title: Effects of safety warnings and risk management plan for Thiazolidinediones in Taiwan.
abstract: OBJECTIVE
  To evaluate changes in thiazolidinedione use and quality of prescription following safety warnings for thiazolidinediones and cardiac risk in 2007, Risk Management Plan (RMP) policy for rosiglitazone in 2010, and warning for pioglitazone and bladder cancer risk in 2010 in Taiwan.
  
  
  METHODS
  We obtained 2003-2011 claims data from Taiwan's National Health Insurance Research Database. Using an interrupted time series design and segmented regression, we estimated changes in monthly prescribing rates for thiazolidinediones among all and prevalent diabetes patients with and without cardiovascular disease history (CV history). We also compared time to prescription of thiazolidinediones among new diabetes patients with CV history before and after each regulatory action using survival analysis.
  
  
  RESULTS
  Among prevalent patients with and without CV history, the prescribing rates of rosiglitazone decreased 36.88% and 28.92% after safety warnings in 2007 respectively. Pioglitazone prescriptions increased 13% among patients with CV history, but no changes were detected among patients without CV history. After rosiglitazone's RMP policy in 2010, large reductions in prescriptions were observed in patients with CV history (-101.67%) and those without CV history (-88.04%). Among new diabetes patients with CV history, cardiac safety warnings in 2007 significantly delayed the prescription of rosiglitazone, but no significant change was found for pioglitazone.
  
  
  CONCLUSIONS
  The Taiwan FDA regulatory actions for thiazolidinediones communicated possible risks of cardiac events and bladder cancer. Different safety regulatory actions had differential impacts on the use of rosiglitazone and pioglitazone and the quality use of these drugs among the high-risk patients.
authors.affiliation: School of Pharmacy and Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Jason C
authors.initials: JC
authors.lastname: Hsu
authors.affiliation: School of Pharmacy and Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Ching-Lan
authors.initials: CL
authors.lastname: Cheng
authors.affiliation: Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
authors.forename: Dennis
authors.initials: D
authors.lastname: Ross-Degnan
authors.affiliation: Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
authors.forename: Anita K
authors.initials: AK
authors.lastname: Wagner
authors.affiliation: Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhang
authors.affiliation: School of Pharmacy and Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yea-Huei
authors.initials: YH
authors.lastname: Kao Yang
authors.affiliation: Division of Drug, Food and Drug Administration, Ministry of Health and Welfare, Taipei, Taiwan.
authors.forename: Li-Ling
authors.initials: LL
authors.lastname: Liu
authors.affiliation: Division of Drug, Food and Drug Administration, Ministry of Health and Welfare, Taipei, Taiwan.
authors.forename: Hsueh-Yung
authors.initials: HY
authors.lastname: Tai
authors.affiliation: Division of Drug, Food and Drug Administration, Ministry of Health and Welfare, Taipei, Taiwan.
authors.forename: Ke-Hsin
authors.initials: KH
authors.lastname: Chen
authors.affiliation: Division of Drug, Food and Drug Administration, Ministry of Health and Welfare, Taipei, Taiwan.
authors.forename: Po-Wen
authors.initials: PW
authors.lastname: Yang
authors.affiliation: Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
authors.forename: Christine Y
authors.initials: CY
authors.lastname: Lu
mesh_terms: D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000453:epidemiology / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000453:epidemiology; D011307:Drug Prescriptions / Q000706:statistics & numerical data; D004363:Drug Utilization / Q000706:statistics & numerical data / Q000639:trends*; D005260:Female; D006801:Humans; D008875:Middle Aged; D061214:Patient Safety; D017891:Pharmacoepidemiology; D012308:Risk Management / Q000379:methods*; D013624:Taiwan / Q000453:epidemiology; D045162:Thiazolidinediones / Q000008:administration & dosage* / Q000009:adverse effects*; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000453:epidemiology / Q000517:prevention & control
chemical_list: D045162:Thiazolidinediones
keywords: Taiwan; pharmacoepidemiology; risk management plan; safety warning; thiazolidinedione; type 2 diabetes