The risk of acute liver injury associated with the use of antibiotics. A methodological comparison across epidemiological data sources

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

  Disease epidemiology

  Other
• If ‘other’, further details on the scope of the study:
  Analysis of discrepancies in results between different databases
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Case-control

  Cohort

  Other
• Non-interventional study design, other:
  Case-crossover, Self-controlled case series, Descriptive study = description of exposure and/or outcome in the whole database during a defined period of time

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. Patients must have attained one year of enrolment with the GP and one year of computerized prescription history.
• Age groups:
  Infants and toddlers (28 days – 23 months)

  Children (2 to < 12 years)

  Adolescents (12 to < 18 years)

  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:
  55700000

Study design details

• Main study objective:
  To assess the association between the use antibiotics and the risk of acute liver injury with different study designs across different primary care databases and to compare the results between databases, across designs to evaluate the impact of design/database/population differences on the outcome of the studied association.
• Data analysis plan:
  Descriptive study of the primary study population including all ages, from 1 Jan 2004 to 31 Dec 2009). Prevalence of antibiotic (AB) use stratified by age, by sex, by indication, by number of prescriptions and by AB class. Incidence of first-time liver failure by age, by sex per calendar year. Retrospective Cohort study: estimates of incidence rate ratios and 95% confidence intervals of acute liver injury associated with current AB as compared to non-use with Poisson regression adjusted by age/sex/ and calendar year categories. Case Control Study: estimates of relative risk and 95% confidence intervals using unconditional logistic regression. Age, sex, calendar year, and other variables will be introduced in the model to control for potential confounding. Case-crossover analysis estimates of the odds of having an event (liver injury while exposed to antibiotic drugs will be compared with the odds of having liver injury while unexposed.

Documents

Study publications

Udo R, Tcherny‐Lessenot S, Brauer R, Dolin P, Irvine D, Wang Y, Auclert L, Juha…

Brauer R, Ruigómez A, Klungel O, Reynolds R, Feudjo Tepie M, Smeeth L, Douglas …

Brauer R, Douglas I, Garcia Rodriguez LA, Downey G, Huerta C, de Abajo F, Bate …

Ruigomez A, Brauer R, Rodríguez LG, Huerta C, Requena G, Gil M, de Abajo F, Dow…