Severe combined immunodeficiency (SCID) is a condition that often results in severe infections and death at young age. Early detection shortly after birth, followed by treatment before infections occur, largely increases the chances of survival. As the incidence of SCID is low, assessing cost-effectiveness of adding screening for SCID to the newborn screening program is relevant for decision making. Lifetime costs and effects of newborn screening for SCID were compared to a situation without screening in the Netherlands in a decision analysis model. Model parameters were based on literature and expert opinions. Sensitivity analyses were performed. Due to earlier detection, the number of deaths due to SCID per 100,000 children was assessed to decrease from 0.57 to 0.23 and a number of 11.7 quality adjusted life-years (QALYs) gained was expected. Total yearly healthcare costs, including costs of screening, diagnostics, and treatment, were €390,800 higher in a situation with screening compared to a situation without screening, resulting in a cost-utility ratio of €33,400 per QALY gained.
Conclusion: Newborn screening for SCID might be cost-effective. However, there is still a lot of uncertainty around the cost-effectiveness estimate. Pilot screening projects are warranted to obtain more accurate estimates for the European situation.
|What is Known:|
• Severe combined immunodeficiency (SCID) is a condition that often results in severe infections and death at a young age.
• As the incidence of SCID is low, assessing cost-effectiveness of adding screening for SCID to the newborn screening program is needed.
What is New:
• Newborn screening for SCID is expected to reduce mortality from 0.57 to 0.23 per 100,000 children at additional healthcare costs of €390,800. The cost-utility ratio is €33,400 per QALY gained.
• Due to large uncertainty around cost-effectiveness estimates, pilot screening projects are warranted for Europe.
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Severe combined immunodeficiency
Hematopoietic stem cell transplantation
T cell receptor excision circle
Quality adjusted life-year
Newborn screening for SCID
Graft versus host disease
Adams SP, Rashid S, Premachandra T, Harvey K, Ifederu A, Wilson MC et al (2014) Screening of neonatal UK dried blood spots using a duplex TREC screening assay. J Clin Immunol 34(3):323–330
Aiuti A, Grazia Roncarolo M, Naldini L (2017) Gene therapy for ADA-SCID, the first marketing approval of an ex vivo gene therapy in Europe: paving the road for the next generation of advanced therapy medicinal products. EMBO Mol Med 9(6):737–740
Blom M, Pico-Knijnenburg I, Sijne-van Veen M, Boelen A, Bredius RGM, van der Burg M, Schielen PCJI (2017) An evaluation of the TREC assay with regard to the integration of SCID screening into the Dutch newborn screening program. Clin Immunol 180:106–110. https://doi.org/10.1016/j.clim.2017.05.007
Brown L, Xu-Bayford J, Allwood Z, Slatter M, Cant A, Davies EG, Veys P, Gennery AR, Gaspar HB (2011) Neonatal diagnosis of severe combined immunodeficiency leads to significantly improved survival outcome: the case for newborn screening. Blood 117(11):3243–3246
Buckley RH (2012) The long quest for neonatal screening for severe combined immunodeficiency. J Allergy Clin Immunol 129(3):597–604
Cameron D, Ubels J, Norström F (2018) On what basis are medical cost-effectiveness thresholds set? Clashing opinions and an absence of data: a systematic review. Glob Health Action 11(1):1447828. https://doi.org/10.1080/16549716.2018.1447828 Review
Chan K, Davis J, Pai SY, Bonilla FA, Puck JM, Apkon M (2011) A Markov model to analyze cost-effectiveness of screening for severe combined immunodeficiency(SCID). Mol Genet Metab 104(3):383–389
Chan A, Scalchunes C, Boyle M, Puck JM (2011) Early vs. delayed diagnosis of severe combined immunodeficiency: a family perspective survey. Clin Immunol 138(1):3–8
Chien Y, Chiang S, Chang K, Yu H, Lee W, Tsai L et al (2015) Incidence of severe combined immunodeficiency through newborn screening in a Chinese population. J Formos Med Assoc 114(1):12–16
Clément MC, Mahlaoui N, Mignot C, Le Bihan C, Rabetrano H, Hoang L, Neven B, Moshous D, Cavazzana M, Blanche S, Fischer A, Audrain M, Durand-Zaleski I (2015) Systematic neonatal screening for severe combined immunodeficiency and severe T-cell lymphopenia: analysis of cost-effectiveness based on French real fielddata. J Allergy Clin Immunol 135(6):1589–1593
de Pagter AP, Bredius RG, Kuijpers TW, Tramper J, van der Burg M, van Montfrans J, Driessen GJ, Dutch working party for Immunodeficiencies (2015) Overview of 15-year severe combined immunodeficiency in the Netherlands: towards newborn blood spot screening. Eur J Pediatr 174:1183–1188
Ding Y, Thompson JD, Kobrynski L, Ojodu J, Zarbalian G, Grosse SD (2016) Cost-effectiveness/cost-benefit analysis of newborn screening for severe combined immune deficiency in Washington state. J Pediatr 172:127–135
European Network for Health Technology Assessment [EUnetHTA] (2015) Methods for health economic evaluations—a guideline based on current practices in Europe. https://www.eunethta.eu/wp-content/uploads/2018/03/Methods_for_health_economic_evaluations.pdf
Ferrua F, Aiuti A (2017) Twenty-five years of gene therapy for ADA-SCID: from bubble babies to an approved drug. Hum Gene Ther 28(11):972–981. https://doi.org/10.1089/hum.2017.175
Heimall J, Cowan MJ (2017) Long term outcomes of severe combined immunodeficiency: therapy implications. Expert Rev Clin Immunol 13(11):1029–1040
Heimall J, Logan BR, Cowan MJ, Notarangelo LD, Griffith LM, Puck JM, Kohn DB, Pulsipher MA, Parikh S, Martinez C, Kapoor N, O'Reilly R, Boyer M, Pai SY, Goldman F, Burroughs L, Chandra S, Kletzel M, Thakar M, Connelly J, Cuvelier G, Davila Saldana BJ et al (2017) Immune reconstitution and survival of 100 SCID patients post-hematopoietic cell transplant: a PIDTC natural history study. Blood 130(25):2718–2727
Kanters TA, Bouwmans CAM, van der Linden N, Tan SS, Hakkaart-van Roijen L (2017) Update of the Dutch manual for costing studies in health care. PLoS One 12(11):e0187477. https://doi.org/10.1371/journal.pone.0187477
Koopmanschap MA, Rutten FFH, Van Ineveld BM, Van Roijen L (1995) The friction cost method for measuring indirect costs of disease. J Health Econ 14:171–189
Kwan A, Church JA, Cowan MJ, Agarwal R, Kapoor N, Kohn DB et al (2013) Newborn screening for severe combined immunodeficiency and T-cell lymphopenia in California: Results of the first 2 years. J Allergy Clin Immunol 132(1):140–150.e7
Kwan A, Abraham RS, Currier R, Brower A, Andruszewski K, Abbott JK, Baker M, Ballow M, Bartoshesky LE, Bonilla FA, Brokopp C, Brooks E, Caggana M, Celestin J, Church JA, Comeau AM, Connelly JA, Cowan MJ, Cunningham-Rundles C, Dasu T, Dave N, de la Morena MT, Duffner U, Fong CT, Forbes L, Freedenberg D, Gelfand EW, Hale JE, Hanson IC, Hay BN, Hu D, Infante A, Johnson D, Kapoor N, Kay DM, Kohn DB, Lee R, Lehman H, Lin Z, Lorey F, Abdel-Mageed A, Manning A, McGhee S, Moore TB, Naides SJ, Notarangelo LD, Orange JS, Pai SY, Porteus M, Rodriguez R, Romberg N, Routes J, Ruehle M, Rubenstein A, Saavedra-Matiz CA, Scott G, Scott PM, Secord E, Seroogy C, Shearer WT, Siegel S, Silvers SK, Stiehm ER, Sugerman RW, Sullivan JL, Tanksley S, Tierce ML 4th, Verbsky J, Vogel B, Walker R, Walkovich K, Walter JE, Wasserman RL, Watson MS, Weinberg GA, Weiner LB, Wood H, Yates AB, Puck JM, Bonagura VR (2014) Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States. JAMA 312(7):729–738. https://doi.org/10.1001/jama.2014.9132
McGhee SA, Stiehm ER, McCabe ER (2005) Potential costs and benefits of newborn screening for severe combined immunodeficiency. J Pediatr 147(5):603–608
Myers LA, Patel DD, Puck JM, Buckley RH (2002) Hematopoietic stem cell transplantation for severe combined immunodeficiency in the neonatal period leads to superior thymic output and improved survival. Blood 99(3):872–878
Pai S-Y, Logan BR, Griffith LM, Buckley RH, Parrott RE, Dvorak CC, Kapoor N, Hanson IC, Filipovich AH, Jyonouchi S, Sullivan KE, Small TN, Burroughs L, Skoda-Smith S, Haight AE, Grizzle A, Pulsipher MA, Chan KW, Fuleihan RL, Haddad E, Loechelt B, Aquino VM, Gillio A, Davis J, Knutsen A, Smith AR, Moore TB, Schroeder ML, Goldman FD, Connelly JA, Porteus MH, Xiang Q, Shearer WT, Fleisher TA, Kohn DB, Puck JM, Notarangelo LD, Cowan MJ, O'Reilly RJ (2014) Transplantation outcomes for severe combined immunodeficiency, 2000-2009. N Engl J Med 371(5):434–446
Puck JM (2012) Laboratory technology for population-based screening for severe combined immunodeficiency in neonates: the winner is T-cell receptor excision circles. J Allergy Clin Immunol 129(3):607–616. https://doi.org/10.1016/j.jaci.2012.01.032
Sanders GD, Neumann PJ, Basu A, Brock DW, Feeny D, Krahn M, Kuntz KM, Meltzer DO, Owens DK, Prosser LA, Salomon JA, Sculpher MJ, Trikalinos TA, Russell LB, Siegel JE, Ganiats TG (2016) Recommendations for conduct, methodological practices, and reporting of cost-effectiveness analyses: second panel on cost-effectiveness in health and medicine. JAMA 316(10):1093–1103
Schwarzer R, Rochau U, Saverno K, Jahn B, Bornschein B, Muehlberger N, Flatscher-Thoeni M, Schnell-Inderst P, Sroczynski G, Lackner M, Schall I, Hebborn A, Pugner K, Fehervary A, Brixner D, Siebert U (2015) Systematic overview of cost-effectiveness thresholds in ten countries across four continents. J Comp Eff Res 4(5):485–504. https://doi.org/10.2217/cer.15.38.
Shearer WT, Dunn E, Notarangelo LD, Dvorak CC, Puck JM, Logan BR, Griffith LM, Kohn DB, O'Reilly RJ, Fleisher TA, Pai SY, Martinez CA, Buckley RH, Cowan MJ (2014) Establishing diagnostic criteria for severe combined immunodeficiency disease (SCID), leaky SCID, and Omenn syndrome: the Primary Immune Deficiency Treatment Consortium experience. J Allergy Clin Immunol 133(4):1092–1098. https://doi.org/10.1016/j.jaci.2013.09.044
van den Berg M, de Wit GA, Vijgen SCM, Busch MCM, Schuit AJ (2008) Kosteneffectiviteit van preventie: kans voor het Nederlandse volksgezondheidsbeleid. Ned Tijdschr Geneeskd 152:1329–1334
Van der Ploeg CPB, Lanting CI, Kauffman-de Boer MA, Uilenburg NN, de Ridder-Sluiter JG, Verkerk PH (2008) Examination of long-lasting parental concern after false-positive results of neonatal hearing screening. Arch Dis Child 93:508–511
Van der Spek J, Groenwold RHH, van der Burg M, van Montfrans JM (2015) TREC based newborn screening for severe combined immunodeficiency disease: a systematic review. J Clin Immunol 35(4):416–430
Verbsky JW, Baker MW, Grossman WJ, Hintermeyer M, Dasu T, Bonacci B, Reddy S, Margolis D, Casper J, Grties M, DeSantes K, Hoffman GL, Brokopp CD, Seroogy CM, Routes JM (2012) Newborn screening for severe combined immunodeficiency; The Wisconsin experience (2008–2011). J Clin Immunol 32(1):82–88
Versteegh M, Knies S, Brouwer W (2016) From good to better: new Dutch guidelines for economic evaluations in healthcare. PharmacoEconomics 34:1071–1074. https://doi.org/10.1007/s40273-016-0431-y
Vogel BH, Bonagura V, Weinberg GA, Ballow M, Isabelle J, Diantonio L et al (2014) Newborn screening for SCID in New York state: experience from the first two years. J Clin Immunol 34(3):289–303
Yee A, De Ravin SS, Elliott E, Ziegler JB (2008) Severe combined immunodeficiency: a national surveillance study. Pediatr Allergy Immunol 19(4):298–302
The decision analysis model used to calculate cost-effectiveness of NBSSCID in this study is an extension of a model kindly provided by Scott Grosse and Yao Ding. We thank Frank Staal, Arjan Lankester, Georget van den Burg, Mandy Jansen, Taco Kuijpers, Joris van Montfrans, and Wendy Rodenburg for their contribution as experts to this study.
Funding for this project was obtained from the National Institute for Public Health and the Environment in the Netherlands (Centre for Population Screening) in order to prepare implementation of NBSSCID in the Netherlands.
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Communicated by Mario Bianchetti
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Van der Ploeg, C.P.B., Blom, M., Bredius, R.G.M. et al. Cost-effectiveness of newborn screening for severe combined immunodeficiency. Eur J Pediatr 178, 721–729 (2019). https://doi.org/10.1007/s00431-019-03346-3
- Newborn screening
- Severe combined immunodeficiency
- Cost-effectiveness analysis
- Decision analysis model