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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

Multi-way sensitivity analysis: Relationship of Treatment Effect and Average Harm.Each box plot represents the distribution of total harm (probability of harm times the magnitude of harm  =  totally QALYs/year lost to harm in treated patients) across quintiles of treatment benefit, represented with the average relative risk reduction in that quintile. The least beneficial simulations are displayed at the top (RRR = 0.07) and the most beneficial trials at the bottom (RRR = 0.82). The red line represents the approximate net harm of aspirin per year (probability of harm = 0.001, magnitude of harm = 0.06 QALYs) and the blue line represents a theoretical medication with a more harm profile (probability of harm = 0.001, magnitude of harm = 10 QALYs or probability of harm = 0.01, magnitude of harm = 1 QALY).
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pone-0114339-g007: Multi-way sensitivity analysis: Relationship of Treatment Effect and Average Harm.Each box plot represents the distribution of total harm (probability of harm times the magnitude of harm  =  totally QALYs/year lost to harm in treated patients) across quintiles of treatment benefit, represented with the average relative risk reduction in that quintile. The least beneficial simulations are displayed at the top (RRR = 0.07) and the most beneficial trials at the bottom (RRR = 0.82). The red line represents the approximate net harm of aspirin per year (probability of harm = 0.001, magnitude of harm = 0.06 QALYs) and the blue line represents a theoretical medication with a more harm profile (probability of harm = 0.001, magnitude of harm = 10 QALYs or probability of harm = 0.01, magnitude of harm = 1 QALY).

Mentions: To inform potential drug development, the relationship between quintiles of total treatment benefit and total harm (probability of harm multiplied by the magnitude of harm) is outlined in Figure 7. As treatment benefit increases, more harmful treatments are potentially consistent with net societal benefit. For medications with a risk as low as aspirin (illustrated by the red line in the figure) a significant number of net beneficial simulations existed even in the least beneficial quintile of total treatment benefit (range of mean relative risk reduction 0.01– mean relative risk reduction 0.14).


Modeling test and treatment strategies for presymptomatic Alzheimer disease.

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

Multi-way sensitivity analysis: Relationship of Treatment Effect and Average Harm.Each box plot represents the distribution of total harm (probability of harm times the magnitude of harm  =  totally QALYs/year lost to harm in treated patients) across quintiles of treatment benefit, represented with the average relative risk reduction in that quintile. The least beneficial simulations are displayed at the top (RRR = 0.07) and the most beneficial trials at the bottom (RRR = 0.82). The red line represents the approximate net harm of aspirin per year (probability of harm = 0.001, magnitude of harm = 0.06 QALYs) and the blue line represents a theoretical medication with a more harm profile (probability of harm = 0.001, magnitude of harm = 10 QALYs or probability of harm = 0.01, magnitude of harm = 1 QALY).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0114339-g007: Multi-way sensitivity analysis: Relationship of Treatment Effect and Average Harm.Each box plot represents the distribution of total harm (probability of harm times the magnitude of harm  =  totally QALYs/year lost to harm in treated patients) across quintiles of treatment benefit, represented with the average relative risk reduction in that quintile. The least beneficial simulations are displayed at the top (RRR = 0.07) and the most beneficial trials at the bottom (RRR = 0.82). The red line represents the approximate net harm of aspirin per year (probability of harm = 0.001, magnitude of harm = 0.06 QALYs) and the blue line represents a theoretical medication with a more harm profile (probability of harm = 0.001, magnitude of harm = 10 QALYs or probability of harm = 0.01, magnitude of harm = 1 QALY).
Mentions: To inform potential drug development, the relationship between quintiles of total treatment benefit and total harm (probability of harm multiplied by the magnitude of harm) is outlined in Figure 7. As treatment benefit increases, more harmful treatments are potentially consistent with net societal benefit. For medications with a risk as low as aspirin (illustrated by the red line in the figure) a significant number of net beneficial simulations existed even in the least beneficial quintile of total treatment benefit (range of mean relative risk reduction 0.01– mean relative risk reduction 0.14).

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