A non-interventional register-based comparative effectiveness study of rhFSH-alfa reference product vs. highly purified human menopausal gonadotropin or rhFSH-alfa biosimilar products for ovarian stimulation in in vitro fertilization or intracytoplasmic sperm injection treatment in Denmark and Sweden – The Nordic Follitropin Alfa Comparative Effectiveness Study (NORD-FACE)

Study type

• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Effectiveness study (incl. comparative)

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  100000095899

  human menopausal gonadotrophin

  100000095902

  follitropin alfa
• Medical condition to be studied:
  Infertility female

Population studied

• Age groups:
  Adults (18 to < 46 years)

  Adults (46 to < 65 years)
• Estimated number of subjects:
  79000

Study design details

• Main study objective:
  To compare rhFSH-alfa reference product with HP-hMG or rhFSH-alfa biosimilar products regarding live birth outcome measures.
• Outcomes:
  The primary outcome is live birth, measured as live birth rate (LBR) per initiated in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) stimulation cycle, cumulative live birth rate (CLBR) per initiated IVF/ICSI stimulation cycle, and CLBR in up to five initiated IVF/ICSI stimulation cycles (termed multiple-cycle MC-CLBR). The secondary outcomes are clinical pregnancy, ongoing pregnancy, oocytes retrieved, embryos transferred, embryos cryopreserved, utilizable embryos, implantation, pregnancy loss, multiple pregnancy, cycle cancellation, OHSS, and treatment-associated costs.
• Data analysis plan:
  The analysis will be conducted in two stages: (i) construction of inverse probability of treatment weighted (IPTW) study cohorts, by modelling rhFSH-alfa reference product vs. HP-hMG treatment initiation and rhFSH-alfa reference product vs. rhFSH-alfa biosimilar product treatment initiation, (ii) estimation of the effect of rhFSH-alfa reference product on the outcomes, compared with the respective comparator drugs. Descriptive analysis will be conducted to describe the baseline characteristics of the study cohorts. For outcomes, rates per 100 units of observations will be estimated with 95% CIs. Adjusted odds ratios with 95% CIs will be estimated from the statistical model weighted with IPTWs and any variables included in the propensity score (PS) that are still unbalanced between the study cohorts after weighting. The analyses will be conducted for each data source separately and combined using meta-analyses, providing a summary estimate for all data sources.