The cost utility and budget impact of adjuvant racecadotril for acute diarrhea in children in Thailand

Figures & data

Figure 1 Cost utility decision tree model structure adaptation for Thailand.

Abbreviations: ORS, oral rehydration solution; T, time.

Table 1 Thailand cost data model inputs and cost calculation

Description	Value	Unit	Source
Racecadotril + ORS
Recommended dose/administration	1.5	mg/kg	Abbott Laboratories^Citation33
Average weight of child (kg)	12.9	kg	NSO,^Citation34 WHO^Citation35
Total dose per administration	19.4	mg	Model calculation (no source)
Number of administrations per day	3	n	Abbott Laboratories^Citation33
Total daily dose	58.05	mg	Model calculation (no source)
Number of milligrams per sachet	30	mg	Abbott Laboratories^Citation33
Number of sachets required (rounded up to nearest whole sachet)	1.94	n	Model calculation (no source) – rounded up to 2
Cost per sachet	26.78	฿	Drug and Medical Supply Information Center^Citation36
Total daily cost racecadotril	53.56	฿	Model calculation (no source)
Total daily cost racecadotril + ORS	58.18	฿	Model calculation (no source)
ORS
Recommended dose/administration	240	mL	Pharaonia Pharmaceuticals (Pharo Pharma)^Citation37
Number of sachets	1	n	Pharaonia Pharmaceuticals (Pharo Pharma)^Citation37
Stool frequency	3*	n	Model assumption (no source)
Total daily dose	3	n	Model calculation (no source)
Average weighted cost per sachet	1.54	฿	Pharaonia Pharmaceuticals (Pharo Pharma)^Citation37
Total daily cost ORS	4.62	฿	Model calculation (no source)
Average cost per primary health care center visit (normal hours)	142.60	฿	Expert opinion^Citation3
National average nonelective inpatient stay (short)	2,824.00	฿	Sutra et al^Citation2

Notes: The average weight for a child under the age of five in Thailand has been calculated as follows: according to the Multiple Indicator Cluster Survey for Thailand 2012, 9.2% of children in Thailand under 5 years are moderately underweight (−2 SD), 2.1% are severely underweight (−3 SD) and 11% are overweight (assumed to be +2 SD).³⁴ Based on this, it was assumed that the remaining children are median weight for age. The average weight, therefore, is 12.9 kg for a 0–60-months old child in Thailand.

* Note that three stools is a minimum, which conservatively estimates (underestimates) the cost of ORS alone for the purpose of the analysis. It is more likely that five sachets will be used if there are five stools per day.

a Expert opinion data from S Treepongkaruna, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, personal communication, May, 2016.

Abbreviations: NSO; National Statistical Office; ORS, oral rehydration solution; SD, standard deviation; WHO, World Health Organization

Table 2 Calculation of average cost of treatment per child per adverse event (R+ORS and/or ORS alone)

Adverse event–severity	Treatment	Drug/admission cost (฿) (reference)	Proportion of all adverse events, %	Proportion cost	Average (−service cost) ฿	Average (+ service cost) ฿
Vomiting – mild	Domperidone	5.77^Citation36	47.5a	2.74	I02.59	I52.59
Vomiting – moderate	Ondansetron IV	I5.89^Citation36	47.5a	7.55
Vomiting – severe	Gastroenteritis in children < 10 years no cc	1,846*,^Citation45	5.0^Citation38	92.30
Average cost per episode of vomiting					I27.59
Fever – mild	Paracetamol (two bottles at 6.90 ฿)	I3.8^Citation36	45a	6.2I	I97.02	247.02
Fever – moderate	Paracetamol (two bottles at 6.90 ฿)	I3.8^Citation36	45a	6.2I
Fever – severe	Gastroenteritis in children < 10 years no cc	1,846*,^Citation45	I0^Citation3	I84.60
Average cost per episode of fever					222.02
Drug allergy – mild	Hydroxyzine	8.92^Citation36	45a	4.0I	442.38	492.38
Drug allergy – moderate	Hydroxyzine	8.92^Citation36	45a	4.0I
Drug allergy – severe	Gastroenteritis in children <10 years, moderate complications	4,344**,^Citation45	I0^Citation3	434.35
Average cost per episode of drug allergy					467.38

Notes:

* Thai DRG code 06580 gastroenteritis in children <10 years no cc (inside UC=฿2,136; outside UC=฿1,557; average ฿1,846.50).

** DRG code 06582 gastroenteritis in children <10 years with moderate complications (inside UC=฿5,024; outside UC=฿3,663; average =฿4,343.5).

a Model assumption.

Abbreviations: cc, comorbidities and complications; DRG, diagnosis related group; IV, intravenous; ORS, oral rehydration solution; R, racecadotril; UC, universal coverage.

Table 3 Budget impact calculation for the population cohort eligible for R+ORS and/or ORS alone

Description	Total	Reference
Total population (n)	66,785,000	Unicef^Citation39
Total children <5 years (n)	3,706,500	Unicef^Citation39
Incidence of diarrhea <5 years (per 100,000)	10%	Sutra et al^Citation2
Number of children <5 years with diarrhea (n)	370,650	Model calculation (no reference)
Percentage of children with diarrhea having ORS	58%	Unicef^Citation40
Percentage of moderate diarrhea (%)	34.7%	Lamberti^Citation41
Number of children eligible for treatment (n)	74,597	Model calculation (no reference)

Abbreviations: ORS, oral rehydration solution; R, racecadotril.

Table 4 Mean cost per patient for drugs, outpatient care, inpatient care and adverse events for R+ORS versus ORS alone

Mean cost per patient ฿	ORS (comparator) ฿	Racecadotril + ORS (intervention) ฿	Difference ฿
Drug cost	15.81	185.20	169.38
Outpatient care	248.12	202.49	−45.63
Inpatient care	2,250.67	217.05	−2,033.62
Adverse events	3.39	2.59	−0.80
Total mean cost per patient	2,518.00	607.33	−1,910.67

Abbreviations: ORS, oral rehydration solution; R, racecadotril.

Figure 2 Incremental cost-effectiveness ratio on the cost utility plane.

Abbreviations: ORS, oral rehydration solution; QALY, quality-adjusted life year; R, racecadotril.

Figure 3 Tornado diagram of deterministic sensitivity analysis.

Notes: Note that due to scale, the QoL parameter of a “well” person is not shown in the tornado diagram; a 20% change in this parameter results in 175% change in the model results.
Abbreviations: AE, adverse event; LOS, length of stay; ORS, oral rehydration solution; QoL, quality of life; R, racecadotril.

Table 5 Budget impact results year 0 (current) to year 5, assuming 5% increase in market share for R+ORS

Year	ORS alone		R+ORS		Total expenditure (฿)	Diarrhea as % of total public health care budget	Cumulative reduction in total expenditure (฿)
	Market share, %	Cohort expenditure (฿)	Market share	Cohort expenditure (฿)
Year 0	100	187,835,249	0%	0	187,835,249	0.0700	−0
Year 1	95	178,443,486	5%	2,265,266	180,708,752	0.0674	−7,126,496
Year 2	90	169,051,724	10%	4,530,532	173,582,256	0.0647	−14,252,993
Year 3	85	159,659,961	15%	6,795,798	166,455,759	0.0620	−21,379,489
Year 4	80	150,268,199	20%	9,061,064	159,329,263	0.0594	−28,505,986
Year 5	75	140,876,436	25%	11,326,330	152,202,766	0.0567	−35,632,482

Abbreviations: ORS, oral rehydration solution; R, racecadotril.

Figure 4 Percentage overall health expenditure current year (0) to year 5 for ORS and R+ORS

Abbreviations: ORS, oral rehydration solution; R, racecadotril.

Table S1 Model adaptation Thailand: base case parameters

Cost parameters
Drug costs	Value	Source
R+ORS
Recommended dose/administration (mg/kg)	1.5	SPC Thailand^Citation1
Average weight of child (kg)	12.9	NSO, WHO^Citation2,Citation3
Number of administrations per day (#)	3	SPC Thailand^Citation1
Number of milligrams per sachet (mg)	30	SPC Thailand^Citation1
Cost per sachet	฿26.78	Abbott Laboratories Thailand price list, data on file, December 2016
Oral rehydration salts
Recommended dose/admin (mL)	240	IMS data from Abbott Laboratories, data on file, December 2016
Number of sachets (#)	1	IMS data from Abbott Laboratories, data on file, December 2016
Cost per sachet	฿1.54	Drug And Medical Supply Information Center, Ministry of Public Health^Citation4
Outpatient care costs
Average cost per polyclinic visit (normal hours)	฿142.60	Model assumptionc
Inpatient care costs
National average nonelective inpatient stay (short)	฿2,824.00	Sutra^Citation5

Adverse event costs
Adverse event	Severity	Description	Drug/admission cost (฿)	Referencea	Proportion of all adverse events	Referenceb	Proportion × cost	Average cost
Vomiting	Mild	Domperidone	5.77	Thai National Drug List^Citation4	47.5%	Model assumptionc	2.74
Vomiting	Moderate	Ondansetron IV	15.89	Thai National Drug List^Citation4	47.5%	Model assumptionc	7.55
Vomiting	Severe	Gastroenteritis in children <10 years no cc	1,846	Thai DRG code 06580*,^Citation12	5.0%	Freedman et al^Citation6	92.30
Vomiting cost (excluding service cost)	Average		0	Model assumptionc	na	na	102.59
Vomiting cost (including service cost)	Average		50	Model assumptionc	na	na	152.59
Average cost vomiting								127.5 9
Fever	Mild	Paracetamol (supps two packs at ฿6.90)	13.8	Thai National Drug List^Citation4	45%	Model assumptionc	6.21
Fever	Moderate	Paracetamol (supps two packs at ฿6.90)	13.8	Thai National Drug List^Citation4	45%	Model assumptionc	6.21
Fever: severe	Severe	Gastroenteritis in children <10 years no cc	1,846	Thai DRG code 06580*,^Citation12	10%	Model assumptionc	184.60
Fever cost (excluding service cost)	Average		0	Model assumptionc	na	na	197.02
Fever cost (including service cost)	Average		50	Model assumptionc	na	na	247.02
Average cost fever								222.0 2
Drug allergy	Mild	Hydroxyzine	8.92	Thai National Drug List^Citation4	45%	Model assumptionc	4.01
Drug allergy	Moderate	Hydroxyzine	8.92	Thai National Drug List^Citation4	45%	Model assumptionc	4.01
Drug allergy	Severe	Gastroenteritis in children <10 years, moderate complications	4,344	Thai DRG code 06582**,^Citation12	10%	Model assumptionc	434.35
Drug allergy cost (excluding service cost)	Average		0	Model assumptionc	na	na	442.38
Drug allergy cost (including service cost)	Average		50	Model assumptionc	na	na	492.38
Average cost drug allergy								467.3 8

Other parameters	Parameter value	Reference
Outpatient care
Proportion on ORS: diarrhea resolves at 48 hours	26%	Lehert et al^Citation7
Proportion on R+ORS: diarrhea resolves at 48 hours	58%	Lehert et al^Citation7
Inpatient care
Proportion on ORS: referred for inpatient stay at 48 hours	36%	Alvarez Calatayud et al ^Citation8
Proportion on R+ORS: referred for inpatient stay at 48 hours	6%	Alvarez Calatayud et al^Citation8
Adverse events
Proportion on ORS: experiencing AEs	16%	Baumer and Joulin^Citation9
Proportion on R+ORS: experiencing AEs	12%	Baumer and Joulin^Citation9
Adverse event frequency
R+ORS
Vomiting	5.1%	Baumer and Joulin^Citation9
Fever	2.3%	Baumer and Joulin^Citation9
Allergic AE	1.3%	Baumer and Joulin^Citation9
ORS (or placebo)
Vomiting	5.8%	Baumer and Joulin^Citation9
Fever	4.6%	Baumer and Joulin^Citation9
Allergic AE	1.4%	Baumer and Joulin^Citation9
Quality of life (utility)
Average QoL <5 years: primary care/outpatient setting	0.7345	Martin et al^Citation10
Average QoL <5 years: secondary care/inpatient setting	0.6145	Martin et al^Citation10
Average QoL: “well” person (no diarrhea)	0.9400	Kind et al^Citation11

Notes:

* DRG code 06580 gastroenteritis children <10 years no cc (inside UC =฿2,136, outside UC =฿1,557, average ฿1,846).

** DRG code 06582 gastroenteritis children <10 years with moderate complications (inside UC =฿5,024; outside UC=฿3,663, average =฿4,343).

a The first reference column refers to the data in the “Drug/admission cost” column.

b The second reference column refers to the data in the “Proportion of all adverse events” column.

c Model assumptions have no source or reference.

Abbreviations: AE, adverse event; cc, comorbidities and complications; DRG, diagnosis related group; IMS, IMS Health; IV, intravenous; na, not available; NSO, National Statistical Office; ORS, oral rehydration solution; QoL, quality of life; R, racecadotril; SPC, summary of product characteristics; supps, suppositories; UC, universal coverage; WHO, World Health Organization.

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