Research

16 pages, 2384 KiB

Open AccessArticle

Modelling the Cost-Effectiveness and Budget Impact of a Newborn Screening Program for Spinal Muscular Atrophy and Severe Combined Immunodeficiency

by Sophy T. F. Shih, Elena Keller, Veronica Wiley, Michelle A. Farrar, Melanie Wong and Georgina M. Chambers

Int. J. Neonatal Screen. 2022, 8(3), 45; https://doi.org/10.3390/ijns8030045 - 20 Jul 2022

Cited by 9 | Viewed by 3681

Abstract

Spinal muscular atrophy (SMA) and severe combined immunodeficiency (SCID) are rare, inherited genetic disorders with severe mortality and morbidity. The benefits of early diagnosis and initiation of treatment are now increasingly recognized, with the most benefits in patients treated prior to symptom onset. [...] Read more.

Spinal muscular atrophy (SMA) and severe combined immunodeficiency (SCID) are rare, inherited genetic disorders with severe mortality and morbidity. The benefits of early diagnosis and initiation of treatment are now increasingly recognized, with the most benefits in patients treated prior to symptom onset. The aim of the economic evaluation was to investigate the costs and outcomes associated with the introduction of universal newborn screening (NBS) for SCID and SMA, by generating measures of cost-effectiveness and budget impact. A stepwise approach to the cost-effectiveness analyses by decision analytical models nested with Markov simulations for SMA and SCID were conducted from the government perspective. Over a 60-year time horizon, screening every newborn in the population and treating diagnosed SCID by early hematopoietic stem cell transplantation and SMA by gene therapy, would result in 95 QALYs gained per 100,000 newborns, and result in cost savings of USD 8.6 million. Sensitivity analysis indicates 97% of simulated results are considered cost-effective against commonly used willingness-to-pay thresholds. The introduction of combined NBS for SCID and SMA is good value for money from the long-term clinical and economic perspectives, representing a cost saving to governments in the long-term, as well as improving and saving lives. Full article

(This article belongs to the Special Issue Newborn Screening for Spinal Muscular Atrophy)

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7 pages, 533 KiB

Open AccessArticle

New-Born Screening for Spinal Muscular Atrophy: Results of a Latvian Pilot Study

by Linda Gailite, Olga Sterna, Maija Konika, Aleksejs Isakovs, Jekaterina Isakova, Ieva Micule, Signe Setlere, Mikus Diriks and Madara Auzenbaha

Int. J. Neonatal Screen. 2022, 8(1), 15; https://doi.org/10.3390/ijns8010015 - 14 Feb 2022

Cited by 10 | Viewed by 3679

Abstract

New disease-modifying treatments have recently been approved for 5q spinal muscular atrophy (SMA) and early treatment has been associated with a better clinical outcome. Accordingly, new-born screening (NBS) for SMA should be implemented to ensure early diagnosis of affected individuals. The aim of [...] Read more.

New disease-modifying treatments have recently been approved for 5q spinal muscular atrophy (SMA) and early treatment has been associated with a better clinical outcome. Accordingly, new-born screening (NBS) for SMA should be implemented to ensure early diagnosis of affected individuals. The aim of this study was to determine the feasibility and usefulness of NBS for SMA in Latvia. Between February and November of 2021, 10,411 parents consented to participation in the study. DNA testing for the SMN1 exon 7 homozygous deletion was conducted using qPCR with fluorescent locked nucleic acid primers. In the first month of testing, reporting of results took up to a maximum of 17 days after samples arrived in the laboratory. However, following familiarisation with the procedure, the median report time was reduced to 11 days after birth. Forty cases required samples to be taken again due to poor quality of the isolated DNA transpiring from either the quality of the blood punch or manual mistakes during DNA isolation. The SMN1 exon 7 homozygous deletion was identified in two individuals, which was subsequently confirmed by multiplex ligation-dependent probe amplification. When a NBS sample is taken 48 to 72 h after birth and transported to the laboratory within two working days after collection according to legal requirements, DNA test results can be reported to healthcare professionals before the 12th day of life. Expansion of our SMA 5q NBS procedure to the whole of Latvia is feasible and would facilitate early diagnosis and result in more effective treatment. We strongly advocate that SMA is added to the national Latvia Recommended Uniform Screening Panel. Full article

(This article belongs to the Special Issue Newborn Screening for Spinal Muscular Atrophy)

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6 pages, 1018 KiB

Open AccessCommunication

Screening of Neonatal UK Dried Blood Spots Using a Duplex SMN1 Screening Assay

by Stuart P. Adams, Emma Gravett, Natalie Kent, Susanne Kricke, Adeboye Ifederu, Mariacristina Scoto, Salma Samsuddin and Francesco Muntoni

Int. J. Neonatal Screen. 2021, 7(4), 69; https://doi.org/10.3390/ijns7040069 - 26 Oct 2021

Cited by 1 | Viewed by 3133

Abstract

Spinal muscular atrophy (SMA) is an autosomal inherited neuromuscular genetic disease caused, in 95% of cases, by homozygous deletions involving the SMN1 gene exon 7. It remains the leading cause of death in children under 2 years of age. New treatments have been [...] Read more.

Spinal muscular atrophy (SMA) is an autosomal inherited neuromuscular genetic disease caused, in 95% of cases, by homozygous deletions involving the SMN1 gene exon 7. It remains the leading cause of death in children under 2 years of age. New treatments have been developed and adopted for use in many countries, including the UK. Success of these treatments depends on early diagnosis and intervention in newborn babies, and many countries have implemented a newborn screening (NBS) or pilot NBS program to detect SMN1 exon 7 deletions on dried blood spots. In the UK, there is no current NBS program for SMA, and no pilot studies have commenced. For consideration of adoption of NBS for a new condition, numerous criteria must be satisfied, including critical assessment of a working methodology. This study uses a commercially available real-time PCR assay to simultaneously detect two different DNA segments (SMN1 exon 7 and control gene RPP30) using DNA extracted from a dried blood spot. This study was carried out in a routine clinical laboratory to determine the specificity, sensitivity, and feasibility of SMA screening in a UK NBS lab setting. Just under 5000 normal DBSs were used alongside 43 known SMA positive DBSs. Study results demonstrate that NBS for SMA using real-time PCR is feasible within the current UK NBS Laboratory infrastructure using the proposed algorithm. Full article

(This article belongs to the Special Issue Newborn Screening for Spinal Muscular Atrophy)

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12 pages, 1391 KiB

Open AccessArticle

Newborn Screening for 5q Spinal Muscular Atrophy: Comparisons between Real-Time PCR Methodologies and Cost Estimations for Future Implementation Programs

by Vanessa Luiza Romanelli Tavares, Frederico Monfardini, Naila Cristina Vilaça Lourenço, Katia Maria da Rocha, Karina Weinmann, Rita Pavanello and Mayana Zatz

Int. J. Neonatal Screen. 2021, 7(3), 53; https://doi.org/10.3390/ijns7030053 - 11 Aug 2021

Cited by 7 | Viewed by 3865

Abstract

Since the approval of modifying therapies for Spinal Muscular Atrophy (SMA), several protocols aiming to screen SMN1 homozygous deletion in a neonatal context have been published. However, no work has compared different methodologies along with detailed implementation costs for centers where the neonatal [...] Read more.

Since the approval of modifying therapies for Spinal Muscular Atrophy (SMA), several protocols aiming to screen SMN1 homozygous deletion in a neonatal context have been published. However, no work has compared different methodologies along with detailed implementation costs for centers where the neonatal screening of SMA has not yet been implemented. Therefore, our work compared different qualitative real-time PCR approaches for SMA screening and the estimated costs of test implementation. Using Brazilian blood samples, the presence and absence (P/A) and melt curve protocols were analyzed. MLPA was used as a confirmatory test. The costs were calculated for the simplex and multiplex tests plus equipment. The test workflow was based on the present experience and literature report. The accuracy of the P/A protocol was 1 (95% CI 0.8677−1) using dried blood spots (DBS). The melt curve protocol also achieved 100% concordance. The consumable costs ranged from USD 1.68 to 4.42 and from USD 2.04 to 12.76 per reaction, for the simplex and multiplex tests, respectively. The equipment acquisition costs ranged from USD 44,817.07 to 467,253.10, with several factors influencing this value presented. Our work presents a framework for decision-making, with a project demonstration of the different assays that will be useful in dealing with the issues of cost and availability of reagents. Moreover, we present a literature review and discussion of important concerns regarding treatment policies. We take the first step towards a future SMA NBS pilot program where it is not yet a reality. Full article

(This article belongs to the Special Issue Newborn Screening for Spinal Muscular Atrophy)

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10 pages, 2741 KiB

Open AccessArticle

Novel Modification of a Confirmatory SMA Sequencing Assay that Can Be Used to Determine SMN2 Copy Number

by Binod Kumar, Samantha Barton, Jolanta Kordowska, Roger B. Eaton, Anne M. Counihan, Jaime E. Hale and Anne Marie Comeau

Int. J. Neonatal Screen. 2021, 7(3), 47; https://doi.org/10.3390/ijns7030047 - 21 Jul 2021

Cited by 3 | Viewed by 2334

Abstract

Promising treatments for spinal muscular atrophy (SMA), the leading genetic cause of infant mortality, prompted calls for inclusion in newborn screening (NBS). In January 2018, the New England Newborn Screening Program (NENSP) began statewide screening for SMA using a tiered algorithm looking for [...] Read more.

Promising treatments for spinal muscular atrophy (SMA), the leading genetic cause of infant mortality, prompted calls for inclusion in newborn screening (NBS). In January 2018, the New England Newborn Screening Program (NENSP) began statewide screening for SMA using a tiered algorithm looking for the absence of SMN1 Exon 7. When results from the first and second tier needed reconciliation, we developed and validated a third tier DNA sequencing assay to ensure the presence or absence of SMN1 Exon 7. All nine infants referred to specialty centers through NBS showed single base substitution of c.840C>T, and were confirmed to have SMA. Further, a minor sequencing protocol modification allowed the estimation of SMN2 copy number in SMA affected patients; we developed and validated a copy-number assay yielding 100% match with seven previously characterized specimens of SMA patients. All nine SMA-affected infants found through NBS were also assayed for SMN2 copy number. Results were comparable but not 100% matched with those that were reported by independent diagnostic laboratories. In conclusion, a sequencing protocol confirms NBS findings from real-time qPCR, and its modified application allows NBS programs that have sequencing capabilities to provide SMN2 copy numbers without the need for additional instrumentation. Full article

(This article belongs to the Special Issue Newborn Screening for Spinal Muscular Atrophy)

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10 pages, 683 KiB

Open AccessArticle

Landscape of Spinal Muscular Atrophy Newborn Screening in the United States: 2018–2021

by Kshea Hale, Jelili Ojodu and Sikha Singh

Int. J. Neonatal Screen. 2021, 7(3), 33; https://doi.org/10.3390/ijns7030033 - 24 Jun 2021

Cited by 25 | Viewed by 3149

Abstract

Newborn screening (NBS) programs identify newborns at increased risk for genetic disorders, linking these newborns to timely intervention and potentially life-saving treatment. In the United States, the Health and Human Services (HHS) Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC) recommends [...] Read more.

Newborn screening (NBS) programs identify newborns at increased risk for genetic disorders, linking these newborns to timely intervention and potentially life-saving treatment. In the United States, the Health and Human Services (HHS) Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC) recommends the disorders for state NBS programs to screen. ACHDNC updated the Recommended Uniform Screening Panel to include Spinal Muscular Atrophy (SMA) in July 2018. As of June 2021, 34 state NBS programs had fully implemented SMA newborn screening, and at least 8 programs were pursuing implementation. This article will review current SMA screening processes, considerations, challenges, and status. Full article

(This article belongs to the Special Issue Newborn Screening for Spinal Muscular Atrophy)

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11 pages, 1008 KiB

Open AccessArticle

Massachusetts’ Findings from Statewide Newborn Screening for Spinal Muscular Atrophy

by Jaime E. Hale, Basil T. Darras, Kathryn J. Swoboda, Elicia Estrella, Jin Yun Helen Chen, Mary-Alice Abbott, Beverly N. Hay, Binod Kumar, Anne M. Counihan, Jacalyn Gerstel-Thompson, Inderneel Sahai, Roger B. Eaton and Anne Marie Comeau

Int. J. Neonatal Screen. 2021, 7(2), 26; https://doi.org/10.3390/ijns7020026 - 23 May 2021

Cited by 14 | Viewed by 4029

Abstract

Massachusetts began newborn screening (NBS) for Spinal Muscular Atrophy (SMA) following the availability of new treatment options. The New England Newborn Screening Program developed, validated, and implemented a screening algorithm for the detection of SMA-affected infants who show absent SMN1 Exon 7 by [...] Read more.

Massachusetts began newborn screening (NBS) for Spinal Muscular Atrophy (SMA) following the availability of new treatment options. The New England Newborn Screening Program developed, validated, and implemented a screening algorithm for the detection of SMA-affected infants who show absent SMN1 Exon 7 by Real-Time™ quantitative PCR (qPCR). We screened 179,467 neonates and identified 9 SMA-affected infants, all of whom were referred to a specialist by day of life 6 (average and median 4 days of life). Another ten SMN1 hybrids were observed but never referred. The nine referred infants who were confirmed to have SMA were entered into treatment protocols. Early data show that some SMA-affected children have remained asymptomatic and are meeting developmental milestones and some have mild to moderate delays. The Massachusetts experience demonstrates that SMA NBS is feasible, can be implemented on a population basis, and helps engage infants for early treatment to maximize benefit. Full article

(This article belongs to the Special Issue Newborn Screening for Spinal Muscular Atrophy)

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10 pages, 1665 KiB

Open AccessEditor’s ChoiceArticle

A Voluntary Statewide Newborn Screening Pilot for Spinal Muscular Atrophy: Results from Early Check

by Katerina S. Kucera, Jennifer L. Taylor, Veronica R. Robles, Kristin Clinard, Brooke Migliore, Beth Lincoln Boyea, Katherine C. Okoniewski, Martin Duparc, Catherine W. Rehder, Scott M. Shone, Zheng Fan, Melissa Raspa, Holly L. Peay, Anne C. Wheeler, Cynthia M. Powell, Donald B. Bailey and Lisa M. Gehtland

Int. J. Neonatal Screen. 2021, 7(1), 20; https://doi.org/10.3390/ijns7010020 - 21 Mar 2021

Cited by 14 | Viewed by 4223

Abstract

Prior to statewide newborn screening (NBS) for spinal muscular atrophy (SMA) in North Carolina, U.S.A., we offered voluntary screening through the Early Check (EC) research study. Here, we describe the EC experience from October 2018 through December 2020. We enrolled a total of [...] Read more.

Prior to statewide newborn screening (NBS) for spinal muscular atrophy (SMA) in North Carolina, U.S.A., we offered voluntary screening through the Early Check (EC) research study. Here, we describe the EC experience from October 2018 through December 2020. We enrolled a total of 12,065 newborns and identified one newborn with 0 copies of SMN1 and two copies of SMN2, consistent with severe early onset of SMA. We also detected one false positive result, likely stemming from an unrelated blood disorder associated with a low white blood cell count. We evaluated the timing of NBS for babies enrolled prenatally (n = 932) and postnatally (n = 11,133) and reasons for delays in screening and reporting. Although prenatal enrollment led to faster return of results (median = 13 days after birth), results for babies enrolled postnatally were still available within a timeframe (median = 21 days after birth) that allowed the opportunity to receive essential treatment early in life. We evaluated an SMA q-PCR screening method at two separate time points, confirming the robustness of the assay. The pilot project provided important information about SMA screening in anticipation of forthcoming statewide expansion as part of regular NBS. Full article

(This article belongs to the Special Issue Newborn Screening for Spinal Muscular Atrophy)

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