ECONOMIC BURDEN OF PRIMARY IMMUNODEFICIENCY IN NATIONAL INSTITUTE OF PEDIATRICS IN MEXICO Maciel-Hernandez Humberto1, Espinosa-Rosales Francisco2, Partida-Gaytan Armando3. 1 M.D.

Master in Health Systems & Health Economics. 2 M.D. Pediatrician, Immunologist Pediatrician. 3 M.D. Pediatrician, Immunologist Pediatrician.

Background: Observational and retrospective study examining the economic burden of disease in children with Primary Immunodeficiency (PID) in the National Institute of Pediatrics in Mexico (INP). Objectives: The aim of this study was to describe health care resource use (HCRU) and disease cost burden in both, children with PID in treatment and children with PID belatedly diagnosed. Methods: 34 cases of IDP were enrolled, registered from 2010 to 2015 in INP (47% agammaglobulinemic type and 29% with common variable immunodeficiency). Clinical histories were reviewed and It was developed a medical-economic model for register HCRU. Local sourced unit costs were used in the calculation for total costs and cost per capita was estimated by using INP attended reference population. Results: Overall, the mean annual cost for patients with PID in treatment was in $11,564 USD and the mean annual cost for children with PID belatedly diagnosed was $16,019 USD. Main cost for patients with belatedly diagnosis were produced for infections: Pneumonia $6,785 USD, Acute Otitis Media $733 USD, Acute Respiratory Infection (upper tract) $843 USD, Sinusitis $609 USD, Septic Arthritis $1,242 USD and Infectious Gastroenteritis $5,805 USD. Cost per capita for patients with PID in treatment were estimated in $0.023 USD and cost per capita for patient with PID belatedly diagnosed was estimated in $0.031 USD.

Conclusions: Belatedly diagnosis for PID in INP has a significant impact on HCRU and associated costs. Timely and effective diagnosis and management of this group of diseases has the potential to reduce disease burden and health care costs. Keywords: primary immunodeficiency, economic burden, cost of illness, health care costs, cost per capita.

It was determined to develop a Cost Analysis Model from the information contained in the clinical records of 34 patients from National Institute of Pediatrics (INP - Mexico). The economic evaluation methodology was designed for comparing: (1) Costs of No-treatment (infections) and (2) Costs of Standardized Treatment. 1. Review of Clinical Records

4. Estimation of Medical Direct Costs

2. Integration of the Technical Protocol

7. Ranking by Specific Weight

5. Total Cost Analysis

3. Design of Medical Economics Templates

8. Estimation of Cost per capita

6. Estimation of Cost per Clinical Service

Medical Economics templates included Infrastructure (medical consultation, emergency room, hospitalization), laboratory and treatment costs. INTERVENCIÓN:

DIAGNÓSTICO Y TRATAMIENTO DE NEUMONÍA

DESCRIPCIÓN: COSTO TOTAL:

DIAGNÓSTICO, TRATAMIENTO, HOSPITALIZACIÓN 61,068.81

1. For the National Institute of Pediatrics, treatment delay represents annual direct costs for USD $16,019 (average per case), mainly for susceptibility to infections. 2. For the 34 cases of INP, the difference in treatment vs notreatment implicates annual savings for USD $151,476

RECURSOS HUMANOS 100001

Cons ul ta de pedi a tría genera l (C.E.P.)

Cons ul ta

10.00

610.00

COSTO TOTAL 6,100.00

100002

Cons ul ta de s ubes peci a l i s ta

IC Inmuno

7.00

849.00

5,943.00

100002

Cons ul ta de s ubes peci a l i s ta

IC Infecto

7.00

849.00

5,943.00

100005

Va l ora ci ón y Ori enta ci ón Nutri ci ona l

Cons ul ta

1.00

242.00

CLAVE

NOMBRE

UNIDAD DE MEDIDA

CANTIDAD POR ACTIVIDAD COSTO UNITARIO

Subtotal Consultas

242.00 18,228.00

URGENCIAS CLAVE 100003

NOMBRE

UNIDAD DE MEDIDA

Atenci ón de urgenci a s

CANTIDAD POR ACTIVIDAD COSTO UNITARIO

Hora

2.00

610.00 Subtotal Urgencias

COSTO TOTAL 1,220.00 1,220.00

HOSPITALIZACIÓN CLAVE

NOMBRE

UNIDAD DE MEDIDA

CANTIDAD POR ACTIVIDAD COSTO UNITARIO

COSTO TOTAL

Oxígeno

Por día

5.00

600059

Nebul i za ci ones por día (Pa quete)

Por día

7.00

805.00

5,635.00

600051

Venopunci ón

Evento

5.00

85.00

425.00

600003

Al i menta ci ón pa rentera l (por día )

Evento

600055

Ca téter por venopunci ón

600026

Hos pi ta l i za ci ón cua l qui er s ervi ci o (por día )

-

1,160.00

-

Pi eza

1.00

219.00

219.00

Día Ca ma

10.00

1,483.00

14,830.00

Subtotal Hospitalización

3. Difference of USD $0.0088 per capita, implicates for Mexico annual savings for USD $1,050,093 (Reference population: 120 Million People)

21,109.00

ESTUDIOS DE DIAGNÓSTICO 500092

Bi ometría Hemá ti ca (BH)

Es tudi o

1.00

129.00

COSTO TOTAL 129.00

402005

Tóra x PA

Es tudi o

5.00

273.00

1,365.00

500214

Proteína C rea cti va

Es tudi o

5.00

66.00

330.00

500234

Ti empo de Protombi na (TP)

Es tudi o

2.00

129.00

258.00

500236

Ti empo de Trombopl a s ti na Pa rci a l a cti va da (TTPa )

Es tudi o

2.00

129.00

258.00

500153

Fi bri nógeno

Es tudi o

2.00

203.00

406.00

500243

Al a ni na Ami notra ns fera s a (ALT)

Es tudi o

3.00

129.00

387.00

500244

As pa rta to Ami notra ns fera s a (AST)

Es tudi o

3.00

129.00

387.00

500338

Bi l i rrubi na Tota l

Es tudi o

3.00

233.00

699.00

500339

Bi l i rrubi na Di recta

Es tudi o

3.00

206.00

618.00

500162

Ga mma Gl uta mi l Tra ns fera s a (GGT)

Es tudi o

3.00

338.00

1,014.00

500216

Proteína s tota l es

Es tudi o

3.00

86.00

258.00

500134

Ni trógeno Urei co uri na ri o

Es tudi o

3.00

86.00

258.00

500133

Crea ti ni na

Es tudi o

3.00

203.00

609.00

500334

Sodi o

Es tudi o

3.00

122.00

366.00

500336

Cl oro

Es tudi o

3.00

126.00

378.00

500098

Ca l ci o

Es tudi o

3.00

86.00

258.00

500157

Fós foro

Es tudi o

3.00

86.00

258.00

500165

Gl ucos a

Es tudi o

3.00

86.00

258.00

500197

Ma gnes i o

Es tudi o

3.00

86.00

258.00

500174

Hemocul ti vo

Es tudi o

2.00

608.00

1,216.00

500163

Ga s ometría (PH,PCO2,HCO3,PO2)

Es tudi o

4.00

261.00

1,044.00

500005

La cta to

Es tudi o

3.00

144.00

432.00

500403

Proca l ci toni na

Es tudi o

3.00

840.00

2,520.00

600015

Ecoca rdi ogra ma

Es tudi o

1.00

2,086.00

2,086.00

500909

Pa nel de 19 vi rus res pi ra tori os por PCR

Es tudi o

1.00

3,977.00

CLAVE

NOMBRE

UNIDAD DE MEDIDA

CANTIDAD POR ACTIVIDAD COSTO UNITARIO

Subtotal Estudios de Diagnóstico

NOMBRE GENÉRICO

NOMBRE COMERCIAL

CANTIDAD TOTAL

COSTO UNITARIO

20.00

18.38

3,977.00

COSTO TOTAL 367.60

1921

Benci l peni ci l i na Sódi ca Cri s ta l i na 1,000,000 UI

Benci l peni ci l i na Sódi ca Cri s ta l i na

106

Pa ra ceta mol 100 mg/ml Fra s co Sol Ora l

Pa ra ceta mol

3.00

3.00

9.00

4332

Budes oni da 0.250 mg. Enva s e con 5 enva s es con 2 ml .

Budes oni da

1.00

209.25

209.25

Subtotal Medicamentos Opción 1

585.85

MEDICAMENTOS: OPCION 2 NOMBRE COMERCIAL

CANTIDAD TOTAL

COSTO UNITARIO

COSTO TOTAL 165.53

CLAVE

NOMBRE GENÉRICO

1937

Gi Ceftri a xona 1g Sol Iny Fa y Di l 10ml

Ceftri a xona

15.00

106

Pa ra ceta mol 100 mg/ml Fra s co Sol Ora l

Pa ra ceta mol

3.00

3.00

9.00

4332

Budes oni da 0.250 mg. Enva s e con 5 enva s es con 2 ml .

Budes oni da

1.00

209.25

209.25

11.04

Cost per Infection: Most expensive infection was Pneumonie (USD $3,392)

20,027.00

TRATAMIENTO MEDICAMENTOS: OPCION 1 CLAVE

4. Financially, expenses for each year of diagnosis delay only could be recovered 7.5 años later after starting treatment.

Subtotal Medicamentos Opción 2

383.78

Subtotal Medicamentos (Promedio de Opciones)

484.81

Specific Technical Protocols were defined from the clinical records.

DIRECT COST OF INFECTIONS IN PRIMARY IMMUNODEFICENCY INFECTIONS CONS ER HOSP LAB TREAT Pneumonia 1,012.67 67.78 1,172.72 1,112.61 26.93 AOM 162.11 10.83 10.34 Pharyngitis / Tonsillitis 128.22 10.83 1.57 Sinusitis 162.11 126.17 16.27 Septic Arthritis 1,950.06 101.67 1,483.83 567.94 39.39 Infectious Gastroenteritis 958.17 101.67 598.33 270.39 6.46 TOTAL 4,373.33 271.11 3,254.89 2,098.78 100.97

Annual Total Cost of all Infections in IDP Children form INP was USD $16,019 ANNUAL COST ALL EVENTS INFECTION EVENTS PER YEAR TOTAL COST Pneumonia 2 6,785.42 AOM 4 733.13 Pharyngitis / Tonsillitis 6 843.78 Sinusitis 2 609.10 Septic Arthritis 0.3 1,242.87 Infectious Gastroenteritis 3 5,805.06 TOTAL ANNUAL 17 16,019.36

PNEUMONIA REQUIRING HOSPITALIZATION WITHOUT COMPLICATIONS. CONSIDERING PROCESS OF 21 DAYS. • • • • • • • • • • •

Pediatrics daily valuation Evaluation by subspecialists Nutritional counseling Antibiotic scheme Oxygen Micronebulization Venipuncture Catheters Parenteral feeding Blood count Chest X-ray

• • • • • • • • • • •

Coagulation times Fibrinogen Liver function tests Kidney function tests Blood cultures Arterial Blood Gasometry Lactate C-Reactive Protein Pro-calcitonin Echocardiogram 19 tests for respiratory viruses

To assess the impact of diagnosis delay costs associated with susceptibility to infections are estimated. INFECTION

ANNUAL FREQUENCY

HORIZON

COSTING CRITERIA

Pneumonia

2

21 days

With hospitalización. Without shock. Without mechanical ventilation.

Pharyngitis / Tonsillitis

6

7 days

Without hospitalización.

AOM

4

10 days

Without hospitalización.

Sinusitis

2

10 days

With hospitalización. Without shock. Without mechanical ventilation.

Septic arthritis

0.5

21 days

With hospitalización. Without shock. Without mechanical ventilation.

Infectious Gastroenteritis

3

10 days

With hospitalización. Without shock. Without mechanical ventilation.

TOTAL 3,392.71 183.28 140.63 304.55 4,142.89 1,935.02 10,099.08

According to INP incidence, cost for 5 years Diagnosis delay was USD 2,723,291$ ANNUAL COST PER DIAGNOSIS DELAY YEARS COST PER CASE PER INCIDENCE 1 16,019.36 544,658.30 2 32,038.72 1,089,316.60 3 48,058.09 1,633,974.90 4 64,077.45 2,178,633.20 5 80,096.81 2,723,291.50

Average annual cost for all IDP treatment in INP was USD $393,181 COST OF TREATMENT PER CASE IN INP $

11,564.17 TOTAL COST OF TREATMENT (ALL CASES) IN INP

Type Agammaglobulinemy Common Variable ID Other IDP Total Annual

N 16 10 8 34

TOTAL 185,026.72 115,641.70 92,513.36 393,181.78

Based on reference population, diagnosis & treatment of IDP could represent savings for Health System in the order of USD $0.0088 per cápita.

Resume COST COMPARISON FOR ALL CASES (INP MEXICO) N=34 TOTAL COST PER CAPITA DIAGNOSIS DELAY (5 years) $ 544,658.30 $ 0.0315 DIGANOSIS & TRETAMENT OF IDP´S $ 393,181.78 $ 0.0227 DIFERENCIA $ 151,476.52 $ 0.0088

References: (1) Coria-Ramírez. Panorama Epidemiológico de las Inmunodeficiencias Primarias en México. Rev Alerg Mex 2010; (2) Ruggero. Primary Immunodeficiency Diseases in Latin America: Epidemiology and Perspectives. Epidemiology Insights Intech 2012; (3) Al-Herz. Primary Immunological Diseases: An update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency. Frontiers in Immunology Primary Immunodeficiencies 2014; (4) LASID. Registro de Inmunodeficiencias Primarias. Sociedad Latinoamericana de Inmunodeficiencias 2015; (5) Notarangelo. Primary immunodeficiencies. J Allergy Clin Immunol 2010; (6) Contreras. Diagnóstico oportuno de la inmunodeficiencia combinada grave a través del tamiz neonatal. Alergia, Asma e Inmunología Pediátricas 2014. Disclosures: The study was supported by CSL Behring Mexico. Scientific information was provided by the National Institute of Pediatrics and the Mexican Foundation for Children with Immunodeficiencies. Acknowledgments: Editorial and graphical support was provided by CSL Behring Mexico. Presented: at the ISPOR 19th Annual European Congress, 29 October-2 November 2016, Austria Center Vienna, Vienna, Austria. Acontact : Dr. Humberto Maciel. [email protected]