Use of national disease registries in the conduct of long-term post-authorisation drug safety studies (LTSSs)

Background: When drugs receive marketing authorisation by regulatory authorities additional surveillance to establish more comprehensive and long-term safety profiles are increasingly a condition of approval. In orphan diseases such as CF, this can be problematic as it may take considerable time to establish a large cumulative post marketing safety experience. The UK CF Registry (UKCFR) represents one of the most mature databases in Europe, with data from more than 10000 patients. Methods: The UKCFR has developed a successful Model for partnership with industry to conduct LTSSs, using existing infrastructure. The model is aimed at improving the safety of medicines and the quality of pharmacovigilance. The unique strength and contribution of registry studies is the ability to compare exposed and unexposed patients in cohorts matched for key characteristics. The Model comprises: High quality data, CF Specialist Lead Investigators; independent study design and analysis input from Imperial College London and robust service agreements between the Cystic Fibrosis Trust, host of the UKCFR, and the companies. As an example of the power of registry studies, disease progression results are cited from 1 of 3 current LTSS. Results: Ivacaftor (IVA) (N=277) and Comparison (COMP) (N=1365) pts matched on genotype severity, age, and sex, were similar in lung function and medication use in 2012 (year prior to IVA commercial availability in UK). Mean ppFEV 1 change from 2012 to 2014 was +6.6 in IVA vs -1.5 in COMP pts. Mean BMI increase was 1.5 for IVA vs 0.3 for COMP pts. Conclusions: Disease Registries are important resources for conducting meaningful longitudinal studies on drug exposure.