Economic and Humanistic Burden in Paediatric Patients with Atopic Dermatitis.

Data concerning the economic and humanistic burden in patients with paediatric atopic dermatitis (AD) and their families are scarce. This retrospective study investigated these burdens in paediatric patients with AD using maintenance treatment with topical corticosteroids and/or conventional systemic immunosuppressants. Patient-reported outcomes regarding quality of life, AD severity, and parental work-related impairment were completed at inclusion. Data on healthcare resource utilization and medication prescription were collected retrospectively over the previous 12 months. Patients were categorized into mild, moderate or severe AD, based on Eczema Area and Severity Index score and medication use. Costs per patient per year per AD severity category were calculated. A total of 101 patients (median age 11.0 years (interquartile range 7.5-14.0), 47.5% men) were included, of whom 38 had mild AD, 37 moderate AD, and 26 severe AD. Mean ± standard deviation (SD) total costs patient per year for mild, moderate and severe AD were €1,812 ± €1,280, €2,680 ± €3,127, and €5,861 ± €3,993, respectively. Highest total direct and indirect costs were found in patients with severe AD, mainly due to higher healthcare and medication costs. Highest humanistic burden was found in patients with moderate AD. For example, the median (interquartile range) Patient-Oriented Eczema Measure score was significantly higher in these patients compared with mild and severe AD (19.0 (15.0-24.0) vs 12.0 (8.8-15.0) and 17.0 (9.5-22.0), respectively). AD in paediatric patients incurs considerable direct and indirect costs, especially in patients with severe AD. The high humanistic burden in patients with moderate AD underlines the need for effective and safe new treatment options for children with AD.

Desirability and acceptability of a treatment-sequencing model in relapsing-remitting multiple sclerosis: A health technology assessment perspective.

OBJECTIVE: Gather health technology assessment (HTA) experts' insights on the desirability and acceptability of treatment-sequencing models applied to relapsing-remitting multiple sclerosis (RRMS). DATA SOURCE/STUDY SETTING: Primary data. STUDY DESIGN: In-depth double-blind semi-structured telephone interviews. DATA COLLECTION/EXTRACTION METHODS: General themes were extracted from qualitative interviews. PRINCIPAL FINDINGS: Although experts confirmed the importance of evaluating the clinical and cost-effectiveness of treatments as part of a sequence, the current HTA decision making framework is not conducive to this. Developing an RRMS treatment-sequencing model that meets HTA requirements is difficult, in particular due to scarcity of effectiveness data in later treatment lines. CONCLUSIONS: At present, a treatment-sequencing model for RRMS may be desirable yet not requested by HTA bodies for their decision making. However, there could be other areas where a treatment-sequencing model for RRMS is of use.

An Integrated Pharmacokinetic-Pharmacodynamic-Pharmacoeconomic Modeling Method to Evaluate Treatments for Adults with Schizophrenia.

INTRODUCTION: Schizophrenia is a chronic mental disorder that worsens with each relapse. Long-acting injectable (LAI) antipsychotics may prevent the exacerbation of symptoms and occurrence of relapses through improved continuity of care. Different dose regimens are available for the LAIs aripiprazole monohydrate (AM) and aripiprazole lauroxil (AL), but their cost effectiveness is unclear. OBJECTIVES: The study aim was to compare costs and effects (relapses) of the different aripiprazole LAI dose regimens to inform clinical and US payer decisions. METHODS: A state-transition model calculated the outcomes of eight LAI dose regimens based on their relapse rates. As effectiveness data from randomized controlled trials were unavailable, relapse rates were modeled using pharmacokinetic and pharmacodynamic evidence. These described blood plasma levels of aripiprazole as a function of AM and AL dose regimens and described the probability of relapse as a function of aripiprazole blood plasma levels. The analysis had a time horizon of 1 year and took the US healthcare payer perspective. The incremental cost per relapse avoided and the probability of cost effectiveness were calculated in deterministic and probabilistic analyses. Scenario analyses explored the model's main assumptions, and results were validated against external data and other cost-effectiveness analyses. RESULTS: Monthly administration of AM 400 mg consistently yielded the lowest predicted number of relapses across deterministic, probabilistic, and scenario analyses. The costs of treatment and relapses were projected to be the lowest with a monthly administration of AL 441 mg. The incremental cost per relapse avoided with AM 400 mg ranged from AM 400 mg being dominant to $US83,300. From willingness-to-pay thresholds of $US30,000 per relapse avoided, the probability of cost effectiveness was highest for AM 400 mg. The validation showed alignment with external data. CONCLUSION: The analysis highlighted the robustness of the novel framework based on pharmacokinetic and pharmacodynamic evidence and demonstrated an application in a postmarketing setting.

An Innovative Approach to Modelling the Optimal Treatment Sequence for Patients with Relapsing-Remitting Multiple Sclerosis: Implementation, Validation, and Impact of the Decision-Making Approach.

INTRODUCTION: An innovative computational model was developed to address challenges regarding the evaluation of treatment sequences in patients with relapsing-remitting multiple sclerosis (RRMS) through the concept of a 'virtual' physician who observes and assesses patients over time. We describe the implementation and validation of the model, then apply this framework as a case study to determine the impact of different decision-making approaches on the optimal sequence of disease-modifying therapies (DMTs) and associated outcomes. METHODS: A patient-level discrete event simulation (DES) was used to model heterogeneity in disease trajectories and outcomes. The evaluation of DMT options was implemented through a Markov model representing the patient's disease; outcomes included lifetime costs and quality of life. The DES and Markov models underwent internal and external validation. Analyses of the optimal treatment sequence for each patient were based on several decision-making criteria. These treatment sequences were compared to current treatment guidelines. RESULTS: Internal validation indicated that model outcomes for natural history were consistent with the input parameters used to inform the model. Costs and quality of life outcomes were successfully validated against published reference models. Whereas each decision-making criterion generated a different optimal treatment sequence, cladribine tablets were the only DMT common to all treatment sequences. By choosing treatments on the basis of minimising disease progression or number of relapses, it was possible to improve on current treatment guidelines; however, these treatment sequences were more costly. Maximising cost-effectiveness resulted in the lowest costs but was also associated with the worst outcomes. CONCLUSIONS: The model was robust in generating outcomes consistent with published models and studies. It was also able to identify optimal treatment sequences based on different decision criteria. This innovative modelling framework has the potential to simulate individual patient trajectories in the current treatment landscape and may be useful for treatment switching and treatment positioning decisions in RRMS.

Optimizing choice of oral interferon-free treatment for genotype 1 hepatitis C virus using testing for NS5A resistance: a cost-utility analysis from the perspective of the Italian National Health Service.

BACKGROUND: Patients with genotype-1 hepatitis C virus infection who have failed to respond to standard therapy or who relapse following treatment may be considered for an interferon-free regimen incorporating a nonstructural protein 5A (NS5A) inhibitor. Sustained virologic response (SVR) with these regimens is typically >90%, but this is reduced in patients with NS5A resistance. European Association for Study of the Liver guidelines recommend simeprevir + sofosbuvir ± ribavirin (SMV+SOF±R) for re-treating patients failing an NS5A inhibitor-containing regimen. An alternative strategy would be to test for NS5A resistance prior to treatment, with therapy optimized based on the results. This study investigates the cost-effectiveness of this strategy. MATERIALS AND METHODS: A Markov model was used to estimate disease progression for treatment-experienced genotype 1 patients with severe fibrosis or compensated cirrhosis. Targeted treatment with either SMV+SOF±R or sofosbuvir + ledipasvir ± ribavirin (SOF+LDV±R) based on pretreatment NS5A resistance testing was compared to routine SOF+LDV±R without testing. Treatment duration was 12 or 24 weeks for patients with severe fibrosis or compensated cirrhosis (Metavir F3/F4). SVR data for the treatment options were based on the results of published clinical trials. The analysis was carried out from the perspective of the Italian National Health Service. RESULTS: Optimized treatment using NS5A resistance testing yielded 0.163 additional QALYs and increased costs of €2,789 per patient versus no testing. The incremental cost-effectiveness ratio (ICER) was €17,078/QALY. Sensitivity analysis identified the SVR attributable to each of the treatment regimens as the most sensitive determinant of ICER (range: €10,055/QALY-€43,501/QALY across plausible range). Probabilistic sensitivity analysis demonstrated that, at a willingness-to-pay threshold of €30,000/QALY, the probability that NS5A-directed treatment will be cost-effective is 81.4%. CONCLUSION: Optimizing therapy with either SMV+SOF±R or SOF+LDV±R based on pretreatment NS5A resistance testing was cost-effective from the perspective of the Italian National Health Service, in treatment-experienced patients with severe fibrosis or compensated cirrhosis.

Comparative cost-effectiveness of focal and total salvage 125I brachytherapy for recurrent prostate cancer after primary radiotherapy.

PURPOSE: Focal salvage (FS) iodine 125 (125I) brachytherapy could be an effective treatment for locally radiorecurrent prostate cancer (PCa). Toxicity is often reduced compared to total salvage (TS) while cancer control can be maintained, which could increase cost-effectiveness. The current study estimates the incremental cost per quality-adjusted life year (QALY) of FS compared to TS. MATERIAL AND METHODS: A decision analytic Markov model was developed, which compares costs and QALYs associated with FS and TS. A 3-year time horizon was adopted with six month cycles, with a hospital perspective on costs. Probabilities for genitourinary (GU) and gastrointestinal (GI) toxicity and their impact on health-related quality of life (SF-36) were derived from clinical studies in the University Medical Center Utrecht (UMCU). Probabilistic sensitivity analysis, using 10,000 Monte Carlo simulations, was performed to quantify the joint decision uncertainty up to the recommended maximum willingness-to-pay threshold of €80,000/QALY. RESULTS: Focal salvage dominates TS as it results in less severe toxicity and lower treatment costs. Decision uncertainty is small, with a 97-100% probability for FS to be cost-effective compared to TS (€0-€80,000/QALY). Half of the difference in costs between FS and TS was explained by higher treatment costs of TS, the other half by higher incidence of severe toxicity. One-way sensitivity analyses show that model outcomes are most sensitive to utilities and probabilities for severe toxicity. CONCLUSIONS: Focal salvage 125I brachytherapy dominates TS, as it has lower treatment costs and leads to less toxicity in our center. Larger comparative studies with longer follow-up are necessary to assess the exact influence on (biochemical disease free) survival and toxicity.