title: Benefit-Risk Assessment, Communication, and Evaluation (BRACE) throughout the life cycle of therapeutic products: overall perspective and role of the pharmacoepidemiologist.
abstract: OBJECTIVE
  Optimizing a therapeutic product's benefit-risk profile is an on-going process throughout the product's life cycle. Different, yet related, benefit-risk assessment strategies and frameworks are being developed by various regulatory agencies, industry groups, and stakeholders. This paper summarizes current best practices and discusses the role of the pharmacoepidemiologist in these activities, taking a life-cycle approach to integrated Benefit-Risk Assessment, Communication, and Evaluation (BRACE).
  
  
  METHODS
  A review of the medical and regulatory literature was performed for the following steps involved in therapeutic benefit-risk optimization: benefit-risk evidence generation; data integration and analysis; decision making; regulatory and policy decision making; benefit-risk communication and risk minimization; and evaluation. Feedback from International Society for Pharmacoepidemiology members was solicited on the role of the pharmacoepidemiologist. The case example of natalizumab is provided to illustrate the cyclic nature of the benefit-risk optimization process.
  
  
  RESULTS
  No single, globally adopted benefit-risk assessment process exists. The BRACE heuristic offers a way to clarify research needs and to promote best practices in a cyclic and integrated manner and highlight the critical importance of cross-disciplinary input. Its approach focuses on the integration of BRACE activities for risk minimization and optimization of the benefit-risk profile.
  
  
  CONCLUSIONS
  The activities defined in the BRACE heuristic contribute to the optimization of the benefit-risk profile of therapeutic products in the clinical world at both the patient and population health level. With interdisciplinary collaboration, pharmacoepidemiologists are well suited for bringing in methodology expertise, relevant research, and public health perspectives into the BRACE process.
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Radawski
authors.affiliation: Colorado School of Public Health, University of Colorado Denver, Denver, CO, USA.
authors.forename: Elaine
authors.initials: E
authors.lastname: Morrato
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Hornbuckle
authors.affiliation: European Medicines Agency, London, UK.
authors.forename: Priya
authors.initials: P
authors.lastname: Bahri
authors.affiliation: Amgen, Inc., Thousand Oaks, CA, USA.
authors.forename: Meredith
authors.initials: M
authors.lastname: Smith
authors.affiliation: Pharmacoepidemiology, Sanofi, Bridgewater, NJ, USA.
authors.forename: Juhaeri
authors.initials: J
authors.lastname: Juhaeri
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Mol
authors.affiliation: Janssen Research & Development, LLC, Titusville, NJ, USA.
authors.forename: Bennett
authors.initials: B
authors.lastname: Levitan
authors.affiliation: Global Pharmacovigilance and Epidemiology, Bristol-Myers Squibb, Pennington, NJ, USA.
authors.forename: Han-Yao
authors.initials: HY
authors.lastname: Huang
authors.affiliation: Risk Management and Epidemiology, Purdue Pharma L.P., Stamford, CT, USA.|Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Paul
authors.identifier: http://orcid.org/0000-0002-7078-7780
authors.initials: P
authors.lastname: Coplan
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Hu
authors.initials: H
authors.lastname: Li
mesh_terms: D003142:Communication; D003362:Cost-Benefit Analysis; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D014943:Global Health; D006801:Humans; D017891:Pharmacoepidemiology; D055553:Prescription Drugs / Q000009:adverse effects / Q000191:economics*; D018570:Risk Assessment
chemical_list: D055553:Prescription Drugs
keywords: benefit-risk assessments; evaluation; pharmacoepidemiology; risk communication