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Modeling test and treatment strategies for presymptomatic Alzheimer disease.

Burke JF, Langa KM, Hayward RA, Albin RL - PLoS ONE (2014)

Bottom Line: Net population benefit was estimated in aggregated QALYs.In the base-case scenario, treatment effects were uniformly positive, and net benefits increased with increasing age at screening.Highly efficacious presymptomatic screen and treat strategies for AD are likely to produce substantial aggregate population benefits that are likely greater than the benefits of aspirin in primary prevention of moderate risk cardiovascular disease (28 QALYS per 1000 patients treated), even in the context of an imperfect treatment delivery environment.

View Article: PubMed Central - PubMed

Affiliation: Dept. of Neurology, University of Michigan, Ann Arbor, Michigan, United States of America; Robert Wood Johnson Clinical Scholars Program, University of Michigan, Ann Arbor, Michigan, United States of America; Center for Clinical Management Research, VAAAHS, Ann Arbor, Michigan, United States of America.

ABSTRACT

Objectives: In this study, we developed a model of presymptomatic treatment of Alzheimer disease (AD) after a screening diagnostic evaluation and explored the circumstances required for an AD prevention treatment to produce aggregate net population benefit.

Methods: Monte Carlo simulation methods were used to estimate outcomes in a simulated population derived from data on AD incidence and mortality. A wide variety of treatment parameters were explored. Net population benefit was estimated in aggregated QALYs. Sensitivity analyses were performed by individually varying the primary parameters.

Findings: In the base-case scenario, treatment effects were uniformly positive, and net benefits increased with increasing age at screening. A highly efficacious treatment (i.e. relative risk 0.6) modeled in the base-case is estimated to save 20 QALYs per 1000 patients screened and 221 QALYs per 1000 patients treated.

Conclusions: Highly efficacious presymptomatic screen and treat strategies for AD are likely to produce substantial aggregate population benefits that are likely greater than the benefits of aspirin in primary prevention of moderate risk cardiovascular disease (28 QALYS per 1000 patients treated), even in the context of an imperfect treatment delivery environment.

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Related in: MedlinePlus

Treatment Effect Validation.Each line represents the proportion of surviving population with AD (estimated prevalence) as the treatment effect size varies assuming all individuals are treated, individuals never discontinue treatment and there is no heterogeneity of treatment effect.
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pone-0114339-g003: Treatment Effect Validation.Each line represents the proportion of surviving population with AD (estimated prevalence) as the treatment effect size varies assuming all individuals are treated, individuals never discontinue treatment and there is no heterogeneity of treatment effect.

Mentions: Figure 2A demonstrates age-related and gender-specific mortality in our base-case scenario without screening or treatment. In addition, Figure 2B demonstrates the estimated incidence of AD by age compared to the Brookmeyer et al equation. [19]Figure 3 displays estimated prevalence of AD by age for a series of simple intervention scenarios (no heterogeneity of treatment effect, no treatment related harm, no treatment discontinuation) where only the relative risk ceiling, and thus the effective relative risk reduction, was specified. A RRR of 0.5 has a marked effect on AD prevalence.


Modeling test and treatment strategies for presymptomatic Alzheimer disease.

Burke JF, Langa KM, Hayward RA, Albin RL - PLoS ONE (2014)

Treatment Effect Validation.Each line represents the proportion of surviving population with AD (estimated prevalence) as the treatment effect size varies assuming all individuals are treated, individuals never discontinue treatment and there is no heterogeneity of treatment effect.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4256252&req=5

pone-0114339-g003: Treatment Effect Validation.Each line represents the proportion of surviving population with AD (estimated prevalence) as the treatment effect size varies assuming all individuals are treated, individuals never discontinue treatment and there is no heterogeneity of treatment effect.
Mentions: Figure 2A demonstrates age-related and gender-specific mortality in our base-case scenario without screening or treatment. In addition, Figure 2B demonstrates the estimated incidence of AD by age compared to the Brookmeyer et al equation. [19]Figure 3 displays estimated prevalence of AD by age for a series of simple intervention scenarios (no heterogeneity of treatment effect, no treatment related harm, no treatment discontinuation) where only the relative risk ceiling, and thus the effective relative risk reduction, was specified. A RRR of 0.5 has a marked effect on AD prevalence.

Bottom Line: Net population benefit was estimated in aggregated QALYs.In the base-case scenario, treatment effects were uniformly positive, and net benefits increased with increasing age at screening.Highly efficacious presymptomatic screen and treat strategies for AD are likely to produce substantial aggregate population benefits that are likely greater than the benefits of aspirin in primary prevention of moderate risk cardiovascular disease (28 QALYS per 1000 patients treated), even in the context of an imperfect treatment delivery environment.

View Article: PubMed Central - PubMed

Affiliation: Dept. of Neurology, University of Michigan, Ann Arbor, Michigan, United States of America; Robert Wood Johnson Clinical Scholars Program, University of Michigan, Ann Arbor, Michigan, United States of America; Center for Clinical Management Research, VAAAHS, Ann Arbor, Michigan, United States of America.

ABSTRACT

Objectives: In this study, we developed a model of presymptomatic treatment of Alzheimer disease (AD) after a screening diagnostic evaluation and explored the circumstances required for an AD prevention treatment to produce aggregate net population benefit.

Methods: Monte Carlo simulation methods were used to estimate outcomes in a simulated population derived from data on AD incidence and mortality. A wide variety of treatment parameters were explored. Net population benefit was estimated in aggregated QALYs. Sensitivity analyses were performed by individually varying the primary parameters.

Findings: In the base-case scenario, treatment effects were uniformly positive, and net benefits increased with increasing age at screening. A highly efficacious treatment (i.e. relative risk 0.6) modeled in the base-case is estimated to save 20 QALYs per 1000 patients screened and 221 QALYs per 1000 patients treated.

Conclusions: Highly efficacious presymptomatic screen and treat strategies for AD are likely to produce substantial aggregate population benefits that are likely greater than the benefits of aspirin in primary prevention of moderate risk cardiovascular disease (28 QALYS per 1000 patients treated), even in the context of an imperfect treatment delivery environment.

Show MeSH
Related in: MedlinePlus