Alert generation using the case-population approach in the French claims databases (ALCAPONE)

Study type

• Study topic:
  Disease /health condition
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Other
• If ‘other’, further details on the scope of the study:
  Pharmacovigilance signal generation
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Other
• Non-interventional study design, other:
  Case-control study, Self-controlled case series, Case-population study

Study drug and medical condition

• Medical condition to be studied:
  Acute myocardial infarction

  Upper gastrointestinal haemorrhage

  Acute kidney injury

  Acute hepatic failure

Population studied

• Short description of the study population:
  Patients with acute liver injury, myocardial infarction, kidney injury, and upper gastrointestinal bleeding identified from the French nationwide healthcare system claim databases SNIIRAM and EGB between 1 January 2009 and 31 December 2014.; Inclusion criteria: ; - Patients presenting ALI, AKI, MI or UGIB between 01/01/2009 and 31/12/2014 ; - And having at least 182 days of healthcare history; ; Exclusion criteria:; - AKI: patients presenting previous renal transplantation or metal intoxication or specific kidney diseases; - ALI: patients presenting liver injury resulting from other causes than potential drug toxicity
• Age groups:
  • Paediatric Population (< 18 years)

    • Neonate

      • Term newborn infants (0 – 27 days)
    • Infants and toddlers (28 days – 23 months)
    • Children (2 to < 12 years)
    • Adolescents (12 to < 18 years)
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)
• Estimated number of subjects:
  66000000

Study design details

• Main study objective:
  The main objectives are:(i) To assess the performance of SNIIRAM for the detection of drug safety signals based on the OMOP reference set and methodologies(ii) To develop on SNIIRAM the case-population approach and assess its performance for safety signal generation based on the OMOP reference set.
• Outcomes:
  This study is based on the validation of the database according to the OMOP reference set (several series of molecules that have - positive controls - or have not - negative controls - been associated with four main events of interest). The identification of the true positive and the true negative drug-event pairs could be considered as the primary outcomes.
• Data analysis plan:
  Three different designs are envisaged:(i) Case-control designOdds ratios (OR) will be calculated using a conditional logistic regression. Several degrees of matching will be considered, going from non-matched approach to disease risk score matching including loose matching on simply age and sex. (ii) Self-controlled case seriesRisk periods will be determined based on exposition and presumed biological mechanisms. Relative incidences (RI) for the risk periods will be computed.(iii) Case-population approachCase population ratio (CPR) will be calculated according to two distinct exposure approaches: a person-time approach and a per-user approach.The following evaluation criteria will be used to compare designs performanceThe receptor operating characteristics (ROC) will be used to choose the best compromise between sensitivity and specificity among the different designs and their variants according to drug-event pair characteristics.