title: Assessment of cardiovascular risk of new drugs for the treatment of diabetes mellitus: risk assessment vs. risk aversion.
abstract: The Food and Drug Administration issued guidance for evaluating the cardiovascular risk of new diabetes mellitus drugs in 2008. Accumulating evidence from several completed trials conducted within this framework raises questions as to whether requiring safety outcome studies for all new diabetes mellitus therapies remains justified. Given the burden of cardiovascular disease in patients with diabetes, the focus should shift towards cardiovascular outcome studies designed to evaluate efficacy (i.e. to determine the efficacy of a drug over placebo or standard care) rather than demonstrating that risk is not increased by a pre-specified safety margin. All stakeholders are responsible for ensuring that new drug approvals occur under conditions of appropriate safety and effectiveness. It is also a shared responsibility to avoid unnecessary hurdles that may compromise access to useful drugs and threaten the sustainability of health systems. It is critical to renew this debate so that stakeholders can collectively determine the optimal approach for developing new drugs to treat type 2 diabetes mellitus.
authors.affiliation: INSERM, Centre d'Investigation Clinique - 1433 and Unité 1116, CHU Nancy, Université de Lorraine and F-CRIN INI-CRCT, 54500 Nancy, France f.zannad@chu-nancy.fr.
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
authors.affiliation: Campbell University College of Pharmacy and Health Sciences, Buies Creek, NC, USA.
authors.forename: Wendy Gattis
authors.initials: WG
authors.lastname: Stough
authors.affiliation: Lipicky, LLC, North Potomac, MD, USA.
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Lipicky
authors.affiliation: Department of Pharmacology, School of Medicine, Universidad Complutense, Madrid, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Tamargo
authors.affiliation: ASH Comprehensive Hypertension Center, The University of Chicago Medicine, Chicago, IL, USA.
authors.forename: George L
authors.initials: GL
authors.lastname: Bakris
authors.affiliation: The Howard Gilman Institute, State University of New York Downstate Medical Center, Brooklyn, NY, USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Borer
authors.affiliation: Scientific Advice Working Party, European Medicines Agency, London, UK Medicines and Healthcare Products Regulatory Agency (MHRA), London, UK Department of Cardiology, Imperial College Healthcare NHS Trust, London, UK.
authors.forename: Maria de Los Angeles
authors.initials: Mde L
authors.lastname: Alonso García
authors.affiliation: CHU de Poitiers, Endocrinologie, Université de Poitiers, INSERM CIC1402, Poitiers, France.
authors.forename: Samy
authors.initials: S
authors.lastname: Hadjadj
authors.affiliation: Deutsches Herzzentrum München, Technische Universität München, Munich, Germany DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Koenig
authors.affiliation: Takeda Pharmaceuticals International, Deerfield, IL, USA.
authors.forename: Stuart
authors.initials: S
authors.lastname: Kupfer
authors.affiliation: Baylor University Medical Center, Baylor Heart and Vascular Institute, Dallas, TX, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: McCullough
authors.affiliation: Diabetes Unit, Hadassah Hebrew University Hospital, Jerusalem, Israel.
authors.forename: Ofri
authors.initials: O
authors.lastname: Mosenzon
authors.affiliation: Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Stuart
authors.initials: S
authors.lastname: Pocock
authors.affiliation: Division of Diabetes, Nutrition, and Metabolic Disorders, Division of Clinical Pharmacology, CHU de Liège, University of Liège, Liège, Belgium.
authors.forename: André J
authors.initials: AJ
authors.lastname: Scheen
authors.affiliation: Division of Endocrinology and Diabetology, Medical University of Graz, Centre for Biomarker Research in Medicine, Graz, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Sourij
authors.affiliation: Laboratory of Experimental Medicine and Endocrinology, University of Leuven, Leuven, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Van der Schueren
authors.affiliation: AstraZeneca, Gothenburg, Sweden.
authors.forename: Christina
authors.initials: C
authors.lastname: Stahre
authors.affiliation: Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington, CT, USA.
authors.forename: William B
authors.initials: WB
authors.lastname: White
authors.affiliation: Hospital Clinic of Barcelona, Barcelona, Spain.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Calvo
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000453:epidemiology*; D003920:Diabetes Mellitus / Q000188:drug therapy*; D017408:Guidelines as Topic; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D018570:Risk Assessment; D012308:Risk Management; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D007004:Hypoglycemic Agents
keywords: Cardiovascular disease; Clinical trials; Diabetes mellitus