Screening medications for association with progression to wet age-related macular degeneration (AMD)

Abstract: Objective There is an urgent need for treatments that prevent or delay development to advanced age-related macular degeneration (AMD). Drugs already on the market for other conditions could affect progression to nAMD. If identified, these drugs could provide insights for drug development targets. The objective of this study was to use a novel data mining method that can simultaneously evaluate thousands of correlated hypotheses, while adjusting for multiple testing, to screen for associations between drugs and delayed progression to nAMD. Design We applied a nested case-control study to administrative insurance claims data to identify cases with nAMD and risk-set sampled controls that were 1:4 variable ratio matched on age, gender and recent healthcare utilization. Methods We used a tree-based scanning method to evaluate associations between hierarchical classifications of drugs that patients were exposed to within 6 months, 7-24 months, or ever prior to their index date. The index date was the date of first nAMD diagnosis in cases. Risk-set sampled controls were assigned the same index date as the case to whom they were matched. The study was implemented using Medicare data from New Jersey and Pennsylvania, and national data from IBM MarketScan Research Database. We set an a priori threshold for statistical alerting at p ≤ 0.01 and focused on associations with large magnitude (relative risks ≥ 2.0). Results Out of nearly 4,000 generic drugs and drug classes evaluated, the method detected 19 distinct drug exposures with statistically significant, large relative risks indicating that cases were less frequently exposed than controls. These included 1) drugs with prior evidence for a causal relationship (e.g. megestrol), 2) drugs without prior evidence for a causal relationship, but potentially worth further exploration (e.g. donepezil, epoetin alfa), 3) drugs with alternative biologic explanations for the association (e.g. sevelamer), and 4) drugs that may have resulted in statistical alerts due to their correlation with drugs that alerted for other reasons. Conclusions This exploratory drug screening study identified several potential targets for follow up studies to further evaluate and determine if they may prevent or delay progression to advanced AMD.