Modeling the economic value of a Chagas’ disease therapeutic vaccine

Figures & data

Table 1. Table of inputs

Variable	Mean Value	Ref
Annual probabilities
Disease characteristics
Megaviscera	0.000225	36
Cardiomyopathy	0.02	18
CHF given cardiomyopathy	0.04	30,36
Death
Cardiomyopathy no CHF	0.04	30,36
Cardiomyopathy CHF	0.3	30,36
Megaviscera surgical complications	0.0225	36,37
Indeterminate stage^a	0.0018	38
Treatment
Care in indeterminate phase	0.5	20
Surgery if Megaviscera	0.05	36
Treatment of chronic disease	0.78	32
Basic treatment (given treatment)	0.308	32
Intermediate treatment (given treatment)	0.538	32
Specialized treatment (given treatment)	0.154	32
Disability weights
Cardiomyopathy no CHF	0.06	39
Cardiomyopathy CHF	0.27	39
Megaviscera	0.24	39
Costs (2011 US$)
Palliative care only CHF^e	43	32
Palliative care only, no CHF	24	32
Basic care CHF^f	63	32
Basic care no CHF^g	57	32
Intermediate care CHF^h	319	32
Intermediate care no CHF	231	32
Specialized care CHF^i	9,816	32
Specialized care no CHF	4,491	32
Megaviscera with surgery	1,025	17
Megaviscera with no surgery	1,014	17
Indeterminate stage	214	17

^a Uniform distribution, lower limit = 0.0017, upper limit = 0.0019. ^bUniform distribution, lower limit = 0.56, upper limit = 0.71. ^cUniform distribution, lower limit = 0.4, upper limit = 0.5. ^dUniform distribution, lower limit = 0.45, upper limit = 0.7. ^eRefers to cases only seeking care to minimize their symptoms, not to prevent or delay progression of disease. ^fConsisted of three general practitioner visits and 0.58 d in the hospital. ^gConsisted of 5.53 general practitioner visits and 0.25 d in the hospital. ^hIncluded outpatient visits, diagnostics, medicine, and hospitalization costs. ⁱIncluded outpatient care, hospitalization, and hospital procedures such as electrocardiography, X-rays and surgery.

Table 2. Desired and minimally acceptable target product profiles (tpps) baseline assumptions for desired and minimally acceptable vaccine targets

Input parameters	Desired TPP	Minimally acceptable TPP
Target population
Age	Children (> 2 y)	Adults (> 16 y)
Disease stage	Indeterminate	Indeterminate
Vaccine characteristics
Cost (all doses)	$46	$200
Indication	Prevent cardiomyopathy	Delay the onset of cardiomyopathy
Efficacy	80%	80%
Dosage	One-dose	Two-dose
Duration of protection	Lifetime	Lifetime
Delay of cardiomyopathy	-	10 y
Side effects
Urticaria	0.001%	0.1%
Carditis	0%	5%
Vaccine induced cardiomyopathy	3%	3%

Table 3. Incremental cost-effectiveness ratio (ICER) for a two-dose vaccine meeting desired vaccine target criteria with no effect on megaviscera

Duration of protection		10 y	20 y	Lifetime
Compliance	SAE Risk
100%
	1%	Vaccine^a	Vaccine	Vaccine
	3%	42^c	Vaccine	Vaccine^b
75%
	1%	Vaccine	Vaccine	Vaccine
	3%	No Vaccine	Vaccine	Vaccine
50%
	1%	Vaccine	Vaccine	Vaccine
	3%	No Vaccine	Vaccine	Vaccine
25%
	1%	No Vaccine	Vaccine	Vaccine
	3%	No Vaccine	No Vaccine	1,075

^a “Vaccine” and “No Vaccine” indicates that the strategy mentioned was economically dominant (was less costly and more effective) over the other for that scenario. ^bVaccine was economically dominant over no vaccine for the baseline scenario (1 dose vaccine, lifetime protection, 100% compliance, 3% risk of SAEs). ^cHighly cost-effective: ICER ≤ $9,867, Cost-effective: ICER $9,868–29,602

Table 4. Incremental cost-effectiveness ratio (ICER) for a multi-dose vaccine meeting minimally acceptable vaccine target criteria with no effect on megaviscera

		2-dose		3-dose		4-dose
Delay in cardiomyopathy		10 y	20 y	10 y	20 y	10 y	20 y
Compliance	SAE Risk
100%
	1%	Vaccine^a,b	Vaccine	Vaccine	Vaccine	Vaccine	Vaccine
	3%	29^c	Vaccine	476^b	Vaccine	No Vaccine	Vaccine
75%
	1%	Vaccine	Vaccine	Vaccine	Vaccine	Vaccine	Vaccine
	3%	145	Vaccine	No Vaccine	Vaccine	No Vaccine	689
50%
	1%	Vaccine	Vaccine	40	Vaccine	212	Vaccine
	3%	1,034	Vaccine	No Vaccine	675	No Vaccine	No Vaccine
25%
	1%	278	Vaccine	790	65	No Vaccine	390
	3%	No Vaccine	2,701	No Vaccine	No Vaccine	No Vaccine	No Vaccine

^a “Vaccine” and “No Vaccine” indicates that the strategy mentioned was economically dominant (was less costly and more effective) over the other for that scenario. ^bHighly cost-effective: ICER ≤ $9,867, Cost-effective: ICER $9,868–29,602. ^cBaseline minimally acceptable vaccine scenario

Table 5. Cost per cardiomyopathy case averted (US$) using desired TPP vaccine^a

	SAE risk	1 dose			2 dose
		Vaccine protection duration
Compliance		10 y	20 y	Lifetime	10 y	20 y	Lifetime
100%	0.1%	-6,326	-5,475	-3,343	-6,407	-5,373	-3,301
	1%	-5,567	-5,428	-3,196	-5,535	-5,011	-3,141
	3%	-4,874	-5,027	-3,005	-143	-4,102	-2,681
	7%	7,413	-3,638	-2,490	- ^b	1,833	-1,188
75%	0.1%	NA	NA	NA	-6,692	-5,381	-3,283
	1%	NA	NA	NA	-4,660	-4,939	-3,109
	3%	NA	NA	NA	8,524	-3,684	-2,571
	7%	NA	NA	NA	- ^b	6,472	-901
50%	0.1%	NA	NA	NA	-5,794	-5,345	-3,227
	1%	NA	NA	NA	-3,489	-4,748	-2,988
	3%	NA	NA	NA	- ^b	-2,698	-2,294
	7%	NA	NA	NA	- ^b	310,407	331
25%	0.1%	NA	NA	NA	-5,381	-4,880	-2,883
	1%	NA	NA	NA	2,291	-3,738	-2,607
	3%	NA	NA	NA	- ^b	3,889	-1,064
	7%	NA	NA	NA	- ^b	- ^b	6,138

NA, Not Applicable. ^aNegative costs, cost savings. ^bVaccination was more costly and caused more cardiomyopathy cases

Table 6. Return on investment analyses for desired TPP vaccine

Total development costs (US$)	Years needed for development	Minimum needed to achieve positive ROI
		No. of people vaccinated in 1st year	coverage of target population in 1st year (%)
$100 million	15	180,000	3.0%
	20	210,000	3.5%
	30	270,000	4.5%
$150 million	15	240,000	4.0%
	20	300,000	5.0%
	30	420,000	7.0%
$200 million	15	330,000	5.5%
	20	420,000	7.0%
	30	540,000	9.0%
$400 million	15	660,000	11.0%
	20	780,000	13.0%
	30	1,020,000	17.0%

Figure 1. Model structure. (A) Health states. Death from Chagas’ related or other causes could occur at any health state, see Table 1 for mortality probabilities. ^aAll individuals entered the model in the Indeterminate health state (B) Transition probabilities for vaccinated individuals in the indeterminate health state. ^aAll individuals on the “Vaccinate” branch received the first dose of the vaccine. Receipt of subsequent doses was dependent upon compliance and the number of doses in a full vaccine course. ^bIncluded, but not limited to cardiomyopathy

Wilson LS, Strosberg AM, Barrio K. Cost-effectiveness of Chagas disease interventions in latin america and the Caribbean: Markov models. Am J Trop Med Hyg 2005; 73:901 - 10; PMID: 16282301

 PubMed Web of Science ®Google Scholar

Yun O, Lima MA, Ellman T, Chambi W, Castillo S, Flevaud L, et al. Feasibility, drug safety, and effectiveness of etiological treatment programs for Chagas disease in Honduras, Guatemala, and Bolivia: 10-year experience of Médecins Sans Frontières. PLoS Negl Trop Dis 2009; 3:e488; http://dx.doi.org/10.1371/journal.pntd.0000488; PMID: 19582142

 PubMed Web of Science ®Google Scholar

Espinosa R, Carrasco HA, Belandria F, Fuenmayor AM, Molina C, González R, et al. Life expectancy analysis in patients with Chagas’ disease: prognosis after one decade (1973-1983). Int J Cardiol 1985; 8:45 - 56; http://dx.doi.org/10.1016/0167-5273(85)90262-1; PMID: 3997291

 PubMed Web of Science ®Google Scholar

Pinotti HW, Habr-Gama A, Cecconello I, Felix VN, Zilberstein B. The surgical treatment of megaesophagus and megacolon. Dig Dis 1993; 11:206 - 15; http://dx.doi.org/10.1159/000171413; PMID: 8222303

 PubMed Web of Science ®Google Scholar

Rassi A Jr., Rassi SG, Rassi A. Sudden death in Chagas’ disease. Arq Bras Cardiol 2001; 76:75 - 96; PMID: 11175486

 PubMedGoogle Scholar

Lee BY, Bacon KM, Connor DL, Willig AM, Bailey RR. The potential economic value of a Trypanosoma cruzi (Chagas disease) vaccine in Latin America. PLoS Negl Trop Dis 2010; 4:e916; http://dx.doi.org/10.1371/journal.pntd.0000916; PMID: 21179503

 PubMed Web of Science ®Google Scholar

Castillo-Riquelme M, Guhl F, Turriago B, Pinto N, Rosas F, Martínez MF, et al. The costs of preventing and treating chagas disease in Colombia. PLoS Negl Trop Dis 2008; 2:e336; http://dx.doi.org/10.1371/journal.pntd.0000336; PMID: 19015725

 PubMedGoogle Scholar

World Health Organization. Global Burden of Disease 2004 Update: Disability Weights for Diseases and Conditions. Geneva, 2004.

 Google Scholar

Basombrío MA, Schofield CJ, Rojas CL, del Rey EC. A cost-benefit analysis of Chagas disease control in north-western Argentina. Trans R Soc Trop Med Hyg 1998; 92:137 - 43; http://dx.doi.org/10.1016/S0035-9203(98)90720-9; PMID: 9764315

 PubMed Web of Science ®Google Scholar