceptions where promising early data from single-arm studies have led to accelerated approvals are not uncommon, particularly for cancer drugs. The challenge for regulators is to balance early evidence of efficacy that might support approval versus the need to establish clinical benefit based on conclusive evidence. Targeted agents offer the promise that knowledge about the mechanism of the disease will help identify patients with tumors likely to respond, resulting in higher efficacy and less toxicity, and earlier regulatory decisions based on convincing evidence of clinical benefit. In this paper, we describe methods and examples of benefit-risk assessment of targeted drugs, recent initiatives from EMA and FDA on improving communication about benefits and risks, and discuss future steps.
authors.affiliation: European Medicines Agency (EMA), London, United Kingdom. Electronic address: francesco.pignatti@ema.europa.eu.
authors.forename: Francesco
authors.initials: F
authors.lastname: Pignatti
authors.affiliation: Läkemedelsverket, Uppsala, Sweden.
authors.forename: Bertil
authors.initials: B
authors.lastname: Jonsson
authors.affiliation: Food and Drug Administration (FDA), Silver Spring, MD, USA.
authors.forename: Gideon
authors.initials: G
authors.lastname: Blumenthal
authors.affiliation: Food and Drug Administration (FDA), Silver Spring, MD, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Justice
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D018570:Risk Assessment
chemical_list: D000970:Antineoplastic Agents
keywords: Benefit-risk balance; Drug regulation; Targeted therapies