The authors find that expanded carrier screening is cost effective (defined as less than $50,000 per QALY gained). Find the paper here at Genetics in Medicine, February 2019.
Carrier screening looks to recessive genes with relatively rare frequencies (less than 1 in 50, sometimes less than 1 in 500), so family history is not helpful in selecting genes to be tested. For several years, AMA CPT has provided a code for "Ashkenazi" carrier panel screening, and in January 2019, AMA released CPT code for pan-ethnic carrier panel screening.* The codes are:
81412 - Ashkenazi Jewish associated disorders (e.g. Bloom syndrome, Canavan disease, cystic fibrosis, familial dysautonomia, Fanconi anemia group C, Gaucher disease, Tay-Sachs disease), genomic sequence analysis panel, must include sequencing of at least 9 genes including ASPA, BLM, CFTR, FANCC, GBA, HEXA, IKBKAP, MCOLN1, and SMPD1.
81443 - Genetic testing for inherited conditions (e.g. cystic fibrosis, Ashkenazi Jewish-associated disoders [e.g. Bloom syndrome, Canavan disease, , Fanconi anemia group C, mucolipidosis type VI, Gaucher disease, Tay-Sachs disease], beta hemoglobinopathies, phenylketonuria, galactosemia), must include sequencing of at least 15 genes (e.g. ACADM, ARSA, ASPA, ATP7B, BCKDHA, BCKDHB, BLM, CFTR, DHCR7, FANCC, G6PC, GAA, GALT, GBA, GBE1, HBB, HEXA, IKBKAP, MCOLN1, PAH).I had some contact as a consultant with the code application for 81443, which took several cycles before being accepted by AMA CPT.
Guideline on Carrier Screening
The ACOG guideline was most recently revised in March 2017, stating:
The goal of genetic screening is to provide individuals with meaningful information they can use to guide pregnancy planning based on their personal values. Ethnic-specific, panethnic, and expanded carrier screening are acceptable strategies for prepregnancy and prenatal carrier screening.Beauchamp et al. 2019
The economics paper builds on elaborate genomic database analysis previously published by Counsyl in 2016 (Haque, JAMA 316:734, here.)
The Beauchamp paper uses extensive carrier rate genetic analysis combined with extensive modeling of future costs, since no one has used carrier screening and then observed actual outcomes for decades into the future.
The economics decision tree is relatively easy to understand:
For example, under ECS testing, large gray box at top, the individual may be at-risk for one of the genes (orange) or not (blue). If at risk (orange), then they may be an intervention (blue) or not (orange) - and so on. For intervention rates if a gene was discovered, the authors modeled 77% observed intervention rates, with 50% and 100% used as comparators.
The economics are based on concurrent panel testing for both partners. Arguably (I think) it can be even a bit more cost-effective to test one partner, and if negative for a recessive gene, stop. Had this approach been use (I think) the economic results would have trended only better.
In their Table 1, the authors present disease costs. For example, the Duchenne/Becker muscular dystrophy track has a recessive frequency (of conception) of 1:3374, lifetime cost of $1.1M, year 0-3 cost of $53,737, and year 0-1 cost of $7013. This gives weighted lifetime, 3 year, and 1 year costs of $345, $16, and $2. 1- and 3-year cost returns were considered relevant to commercial health plans. Remember, that is just one of the many conditions modeled, so it is just one track of the full cost/QALY analyses.
Most models produced 3-year cost/QALY as below $50,000, and cost/QALY was similar to BRCA testing in adults (see their Figure 2).
Understandably, cost effectiveness was stronger when lower test prices were used ($500, $1000, and $2000 were modeled).
* The code was passed in May 2017, making it too late for the January 2018 annual CPT book. It went through the summer 2018 CMS crosswalk process, with CMS pricing finalized in November 2018. The code was first published for the 2019 CPT book. Note that CMS gapfills or crosswalks all new lab CPT codes, whether they are likely to have Medicare use or coverage or not.