Bedaquiline- versus injectable-containing drug-resistant tuberculosis regimens: a cost-effectiveness analysis

Figures & data

Figure 1. Analysis development.

Table 1. Model assumptions used to derive analysis inputs.

Input	Value (2018)			Assumptions	Source
	Russia	India	South Africa
MDR-TB-treated population	25,883	33,276	11,489	Adjusted to 2018 value based on estimates of CAGR 2000–2040	WHO Global TB Report 2017 [1]; Sharma et al., 2017 [36]
XDR-TB-treated population	1,784	2,502	645	Adjusted to 2018 value based on estimates of CAGR 2000–2040	WHO Global TB Report 2017 [1]; Sharma et al., 2017 [36]
SCR/LCR split	0/100	70/30	80/20	Constant across the 5-year analysis horizon	WHO Global TB Report 2017 [1];
Drug regimen costs (injectable-containing regimens)	$1,666 (LCR)	$522 (SCR); $1,987 (LCR)	$736 (SCR); $2,243 (LCR)	Assumes kanamycin used as the injectable in regimen; Adjusted for percentage use of regimen, if multiple regimens recommended; Prices do not include value-added tax (VAT).	Stop TB Partnership [34]; National Pharmaceutical Pricing Authority, Government of India [35]; Russia register and Unified information system for procurement [37,38]
Total hospitalization cost per patient (injectable-containing regimens)	$98,245 (LCR)	$494 (SCR); $885 (LCR)	$982 (SCR); $1,659 (LCR)	Cost per hospitalization considers all treated patients (Russia and India); As South Africa recently moved away from inpatient treatment, adjustment was made for historical values based on current inpatient stay rate (10%); SCR value determined by applying duration adjustment (10/18 months = 55%) for India & South Africa.	Lu et al., 2017 [19]; Pooran et al., 2013 [39]
Ototoxicity costs (injectable-containing regimens)	$424	$418 (SCR); $1,012 (LCR)	$474 (SCR); $1,039 (LCR)	Percent experiencing ototoxicity multiplied by sum of ototoxicity management costs per patient plus incremental switching costs per patient related to alternative regimen	Falzon et al, 2017 [41]; Schnippel et al., 2018 [40];
Nephrotoxicity costs	$830	$220	$442	Percent experiencing nephrotoxicity multiplied by cost per nephrotoxicity treatment; South Africa costs adjusted for other geographies based on purchasing power parity (PPP) (OECD) [46]	Schnippel et al., 2018 [40]
Laboratory testing, X-ray, and monitoring costs	$2,260	$908	$2,056	Adjusted to 2018 value based on historical inflation; China used as analog for Russia and South Africa, Nepal used as analog for India; Outpatient costs were not included as they were not significantly different between regimens, and very small relative to other costs.	Vassal, 2013 [22]; Lu et al., 2017 [19]
Anemia costs	$1,745	$463	$929	Percent experiencing anemia multiplied by cost per anemia treatment; South Africa costs adjusted for other geographies based on PPP (OECD) [46]	Schnippel et al., 2018 [40]
Surgical costs	$27	$38	$0	South Africa costs adjusted for other geographies based on PPP (OECD) [46]	Pooran et al., 2013 [39]
End-of-life costs	$7	$0	$3	South Africa costs adjusted for other geographies based on PPP (OECD) [46]	Pooran et al., 2013 [39]

Table 2. Determination of costs of treatment of XDR-TB.

Input	XDR scaling factor	Assumptions	Source
Drug regimen costs	1X	XDR-TB patients are treated with LCR	Stop TB Partnership [34]; National Pharmaceutical Pricing Authority, Government of India [35]; Russia register and Unified information system for procurement [37,38]
Laboratory testing, X-rays, and monitoring costs	3X	XDR-TB patients incur more testing, X-ray, and monitoring costs than MDR patients	Marks et al. [32], Pooran et al. [39]. based on ratio of XDR and MDR treatment costs
Hospitalization costs	3X (1X for Russia)	Hospitalization rate, duration, and cost is expected to be higher for XDR-TB than for MDR-TB; In Russia, costs of XDR-TB and MDR-TB are similar given that they both have high rates of prolonged hospitalization	Marks et al. [32], Pooran et al. [39]. based on ratio of XDR and MDR treatment costs
End-of-life care costs	3X	Higher mortality is assumed to drive higher end-of-life care costs	Marks et al. [32], Pooran et al. [39]. based on ratio of XDR and MDR treatment costs
Surgical intervention costs	3X	More severe disease is expected to increase both rate and costs of surgical intervention	Marks et al. [32], Pooran et al. [39]. based on ratio of XDR and MDR treatment costs
Nephrotoxicity costs	3X	More severe disease is expected to increase both rate and costs of nephrotoxicity	Marks et al. [32], Pooran et al. [39] based on ratio of XDR and MDR treatment costs; Nephrotoxicity rate: Schnippel et al. [44]
Anemia costs	1X	Anemia rates for both MDR-TB and XDR-TB are assumed to be the same	Anemia rate and cost: Schnippel et al. [40]
Ototoxicity costs	1X	Ototoxicity rates and costs are not expected to change for XDR-TB, since they are related to the regimen	Cost: Schnippel et al. [40]; Ototoxicity rate: Falzon et al, 2017 [41]

Table 3. Scenarios included in the analysis.

Scenario	Country	Prevalence source	Regimen pricing	Injectable used	SCR/LCR usage rate	Time to BDQ conversion	Ototoxicity rate [8,41]	Nephrotoxicity rate [8,40]
Base case	India	WHO	SCR: $522 inj., $947 BDQ LCR: $1,987 inj., $2,254 BDQ	Kanamycin	70/30	SCR – 2 years; LCR – 4 years	43%	10%
	South Africa	WHO	SCR: $736 inj., $1,053 BDQ LCR: $2,243 inj., $2,276 BDQ	Kanamycin	80/20	SCR – 2 years; LCR – 4 years	43%	10%
2018 GDF pricing [49]	India	WHO	SCR: $571 inj., $937 BDQ LCR: $812 inj., $1,112 BDQ	Kanamycin	70/30	SCR – 2 years; LCR – 4 years	43%	10%
	South Africa	WHO	SCR: $571 inj., $937 BDQ LCR: $812 inj., $1,112 BDQ	Kanamycin	80/20	SCR – 2 years; LCR – 4 years	43%	10%
NSP prevalence, local procurement, and capreomycin [35,52]	India	India NSP w/kanamycin India NSP w/capreomycin	SCR: $160 inj., $736 BDQ LCR: $1,896 inj., $2,460 BDQ SCR: $409 inj., $736 BDQ LCR: $1,598 inj., $2,789 BDQ	Kanamycin Capreomycin	70/30	SCR – 2 years; LCR – 4 years	17%	20%
100% conversion to BDQ	Compares base case scenario with either 100% injectable use or 100% BDQ use, in Russia, India, and South Africa. Calculated ICER and number of treatment successes

Figure 2. (A) Short-course (SCR) regimen cost per treatment success, 2018. (B) Long-course (LCR) regimen cost per treatment success, 2018. (C) ACER of BDQ-containing regimens relative to ACER of injectable-containing regimens, 2018.

Table 4. SCR and LCR cost per treatment success without ototoxicity 2018.

	SCR cost per treatment success without ototoxicity, 2018				LCR cost per treatment success without ototoxicity, 2018
	India		South Africa		Russia		India		South Africa
Cost	SCR w/Inj.	SCR w/BDQ	SCR w/Inj.	SCR w/BDQ	LCR w/Inj.	LCR w/BDQ	SCR w/Inj.	SCR w/BDQ	SCR w/Inj.	SCR w/BDQ
Drug regimen	$1,186	$1,121	$1,677	$1,252	$3,933	$3,186	$7,037	$2,956	$7,965	$2,993
Hospitalization	$1,070	$493	$2,126	$879	$227,630	$85,465	$3,888	$1,164	$7,114	$2,038
Injection-related AE	$1,461	$0	$1,788	$0	$1,670	$0	$4,570	$0	$4,628	$0
Other	$2,067	$1,024	$4,500	$2,599	$5,880	$3,332	$4,186	$1,347	$8,888	$3,353
Total	$5,785	$2,639	$10,090	$4,730	$239,112	$91,983	$19,681	$5,467	$28,595	$8,384
Difference compared to injectable	N/A	($3,147)	N/A	($5,361)	N/A	($147,129)	N/A	($14,214)	N/A	($20,211)

Figure 3. Modeling the impact of scenario 1.

Figure 4. Modeling the impact of scenario 2.

Figure 5. Modeling the impact of scenario 3.

Table 5. ICER calculation.

	Russia	India	South Africa
100% injectable-containing regimen cost	$2,798,552,108	$130,839,301	$65,339,932
100% injectable-containing regimen cost w/o hospitalization	$255,704,512	$94,546,524	$54,171,994
100% injectable Tx successes	14,101	24,984	8,826
100% BDQ-containing regimen cost	$1,939,880,295	$101,035,213	$52,504,494
100% BDQ-containing regimen cost w/o hospitalization	$192,340,629	$69,853,442	$44,106,982
100% BDQ Tx successes	21,089	28,844	9,906
ICER	–$122,878	–$7,721	–$10,341
ICER without hospitalization	–$9,068	–$6,397	–$7,775

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