Risk estimation and value-of-information analysis for three proposed genetic screening programs for chronic beryllium disease prevention

Genetic differences (polymorphisms) among members of a population are thoug ht to influence susceptibility to various environmental exposures. In pract ice, however, this information is rarely incorporated into quantitative ris k assessment and risk management. We describe an analytic framework for pre dicting the risk reduction and value-of-information (VOI) resulting from sp ecific risk management applications of genetic biomarkers, and we apply the framework to the example of occupational chronic beryllium disease (CBD), an immune-mediated pulmonary granulomatous disease. One described Human Leu kocyte Antigen gene variant, HLA-DP beta 1*0201, contains a substitution of glutamate for lysine at position 69 that appears to have high sensitivity (similar to 94%) but low specificity (similar to 70%) with respect to CBD a mong individuals occupationally exposed to respirable beryllium. The expect ed postintervention CBD prevalence rates for using the genetic variant (1) as a required job placement screen, (2) as a medical screen for semiannual in place of annual lymphocyte proliferation testing, or (3) as a voluntary job placement screen are 0.08%, 0.8%, and 0.6%, respectively, in a hypothet ical cohort with 1% baseline CBD prevalence. VOI analysis is used to examin e the reduction in total social cost, calculated as the net value of diseas e reduction and financial expenditures, expected for proposed CBD intervent ion programs based on the genetic susceptibility test. For the example coho rt, the expected net VOI per beryllium worker for genetically based testing and intervention is $13,000, $1,800, and $5,100, respectively, based on a health valuation of $1.45 million per CBD case avoided. VOI results for alt ernative CBD valuations are also presented. Despite large parameter uncerta inty, probabilistic analysis predicts generally positive utility for each o f the three evaluated programs when avoidance of a CBD case is valued at $1 million or higher. Although the utility of a proposed risk management prog ram may be evaluated solely in terms of risk reduction and financial costs, decisions about genetic testing and program implementation must also consi der serious social,legal, and ethical factors.