Innovations in Post-Marketing Safety Research

This thesis proposes ways of improving drug safety during the post-marketing phase and underlines the importance of proactive pharmacovigilance. Regulations require that the pharmaceutical industry establishes pharmacovigilance systems to monitor the safety of their products. Currently there are gaps in the safety net, made manifest by the number of market withdrawals due to safety reasons and the impact of serious adverse drug reactions post-marketing. More effective methods need to be developed to identify serious adverse drug reactions at an earlier stage and to facilitate decision-making. The studies in this thesis identify several ways to use available data more efficiently; like using information about same class drugs, establishing trial databases for post-hoc analysis and limiting uncertainties regarding off-label use by making use of patient characteristics. Furthermore, we propose a Bayesian approach to combine data from clinical trials and observational studies to aid decision-making. New ways of looking at available information and methods for combining this data can be used to make appropriate pharmacovigilance decisions by both the industry and regulators.

Results

• Innovations in Post-Marketing Safety Research (thesis)
• Stefansdottir G, Zoungas S, Chalmers J, Kengne AP, Knol MJ, Leufkens HG, Patel A, Woodward M, Grobbee DE, De Bruin ML. Intensive glucose control and risk of cancer in patients with type 2 diabetes. In: Diabetologia, 2011; 54(7): 1608-14. (journal publication)
• Stefansdottir G, De Bruin ML, Knol MJ, Grobbee DE, Leufkens HG. Randomized controlled trials of COX-2 inhibitors: an analysis of doses used and trends over time to investigate implications for comparative safety. In: Medicine Saf, 2011; 34(9): 783-92. (journal publication)
• Stefansdottir G, Knol MJ, Arnardottir AH, Van der Elst ME, Grobbee DE, Leufkens HG, et al. Safety learning from medicines of the same class: room for improvement. In: Clin Pharmacol Ther, 2012; 91(5): 872-80. (journal publication)
• Stefansdottir G, Zoungas S, Chalmers J, Knol MJ, Leufkens HG, Patel A, et al. The post-hoc use of randomized controlled trials to explore drug associated cancer outcomes: Methodological challenges. In: Current Drug Safety, 2013. (journal publication)