Cost-effectiveness of asenapine in the treatment of bipolar I disorder patients with mixed episodes

Figures & data

Figure 1. Economic model health states and transitions.

Table 1. Clinical input data for acute and maintenance phases.

Input value by treatment type	Probability per cycle (95% CI)			Source & notes
Acute phase: treatment response
Asenapine	0.46 (0.34, 0.59)			ARES post-hoc analyses
Olanzapine	0.38 (0.27, 0.49)			ARES post-hoc analyses
Asenapine + (VPA or Li)	0.59 (0.47, 0.71)			Use upper 95% CL from ASE
Olanzapine + (VPA or Li)	0.49 (0.38, 0.59)			Use upper 95% CL from OLA
No treatment^a	0.24 (0.12, 0.40)			ARES post-hoc analyses
Maintenance: transition to ‘sub-acute’ and ‘stable’ states
Acute phase non-responder to sub-acute	0.35			Assumption
Sub-acute to stable	0.60			Assumption
Maintenance: transition to ‘minimal VPA or Li’
No treatment	0.017^a			31^b
Asenapine	0.013			^c
Olanzapine	0.013			30
(ASE or OLA) + VPA	0.014			30^d
(ASE or OLA) + Li	0.016			30^e
(ASE or OLA) + VPA + Li	0.014			^f
Quetiapine + (VPA or Li)	0.012			30
Maintenance: relapse	Mania	Mixed	Depression
Asenapine	0.002	0.004	0.012	^c
Olanzapine	0.002	0.004	0.012	32
(ASE or OLA) + VPA	0.007	0.013	0.004	32^d
(ASE or OLA) + Li	0.006	0.011	0.006	32^e
(ASE or OLA) + VPA + Li	0.007	0.013	0.004	^f
Quetiapine + (VPA or Li)	0.007	0.005	0.019	33
Minimal VPA or Li	0.007	0.012	0.005	^g
Adverse events: incidence at 3 weeks	Weight gain	EPS
Asenapine	0.14 (0.08, 0.23)	0.11 (0.06, 0.19)		38
Olanzapine	0.26 (0.18, 0.35)	0.10 (0.05, 0.17)		38
(ASE or OLA) + VPA	0.08 (0.00, 0.16)	0.11		Average of ASE and OLA
(ASE or OLA) + Li	0.04 (0.00, 0.15)	0.08 (0.00, 0.17)		38
Quetiapine + (VPA or Li)	0.14	0.09		33

^aProbability not used in model – shown for reference only; ^bcurve fitted to function in Ekman et al.31; ^cassumed same value as OLA; ^dvalue for VPA used; ^evalue for Li used; ^fassumed same as VPA; ^gaverage of Li and VPA calculated.

Table 2. Relapse episode duration and length of associated inpatient stay in patients admitted to hospital.

Episode type	In-patient LOS (days)34	Overall episode duration (days)32	Overall episode duration (weeks)	Number of 4-week cycles
Mania	33.8	57.3	8.2	2
Mixed	66.0	111.9	16.0	4
Depression	51.9	137.9	19.7	5

Table 3. Utility values.

Health state	Published utility value	Age and sex-adjusted utility multiplier	Source
Acute episodes
Manic
Inpatient (80%)	0.25	0.28	48
CRT (20%)	0.60	0.66	48
Mixed
Inpatient (80%)	0.68	0.75	post-hoc analysis38
CRT (20%)	0.68	0.75
Depressive
Inpatient (10%)	0.29	0.33	48
Outpatient (70%)	0.61	0.68	49
CRT (20%)
Recovery
Sub-acute	0.80	0.90
Stable	0.84	0.94	38
Adverse events
Weight gain	0.83	0.93	50
EPS	0.72	0.81^a	50

^aDisutility of EPS only applied during acute phase as assumed to be appropriately managed during maintenance phase.

Table 4. Drug dosages, acquisition, and monitoring costs.

Treatment	Daily dose (mg)	Unit cost per mg (£)	Daily cost (£)	3-weekly monitoring costs – acute phase (£)	Annual monitoring costs – maintenance phase (£)
Asenapine	18.3	0.171	3.13	37.85	4.56
Olanzapine	14.8	0.004	0.06	37.85	4.56
Quetiapine	613.8	0.000,3	0.19	NA	7.90
VPA	1735.4	0.000,65	1.12	12.32	4.56
Li	1126.3	0.000,084	0.09	42.77	18.61
Li + VPA	–	–	1.22^a	49.54	18.61

^aThe daily cost of combination therapy Li + VPA was calculated as the sum of Li and VPA.

Table 5. Healthcare resources consumed (source: Soares-Weiser et al.32).

	Unit cost (£)	Stable BD-I^a	Manic or mixed episodes		Depressive episodes
			Management setting		Management setting
			Inpatient	CRT^b	Inpatient	CRT	Outpatient^c
Management setting balance		n/a	80%	20%	10%	20%	70%
Psychiatric consultant
Number of visits by length
45 minutes	180.75	0	1	1	1	1	1
30 minutes	120.50	0	1	1	1	1	1
20 minutes	80.33	1	3	3	3	3	3
SHO visits (20 minutes)	16.40	4	4	4	4	4	5
GP visits
Number of visits by length
20 minutes	58.67	0	2	2	2	2	2
10 minutes	29.33	9	7	7	7	7	8
CPN visit (30 minutes)	54.12	13	13	12	13	12	14
CRT visits	66.41	0	0	15	0	15	0
Days as inpatient	330.65	0	33.8 (manic), 66.0 (mixed)	0	51.9	0	0

^aResource consumption for ‘Stable’ represents annual baseline resource consumption for all BD-I patients, per-episode resource consumption is added as required on top. ^bCRT, Crisis Resolution Team; ^coutpatient care = ‘enhanced outpatient care’, as described in Soares-Weiser et al.32; SHO, Senior house officer; CPN, Community Psychiatric Nurse.

Table 6. Adverse event (weight gain and EPS) costs.

		Cost per cycle (£)
AE type	Service	Acute phase (3-week)	Maintenance phase (4-week)	Sources
Weight gain	Dietician	6.40	0.00	42^a
	GP	10.09	0.00	42^b
	Total	16.49	0.00
EPS	Consultant	80.33	0.00	42^c
	Medication	11.52	15.36	41^d
	Total	91.85	15.36

^aDietician, billed at £32/hour, is seen for 12 minutes; ^b20% of patients see a GP (reflecting the proportion of mixed episode patients being treated in the community rather than in hospital), for 17.2 minutes regarding their weight gain; ^cassume one 20-minute psychiatric consultation per cycle at a rate of £241/hour to cover EPS; ^d EPS medication: procyclidine dosed at 30 mg/day, cost is £2.56 for a 28-pack of 5 mg generic tablets.

Table 7. Base case analysis results (5 years and 9 weeks).

Drug	Phase	Benefits			Costs (£)
		Life years	QALYs excluding AEs	QALYs including AEs	Treatment	AEs	Health states	Total
ASE	Acute	0.173	0.1271	0.1233	351	38	10,235	10,624
	Maintenance	4.6391	3.7809	3.7485	3312	76	18,234	21,622
	Total	4.8121	3.908	3.8718	3663	113	28,469	32,246
OLA	Acute	0.173	0.1257	0.1211	165	40	11,238	11,443
	Maintenance	4.6388	3.7779	3.7319	1184	70	19,524	20,778
	Total	4.8119	3.9036	3.8531	1349	110	30,762	32,221
Increment	Acute	0	0.0014	0.0021	186	−2	−1003	−820
	Maintenance	0.0003	0.003	0.0166	2128	6	−1290	844
	Total	0.0003	0.0044	0.0187	2314	4	−2293	24

Note: Values in italics have been rounded, but reflect those used to calculate the base case ICER (£1302 per QALY gained).

Figure 2. Results of deterministic sensitivity analyses in a tornado diagram.

Figure 3. Cost-effectiveness acceptability curve for treatment with ASE vs OLA.

Figure 4. PSA scatterplot on cost-effectiveness plane for asenapine vs olanzapine.

Ekman M, Lindgren P, Miltenburger C, et al. Cost effectiveness of quetiapine in patients with acute bipolar depression and in maintenance treatment after an acute depressive episode. Pharmacoeconomics 2012;30:513-30

 PubMed Web of Science ®Google Scholar

Vieta E, Gunther O, Locklear J, et al. Effectiveness of psychotropic medications in the maintenance phase of bipolar disorder: a meta-analysis of randomized controlled trials. Int J Neuropsychopharmacol 2011;14:1029-49

 PubMed Web of Science ®Google Scholar

Soares-Weiser K, Bravo VY, Beynon S, et al. A systematic review and economic model of the clinical effectiveness and cost-effectiveness of interventions for preventing relapse in people with bipolar disorder. Health Technol Assess 2007;11:iii-206

 PubMed Web of Science ®Google Scholar

Vieta E, Suppes T, Ekholm B, et al. Long-term efficacy of quetiapine in combination with lithium or divalproex on mixed symptoms in bipolar I disorder. J Affect Disord 2012;142:36-44

 PubMed Web of Science ®Google Scholar

Post-hoc analysis of ARES trial dataset. Data on File. 2013

 Google Scholar

Department of Health. Hospital Episode Statistics, Admitted Patient Care - England 2011–12. 2013. http://www.hscic.gov.uk/searchcatalogue?productid=9161&q=title%3a%22Hospital+Episode+Statistics%3a+Admitted+patient+care%22&sort=Relevance&size=10&page=1#top. [Last accessed 16 December 2013]

 Google Scholar

Revicki DA, Hanlon J, Martin S, et al. Patient-based utilities for bipolar disorder-related health states. J Affect Disord 2005;87:203-10

 PubMed Web of Science ®Google Scholar

Hayhurst H, Palmer S, Abbott R, et al. Measuring health-related quality of life in bipolar disorder: relationship of the EuroQol (EQ-5D) to condition-specific measures. Qual Life Res 2006;15:1271-80

 PubMed Web of Science ®Google Scholar

Briggs A, Wild D, Lees M, et al. Impact of schizophrenia and schizophrenia treatment-related adverse events on quality of life: direct utility elicitation. Health Qual Life Outcomes 2008;6:105

 PubMed Web of Science ®Google Scholar

Curtis L. Unit costs of social health care. Canterbury, UK: Personal Social Services Research Unit, University of Kent, 2012

 Google Scholar

Joint Formulary Committee. British national formulary (BNF) 66, 66th edn. London: British Medical Association and The Royal Pharmaceutical Society of Great Britain, 2013

 Google Scholar