New user active comparator cohort

Study Type/s

New user active comparator cohort studies are classified as ‘complex’ analyses.

Study Design

New user cohorts.

Participant/s

At least two cohorts, including a cohort of new users of at least one drug/medicinal product under investigation (target cohort) and a cohort of new users of at least one drug/medicinal product as an active comparator (comparator cohort). Typically, new user cohorts exclude previous users of either cohort in the previous year as well as people with <1 year of data visibility before inclusion.

Follow-up

Participants in each cohort will be followed from therapy initiation date (index date). Two possibilities of analyses will be offered:

  • In a ‘fixed’ follow-up analysis, follow-up will continue until death, loss to follow-up or a pre-specified time period (e.g., 3 years) regardless of treatment duration
  • In an ‘on treatment’ analysis, follow-up will continue until treatment cessation, death, or loss of follow-up

Outcome/s

One or more study outcomes will be pre-specified, based on previous DARWIN EU algorithms or newly developed and validated ones.

In addition, a long list of negative control outcomes will be assessed, which are not known to have a causal association with the drug/s or medicinal product/s under study.

Analyses

Details will be discussed during programming of pipelines, but new users cohort analyses will include:

  • Large-scale characterisation of participants in the target and comparator cohorts, including all features available in the data before or on index date
  • Large-scale propensity scores (LSPS) will be estimated as the probability of exposure (target cohort) conditional on all available covariates available in the data with a prevalence >1%. LSPS will be estimated using Lasso regression
  • Incidence rate/s of each of the outcomes of interest in the target and comparator cohorts after LSPS matching, stratification, or inverse probability weighting
  • Diagnostic/s:
    • Covariate balance
    • Equipoise: plots of the distribution of the propensity score stratified by target vs comparator cohort
    • Analyses will not be conducted where there is insufficient data, based on a pre-specified minimum detectable rate ratio (e.g., MDRR>5)
    • Optional: In addition to the two above, residual confounding/systematic error will be available for estimation, as based on the number of negative control outcomes significantly associated with the exposure of interest
  • Rate Ratios or Hazard Ratio/s and 95% confidence intervals will be estimated using Poisson or Cox models respectively, comparing the target vs comparator (reference) cohorts after LSPS matching, stratification, or inverse probability weighting
  • Optionally, calibrated RR or HR will be estimated after empirical calibration using negative control outcomes
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