PRM7 - Prospective Benefit-Risk Monitoring Of New Drugs For Rapid Assessment Of Net Favorability In Electronic Healthcare Data

Abstract

Benefit-risk assessment (BRA) methods can combine measures of benefits and risks into a single value. We examined BRA metrics for prospective monitoring of new drugs in electronic healthcare data. Using two databases, we emulated prospective monitoring of three drugs versus comparators (rofecoxib vs. non-selective non-steroidal anti-inflammatory drugs [ns-NSAIDs], prasugrel versus clopidogrel, and denosumab versus bisphosphonates) beginning at market entry of each drug of interest and using a sequential propensity score matched cohort design. We applied four BRA metrics: number needed to treat and number needed to harm (NNT|NNH); incremental net benefit (INB) with maximum acceptable risk [MAR], INB with relative-value adjusted life years [RVALYs], and INB with quality-adjusted life years [QALYs]. We determined whether and when the bootstrapped 99% confidence interval (CI) for each metric excluded zero, indicating net favorability of one drug over the other. For rofecoxib, all four metrics yielded a negative value, suggesting net favorability of ns-NSAIDs over rofecoxib, and the 99% CI for all but the NNT|NNH excluded the null during follow-up. For prasugrel, only the 99% CI for INB-QALY excluded the null, but trends in values over time were similar across the four metrics, suggesting overall net favorability of prasugrel versus clopidogrel. The 99% CI for INB-RVALY and INB-QALY excluded the null in the denosumab example, suggesting net favorability of denosumab over bisphosphonates. Prospective benefit-risk monitoring can be used to determine net favorability of a new drug in electronic healthcare data. In three examples, existing BRA metrics produced qualitatively similar results but differed with respect to alert generation. INB-QALY produced the most conclusive findings across the three examples.