neonatal screening for inborn errors of metabolism

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Neonatal screening Inborn errors of metaboli Pedro Serrano Aguilar Iván Castilla Rodríguez Laura Vallejo-Torres Lidia García Pérez Cristina Valcárcel Nazco SESCS

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Page 1: Neonatal screening  for inborn errors of metabolism

Neonatal screening for Inborn errors of metabolism

Pedro Serrano AguilarIván Castilla RodríguezLaura Vallejo-TorresLidia García PérezCristina Valcárcel Nazco

SESCS

Page 2: Neonatal screening  for inborn errors of metabolism

Contenidos de la presentación

• Threats, challenges and opportunities for Health Systems

• Heterogeinity in newborn screening programs (NSP)

• Towards uniformity of NSP in developed countries

• The role of Health Technology Assessment and ecomomic evaluation to guide NSP development

Page 3: Neonatal screening  for inborn errors of metabolism

• Aging and chronicity

• Exponential growing of technological development and adoption • Societal increasing expectations and demands

• Variations in practices and inappropriate use of medical resources

• Making room for rare diseases

• Restrictive economic scenary

Current Oportunities, challenges and threats for Health Systems

Page 4: Neonatal screening  for inborn errors of metabolism

Medical practice variations Evidence Based

Medicine

Health Technology AssessmentSystematic Rewiews

Meta-analysisCost-effectiveness

Clinical Practice GuidelinesComputarized decission support

toolsTools for shared decision making

Risk-sharing contractsPayment by results

20 years of Concepts, Disciplines and Tools development

to reduce uncertainty in decission making

Page 5: Neonatal screening  for inborn errors of metabolism

Variations in Newborn screening in developed countries (2012)

Country Screening Panel (Number of disorders)Metabolic Endocrinological Cystic Fibrosis Hemoglob.

Austria 26 2 Yes -

Belgium-Flemish 9 2 - -

Belgium-French 6 1 - -

Finland - 1 - -

France 1 2 Yes 1

Germany 12 2 Yes -

Spain-Galicia 39 2 Yes -

SpainCanary Islands

1 1 Yes -

UK 2 1 Yes 3

USA 22 2 Yes 3

Page 6: Neonatal screening  for inborn errors of metabolism

Procedural variations among Newbon Screening Programs

• Place (Hospital vs. Primary Care) for sample taking

• Time after birht for sample taking

• MS/MS vs conventional technical procedures

• Cut-off points for screening tests

• Organizational

• Quality control programs

Page 7: Neonatal screening  for inborn errors of metabolism

Wilson and Jungner classic screening criteria (WHO-1968)

1. The condition sought should be an important health problem.

2. There should be an accepted treatment for patients with recognized disease.

3. Facilities for diagnosis and treatment should be available.

4. There should be a recognizable latent or early symptomatic stage.

5. There should be a suitable test or examination.

6. The test should be acceptable to the population.

7. The natural history of the condition should be adequately understood.

8. There should be an agreed policy on whom to treat as patients.

9. Costs of case-finding (with diagnosis and treatment) should be balanced to medical care.

10. Case-finding should be a continuing process.

Wide variations despite sharing the same guiding criteria

Page 8: Neonatal screening  for inborn errors of metabolism

Why so wide variations in health policy decisions ?• High degree of uncertainty for all countries

• Differences in interpretation and management of these uncertainties

• Specific epidemiological scenarios

• Pre-existing regional differences

• Differences in availability of technical means and clinical expertise

• Differences in economic resources to ensure sustainability

• Differences in overall health priorities

• Pressure groups

• Technological imperative

Page 9: Neonatal screening  for inborn errors of metabolism

Why so wide variations in neonatal screening ?

Overall scientific basis for decisions: Wilson and Jungner criteria (general to guide decisions) Guidelines of scientific societies (scarce and consensus based) Expert groups Literature surveys (scarce and low validity) National/regional research (scarce and limited validity)

Local availability of valid data: Epidemiological evidence low availability Course of disease not known for most diseases Clinical management uncertain Health / Social benefits uncertain Cost-effectiveness uncertain (sensitivity analysis) Implementation costs estimated

Page 10: Neonatal screening  for inborn errors of metabolism

Watson MS, Mann MY, Lloyd-Puryear MA, Rinaldo P, Howell RR, American College of Medical Genetics Newborn Screening Expert Group. Newborn Screening: Toward a Uniform Screening Panel and System—Executive Summary. PEDIATRICS Volume 117, Number 5, May 2006. ww.pediatrics.org/cgi/doi/10.1542/peds.2005-2633I

Uniformity of Newborn Screening in the US of America (2006)

American Academy of Pediatrics Maternal and Child Health Bureau of Health Resources and Services AdministrationAmerican College of Medical Genetics (ACMG)

American Academy of Pediatrics Maternal and Child Health Bureau of Health Resources and Services AdministrationAmerican College of Medical Genetics (ACMG)

ACMG developed recommendations on state newborn screening programs :

1.- Uniform condition panel 2.- Policies and procedures 3.- Minimal standards 4.- Decision matrix for potential program expansion 5.- Value of a national process for quality assurance

ACMG developed recommendations on state newborn screening programs :

1.- Uniform condition panel 2.- Policies and procedures 3.- Minimal standards 4.- Decision matrix for potential program expansion 5.- Value of a national process for quality assurance

Work process:

ParticipativeComplex: stage-based and iterativeEvidence and opinion basedMarginal consideration of costs

Work process:

ParticipativeComplex: stage-based and iterativeEvidence and opinion basedMarginal consideration of costs

Main criteria for condition selection:

Identification at 24-48 h. after birthAvailability of valid testAvailability of efficacious treatmentDemonstration of benefits

Main criteria for condition selection:

Identification at 24-48 h. after birthAvailability of valid testAvailability of efficacious treatmentDemonstration of benefits

Natowicz M. Newborn screening—setting evidence-based policy for protection. N Engl J Med 2006;353(9):867–870. Botkin JR, Clayton EW, Fost NC, et al. Newborn screening technology: proceed with caution. Pediatrics 2006;117:1793–1799. ISI

Page 11: Neonatal screening  for inborn errors of metabolism

Slower and incomplete movements from the European Union

Page 12: Neonatal screening  for inborn errors of metabolism

Towards health policies uniformity in Spain: Overall framework

• Law for the Cohesion and Quality Improvement in the NHS

• Quality Improvement Plan for the NHS

• Spanish network for Health Technology Assessment

• Inter-territorial Board of the National Health System.

• Benefits Catalog for the National Health System.

Page 13: Neonatal screening  for inborn errors of metabolism

Towards uniformity in NSP in Spain: working groups

Inter-territorial Board of the National Health System

Ministry of Health, Social Services and Equality

Page 14: Neonatal screening  for inborn errors of metabolism

Cost-effectiveness assessment for NSP in Spain

Page 15: Neonatal screening  for inborn errors of metabolism

Uniformity of Newborn Screening in Spain

Sickle cell anemia

Page 16: Neonatal screening  for inborn errors of metabolism

Spanish Newborn screening Information System

Page 17: Neonatal screening  for inborn errors of metabolism

What is Health Technology Assessment (HTA) ?

Systematic evaluation of the characteristics and potential effects of health care technologies on the populations health and the sustainability of health services.

HTA reports include:

• Technical properties

• Efficacy / Effectiveness

• Safety

• Economic evaluation (cost/effectiveness)

• Impact on Organization, social, legal, ethical and political issues.

Page 18: Neonatal screening  for inborn errors of metabolism

Main objective of HTA

• Guiding the introduction, diffussion and adequate use of HT according to the best available scientific knowledge on efficacy, safety and cost-effectiveness.

- To avoid the adoption of non effective technologies

- To promote the early incorporation and diffussion of cost-effective technologies

Page 19: Neonatal screening  for inborn errors of metabolism

Grupo de

pacientes

Alternativa B

Alternativa A

Impacto sobre el estado de salud

Impacto sobre costes

Impacto sobre costes

Impacto sobre el estado de salud

i. Supervivenciaii. Calidad de vidaiii. Capacidad para trabajar

i. Hospitalizacionesii. Medicamentosiii. Procesos médicosiv. Costes para los familiares y la comunidad

i. Hospitalizacionesii. Medicamentosiii. Procesos médicosiv. Costes para los familiares y la comunidad

i. Supervivenciaii. Calidad de vidaiii. Capacidad para trabajar

What is an economic evaluation ?

Ca – Cb €ICER: ----------------------------- Ea – Eb LYG /QALYs

Page 20: Neonatal screening  for inborn errors of metabolism

Simulation modellingSimulation modelling

Sample size

Sample size

Ethical problemsEthical

problems

Time and costs to

get results

Time and costs to

get results

Methods for cost-effectiveness assessment?

Clinical trialClinical trial

Page 21: Neonatal screening  for inborn errors of metabolism

Willingness to pay threshold

UK-NICE20.000 – 30.000

£/QALY

UK-NICE20.000 – 30.000

£/QALY

EE.UU.50.000 $/QALY

EE.UU.50.000 $/QALY

SPAIN30.000 €/QALY

SPAIN30.000 €/QALY

Page 22: Neonatal screening  for inborn errors of metabolism

ECM Concepto Incremental [IC 95%] ICER [IC 95%]

Screening base: PKU + MCADD

Costs 6,75 € [6,15 €; 7,45 €]38.366,05 €/LYG

[23.490,84; 67.984,51]LYG 0,00018

[0,00011; 0,00026]

Base + LCHADD

Costs 7,07 € [6,40 €; 7,77 €]33.228,86 €/LYG

[20.832,09; 59.198,35]LYG 0,00021[0,00013; 0,00031]

Base + LCHADD + GA1

Costs 11,19 € [8,87 €; 14,61 €]

36.708,59 €/LYG[21.223,01; 73.163,78]

LYG 0,00030[0,00020; 0,00042]

Base + LCHADD + GA1 + MSUD

Costs 14,85 € [10,56 €; 21,04 €]

41.229,84 €/LYG[21.849,91; 88.010,25]

LYG 0,00036[0,00024; 0,00048]

Base + LCHADD + GA1 + MSUD + HCN

Costs 20,71 € [13,90 €; 27,50 €]

49.067,94 €/LYG[25.508,50; 92.546,28]LYG 0,00042

[0,00030; 0,00055]

Base + LCHADD + GA1 + MSUD + HCN + IVA

Costs 21,47 € [14,85 €; 28,33 €]

50.315,21 €/LYG[26.772,58; 95.042,27]

LYG 0,00043[0,00030; 0,00055]

ICER for NSP from Health Services perspective (Spain)

Page 23: Neonatal screening  for inborn errors of metabolism

ECM Concept Incremental [IC 95%] ICER [IC 95%]

Screning base: PKU + MCADD

Costs 3,55 € [2,55 €; 4,31 €]20.720,24 €/LYG

[10.041,37; 39.548,75]LYG 0,00017 [0,00011; 0,00025]

Base + LCHADDCosts 3,11 € [1,92 €; 4,10 €]

15.031,14 €/LYG[6.527,72; 32.289,76]LYG 0,00021

[0,00013; 0,00029]

Base + LCHADD + GA1Costs 4,53 € [2,44 €; 7,39 €]

15.436,07 €/LYG[5.920,19; 39.063,02]

LYG 0,00029[0,00019; 0,00041]

Base + LCHADD + GA1 + MSUD

Costs 7,03 € [3,30 €; 11,75 €] 20.091,26 €/LYG

[6.879,24; 50.646,71]LYG 0,00035

[0,00023; 0,00048]

Base + LCHADD + GA1 + MSUD + HCN

Costs 10,62 € [5,80 €; 15,68 €] 25.722,22 €/LYG

[10.609,77; 53.665,13]LYG 0,00041

[0,00029; 0,00055]

Base + LCHADD + GA1 + MSUD + HCN + IVA

Costs 11,20 € [6,56 €; 16,13 €] 26.718,68 €/LYG

[11.819,70; 56.933,91]LYG 0,00042

[0,00028; 0,00055]

ICER for NSP from the Social perspective (Spain)

Page 24: Neonatal screening  for inborn errors of metabolism

Limitations of Cost-effectiveness analyses

• Lack of valid data on transitional probabilities along the disease (Literature review)

• Sensitivity and especificity data from the NSP not robust for several disorders (literature review).

• Conservative assumption based on just one clinical decompensation along the life (expert judgment)

• Difficulties estimating the differential use of resources between screened and not screened children (expert judgment)

• Lack of data on Quality of life as effectiveness measure precludes the use of QALYs

• Using Life Years Saved as effectiveness measure limits health benefit measurement to very long time periods

Page 25: Neonatal screening  for inborn errors of metabolism

Theoretical considerations on HTA for Rare Diseases

• Could screening criteria for RD be less demanding than for common diseases?

• Is treatment availability an absolut requirement ?

• Value of the information for the families ?

• Value of the information for research ?

• Role of costs and Cost-effectiveness considerations

• Specific threshold of willingness to pay for RD and NSP?

Page 26: Neonatal screening  for inborn errors of metabolism