Mapping the Value for Money of Precision Medicine: A Systematic Literature Review and Meta-Analysis

OBJECTIVES: The cost and effectiveness of precision medicine (PM) are the biggest concerns affecting its clinical adoption. This study aimed to summarise the magnitude of cost-effectiveness of PM and quantify sources of heterogeneity.

METHODS: We performed a systematic literature review of cost-effectiveness analysis (CEA) of PM between Jan 1, 2011 and July 8, 2021, and extracted data including incremental quality-adjusted life-years and incremental costs. Based on a willingness-to-pay threshold of one-time gross domestic product per capita of each study country, we calculated incremental net monetary benefit (INB). We estimated the pooled INB with random-effects meta-analyses, and studied heterogeneity and biases with random-effects meta-regressions and jackknife sensitivity analyses.

RESULTS: We identified 5187 unique references and included 275 CEAs with 463 datasets in the meta-analyses. Genetic testing appeared very cost-effective if it was a screening, diagnostic or companion test (pooled INBs, $48,152, $8,869, $5,693, p-values<0.001), in the form of multigene panel testing, single gene profiling and whole genome sequencing (pooled INBs, $31,026, $3,893, $2,429, p<0.001), and applied in Americas and Europe (pooled INBs, $44,972, $5,005, p<0.001). However, the pooled INBs of various genetic test types were specific to disease domains, and incremental effectiveness was the most important predictor of INBs across genetic test types in meta-regressions. Other essential predictors of variability in INBs included target age and sex, model perspective and type, test accuracy, treatment compliance, quality of cost data and study bias. On the other hand, gene therapy was unlikely to be cost-effective (pooled INB, $125,000, 95% CI -914,000 to 1,160,000) unless it was part of early-stage evaluation (i.e. hypothetical intervention), or funded by for-profit private sectors.

CONCLUSIONS: Genetic testing in particular screening, diagnostic and companion tests is likely cost-effective, but the value for money is sensitive to disease domains and influenced by test-treatment effectiveness and certain local conditions.