Economic and pharmaco-economic analysis of acromegaly treatment: a systematic review

Figures & data

Figure 1. PRISMA flow diagram [13].

Table 1. Characteristics of the studies included in the systematic review.

Authors	Publication year	Country	Number of participants	Time span	Type of costs	Type of outcomes	Type of analysis	Interventions compared	CHEC list (max 19)
Wilson et al. [14]	1999	Canada	53	Not specified	direct	person months in different health state; GH and IGF-1 levels	CEA + modeling	Surgical treatment alone versus. surgical and medical treatment in combination	NA
Wilson et al. [15]	2001	Canada	53	49 months	direct	person months in different health state; GH and IGF-1 levels	CCA	Surgical treatment alone versus. surgical and medical treatment in combination	8
Moore et al. [6]	2002	UK		2 years	direct	mortality and quality of life	SR + CEA, CUA	Somatostatin analogues versus. current therapy (dopamine agonists)	16
Didoni et al. [16]	2004	Italy	134	7 years	direct (diagnostic tests, surgery, radiotherapy, specialist visits and drugs)	NA	COI	Surgical and medical treatment	8
Abrams et al. [17]	2007	Belgium	21	36 weeks	direct (for medicines)	IGF-I and GH levels	CCA	Lanreotide depot once every 4 weeks versus. lanreotide depot every 6 weeks	11
Luque-Ramírez et al. [18]	2007	Spain	11	4 years	direct (peri- and post-operative: hospitalizations, surgery, medicines, tests, specialist visits, radiotherapy)	NA	COI	Surgical and medical treatment	10
Connock et al. [7]	2007	UK		50 years	direct	IGF-1 values; QALYs	SR and CEA +  modeling	Pegvisomant versus. standard therapy	NA
Valentim et al. [19]	2008	Brazil	276	2 years	direct	IGF-I and GH levels	CEA	Octreotide LAR versus. lanreotide SR	11
Salinas et al. [20]	2009	Mexico		18 months	direct	% of patients achieving a reduction in IGF-1 and GH levels	CEA + decision tree model	Monotherapy with octreo-tide LAR® versus. sequential therapy with lanreotide Autogel® and octreotide LAR® or vice versa	NA
Biermasz et al. [21]	2009	Netherlands	100	life-long	direct	success rates	modeling, CEA	SSA, surgery as primary or secondary treatment	NA
Moore et al. [22]	2009	UK		20 years	direct (lab tests, medicines, MRI scans)	IGF-1 levels; QALY; LYG	SR + CEA (modeling)	Pegvisomant versus standard care (SSA).	NA
Fujii et al. [23]	2012	Brazil		37 years	direct	LYG, QALYs, cases of DM, HBP, MI, JR and number of life years without DM, HBP or MI	modeling, CEA	Pegvisomant versus. standard therapy	NA
Alfonso-Cristancho et al. [24]	2012	Colombia		2 years	direct medical costs	IGF-I and GH levels	CEA - decision modeling	Octreotide versus lanreotide	NA
Roset et al. [25]	2012	Spain		2 years	direct (at 2009 prices and adjusted to the Spanish consumer price index in 2010)	NA	COI	SSA and surgery	9
Tasdemir et al. [26]	2014	France	88	1year	Direct (lab tests, medicines, visits, hospitalizations, diagnostic procedures) and indirect (lost productivity)	NA	COI	Surgical and medical treatment	11
Kousoulakou et al. [27]	2014	Greece		30 years for CMA; 5 years for BIA	direct (administration setting, drug wastage and time required, lab and imaging tests)	NA	CMA, BIA	Lanreotide Autogel versus Octreotide LAR	10
Tasdemir et al. [28]	2014	Italy	86	1 year	direct (lab tests, medicines, visits, hospitalizations, diagnostic procedures) and indirect costs (lost productivity)	IGF-1 and GH	COI	Surgical and medical treatment	11
Broder et al. [29]	2014	United States	2171	1 year	direct costs (medicines, co-morbidities)	NA	COI	Surgical and medical treatment	9
Ferreira et al. [30]	2015	Brazil		35 years	direct	‘years of life’ and ‘years living with disease control’	CEA modeling; BIA	Pegvisomant versus octreotide LAR	NA
Hahl et al. [31]	2015	Finland		30 years	direct (annual visits, monitoring, comorbidity costs)	biochemical parameters; QALY	5 state Markov model: CEA and CUA	Pasireotide versus pegvisomant + somatostatin analogues	NA
Margusino-Framiñán et al. [32]	2015	Spain			direct (medicines)	cure rates %	CEA	Preoperative SSA treatment versus only surgery	16
Placzek et al. [33]	2015	United States	757	1 year	direct (inpatient hospitalizations, ER visits, physician office visits, other outpatient services, prescription costs, total direct costs (medical costs plus prescription drug costs), and out-of-pocket (patient-paid) costs)	NA	COI	Surgical and medical treatment	12
Chuang et al. [34]	2015	United States	397	1 year	direct (hospital outpatient visits, physician office visits; neurosurgeon visits, inpatient hospitalization, medicines)	NA	COI	Surgical and medical treatment	12
Sliwczynski et al. [35]	2016	Poland	2390	1 year	direct	NA	COI	Surgical and medical treatment	9
Carlqvist and Wilen-Koort [36]	2016	Sweden		life-long	direct and indirect	QALYs	CUA + Markov model	Pasireotide long-acting versus. continued use of a first-line SSA.	NA
Lesén et al. [37]	2016	Sweden	529	1 year	direct and indirect	NA	COI (2013^a)		7
Xuan et al. [38]	2017	China		1 year	direct (medications, comorbidities, side effects, administration)	% of patients achieving normalization of IGF-1 or GH levels.	CEA - decision tree model	Octreotide long-acting release (LAR) versus lanreotide slow release (SR)	NA
Elbaum and Bolanowski [39]	2017	Poland	20	1 year	direct costs (surgery, medicines, radiotherapy)	NA	COI	Surgical and medical treatment	8
Kamusheva et al. [40]	2017	Bulgaria	22	1 year	direct costs (medicines)	QoL	CCA	Medical treatment	11
Peral et al. [41]	2017	Spain		life-long	direct medical costs (2016)	QALYs	CEA - Markov model	Second line treatments (pegvisomant and pasireotide) in patients resistant to SSA	NA
Liu et al. [42]	2018	United States	106	3 months	indirect (out-of-pocket cost, sick leave, leave of absence, direct loss of job due to acromegaly, unemployment, assistance to perform household chores, and family member loss of income)	QoL	COI + outcomes description	Surgical and medical treatment	9
Rusenova et al. [43]	2018	Bulgaria	180	1 year	direct (medicines)	NA	CA	Medical treatment	8
Korkmaz et al. [44]	2019	Turkey	135	50.9+/ -25.7 months	direct costs	remission rates	CCA	Preoperative somatostatin analogue (SSA) treatment	12

BIA: budget impact analysis; CA: cost analysis; CCA: cost consequences analysis; CEA: cost-effectiveness analysis; CHEC list: The Consensus Health Economic Criteria (CHEC) list; CMA: cost minimization analysis; COI: cost-of-illness analysis; CUA: cost utility analysis; DM: diabetes mellitus; GH: growth hormone; HBP: high blood pressure; IGF-1 - Insulin-like growth factor 1; JR:  joint replacement surgeries; LAR: long-acting release; LYG: life years gained; MI: myocardial infarction; MRI: magnetic resonance imaging; NA: not applicable; QALYs: quality adjusted life years; QoL: quality of life; SR: systematic review; SSA: somatostatin analogues; UK: United Kingdom.

^a Year of performing the cost analysis.

Table 2. Economic burdens presented as annual per patient costs of acromegaly treatment.

Authors	Country	Direct costs								Total direct costs	Indirect costs	Total costs	Total costs per patient inflated to 2018 values using local inflation rates	Total costs per patient converted to euro values based on end of 2018 exchange rates
		Medicines	Hospitalization	Lab tests	Surgery	Diagnostic procedures	Radiotherapy	Visits	Comorbidities
Abrams et al. [17]	Belgium	+								10,170.00 €	–	10,170.00 €	11,932.27 €	11,932.27 €
Kamusheva et al. [40]	Bulgaria	+								28,217.04 BGN	–	28,217.04 BGN	29,100.65 BGN	14,878.93 €
Rusenova et al. [43]	Bulgaria	+								11,600.00 €	–	11,600.00 €	11,600.00 €	11,600.00 €
Wilson et al. [14]	Canada	+								$8,700.00	–	$8,700.00	12,828.63 €	12,828.63 €
Wilson et al. [15]	Canada	+								$8,111.00	–	$8,111.00	11,276.19 €	11,276.19 €
Tasdemir et al. [26]	France	+	+	+		+		+			+	54,200.00 €	55,820.04 €	55,820.04 €
Didoni et al. [16]	Italy	+			+	+	+	+			–	10,250.72 €	12,419.27 €	12,419.27 €
Tasdemir et al. [28]	Italy	+	+	+		+		+			+	28,300.00 €	29,260.35 €	29,260.35 €
Salinas et al. [20]	Mexico	+									–	$27,744.03	$41,235.73	37,027.98 €
Sliwczynski et al. [35]	Poland									PLN 64,699.20	–	PLN 64,699.20	PLN 66,793.87	15,573.07 €
Elbaum and Bolanowski [39]	Poland	+			+		+			20,652.00 €	–	20,652.00 €	20,911.30 €	20,911.30 €
Luque–Ramírez et al. [18]	Spain	+	+	+	+		+	+		8,473.00 €		8,473.00 €	8,972.83 €	8,972.83 €
Roset et al. [25]	Spain	+			+					11,665.00 €		11,665.00 €	12,033.49 €	12,033.49 €
Lesén et al. [37]	Sweden									+	+	12,000.00 €	12,544.95 €	12,544.95 €
Korkmaz et al. [44]	Turkey									3,788.40 €		3,788.40 €	3,788.40 €	3,788.40 €
Moore et al. [6]	UK	+								£5,673.00		£5,673.00	£7,827.88	8,875.48 €
Connock et al. [7]	UK	+								£24,508.22		£24,508.22	£29,774.09	33,758.74 €
Moore et al. [22]	UK	+		+		+				£22,945.50		£22,945.50	£26,672.73	30,240.24 €
Broder et al. [29]	United States	+							+	$24,900.00		$24,900.00	$26,509.57	23,804.78 €
Placzek et al. [33]	United States	+	+		+			+		$21,855.00		$21,855.00	$23,021.49	20,672.60 €
Chuang et al. [34]	United States	+			+			+		$49,674.60	–	$49,674.60	$104,651.86	93,974.57 €
Liu et al. [42]	United States									–	$16,014.00	$16,014.00	$16,014.00	14,380.12 €

Figure 2. Annual per patient costs in different countries inflated and based on 2018 exchange rates.

Table 3. Economic burden presented as annual acromegaly costs in absolute value and as % of GDP.

Authors	Publication year	Country	Annual total cost for all patients	Annual cost for all patients	inflated to 2018 values using local inflation rates	converted to euro values based on end of 2018 exchange rates	GDP (2018) in euro	% of GDP (2018)	type of cost
Rusenova et al. [43]	2018	Bulgaria	2,000,000.00 €	2,000,000.00 €	2,000,000.00 €	2,000,000.00 €	58,354,765,450.88 €	0.00343%	direct costs
Wilson LS [15]	2001	Canada	$14,700,000.00	$14,700,000.00	$20,436,442.28	13,596,827.67 €	1,537,302,188,091.39 €	0.00088%	direct costs
Alfonso-Cristancho et al. [24]	2012	Colombia	26,903,808.00	COP$ 26,903,808.00 (octreotide)	COP$ 33,224,684.66	8,900.09 €	299,192,409,902.78 €	0.00001%	direct costs
			41,563,283.50	COP$ 41,563,283.50 (lanreotide)	COP$ 51,328,309.65	13,749.61 €
Kousoulakou et al. [27]	2014	Greece	4,440,000	4,440,000.00 €	4,475,514.10 €	4,475,514.10 €	196,785,304,001.31 €	0.00227%	direct costs
Biermasz et al. [21]	2009	Netherlands	2,878,787.88	2,878,787.88 €	3,139,751.32 €	3,139,751.32 €	819,823,836,723.98 €	0.00038%	direct costs
Lesén et al. [37]	2016	Sweden	6,328,000.00	6,328,000.00 €	6,985,226.50 €	6,615,368.71 €	494,905,790,187.23 €	0.00134%	direct + indirect

GDP: gross domestic product.

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