Alpha-1 antitrypsin (AAT) deficiency is a genetic disorder that may predispose to early-onset emphysema and to liver disease. The availability of effective interventions (such as primary avoidance of smoking, smoking cessation, and augmentation therapy) invites the question of whether early detection of alpha-1 antitrypsin deficiency is cost-effective, both through population-based screening or case-finding. Because no randomized controlled trials of population-based screening for alpha-1 antitrypsin deficiency is available or likely to be, the current study was undertaken to examine the cost-effectiveness of screening for AAT deficiency.
A Markov-based decision model was created to assess the cost-effectiveness of population screening for alpha-1 antitrypsin (AAT) deficiency, comparing strategies of: 1) screen all newborns, 2) screen all 10 year-old children, and 3) do not screen. Hypothetical cohorts were analyzed from birth and followed over time until death using Monte Carlo simulation. Screenees found to have PI*ZZ AAT deficiency received the benefits of lower smoking rates and were offered augmentation therapy. In keeping with reported experience, most (96%) non-screened AAT deficient individuals remained undiagnosed and, therefore, missed these benefits.
Screening all newborns cost nearly $422,000 per quality-adjusted life-year (QALY) gained. Delaying screening until age 10 decreased the incremental cost-effectiveness ratio (ICER) to nearly $317,000. In sensitivity analysis, when the prevalence of PI*ZZ individuals increased from a baseline of 1.96 to 16 per 10,000, the ICER for newborn screening decreased below $100,000 per QALY. When the cost of screening and augmentation therapy were decreased simultaneously with increasing PI*ZZ prevalence, there were many scenarios in which the ICER decreased below $50,000.
We conclude that while population-based screening for AAT deficiency is not cost-effective under current conditions, cost-effectiveness criteria could be satisfied when case-finding in a high prevalence population is undertaken.
The current study advances understanding of the advisability of population-based screening and can serve as a model for the broader consideration of screening for other genetic conditions.
T.R. Gildea, None.