Oncology orphan drugs: An evidence assessment, network meta-analysis, and cost-effectiveness analysis

Background;Approximately 1/3 of recently approved drugs in the United States (U.S.) were indicated for rare diseases (orphan drugs). Oncology indications comprised the largest sub-category. Overall, orphan drugs have not been well-studied and there is greater uncertainty about their value when compared to drugs for common diseases.;Objective;To critically assess the comparative effectiveness data supporting oncology orphan drugs marketed in the U.S. and to evaluate the clinical and economic value of therapies indicated for chronic lymphocytic leukemia (CLL).;Methods;I performed a systematic literature review to identify the level of evidence supporting 47 oncology orphan drugs marketed in the U.S. and applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework and Quality of Health Economic Studies (QHES) instrument to review the quality of evidence. I conducted a network meta-analysis using a Bayesian statistical approach to estimate the relative treatment effect of therapies for treatment-naive CLL. Lastly, I conducted a cost-effectiveness analysis of salvage therapies for double-refractory CLL. The analysis was performed from a U.S. healthcare payer perspective and used a decision analytic model to estimate life expectancy, quality-adjusted life years (QALYs), and costs over a lifetime horizon.;Results;Results from the systematic literature review and evidence assessment showed that oncology orphan drugs marketed in the U.S. have varying levels and quality of clinical evidence and a paucity of evidence demonstrating their economic value. Network meta-analysis method is useful for synthesizing available evidence and estimating relative treatment effects of competing therapies in the absence of head-to-head trials. However, because the method is based on model simulation, clinical validation of results is necessary. Based on limited clinical evidence and lack of explicit reimbursement policies for orphan drugs, it is uncertain if ofatumumab would be considered cost-effective for treatment of double-refractory CLL.;Conclusion;Current levels of evidence for oncology orphan drugs may not be sufficient to support decision-making practices consistent with evidence-based medicine. Innovative analytic and policy approaches are needed in order to implement a value assessment framework for orphan drugs that is consistent with principles of comparative effectiveness research.