Health economic study dr amir hamzah

Health Economic Study inMalaysia

Amir Hamzah Abdul LatiffMMed, MRCP, FACAAI

Consultant Paediatrician & Clinical Immunologist/AllergistPantai Hospital Kuala Lumpur

PresidentMalaysian Society of Allergy & Immunology (MSA))

The recommendation

Recommendation 2 – HYDROLYSED FORMULA

For infants at increased risk of allergic disease and who cannot

be exclusively breastfed for the first 4 to 6 months, a hydrolysed

formula appears to offer advantages to reduce the risk of cow’s

milk protein allergy and allergic disease.

(Strength of recommendation – A)

1. Partially hydrolysed whey formula and extensively hydrolysed

casein formula reduce the risk of atopic dermatitis and cow’s

milk protein allergy to regular cow’smilk protein formula. 47,48

2. When considering a hydrolysed formula, it is advised tochoose one with reduced allergenicity that has been proven

or confirmed. 47

Economic impact of using partially hydrolyzed whey infant formula

versus standard cow’s milk formula

in the prevention of atopic dermatitis (AD)

Some Definitions

• Economics

o Study of the allocation of scarce resources

• Health Economics

o Economic principles applied to healthcare

• Pharmaco-economics

o Economic principles applied to drug therapy

• Economic Evaluation

o main decision making tool in economics

o Economic evaluation is about efficiency and is:‘the comparative analysis of alternative courses of action in terms of both their costs and consequences’

(Drummond, 1997)

Types of economic evaluation

• Cost minimisation analysiso Equal outcomes / clinical benefit assumed

o Which has lowest overall total costs?

• Cost Benefit analysiso Both costs and outcomes expressed in monetary value

o Difficult to value all health benefits in monetary terms

• Cost Effectiveness analysiso Outcomes expressed in natural units

o Cost per “% drop in blood pressure” / cure

• Cost Utility analysis o Outcomes expressed in QALYs

o Cross disease comparisons possible

o Considered current gold standard measure

Background & Objective

Background

Although infants should be breastfed for as long as appropriate, some are not exclusively breastfed

Infants who are not exclusively breastfed may be fed with standard cow’s milk formula (CMF) or alternate formulas, such as partially hydrolyzed-whey formula (pHF-W)

Clinical trial data has shown that the incidence of atopic dermatitis (AD) is higher among healthy at-risk children initially fed with CMF vs. children fed pHF-W

The economic impact of early feeding with CMF or pHF-W when considering the reduction in AD is unknown

Objective

• To estimate the economic impact of feeding high-risk infants

with partially hydrolyzed 100% whey based formula (pHF-W)

instead of standard cow’s milk formula (CMF) for the first 4

months of life as an nutritional intervention in the prevention

of atopic dermatitis (AD).

Lower Costs

Higher Costs

More EffectiveLess Effective

Health Economic Evaluation

Formula Cost

How about other costs?


Formula costs and other

costs

For which non-economic

advantages?

AD treatment costs(Dietary, medical)



Costs

Non-Economic

Advantages

Quality of life of children

FormulaAD (tests, visits, formula change,

medicines)

Quality of life of parents

Cost Effectiveness Ratio

CER = (Increase in Cost)

(Improved Effectiveness)

CER = (Cost of Treatment 1 – Cost of Treatment 2)

(Effectiveness of Treatment 1 - Effectiveness of Treatment 2)

Methods

Model Overview

Model Overview

Method Cost effectiveness (Markov) model using Microsoft Excel

Intervention First 4 months of life, feeding with pHF-W vs. CMF [based on GINI study]

Target population “At risk” (atopic heredity) healthy infants living in developed urban area who are notexclusively breastfed and who would otherwise receive CMF

Cost considered All (“societal perspective”), regardless of who incurs these costs, per child

Data sources Published literature, Opinion/data assumptions from KOLs, andPricing and market share data from Nestle affiliates

Analytical timeline Infant formula feeding for prevention of AD =4 months

Full analytical horizon = 6 years

Outcomes measures Cost, AD incidence, time spent post-AD diagnosis, AD symptoms-free days, quality adjusted life years (QALYs)

Discount rate 3% per year for costs and clinical effects (i.e., QALYs)*

Sensitivity analysis Univariate deterministic and multivariate probabilistic

*In the model, costs and benefits occur at different time points. A common practice in cost–benefit analysis, called discounting, is toexpress all costs and benefits in terms of their present value by assigning smaller weights to those that occur further away in thefuture than to those occurring more recently. Discounting makes costs and benefits occurring at different times comparable.

Key Model Parameters / Assumptions

Key Model Parameters / Assumptions

Age Groupings• <1 year• 1-6 years

Treatment modality categories (for AD)• Dietary (change in infant formula)• Pharmacological• Combined dietary and pharmacological

Maximum duration of formula use(age when formula feed ends)

• 1 yr (hence: from 1 yr onward, treated pharmacologically only)

AD severity categories• Mild• Moderate• Severe

Body location • Model does not distinguish location of AD symptoms on body

Medical perspective • Model considers paediatrician outlook

Quantities of formula• Daily quantity of infant formula consumed adjusted for age-specific

nutritional requirements and infant formula product labels

Model Concept

Birth (No AD history)

[A]

Initiate CMF or

pHF-W [B]

AD episode on CMF or pHF-W [C]

Switch to next

formula 1 + add drug

1 [E]

Switch to next

formula 2 + add drug 1

[K]

ADCS on next

formula 1 [G]

Switch to next

formula 2 [H]

Switch to next

formula 1 [D]

Stay on CMF or pHF-W,

add drug 2 [M]


add drug 3 [N]

ADCS on CMF or

pHF-W [L]


add drug 1 [F]

Initial AD episode (by

severity)

No Response

Switch to next

formula 2 + add drug 1

[J]

No Response

ADCS on next

formula 2 [I]

Response

Res

po

nse Flare

Response

Response

Response

Flar

e

No Response No Response

Flare

Flar

e

No Response

Response

Flare

No AD

No AD

No AD

Moderate AD

Severe

Mild

No ADfed with pHF-W

for 4 months

Moderate AD

Severe

Mild

No ADfed with CMF for

4 months

• Incidence of AD depends on formula• Choice of AD management depends on severity and age group• Response rates vary by therapy• Flares vary by severity

Simplified Model Structure

Dietary

Pharmacologic

or AD Controlled

Flare

Infant age 0without AD

responses

incidence

flares

management

Dietary+ Pharmacologic

No Flare

Star

t h

ere

Model Inputs and Sources

Model Input Source

Incidence of AD von Berg et al, Allergy Clin Immunol, 2008 (GINI study)

Utility of AD by severityPitt et al, Br J Dermatol, 2006; Stevens et al, Br J Dermatol, 2005

Severity of AD (Proportion of AD patients mild vs. mod/severe)

Approach to management of AD (use of formula change, medical, combo for AD treatment)

Diagnostic testing upon initial development of AD

Formula change - Change in initial formula for treatment (0-1 yr of age)

Time to Formula switch

Medical treatment used by age group

Response rates to AD treatment (infant formula only and combination treatment)

Response rates to 1st, 2nd and 3rd line medical treatment

Probability of AD flare

Hospitalization due to AD

Resource utilization – Number of Physician visits

Medical treatment used (specific products and quantities)

Primarily: KOL survey,

Secondarily: Nestle Malaysia (as needed)

Daily quantity of infant formula consumed due to partial breastfeeding

Infant Formula costs

Physician visit costs

Lab test costs

Hospitalization costs

Medical treatment costs

Indirect costs

Primarily: Nestle Malaysia

*Model inputs and sources listed have been reviewed/discussed with Nestle and KOLs at a previous meetings.

Main Results

Model-based Estimated Time to AD Diagnosis

61%

75%

14%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

0 52 104 156 208 260 312

Pe

rce

nt

surv

ivin

g w

ith

ou

t A

D d

iagn

osi

s

Weeks since birth

CMF pHF-W

pHF-W reduces the proportion of patients developing AD by 14 percentage points

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

0 1 2 3 4 5 6

Cu

mu

lati

ve p

rop

ort

ion

of

infa

nts

d

eve

lop

ing

AD

as

rep

ort

ed

in G

INI

Years

Cumulative Incidence of AD & Average Time Spent Post-AD Diagnosis

CMF Time after AD =1.69 years

pHF-W Time after AD =1.01 years

39%

14%

pHF-W reduces the proportion of patients developing AD by 14 percentage points and reduces the time spend post-initial-AD diagnosis

25%

Cumulative Discounted Total Costs (Malaysian Ringgit $)

$2882

$1766

Difference = $1116

$0

$500

$1,000

$1,500

$2,000

$2,500

$3,000

$3,500

0 52 104 156 208 260 312

Dis

cou

nte

d c

um

ula

tive

co

sts

for

an a

vera

ge

infa

nt

en

teri

ng

the

mo

de

l

Weeks since birth

PHF-W CMF

pHF-W reduces the cumulative costs associated with AD by $1,116 at 6 yearspHF-W is also less expensive over almost the entire period

Direct and Indirect Costs by Category(Malaysian Ringgit $)

$-

$500

$1,000

$1,500

$2,000

$2,500

$3,000

$3,500

CMF pHF-W

Indirect Costs

Hospitalization

Nurse calls

Lab tests

Pharmacological treatments

Visits

Note: Indirect costs include time loss for taking care of AD child, travel to clinic, and time loss to go to the lab

The cost of AD are largely driven by visit, pharmacological treatment, and indirect costs (each accounting for about 1/3 of costs)

pHF-W reduces costs for all key categories

Discounted costs (Malaysian Ringgit $) per child CMF pHF-W Difference

Direct $1,966 $1,216 -$750Indirect# $916 $550 -$366

Total $2,882 $1,766 -$1,116

Undiscounted effects (per child)

Percent with AD 39% 25% -14%

Number of days with AD symptoms 93.04 55.11 -37.93Quality-adjusted life-years 5.90 5.94 0.04

Cost effectiveness ratios (all discounted)

Discounted incremental cost per AD case avoided Dominant

Discounted incremental cost per AD day avoided Dominant

Discounted incremental cost per quality-adjusted life year gained Dominant

Cost and Cost-Effectiveness

# Indirect costs include time loss for taking care of AD child, travel to clinic, and time loss at the lab*Dominant means that pHF-W is less expensive and more effective than CMF

pHF-W decreases costs, the risk of AD, and the number of days with symptoms, and increases QALYsSince it is less expensive and more effective, it is considered to be a “dominant” option in health

economic jargon

Sensitivity Analyses

Univariate Sensitivity Analysis

Tornado Chart of Cost Difference (pHF-W vs. CMF)

The model results are most sensitive to the assumptions about the incidence of AD and the degree to which CMF is associated with a higher risk of AD than pHF-W

Multivariate Probabilistic Sensitivity Analysis

-$2,500

-$2,000

-$1,500

-$1,000

-$500

$0

$500

0.00 0.02 0.04 0.06 0.08 0.10 0.12 0.14 0.16 0.18 0.20

ΔC

ost

ΔQALY

Median

CI region

Base Case

Number of Simulations ran – 5,000

When the model is run 5,000 times, and each time with different inputs for each variable (which are selected according to a pre-specified, e.g. normal distribution), the results change both in terms of cost savings and QALY gained. The figure is above is a

scatter plot of the net costs and net QALY differences for these 5,000 runs

The base case results and median results across the 5,000 simulations are very consistentpHF-W is cost saving in almost all runs

the cost savings range from $650 to $1464 per child; the QALY gains range from 0.017 to 0.079

Model-Derived Cost of AD

Total Cost per Child with AD

Notes: all costs are undiscounted; restricted means (as follow up ends at the end of age 6); expressed in Malaysian Ringgit.*Cost per year is not cost over 6-year follow up divided by 6 years – it is rather the cost over 6-year follow-up divided by thenumber of years post AD diagnosis. The same applies for the number of visits.

Direct costs/child with AD over 6-year follow up* $5378

Total costs/child with AD over 6-year follow up* $7851

Direct costs/child with AD per year $1289

Total costs/child with AD per year $1882

Number of visits/child with AD over 6-year follow up:* GP and specialist 28.9

Number of visits/child with AD per year: GP and specialist 6.92

Number of visits/child with AD per year: GP 5.06

Number of visits/child with AD per year: Specialists 1.86

The cost of AD per child who develops AD over the 6-year period is $7851The annual cost per year is $1,882

The number of visits over the 6-year period is approximately 29The number of visits/year after AD develops is approximately 7, including 5 with GPs and 2 with specialists

Cross-country Comparisons

Estimated Annual GP Visits for Incident AD Case

The average annual number of visits per incident AD case are estimated at approximately 4.24, 4.73, and 1.89 for Indonesia, Malaysia, and Singapore, respectively.

Study Country Population Pub Year Mild Moderate Severe Total

Chang and Sung U.S. Patients with an AD diagnosis 2005 1.74Pharmerit Singapore >0-6 Years 2013 2.35Barbeau and Lalonde Canada 6 months to 84 years 2004 2.31 3.19 5.74 3.59Ngamphaiboon et al Thailand Children aged 0-5 2012 4 8 13 4.27a

Ngamphaiboon et al Thailand Children aged 0-5 2012 4 8 12 4.58b

Pharmerit U.S. >0-6 Years 2013 5.05Mertens et al Germany >1 year (average 23) 2012 5.40Pharmerit Malaysia >0-6 Years 2013 6.92Pharmerit Indonesia >0-6 Years 2013 8.12Pharmerit Philippines >0-6 Years 2013 11.06Su et al Australia 4 mos-15yrs at dermatology clinic 1997 7.0 13.0 23.2 12.88

Taylor et al U.K.

Paediatric patients with CMA who started nutrition with eHF

2012 13.1

Paediatric patients with CMA who started nutrition with AAF

2012 17.5

a – atopic dermatitis, not specific to cow’s milk allergyb – atopic dermatitis, specific to cow’s milk allergy

Compares reasonably well with rest of literature

Literature Review – Annual AD costs

a – atopic dermatitis, not specific to cow’s milk allergyb – atopic dermatitis, specific to cow’s milk allergy* Figure in parenthesis when excluding cost of GP visits

Study Country Costs Age Severity Year of data Annual Cost (US$)Annual Cost (2013)

(US$)

Ngamphaiboon 2012 Thailand Direct Children aged 0-5 Alla 2010 175 184a

Ngamphaiboon 2012 Thailand Direct Children aged 0-5 Allb 2010 310 338b

Pharmerit Malaysia Direct 0-6 yrs All 2013 388 (308)* 388 (308)*

Pharmerit Philippines Direct 0-6 yrs All 2013 433 433

Pharmerit Philippines Total 0-6 yrs All 2013 443 443

Su 1997 Australia Total 4 mos-15yrs Mild 1997 263 477

Pharmerit Malaysia Total 0-6 yrs All 2013 566 (486)* 566 (486)*

Pharmerit Indonesia Direct 0-6 yrs All 2013 220 682

Pharmerit Indonesia Total 0-6 yrs All 2013 689 689

Ellis 2002 U.S. Direct Pediatrics NA 2001 450 705

Barbeau 2004 Canada Total 6 mos-84yrs All 2002 618* 742

Ellis 2002 U.S. Direct All NA 2001 580 910

Pharmerit U.S. Direct 0-6 yrs All 2013 945 945

Pharmerit Singapore Direct 0-6 yrs All 2013 958 958

Pharmerit Singapore Total 0-6 yrs All 2013 1,070 1,070

Fivenson 2002 U.S. Direct All (mean 17yrs) NA 1997 609 1,104

Ellis 2002 U.S. Direct Pediatrics NA 2001 740 1,160

Pharmerit U.S. Total 0-6 yrs All 2013 1,071 1,071

Su 1997 Australia Total 4 mos-15yrs Mod 1997 653 1,184

Fivenson 2002 U.S. Direct 0-4 yrs NA 1997 725 1,314

Ellis 2006 Multinational Total 2-17 yrs, conventional medsMild-Mod

2004 1,253 1,725

Su 1997 Australia Total 4 mos-15yrs Sev 1997 1,001 1,815

Ellis 2002 U.S. Direct All NA 2001 1,250 1,960

Ellis 2006 Multinational Total 2-17 yrs, pimecrolimusMild-Mod

2004 2,581 3,553

The annual cost of AD/child who develops AD (converted in $US) appears within range of other estimates

Limitations and strengths• Model structure is simplification of reality but nevertheless attempts to

capture treatment patterns and costs with a high degree of detail

• Results are based on survey of KOLs

• The impact on the AD child’s parent’s productivity loss while at work was only partially considered whereas the impact on the parent’s quality of life was entirely excluded

• Longer-term impact of AD was excluded; that is, all costs were restricted to the first 6 years, hence means are somewhat biased

• Costs for other allergies (e.g., allergic rhinitis) potentially affected by the use of pHF-W vs. CMF were also excluded

• Cost of AD and number of visits for AD were within range of other published studies

Conclusions

• Over the 6-year follow-up period, use of pHF-W instead of CMF among high-risk

infants results in:

• costs savings (-$1,116)

• avoided AD cases (-14% absolute percentage),

• additional days without AD symptoms (+38 days),

• Additional years without AD diagnosis (+0.68 years, i.e., just over 8 months), and

• QALY gains (+0.04 QALYs).

• pHF-W appears to be a cost effective strategy for the prevention of AD in high-risk

infants.

Abstract

Cost Effectiveness of Partially Hydrolyzed Whey Protein Formula in the Primary Prevention of Atopic Dermatitis in At-Risk Urban Infants in Malaysia

Bhanegaonkar AJ 1, Horodniceanu EG1, Abdul Latiff AH2, Woodhull S3, Khoo PC3, Detzel P4, Ji J1, Botteman MF1

Objectives: To estimate the economic impact of feeding high-risk infants with partially hydrolyzed 100% whey based formula (pHF-W) instead of standard cow’s milk formula (CMF) for the first 4 months of life as a nutritional intervention in the prevention of atopic dermatitis (AD).

Methods: A cohort Markov model was developed to simulate, from birth through age 6, the incidence and cost of AD in high-risk infants fed with pHF-W instead of CMF during the first 4 months of life. Data sources included published literature, market data, and key opionion leader inputs. Key modeled outcomes included reduction in AD risk, time spent post-AD diagnosis, AD-free days, quality-adjusted life years (QALYs), and costs. All results were discounted by 3% per year. Costs were expressed in 2013 Malaysian Ringgit ($).

Results: Feeding high-risk infants pHF-W instead of CMF resulted in an estimated absolute 14 percentage point reduction in the risk of AD, a reduction in the time spent post-AD diagnosis of 8.16 months (95% CI: 5.40, 10.03) per child, and an additional 38(95% CI: 16, 62) AD-free days per child. The AD-related cost estimates when feeding high-risk infants with pHF-W or CMF were $1,766 (95% CI: $1,389, $2,267) and $2,882 (95% CI: $2,531, $3,239) per child, respectively, resulting in a net difference in favor of pHF-W of $1,116 (95% CI: $650, $1464) per child. Considering those who do develop AD, the mean annual cost of AD was $1882 (across both arms) per child with AD. The mean cost of AD over the entire period was $7851 (across both arms) per child with AD.

Conclusions: Using pHF-W instead of CMF in high-risk infants is expected to result in reduction in the burden of AD and save $1,116 per child.

Health economic study dr amir hamzah

Health & Medicine

Transcript of Health economic study dr amir hamzah