title: Global benefit-risk assessment in designing clinical trials and some statistical considerations of the method.
abstract: When characterizing a therapy, the efficacy and the safety are two major aspects under consideration. In prescribing a therapy to a patient, a clinician puts the two aspects together and makes a decision based on a consolidated thought process. The global benefit-risk (GBR) measures proposed by Chuang-Stein et al. (Stat. Med. 1991; 10:1349-1359) are useful in facilitating the thinking, and creating the framework for making statistical comparisons based on benefit-risk point of view. This article describes how a GBR linear score was defined and used as the primary outcome measure in a clinical trial design. The robustness of the definitions of 'benefit' and 'risk' are evaluated using different criteria. The sensitivity of the pre-specified weights is also analyzed using alternative weights; one of those was determined by the relative to an identified distribution integral transformation approach (Biometrics 1958; 14:18-38). Statistical considerations are illustrated using pooled data from clinical trials studying antidepressant. The pros and cons for using GBR assessments in the setting of clinical trials are discussed.
authors.affiliation: Abbott Laboratories, Abbott Park, IL 60064, USA. yili.pritchett@abbott.com
authors.forename: Yili Lu
authors.initials: YL
authors.lastname: Pritchett
authors.forename: Roy
authors.initials: R
authors.lastname: Tamura
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods / Q000706:statistics & numerical data; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000379:methods* / Q000706:statistics & numerical data*; D012107:Research Design / Q000706:statistics & numerical data*; D018570:Risk Assessment / Q000379:methods / Q000706:statistics & numerical data