title: Uptake of new drugs in the early post-approval period in the Mini-Sentinel distributed database.
abstract: Several factors limit the statistical power of drug safety surveillance during the early post-approval period, including uptake of the drug and lag in data availability. This study characterized new drug uptake in the Mini-Sentinel Distributed Database and determined statistical power to detect levels of risk in post-launch safety assessments.
  
  
  
  The cumulative exposure among initiators of 46 new molecular entities approved from 2008 to 2011 was assessed. Using a Poisson estimation method, minimum incidence rate ratios (IRRs) detectable, with 80% power, were calculated under varying background incidence rates.
  
  
  
  Twelve products (26.1%) had more than 15 000 new users after 2 years. With comparator group incidence rate of 1/1000 person-years, 16 (33.3%) products had enough exposure to detect an IRR of 5 with 24 months of data collected that would be available for assessment at 33 months post-launch. With an incidence rate of 5/1000 person-years, 23 (50%) products had enough exposure to detect an IRR of ≥3 with 2 years of data collected. At 33 months post-launch, only two (4.3%) of the drugs examined had enough data availability to detect IRR of <2, and eight (17.4%) of <3, with a background rate of 1/1000 person-years.
  
  
  
  This study highlights the importance of drug uptake and data availability in early post-approval drug safety surveillance in Mini-Sentinel. There is limited ability to detect rate ratios below three for events with background rates of 1/1000 person-years or lower. This is largely due to low product uptake. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: CDER Office of Surveillance and Epidemiology, U.S. Food and Drug Administration, Silver Spring, MD, USA.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Katrina
authors.initials: K
authors.lastname: Mott
authors.affiliation: CDER Office of Surveillance and Epidemiology, U.S. Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Graham
authors.affiliation: Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute, Boston, MA, USA.
authors.forename: Sengwee
authors.initials: S
authors.lastname: Toh
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Gagne
authors.affiliation: CDER Office of Biostatistics, U.S. Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Levenson
authors.affiliation: CDER Office of Biostatistics, U.S. Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Ma
authors.affiliation: CDER Office of Surveillance and Epidemiology, U.S. Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Marsha E
authors.initials: ME
authors.lastname: Reichman
mesh_terms: D003195:Computer Communication Networks; D016208:Databases, Factual; D017277:Drug Approval; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D006801:Humans; D004364:Pharmaceutical Preparations / Q000008:administration & dosage; D017891:Pharmacoepidemiology / Q000379:methods; D016012:Poisson Distribution; D011358:Product Surveillance, Postmarketing / Q000379:methods / Q000706:statistics & numerical data*; D018570:Risk Assessment / Q000379:methods; D018571:Sentinel Surveillance; D013997:Time Factors; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D004364:Pharmaceutical Preparations
keywords: Sentinel; active surveillance; distributed databases; drug safety; new molecular entities; pharmacoepidemiology