WP6 replication study: The risk of liver injury associated with the use of antibiotics: A study using a US database with linkage with hospital data

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Validation of study variables (exposure outcome covariate)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Case-control

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (J01) ANTIBACTERIALS FOR SYSTEMIC USE

  ANTIBACTERIALS FOR SYSTEMIC USE
• Medical condition to be studied:
  Liver injury

Population studied

• Short description of the study population:
  Patients of all ages with an active or died registration status during the study period of January 1st, 2004 to December 31st, 2009 in the Clinformatics Data Mart. Patients had to attained one year of enrolment in the database at the beginning of the study period.
• Age groups:
  • Adults (18 to < 46 years)
  • Adults (46 to < 65 years)
  • Adults (65 to < 75 years)
  • Adults (75 to < 85 years)
  • Adults (85 years and over)
• Estimated number of subjects:
  80000

Study design details

• Main study objective:
  To assess the association between antibiotics use and idiopathic acute liver injury by replicating a nested case-control design in a US claims database
• Outcomes:
  To estimate the risk of acute liver injury associated with antibiotics exposure (users and non-users), To estimate the risk of acute liver injury associated with various antibiotics classes, To estimate the risk of acute liver injury associated with specific individual antibiotics, To assess the effect of dose and duration of use for specific individual antibiotics, To validate cases of liver injury using information from patients’ hospital records, To describe the patterns of use of various antibiotics classes and of specific individual antibiotics in the US and to compare with patterns of use in the UK as observed in GPRD, To replicate the analysis using a population-based case-control design
• Data analysis plan:
  We will compute odds ratios (OR) and 95% confidence intervals of first occurrence of idiopathic acute liver injury associated with current use of antibiotics (as a group and different classes and individual drugs when possible) as compared to non-use with conditional logistic regression.