Cost-effectiveness of several atypical antipsychotics in orally disintegrating tablets compared with standard oral tablets in the treatment of schizophrenia in the United States

Figures & data

Figure 1.  Conceptual view of the Monte Carlo Micro-simulation (MCM) model. AE, treatment-emergent adverse event; EPS, extrapyramidal symptoms; Patient’s Treatment Status at the End of Quarter: C, Continue; D, Discontinue; S, Switch.

Table 1.  Adherence rates by medication.

Medications	Full adherence	Partial adherence	Non-adherence	Data source
Olanzapine	23%	43%	34%	Ahn et al.25, Ascher-Svanum et al.23
Risperidone	21%	39%	40%
Aripiprazole	19%	35%	46%	Assumption: equal to quetiapine; Furiak et al.16
ODT Olanzapine	37%	29%	34%	Karagianis et al.24
ODT Risperidone	35%	25%	40%
ODT Aripiprazole	33%	21%	46%

ODT, orally disintegrating tablet [formulation]; Using the Medication Possession Ratio (MPR), adherence levels are defined as: full adherence (MPR ≥ 80%), partial adherence (MPR ≥ 60%, <80%), and non-adherence (MPR < 60%).

Table 2.  Adherence rates by adherence level in cycle following relapse.

Adherence level prior to relapse	Full adherence after relapse	Partial adherence after relapse	Non-adherence after relapse	Data source
Full adherence	92.03%	1.45%	6.52%	Ascher-Svanum et al.23
Partial adherence	75.00%	12.50%	12.50%
Non-adherence	38.70%	9.70%	51.60%

Using the Medication Possession Ratio (MPR), adherence levels are defined as: full adherence (MPR ≥ 80%), partial adherence (MPR ≥ 60%, <80%), and non-adherence (MPR < 60%).

Table 3.  Relapse rates requiring and not requiring hospitalization.

Parameter	Value (%)			Data source
	Full adherence	Partial adherence	Non-adherence
Requiring hospitalization—For initial relapse
Olanzapine	2.0%	3.6%	5.2%	Lieberman et al.26; Lieberman et al. [erratum]27; Gilmer et al.20
Risperidone	3.5%	6.4%	9.2%
Aripiprazole	4.7%	8.5%	12.2%	Assumed same as ziprasidone. Zimbroff et al.28
ODT Olanzapine	2.0%	3.6%	5.2%	Lieberman et al.26; Lieberman et al. [erratum]27; Gilmer et al.20
ODT Risperidone	3.5%	6.4%	9.2%
ODT Aripiprazole	4.7%	8.5%	12.2%	Assumed same as ziprasidone. Zimbroff et al.28
Not requiring hospitalization
Olanzapine	2.0%	3.2%	4.8%	Lieberman et al.26; Lieberman et al. [erratum]27; Gilmer et al.20; Edwards et al.32
Risperidone	3.5%	5.7%	8.5%
Aripiprazole	4.7%	7.5%	11.3%	Assumed same as ziprasidone. Zimbroff et al.28
ODT Olanzapine	2.0 %	3.2%	4.8%	Lieberman et al.26; Lieberman et al. [erratum]27; Gilmer et al.20; Edwards et al.32
ODT Risperidone	3.5%	5.7%	8.5%
ODT Aripiprazole	4.7%	7.5%	11.3%	Assumed same as ziprasidone. Zimbroff et al.28

ODT, orally disintegrating tablet [formulation].

Table 4.  Adjusted relapse rates given a history of relapse.

History of relapse	Full adherence	Partial adherence	Non-adherence	Data source
Probability given history of one relapse	19%	40%	58%	Olfson et al.30; Tiihonen et al.31
Probability given history of two relapses	36%	75%	100%
Probability given history of three relapses	42%	88%	100%

Table 5.  Probability of multiple relapses within a single quarter.

Multiple relapse type	Value	Data source
Additional inpatient relapse given one prior relapse	20%	Edwards et al.32
Additional outpatient relapse given one prior relapse	75%

Table 6.  Probability of suicide event given adherence level.

Probability of suicide event	Fully adherent	Partially adherent	Non-adherent	Data source
Probability of suicide attempt	0.25%	0.76%	1.00%	Ahn et al.25
Probability suicide attempt is fatal	10.00%			Siris33
Cost of non-fatal suicide attempt	$140 (in addition to relapse costs)			Assumption: Furiak et al.16
Healthcare cost of fatal suicide attempt	$0			Assumption: Furiak et al.16, Edwards et al.32

Table 7.  Treatment emergent adverse event values.

Parameter	Value (%)	Data source
Adverse event rates for EPS
Olanzapine	15.5%	Carlson et al.36
Risperidone	24.7%
Aripiprazole	21.0%	Fleischhacker et al.35
ODT Olanzapine	15.5%	Assume ODT is equal to its respective SOT formulation
ODT Risperidone	24.7%
ODT Aripiprazole	21.0%
Adverse event rates for clinically significant weight gain (≥7%)
Olanzapine	30.0%	Lieberman et al.26
Risperidone	14.0%
Aripiprazole	7.3%	Fleischhacker et al.35
ODT Olanzapine	30.0%	Assumption: ODT is equal to its respective SOT formulation
ODT Risperidone	14.0%
ODT Aripiprazole	7.3%
Adverse event rates for diabetes
Olanzapine	3.3%	Lambert et al.34
Risperidone	3.2%
Aripiprazole	2.0%
ODT Olanzapine	3.3%	Assume ODT is equal to its respective SOT formulation
ODT Risperidone	3.2%
ODT Aripiprazole	2.0%
Adverse event rates for hyperlipidemia
Olanzapine	16.8%	Lieberman et al.26;
Risperidone	14.0%	Lambert et al.34;
Aripiprazole	3.6%	Olfson et al.30
ODT Olanzapine	16.8%	Assumption: ODT is equal to its respective SOT formulation
ODT Risperidone	14.0%
ODT Aripiprazole	3.6%

EPS, extrapyramidal symptoms; ODT, orally disintegrating tablet [formulation]; SOT, standard oral tablet [formulation].

Table 8.  Treatment discontinuation rates.

Parameter	Value (%)				Data Source
Annual all-cause discontinuation rates
Olanzapine	54%				Lieberman et al.26
Risperidone	63%				Lieberman et al.26
Aripiprazole	61%				Fleischhacker et al.35
ODT Olanzapine	54%				Assumption: ODT is equal to its respective SOT formulation
ODT Risperidone	63%
ODT Aripiprazole	61%
Annual discontinuation rates by reason
	Lack of efficacy	Intolerability	Patient decision	Other
Olanzapine	13%	16%	20%	5%	Lieberman et al.26
Risperidone	22%	10%	22%	9%	Lieberman et al.26
Aripiprazole	15%	18%	23%	5%	Fleischhacker et al.35
ODT Olanzapine	13%	16%	20%	5%	Assumption: ODT is equal to its respective SOT formulation
ODT Risperidone	22%	10%	22%	9%
ODT Aripiprazole	15%	18%	23%	5%

ODT, orally disintegrating tablet [formulation]; SOT, standard oral tablet [formulation].

Table 9.  Treatment switch patterns by reason for switching.

Medication switch to→	OLZ/ODT-OLZ	RIS/ODT-RIS	ARI/ODT-ARI	Ziprasidone-SOT	Clozapine-SOT
Medication switched from ↓ by reason
Lack of efficacy
OLZ/ODT-OLZ	0%	0%	0%	0%	100%
RIS/ODT-RIS	100%	0%	0%	0%	0%
ARI/ODT-ARI	50%	50%	0%	0%	0%
Weight gain/diabetes/hyperlipidemia
OLZ/ODT-OLZ	0%	0%	100%	0%	0%
RIS/ODT-RIS	0%	0%	100%	0%	0%
ARI/ODT-ARI	0%	0%	0%	100%	0%
EPS
OLZ/ODT-OLZ	0%	0%	100%	0%	0%
RIS/ODT-RIS	50%	0%	50%	0%	0%
ARI/ODT-ARI	100%	0%	0%	0%	0%
Patient preference
OLZ/ODT-OLZ	0%	70%	30%	0%	0%
RIS/ODT-RIS	70%	0%	30%	0%	0%
ARI/ODT-ARI	70%	30%	0%	0%	0%

ARI, aripiprazole; EPS, extrapyramidal symptoms; OLZ, olanzapine; RIS, risperidone; ODT, orally disintegrating tablet [formulation]; SOT, standard oral tablet [formulation].

Table 10.  Utility values for health states and disutility multipliers for treatment-emergent adverse events.

Parameter	Value			Data source
	Full adherence	Partial adherence	Non-adherence
Health states
While stable	0.88	0.75	0.75	Lenert et al.37; Expert opinion
Outpatient relapse	0.74	0.63	0.63
Inpatient psychiatric relapse	0.53	0.53	0.42
TEAE
EPS	0.888			Lenert et al.37
Clinically significant weight gain	0.959
Diabetes	0.888			Assumption: diabetes, hyperlipidemia and metabolic syndrome, utilities equal EPS utility in Lenert et al.37
Hyperlipidemia	0.888

EPS, extrapyramidal symptoms; ODT, orally disintegrating tablet [formulation]; TEAE, treatment-emergent adverse event.

Table 11.  Economic input parameters; medication costs.

	Cost (US Dollars)	Mean modal daily dose (mg)	Data source
Olanzapine	$21.06	15	NWP Prices: Analysource Data40 Doses: Conley and Mahmoud38; Tunis et al.41; Lieberman et al.26; Kern et al.39 Assumption: Generic risperidone NWP price = $0.83 per 4 mg/day
Risperidone	$0.83	4
Aripiprazole	$14.27	15
ODT Olanzapine	$22.04	15
ODT Risperidone	$15.46	4
ODT Aripiprazole	$16.99	15

Table 12.  Economic input parameters: health service resource utilization.

Health service	Per stable quarter*	Per outpatient relapse event*	Per inpatient relapse event*	EPS*	Clinically significant weight gain*	Diabetes	Hyper- lipidemia	Data source
Hospitalization, days	0.0	0.0	11.7**	0.0	0.0	0	0	*Edwards 2005^32 *Furiak 2009^16 **AHRQ HCUP^29
Day hospital treatment, days	0.0	1.25	1.25	0.0	0.0	0	0
Emergency room visits, no.	0.0	1.0	1.0	0.0	0.0	0	0
Physician visits, no.	3.0	1.0	1.0	1.0	0.5	0	0
Mental health clinic visits, no.	4.5	2.0	2.0	1.0	2.5	0	0
Home care, hours	0.0	2.75	2.75	0.0	0.0	0	0
Group intervention, hours	1.5	1.5	1.5	0.0	5.0	0	0
Nutritionist visits, hours	0.0	0.0	0.0	0.0	2.5	0	0

EPS = extrapyramidal symptoms; no. = number; NWP = 2010 net wholesale price; ODT = orally disintegrating tablet [formulation]

Table 13.  Economic input parameters: unit costs of health service resources.

Health services	Unit cost (US Dollars) ^42	Data source
Inpatient hospital, per day	$828	AHRQ HUCP^29
Day hospital treatment, per day	$501
Emergency room visit, per visit	$480
Outpatient Care		Edwards, 2005^32
Physician visit, per visit	$74
Mental health clinic visit	$75
Home healthcare, per hour	$82
Group therapy, per hour	$71
Nutritionist visit, per hour	$111

EPS = extrapyramidal symptoms; no. = number; NWP = 2010 net wholesale price; ODT = orally disintegrating tablet [formulation]

Table 14.  Economic input parameters: costs of adverse events.

Adverse event	Cost (US Dollars)	Unit	Data source
Diabetes	$600	Per quarter costs, costs of total care	Vera-Llonch, 2004^43; BLS CPI^42
Hyperlipidemia	$225	Per quarter statin therapy	Online drugstore costs^45
EPS	$12	Per quarter anticholinergic therapy	Online drugstore costs^45
Metabolic monitoring (laboratory costs)	$40	At therapy initiation, at 4 and 12 months; every 4 months if clinically significant weight gain	Marder, 2004^44

EPS = extrapyramidal symptoms; no. = number; NWP = 2010 net wholesale price; ODT = orally disintegrating tablet [formulation]

Figure 2.  Base case clinical outcomes: Relapse rates. ARIP, aripiprazole; ODT, orally disintegrating tablet [formulation]; OLZ, olanzapine; RIS, risperidone.

Figure 3.  Base case clinical outcomes—Inpatient relapses. Mean number of inpatient relapses per patient. ARIP, aripiprazole; ODT, orally disintegrating tablet [formulation]; OLZ, olanzapine; RIS, risperidone.

Figure 4.  Base case clinical outcomes—Mean QALYs gained. ARIP, aripiprazole; ODT, orally disintegrating tablet [formulation]; OLZ, olanzapine; QALYs, quality-adjusted life years; RIS. risperidone.

Figure 5.  Base case economic outcomes. ARIP, aripiprazole; ODT, orally disintegrating tablet [formulation]; OLZ, olanzapine; RIS, risperidone.

Table 15.  Base case cost-effectiveness results.

	Total cost (US Dollars)	Mean QALYs	ICER (Cost/QALY)
Olanzapine	$9,533	0.733	$19,643
Risperidone	$8,881	0.718	$39,966
Aripiprazole	$12,589	0.715	Dominated
ODT Olanzapine	$9,808	0.747	–
ODT Risperidone	$10,922	0.731	Dominated
ODT Aripiprazole	$12,863	0.728	Dominated

ODT, orally disintegrating tablet [formulation]; QALY, quality-adjusted life years.

Table 16.  Base case relapse rates.

	Relapse rate resulting in an inpatient admission	Relapse rate resulting in an outpatient visit	Proportion of stable patients (never relapsed)	Mean number of inpatient relapses per person
Olanzapine	16%	15%	71%	0.312
Risperidone	26%	23%	55%	0.529
Aripiprazole	33%	30%	44%	0.685
ODT Olanzapine	15%	14%	72%	0.297
ODT Risperidone	25%	23%	56%	0.507
ODT Aripiprazole	32%	29%	46%	0.659

ODT, orally disintegrating tablet [formulation].

Table 17.  One-way sensitivity analysis and QALY ICERs for ODT olanzapine vs olanzapine (standard oral tablet formulation).

	Parameter values		ICER
	ODT Olanzapine	Olanzapine	ODT Olanzapine vs Olanzapine
Absolute proportion of patients fully adherent	23%	23%	Dominated
	33%	23%	$27,100
	37%*	23%	$19,643
	53%	23%	$8,700
Absolute rates of annual discontinuation	60%	54%	$15,923
	54%*	54%	$19,643
	48%	54%	$20,750
	42%	54%	$22,942
Relative risk of relapse	1.00*	1.00	$19,643
	0.85	1.00	Dominant
	0.80	1.00	Dominant
	0.75	1.00	Dominant
Cost of therapy, US dollars	$21.06	$21.06	$8,071
	$22.04*	$21.06	$19,643
	$22.04*	$22.04	$8,571

*Indicates model base case value.

ICER, incremental cost-effectiveness ratios; ODT, orally disintegrating tablet [formulation].

Figure 6.  Proportion of cohorts at or below selected ICER thresholds varying proportion of patients fully adherent. *The increase in full adherence for olanzapine ODT is assumed to come from the partially adherent patients. ICER, incremental cost-effectiveness ratios; ODT, orally disintegrating tablet [formulation]; OLZ, olanzapine.

Figure 7.  Proportion of cohorts at or below selected ICER thresholds varying the absolute difference in annual discontinuation rate. ICER, incremental cost-effectiveness ratios; ODT, orally disintegrating tablet [formulation]; OLZ, olanzapine.

Figure 8.  Proportion of cohorts at or below selected ICER thresholds varying the relative risk of relapse. Relative risk (RR) is used to calculate ODT OLZ relapse rates relative to OLZ (ODT OLZ = RR * OLZ). ICER, incremental cost-effectiveness ratios; ODT, orally disintegrating tablet [formulation]; OLZ, olanzapine.

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