title: Effect of US Food and Drug Administration's Cardiovascular Safety Guidance on Diabetes Drug Development.
abstract: In 2008, the US Food and Drug Administration (FDA) issued guidance on the need for cardiovascular outcome trials to assess the safety of new diabetes medications. Using two large commercial databases, we evaluated the effect of the FDA's cardiovascular safety guidance on drug development for type 2 diabetes as well as a comparison group of drugs intended to treat other alimentary and metabolic conditions. The FDA's guidance was associated with a 31% differential decrease in the rate of diabetes drugs entering phase II trials, but the remaining drugs were significantly more likely to target novel biological pathways (72% of drugs had novel mechanisms after the guidance vs. 49% before the guidance). No differential changes were observed for phase I and phase III trials. There was no measurable improvement during the study period in glycemic efficacy among investigational products entering phase III trials. This research highlights how regulatory actions can impact pharmaceutical innovation.
authors.affiliation: Program on Regulation, Therapeutics, and Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Hwang
authors.affiliation: Program on Regulation, Therapeutics, and Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Franklin
authors.affiliation: Program on Regulation, Therapeutics, and Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Kesselheim
mesh_terms: D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D002986:Clinical Trials as Topic / Q000379:methods; D016208:Databases, Factual / Q000639:trends; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D015507:Drugs, Investigational / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014481:United States / Q000453:epidemiology; D014486:United States Food and Drug Administration / Q000331:legislation & jurisprudence / Q000592:standards*
chemical_list: D015507:Drugs, Investigational; D007004:Hypoglycemic Agents