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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

Two-way sensitivity analysis: Magnitude vs. Probability of Harm.The net societal benefit in QALYs/1,000 patients screened is indicated by the colors/shades in the two-dimensional panel as the probability of harm per year is increased across the x-axis and the magnitude of harm (in QALYs/event) along the y-axis.
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pone-0114339-g005: Two-way sensitivity analysis: Magnitude vs. Probability of Harm.The net societal benefit in QALYs/1,000 patients screened is indicated by the colors/shades in the two-dimensional panel as the probability of harm per year is increased across the x-axis and the magnitude of harm (in QALYs/event) along the y-axis.

Mentions: Given that the base-case scenario represents a highly favorable scenario (good efficacy and low treatment-related harm), we explored the interaction of these two factors in a two-way sensitivity analysis. We found that even when harm was relatively probable (4%/year), aggregate net population benefit persisted when treatment-related harm was moderate (0.3 QALYs lost per adverse event). Similarly, net benefit persisted for relatively uncommon (1%/year) but very severe adverse events (2 QALYs lost per adverse event) in the context of highly effective therapies. (Figure 5).


Modeling test and treatment strategies for presymptomatic Alzheimer disease.

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

Two-way sensitivity analysis: Magnitude vs. Probability of Harm.The net societal benefit in QALYs/1,000 patients screened is indicated by the colors/shades in the two-dimensional panel as the probability of harm per year is increased across the x-axis and the magnitude of harm (in QALYs/event) along the y-axis.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0114339-g005: Two-way sensitivity analysis: Magnitude vs. Probability of Harm.The net societal benefit in QALYs/1,000 patients screened is indicated by the colors/shades in the two-dimensional panel as the probability of harm per year is increased across the x-axis and the magnitude of harm (in QALYs/event) along the y-axis.
Mentions: Given that the base-case scenario represents a highly favorable scenario (good efficacy and low treatment-related harm), we explored the interaction of these two factors in a two-way sensitivity analysis. We found that even when harm was relatively probable (4%/year), aggregate net population benefit persisted when treatment-related harm was moderate (0.3 QALYs lost per adverse event). Similarly, net benefit persisted for relatively uncommon (1%/year) but very severe adverse events (2 QALYs lost per adverse event) in the context of highly effective therapies. (Figure 5).

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