International Active Surveillance study - Folate and Oral Contraceptive Utilization Study (INAS-FOCUS)

Study type

• Study topic:
  Disease /health condition

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

  Drug utilisation

  Effectiveness study (incl. comparative)
• Data collection methods:
  Primary data collection

Non-interventional study

• Non-interventional study design:
  Cohort

  Other
• Non-interventional study design, other:
  Large, transatlantic, prospective, non-interventional, long-term cohort study, intensive monitoring schemes

Study drug and medical condition

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

  DIENOGEST

  ETHINYLESTRADIOL

  FOLIC ACID
• Medical condition to be studied:
  Thrombosis

  Acute myocardial infarction

  Ischaemic stroke

  Oral contraception

  Pregnancy on oral contraceptive

Population studied

• Short description of the study population:
  The study participants are women who; • are new users of an OC (first ever use, recurrent use with and without pill break); • are willing to participate in this long-term follow-up study Women will be categorized into three different groups depending on OC-user characteristics. These groups have been previously found to be important in assessing cardiovascular risk. The groups are defined as 1) OC starters (firsttime users), 2) recurrent users with a break (re-starters and switchers with a break) and 3) recurrent users without a pill-intake break.; There are no specific medical inclusion or exclusion criteria. However, women; • who are not cooperative/available for follow-up may be excluded from study participation; • with a language barrier will not be eligible for study inclusion
• Age groups:
  Adolescents (12 to < 18 years)

  Adults (18 to < 46 years)

  Adults (46 to < 65 years)
• Special population of interest:
  Women of childbearing potential not using contraception

  Women of childbearing potential using contraception
• Estimated number of subjects:
  80000

Study design details

• Main study objective:
  To assess the risks of short and long-term use of DRSP/EE plus 451mcg of metafolin and of established OCs in a study population that is representative for the actual users of the individual preparations. The main clinical outcomes are:1. Venous thromboemobolic events2. Acute myocardial infaction3. C
• Outcomes:
  The primary variable for inferential statistics is VTE. The null hypothesis to be tested is that the VTE hazard ratio for DRSP/EE/metafolin compared to established OCs is higher or equal to two.The risk of Cerebrovascular accidents will also be assessed and primary outcomes of interest with a similar non-inferiority design. Analyse the drug utilization patterns of OCs under routine medical conditionsCharacterise the baseline risk of users of individual formulationsEstablish risks of OCs in adolescent populationsInvestigate pregnancy related data on discontinuation of OCsCharacterise folate intake of users of OCsColorectal CancerOther Cancer entities
• Data analysis plan:
  The study is designed to analyse rare and very rare events (less than 1/10,000WY). VTE and ATE prevalence estimates are based on the EURAS-OC results. A non-inferiority approach will be used for all hypothesis.Adjusted and Crude Hazard ratios will be provided for all primary outcomes with stratification of women into user categories (new, re-starter or switcher (with or without break). The adjusted model will be based on known risk factors for VTE and ATE.A detailed statistical analysis plan will be developed by the Principal Investigator during the first year after study start. The final analysis plan will be approved by the Safety Monitoring and Advisory Council before the first interim analysis of follow-up data.

Documents

Study results

IFOC_FinalStudyReport_Public Version 20200819