| Drug approval regulations for market-entry often only require that medications be proven efficacious compared to placebo. This drug approval policy creates a gap in information for clinicians and policy makers to make informed decisions between treatment options. Comparative effectiveness research seeks to address these knowledge gaps, primarily through the use of administrative data and network meta-analysis (NMA). The use of bisphosphonates for the treatment of osteoporosis is representative of this problem. In Canada, there are currently four approved bisphosphonates indicated for the treatment of osteoporosis. This thesis is comprised of three unique projects contributing to comparative effectiveness research of bisphosphonate therapy. The projects address methodological gaps in the development and uses of the disease risk score (DRS), a confounder summary score, and clinical gaps in the comparative safety of bisphosphonates leveraging NMA methodology. The methodological findings of the thesis raise caution towards the standard practice of applying the DRS in situations where policy-induced bias is present, suggest the need for more consistent nomenclature for the DRS, and points to future areas for development of the DRS. The clinical findings of the thesis demonstrate little difference in serious adverse events between oral bisphosphonates. Future research should address questions related to the impact of comparative safety and adherence of bisphosphonates. Overall, this dissertation addresses important gaps in utilization and applications of the DRS, implications of policy-induced selection bias, and comparative safety and adherence of bisphosphonate therapy. |
