Cost-effectiveness of infant hypoallergenic formulas to manage cow’s milk protein allergy in France

Figures & data

Figure 1. Model structure22.

Table 1. Annual probabilities of atopic manifestations, being symptom free and cumulative incidence of being tolerant to cow’s milk per comparator.

Formula	Time	Allergic urticaria^1	Eczema^1	Asthma^1	Rhinoconjunctivitis^1	Symptom free^2	CM tolerance^3
AAF^4	Year 1	0.151	0.289	0.000	0.178	0.381	0.016
	Year 2	0.097	0.082	0.069	0.138	0.615	0.099
	Year 3	0.041	0.041	0.192	0.041	0.685	0.192
EHCF+LGG^4	Year 1	0.026	0.000	0.001	0.000	0.972	0.411
	Year 2	0.056	0.096	0.014	0.053	0.782	0.641
	Year 3	0.041	0.041	0.109	0.056	0.753	0.809
EHWF^4	Year 1	0.081	0.220	0.083	0.082	0.535	0.195
	Year 2	0.055	0.014	0.055	0.069	0.807	0.314
	Year 3	0.083	0.055	0.138	0.152	0.572	0.425
RHF	Year 1	0.082	0.096	0.001	0.095	0.726	0.153
	Year 2	0.151	0.137	0.109	0.110	0.493	0.264
	Year 3	0.041	0.083	0.151	0.138	0.586	0.412

AAF, amino acid-based formula; CM, cow’s milk; EHCF+LGG, extensively hydrolyzed casein formula with added Lactobacillus rhamnosus Gorbach Goldin; EHWF, extensively hydrolyzed whey formula; RHF, rice hydrolyzed formula.

¹Sourced from Nocerino et al [15].

²Calculated as one minus the sum of the annual probabilities of allergic urticaria, eczema, asthma and rhinoconjunctivitis for that cycle. ³Cumulative probabilities.

⁴Annual probabilities previously published in Martins et al. [29].

Table 2. Unit costs of healthcare resources and nutrition, per perspective.

	Unit Cost (€)			Sources
Perspective	Collective^1	FNHI	Families
General pediatrician (child < 2 years)
Hospital	32.0	32.0	-	[34,35]
Private practice with capped fees	32.0	22.4	9.6
Private practice with uncapped fees^2	32.0	19.6	12.4
General pediatrician (child 2 to 16 years)
Hospital	32.0	32.0	-
Private practice with capped fees	32.0	22.4	9.6
Private practice with uncapped fees^2	32.0	16.1	15.9
Initial visit Specialist
Hospital	50.0	50.0	-
Private practice with capped fees	50.0	35.0	15.0
Private practice with uncapped fees^2	50.0	35.0	15.0
Follow-up visit Specialist
Hospital	30.0	30.0	-
Private practice with capped fees	30.0	21.0	9.0
Private practice with uncapped fees^2	30.0	16.1	13.9
Initial visit dietitian				Assumption
Hospital	50.0	50.0	-
Private practice^2	50.0	0.0	50.0
Follow-up visit dietitian
Hospital	30.0	30.0	-
Private practice^2	30.0	0.0	30.0
Accident & emergency attendance	48.0	48.0	-	[36]
Hospital admission^3	1742.3	1742.3	-	[38]
Allergy and laboratory tests^2				[37,45]
Skin prick	37.2	26.0	11.1
IgE	16.0	11.2	4.8
Oral food challenge	42.7	42.7	-
Hemogram	10.0	7.0	3.0
Biochemistry	5.8	4.1	1.7
Blood test collection	4.0	4.0	-
Chest X-Ray	31.7	22.2	9.5
Nasal endoscopy	30.8	30.8	-
Medicines
Emergency food allergy kit
H1 antihistamines	1.84	0.50	1.35	[43]
H1 antihistamines + adrenaline autoinjector	59.02	37.66	21.36
Emergency asthma kit
β2 + spacer	19.63	9.32	10.31	[43,44,46]
β2 + spacer + oral corticosteroid	20.87	10.13	10.74
Emollients (cost per tube)	10.65	0.09	10.56	[43,47–49]
Topical corticosteroids (cost per tube)	1.42	0.92	0.50	[43]
Monthly prescription for antihistamines	2.45	0.59	1.86
Monthly prescription for inhaled corticosteroids	12.03	7.19	4.84
Diet
CM free packed lunch	1.63	-	1.63	[42]
CM free dessert^4	0.36	0.31	0.05	[50]
Infant hypoallergenic formulas^5 (per 100 ml of reconstituted formula)				[39,40,50]
AAF	2.13	1.79	0.34
EHCF+LGG	0.76	0.49	0.27
EHWF	0.69	0.47	0.22
RHF	0.49	-	0.49

AAF, amino acid-based formula; β2, beta-2 adrenergic receptor agonist; CM, cow’s milk; EHCF+LGG, extensively hydrolyzed casein formula with added Lactobacillus rhamnosus Gorbach Goldin; EHWF, extensively hydrolyzed whey formula; FNHI, French National Health Insurance; IgE, immunoglobulin E; RHF, rice hydrolyzed formula.

¹The Collective perspective combines costs incurred by the FNHI and families.

²In the base case, uncapped fees are assumed the same as capped fees and the cost of a private appointment is assumed to be equal to an appointment at the hospital. This was conservatively assumed in the base case, as there is no data informing how much higher these costs would be on average for families.

³The cost of a hospital admission was calculated as the average of costs per admission due to various nutritional disorders in children with severity level 1 in 2018, and admissions with a very short duration.

⁴It was assumed that each child would consume 100 g per day (4.6 g of Neocate Spoon®) powder.

⁵Infant hypoallergenic formula unit costs and market shares are presented in Supplemental Data (Table S2).

Table 3. Estimates of resource use in the model (experts panel).

	Mean units per average child, per year
Symptoms	CMPA (upfront)	Eczema			Allergic urticaria and other signs			Asthma			Rhinoconjunctivitis
Time since formula feeding initiation	Year 1	Year 1	Year 2	Year 3	Year 1	Year 2	Year 3	Year 1	Year 2	Year 3	Year 1	Year 2	Year 3
General pediatrician visits	4.88	3.63	1.88	1.13	1.13	0.88	0.75	3.25	2.63	1.81	0.13	0.63	1.00
Pediatric allergist visits	0.41	0.04	0.03	0.02	1.03	1.06	0.59	0.46	0.42	0.41	0.44	0.44	0.44
Pediatric gastroenterologist visits	0.19	-	-	-	-	-	-	-	-	-	-	-	-
Pediatric dermatologist visits	-	0.62	0.57	0.55	-	-	-	-	-	-	-	-	-
Pediatric pulmonologist visits	-	-	-	-	-	-	-	0.69	0.59	1.66	-	-	-
Otolaryngologist visits	-	-	-	-	-	-	-	-	-	-	0.01	0.09	0.24
Ophthalmologist visits	-	-	-	-	-	-	-	-	-	-	0.01	0.01	0.01
Dietitian visits	0.06	-	-	-	-	-	-	-	-	-	-	-	-
Accident and emergency attendances	0.54	0.08	0.06	0.18	0.16	0.14	0.08	1.43	0.69	0.44	0.00	0.00	0.00
Hospital admissions	0.02	-	-	-	0.06	0.04	0.01	0.51	0.38	0.17	-	-	-
Emergency food allergy kit prescription (% prescribed)	-	-	-	-	-	-	-	-	-	-	-	-	-
H1 antihistamines	18%	-	-	-	-	-	-	-	-	-	-	-	-
H1 antihistamines and adrenaline autoinjector	12%	-	-	-	-	-	-	-	-	-	-	-	-
Emergency asthma kit prescription (% prescribed)	-	-	-	-	-	-	-	-	-	-	-	-	-
β2 and spacer	-	-	-	-	-	-	-	60%	60%	60%	-	-	-
β2, spacer and oral corticosteroid	-	-	-	-	-	-	-	48%	48%	48%	-	-	-
Emollient’s prescription (tubes per month)	-	1.22	1.21	1.10	-	-	-	-	-	-	-	-	-
Duration of treatment (months)	-	9.00	9.00	9.00	-	-	-	-	-	-	-	-	-
Topical corticosteroid’s prescription (tubes per month)	-	0.65	0.55	0.56	-	-	-	-	-	-	-	-	-
Duration of treatment (months)	-	4.50	4.50	4.50	-	-	-	-	-	-	-	-	-
Oral antihistamines prescription (average time on treatment, months)	-	0.06	0.36	0.70	2.17	3.97	3.97	-	-	-	0.00	0.02	0.03
Inhaled corticosteroids prescription (average time on treatment, months)	-	-	-	-	-	-	-	4.96	3.36	2.49	-	-	-
Packed lunch (% prescribed)	34%	-	-	-	-	-	-	-	-	-	-	-	-
CMP free dessert (mean units per day)	1.19	-	-	-	-	-	-	-	-	-	-	-	-
Skin prick tests	0.74	0.15	0.15	0.15	0.72	0.72	0.72	1.10	1.10	1.10	-	-	-
IgE blood tests	2.14	0.18	0.18	0.18	0.09	0.09	0.09	0.90	0.90	0.90	0.88	0.88	0.88
Laboratory tests	1.00	-	-	-	0.36	0.36	0.36	0.24	0.24	0.24	0.50	0.50	0.50
Oral food challenge	0.63	-	-	-	-	-	-	-	-	-	-	-	-
Chest x-ray	-	-	-	-	-	-	-	0.61	0.61	0.61	-	-	-
Nasal endoscopy	-	-	-	-	-	-	-	-	-	-	0.04	0.04	0.04

β2, beta-2 adrenergic receptor agonist; CMP, cow’s milk proteins; CMPA, cow’s milk proteins allergy; IgE, immunoglobulin E.

Table 4. Base case deterministic results per symptom free and tolerance to cow’s milk, and perspective (discounted).

	Total costs (€)		Clinical outcomes	Incremental costs (€)		Incremental clinical outcomes	ICER^1
Perspective	Collective	FNHI		Collective	FNHI		Collective	FNHI
Probability of being symptom free at 3 years
EHCF+LGG	2,275	1,434	0.717	-	-	-	-	-
RHF	2,949	-	0.558	674	-	−0.159	dominated	-
EHWF	3,523	2,309	0.544	1,248	875	−0.172	dominated	dominated
AAF	10,539	8,467	0.652	8,264	7,033	−0.065	dominated	dominated
Life years without symptoms at 3 years
EHCF+LGG	2,275	1,434	2.452	-	-	-	-	-
RHF	2,949	-	1.765	674	-	−0.687	dominated	-
EHWF	3,523	2,309	1.866	1,248	875	−0.586	dominated	dominated
AAF	10,539	8,467	1.633	8,264	7,033	−0.819	dominated	dominated
Probability of cow’s milk tolerance at 3 years
EHCF+LGG	2,275	1,434	0.770	-	-	-	-	-
RHF	2,949	-	0.392	674	-	−0.378	dominated	-
EHWF	3,523	2,309	0.405	1,248	875	−0.365	dominated	dominated
AAF	10,539	8,467	0.183	8,264	7,033	−0.587	dominated	dominated
Life years with cow’s milk tolerance at 3 years
EHCF+LGG	2,275	1,434	1.805	-	-	-	-	-
RHF	2,949	-	0.803	674	-	−1.003	dominated	-
EHWF	3,523	2,309	0.906	1,248	875	−0.899	dominated	dominated
AAF	10,539	8,467	0.295	8,264	7,033	−1.510	dominated	dominated

AAF, amino acid-based formula; EHCF+LGG, extensively hydrolyzed casein formula with added Lactobacillus rhamnosus Gorbach Goldin; EHWF, extensively hydrolyzed whey formula; FNHI, French National Health Insurance; ICER, incremental cost-effectiveness ratio; RHF, rice hydrolyzed formula.

¹Calculated as the difference in costs divided by the difference in clinical outcomes.

Figure 2. Costs per healthcare resource in the cost-effectiveness model, per perspective.

Figure 3. Tornado diagrams for EHCF+LGG versus EHWF (Collective perspective).

Figure 4. Probabilistic results displayed on cost-effectiveness plane (Collective perspective).

Figure 5. Cost-effectiveness acceptability curves (Collective perspective).

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