Influence of safety advisories on drug utilization: an international interrupted time series study

Study type

• Study type:
  Non-interventional study
• Scope of the study:
  Drug utilisation

Non-interventional study

• Non-interventional study design:
  Other
• Non-interventional study design, other:
  Interrupted-time series

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  ARIPIPRAZOLE

  AZITHROMYCIN

  CANAGLIFLOZIN

  CITALOPRAM

  CLOPIDOGREL

  DABIGATRAN

  DAPAGLIFLOZIN

  DENOSUMAB

  DRONEDARONE

  EMPAGLIFLOZIN

Population studied

• Age groups:
  • Preterm newborn infants (0 – 27 days)
  • Term newborn infants (0 – 27 days)
  • 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:
  93000000

Study design details

• Main study objective:
  The primary objective of the study is to evaluate the impact of drug safety advisories on drug utilization, using an interrupted time series approach to compare a country with a given advisory to a control country without a similar advisory.
• Outcomes:
  The primary outcome for analysis in this study will be the monthly rate of drug utilization relevant to the included advisories. The rate of drug utilization will be defined as the number of prescriptions prescribed or dispensed per 100,000 patients with prescription drug coverage in that month. 1.For advisories with specific advice on dosage level: we will measure the rate of drug utilization as the number of defined daily doses prescribed or dispensed per 100,000 patients.
• Data analysis plan:
  For the primary analysis of each index advisory with at least one potential discordant control variable, we will evaluate the impact of the index advisory on drug utilization in comparison to a discordant control country. This will involve:a) Identification of the index advisory and potential discordant controls (with data on drug advisories and drug approval and withdrawal dates)b) Identifying the relevant periods of follow-up for each country and the rate of drug utilization for each of 36 months of follow-up.c) Selecting a discordant control for comparison from among potential discordant controlsd) Modelling drug utilization in the country with the index advisory, and separately for discordant control countrye) Estimating the absolute and relative change in drug utilization due to the advisory