Cost-effectiveness analyses of breast cancer medications use in developing countries: a systematic review

Figures & data

Figure 1. The PRISMA flow diagram of the articles’ selection process

Table 1. General characteristics of the included articles of CEAs

Publication	Year	Country	Journal	Journal category
Shih C. et. el.^[Citation25]	2009	Taiwan	PharmacoEconomics	Q1
Buendía J. et. el^[Citation26]	2013	Colombia	Biomédica	Q3
Gershon N. et. el^[Citation27]	2019	11 countries of Sub-Saharan Africa (Congo, Ethiopia, Guinea, Kenya, Namibia, Nigeria, Rwanda, Uganda, Zambia, Zimbabwe, and South Africa)	Cost Effectiveness and Resource Allocation	Q2
Genuino A. et. el^[Citation28]	2019	Philippines	BMC Health Services Research	Q1
Gupta N. et. el^[Citation29]	2020	India	Journal of Clinical Oncology	Q1
Fonseca M. et. el.^[Citation30]	2009	Brazil	Revista da Associacao Medica Brasileira	Q3
Pichon-Riviere A. et. el.^[Citation31]	2015	Seven countries from Latin America (Argentina, Bolivia, Brazil, Chile, Colombia, Peru, Uruguay)	International Journal of Technology Assessment in Health Care	Q2
Ansaripour A. et. el.^[Citation32]	2017	Iran	PharmacoEconomics	Q1
Chicaíza-Becerra L. et. el.^[Citation33]	2014	Colombia	Revista de Salud Pública	Q4
Aboutorabi A. et. el.^[Citation34]	2015	Iran	Global Journal of Health Science	Q3
Leung H. et. el.^[Citation35]	2018	Taiwan	Expert Review of Pharmacoeconomics & Outcomes Research	Q2
Chen W. et. el.^[Citation36]	2009	China	Value in Health	Q1
Ye M. et. el.^[Citation37]	2018	China	BioMed Research International	Q2
Lang H. et. el.^[Citation38]	2016	Taiwan	Journal of Medical Economics	Q2

Table 2. Objectives, comparators, population characteristics, and main conclusions of the included CEAs

Clinical classification (tumor subtype/settings)	Publication [author (year)]	Comparators		Study conclusion
		Comparator 1	Comparator 2
All BC patients did mastectomy or lumpectomy/Adjuvant	Shih C. [2009,^Citation25]	Cyclophosphamide+ epirubicin+ fluorouracil (CEF)	Cyclophosphamide+ methotrexate+ fluorouracil (CMF)	CEF was not cost effective in the treatment of patients with breast cancer in Taiwan. In terms of ICER, CEF was dominated by CMF at the WTP-threshold of (WTP) of Taiwanese dollars $NT 1,500, 000 ($US 80,000).
Hormone receptor- positive/Adjuvant	Fonseca M. [2009,^Citation30]	Anstrazole	Tamoxifen	Anastrozole was cost-effective compared with tamoxifen at an ICER of R$ 27,326.80 per patient-life-years gained at a WTP threshold of R$ 29,229.00, with R$ 1.00 equaling approximately US$ 0.40 in Brazil, 2009.
	Ye M. [2018,^Citation37]	Aromatase inhibitor (AI), letrozole, for 5 years	Regimen 1: Tamoxifen adjuvant for 5 years Regimen 2: Tamoxifen 2–3 years then AI (letrozole up to year 5)	The AI 5-year strategy with letrozole is more cost-effective than the tamoxifen- 5 years strategy (regimen 1) and the AI switch strategy (regimen 2). The ICER or having AI 5-year strategy with letrozole over tamoxifen 5-year strategy was CNY ¥38,092/QALY gained. The ICER of 5 years of letrozole versus 2–3 years of tamoxifen and then letrozole was CNY ¥68,233/QALY gained. Both ICERs are compared to a WTP threshold of CNY ¥171,000 (3 GDP per capita in China, 2016).
HER2 positive/Adjuvant	Chen W. [2009,^Citation36]	Trastuzumab adjuvant	Adjuvant docetaxel+ Doxorubicin+ cyclophosphamide	1-year adjuvant trastuzumab treatment was cost-effective across the different cities of China. The ICER was US$7564, US$7933, and US$7929 in Beijing, Shanghai, and Guangzhou, respectively per patient-life year gained, and was US$7676, US$8049, and US$8046, respectively per QALY gained at a WTP-threshold of 3 GDP.
	Aboutorabi A. [2015,^Citation34]	Trastuzumab adjuvant + Standard therapy	No trastuzumab (standard therapy only)	1-year adjuvant trastuzumab was not cost-effective. ICER for adjuvant trastuzumab versus no trastuzumab was of US$ 54,223 per patient-life-year gained and US$ 51,302 per QALY which are higher than the estimated Iranian WTP threshold- to be between 10,000 to15,000 USD (WHO, 2014a).
	Pichon-Riviere A. [2015,^Citation31]	Trastuzumab adjuvant	No trastuzumab (standard therapy only)	Trastuzumab adjuvant therapy was not cost effective compared to standard therapy in all the seven Latin American countries included in the analysis. ICER ranged from US$ 24,700 to US$ 60,800 per patient life year gained, and from US$ 42,100 to US$ 110,300 per QALY gained, at a WTP threshold of 1 GDP for each country (variable depending on GDP for each of the included countries).
	Lang H. [2016,^Citation38]	Trastuzumab adjuvant + standard therapy	No trastuzumab (standard therapy only)	1-year adjuvant trastuzumab treatment was cost-effective. The ICER was US 51,863 USD per QALY gained which is less to the WTP threshold of as US$ 67,065 (NTD 2,011,950; 1 USD = NT$30 in Taiwan 2015).
	Ansaripour A. [2017,^Citation32]	Trastuzumab adjuvant	No trastuzumab (standard therapy only)	A 6-month treatment with adjuvant trastuzumab was more cost-effective than 1-year adjuvant trastuzumab versus no adjuvant trastuzumab. ICER for 1-year adjuvant trastuzumab vs no trastuzumab was €13,279 per patient-life-year gained, and €16,695 per QALY gained. Whereas, for the 6-month adjuvant trastuzumab regimen vs no trastuzumab, ICER was €11,664 per patient-life-year gained, and €14,625 per QALY gained compared to a WTP-threshold of €21,000 per QALY (€1 = 34,000 rials) as reported in the World Bank for Iran, 2011.
	Gershon N. [2019,^Citation27]	Trastuzumab adjuvant + standard therapy	No trastuzumab (standard therapy only)	Trastuzumab adjuvant therapy was not cost effective compared to standard therapy in the 11 African countries of interest. The ICER ranged from US$ 18,709 to US$ 21,321 per patient-life year gained, and US$ 19,534 to US$ 21,697 per QALY gained, at a WTP threshold of 1 GDP for each of the analyzed countries (variable depending on the GDP of each country).
	Genuino A. [2019,^Citation28]	1 year of adjuvant trastuzumab + standard chemotherapy	Standard chemotherapy alone (doxorubicin +cyclophosphamide + docetaxel)	1-year of adjuvant trastuzumab therapy was not cost-effective compared to standard chemotherapy alone for those patients in Philippines. Trastuzumab ICER from the healthcare system perspective was PHP 377,009 per patient-life-year gained and PHP 453,505/QALY gained. From the societal perspective, ICER was PHP 458,686/QALY gained. The WTP threshold of as per the Formulary Executive Council in Philippines is PHP 120,000 per QALY (2017 Exchange Rate: 1 USD = PHP 49.9230 in Philippines).
	Gupta N. [2020,^Citation29]	trastuzumab adjuvant+ adjuvant Chemotherapy	adjuvant chemotherapy alone (anthracycline and taxane-based drugs)	1-year adjuvant trastuzumab treatment was not cost effective in India at the current price compared to adjuvant chemotherapy alone. The ICER of adjuvant trastuzumab was of INR 156,291 (US$2,235) per patient-life year gained and INR 178,877 (US$2,558) per QALY gained at a WTP threshold of 1 GDP in 2019 in India.
HER 2 positive/Metastatic	Buendía J. [2013,^Citation26]	Trastuzumab + standard therapy	No trastuzumab (standard therapy only)	1-year adjuvant trastuzumab treatment was not cost-effective. ICER was of US$ 69,701 per patient-life year gained, and US$ 71,491 per QALY gained, which is higher than the assumed WTP threshold of US$ 15,000 in Colombia as per the WHO cost-effectiveness threshold of 3 times GDP per capita: US$ 15,000 in Colombia, 2010.
	Chicaíza-Becerra L. [2014,^Citation33]	Lapatinib+ capecitabine (L + C)	Trastuzumab+ (capecitabine, vinorelbine or a taxane).	L + C was cost-effective compared to its comparators, and has dominated its other comparators (-ve ICER), at the recommended WHO threshold of 3 GDP, three times COP 11,216,656 USD (average Colombian exchange rate in 2009 was COP 2,156 USD per dollar).
	Leung H. [2018,^Citation35]	Pertuzumab + Trastuzumab and Docetaxel (TDP)	Trastuzumab and Docetaxel (TD) only	TDP was not cost-effective compared to TD. The ICER was NT$18,999,687 (US$ 593,741) per QALY gained which is higher than the determined WTP-threshold of NT$2,162,880 (US$ 67,590, 1 US$ = 32NT$) per QALY gained in Taiwan.

Table 3. Pharmacoeconomic characteristics and the synthesis of quality assessment results (by the reviewers)

Publication [1^st author (year)]	Perspective	P’economic model/approach	Effectiveness unit		Discounting	Sensitivity analysis		Time horizon	Quality assessment result (QHES scores)
			LYs	QALY		Deterministic	Probabilistic
Shih C. [2009,^Citation25]	Healthcare payer (Taiwanese government)	Net benefit regression	✓	-	-	-	✓	3 years	84
Buendía J. [2013,^Citation26]	Healthcare payer perspective (not clear who is really the payer)	Markov Model	✓	✓	✓	✓	✓	lifetime	95
Gershon N. [2019,^Citation27]	Societal perspective	Markov Model	✓	✓	✓	-	✓	lifetime	90
Genuino A. [2019,^Citation28]	Healthcare system perspective & Societal perspective	Markov Model	✓	✓	✓	✓	✓	lifetime	95
Gupta N. [2020,^Citation29]	Societal perspective	Markov Model	✓	✓	✓	-	✓	lifetime	87
Fonseca M. [2009,^Citation30]	Private healthcare payer perspective (insurance companies, healthcare plans, health maintenance organizations and healthcare cooperatives)	Markov Model	✓	-	✓	✓	✓	lifetime	89
Pichon-Riviere A. [2015,^Citation31]	Healthcare payer perspective (perspective of each country’s healthcare system)	Markov Model	✓	✓	✓	✓	✓	lifetime	93
Ansaripour A. [2017,^Citation32]	Healthcare perspective (Iranian healthcare system perspective)	Markov Model	✓	✓		✓	✓	lifetime	90
Chicaíza-Becerra L. [2014,^Citation33]	Third party (insurance companies)	Markov Model	✓	-	✓	✓*	✓	5 years	85
Aboutorabi A. [2015,^Citation34]	Healthcare perspective (Iranian Health System)	Markov Model	✓	✓	✓	✓	-	20 years	99
Leung H. [2018,^Citation35]	Healthcare payer (National Health Insurance Bureau NHBI)	Markov Model	-	✓	✓	✓	✓	5 years	92
Chen W. [2009,^Citation36]	Third party (insurance)	Markov Model	✓	-	✓	-	✓	lifetime	96
Ye M. [2018,^Citation37]	Healthcare perspective (Chinese healthcare perspective)	Markov Model	✓ **	✓	✓	✓	✓	lifetime	99
Lang H. [2016,^Citation38]	Third party (National Health Insurance NHI)	Markov Model	-	✓	✓	✓	✓	20 years lifetime	80

* Mentioned but not clear

** Measured life years, but the main aim was QALYs and ICER was only calculated for QALYs

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