Study type

Study topic

Human medicinal product

Study type

Non-interventional study

Scope of the study

Assessment of risk minimisation measure implementation or effectiveness

Data collection methods

Secondary use of data
Non-interventional study

Non-interventional study design

Cohort
Study drug and medical condition

Anatomical Therapeutic Chemical (ATC) code

(M03BX07) tetrazepam
tetrazepam
(N03AE01) clonazepam
clonazepam
(N05BA) Benzodiazepine derivatives
Benzodiazepine derivatives
(N05CD) Benzodiazepine derivatives
Benzodiazepine derivatives
(N05CF) Benzodiazepine related drugs
Benzodiazepine related drugs
Population studied

Short description of the study population

The French and the UK adult population, including both genders.
Patients aged 18 and more, patients with First Registration Date or Current Registration Date > 12 months, acceptable Patient Flag (patients records meeting sufficient quality standard for research) (for CPRD), patients whose practice consented for linkage scheme (ONS mortality data available) (for CPRD) were included.

Age groups

  • 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

120000
Study design details

Main study objective

The aim of this project will be to investigate mortality associated with benzodiazepine derivatives or related substances exposure in France and in the UK.

Outcomes

All-cause mortality, Cause-specific mortality

Data analysis plan

The role of potential confounding or explanatory variables will be taken into account by the extended Cox regression model. A univariate analysis will be first performed to select the variables with a p value<0.2, followed by a multivariate approach using the Cox proportional hazard regression model with time dependent covariates, with stratification on the matched pairs. Continuous variables will be tested for linearity. Relevant interactions between covariates will be checked. Proportional hazards assumption will be tested for all covariates. The estimation of the crude and adjusted Hazard Ratio and their 95% confidence interval will be provided.