Assoc Prof Asrul Akmal Shafie

SCHOOL OF PHARMACEUTICAL SCIENCES


International Fellow,

International Society for Pharmacoeconomics &

Outcomes Research

Program Chairman,

Universiti Sains Malaysia

COST-EFFECTIVE PRICE OF DENGUE VACCINATION IN MALAYSIA

Assoc Prof Dr Asrul Akmal Shafie [email protected]

mailto:[email protected]


Outline

• What is cost-effective price & how to assess it?

• How do we measure the economic impact of dengue vaccination?

• Which dengue vaccination strategies give the best value?


What is Cost-Effective Price?:

How Much Would You Pay for …

We put price to reflect the value of the benefit we think it should be

Price ≤ value = cost-effective

Price > value ≠ cost-effective

Cost-effective price is the max price for the expected value of benefit

• Price threshold = upper limit of the vaccination price for the intervention to be considered cost-effective as defined by decision makers/WHO*

*http://www.who.int/choice/costs/CER_thresholds/en/

http://www.who.int/choice/costs/CER_thresholds/en/

http://www.who.int/choice/costs/CER_thresholds/en/



Translating to Research

• Value = NET MONETARY BENEFIT (NMB)

• = Benefit – Cost

• So, BENEFIT

Avoidance of dengue treatment

Avoidance of productivity losses

Avoidance of HRQoL losses

Avoidance of death

COSTS

Vaccine administration

-

DALY

Economic Impact



Translating to Research

Pthreshold = ∆ 𝐷𝐴𝐿𝑌𝑠 𝑙𝑜𝑠𝑡 𝑋 𝐶𝐸 𝑇ℎ𝑟𝑒𝑠ℎ𝑜𝑙𝑑+ ∆𝑑𝑖𝑠𝑒𝑎𝑠𝑒 𝑐𝑜𝑠𝑡𝑠+ ∆𝑎𝑑𝑚.𝑐𝑜𝑠𝑡𝑠

𝑁𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑑𝑜𝑠𝑒𝑠

∆: 𝑑𝑖𝑓𝑓𝑒𝑟𝑒𝑛𝑐𝑒 𝑏𝑒𝑡𝑤𝑒𝑒𝑛 𝑠𝑡𝑎𝑛𝑑𝑎𝑟𝑑 𝑜𝑓 𝑐𝑎𝑟𝑒 𝑖𝑒. ℎ𝑒𝑟𝑒 𝑛𝑜 𝑣𝑎𝑐𝑐𝑖𝑛𝑎𝑡𝑖𝑜𝑛 𝑎𝑛𝑑 𝑣𝑎𝑐𝑐𝑖𝑛𝑎𝑡𝑖𝑜𝑛 𝑠𝑡𝑟𝑎𝑡𝑒𝑔𝑦

DALYs and costs are discounted

∆ effectiveness


How to Determine the CE Price of Dengue Vaccine?

= Avoidance of dengue treatment +

CRITERIA ITEM VALUATION PUBLISHED

COST (US$)

COST PER CASE

2013 (US$)

Dengue Treatment

Ambulatory/

Direct Medical

Average operating budget in

public clinics

297.93

(2009) 326.51

Hospitalized/

Direct Medical

Weighted average operating

expenditure in UMMC, public

district hospitals and WHO-

CHOICE

613.65

(2009) 672.51

Public Provider’s Perspective

1. Suaya, J. A., et al. (2009). "Cost of dengue cases in eight countries in the Americas and Asia: a prospective study." Am J Trop Med Hyg 80(5): 846-855.

2. Shepard, D. S., et al. (2012). "Use of multiple data sources to estimate the economic cost of dengue illness in Malaysia." Am J Trop Med Hyg 87(5): 796-805.


How to Determine the CE Value of Dengue Vaccine?

= + Avoidance of Productivity Losses +

Loss of school day Loss of work productivity

Ambulatory

Mean±SD loss of school day: 3.2±2.3 days

Hospitalized

Mean±SD loss of school day: 4.1±2.1 days

Ambulatory

Mean±SD loss of work productivity: 7.2±2.6 days

Hospitalized

Mean±SD loss of work productivity: 8.8±2.7 days

Suaya, J. A., et al. (2009). Am J Trop Med Hyg 80(5): 846-855.


Societal Perspective

CRITERIA ITEM VALUATION PUBLISHED COST

(US$)

COST PER CASE 2013

(US$)

Dengue

Treatment

Ambulatory/ Indirect Minimum wages or cost/

school day 176.36 (2009) 193.28

Hospitalized/ Indirect Minimum wages or cost/

school day 200.55 (2009) 219.79


= + Avoidance of productivity losses to receive treatment


Public Provider & Societal Perspective

CRITERIA ITEM VALUATION SOURCE /

REFERENCE

COST 2013

PER DOSE

(US$)

PUBLIC

PROVIDER

COST PER

DOSE (US$)

SOCIETAL

COST PER

DOSE

(US$)

Dengue

Vaccination

Program

Ad

min

istr

atio

n

Personnel MOH salary scale Ministry of Health

Clinician’s opinion

3.58 3.58

(Provider) 5.96

(Societal)

Equipment &

consumable

items

MOH price list

Treatment of

adverse events

Average cost in

Malaysia public

healthcare center

Clinician’s opinion

WHO-CHOICE

Indirect

Weighted

minimum wages

and cost per

school day

Ministry of

Human Resource

Malaysia

Suaya 2009

2.38 -


= - cost of Administering Vaccine


Using Dynamic Transmission Model to Determine the ∆

1. Coudeville L, Garnett G [2012] PloS One

2. Amaku M, Coudeville L, Massad E [2012] Rev. Inst. Med. trop. S. Paulo

Key features

Compartmental model (deterministic)

Host-vector interactions

Interaction between the 4 serotypes

Age-specific level of incidence & disease transmission

Host and vector population growth

Seasonality

Serotype-specific impact of vaccination

Vaccinated

Flow diagram

- 4 serotypes -

Vectors

Incub1

Susceptible

Infec1

Infec2

Infec3

Infec4

Incub2

Incub3

Incub4

Vectors

Incub1

Susceptible

Infec1

Infec2

Infec3

Infec4

Incub2

Incub3

Incub4

VaccinatedSusceptible

Short-termimmunity

Long-term immunity

Hosts – Dengue 2

Latent infection

Dengue Fever

DHF/DSSAsymptomatic

InfectionDengue Fever

DHF/DSSAsymptomatic

Infection


Latent infection

Short-termimmunity

Long-termimmunity

Hosts – Dengue 1

Dengue Fever

DHF/DSSAsymptomatic


DHF/DSSAsymptomatic

Infection

Susceptible

Short-term immunity

Long-termimmunity

Hosts – Dengue 3

Dengue Fever

DHF/DSSAsymptomatic


DHF/DSSAsymptomatic

Infection

Latent infection


Short-termimmunity

Long-termimmunity

Hosts – Dengue 4

Dengue Fever

DHF/DSSAsymptomatic


DHF/DSSAsymptomatic

Infection

Latent infection


WHAT IS THE ECONOMIC IMPACT & COST-EFFECTIVE PRICE OF DENGUE VACCINE IN

MALAYSIA?

R13C30


Evaluated Strategies

NATIONWIDE HOTSPOT

Strategy R9C17 R9C30 R13C30 R9C17 R9C30 R13C30

Compliance 95% 66%

60%

95% 64%

59%

N 8,429,404 12,572,912

10,619,309

1,531,057

2,283,654

1,928,816

*Hotspots: Kuala Lumpur, Petaling, Putrajaya, Klang, Hulu Langat & Gombak

**Catchup within 1 year


Simulation Parameters

Simulation Parameters Values

Reporting factors – Hospitalized2 1.7

Reporting factors – Ambulatory2 3.79

Vaccine Wastage1 20%

Discount Rate3 3%

Vaccine Protection4 10 years

GDP/capita 2013 (IMF 2014) 10456.89 $

1. Ministry of Health Malaysia key personnel expert opinion.

2. Shepard, D.S., et al. [2012] Am J Trop Med Hyg, 87(5): p. 796-805.

3. Malaysia Pharmacoeconomics Guidelines.

4. Assumptions.


THS R13C30 Health Impact

No Vaccination

Vaccination

Dengue cases

904,259

450,983

No Vaccine

With Vaccine

50% (95%CI 33-65%)

Dengue deaths

52% (95%CI 35-68%)

No Vaccine

With Vaccine

973

464

Disability-Adjusted-Life-Year (DALY) 32,387.5

15,528

No Vaccine

With Vaccine

No Vaccination

With Vaccination

52% (95%CI 35-67%)

53% (95%CI 36-68%)

Life Year Lost

No Vaccine

With Vaccine

10,551

22,377.5


Summary : Economic Impact

Disease Cost With Vaccine (Provider)

324.98

664.06

158.04

334.59

291.19

598.11

141.67

300.61 370.90

756.96

176.17

374.87

0

100

200

300

400

500

600

700

800

Targeted Hotspot R13C30 Nationwide R13C30

US$

M

ILLI

ON

S

Disease Cost With Vaccine (Societal) Productivity Loss With Vaccine

Disease Cost Without Vaccine (Provider) Disease Cost Without Vaccine (Societal) Productivity Loss Without Vaccine

↓51% (95%CI 60-38%)

↓52% (95%CI 60-39%)

↓50% (95%CI 61-39%)

↓50% (95%CI 60-38%)

↓50% (95%CI 60-39%)

↓52% (95%CI 60-38%)

Period 2016-2025


Scenario Dengue Cases

Averted

Dengue Deaths Averted

Life Year Lost Averted

DALY Averted

THS R13C30 448,124 (50%) 509 (52%) 11,785 (53%) 16,751 (52%)

THS R9C30 474,857 (52%) 537 (56%) 12,427 (56%) 17,721 (55%)

THS R9C17 365,510 (41%) 415 (43%) 9,747 (44%) 13,815 (43%)

NW R13C30 1,060,222 (50%) 1,202 (53%) 27,834(56%) 39,584(52%)

NW R9C30 1,122,456 (53%) 1,271 (56%) 29,432 (56%) 41,918 (55%)

NW R9C17 858,559 (41%) 976 (43%) 22,927 (44%) 32,479 (43%)

Summary : Health Impact

Period 2016-2025


Scenario Total Disease Cost Reduction

US$ % Reduction

THS R13C30 163,859,846 51%

THS R9C30 173,952,237 54%

THS R9C17 132,487,470 41%

NW R13C30 386,962,641 52%

NW R9C30 410,918,544 55%

NW R9C17 311,284,079 42%

Summary : Economic Impact

Public Provider Period 2016-2025


0

$46.00 $40.92

$38.13

$17.63 $15.49 $14.23

$93.00 $95.00

$105.00

0

$70.65

$62.81 $58.61

$26.82 $23.52 $21.61

$8.13 $3.81

$19.05

$40.87

$85.71

0

20

40

60

80

100

120

US$ per dose PROVIDER US$ per dose SOCIETAL

CE Price of All Dengue Vaccine

* Source: Bahagian Perkhidmatan Farmasi, MOH. Updated December 2013

Price of Other Vaccine CE Price in Literature CE Price DEN Vac


Cost-Effectiveness Threshold Price: Univariate Sensitivity Analysis

Public Provider’s Perspective: Highly Cost-Effective Price

46.72

44.84

40.95

52.19

58.79

34.13

68.46

34.53

30.63

45.28

46.43

51.05

39.8

42.19

58.68

43.11

67.85

82.33

25 35 45 55 65 75 85

Vaccine administration cost (80%/120%)

Vaccine coverage rate for catch up (20%/80%)

Cost of dengue disease (80%/120%)

Vaccine Wastage (10%/30%)

Discount rate (0%/5%)

Reporting factors - Hospitalized (1/2.45)

Model time horizon (5/30 years)

Vaccine protection duration (5/30 years)

Reporting factors - Ambulatory (1/10.38)

Highly Cost-Effectiveness Threshold Price/dose, US$

Upper

Lower

THS R13C30

46.00


Conclusion

• Dengue vaccination in Malaysia reduces the dengue related health and economic burden ranging from 41-56% for different strategies.

• A vaccination program would be highly cost-effective at a price below US$46 from the provider perspective in the targeted hotspot R13C30 scenario.

• The presence of assumptions and uncertainties in key parameters, but have been assessed through DSA and PSA

• Burden of dengue disease in this study only captures dengue treatment. Other factors such as dengue related deaths, long-term sequelae of dengue disease, vector prevention & control, surveillance, loss in tourism and loss in foreign investment were not included.


THANK YOU

Acknowledgement and appreciation to:

• Ms Yeo Hui Yee, MSc Candidate

• Sanofi for the research grant.

• Laurent Coudeville, Lucas Steinberg, Sanofi Pasteur

• Dr Balvinder, Dr Amar, Dr Rohani, MoH Malaysia

• Shafie AA, Yeo HY, Coudeville L, Gill BS, Steinberg L. A dynamic transmission model

for dengue virus in Malaysia. (in submission)

• Yeo HY, Shafie AA, Coudeville L, Steinberg L, Gill BS, Jahis R, Amar-Singh HSS.

The potential cost-effectivenss of different dengue vaccination program in Malaysia:

assessment using dynamic transmission model (in submission)


Vaccine Administration Cost Estimates (Provider Perspective)

Sectors Items Costs/Dose Reference Notes

Personnel

Medical Officer x1

US$ 2.72 • Clinician’s opinion • Ministry of Health

salary scale

• This team can vaccinate 100 subjects per day.

Staff Nurses x2

Community Nurses x3

Healthcare Assistant x1

Driver x1

Variable

Syringe x1

US$ 0.30 • Clinician’s opinion • Ministry of Health

purchase price

• Vaccine will be marketed as 5-dose vial with diluent supplied.

Needle x1

Gloves x1

Alcohol Swab x1

Sharp Bin + Disposal

Fixed

Pharmaceutical Fridge x1

US$ 0.55

• Clinician’s opinion • Ministry of Health

purchase price • Malaysia NIP

Handbook

• These equipment would cover the vaccination of 100 subjects per day over their useful lifespan.

Vehicle x2

Portable Ice Box x10

Dial Thermometer x10

Adverse Events Ambulatory Treatment US$ 0.01 • Clinician’s opinion • CPG Dengue • WHO-CHOICE1

• 1% with minor adverse event will seek treatment.

Total Cost/ Dose = US$ 3.58

1. WHO-CHOICE = World Health Organization Choosing Intervention That Are Cost-Effective


Summary : Total Vaccine Administration Cost

Provider & Societal Period 2016-2025

Scenario Provider Perspective

US$ Societal Perspective

US$

THS R13C30 25,164,652 6,998,654

THS R9C30 29,050,475 8,099,966

THS R9C17 24,739,279 6,891,059

NW R13C30 139,368,344 38,772,172

NW R9C30 161,080,465 44,895,612

NW R9C17 136,204,786 37,939,473

Documents

Assoc Prof Asrul Akmal Shafie