Estimated economic benefits from low-frequency administration of atypical antipsychotics in treatment of schizophrenia: a decision model.

The objective of this study was to quantify the direct medical resources used and the corresponding burden of disease in the treatment of patients with schizophrenia. Because low-frequency administration (LFA) of risperidone guarantees adherence during treatment intervals and offers fewer opportunities to discontinue, adherence and persistence were assumed to improve, thereby reducing relapses of major symptoms.A decision tree model including Markov processes with monthly cycles and a five-year maximum timeframe was constructed. Costs were adapted from the literature and discounted at a 3% annual rate. The population is a demographically homogeneous cohort of patients with schizophrenia, differentiated by initial disease severity (mildly ill, moderately ill, and severely ill). Treatment parameters are estimated using published information for once-daily risperidone standard oral therapy (RIS-SOT) and once-monthly risperidone long-acting injection (RIS-LAI) with LFA therapy characteristics derived from observed study trends. One-year and five-year results are expressed as discounted direct medical costs and mean number of relapses per patient (inpatient, outpatient, total) and are estimated for LFA therapies given at three, six, and nine month intervals.The one-year results show that LFA therapy every 3 months (LFA-3) ($6,088) is less costly than either RIS-SOT ($10,721) or RIS-LAI ($9,450) with similar trends in the 5-year results. Moreover, the model predicts that LFA-3 vs. RIS-SOT vs. RIS LAI therapy will reduce costly inpatient relapses (0.16 vs. 0.51 vs. 0.41). Extending the interval to six (LFA-6) and nine (LFA-9) months resulted in further reductions in relapse and costs.Limitations include the fact that LFA therapeutic options are hypothetical and do not yet exist and limited applicability to compare one antipsychotic agent versus another as only risperidone therapy is evaluated. However, study results have quantified the potential health state improvements and potential direct medical cost savings achievable with the development and use of LFA medication delivery technologies.

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

OBJECTIVE: Although the use of innovative drug delivery systems, like orally disintegrating antipsychotic tablets (ODT), may facilitate medication adherence and help reduce the risk of relapse and hospitalization, no information is available about the comparative cost-effectiveness of standard oral tablets (SOT) vs ODT formulations in the treatment of schizophrenia. This study compared the cost-effectiveness of olanzapine ODT and olanzapine SOT in the usual treatment of outpatients with schizophrenia from a US healthcare perspective. The study also compared olanzapine ODT with risperidone and aripiprazole, two other atypical antipsychotics available in both ODT and SOT formulations. METHODS: Published medical literature and a clinical expert panel were used to populate a 1-year Monte Carlo Micro-simulation model. The model captures clinical and cost parameters including adherence levels, treatment discontinuation by reason, relapse with and without inpatient hospitalization, quality-adjusted life years (QALYs), treatment-emergent adverse events, healthcare resource utilization, and associated costs. Key outcomes were total annual direct cost per treatment, QALY, and incremental cost-effectiveness (ICER) per 1 QALY gained. RESULTS: Based on model projections, olanzapine ODT therapy was more costly ($9808 vs $9533), but more effective in terms of a lower hospitalization rate (15% vs 16%) and better QALYs (0.747 vs 0.733) than olanzapine SOT therapy. Olanzapine ODT was more cost-effective than olanzapine SOT (ICER: $19,643), more cost-effective than risperidone SOT therapy (ICER: $39,966), and dominant (meaning less costly and more effective) than risperidone ODT and aripiprazole in ODT or SOT formulations. LIMITATIONS: Lack of head-to-head randomized studies comparing the three studied atypical antipsychotics required making input assumptions that need further study. CONCLUSIONS: This micro-simulation found that the utilization of olanzapine ODT for the treatment of schizophrenia is predicted to be more cost-effective than any other ODT or SOT formulations of the studied atypical antipsychotic medications.

Screening and treatment for Alzheimer's disease: predicting population-level outcomes.

BACKGROUND: Advances in screening and treatment are needed to mitigate increasing prevalence of dementia due to Alzheimer's disease (DAT). Current proposals to revise Alzheimer's disease (AD) diagnostic criteria incorporate diagnostic biomarkers. Such revisions would allow identification of persons with AD pathology before the onset of dementia. The population-level impact of screening for preclinical AD and treating with a disease-modifying agent is important when evaluating new biomarkers and medications. METHODS: A published computer simulation model assigned AD-related event times, such that delays in disease progression due to therapy effectiveness can be estimated for a preclinical AD cohort. Attributes such as screening sensitivity/specificity, treatment efficacy, age at first screening, and rescreening intervals were varied. Outcomes included incident mild cognitive impairment (MCI-AD), incident DAT, and number of patients recommended for treatment. RESULTS: One-time screening at age 65 years, 50% efficacy, and literature-based proxy persistence rates yielded 12.4% incidence of MCI-AD and 0.9% decrease in DAT incidence from base case of no screening/treatment. Modest reductions in incident MCI-AD and DAT were observed with more sensitive testing. Reducing specificity yielded greater reductions in MCI-AD and DAT cases, albeit by treating more patients. Probabilistic sensitivity analysis predicted that for a cohort of patients aged 65 years, the number that needed to be treated to avoid one AD case was 11.6 (range: 5.7-104). CONCLUSION: The reduction in MCI-AD and DAT depends on initial screening age, screening frequency, and specificity. When considering population-level impact of screening-treatment, the effect of these parameters on incidence would need to be weighed against the number of individuals screened and treated.

Cost-effectiveness of olanzapine long-acting injection in the treatment of patients with schizophrenia in the United States: a micro-simulation economic decision model.

OBJECTIVE: To compare, from the perspective of third-party payers in the United States health care system, the cost-effectiveness of olanzapine long-acting injection (LAI, depot) with alternative antipsychotic agents including risperidone-LAI, paliperidone-LAI, haloperidol-LAI, and oral olanzapine, in the treatment of patients with schizophrenia who have been non-adherent or partially adherent with oral antipsychotics. RESEARCH DESIGN AND METHODS: A 1-year micro-simulation economic decision model was developed to simulate the dynamics of usual care of patients with schizophrenia who continue, discontinue, switch, or restart their medication. The model uses a range of clinical and cost parameters including adherence levels, relapse with and without hospitalization, quality-adjusted life years (QALYs), treatment discontinuation rates by reason, treatment-emergent adverse events, suicide, health care resource utilization, and direct health care costs. Published medical literature and a clinical expert panel were used to develop baseline model assumptions. OUTCOME MEASURES: Key model outputs include annual total direct cost (US$) per treatment and incremental cost-effectiveness values per additional QALY gained. RESULTS: Model results found that the olanzapine-LAI treatment strategy was more effective (greater QALYs) and less costly than risperidone-LAI, paliperidone-LAI, and haloperidol-LAI. In addition, olanzapine-LAI was both more effective and more costly, with an estimated incremental cost/QALY of $26,824 compared to oral olanzapine. The base-case and multiple sensitivity analyses found olanzapine-LAI to remain within acceptable cost-effective ranges (<$50,000) in terms of incremental cost/QALY gained. CONCLUSIONS: This micro-simulation model finds the olanzapine-LAI treatment strategy to result in better effectiveness and to be a cost-effective alternative compared to oral olanzapine and the LAI formulations of risperidone, paliperidone, and haloperidol in the treatment of non-adherent and partially adherent patients with schizophrenia in the United States. A key limitation is the assumption how LAI therapies compare to oral counterparts due to sparse head-to-head data. Further research is needed to verify baseline assumptions.

Modeling screening, prevention, and delaying of Alzheimer's disease: an early-stage decision analytic model.

BACKGROUND: Alzheimer's Disease (AD) affects a growing proportion of the population each year. Novel therapies on the horizon may slow the progress of AD symptoms and avoid cases altogether. Initiating treatment for the underlying pathology of AD would ideally be based on biomarker screening tools identifying pre-symptomatic individuals. Early-stage modeling provides estimates of potential outcomes and informs policy development. METHODS: A time-to-event (TTE) simulation provided estimates of screening asymptomatic patients in the general population age > or =55 and treatment impact on the number of patients reaching AD. Patients were followed from AD screen until all-cause death. Baseline sensitivity and specificity were 0.87 and 0.78, with treatment on positive screen. Treatment slowed progression by 50%. Events were scheduled using literature-based age-dependent incidences of AD and death. RESULTS: The base case results indicated increased AD free years (AD-FYs) through delays in onset and a reduction of 20 AD cases per 1000 screened individuals. Patients completely avoiding AD accounted for 61% of the incremental AD-FYs gained. Total years of treatment per 1000 screened patients was 2,611. The number-needed-to-screen was 51 and the number-needed-to-treat was 12 to avoid one case of AD. One-way sensitivity analysis indicated that duration of screening sensitivity and rescreen interval impact AD-FYs the most. A two-way sensitivity analysis found that for a test with an extended duration of sensitivity (15 years) the number of AD cases avoided was 6,000-7,000 cases for a test with higher sensitivity and specificity (0.90,0.90). CONCLUSIONS: This study yielded valuable parameter range estimates at an early stage in the study of screening for AD. Analysis identified duration of screening sensitivity as a key variable that may be unavailable from clinical trials.

Cost-effectiveness model comparing olanzapine and other oral atypical antipsychotics in the treatment of schizophrenia in the United States.

BACKGROUND: Schizophrenia is often a persistent and costly illness that requires continued treatment with antipsychotics. Differences among antipsychotics on efficacy, safety, tolerability, adherence, and cost have cost-effectiveness implications for treating schizophrenia. This study compares the cost-effectiveness of oral olanzapine, oral risperidone (at generic cost, primary comparator), quetiapine, ziprasidone, and aripiprazole in the treatment of patients with schizophrenia from the perspective of third-party payers in the U.S. health care system. METHODS: A 1-year microsimulation economic decision model, with quarterly cycles, was developed to simulate the dynamic nature of usual care of schizophrenia patients who switch, continue, discontinue, and restart their medications. The model captures clinical and cost parameters including adherence levels, relapse with and without hospitalization, quality-adjusted life years (QALYs), treatment discontinuation by reason, treatment-emergent adverse events, suicide, health care resource utilization, and direct medical care costs. Published medical literature and a clinical expert panel were used to develop baseline model assumptions. Key model outcomes included mean annual total direct cost per treatment, cost per stable patient, and incremental cost-effectiveness values per QALY gained. RESULTS: The results of the microsimulation model indicated that olanzapine had the lowest mean annual direct health care cost ($8,544) followed by generic risperidone ($9,080). In addition, olanzapine resulted in more QALYs than risperidone (0.733 vs. 0.719). The base case and multiple sensitivity analyses found olanzapine to be the dominant choice in terms of incremental cost-effectiveness per QALY gained. CONCLUSION: The utilization of olanzapine is predicted in this model to result in better clinical outcomes and lower total direct health care costs compared to generic risperidone, quetiapine, ziprasidone, and aripiprazole. Olanzapine may, therefore, be a cost-effective therapeutic option for patients with schizophrenia.

Medication adherence levels and differential use of mental-health services in the treatment of schizophrenia.

BACKGROUND: Adherence to antipsychotics for schizophrenia is associated with favorable clinical outcomes. This study compared annual mental-health service utilization by recent medication adherence levels for patients treated for schizophrenia, and assessed whether adherence levels change from pre- to post-psychiatric hospitalization. METHODS: We analyzed data from a large prospective, non-interventional study of patients treated for schizophrenia in the United States, conducted between 7/1997 and 9/2003. Detailed mental-health resource utilization was systematically abstracted from medical records and augmented with patients' self report. Medication possession ratio (MPR) with any antipsychotic in the 6 months prior to enrollment was used to categorize patients as: adherent (MPR >or= 80%, N = 1758), partially adherent (MPR >or= 60% < 80%, N = 36), or non-adherent (MPR < 60%, N = 216). Group comparisons employed propensity score-adjusted bootstrap re-sampling methods with 1000 iterations, adjusting for baseline patient demographic and clinical characteristics identified a priori. RESULTS: Adherent patients had a lower rate of psychiatric hospitalization compared with partially adherent and non-adherent patients (p < 0.001) and were more likely than non-adherent to engage in group therapy, individual therapy, and medication management. Most patients (92.0%) who were adherent in the 6 months prior to hospital admission continued to be adherent 6 months following hospitalization. However, 75.0% of previously partially adherent became adherent, and 38.7% of previously non-adherent became adherent following hospitalization. CONCLUSION: Adherence is associated with lower utilization of acute care services and greater engagement in outpatient mental-health treatment. Adherence is a potentially dynamic phenomenon, which may improve, at least temporarily, following patients' psychiatric hospitalizations.

Development, validation, and application of a microsimulation model to predict stroke and mortality in medically managed asymptomatic patients with significant carotid artery stenosis.

OBJECTIVE: To develop a model to predict stroke-free survival and mortality over a multiyear time frame for a trial-excluded population of medically managed asymptomatic patients with significant carotid artery stenosis. METHODS: We calibrated, validated, and applied a Monte Carlo microsimulation model. For calibration we adjusted general-population mortality and stroke risks to capture these risks specific to asymptomatic carotid stenosis patients. For validation, we compared model-predicted and actual stroke-free survival curves and stroke counts from a population of comparable patients. For application, the validated model predicted stroke-free survival for a hypothetical medically managed arm of a recent single-arm carotid revascularization trial. RESULTS: For each month in the 60-month time frame, the model-predicted and actual calibration trial stroke-free survival curves were not statistically different (P > 0.62). In validation, the calibrated model's stroke-free survival curvematched the actual curve from an independent population; beyond 24 months, the model-predicted and actual curves were not statistically different (P > 0.32). We also compared model-predicted and actual number of strokes from the independent trial. The model predicted 187.25 strokes (95% confidence interval 161.49-213.01), while the actual number was 171.6, within 1.22 standard deviations of the simulated mean. CONCLUSIONS: Given the absence of medically managed populations in recent carotid stenosis trials, our model can estimate stroke-free survival and mortality data for these patients. The model may also estimate the effectiveness of novel medical and procedural therapies for stroke prevention. These effectiveness estimates can inform the development of policies, guidelines, or cost-effectiveness analyses when only single-arm trial data exist.