Alzheimer's disease Archimedes condition‐event simulator: Development and validation

Kansal, Anuraag R.; Tafazzoli, Ali; Ishak, K. Jack; Krotneva, S.

doi:10.1016/j.trci.2018.01.001

Cited by 23 publications

(34 citation statements)

References 29 publications

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“…AD Alzheimer's disease, IPECAD International Pharmaco-Economic Collaboration on Alzheimer's Disease, LY life-year, MCI mild cognitive impairment, SveDem Swedish Dementia registry. Sources: Kansal et al [54]; Green et al [51]; Vermunt et al [53]; Wimo et al [30]; IPECAD Modeling Group [52] economic, and societal value of aducanumab for the treatment of patients with early AD.…”

Section: Discussionmentioning

confidence: 99%

“…The published models included in the comparison were selected to reflect the diversity of modeling approaches and data sources used to model the AD continuum. In particular, the selected models included a Markov model with a structure similar to that of the current model using Swedish Dementia (SveDem) registry data [ 30 ], an open-source Markov model (v.1.1) from the International Pharmaco-Economic Collaboration on Alzheimer’s Disease (IPECAD) with multi-dimensional symptom health states for dementia using NACC data [ 51 , 52 ], a multi-state statistical model using combined data from six longitudinal cohort studies [ 53 ], and the Alzheimer’s Disease–Archimedes Condition Event (AD-ACE) simulation model with continuous biomarker and symptom trajectories using data from the Alzheimer’s Disease Neuroimaging Initiative and the Assessment of Health Economics in Alzheimer’s Disease project [ 54 ]. The model comparisons were adjusted to account for baseline age.…”

Section: Methodsmentioning

confidence: 99%

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Predicted Lifetime Health Outcomes for Aducanumab in Patients with Early Alzheimer’s Disease

et al. 2021

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Introduction: Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disease that places a substantial burden on patients and caregivers. Aducanumab is the first AD therapy approved by the US Food and Drug Administration to reduce a defining pathophysiological feature of the disease, brain amyloid plaques. In the phase 3 clinical trial EMERGE (NCT02484547), aducanumab reduced clinical decline in patients with mild cognitive impairment (MCI) due to AD and mild AD dementia and confirmed amyloid pathology. Methods: We used a Markov modeling approach to predict the long-term clinical benefits of aducanumab for patients with early AD based on EMERGE efficacy data. In the model, patients could transition between AD severity levels (MCI due to AD; mild, moderate, and severe AD dementia) and care settings (community vs. institution) or transition to death. The intervention was aducanumab added to standard of care (SOC), and the comparator was SOC alone. Data sources for base-case and scenario analyses included EMERGE, published National Alzheimer's Coordinating Center analyses, and other published literature. Results: Per patient over a lifetime horizon, aducanumab treatment corresponded to 0.65 incremental patient quality-adjusted life-years (QALYs) and 0.09 fewer caregiver QALYs lost compared with patients treated with SOC. Aducanumab treatment translated to a lower lifetime probability of transitioning to AD dementia, a lower lifetime probability of transitioning to institutionalization (25.2% vs. 29.4%), delays in the median time to transition to AD dementia (7.50 vs. 4.92 years from MCI to moderate AD dementia or worse), and an incremental median time in the community of 1.32 years compared with SOC.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Predicted Lifetime Health Outcomes for Aducanumab in Patients with Early Alzheimer’s Disease

et al. 2021

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“…We selected the AD Archimedes Condition Event (ACE) simulator version 3.2 (Evidera), a Microsoft Excel–based patient-level microsimulation model that has been validated against a well-known AD data set (the Uniform Data Set [UDS] from the US National Alzheimer Coordinating Center [NACC-UDS]) and a recent clinical trial of an amyloid-targeted treatment in patients with MCI or mild dementia due to AD (A Study to Evaluate Safety, Tolerability, and Efficacy of Lecanemab in Subjects With Early Alzheimer's Disease [ NCT01767311 ]). 8 , 9 This model allows us to estimate the natural history of individuals from MCI to severe dementia due to AD and the potential effects of disease-modifying treatments on disease progression. It describes disease progression through changes in the underlying biomarkers associated with AD, including measures of amyloid and tau levels, and their connections to the clinical presentation of AD, including various patient-level scales of cognition, behavior, function, and dependence.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of the Cost-effectiveness of Drug Treatment for Alzheimer Disease in a Simulation Model That Includes Caregiver and Societal Factors

et al. 2021

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IMPORTANCEThe possibility of widespread use of a novel effective therapy for Alzheimer disease (AD) will present important clinical, policy, and financial challenges. OBJECTIVE To describe how including different patient, caregiver, and societal treatment-related factors affects estimates of the cost-effectiveness of a hypothetical disease-modifying AD treatment. DESIGN, SETTING, AND PARTICIPANTS In this economic evaluation, the Alzheimer Disease Archimedes Condition Event Simulator was used to simulate the prognosis of a hypothetical cohort of patients selected from the Alzheimer Disease Neuroimaging Initiative database who received the diagnosis of mild cognitive impairment (MCI). Scenario analyses that varied costs and quality of life inputs relevant to patients and caregivers were conducted. The analysis was designed and conducted from June 15, 2019, to September 30, 2020. EXPOSURES A hypothetical drug that would delay progression to dementia in individuals with MCI compared with usual care. MAIN OUTCOMES AND MEASURES Incremental cost-effectiveness ratio (ICER), measured by cost per quality-adjusted life-year (QALY) gained. RESULTSThe model included a simulated cohort of patients who scored between 24 and 30 on the Mini-Mental State Examination and had a global Clinical Dementia Rating scale of 0.5, with a required memory box score of 0.5 or higher, at baseline. Using a health care sector perspective, which included only individual patient health care costs, the ICER for the hypothetical treatment was $192 000 per QALY gained. The result decreased to $183 000 per QALY gained in a traditional societal perspective analysis with the inclusion of patient non-health care costs. The inclusion of estimated caregiver health care costs produced almost no change in the ICER, but the inclusion of QALYs gained by caregivers led to a substantial reduction in the ICER for the hypothetical treatment, to $107 000 per QALY gained in the health sector perspective. In the societal perspective scenario, with the broadest inclusion of patient and caregiver factors, the ICER decreased to $74 000 per added QALY. CONCLUSIONS AND RELEVANCEThe findings of this economic evaluation suggest that policy makers should be aware that efforts to estimate and include the effects of AD treatments outside those on patients themselves can affect the results of the cost-effectiveness analyses that often underpin assessments of the value of new treatments. Further research and debate on including these factors in assessments that will inform discussions on fair pricing for new treatments are needed.

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“…These include the use of multiple domains to improve a classical Markov structure 31 and the extension of an individual-level simulation to consider prodromal AD. 32 A decade passed before this study could perform the DES for AD. In turn, LMICs should pay more attention to learn and adopt these modeling advancements so that a decision that requires finer methodology can be made with a higher level of accuracy.…”

Section: Discussionmentioning

confidence: 99%

Application of Discrete-Event Simulation in Health Technology Assessment: A Cost-Effectiveness Analysis of Alzheimer’s Disease Treatment Using Real-World Evidence in Thailand

Kongpakwattana

Chaiyakunapruk

2020

Value in Health

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Objectives: Decision-analytic models for Alzheimer's disease (AD) have been advanced to a discrete-event simulation (DES), in which individual-level modeling of disease progression across continuous severity spectra become feasible. This study aimed to apply DES to perform cost-effectiveness analysis of AD treatment in Thailand.Methods: A data set of Thai AD patients, representing unique demographic and clinical characteristics, was bootstrapped to generate a baseline cohort of 50 000 patients. Each patient was cloned and assigned to donepezil, galantamine, rivastigmine, memantine, or no treatment. Correlated changes in cognitive and behavioral status over time were developed using patientlevel data. Treatment effects were obtained from the most recent network meta-analysis. Treatment persistence; mortality; and predictive equations for functional status, costs (Thai baht in 2017), and quality-adjusted life-year (QALY) were derived from country-specific real-world data.Results: From a societal perspective, only the prescription of donepezil to AD patients with all disease-severity levels was found to be cost-effective (incremental cost-effectiveness ratio): 138 524 Thai baht/QALY ($4062/QALY)]. Regardless of whether the treatment-stopping rule when the mini-mental state examination score ,10 was introduced, providing early treatment with donepezil to mild AD patients further reduced the incremental cost-effectiveness ratio. Extensive sensitivity analyses indicated robust simulation findings.Conclusions: Discrete-event simulation greatly enhances the real-world representativeness of decision-analytic models for AD. Donepezil is the most cost-effective treatment option for AD in Thailand and is worth being considered for universal financial coverage. Application of DES in heath technology assessment should be encouraged, especially when the validity of the model is questionable with classical modeling methods.

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Alzheimer's disease Archimedes condition‐event simulator: Development and validation

Cited by 23 publications

References 29 publications

Predicted Lifetime Health Outcomes for Aducanumab in Patients with Early Alzheimer’s Disease

Predicted Lifetime Health Outcomes for Aducanumab in Patients with Early Alzheimer’s Disease

Evaluation of the Cost-effectiveness of Drug Treatment for Alzheimer Disease in a Simulation Model That Includes Caregiver and Societal Factors

Application of Discrete-Event Simulation in Health Technology Assessment: A Cost-Effectiveness Analysis of Alzheimer’s Disease Treatment Using Real-World Evidence in Thailand

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