Cost-effectiveness analysis of atypical long-acting antipsychotics for treating chronic schizophrenia in Finland

Abstract

Objective:

In Finland, regional rates of schizophrenia exceed those in most countries, impacting the healthcare burden. This study determined the cost-effectiveness of long-acting antipsychotic (LAI) drugs paliperidone palmitate (PP-LAI), olanzapine pamoate (OLZ-LAI), and risperidone (RIS-LAI) for chronic schizophrenia.

Method:

This study adapted a decision tree analysis from Norway for the Finnish National Health Service. Country-specific data were sought from the literature and public documents, guided by clinical experts. Costs of health services and products were retrieved from literature sources and current price lists. This simulation study estimated average 1-year costs for treating patients with each LAI, average remission days, rates of hospitalization and emergency room visits and quality-adjusted life-years (QALY).

Results:

PP-LAI was dominant. Its estimated annual average cost was €10,380/patient and was associated with 0.817 QALY; OLZ-LAI cost €12,145 with 0.810 QALY; RIS-LAI cost €12,074 with 0.809 QALY. PP-LAI had the lowest rates of hospitalization, emergency room visits, and relapse days. This analysis was robust against most variations in input values except adherence rates. PP-LAI was dominant over OLZ-LAI and RIS-LAI in 77.8% and 85.9% of simulations, respectively. Limitations include the 1-year time horizon (as opposed to lifetime costs), omission of the costs of adverse events, and the assumption of universal accessibility.

Conclusion:

In Finland, PP-LAI dominated the other LAIs as it was associated with a lower cost and better clinical outcomes.     

Validation of an economic model of paliperidone palmitate for chronic schizophrenia

Abstract

Objective:

Model validation is important, but seldom applied in chronic schizophrenia. Validation consists of verifying the model itself for face validity (i.e., structure and inputs), cross-validation with other models assessing the same issue, and comparison with real-life outcomes. The primary purpose was to cross-validate a recent pharmacoeconomic model comparing long-acting injectable (LAI) antipsychotics for treating chronic schizophrenia in Sweden. The secondary purpose was to provide external validation.

Methods:

The model of interest was a decision tree analysis with a 1-year time horizon with costs in 2011 Swedish kroner. Drugs analyzed included paliperidone palmitate (PP-LAI), olanzapine pamoate (OLZ-LAI), risperidone (RIS-LAI), haloperidol (HAL-LAI), and oral olanzapine (oral-OLZ). Embase and Medline were searched from 1990–2012 for models examining LAIs. Articles were retrieved, with data extracted for all drugs compared including: expected costs, rates of hospitalization, proportion of time not in relapse, and associated QALYs. Outcomes from the model of interest were compared with those from other articles; costs were projected to 2012 using the consumer price index.

Results:

Twenty-six studies were used for validation; 14 of them provided evidence for cross-validation, 13 for external validation, and four for cost. In cross-validation, cost estimates varied ?1.8% (range: ?12.4–20.1%), hospitalizations 5.2% (?12.1–3.1%), stable disease 2.5% (?5.6–1.5%), QALYs 9.0% (4.3% after removing outliers). All estimates of clinical outcomes were within 15%. In external validation, hospitalization rates varied by 6.3% (?0.7–11.3%). The research was limited by data availability and validity of the original results.

Conclusion:

Other models validated the outputs of our model very well.     

The threshold rate of oral atypical anti-psychotic adherence at which paliperidone palmitate is cost saving

Abstract

Objective:

To identify, estimate, and compare ‘real world’ costs and outcomes associated with paliperidone palmitate compared with branded oral atypical anti-psychotics, and to estimate the threshold rate of oral atypical adherence at which paliperidone palmitate is cost saving.

Methods:

Decision analytic modeling techniques developed by Glazer and Ereshefsky have previously been used to estimate the cost-effectiveness of depot haloperidol, LAI risperidone, and, more recently, LAI olanzapine. This study used those same techniques, along with updated comparative published clinical data, to evaluate paliperidone palmitate. Adherence rates were based on strict Medication Event Monitoring System (MEMS) criteria. The evaluation was conducted from the perspective of US healthcare payers.

Results:

Paliperidone palmitate patients had fewer mean annual days of relapse (8.7 days; 6.0 requiring hospitalization, 2.7 not requiring hospitalization vs 17.8 days; 12.4 requiring hospitalization, 5.4 not requiring hospitalization), and lower annual total cost ($20,995) compared to oral atypicals (mean $22,481). Because paliperidone palmitate was both more effective and less costly, it is considered economically dominant. Paliperidone palmitate saved costs when the rate of adherence of oral atypical anti-psychotics was below 44.9% using strict MEMS criteria. Sensitivity analyses showed results were robust to changes in parameter values. For patients receiving 156?mg paliperidone palmitate, the annual incremental cost was $1216 per patient (ICER?=?$191 per day of relapse averted). Inclusion of generic risperidone (market share 18.6%) also resulted in net incremental cost for paliperidone palmitate ($120; ICER?=?$13). Limitations of this evaluation include use of simplifying assumptions, data from multiple sources, and generalizability of results.

Conclusions:

Although uptake of LAIs in the US has not been as rapid as elsewhere, many thought leaders emphasize their importance in optimizing outcomes in patients with adherence problems. The findings of this analysis support the cost-effectiveness of paliperidone palmitate in these patients.     

Economic and clinical comparison of atypical depot antipsychotic drugs for treatment of chronic schizophrenia in the Czech Republic

Abstract

Purpose:

The Czech Republic is faced with making choices between pharmaceutical products, including depot injectable antipsychotics. A pharmacoeconomic analysis was conducted to determine the cost-effectiveness of atypical depots.

Methods:

An existing 1-year decision-analytic framework was adapted to model drug use in this healthcare system. The average direct costs to the General Insurance Company of the Czech Republic of using paliperidone palmitate (Xeplion®), risperidone (Risperdal Consta®), and olanzapine pamoate (Zypadhera®) were determined. Literature-derived clinical rates populated the model, with costs adjusted to 2012 Euros using the consumer price index. Outcomes included quality-adjusted life-years (QALYs), days in remission, and proportions hospitalized or visiting emergency rooms. One-way sensitivity analyses were calculated for all important inputs. A multivariate probability analysis was used to examine the stability of results using 10,000 iterations of simulated input over reasonable ranges of all included variables.

Results:

Expected average costs/per patient treated were €5377 for PP-LAI, €6118 for RIS-LAI, and €6537 for OLZ-LAI. Respective QALYs were 0.817, 0.809, and 0.811; ER visits were 0.127, 0.134, and 0.141; hospitalizations were 0.252, 0.298, and 0.289. Results were generally robust in sensitivity analyses. PP-LAI dominated RIS-LAI and OLZ-LAI in 90.2% and 92.1% of simulations, respectively. Results were insensitive to drug prices but sensitive to adherence and hospitalization rates.

Conclusions:

PP-LAI dominated the other two drugs, as it had a lower overall cost and superior clinical outcomes, making it the preferred choice. Using PP-LAI in place of RIS-LAI for chronic relapsing schizophrenia would reduce the overall costs of care for the healthcare system.     

艾司西酞普兰与文拉法辛治疗抑郁障碍的成本-效果分析

目的对常用的抗抑郁药物艾司西酞普兰与文拉法辛治疗抑郁障碍进行成本-效果分析。方法将78例符合《中国精神障碍分类与诊断标准》（第三版）抑郁发作诊断标准的抑郁障碍患者随机分为两组,分别给予艾司西酞普兰或文拉法辛治疗8周,观察两组治疗方案的疗效及安全性,运用药物经济学的成本-效果分析方法进行评价。结果艾司西酞普兰、文拉法辛组治疗药品成本分别为663.04元和1164.80元;有效率分别为82.05%和84.62%;不良反应发生率分别为30.77%和28.21%。结论根据药物经济学评价,艾司西酞普兰组优于文拉法辛组。     

Cost effectiveness of paliperidone palmitate versus oral antipsychotics in patients with schizophrenia and a history of criminal justice involvement

Abstract

Objective:

Conduct a cost effectiveness analysis for the Paliperidone palmitate Research In Demonstrating Effectiveness (PRIDE) trial.     

Healthcare utilization and costs of veterans health administration patients with schizophrenia treated with paliperidone palmitate long-acting injection or oral atypical antipsychotics

Abstract

Objective:

This study aimed to compare real world healthcare costs and resource utilization between patients with schizophrenia treated with paliperidone palmitate long-acting injection (PP) and oral atypical antipsychotics (OAT).     

奇正消痛贴膏治疗急性腰扭伤的药物经济学评价

目的基于社会角度,通过成本-效果分析和成本-效用分析评价奇正消痛贴膏与双氯芬酸钠乙二胺乳胶剂治疗急性腰扭伤的经济学优劣,为急性腰扭伤的治疗方案选择提供依据。方法选取2012年7月至2013年6月来自北京、上海、广州和通辽4个城市5所三级医院的急性腰扭伤患者295例,其中奇正消痛贴膏治疗组152例,双氯芬酸钠乙二胺乳胶剂治疗组143例。选取疼痛消失时间为效果指标,质量调整生命年(QALYs)为效用指标,进行成本-效果分析及成本-效用分析。结果与双氯芬酸钠乙二胺乳胶剂治疗组相比,奇正消痛贴膏治疗组疼痛消失时间显著缩短(8.26 d对9.23 d,P<0.001),且获得更多的QALYs(0.0362对0.0359,P=0.597),但治疗成本也更高(308.52元对297.43元,P=0.697)。增量成本效果比(ICER)为-11.43元/d,即减少1天疼痛时间需多花费11.43元。增量成本效用比(ICUR)为36 966.67元/QALY,低于世界卫生组织(WHO)所建议的成本效用阈值115 000元(人均GDP的3倍)。结论在急性腰扭伤的治疗中,外用止痛药物奇正消痛贴膏是非常具有成本-效益的治疗方案。     

Estimated medical cost reductions for paliperidone palmitate vs placebo in a randomized,double-blind relapse-prevention trial of patients with schizoaffective disorder

Abstract

Objective:

The objective of this economic model was to estimate the difference in medical costs among patients treated with paliperidone palmitate once-monthly injectable antipsychotic (PP1M) vs placebo, based on clinical event rates reported in the 15-month randomized, double-blind, placebo-controlled, parallel-group study of paliperidone palmitate evaluating time to relapse in subjects with schizoaffective disorder.     

博思清与维思通治疗精神分裂症的药物经济学分析

目的比较博思清与维思通治疗精神分裂症的成本-效果。方法对50例住院精神分裂症患者应用博思清与维思通进行治疗,疗程6周。采用成本-效果分析法对两组进行分析。结果博思清与维思通治疗精神分裂症的有效率分别为96.0%和92.0%,两者疗效无显著性差异(P>0.05),成本分别为638.16元和647.8元。结论博思清治疗精神分裂症疗效与维思通相当,但起效更快,博思清(阿立哌唑)治疗精神分裂症较经济。     

A comparison of treatment patterns,healthcare resource utilization,and costs among young adult Medicaid beneficiaries with schizophrenia treated with paliperidone palmitate or oral atypical antipsychotics in the US

Abstract

Background: Much of the burden associated with schizophrenia is attributed to its early onset and chronic nature. Treatment with once monthly paliperidone palmitate (PP1M) is associated with lower healthcare utilization and better adherence as compared to oral atypical antipsychotics (OAAs). This study aimed to evaluate real-world effectiveness of PP1M and OAA therapies among US-based adult Medicaid patients with schizophrenia, overall and among young adults aged 18–35 years.

Methods: Adult patients with a diagnosis of schizophrenia and at least two claims for PP1M or OAA between January 1, 2010 and December 31, 2014 were selected from the IBM Watson Health MarketScan Medicaid Database. Treatment patterns and healthcare resource utilization and costs were compared between PP1M and OAA treatment groups following inverse probability of treatment (IPT) weighting to adjust for potential differences. Utilization and cost outcomes were estimated using OLS and weighted Poisson regression models.

Results: After IPT weighting, the young adult PP1M and OAA cohorts were comprised of 3,095 and 3,155 patients, respectively. PP1M patients had a higher duration of continuous treatment exposure (168.2 vs 132.5 days, p?=?.004) and better adherence on the index medication (proportion of days covered ≥80%: 19.0% vs 17.1%, p?<?.049). Young adults treated with PP1M were 37% less likely to have an all-cause inpatient admission (odds ratio [OR]?=?0.63, 95% confidence interval [CI]?=?0.53–0.74) and 33% less likely to have an ER visit (OR?=?0.67, 95% CI?=?0.55–0.81) compared to OAA young adult patients, but 27% more likely to have an all-cause outpatient office visit (OR?=?1.27, 95% CI?=?1.02–1.56). PP1M patients incurred significantly lower medical costs as compared to OAA patients.

Conclusions: Medicaid patients with schizophrenia treated with PP1M have higher medication adherence and have fewer hospitalizations as compared to patients treated with OAAs. PP1M may lead to reduced healthcare utilization and improved clinical outcomes.     

Adapting a global cost-effectiveness model to local country requirements: posaconazole case study

Abstract

Background:

Many countries have various requirements for local economic analyses to assess the value of a new health technology and/or to secure reimbursement. This study presents a case study of an economic model developed to assess the cost-effectiveness of posaconazole vs standard azole therapy (fluconazole/itraconazole) to prevent invasive fungal infections (IFIs), which was adapted by at least 11 countries.

Methods:

Modeling techniques were used to assess the cost-effectiveness of posaconazole vs fluconazole/itraconazole as IFI prophylaxis in patients with acute myelogenous leukemia or myelodysplastic syndromes and chemotherapy-induced neutropenia. For the core model, the probabilities of experiencing an IFI, IFI-related death, and death from other causes were estimated from clinical trial data. Long-term mortality, drug costs, and IFI treatment costs were obtained from secondary sources. Locally changed parameters were probabilities of long-term death and survival, currency, drug costs, health utility, IFI treatment costs, and discount rate.

Results:

Locally adapted cost-effective modeling studies indicate that prophylaxis with posaconazole, compared with fluconazole/itraconazole, prolongs survival, and, in most countries, is cost-saving. In all countries, the model predicted that prophylaxis with posaconazole would be associated with an increase in life-years, with increases ranging from 0.016–0.1 life-year saved. In all countries, use of the model led to posaconazole being approved by the appropriate reimbursement authority.

Limitations:

The study did not have power to detect differences between posaconazole and fluconazole or itraconazole separately. The risk of death after 100 days was assumed to be equal for those who did and did not develop an IFI, and equal probabilities of IFI-related and other death during the trial period were used for both groups.

Conclusions:

A core economic model was successfully adapted locally by several countries. The model showed that posaconazole was cost-saving or cost-effective vs fluconazole/itraconazole and led to positive reimbursement listings.     

Cost effectiveness of paliperidone palmitate versus risperidone long-acting injectable and olanzapine pamoate for the treatment of patients with schizophrenia in Sweden

Abstract

Objective:

To model the cost effectiveness of paliperidone palmitate (paliperidone long-acting injectable; PLAI), a new once-monthly long-acting antipsychotic therapy, compared with risperidone long-acting injectable (RLAI) and olanzapine pamoate (OLAI), in multi-episode patients (two or more relapses) with schizophrenia in Sweden.

Methods:

A Markov decision analytic model was developed to simulate the history of a cohort of multi-episode patients transitioning through different health states on a monthly basis over a 5-year time horizon from the perspective of the Swedish healthcare system. Therapeutic strategies consisted of starting treatment with RLAI (mean dose 37.5?mg every 2 weeks), PLAI (mean dose 75?mg equivalent (eq.) every month) or OLAI (150?mg every 2 weeks or 300?mg every 4 weeks). Probability of relapse, level of adherence, side-effects (extrapyramidal symptoms, tardive dyskinesia, weight gain and diabetes) and treatment discontinuation (switch) were derived from long-term observational data when feasible. Incremental cost-effectiveness outcomes, discounted at 3% annually, included cost per quality-adjusted life-year (QALY) and cost per relapse avoided (expressed in 2009 Swedish Krona SEK).

Results:

Relative to RLAI and OLAI, PLAI is economically dominant: more effective (additional QALYs, less relapses) and less costly treatment option over a 5-year time horizon. The results were robust when tested in sensitivity analysis.

Limitations:

The impact of once-monthly treatment on adherence levels is not yet known, and not all variables that could impact on real-world outcomes and costs were included in this model.

Conclusion:

PLAI was cost saving from a Swedish payer perspective compared with RLAI and OLAI in the long-term treatment of multi-episode (two or more relapses) schizophrenia patients.