Validation of an economic model of paliperidone palmitate for chronic schizophrenia

Figures & data

Table 1. List of rejected studies and reasons.

Reason for rejection	Number rejected	First author (year) of rejected articles
Inappropriate outcomes (no usable data)	17	Asseburg (2012)12, Barnett (2012)4, Beard (2006)13, Carswell (2010)14, Heeg (2005)15, Jerrell (2002)16, Kim (2011)17, Knapp (2008)6, Law (2007)18, Obradovic (2007)19, Phanthunane (2011)20, Schooler (1997)21, Spill (2010)22, Taylor (2007)23, Taylor (2009)24, Tiihonen (2011)25, Young (2006)26
Did not separate depot drugs	1	Peng (2011)27
No 12 month data	3	Castro-Costa (2008)28, Chang (2009)29, Fuller (2009)30
Duplicate	7	Edwards (2005)31, Einarson (2012)32, Laux (2005)33, Llorca (2005)34, Peuskens (2010)35, Yang (2005)36, Yang (2009)37
Total	28

Table 2. Cost verification with other models done in the Swedish healthcare system.

Drug	First author (year)	Model	Costing year	Total cost (SEK 2012)	% Difference
PP-LAI	Berntsson (2012)9	decision tree	2011	193,718
	Mehnert (2012)38	Markov model	2009	193,747	+0.02%
		Average (all models)		193,732
RIS-LAI	Berntsson (2012)9	decision tree	2011	225,749
	Mehnert (2012)38	Markov model	2009	198,176	−12.2%
	Hensen (2010)39	discrete event simulation	2007	239,178	+5.9%
	Willis (2010)40	chart review/regression	2006	173,721	−23.0%
		Average (other models)		203,692	−9.8%
		Average (all models)		209,206
OLZ-LAI	Berntsson (2012)9	decision tree	2011	234,646
	Mehnert (2012)38	Markov model	2009	205,607	−12.4%
		Average (all models)		220,127
HAL-LAI	Berntsson (2012)9	decision tree	2011	248,571
	Hensen (2010)39	discrete event simulation	2007	298,584	+20.1%
		Average (all models)		273,578
oral-OLZ	Berntsson (2012)9	decision tree	2011	254,710
	Hensen (2010)39	discrete event simulation	2007	211,200	−17.1%
	Lindström (2011)41	Markov model	2004	243,384	−4.4%
		Average (other models)		227,292	−10.8%
		Average (all models)		236,431

HAL, haloperidol decanoate; LAI, long-acting injection; OLZ, olanzapine; PP, paliperidone plamitate; RIS, risperidone; SEK, Swedish kroner (SEK 1 = 0.1185 €).

Table 3. Clinical output verification.

			Cross-validation			External validation
Outcome	Drug	Value	Value	First author (year)	Economic model	Value	First author (year)	Model
Hospitalization	PP-LAI	0.252	0.283	average
			0.236	Edwards (2012)42	decision tree
			0.330*	Furiak (2011)43	microsimulation
	RIS-LAI	0.330	0.295	average		0.323	average
			0.259	Edwards (2005)44	decision tree	0.332	Chang (2012)45	claims database
			0.330	Furiak (2011)43	microsimulation	0.180	Fleischhacker (2003)46	observational trial extension
						0.282	Lambert (2011)5	observational trial extension
						0.446	Niaz (2007)47	chart review
						0.204	Olivares (2009)48	registry
						0.457	Ren (2011)49	administrative database
						0.385	Rosenheck (2011)7	pragmatic trial
						0.333	Su (2009)50	claims database
						0.220	Taylor (2008)51	chart review
						0.391	Willis (2010)40	chart review
	OLZ-LAI	0.280	0.210	Furiak (2011)43	microsimulation
	HAL-LAI	0.469	0.466	average		0.356	Conley (2003)52	patient records
			0.658	Edwards (2005)44	decision tree
			0.550	Furiak (2011)43	microsimulation
			0.190	Glazer (1996)53	decision tree
	oral-OLZ	0.492	0.371	average		0.423	average
			0.312	Ascher-Svanum (2012)54	microsimulation	0.400	Rosenheck (2011)7	pragmatic trial
			0.412	Edwards (2005)44	decision tree	0.445	Tiihonen (2006)25	linked databases
			0.326	Edwards (2008)55	decision tree
			0.486	Edwards (2012)42	decision tree
			0.320	Furiak (2011)43	microsimulation
QALYs	PP-LAI	0.817	0.749	average
			0.667*	Furiak (2011)43	microsimulation
			0.830	Mehnert (2012)38	Markov model
	RIS-LAI	0.804	0.751	average
			0.667	Furiak (2011)43	microsimulation
			0.773	Hensen (2010)39	discrete event simulation
			0.812	Mehnert (2012)38	Markov model
	OLZ-LAI	0.812	0.754	average
			0.711	Furiak (2011)43	microsimulation
			0.796	Mehnert (2012)38	Markov model
	HAL-LAI	0.776	0.694	average
			0.648	Furiak (2011)43	microsimulation
			0.741	Hensen (2010)39	discrete event simulation
	oral-OLZ	0.773	0.679	average
			0.780	Ascher-Svanum (2011)56	modeled head-to-head RCT
			0.705	De Ridder (2009)57	regression
			0.677	Furiak (2011)43	microsimulation
			0.731	Furiak (2009)58	microsimulation
			0.755	Hensen (2010)39	discrete event simulation
			0.425	Lindström (2011)41	Markov model
Proportion of time not relapsed	PP-LAI	0.903		none found
	RIS-LAI	0.874	0.877	average
			0.844	Chue (2005)59, Hensen (2005)39	discrete event simulation
			0.827	De Graeve (2005)60	decision tree
			0.961	Edwards (2005)44	decision tree
	OLZ-LAI	0.892		none found
	HAL-LAI	0.817	0.762	average
			0.573	De Graeve (2005)60	decision tree
			0.812	Hensen (2010)39, Chue (2005)59	discrete event simulation
			0.901	Edwards (2005)44	decision tree
	oral-OLZ	0.819	0.805	average
			0.748	De Graeve (2005)60	decision tree
			0.938	Edwards (2005)44	decision tree
			0.955	Edwards (2008)55	decision tree
			0.839	Hensen (2010)39	discrete event simulation
			0.694	Lecomte (2000)61	Markov model

HAL, haloperidol; LAI, long-acting injection; OLZ, olanzapine, PP, paliperidone palmitate; RCT, randomized controlled trial; QALY, quality adjusted life-year; RIS, risperidone

*Did not use PP-LAI specific data; assumed all input values equal to those of RIS-LAI.

Asseburg C, Willis M, Löthgren M, et al. Hospitalisation utilisation and costs in schizophrenia patients in finland before and after initiation of risperidone long-acting injection. Schizophr Res Treatment 2012; 2012:791468

 PubMedGoogle Scholar

Barnett PG, Scott JY, Krystal JH, et al; CSP 555 Research Group. Cost and cost-effectiveness in a randomized trial of long-acting risperidone for schizophrenia. J Clin Psychiatry 2012;73:696-702

 PubMedGoogle Scholar

Beard SM, Maciver F, Clouth J, et al. A decision model to compare health care costs of olanzapine and risperidone treatment for schizophrenia in Germany. Eur J Health Econ 2006;7:165-72

 PubMedGoogle Scholar

Carswell C, Wheeler A, Vanderpyl J, et al. Comparative effectiveness of long-acting risperidone in New Zealand: a report of resource utilization and costs in a 12-month mirror-image analysis. Clin Drug Investig 2010;30:777-87

 PubMed Web of Science ®Google Scholar

Heeg B, Buskens E, Knapp M, et al. Modelling the treated course of schizophrenia: development of a discrete event simulation model. Pharmacoeconomics 2005;23(1 Suppl):17-33

 PubMedGoogle Scholar

Jerrell JM. Cost-effectiveness of risperidone, olanzapine, and conventional antipsychotic medications. Schizophr Bull 2002;28:589-605

 PubMed Web of Science ®Google Scholar

Kim K, Aas E. Cost-effectiveness analysis of olanzapine and risperidone in Norway. J Ment Health Policy Econ 2011;14:125-35

 PubMed Web of Science ®Google Scholar

Knapp M, Windmeijer F, Brown J, et al; SOHO Study Group. Cost-utility analysis of treatment with olanzapine compared with other antipsychotic treatments in patients with schizophrenia in the pan-European SOHO study. Pharmacoeconomics 2008;26:341-58

 PubMed Web of Science ®Google Scholar

Law WL, Hui HY, Young WM, et al. Atypical antipsychotic therapy for treatment of schizophrenia in Hong Kong Chinese patients–a cost analysis. Int J Clin Pharmacol Ther 2007;45:264-70

 PubMed Web of Science ®Google Scholar

Obradovic M, Mrhar A, Kos M. Cost-effectiveness of antipsychotics for outpatients with chronic schizophrenia. Int J Clin Pract 2007;61:1979-88

 PubMed Web of Science ®Google Scholar

Phanthunane P, Vos T, Whiteford H, et al. Cost-effectiveness of pharmacological and psychosocial interventions for schizophrenia. Cost Eff Resour Alloc 2011;9:6

 PubMedGoogle Scholar

Schooler NR, Keith SJ, Severe JB, et al. Relapse and rehospitalization during maintenance treatment of schizophrenia. The effects of dose reduction and family treatment. Arch Gen Psychiatry 1997;54:453-63

 PubMed Web of Science ®Google Scholar

Spill B, Silvia Konoppa S, Kissling W, et al. Long-term observation of patients successfully switched to risperidone long-acting injectable: a retrospective, naturalistic 18-month mirror-image study of hospitalization rates and therapy costs. Int J Psychiatry Clin Pract 2010;14:53-62

 PubMed Web of Science ®Google Scholar

Taylor D, Hayhurst K, Kerwin R. A controlled, mirror-image study of second-generation antipsychotics in the treatment of schizophrenia. Int Clin Psychopharmacol 2007;22:133-6

 PubMed Web of Science ®Google Scholar

Taylor D, Fischetti C, Sparshatt A, et al. Risperidone long-acting injection: a 6-year mirror-image study of healthcare resource use. Acta Psychiatr Scand 2009;120:97-101

 PubMed Web of Science ®Google Scholar

Tiihonen J, Haukka J, Taylor M, et al. A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia. Am J Psychiatry 2011;168:603-9

 PubMed Web of Science ®Google Scholar

Young CL, Taylor DM. Health resource utilization associated with switching to risperidone long-acting injection. Acta Psychiatr Scand 2006;114:14-20

 PubMed Web of Science ®Google Scholar

Peng X, Ascher-Svanum H, Faries D, et al. Decline in hospitalization risk and health care cost after initiation of depot antipsychotics in the treatment of schizophrenia. Clinicoecon Outcomes Res 2011;3:9-14

 PubMedGoogle Scholar

Castro-Costa E, Andrade JM, Quites L. Long-acting injectable risperidone improves quality of life in schizophrenic patients: a clinical case series. Rev Bras Psiquiatr 2008;30:403-4

 PubMed Web of Science ®Google Scholar

Chang HC, Tang CH, Tsai SJ, et al. Long-acting injectable risperidone and hospital readmission: a mirror-image study using a national claim-based database in Taiwan. J Clin Psychiatry 2009;70:141

 PubMed Web of Science ®Google Scholar

Fuller M, Shermock K, Russo P, et al. Hospitalisation and resource utilisation in patients with schizophrenia following initiation of risperidone long-acting therapy in the Veterans Affairs Healthcare System. J Med Econ 2009;12:317-24

 PubMedGoogle Scholar

Edwards NC, Locklear JC, Rupnow MF, et al. Cost effectiveness of long-acting risperidone injection versus alternative antipsychotic agents in patients with schizophrenia in the USA. Pharmacoeconomics 2005;23(1 Suppl):75-89

 PubMedGoogle Scholar

Einarson TR, Geitona M, Chaidemenos A, et al. Pharmacoeconomic analysis of paliperidone palmitate for treating schizophrenia in Greece. Ann Gen Psychiatry 2012;11:18

 PubMed Web of Science ®Google Scholar

Laux G, Heeg B, van Hout BA, et al. Costs and effects of long-acting risperidone compared with oral atypical and conventional depot formulations in Germany. Pharmacoeconomics 2005;23(1 Suppl):49-61

 PubMed Web of Science ®Google Scholar

Llorca PM, Miadi-Fargier H, Lançon C, et al. [Cost-effectiveness analysis of schizophrenic patient care settings: impact of an atypical antipsychotic under long-acting injection formulation]. Encephale 2005;31:235-46

 PubMed Web of Science ®Google Scholar

Peuskens J, Olivares JM, Pecenak J, et al. Treatment retention with risperidone long-acting injection: 24-month results from the Electronic Schizophrenia Treatment Adherence Registry (e-STAR) in six countries. Curr Med Res Opin 2010;26:501-9

 PubMed Web of Science ®Google Scholar

Yang YK, Tarn YH, Wang TY, et al. Pharmacoeconomic evaluation of schizophrenia in Taiwan: model comparison of long-acting risperidone versus olanzapine versus depot haloperidol based on estimated costs. Psychiatry Clin Neurosci 2005;59:385-94

 PubMed Web of Science ®Google Scholar

Yang L, Li M, Tao LB, et al. Cost-effectiveness of long-acting risperidone injection versus alternative atypical antipsychotic agents in patients with schizophrenia in China. Value Health 2009;12(3 Suppl):S66-9

 Google Scholar

Berntsson A, Einarson TR, Eriksson L, et al. Pharmacoeconomics of depot antipsychotics for treating chronic schizophrenia in Sweden. Presented at the 53rd Annual Meeting of the Scandinavian College of Neuro-Psychopharmacology, Copenhagen, Denmark, April 25–27, 2012

 Google Scholar

Mehnert A, Nicholl D, Pudas H, et al. Cost effectiveness of paliperidone palmitate versus risperidone long-acting injectable and olanzapine pamoate for the treatment of patients with schizophrenia in Sweden. J Med Econ 2012;15:844-61

 PubMedGoogle Scholar

Hensen M, Heeg B, Löthgren M, et al. Cost effectiveness of long-acting risperidone in Sweden. Appl Health Econ Health Policy 2010;8:327-41

 PubMedGoogle Scholar

Willis M, Svensson M, Löthgren M, et al. The impact on schizophrenia-related hospital utilization and costs of switching to long-acting risperidone injections in Sweden. Eur J Health Econ 2010;11:585-94

 PubMed Web of Science ®Google Scholar

Lindström E, Eberhard J, Fors BM, et al. A pharmacoeconomic analysis of sertindole in the treatment of schizophrenia in Sweden. Nord J Psychiatry 2011;65:403-13

 PubMed Web of Science ®Google Scholar

Edwards NC, Muser E, Doshi D, et al. The threshold rate of oral atypical anti-psychotic adherence at which paliperidone palmitate is cost saving. J Med Econ 2012;15:623-34

 PubMedGoogle Scholar

Furiak NM, Ascher-Svanum H, Klein RW, et al. Cost-effectiveness of olanzapine long-acting injection in the treatment of patients with schizophrenia in the United States: a micro-simulation economic decision model. Curr Med Res Opin 2011;27:713-30

 PubMed Web of Science ®Google Scholar

Edwards NC, Rupnow MF, Pashos CL, et al. Cost-effectiveness model of long-acting risperidone in schizophrenia in the US. Pharmacoeconomics 2005;23:299-314

 PubMed Web of Science ®Google Scholar

Chang HC, Tang CH, Huang ST, et al. A cost-consequence analysis of long-acting injectable risperidone in schizophrenia: a one-year mirror-image study with national claim-based database in Taiwan. J Psychiatr Res 2012;46:751-6

 PubMed Web of Science ®Google Scholar

Fleischhacker WW, Eerdekens M, Karcher K, et al. Treatment of schizophrenia with long-acting injectable risperidone: a 12-month open-label trial of the first long-acting second-generation antipsychotic. J Clin Psychiatry 2003;64:1250-7

 PubMed Web of Science ®Google Scholar

Lambert T, Olivares JM, Peuskens J, et al. Effectiveness of injectable risperidone long-acting therapy for schizophrenia: data from the US, Spain, Australia, and Belgium. Ann Gen Psychiatry 2011;10:10

 PubMed Web of Science ®Google Scholar

Niaz OS, Haddad PM. Thirty-five months experience of risperidone long-acting injection in a UK psychiatric service including a mirror-image analysis of in-patient care. Acta Psychiatr Scand 2007;116:36-46

 PubMed Web of Science ®Google Scholar

Olivares JM, Peuskens J, Pecenak J, et al; e-STAR Study Group. Clinical and resource-use outcomes of risperidone long-acting injection in recent and long-term diagnosed schizophrenia patients: results from a multinational electronic registry. Curr Med Res Opin 2009;25:2197-206

 PubMed Web of Science ®Google Scholar

Ren XS, Crivera C, Sikirica M, et al. Evaluation of health services use following the initiation of risperidone long-acting therapy among schizophrenia patients in the veterans health administration. J Clin Pharm Ther 2011;36:383-9

 PubMed Web of Science ®Google Scholar

Rosenheck R, Swartz M, McEvoy J, et al. Second-generation antipsychotics: reviewing the cost-effectiveness component of the CATIE trial. Expert Rev Pharmacoecon Outcomes Res 2007;7:103-11

 PubMedGoogle Scholar

Su KP, Chang HC, Tsai SJ, et al. Relapse and long-acting injectable risperidone: a 1-year mirror image study with a national claims database in Taiwan. Value Health 2009;12(Suppl):S118-21

 PubMedGoogle Scholar

Taylor M, Currie A, Lloyd K, et al. Impact of risperidone long acting injection on resource utilization in psychiatric secondary care. J Psychopharmacol 2008;22:128-31

 PubMed Web of Science ®Google Scholar

Conley RR, Mahmoud R. A randomized double-blind study of risperidone and olanzapine in the treatment of schizophrenia or schizoaffective disorder. Am J Psychiatry 2001;158:765-74

 PubMed Web of Science ®Google Scholar

Glazer WM, Ereshefsky L. A pharmacoeconomic model of outpatient antipsychotic therapy in “revolving door” schizophrenic patients. J Clin Psychiatry 1996;57:337-45

 PubMed Web of Science ®Google Scholar

Ascher-Svanum H, Furiak NM, Lawson AH, et al. Cost-effectiveness of several atypical antipsychotics in orally disintegrating tablets compared with standard oral tablets in the treatment of schizophrenia in the United States. J Med Econ 2012;15:531-47

 PubMedGoogle Scholar

Edwards NC, Pesa J, Meletiche DM, et al. One-year clinical and economic consequences of oral atypical antipsychotics in the treatment of schizophrenia. Curr Med Res Opin 2008;24:3341-55

 PubMed Web of Science ®Google Scholar

Ascher-Svanum H, Stensland MD, Peng X, et al. Cost-effectiveness of olanzapine vs. aripiprazole in the treatment of schizophrenia. Curr Med Res Opin 2011;27:115-22

 PubMed Web of Science ®Google Scholar

De Ridder A, De Graeve D. Comparing the cost effectiveness of risperidone and olanzapine in the treatment of schizophrenia using the net-benefit regression approach. Pharmacoeconomics 2009;27:69-80

 PubMed Web of Science ®Google Scholar

Furiak NM, Ascher-Svanum H, Klein RW, et al. Cost-effectiveness model comparing olanzapine and other oral atypical antipsychotics in the treatment of schizophrenia in the United States. Cost Eff Resour Alloc 2009;7:4

 PubMedGoogle Scholar

Chue PS, Heeg B, Buskens E, et al. Modelling the impact of compliance on the costs and effects of long-acting risperidone in Canada. Pharmacoeconomics 2005;23(1 Suppl):62-74

 PubMedGoogle Scholar

De Graeve D, Smet A, Mehnert A, et al. Long-acting risperidone compared with oral olanzapine and haloperidol depot in schizophrenia: a Belgian cost-effectiveness analysis. Pharmacoeconomics 2005;23(1 Suppl):35-47

 PubMedGoogle Scholar

Lecomte P, De Hert M, van Dijk M, et al. A 1-year cost-effectiveness model for the treatment of chronic schizophrenia with acute exacerbations in Belgium. Value Health 2000;3:1-11

 PubMedGoogle Scholar