Patient-level Simulation Model Research Articles

Long‐term cost‐effectiveness of a Patient Empowerment Programme for type 2 diabetes mellitus in primary care

To evaluate the long-term cost-effectiveness of a Patient Empowerment Programme (PEP) for type 2 diabetes mellitus (DM) in primary care. PEP participants were subjects with type 2 DM who enrolled into PEP in addition to enrolment in the Risk Assessment and Management Programme for DM (RAMP-DM) at primary care level. The comparison group was subjects who only enrolled into RAMP-DM without participating in PEP (non-PEP). A cost-effectiveness analysis was conducted using a patient-level simulation model (with fixed-time increments) from a societal perspective. We incorporated the empirical data from a matched cohort of PEP and non-PEP groups to simulate lifetime costs and outcomes for subjects with DM with or without PEP. Incremental cost-effectiveness ratios (ICER) in terms of cost per quality adjusted life year (QALY) gained were calculated. Probabilistic sensitivity analysis was conducted with results presented as a cost-effectiveness acceptability curve. With an assumption that the PEP effect would last for 5 years as shown by the empirical data, the incremental cost per subject was US $197 and the incremental QALYs gained were 0.06 per subject, which resulted in an ICER of US $3290 per QALY gained compared with no PEP across the lifetime. Probabilistic sensitivity analysis showed 66% likelihood that PEP is cost-effective compared with non-PEP when willingness-to-pay for a QALY is ≥US $46 153 (based on per capita GDP 2017). Based on this carefully measured cost of PEP and its potentially large benefits, PEP could be highly cost-effective from a societal perspective as an adjunct intervention for patients with DM.

Cost-effectiveness of indacaterol/glycopyrronium in comparison with salmeterol/fluticasone combination for patients with moderate-to-severe chronic obstructive pulmonary disease: a LANTERN population analysis from Singapore.

In light of the growing evidence base for better clinical results with the use of the dual bronchodilator indacaterol/glycopyrronium (IND/GLY) over inhaled corticosteroid-containing salmeterol/fluticasone combination (SFC), this study aimed to evaluate the cost-effectiveness of IND/GLY over SFC in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) who are at low risk of exacerbations, in the Singapore healthcare setting. A previously published patient-level simulation model was adapted for use in Singapore by applying local unit costs. The model was populated with clinical data from the LANTERN and ECLIPSE studies. Both costs and health outcomes were predicted for the lifetime horizon from a payer's perspective and were discounted at 3% per annum. Costs were expressed in 2015 USD exchange rates. Uncertainty was assessed through probabilistic sensitivity analysis. Compared to SFC, use of IND/GLY increased mean life expectancy by 0.316 years and mean quality-adjusted life years (QALYs) by 0.246 years, and decreased mean total treatment costs (drug costs and management of associated events) by USD 1,474 over the entire lifetime horizon. IND/GLY was considered to be 100% cost-effective at a threshold of 1 × gross domestic product per capita. The cost-effectiveness acceptability curve showed that IND/GLY was 100% cost-effective at a willingness-to-pay threshold of USD 0 (additional cost) when compared to SFC. IND/GLY was estimated to be highly cost-effective compared to SFC in patients with moderate-to-severe COPD who are not at high risk of exacerbations in the Singapore healthcare setting.

PMS42 - Cost-Effectiveness of Sequential Treatment Strategies with Tnf-Inhibitors in Patients with Ankylosing Spondylitis: A Patient-Level Simulation Model

To assess cost-effectiveness of sequential treatment strategies after inadequate response to treatment with one, two, or three tumor necrosis factor (TNF) inhibitors in patients with ankylosing spondylitis (AS). Patient-level Markov models were constructed from the US healthcare payer’s perspective. Initially, treatment responses were generated at the end of 12-week treatment based on recent meta-analyses of TNF-inhibitors for treatment of AS. Patients who responded to treatment would enter a “Responders” Markov model with 3 health states: death, withdrawal, or continuing treatment with TNF-inhibitor. Patients entered a “Non-Responders” Markov model with 2 health states: death or continuing conventional care (CC), if they inadequately responded to treatment. In sequential treatment strategy with two TNF-inhibitors, patients who inadequately responded to treatment with the first TNF-inhibitor received a second TNF-inhibitor. For sequential treatment strategy with three TNF-inhibitors, patients received a third TNF-inhibitor if they failed both first and second TNF-inhibitors. Health utility was estimated based on the BASFI and BASDAI scores. The models accounted for real-world adherence of TNF-inhibitor treatment. One-way and probabilistic sensitivity analyses were performed to test the robustness and uncertainty of the model results. Over 40-year time horizon and 100,000 simulated patients for each treatment strategy, base-case results produced average total discounted per-patient costs of $43,598, $115,778, $149,923, and $167,905; and quality-adjusted life years (QALYs) per patient of 8.571, 10.140, 11.532, and 12.317 for CC, treatment strategies with one TNF-inhibitor, two TNF-inhibitors, and three TNF-inhibitors, respectively. The sequential treatment with three TNF-inhibitors was the most cost-effective treatment strategy with an incremental cost-effectiveness ratio of $23,948/QALY relative to treatment strategy with one TNF-inhibitor. The current study suggested that all 3 sequential treatment strategies with TNF-inhibitors are cost-effective compared to the conventional care with the sequential treatment with three TNF-inhibitors was the most cost-effective and optimal treatment strategy.

A model to predict disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD): the ADPKD Outcomes Model

BackgroundAutosomal dominant polycystic kidney disease (ADPKD) is the leading inheritable cause of end-stage renal disease (ESRD); however, the natural course of disease progression is heterogeneous between patients. This study aimed to develop a natural history model of ADPKD that predicted progression rates and long-term outcomes in patients with differing baseline characteristics.MethodsThe ADPKD Outcomes Model (ADPKD-OM) was developed using available patient-level data from the placebo arm of the Tolvaptan Efficacy and Safety in Management of ADPKD and its Outcomes Study (TEMPO 3:4; ClinicalTrials.gov identifier NCT00428948). Multivariable regression equations estimating annual rates of ADPKD progression, in terms of total kidney volume (TKV) and estimated glomerular filtration rate, formed the basis of the lifetime patient-level simulation model. Outputs of the ADPKD-OM were compared against external data sources to validate model accuracy and generalisability to other ADPKD patient populations, then used to predict long-term outcomes in a cohort matched to the overall TEMPO 3:4 study population.ResultsA cohort with baseline patient characteristics consistent with TEMPO 3:4 was predicted to reach ESRD at a mean age of 52 years. Most patients (85%) were predicted to reach ESRD by the age of 65 years, with many progressing to ESRD earlier in life (18, 36 and 56% by the age of 45, 50 and 55 years, respectively). Consistent with previous research and clinical opinion, analyses supported the selection of baseline TKV as a prognostic factor for ADPKD progression, and demonstrated its value as a strong predictor of future ESRD risk. Validation exercises and illustrative analyses confirmed the ability of the ADPKD-OM to accurately predict disease progression towards ESRD across a range of clinically-relevant patient profiles.ConclusionsThe ADPKD-OM represents a robust tool to predict natural disease progression and long-term outcomes in ADPKD patients, based on readily available and/or measurable clinical characteristics. In conjunction with clinical judgement, it has the potential to support decision-making in research and clinical practice.

Cost-effectiveness of enzyme replacement therapy with alglucosidase alfa in adult patients with Pompe disease

BackgroundPompe disease is a rare, progressive, metabolic disease, and the first treatable inheritable muscle disorder. Enzyme replacement therapy (ERT) with alglucosidase alfa is disease specific and the only medicinal product authorized for the treatment of Pompe disease. Costs of ERT are very high as for most orphan drugs. This study investigates the cost-effectiveness of ERT compared to supportive treatment in adult patients with Pompe disease.MethodsSurvival probabilities were estimated from an international observational dataset (n = 283) using a time-dependent Cox model. Quality of life was estimated on a Dutch observational dataset using a previously developed conceptual model which links clinical factors to quality of life. Costs included costs of ERT, costs of drug administration and other healthcare costs. Cost-effectiveness was estimated using a patient-level simulation model (n = 90), synthesising the information from underlying models for survival, quality of life and costs. The cost-effectiveness model estimated the (difference in) lifetime effects and costs for both treatments. Two scenarios were modelled: (1) a worse case scenario with no extrapolation of the survival gain due to ERT beyond the observed period (i.e. from 10 years onwards); and (2) a best case scenario with lifetime extrapolation of the survival gain due to ERT. Effects were expressed in (quality adjusted) life years (QALYs). Costs were discounted at 4.0% and effects at 1.5%.ResultsSubstantial increases in survival were estimated – discounted incremental life years of ERT ranged from 1.9 years to 5.4 years in the scenarios without and with extrapolation of survival gains beyond the observed period. Quality of life was also significantly better for patients receiving ERT. Incremental costs were considerable and primarily consisted of the costs of ERT. Incremental costs per QALY were €3.2 million for scenario 1 and €1.8 million for scenario 2.ConclusionsThe availability of extended, prospectively collected, longitudinal observational data on the most important input parameters required to construct a cost-effectiveness model is quite exceptional for orphan diseases. The cost-effectiveness model showed substantial survival gains from ERT. Despite these substantial gains, ERT was not cost-effective in the treatment of adult Pompe disease because of the high cost of treatment.

Indacaterol/glycopyrronium is cost-effective compared to salmeterol/fluticasone in COPD: FLAME-based modelling in a Swedish population

BackgroundThis study assessed the cost-effectiveness of indacaterol/glycopyrronium (IND/GLY) versus salmeterol/fluticasone (SFC) in chronic obstructive pulmonary disease (COPD) patients with moderate to very severe airflow limitation and ≥1 exacerbation in the preceding year.MethodsA previously published and validated patient-level simulation model was adapted using clinical data from the FLAME trial and real-world cost data from the ARCTIC study. Costs (total monetary costs comprising drug, maintenance, exacerbation, and pneumonia costs) and health outcomes (life-years (LYs), quality-adjusted life-years (QALYs)) were projected over various time horizons (1, 5, 10 years, and lifetime) from the Swedish payer’s perspective and were discounted at 3% annually. Uncertainty in model input values was studied through one-way and probabilistic sensitivity analyses. Subgroup analyses were also performed.ResultsIND/GLY was associated with lower costs and better outcomes compared with SFC over all the analysed time horizons. Use of IND/GLY resulted in additional 0.192 LYs and 0.134 QALYs with cost savings of €1211 compared with SFC over lifetime. The net monetary benefit (NMB) was estimated to be €8560 based on a willingness-to-pay threshold of €55,000/QALY. The NMB was higher in the following subgroups: severe (GOLD 3), high risk and more symptoms (GOLD D), females, and current smokers.ConclusionIND/GLY is a cost-effective treatment compared with SFC in COPD patients with mMRC dyspnea grade ≥ 2, moderate to very severe airflow limitation, and ≥1 exacerbation in the preceding year.

Propofol or benzodiazepines for short- and long-term sedation in intensive care units? An economic evaluation based on meta-analytic results.

PurposeThis evaluation compares propofol and benzodiazepine sedation for mechanically ventilated patients in intensive care units (ICUs) in order to identify the potential economic benefits from different payers’ perspectives.MethodsThe patient-level simulation model incorporated efficacy estimates from a structured meta-analysis and ICU-related costs from Italy, Germany, France, UK, and the USA. Efficacy outcomes were ICU length of stay (LOS), mechanical ventilation duration, and weaning time. We calculated ICU costs from mechanical ventilation duration and ICU LOS based on national average ICU costs with and without mechanical ventilation. Three scenarios were investigated: 1) long-term sedation >24 hours based on results from randomized controlled trials (RCTs); 2) long-term sedation based on RCT plus non-RCT results; and 3) short-term sedation <24 hours based on RCT results. We tested the model’s robustness for input uncertainties by deterministic (DSA) and probabilistic sensitivity analyses (PSA).ResultsIn the base case, mean savings with propofol versus benzodiazepines in long-term sedation ranged from €406 (95% confidence interval [CI]: 646 to 164) in Italy to 1,632 € (95% CI: 2,362 to 880) in the USA. Inclusion of non-RCT data corroborated these results. Savings in short-term sedation ranged from €148 (95% CI: 291 to 2) in Italy to €502 (95% CI: 936 to 57) in the USA. Parameters related to ICU and mechanical ventilation had a stronger influence in the DSA than drug-related parameters. In PSA, propofol reduced costs and ICU LOS compared to benzodiazepines in 94%–100% of simulations. The largest savings may be possible in the UK and the USA due to higher ICU costs.ConclusionCurrent ICU sedation guidelines recommend propofol rather than midazolam for mechanically ventilated patients. This evaluation endorses the recommendation as it may lead to better outcomes and savings for health care systems, especially in countries with higher ICU-related costs.

Quantifying the Trade-off Between Improved Glycemic Control and Severe Hypoglycemia Risk in Patients with Type 1 Diabetes: A Health Economic Analysis in the Uk

The Diabetes Control and Complications Trial (DCCT) established that intensive glycemic control results in improved long-term microvascular outcomes in patients with type 1 diabetes (T1D). The DCCT also, however, reported a threefold increase in severe hypoglycemia rates in intensively-managed patients relative to conventionally-managed patients. The present analysis used modern computer simulation techniques to quantify this trade-off between glycemic control and severe hypoglycemia risk. A complication cost analysis was conducted with the PRIME Diabetes Model, a long-term, externally audited and validated patient-level simulation model of T1D. A Poisson regression model from the DCCT was used to establish the expected glycated hemoglobin (HbA1c) levels attained in populations with average severe hypoglycemia rates of 0.4 and 0.6 events per year. These scenarios were used as the basis of the analysis, modeling incremental costs associated with diabetes complication incidence in the two scenarios over patient lifetimes. Costs were reported in 2016 pounds sterling, with future costs and effects discounted at 3.5% per annum. Populations of patients with average severe hypoglycemia rates of 0.4 and 0.6 events per year would be anticipated to have mean HbA1c levels of 8.54% and 7.38% respectively based on DCCT data. The increased hypoglycemia (low HbA1c) scenario improved quality-adjusted life expectancy relative to the lower hypoglycemia rate scenario, yielding an improvement of 0.30 quality-adjusted life years, despite an increase in cumulative incidence of hypoglycemia-related mortality from 0.78% to 0.91%. Average complication costs decreased by GBP 928 from GBP 23,632 to GBP 22,703 with improved glycemic control. The present analysis demonstrated the utility of computer simulation models such as the PRIME Diabetes Model in evaluating treatment guidelines. The analysis showed that the trade-offs of increased hypoglycemia and hypoglycemia-related mortality are more than offset by improvements in quality of life and reductions in cost at the population level.

Evaluating The Importance Of Realistically Simulating Risk Factor Progression Over Time: A Health Economic Modeling Analysis In Type 1 Diabetes

Glycated hemoglobin (HbA1c) is an important surrogate measure of glycemic control in patients with diabetes and is a key risk factor for many diabetes-related complications. As a result, HbA1c plays an important role in many long-term health economic models. The aim of the present analysis was to evaluate the importance of realistically simulating HbA1c progression over time in patients with type 1 diabetes in a health economic model. The PRIME Diabetes Model, a long-term, externally audited and validated, patient-level simulation model of type 1 diabetes was used to model long-term clinical and cost outcomes. Scenarios were based on either a linear assumption for HbA1c progression, or a target-driven HbA1c model, capturing covariance, developed from patient-level data from the Diabetes Control and Complications Trial (DCCT). Parameters significantly covarying with baseline and subsequent HbA1c were incorporated into covariance matrices in the target-driven model. The model used age and recent severe hypoglycemic episodes to derive patient-specific HbA1c targets. Costs were reported in 2016 pounds sterling. Simulating HbA1c progression based on patient-level data was shown to affect the projected cumulative incidence of diabetes-related complications, life expectancy, quality-adjusted life expectancy and the cost of complications versus the standard linear approach. Quality-adjusted life expectancy was 0.18 QALYs higher with simulated HbA1c progression. The reduction in diabetes-related complications projected with simulated HbA1c progression decreased overall direct costs per patient by GBP 3,062 over patient lifetimes. Long-term projections using the PRIME Diabetes Model indicate that realistically simulating the progression of important risk factors, such as HbA1c, over time can influence the outcomes of a health economic analysis compared with standard linear assumptions. Simulating risk factor progression, informed by analysis of patient-level data, may directly influence the outcomes of economic evaluations in diabetes and should be taken into consideration by modelers and decision-makers.

The cost-utility of point-of-care troponin testing to diagnose acute coronary syndrome in primary care

BackgroundThe added value of using a point-of-care (POC) troponin test in primary care to rule out acute coronary syndrome (ACS) is debated because test sensitivity is inadequate early after symptom onset. This study investigates the potential cost-utility of diagnosing ACS by a general practitioner (GP) when a POC troponin test is available versus GP assessment only.MethodsA patient-level simulation model was developed, representing a hypothetical cohort of the Dutch population (>35 years) consulting the GP with chest complaints. All health related consequences as well as cost consequences were included. Both symptom duration, selection of patients in whom the POC troponin test is performed, and test performance at different time points were incorporated. Health outcomes were expressed as Quality-Adjusted Life Years (QALYs). The main outcome parameters involve the effect of POC troponin testing on (in)correct hospital referrals, QALYs, and costs.ResultsThe POC troponin strategy decreases the referral rate in non-ACS patients from 38.46% to 31.85%. Despite a small increase in non-referral among ACS patients from 0.22% to 0.27%, the overall health effect is negligible. Costs will decrease with €77.25/patient (95% CI €-126.81 to €-33.37).ConclusionsThe POC troponin strategy is likely cost-saving, by reducing hospital referrals. The small increase in missed ACS patients can be partly explained by conservative assumptions used in the analysis. Besides, current developments in POC troponin tests will likely further improve their diagnostic performance. Therefore, future prospective studies are warranted to investigate whether those developments make the POC troponin test to a safe and cost-effective diagnostic tool for diagnosing ACS in general practices.

Economic evaluation of strategies for restarting anticoagulation therapy after a first event of unprovoked venous thromboembolism

Background Following at least 3 months of anticoagulation therapy after a first unprovoked venous thromboembolism (VTE), there is uncertainty about the duration of therapy. Further anticoagulation therapy reduces the risk of having a potentially fatal recurrent VTE but at the expense of a higher risk of bleeding, which can also be fatal. Objective An economic evaluation sought to estimate the long-term cost-effectiveness of using a decision rule for restarting anticoagulation therapy vs. no extension of therapy in patients based on their risk of a further unprovoked VTE. Methods A Markov patient-level simulation model was developed, which adopted a lifetime time horizon with monthly time cycles and was from a UK National Health Service (NHS)/Personal Social Services (PSS) perspective. Results Base-case model results suggest that treating patients with a predicted 1 year VTE risk of 17.5% or higher may be cost-effective if decision makers are willing to pay up to £20 000 per quality adjusted life year (QALY) gained. However, probabilistic sensitivity analysis shows that the model was highly sensitive to overall parameter uncertainty and caution is warranted in selecting the optimal decision rule on cost-effectiveness grounds. Univariate sensitivity analyses indicate variables such as anticoagulation therapy disutility and mortality risks were very influential in driving model results. Conclusion This represents the first economic model to consider the use of a decision rule for restarting therapy for unprovoked VTE patients. Better data are required to predict long-term bleeding risks during therapy in this patient group.

Economic Evaluation of Tobramycin Inhalation Powder for the Treatment of Chronic Pulmonary Pseudomonas aeruginosa Infection in Patients with Cystic Fibrosis.

BackgroundChronic lung infection with Pseudomonas aeruginosa occurs in approximately 50% of patients with cystic fibrosis (CF). This infection further compromises lung function, and significantly contributes to the increased healthcare costs.ObjectivesInhaled tobramycin, used to manage P. aeruginosa infection in CF patients, is available as powder (tobramycin inhalation powder, TIP) and solution (tobramycin inhalation solution, TIS). Evidence suggests increased adherence with the use of TIP over TIS. Hence, this analysis aimed to evaluate the potential pharmacoeconomic benefit of increased adherence with TIP over TIS in the US setting.MethodsA patient-level simulation model was developed to compare TIP with TIS. Both costs and benefits were predicted over a 10-year time horizon from a payer’s perspective, and were discounted annually at 3%. All costs were presented in 2016 US dollars.ResultsTIP was associated with greater quality-adjusted life-years (by 0.27) and lower total costs (by US$36,168) as compared with TIS over a 10-year time horizon. TIP-treated patients experienced a decreased mean number of exacerbations than TIS-treated patients (39.24 vs 50.20). Furthermore, administration of TIP via the T-326 Inhaler was associated with significant cost savings per patient, because of the nebulizer required for administering TIS (by US$1596) and exacerbation costs (by US$76,531). Probabilistic sensitivity analysis showed that TIP was dominant over TIS in 100% of the simulations.ConclusionTIP is likely to be a more cost-effective treatment than TIS, and therefore may reduce the economic burden of CF.

Simulation Modelling in Ophthalmology: Application to Cost Effectiveness of Ranibizumab and Aflibercept for the Treatment of Wet Age-Related Macular Degeneration in the United Kingdom

Previously developed models in ophthalmology have generally used a Markovian structure. There are a number of limitations with this approach, most notably the ability to base patient outcomes on best-corrected visual acuity (BCVA) in both eyes, which may be overcome using a different modelling structure. Simulation modelling allows for this to be modelled more precisely, and therefore may provide more accurate and relevant estimates of the cost effectiveness of ophthalmology interventions. This study aimed to explore the appropriateness of simulation modelling in ophthalmology, using the disease area of wet age-related macular degeneration (wAMD) as an example. A de novo economic model was built using a patient-level simulation, which compared ranibizumab with aflibercept in wAMD. Disease progression was measured using BCVA. Health-related quality of life (HRQoL) was estimated using a regression analysis linking BCVA in each eye to utility. The analysis was from the perspective of the National Health Service in the UK. Five different regression models were explored and were based on BCVA in either one eye or both eyes. The model outputs provide some evidence to support the hypothesis that the analyses using the two-eye models for estimating HRQoL generate a more accurate estimation of incremental quality-adjusted life-years (QALYs) associated with the positive treatment effect for ranibizumab versus aflibercept. Second-order analysis broadly supported these findings, and showed that the variation in incremental costs was slightly lower than in incremental QALYs. The second-order analysis estimated similar incremental costs and a greater overall variation in incremental QALYs than the first-order analysis, suggesting important non-linearities within the model. This analysis suggests that patient-level simulation models may be well suited to representing the real-world patient pathway in wAMD, particularly when aspects of disease progression cannot be adequately captured using a Markov structure. The benefits of a simulation approach can be demonstrated in the modelling of HRQoL as a function of BCVA in both eyes.

The Cost-Effectiveness of Ranibizumab Treat and Extend Regimen Versus Aflibercept in the UK.

Wet age-related macular degeneration (AMD) is a chronic eye condition that causes severe deterioration of vision and even blindness. Current wet AMD treatment in the UK involves the vascular endothelial growth factor inhibitors ranibizumab and aflibercept. Patients with wet AMD require frequent and long-term monitoring for treatment to be effective, contributing to a substantial resource burden at wet AMD centers. The European license for ranibizumab was recently updated with an individualized 'treat and extend' (T&E) regimen, comprising a structured monitoring and treatment protocol. This study evaluated the cost-effectiveness of ranibizumab T&E versus aflibercept within a UK setting. An individual patient-level simulation model was developed utilizing treatment effects from a network meta-analysis of randomized controlled trials. The model was conducted from a UK National Health Service (NHS) perspective over a lifetime horizon and the base case utilized probabilistic sensitivity analysis to assess uncertainty in the model. Additional scenario analyses were conducted to assess the impact of changes to the model inputs. Ranibizumab T&E was found to be more effective and less costly than aflibercept, providing, on average, an additional 1.058 quality-adjusted life years (QALYs) and a cost-saving of £19,604 over a lifetime horizon. At list price, ranibizumab T&E was found to be cost-effective versus aflibercept in 100% of simulations at a willingness-to-pay threshold of £20,000 per QALY. The robustness of the results was tested in several scenario analyses; ranibizumab T&E was found to be more effective, and less costly, than aflibercept in the vast majority of cases. This evaluation suggests that treating patients with ranibizumab according to the T&E regimen could be a better use of NHS resources than aflibercept, and could, therefore, be considered as a first-line regimen for patients with wet AMD in the UK. Novartis Pharmaceuticals UK Limited.

Individual patient information to select patients for different radiation techniques

Background and purposeProton therapy is an emerging technique in radiotherapy which results in less dose to the normal tissues with similar target dose than photon therapy, the current standard. Patient-level simulation models support better decision making on which patients would benefit most. Materials and methodsA simulation model was developed tracking individual patients' status regarding the primary tumour and multiple complications. As a proof of principle, the model was populated based on information from a cohort of 1013 head and neck cancer patients. Dose–volume parameters for photon and proton radiation treatment plans were then fed into the model to compare outcomes in terms of length and quality of life and select patients that would benefit most. ResultsThe illustrative model could adequately replicate the outcomes of photon therapy in the cohort. Improvements from proton therapy varied considerably between patients. The model projects medium-term outcomes for specific individuals and determines the benefits of applying proton rather than photon therapy. ConclusionsWhile the model needs to be fed with more and especially recent data before being fully ready for use in clinical practice, it could already distinguish between patients with high and low potential benefits from proton therapy. Benefits are highest for patients with both good prognosis and high expected damage to adjacent organs. The model allows for selecting such patients a priori based on patient relevant outcomes.

Treatment cost and life expectancy of diffuse large B-cell lymphoma (DLBCL): a discrete event simulation model on a UK population-based observational cohort

BackgroundDiffuse large B-cell lymphoma (DLBCL) is the commonest non-Hodgkin lymphoma. Previous studies examining the cost of treating DLBCL have generally focused on a specific first-line therapy alone; meaning that their findings can neither be extrapolated to the general patient population nor to other points along the treatment pathway. Based on empirical data from a representative population-based patient cohort, the objective of this study was to develop a simulation model that could predict costs and life expectancy of treating DLBCL.MethodsAll patients newly diagnosed with DLBCL in the UK’s population-based Haematological Malignancy Research Network (www.hmrn.org) in 2007 were followed until 2013 (n = 271). Mapped treatment pathways, alongside cost information derived from the National Tariff 2013/14, were incorporated into a patient-level simulation model in order to reflect the heterogeneities of patient characteristics and treatment options. The NHS and social services perspective was adopted, and all outcomes were discounted at 3.5 % per annum.ResultsOverall, the expected total medical costs were £22,122 for those treated with curative intent, and £2930 for those managed palliatively. For curative chemotherapy, the predicted medical costs were £14,966, £23,449 and £7376 for first-, second- and third-line treatments, respectively. The estimated annual cost for treating DLBCL across the UK was around £88–92 million.ConclusionsThis is the first cost modelling study using empirical data to provide ‘real world’ evidence throughout the DLBCL treatment pathway. Future application of the model could include evaluation of new technologies/treatments to support healthcare decision makers, especially in the era of personalised medicine.

COST-EFFECTIVENESS OF STRUCTURED EDUCATION IN CHILDREN WITH TYPE-1 DIABETES MELLITUS.

Kids in Control OF Food (KICk-OFF) is a 5-day structured education program for 11- to 16-year-olds with type 1 diabetes mellitus (T1DM) who are using multiple daily insulin injections. This study evaluates the cost-effectiveness of the KICk-OFF education program compared with the usual care using data from the KICk-OFF trial. The short-term within-trial analysis covers the 2-year postintervention period. Data on glycated hemoglobin (HbA1c), severe hypoglycemia, and diabetic ketoacidosis (DKA) were collected over a 2-year follow-up period. Sub-group analyses have been defined on the basis of baseline HbA1c being below 7.5 percent (58.5 mmol/mol) (low group), between 7.5 percent and 9.5 percent (80.3 mmol/mol) (medium group), and over 9.5 percent (high group). The long-term cost-effectiveness evaluation has been conducted by using The Sheffield Type 1 Diabetes Policy Model, which is a patient-level simulation model on T1DM. It includes long-term microvascular (retinopathy, neuropathy, and nephropathy) and macrovascular (myocardial infarction, stroke, revascularization, and angina) diabetes-related complications and acute adverse events (severe hypoglycemia and DKA). The most favorable within-trial scenario for the KICk-OFF arm led to an incremental cost-effectiveness ratio (ICER) of £23,688 (base year 2009) with a cost-effectiveness probability of 41.3 percent. Simulating the long-term complications using the full cohort data, the mean ICER for the base case was £28,813 (base year 2011) and the probability of the KICk-OFF intervention being cost-effective at £20,000/QALY threshold was 42.6 percent, with considerable variation due to treatment effect duration. For the high HbA1c sub-group, the KICk-OFF arm was "dominant" (meaning it provided better health gains at lower costs than usual care) over the usual care arm in each scenario considered. For the whole study population, the cost-effectiveness of KICk-OFF depends on the assumption for treatment effect duration. For the high baseline HbA1c sub-group, KICk-OFF arm was estimated to be dominant over the usual care arm regardless of the assumption on the treatment effect duration.

Comparison between traditional and goal directed perfusion in cardiopulmonary by-pass. Adaptation of a differential cost analysis

BACKGROUND: A previous patient-level discrete event simulation (DES) model was developed to perform an economic evaluation of GDP strategy with respect to TP in US. Aim of this supplement is provide results of the adaptations of the differential cost analysis to Belgium, Canada, France, Germany, Italy, and UK. METHODS: A Discrete Event Simulation model was developed to compare TP and GDP strategy in patients undergoing CPB. National perspective was adopted to calculate costs associated to each event while GDP strategy was exploited the introduction of Sorin Heartlink (HL) Card/GDP Card and Sorin Connect (electronic data management system). RESULTS: GDP reduces the total cost with respect to traditional perfusion; furthermore the cost of GDP strategy (Sorin GDPTM Monitor and Sorin ConnectTM) is completely offset by the saving in hospital stay. CONCLUSION: GDP seems to improve significantly the main outcomes related to CPB surgery, when compared to TP techniques. Additional costs due to perform GDP strategy have no impact on the total cost since completely offset by the savings in hospital cost.

Incorporating Psychological Predictors of Treatment Response into Health Economic Simulation Models: A Case Study in Type 1 Diabetes.

. Health economic modeling has paid limited attention to the effects that patients' psychological characteristics have on the effectiveness of treatments. This case study tests 1) the feasibility of incorporating psychological prediction models of treatment response within an economic model of type 1 diabetes, 2) the potential value of providing treatment to a subgroup of patients, and 3) the cost-effectiveness of providing treatment to a subgroup of responders defined using 5 different algorithms. . Multiple linear regressions were used to investigate relationships between patients' psychological characteristics and treatment effectiveness. Two psychological prediction models were integrated with a patient-level simulation model of type 1 diabetes. Expected value of individualized care analysis was undertaken. Five different algorithms were used to provide treatment to a subgroup of predicted responders. A cost-effectiveness analysis compared using the algorithms to providing treatment to all patients. . The psychological prediction models had low predictive power for treatment effectiveness. Expected value of individualized care results suggested that targeting education at responders could be of value. The cost-effectiveness analysis suggested, for all 5 algorithms, that providing structured education to a subgroup of predicted responders would not be cost-effective. . The psychological prediction models tested did not have sufficient predictive power to make targeting treatment cost-effective. The psychological prediction models are simple linear models of psychological behavior. Collection of data on additional covariates could potentially increase statistical power. . By collecting data on psychological variables before an intervention, we can construct predictive models of treatment response to interventions. These predictive models can be incorporated into health economic models to investigate more complex service delivery and reimbursement strategies.

The quality of economic evaluations of ultra-orphan drugs in Europe - a systematic review.

An orphan disease is defined in the EU as a disorder affecting less than 1 in 2 000 individuals. The concept of ultra-orphan has been proposed for diseases with a prevalence of less than 1:50 000. Drugs for ultra-orphan diseases are amongst the most expensive medicines on a cost-per-patient basis. The extremely high prices have prompted initiatives to evaluate cost-effectiveness and cost-utility in EU-member states. The objective of this review was to evaluate the quality of cost-effectiveness and cost-utility studies on ultra-orphan drugs. We searched 2 databases and the reference lists of relevant systematic reviews. Studies reporting on full economic evaluations, or at least aiming at such evaluation, were eligible for inclusion. Quality was assessed with the use of the Consensus on Health Economic Criteria (CHEC)-list. Two-hundred-fifty-one studies were identified. Of these, 16 fitted our inclusion criteria. A study on enzyme replacement and substrate reduction therapies for lysosomal storage disorders did not perform a full economic evaluation due to the high drug costs and the lack of a measurable effect on either clinical or health-related quality of life outcomes. Likewise, a cost-effectiveness analysis of laronidase for mucopolysaccharidosis type 1 was considered unfeasible due to lack of clinical effectiveness data, while in the same study a crude model was used to estimate cost-utility of enzyme replacement therapy (ERT) for Fabry disease. Three additional studies, one on ERT for Fabry disease, one on ERT for Gaucher disease and one on eculizumab for paroxysmal nocturnal haemoglobinuria, used an approach that was too simplistic to lead to a realistic estimate of the incremental cost-effectiveness (ICER) or cost-utility ratio (ICUR). In all other studies (N = 11) more sophisticated pharmacoeconomic models were used to estimate cost-effectiveness and cost-utility of the specific drug, mostly ERT or drugs indicated for pulmonary arterial hypertension (PAH). Seven studies used a Markov-state-transition model. Other models used were patient-level simulation models (N = 3) and decision trees (N = 1). Only 4 studies adopted a societal perspective. All but 2 studies discounted costs and effects appropriately. Drugs for metabolic diseases appeared to be significantly less cost-effective than drugs indicated for PAH, with ICERs ranging from €43 532 (Gaucher disease) to €3 282 252 (Fabry disease). Quality of studies using a Markov-state-transition or patient-level simulation model is in general good with 14–19 points on the CHEC-list. We therefore conclude that economic evaluations of ultra-orphan drugs are feasible if pharmacoeconomic modelling is used. Considering the need for modelling of several disease states and the small patient groups, a Markov-state-transition model seems to be most suitable type of model. However, it should be realised that ultra-orphan drugs will usually not meet the conventional criteria for cost-effectiveness. Nevertheless, ultra-orphan drugs are often reimbursed. Further discussion on the use of economic evaluations and their consequences in case of ultra-orphan drugs is therefore warranted.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-015-0305-y) contains supplementary material, which is available to authorized users.