Economic evaluation of a 100% whey-based partially hydrolyzed infant formula in the prevention of atopic dermatitis among Swiss children

Figures & data

Figure 1.  Decision tree model depicting the treatment patterns of atopic dermatitis in Switzerland in a population ranging from newborns to 3-year olds.

Table 1.  Epidemiological and clinical parameters applied in the model.

	Quantity applied	Reference
Initial Cohort
Newborns in Switzerland in 2009	80,000	25
Exclusively breastfed infants in Switzerland	14%	26
Percentage of ‘at risk’ newborns	33%	4–6
Infants forming starting cohort	22,933	Calculation
Of formula-fed infants in Switzerland, average percentage who are exclusively formula-fed	7%	Calculation26
Of formula-fed infants in Switzerland, average percentage who are both formula-fed and breastfed	93%	Calculation26
Relative Risk of developing AD (PHF-W vs SF)
Time points
0–3 months	0.25	16,24
3–6 months	0.35	16,24
6–12 months	0.81	16,24
12–18 months	0.82	16,24
18–24 months	0.83	16,24
24–30 months	0.84	16,24
30–36 months	1.06	16,24
Incidence rates of AD
With SF
0–3 months	3.87%	16,24
3–6 months	3.87%	16,24
6–12 months	4.73%	16,24
12–18 months	1.17%	16,24
18–24 months	1.17%	16,24
24–30 months	1.76%	16,24
30–36 months	1.76%	16,24
With PHF-W
0–3 months	0.97%	16,24
3–6 months	1.35%	16,24
6–12 months	3.83%	16,24
12–18 months	0.96%	16,24
18–24 months	0.97%	16,24
24–30 months	1.48%	16,24
30–36 months	1.86%	16,24
Distribution of cases of AD
Mild	75%	EO
Moderate	15%	EO
Severe	10%	EO
Treatment approach of infants less that 6 months old
Medical treatment approach
Mild	100%	EO
Moderate	90%	EO
Severe	90%	EO
Combined treatment approach
Mild	0%	EO
Moderate	10%	EO
Severe	10%	EO
Estimated response rates to first-line treatment
Mild	90%	EO
Moderate	88%	EO
Severe	80%	EO
Estimated response rates to second-line treatment
Mild	100%	EO
Moderate	100%	EO
Severe	100%	EO
Mortality rate in the general Swiss population
At the end of the first year of life	0.48%	27
At the end of the second year of life	0.04%	27

Note: Expert opinion was provided by Dr Dominique Belli.

AD, Atopic dermatitis; EO, Expert opinion; PHF-W, Nestlé brand of 100% whey-based partially hydrolyzed formula; SF, Standard cow’s milk formula.

Table 2.  Economic parameters applied in the model.

	Quantity applied	Reference	Cost per unit	Reference
Formula
PHF-W (Nestlé – Beba HA®)	Varied with the age of the subject and with the rate of partial breastfeeding^a	Calculation	CHF 34.70/1000 g	^b
SF (Danone – Aptamil 1®)		Calculation	CHF 30.30/1000 g	^b
EHF-Whey (Nestlé – Althera®; Alfaré)		Calculation	CHF 59.50/1000 g	^b
Amino Acid Based Formula (Nutricia – Neocate®)		Calculation	CHF 164.50/1000 g	^b
Medical visits
General pediatrician, Dermatologist or allergist	1 visit for 90% of mild cases, 2 visits for 10% of mild cases and 3 visits for moderate or severe cases	EO	CHF 65.00/initial visit; CHF 32.50/subsequent visits	EO
Hospitalization	1.5% of moderate or severe cases	EO	CHF 6017.75/hospitalization	EO
Treatment
Emollient cream (Excipial Lipolotion® or Excipial Hydrolotion®)	250 g per 3-month period, used for 2–3 months in mild AD and 6 months in moderate or severe AD	EO	CHF 12.70/200 g tube	28
Class II topical corticosteroids	Mild cases and 50% of moderate cases use 30 g; the remaining 50% of moderate cases and all severe cases use 100 g	EO
Betamethasone dipropionate (Diprosone Crème®^)			CHF 15.15/30 g tube	28
			CHF 36.85/100 g tube	28
Mometasone (Elocom Crème®)			CHF 17.95/30 g tube	28
			CHF 26.75/50 g tube	28
Class III topical corticosteroids	Severe cases above 1-year old use 100 g	EO
Betamethasone dipropionate (Diprolène Crème®)			CHF 15.90/30 g tube	28
Methylprednisolone aceponate (Advantan®)			CHF 25.00/50 g tube	28
Immunosuppressants	50% of moderate cases use 30 g; the remaining 50% moderate cases and all severe cases use two 60 g
Pimecrolimus (Elidel®)		EO	CHF 64.00/30 g tube	28
			CHF 99.00/60 g tube	28
Tacrolimus (Protopic®)		EO	CHF 72.95/30 g tube	28
			CHF 115.85/60 g tube	28
Laboratory tests
Specific IgE Test	Used once in 40% of moderate or severe cases of AD	EO	CHF 41.59/test	^c
Prick Test	Used once in 40% of moderate or severe cases of AD	EO	CHF 55.79/test	^c
Oral Provocation Test	Used once in 5% of severe cases of AD	EO	CHF 274.48/test	^c
MOH reimbursement rates
Infant formulas (except amino-acid based formula)	90%	Assumption
Amino-acid based formula	0%	EO
Prescribed medication	90%	EO
Emollients	90%	EO
Medical visits, laboratory testing, and hospitalization	90%	EO
Participation in the workforce in Switzerland	57.80%	29
Time loss
Physician visits and laboratory testing	4 h for each visit	Assumption	CHF 38.26/hour	30,31
Child care for 2 days after the initial medical visit	8 h per day	Assumption	CHF 38.26/hour	30,31
Application of emollient cream	20 min daily over the application period	Assumption	CHF 38.26/hour	30,31
Application of topical medications (corticosteroids and immunosuppressants)	10 min daily over the application period	Assumption	CHF 38.26/hour	30,31
Hospitalization	5 days, 7.27 h per day	EO	CHF 38.26/hour	30,31
Travel	Travel to and from physician visits or laboratory testing (10 km each way)	Assumption	CHF 37.45/2-way trip	32,33

^aThe full breakdown of the daily quantity of formula consumed over 6 months is available upon request.

^bBased on a survey of costs in pharmacies.

^cBased on a survey of a laboratory clinic in Canton Fribourg, Switzerland.

Note: Expert opinion was provided by Dr Dominique Belli.

AD, Atopic dermatitis; EHF, Extensively hydrolyzed formula; EO, Expert opinion; MOH, Ministry of Health; PHF-W, Nestlé brand of 100% Whey-based partially hydrolyzed formula; SF, Standard cow’s milk formula; Tx, Treatment.

Table 3.  Base case results presented from the perspective of the Ministry of Health, of the family of the subject and of society as a whole.

	PHF-W	SF
Outcomes
Number of cases	2287	3940
Avoided cases	1653
Costs
Ministry of Health perspective
Cost of formula	CHF 14,398,641	CHF 12,519,931
Physician costs	CHF 173,830	CHF 299,444
Treatment costs	CHF 109,013	CHF 196,925
Hospitalization costs	CHF 46,457	CHF 80,029
Costs of lab tests	CHF 10,844	CHF 18,681
Total cost	CHF 14,738,785	CHF 13,115,010
Incr cost		CHF 1,623,775
Incr C/AC (ICER)		CHF 982
Family perspective
Cost of formula	CHF 1,602,980	CHF 1,402,632
Physician costs	CHF 19,314	CHF 33,272
Treatment costs	CHF 12,113	CHF 21,881
Hospitalization costs	CHF 5162	CHF 8892
Costs of lab tests	CHF 1205	CHF 2076
Cost of time lost	CHF 5,019,849	CHF 8,672,290
Travel costs	CHF 221,129	CHF 380,506
Total cost	CHF 6,881,752	CHF 10,521,547
Incr cost		−CHF 3,639,795
Incr C/AC (ICER)*		−CHF 2202
Societal perspective
Total cost	CHF 21,620,537	CHF 23,636,558
C/AC	CHF 1047	CHF 1244
Incr cost		−CHF 2,016,021
Incr C/AC (ICER)*		−CHF 1220

*Negative ICERs are indicative of cost savings due to the prevention of AD cases with PHF-W vs. SF, and hence indicate dominance of PHF-W over SF.

C/AC, Cost per avoided case; Incr, Incremental; ICER, Incremental cost-effectiveness ratio; PHF-W, Nestlé brand of 100% Whey-based partially hydrolyzed formula; SF, Standard cow’s milk formula.

Table 4.  Results of the one-way sensitivity analyses presented from the perspective of the Ministry of Health, of the family of the subject and of society as a whole.

	Outcomes		Costs in CHF
	Cases		Ministry of Health			Subject’s family			Society
	PHF-W	SF	PHF-W	SF	ICER*	PHF-W	SF	ICER*	PHF-W	SF	ICER*
Base case	2287	3940	14,738,785	13,115,010	982	6,881,752	10,521,547	−2202	21,620,537	23,636,558	−1220
Sensitivity analyses
MOH covered 100% of infant formula program	2287	3940	16,337,828	14,503,226	1110	5,282,709	9,133,332	−2330	21,620,537	23,636,558	−1220
MOH covered 65% of infant formula program	2287	3940	10,741,178	9,644,472	663	10,879,359	13,992,086	−1883	21,620,537	23,636,558	−1220
MOH covered 35% of infant formula program	2287	3940	5,944,049	5,479,825	281	15,676,488	18,156,732	−1500	21,620,537	23,636,558	−1220
MOH covered 15% of infant formula program	2287	3940	2,745,964	2,703,395	26	18,874,573	20,933,163	−1245	21,620,537	23,636,558	−1220
MOH covered 12.98% of infant formula program	2287	3940	2,423,094	2,423,094	0	19,197,443	21,213,463	−1220	21,620,537	23,636,558	−1220
MOH covered 0% of milk program	2287	3940	347,399	621,072	−166	21,273,137	23,015,486	−1054	21,620,537	23,636,558	−1220
Increased the cost of SF by 10% to CHF 33.33	2287	3940	14,738,785	14,364,404	226	6,881,752	10,660,369	−2286	21,620,537	25,024,773	−2059
Decreased the cost of SF by 10% to CHF 27.27	2287	3940	14,738,785	11,865,616	1738	6,881,752	10,382,726	−2118	21,620,537	22,248,342	−380
Applied the highest available market cost of SF (CHF 18.80 per 600 g)	2287	3940	14,738,785	13,799,534	568	6,881,752	10,597,606	−2248	21,620,537	24,397,140	−1680
Applied the lowest available market cost of SF (CHF 15.20 per 600 g)	2287	3940	14,738,785	11,275,999	2095	6,881,752	10,317,213	−2078	21,620,537	21,593,211	17
Hypothetical rate of ‘at risk’ patients was 50%	3431	5911	22,108,177	19,672,515	982	10,322,628	15,782,321	−2202	32,430,805	35,454,836	−1220
Hypothetical rate of ‘at risk’ patients was 20%	1372	2364	8,843,271	7,869,006	982	4,129,051	6,312,928	−2202	12,972,322	14,181,935	−1220
The lower bound CI of the relative risk was used	1267	3940	14,584,854	13,115,010	550	4,523,000	10,521,547	−2244	19,107,853	23,636,558	−1694
The upper bound CI of the relative risk was used	4098	3940	15,014,678	13,115,010	−12,034	11,073,117	10,521,547	−3494	26,087,795	23,636,558	−15,528
The lower bound CI of incident rates was used	1640	2702	14,640,732	12,921,716	1619	5,384,098	7,646,027	−2130	20,024,831	20,567,743	−511
The upper bound CI of incident rates was used	2951	5179	14,838,953	13,307,774	687	8,414,660	13,395,943	−2235	23,253,613	26,703,717	−1548
Used the relative risks reported by Alexander and Cabana	2006	3940	14,700,935	13,115,010	820	6,241,036	10,521,547	−2212	20,941,971	23,636,558	−1393
The rounded down number of cans was used	2287	3940	14,021,865	12,487,244	928	6,801,959	10,451,344	−2208	20,823,823	22,938,588	−1279
Excluded the use of laboratory tests from the diagnostic approach	2287	3940	14,727,941	13,096,329	987	6,880,547	10,519,472	−2201	21,608,488	23,615,801	−1214
Excluded transportation costs	2287	3940	14,738,785	13,115,010	982	6,660,623	10,141,041	−2106	21,399,408	23,256,052	−1123
Excluded the cost of productivity time lost for the application of emollients	2287	3940	14,738,785	13,115,010	982	3,884,985	5,359,231	−892	18,623,769	18,474,241	90
Excluded the cost of productivity time lost for the application of corticosteroids	2287	3940	14,738,785	13,115,010	982	6,712,850	10,205,637	−2113	21,451,634	23,320,647	−1131
Medical visits and laboratory tests were aligned in time	2287	3940	14,738,785	13,115,010	982	6,846,745	10,461,244	−2187	21,585,530	23,576,254	−1204
Cost of leisure time lost was not taken into account	2287	3940	14,738,785	13,115,010	982	4,763,376	6,861,841	−1270	19,502,160	19,976,851	−287
Excluded the cost of leisure time and shifted the cost of productivity time lost to society	2287	3940	14,738,785	13,115,010	982	1,861,903	1,849,258	8	19,502,160	19,976,851	−287
No day lost due to child care at home	2287	3940	14,738,785	13,115,010	982	5,625,711	8,357,855	−1653	20,364,495	21,472,865	−671
No time lost due to hospitalization	2287	3940	14,738,785	13,115,010	982	6,869,977	10,501,263	−2197	21,608,762	23,616,273	−1214
Excluded hospitalization	2287	3940	14,692,328	13,034,981	1003	6,864,815	10,492,371	−2195	21,557,142	23,527,352	−1192
Time Horizon – 6 months	532	1773	14,475,625	12,779,626	1366	2,824,782	5,481,385	−2140	17,300,407	18,261,011	−774
Time Horizon – 3 years, discounted at 2.5%	4597	6509	15,111,674	13,533,067	826	12,307,633	16,565,125	−2227	27,419,307	30,098,193	−1401
Time Horizon – 3 years, discounted at 5%	4509	6412	15,098,120	13,518,254	830	12,103,219	16,342,398	−2227	27,201,339	29,860,651	−1397
Time Horizon – 3 years, discounted at 10%	4348	6237	15,073,525	13,491,349	838	11,732,330	15,937,931	−2226	26,805,855	29,429,280	−1389
Time Horizon – 3 years, only costs discounted at 2.5%	4692	6612	15,111,674	13,533,067	822	12,307,633	16,565,125	−2217	27,419,307	30,098,193	−1395
Time Horizon – 3 years, only costs discounted at 5%	4692	6612	15,098,120	13,518,254	823	12,103,219	16,342,398	−2208	27,201,339	29,860,651	−1385
Time Horizon – 3 years, only costs discounted at 10%	4692	6612	15,073,525	13,491,349	824	11,732,330	15,937,931	−2190	26,805,855	29,429,280	−1366

*Negative ICERs indicate dominance of PHF-W over SF. CI, Confidence interval; EHF, Extensively hydrolyzed formula; ICER, Incremental cost-effectiveness ratio; MOH, Ministry of Health; PHF-W, Nestlé brand of 100% Whey-based partially hydrolyzed formula; SF, Standard cow’s milk formula.

Figure 2.  Results of the Monte Carlo simulations from the Ministry of Health, family, and societal perspectives. These findings are presented for a population of 80,000 newborns (as in Switzerland in 2009), of which 22,903 were deemed to be ‘at risk’ and not exclusively breastfed. The presented incremental cost-effectiveness ratios were obtained by dividing the average incremental costs by the average avoided cases of AD which were generated from the 10,000 Monte Carlo simulations. The base case incremental cost-effectiveness ratios were CHF 982, −CHF 2,202, and −CHF 1,220 from the MOH, family, and societal perspectives, respectively. MOH, Ministry of Health.

Table 5.  Parameter estimates and distributions for variables tested in the Monte Carlo sensitivity analysis.

Parameter	Distribution type^a	Selected range
MOH milk program coverage for prevention	Uniform	13.98–100%
Alternative to PHF-W in case of discontinuation	Uniform	PHF-W 50–100%, SF and EHF-Whey 0–25%
Relative risk	Log Normal	Within the 95%CI
Incidence rates consideration	Triangular	Most likely = BC, minimum and maximum = LB and UB of the 95%CI
Rounding down or up the number of cans used	DUD	Round down or up
MOH medication coverage	Uniform	80–100%
MOH hospitalization coverage	Uniform	80–100%
MOH physician coverage	Uniform	80–100%
MOH lab test coverage	Uniform	80–100%
Cost of laboratory tests	Uniform	0–100% of BC costs
Transportation costs	Uniform	0–150% of BC costs
Cost of time lost	Uniform	0–150% of BC costs
Cost of time lost for laboratory tests	Uniform	0–100% of BC costs
Days lost due to child at home	DUD	1 or 2 days
Cost of hospitalization	Uniform	0–150% of BC costs
Time horizon	DUD	6 months, 1 year, 3 years
Discount rate beyond 1 year	DUD	2.5%, 5%, 10%
Discounting of outcomes beyond 1 year	DUD	Include or exclude
Monte Carlo Results	MOH	Family	Society
PHF-W
Average costs	CHF 9,242,558	CHF 11,015,777	CHF 20,259,011
Average number of AD cases	2,598	2,598	2,598
SF
Average costs	CHF 8,248,899	CHF 12,478,118	CHF 20,728,081
Average number of AD cases	4,070	4,070	4,070
Monte Carlo ICERs^b*	CHF 675	−CHF 994	−CHF 319
Median ICERs^c*	CHF 672	−CHF 928	−CHF 183
Distribution^d
Quadrant 1	99.28%	20.49%	44.60%
Quadrant 2	0.18%	0.18%	0.18%
Quadrant 3	0.00%	0.00%	0.00%
Quadrant 4	0.54%	79.33%	55.22%

^aA uniform distribution was applied when only two data points were available with an assumed equal likelihood for all points in between while a discrete uniform distribution was applied when only two or three specific data points were considered likely. A triangular distribution was used when determining whether to use the base case incidence rates or the upper or lower bound of the 95% confidence interval as reported by Iskedjian et al.24 As these data points were not distributed normally, a triangular distribution, which appeared to best fit the data set, was applied. As argued by Briggs et al.36, a log normal distribution was applied to the relative risk of developing AD.

^bThese Monte Carlo ICERs were obtained by dividing the average incremental costs by the average avoided cases of AD which were generated from the 10,000 Monte Carlo simulations.

^cThese median ICERS were generated from each Monte Carlo simulation (accounting for the incremental costs and outcomes of each simulation).

^dThe four quadrants are depicted in Figure 2. Quadrant 1 is associated with potential cost-effectiveness of PHF-W as it displays positive incremental costs and avoided cases. Quadrant 2 represents dominance by SF, as incremental costs for PHF-W vs SF are positive while avoided cases are negative. Quadrant 3 represents the unlikely scenario where incremental costs are negative but so are avoided cases. Quadrant 4 denotes dominance by PHF-W over SF as incremental costs and avoided cases are both negative. *Negative ICERs indicate dominance of PHF-W over SF.

AD, Atopic dermatitis; BC, Base case; CI, Confidence interval; DUD, Discrete uniform distribution; EHF, Extensively hydrolyzed formula; ICER, Incremental cost-effectiveness ratio; LB, Lower bound; MOH, Ministry of Health; PHF-W, Nestlé brand of 100% Whey-based partially hydrolyzed formula; SF, Standard cow’s milk formula; UB, Upper bound.

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