title: An observational study of cholecystectomy in patients receiving tegaserod.
abstract: BACKGROUND
  Registrational studies of patients treated with tegaserod for irritable bowel syndrome (IBS) suggest an increased risk for cholecystectomy versus treatment with placebo.
  
  
  OBJECTIVE
  To study cholecystectomy rates in association with tegaserod within a large administrative medical claims database.
  
  
  METHODS
  Patients were drawn from a large population within the US with commercial medical insurance. The primary analysis consisted of a comparison of the observed incidence rate for cholecystectomy claims among a large cohort of new-to-therapy tegaserod users with an incidence rate published for tegaserod-naive patients classified with IBS within the same insured population.
  
  
  RESULTS
  An inception cohort of 7475 individuals with up to 103 weeks of claims history following initiation of therapy with tegaserod was identified. After a follow-up of 3 months (and thus similar to the longest registrational trials), the observed cholecystectomy incidence rate was 340 per 10,000 person-years (95% CI 258, 442). The rate of cholecystectomy was highest in the earliest months of observation following initiation of tegaserod. The observed cholecystecomy incidence rate is 2.9 times higher than an IBS-specific rate of 119 per 10,000 person-years as published for patients so classified within the same insured population.
  
  
  CONCLUSIONS
  Based on a large, inception cohort, we report a strong temporal association between the initiation of tegaserod therapy and an increased rate for cholecystectomy. The effect size at 3 months was similar to the relative risk for cholecystectomy reported in registrational studies comparing tegaserod with placebo. As misclassification of initial diagnosis for patients presenting with biliary colic-like symptoms may occur, precise measurements of tegaserod-related relative risk for cholecystectomy from observational studies are problematic and will require prospective studies.
authors.affiliation: Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA. allen.brinker@fda.hhs.gov
authors.forename: Allen
authors.initials: A
authors.lastname: Brinker
authors.forename: Stephanie D
authors.initials: SD
authors.lastname: Schech
authors.forename: Margaret
authors.initials: M
authors.lastname: Burgess
authors.forename: Mark
authors.initials: M
authors.lastname: Avigan
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002763:Cholecystectomy / Q000706:statistics & numerical data*; D005260:Female; D005765:Gastrointestinal Agents / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D015994:Incidence; D007211:Indoles / Q000009:adverse effects* / Q000627:therapeutic use; D007223:Infant; D007345:Insurance Claim Review; D043183:Irritable Bowel Syndrome / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D017366:Serotonin Receptor Agonists / Q000009:adverse effects* / Q000627:therapeutic use; D013997:Time Factors; D014481:United States
chemical_list: D005765:Gastrointestinal Agents; D007211:Indoles; D017366:Serotonin Receptor Agonists; C105050:tegaserod