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.     

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

Background: A new depot formulation of paliperidone has been developed that provides effective treatment for schizophrenia for 3 months (PP3M). It has been tested in phase-3 trials, but no data on its cost-effectiveness have been published.

Purpose: To determine the cost-effectiveness of PP3M compared with once-monthly paliperidone (PP1M), haloperidol long-acting therapy (HAL-LAT), risperidone microspheres (RIS-LAT), and oral olanzapine (oral-OLZ) for treating chronic schizophrenia in The Netherlands.

Methods: A previous 1-year decision tree was adapted, based on local inputs supplemented with data from published literature. The primary analysis used DRG costs in 2016 euros from the insurer perspective, as derived from official lists. A micro-costing analysis was also conducted. For the costing scenario, official list prices were used. Clinical outcomes included relapses (treated as outpatients, requiring hospitalization, total), and quality-adjusted life-years (QALYs). Rates and utility scores were derived from the literature. Economic outcomes were the incremental cost/QALY-gained or relapse-avoided. Model robustness was examined in scenario, 1-way, and probability sensitivity analyses.

Results: The expected cost was lowest with PP3M (8,781€), followed by PP1M (10,325€), HAL-LAT (11,278€), RIS-LAT (11,307€), and oral-OLZ (13,556€). PP3M had the fewest total relapses/patient (0.36, 0.94, 1.39, 1.21, and 1.70, respectively), hospitalizations (0.11, 0.46, 0.40, 0.56, and 0.57, respectively), emergency room visits (0.25, 0.48. 0.99, 0.65, and 1.14, respectively) and the most QALYs (0.847, 0.735, 0.709, 0.719, and 0.656, respectively). In both cost-effectiveness and cost-utility analyses, PP3M dominated all other drugs. Sensitivity analyses confirmed base case findings. In the costing analysis, total costs were, on average, 31.9% higher than DRGs.

Conclusions: PP3M dominated all commonly used drugs. It is cost-effective for treating chronic schizophrenia in the Netherlands. Results were robust over a wide range of sensitivity analyses. For patients requiring a depot medication, such as those with adherence problems, PP3M appears to be a good alternative anti-psychotic treatment.     

Cost-effectiveness of aripiprazole once-monthly compared with paliperidone palmitate once-monthly injectable for the treatment of schizophrenia in the United States

Objective:

To develop a decision-analytic model to estimate the cost-effectiveness of initiating maintenance treatment with aripiprazole once-monthly (AOM) vs paliperidone long-acting injectable (PLAI) once-monthly among patients with schizophrenia in the US.

Methods:

A decision-analytic model was developed to evaluate a hypothetical cohort of patients initiating maintenance treatment with AOM or PLAI. Rates of relapse, adverse events (AEs), and direct medical costs were estimated for 1 year. Patients either remained on initial treatment or discontinued treatment due to lack of efficacy, AEs, or other reasons, including non-adherence. Data from placebo-controlled pivotal trials and product prescribing information (PI) were used to estimate treatment efficacy and AEs. Analyses were performed assuming dosing of clinical trials, real-world practice, PIs, and highest therapeutic dose available, because of variation in practice settings. The main outcome of interest was incremental cost per schizophrenia hospitalization averted with AOM vs PLAI.

Results:

Based on placebo-controlled pivotal trials’ dosing, AOM improved clinical outcomes by reducing schizophrenia relapses vs PLAI (0.181 vs 0.277 per person per year [pppy]) at an additional cost of US$1276 pppy, resulting in an incremental cost-effectiveness ratio (ICER) of US$13,280/relapse averted. When PI dosing was assumed, this ICER increased to US$19,968/relapse averted. When real-world dosing and highest available dosing were assumed, AOM was associated with fewer relapses and lower overall treatment costs vs PLAI.

Conclusions:

AOM consistently provided favorable clinical benefits. Under various dosing scenarios, AOM results indicated fewer relapses at lower overall costs or a reasonable cost-effectiveness threshold (i.e., less than the cost of a hospitalization relapse) vs PLAI. Given the heterogeneous nature of schizophrenia and variability in treatment response, health plans may consider open access for treatments like AOM. Since model inputs were based on data from separate placebo-controlled trials, generalization of results to the real-world setting is limited.     

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.     

Cost-effectiveness of 3-month paliperidone treatment for chronic schizophrenia in Spain

Background: A 3-month long treatment of paliperidone palmitate (PP3M) has been introduced as an option for treating schizophrenia. Its cost-effectiveness in Spain has not been established.

Aims: To compare the costs and effects of PP3M compared with once-monthly paliperidone (PP1M) from the payer perspective in Spain.

Methods: This study used the recently published trial by Savitz et al. as a core model over 1 year. Additional data were derived from the literature. Costs in 2016 Euros were obtained from official lists and utilities from Osborne et al. The authors conducted both cost-utility and cost-effectiveness analyses. For the former, the incremental cost per quality-adjusted life-year (QALY) gained was calculated. For the latter, the outcomes were relapses and hospitalizations avoided. To assure the robustness of the analyses, a series of 1-way and probability sensitivity analyses were conducted.

Results: The expected cost was lower with PP3M (4,780€) compared with PP1M (5,244€). PP3M had the fewest relapses (0.080 vs 0.161), hospitalizations (0.034 v.s 0.065), and emergency room visits (0.045 v.s 0.096) and the most QALYs (0.677 v.s 0.625). In both cost-effectiveness and cost-utility analyses, PP3M dominated PP1M. Sensitivity analyses confirmed base case findings. For the primary analysis (cost-utility), PP3M dominated PP1M in 46.9% of 10,000 simulations and was cost-effective at a threshold of 30,000€/QALY gained.

Conclusions: PP3M dominated PP1M in all analyses and was, therefore, cost-effective for treating chronic relapsing schizophrenia in Spain. For patients who require long-acting therapy, PP3M appears to be a good alternative anti-psychotic treatment.     

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.     

Recovery outcomes of schizophrenia patients treated with paliperidone palmitate in a community setting: patient and provider perspectives on recovery

Objectives:

This study evaluated the effect of paliperidone palmitate long-acting injectable (LAI) antipsychotic on recovery-oriented mental health outcomes from the perspective of healthcare providers and patients during the treatment of patients with schizophrenia or schizoaffective disorders.

Methods:

Archival data for patients with a primary diagnosis of schizophrenia or schizoaffective disorder receiving ≥6 months of paliperidone palmitate LAI were retrieved from the electronic medical records system at the Mental Health Center of Denver. Mental health recovery was assessed from both a provider’s (Recovery Markers Inventory [RMI]) and patient’s (Consumer Recovery Measure [CRM]) perspective. A three-level hierarchical linear model (HLM) was utilized to determine changes in CRM and RMI scores by including independent variables in the models: intercept, months from treatment (slope), treatment time period (pretreatment and treatment), age, gender, primary diagnosis, substance abuse diagnosis, concurrent medications, and adherence to paliperidone palmitate LAI.

Results:

A total of 219 patients were identified and included in the study. Results of the final three-level HLMs indicated an overall increase in CRM scores (p?<?0.05), an overall increase (p?<?0.01), and an increased rate of change (p?<?0.05) in RMI scores during the paliperidone palmitate LAI treatment period vs the pre-treatment period.

Limitations:

This study contained a retrospective, non-comparative design, and did not adjust for multiplicity

Conclusions:

The current study demonstrates that changes in recovery-oriented mental health outcomes can be detected following the administration of a specific antipsychotic treatment in persons with schizophrenia or schizoaffective disorders. Furthermore, patients receiving paliperidone palmitate LAI can effectively improve recovery-oriented outcomes, thereby supporting the drug’s use as schizophrenia treatment from a recovery-oriented perspective.     

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.     

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).     

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.     

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 resource usage of schizophrenia patients initiating long-acting injectable antipsychotics vs oral

Abstract

Objective:

To compare hospitalizations and incidence of relapses among patients with schizophrenia initiating long-acting injectable (LAI) antipsychotics vs oral antipsychotics.     

Impact of risperidone long-acting injectable on hospitalisation and medication use in Canadian patients with schizophrenia

Summary

A retrospective chart review was used to assess hospitalisation and medication switching in patients with schizophrenia initiated on either intramuscular risperidone long-acting injectable (RLAI) (n=69) or oral atypical antipsychotics (n=93) in Canada.

In the RLAI-treated patients, compared with an identical period prior to RLAI use (40.8 months), there were significant decreases in hospitalisation (50.7 vs. 4.3%; p<0.0001) and duration of hospitalisation (23.5 vs. 0.3 days per patient; p<0.0001) when patients were switched to RLAI (mean treatment period 41.5 months). Compared with patients receiving oral atypicals for 57.2 months, RLAI patients had a reduced risk of hospitalisation (95% confidence interval 1.8–16.5% vs. 54.7–76.4%) and medication switching (95% confidence interval 34.6–58.4% vs. 55.7–76.4%).

By virtue of its periodic intramuscular administration, RLAI offers the efficacy and tolerability of an atypical medication without the compliance issues associated with oral drugs, and leads to significant decreases in hospitalisation.     

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。     

Budget impact analysis of long acting injection for schizophrenia in Japan

Abstract

Aims: To estimate the budgetary impact of providing additional reimbursement for long acting injections for schizophrenia patients in psychiatric hospital settings in Japan to improve patient outcomes in schizophrenia.

Methods: Budget impact analysis of change in reimbursement policy using a prevalence-based model over a five-year time horizon. The results are reported as net change in expenditure and consequent cost/savings in Japanese yen at the time of analysis.

Results: The budget impact analysis shows that an increase in reimbursement for LAIs could lead to cumulative savings of an estimated 36.6 billion JPY over five years. These savings result from a decrease in hospitalization costs and an increased usage of LAI (assumed to be 10%). Based on the sensitivity analysis, the saving estimates are most sensitive to change in market share of generic and branded oral antipsychotics.

Limitations: Historical data were used to estimate the future costs of drug and hospitalization; however, it is not the best predictor of future, hence a source of potential bias. A good level of treatment adherence with oral antipsychotics was assumed, which is generally not the case; therefore, we might have overestimated the effectiveness of oral atypical antipsychotics. Additionally, the drug cost due to reimbursement might have also been overestimated because in clinical setting, the increase of LAI use may not have reached 10% of the market share. Lastly, patients’ behavior was derived from models, which may have loosely approximated the reality.

Conclusions: An additional reimbursement for the use of LAI in schizophrenia patients is likely to be cost neutral/cost saving and should be considered as a policy option to improve patient outcomes and budget sustainability.     

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.     

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.     

Medication adherence and discontinuation of long-acting injectable versus oral antipsychotics in patients with schizophrenia or bipolar disorder

Aims: To examine medication adherence and discontinuation in two separate groups of patients with schizophrenia or bipolar disorder (BD), who began receiving a long-acting injectable antipsychotic (LAI) versus those who changed to a different oral antipsychotic monotherapy.

Materials and methods: The Truven Health Analytics MarketScan Multi-State Medicaid claims database was used to identify patients with schizophrenia; Truven Health Analytics MarketScan Commercial and Medicaid claims databases were used to identify patients with BD. The analyses included adult patients (≥18 years) who either began receiving an LAI (no prior LAI therapy) or changed to a different oral antipsychotic (monotherapy). The first day of initiating an LAI or changing to a new oral antipsychotic was the index date. Linear and Cox regression models were conducted to estimate medication adherence (proportion of days covered [PDC]) and time to medication discontinuation (continuous medication gap ≥60 days), respectively. Models adjusted for patient demographic and clinical characteristics, baseline medication use, and baseline ED or hospitalizations.

Results: Patients with schizophrenia (N?=?5638) who began receiving LAIs had better medication adherence (5% higher adjusted mean adherence) during the 1 year post-index period and were 20% less likely to discontinue their medication during the entire follow-up period than patients who changed to a different oral antipsychotic monotherapy, adjusting for differences between LAI users and oral users. Similarly, patients with BD (N?=?11,344) who began receiving LAIs also had 5% better medication adherence and were 19% less likely to discontinue their medication than those using oral antipsychotics.

Limitations: Clinical differences unmeasurable in this database may have been responsible for the choice of LAI versus oral antipsychotics, and these differences may be responsible for some of the adherence advantages observed.

Conclusions: This real-world study suggests that patients with schizophrenia or BD who began receiving LAIs had better medication adherence and lower discontinuation risk than those who changed to a different oral antipsychotic monotherapy.