European Active Surveillance Study of Women Taking Hormone Replacement Therapy (HRT)

• Venous and arterial thromboembolism [ Time Frame: within 6 years ] [ Designated as safety issue: Yes ]
  

The safety of a novel drug product containing a new chemical entity should be assessed in an extensive post marketing safety surveillance program. It is also prudent to assess both, the safety outcomes that relate specifically to the targeted population, as well as those that could potentially be related to the special pharmacological characteristics of the novel drug product. Differentiating between the inherent background population risk and a potential incremental risk due to treatment is often challenging. Active safety surveillance using valid epidemiological study designs has been proven to be a pertinent and reliable method to approach this endeavour.

The primary objective of the study, the European Active Surveillance Study of Women taking HRT (EURAS-HRT), is to compare incidence rates of serious adverse events in users of all types of newly prescribed oral HRT products. This active surveillance study will assess pertinent cardiovascular outcomes in new HRT users over a study period of 3 to 6 years. Also, all other serious adverse events will be reported.

The new drug product under surveillance in the EURAS - HRT study is Angeliq®, which contains the novel synthetic progestagen drospirenone (DRSP) combined with estradiol. In addition, all other oral combined HRT products with a novel progestagen that will be newly marketed during the study period could be included in this study. These new HRT products will be compared with established HRT products.

As estrogen/progestagen combinations increase the risk for thromboembolism, all new drug products that contain a novel estrogen or progestagen should be investigated for their influence on venous and arterial thromboembolic events rates. A large, prospective, controlled cohort study of OC users (EURAS OC study), which compared DRSP-containing OC users with other OC users, demonstrated that DRSP is not associated with an increased incidence for any of the above-mentioned adverse events in OC users. However, because OC users are two to three decades younger than the typical HRT user the results of the OC study can only partially be extrapolated to older age groups.

The combined cohort will include at least 30,000 women recruited in several European countries. At least 90,000 years of observation are expected from the field work which will end around 2010.

The participating women will complete a baseline survey using a self-administered questionnaire to describe the baseline risk. After 6 months, 12 months, and then on an annual basis, they will fill out a questionnaire in which they record complaints and events during the use of the prescribed HRTs. All adverse outcomes (including cancer) occurring during the observational period will be evaluated additionally. Reported serious adverse events will be validated and analyzed.

Based on experience obtained in previous HRT studies, complex sources of bias and confounding are expected. Multivariate methods will therefore be used to adjust for confounding. This study will emphasize absolute as opposed to relative risk estimates.