title: Methodology of a reevaluation of cardiovascular outcomes in the RECORD trial: study design and conduct.
abstract: BACKGROUND
  In 2010, after regulatory review of rosiglitazone licensing, the US Food and Drug Administration (FDA) requested a reevaluation of cardiovascular end points in the RECORD trial.
  
  
  METHODS
  Automated screening of the original clinical trial database and manual case report form review were performed to identify all potential cardiovascular and noncardiovascular deaths, and nonfatal myocardial infarction (MI) and stroke events. Search techniques were used to find participants lost to follow-up, and sites were queried for additional source documents. Suspected events underwent blinded adjudication using both original RECORD end point definitions and new FDA end point definitions, before analysis by the Duke Clinical Research Institute.
  
  
  RESULTS
  The reevaluation effort included an additional 328 person-years of follow-up. Automated screening identified 396 suspected deaths, 2,052 suspected MIs, and 468 suspected strokes. Manual review of documents by Duke Clinical Research Institute clinical events classification (CEC) coordinators identified an additional 31 suspected deaths, 49 suspected MIs, and 28 suspected strokes. There were 127 CEC queries issued requesting additional information on suspected deaths; 43 were closed with no site response, 61 were closed with a response that no additional data were available, and additional data were received for 23. Seventy CEC queries were issued requesting additional information for suspected MI and stroke events; 31 were closed with no site response, 20 were closed with a response that no additional data were available, and 19 resulted in additional data.
  
  
  CONCLUSIONS
  Comprehensive procedures were used for rigorous event reascertainment and readjudication in a previously completed open-label, global clinical trial. These procedures used in this unique situation were consistent with other common approaches in the field, were enhanced to address the FDA concerns about the original RECORD trial results, and could be considered by clinical trialists designing event readjudication protocols for drug development programs that have been completed.
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA. renato.lopes@duke.edu
authors.forename: Renato D
authors.initials: RD
authors.lastname: Lopes
authors.forename: Sheila
authors.initials: S
authors.lastname: Dickerson
authors.forename: Gail
authors.initials: G
authors.lastname: Hafley
authors.forename: Shana
authors.initials: S
authors.lastname: Burns
authors.forename: Sandra
authors.initials: S
authors.lastname: Tourt-Uhlig
authors.forename: Jennifer
authors.initials: J
authors.lastname: White
authors.forename: L Kristin
authors.initials: LK
authors.lastname: Newby
authors.forename: Michel
authors.initials: M
authors.lastname: Komajda
authors.forename: John
authors.initials: J
authors.lastname: McMurray
authors.forename: Robert
authors.initials: R
authors.lastname: Bigelow
authors.forename: Philip D
authors.initials: PD
authors.lastname: Home
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
mesh_terms: D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D009026:Mortality; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000453:epidemiology; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D000077154:Rosiglitazone; D020521:Stroke / Q000139:chemically induced* / Q000453:epidemiology; D045162:Thiazolidinediones / Q000009:adverse effects*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone