Cost-effectiveness of 3-month paliperidone therapy for chronic schizophrenia in the Netherlands

Figures & data

Figure 1. Decision tree used to model the economic analyses. Abbreviations. HAL, Haloperidol long acting injectable; RIS, risperidone long acting injectable; OLZ, olanzapine oral.

Table 1. Clinical inputs and their sources.

Drug	Category	Item	Rate	Source
PP3M	Clinical rate	Hospitalized	0.141	PP1M rate pro-rated via Savitz et al.^33
		Non-hospitalized relapse	0.152	PP1M rate pro-rated via Savitz et al.^33
		Switch due to adverse events	0.063	Pro-rated via Savitz et al.^33
		Switch due to lack of efficacy	0.087	Pro-rated via Savitz et al.^33
		Dropouts (non-AE, non-LoE)	0.328	PP1M rate pro-rated via Savitz et al.^33
	Drug dosing	Dose (mg)	332	PP1M dose ×3.5, as per EMA Trevicta Summary^67
		Dosing interval	Every 3 months	EMA Trevicta Summary^67
		Restarting regimen after missing doses	If <4 months, give usual dose; if 4–9 months, stabilize with equivalent dose of PP1M immediately and 1 week later, then PP3M every 3 months	EMA Trevicta Summary^67
PP1M	Clinical rate	Hospitalized	0.194	Pro-rated from RIS-LAT using the ratio of hospitalization rates from 6 trials (n = 1883) (Baser et al.^68; Taylor and Olofinjana^69; Fu^70; Hough et al.^64; Savitz et al.^33; Zhang et al.^71)
		Non-hospitalized relapse	0.132	Decuypere et al.^42
		Switch due to adverse events	0.089	7 trials (n = 1976) (Attard et al.^70; Zhang^72; Alphs et al.^73; Fu et al.^74; Hough et al.^64; McEvoy et al.^75; Savitz et al.^33)
		Switch due to lack of efficacy	0.123	6 trials (n = 1988) (Attard et al.^70; Zhang et al.^71; Alphs et al.^73; Fu et al.^74; McEvoy et al.^75; Savitz et al.^33)
		Dropouts	0.463	Decuypere et al.^42
	Drug dosing	Dose (mg)	95 mg	Decuypere et al.^42
		Dosing interval	monthly	EMA Summary Xeplion^28
		Restarting regimen after missing doses	Same dose immediately and 1 week later, then monthly	EMA Summary Xeplion^28
RIS-LAT	Clinical rate	Hospitalized	0.267	20 observational studies (n = 7,033) (Bitter et al.^76; Chan et al.^77; Chang et al.^78; Chue et al.^79; Deslandes et al.^80; Huang et al.^81; Koczerginski and Arshoff^82; Lammers et al.^83; Leal et al.^84; Llorca et al.^85; Lloyd et al.^86; Mihaljevic-Peres et al.^87; Niaz and Haddad^47; Olivares et al.^88; Ren et al.^89; Rossi et al.^90; Taylor and Olofinjana^69; Taylor et al.^91; Williams et al.^92; Yu et al.^93)
		Non-hospitalized relapse	0.145	5 observational studies (n = 848) (Chan et al.^77; Chang et al.^78; Koczerginski and Arshoff^82; Leal et al.^84; Yu et al.^93)
		Switch due to adverse events	0.147	Decuypere et al.^42
		Switch due to lack of efficacy	0.203	Decuypere et al.^42
		Dropouts	0.444	Decuypere et al.^42
	Drug dosing	Dose (mg)	37.7 mg	Decuypere et al.^42
		Dosing interval	Every 2 weeks	Risperdal Consta EMA^94
		Restarting regimen after missing doses	Resume prior regimen	Risperdal Consta EMA^94
HAL-LAT	Clinical rate	Hospitalized	0.214	3 observational studies (n = 744) (Conley et al.^95; Huang et al.^81; Yu et al.^93)
		Non-hospitalized relapse	0.370	Yu et al.^93
		Switch due to adverse events	0.113	Decuypere et al.^42
		Switch due to lack of efficacy	0.156	Decuypere et al.^42
		Dropouts	0.480	Decuypere et al.^42
	Drug dosing	Dose (mg)	100 mg	Decuypere et al.^42
		Dosing interval	55% every 4 weeks, 11% every 3 weeks, 25% every 2 weeks, 9% weekly	Shi et al.^96
		Restarting regimen after missing doses	Same
oral-OLZ	Clinical rate	Hospitalized	0.314	10 studies (n = 12,913) (Ascher-Svanum et al.^97; Baser et al.^68; Bitter et al.^76; Conley et al.^95; Patel et al.^98; Vanasse et al.^99; Williams et al.^100; Yu et al.^101; Lieberman et al.^102; Meltzer et al.^103)
		Non-hospitalized relapse	0.470	Yu et al.^93
		Switch due to adverse events	0.228	RIS-LAT rate adjusted via Olivares et al.^44
		Switch due to lack of efficacy	0.165	RIS-LAT rate adjusted via Olivares et al.^44
		Dropouts	0.498	RIS-LAT rate adjusted via Olivares et al.^44
	Drug dosing	Dose (mg)	12.8	18 observational studies in 17 papers (n = 14,152) (Chan et al.^77; Dossenbach et al.^104; Garcia-Cabeza et al.^105; Gaviria et al.^29; Gibson et al.^106; Gomez et al.^107; Kasper et al.^108; Kilian et al.^109; Kraemer et al.^110; Kumar et al.^111; Mladsi et al.^112; Rascati et al.^113; Sacristan et al.^114; Snaterse and Welch^115; Takahashi et al.^116; Tiihonen et al.^117; Williams et al.^100)
		Dosing interval	Daily
		Restarting regimen after missing doses	restart using same regimen
clozapine	Clinical rate	Success	0.402	4 observational studies (n = 433) (Buchanan et al.^118; Essock et al.^119; Kane et al.^120; Rosenheck et al.^121)
	Drug dosing	Dose (mg)	418	21 trials in 20 papers (n = 798) (Bitter et al.^76; Bondolfi et al.^122; Breier and Hamilton^123; Buchanan et al.^118; Conley et al.^95; Henderson et al.^124; Hong et al.^125; Josaissen et al.^126; Kane et al.^120^,^127; Klieser et al.^128; Krakowski et al.^129; Kumra et al.^130; McGurk et al.^131; Moresco et al.^132; Naber et al.^133; Sacchetti et al.^134; Tollefson et al.^135; Volavka et al.^136; Wahlbeck et al.^137)
		Dosing interval	Daily	clozapine opinion^138
placebo (oral)	Clinical rate	Relapses	0.683	9 trials in 7 papers (n = 564) (Chen et al.^139; Crow et al.^140; Hogarty and Goldberg^141; Hogarty and Ulrich^142; Kane et al.^143; McCreadie et al.^144; McGlashan et al.^145)
placebo (1-monthly)	Clinical rate	Relapses	0.415	4 trials (n = 511) (Eklund and Forsman^146; Fu et al.^74; Hough et al.^64; Kane et al.^27)
placebo (3-monthly)	Clinical rate	Relapses	0.290	Berwaerts et al.^32

Abbreviations. HAL-LAT, haloperidol decanoate therapy; OLZ, olanzapine; PP1M, paliperidone monthly injection; PP3M, paliperidone 3-monthly injection; RIS-LAT, risperidone long-acting therapy.

Table 2. List of DRG codes in The Netherlands used to reimburse treatments for schizophrenia and other major psychoses, time allotments and reimbursement amounts for each DRG category.

DRG code	Minutes/patient/year	Cost/patient/year
230	250–799	$1,232.38
184	800–1,799	$2,370.33
066	1,800–2,999	$4,422.96
067	3,000–5,999	$7,656.82
068	6,000–11,999	$14,200.24
143	12,000–17,999	$24,171.91
144	18,000–23,999	$34,256.88
185	24,000–23,999	$41,468.24
186	30,000–29,999	$67,716.51

Abbreviations. DRG, diagnosis-related group.

Data source: DBC tarivien 2016⁴⁹.

Table 3. Costs of resources used in the analysis^a.

Cost centre	Resource	Cost^b	Source
Drugs	Paliperidone 3-month injection	3.5577 €/mg	Staatscourant^147
	Paliperidone 1-month injection	4.1974 €/mg	Staatscourant^147
	Risperidone long-acting injection	3.7702 €/mg	Staatscourant^147
	Haloperidol decanoate injection	0.5002 €/mg	Staatscourant^147
	olanzapine tablets	0.0212 €/mg	Staatscourant^147
	Clozapine tablets	0.0020 €/mg	Staatscourant^147
Medical care	Psychiatrist	113.31 €/visit	ZIN^148
	Injection fee	65.00€	ZIN^148
	Primary care physician	66.77€	ZIN^148
	Social worker	65.76€	ZIN^148
Institutional care	Hospital acute psychiatric unit	2,038.60€	ZIN^148
	Acute care (DRG)	374€	NZA^149
	Day hospital	164.91€	ZIN^148
Tests	Clozapine level	18.38€	SHL^150
	Blood test	4.12€	ZIN^148

^a All costs are expressed in 2016 euros.

^b Costs for drugs are the average price across all available strengths.

Table 4. Utilities used in the research.

State	PP3M	PP1M	RIS-LAT	HAL-LAT	oral-OLZ	clozapine
Stable disease	0.890	0.840	0.795	0.790	0.790	0.790
Relapse - ER visit (outpatient)	0.690	0.665	0.643	0.640	0.640	0.640
Relapse - hospitalized	0.490	0.490	0.490	0.490	0.490	0.490

Abbreviations. ER, emergency room; HAL-LAT, haloperidol decanoate therapy; OLZ, olanzapine; PP1M, paliperidone 1-monthly injection; PP3M, paliperidone 3-monthly injection; RIS-LAT, risperidone long-acting therapy.

Table 5. Outcomes from the pharmacoeconomic analysis.

Drug	Expected cost^a using DRGs	Expected cost^a using microcosting	Total relapses	Hospital admissions	Emergency room visits	QALYs	Economic outcome
PP3M	€8,781	€12,927	0.36	0.11	0.25	0.847	Dominant
PP1M	€10,325	€13,148	0.94	0.46	0.48	0.735	Dominated
HAL-LAT	€11,278	€13,801	1.39	0.40	0.99	0.709	Dominated
RIS-LAT	€11,307	€14,650	1.21	0.56	0.65	0.719	Dominated
oral-OLZ	€13,556	€18,335	1.70	0.57	1.14	0.656	Dominated

^a Costs are expressed in 2016 euros.

Abbreviations. HAL-LAT, haloperidol decanoate therapy; OLZ, olanzapine; PP1M, paliperidone palmitate 1-monthly injection; PP3M, paliperidone 3-monthly injection; QALY, quality adjusted life-year; RIS-LAT, risperidone microspheres therapy.

Figure 2. Scatterplot of cost-utility results between PP3M and PP1M using (a) DRGs and (b) microcosting.

Table 6. Validation of the cost-utility model.

Parameter	Drug	Rate in present analysis	Validation rate	Difference	% difference	Validation source
Expected cost	PP3M	€8,781	€8,783	–€2	−0.02%	De Moor et al.^37
	PP1M	€10,325	€10,176	€149	1.4%	Druais et al.^52
	HAL-LAT	€11,278	€11,025	€253	2.2%	Druais et al.^52
	RIS-LAT	€11,307	€10,990	€317	2.8%	Druais et al.^52
	oral-OLZ	€13,556	€10,076	€3,480	25.7%	Druais et al.^52
Expected QALYs	PP3M	0.847	0.850	−0.003	−0.4%	Average of PP1M rate from 10 studies + PP3M-PP1M difference from Osborne^51
	PP1M	0.735	0.753	−0.018	−2.4%	Druais et al.^52
	HAL-LAT	0.719	0.753	−0.034	−4.7%	Druais et al.^52
	RIS-LAT	0.709	0.725	−0.016	−2.2%	Druais et al.^52
	oral-OLZ	0.656	0.711	−0.055	−8.4%	Druais et al.^52

HAL-LAT, haloperidol decanoate; OLZ, olanzapine; PP1M, paliperidone palmitate 1-monthly injection; PP3M, paliperidone 3-monthly injection; QALY, quality adjusted life-year; RIS-LAT, risperidone microspheres depot.

Figure A1. PP3M vs RIS-LAT.

Figure A2. PP3M vs HAL-LAT.

Figure A3. PP3M vs oral olanzapine.

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