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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: Distribution of Intervention Parameters in Beneficial vs. Non-beneficial trials.Box plots of the distribution of intervention parameters across the range of parameters studied. X-axis for each individual plot represents the range of parameter values. Total harm represents the combination of the probability and magnitude of harm in average total QALYs/year lost to harm in treated patients. This parameter was truncated at a value of 0.2 (one QALY lost for every five patient-years) so that the distribution in beneficial trials could be more clearly seen.
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pone-0114339-g006: Multi-way sensitivity analysis: Distribution of Intervention Parameters in Beneficial vs. Non-beneficial trials.Box plots of the distribution of intervention parameters across the range of parameters studied. X-axis for each individual plot represents the range of parameter values. Total harm represents the combination of the probability and magnitude of harm in average total QALYs/year lost to harm in treated patients. This parameter was truncated at a value of 0.2 (one QALY lost for every five patient-years) so that the distribution in beneficial trials could be more clearly seen.

Mentions: Out of 10,000 simulations, 318 resulted in a net societal benefit. Parameter distributions in the trial simulations that resulted in net societal benefit are compared to those that did not in Figure 6. Across the speculative range of parameters included in this analysis, the total harm in QALYs per year (probability of harm * magnitude of harm) was the most important parameters as 75% of beneficial trials had a total harm of less than 0.007 QALYs per year and 95% had total harm less than 0.02 QALYs/year. Treatment effect was also an important parameter as the mean relative risk reduction in beneficial trials was 0.55 vs. 0.41 in non-beneficial trials. Discontinuation rates were lower in beneficial trials (mean rate 5.4% vs. 10.1%) and specificity was higher (mean spec 81% vs. 75%). Sensitivity was only modestly higher in beneficial vs. non-beneficial trials (76% vs. 75%). For mean relative risk reduction, discontinuation rates, sensitivity and specificity, simulations with net societal benefit existed across nearly the entire range of parameters explored.


Modeling test and treatment strategies for presymptomatic Alzheimer disease.

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

Multi-way sensitivity analysis: Distribution of Intervention Parameters in Beneficial vs. Non-beneficial trials.Box plots of the distribution of intervention parameters across the range of parameters studied. X-axis for each individual plot represents the range of parameter values. Total harm represents the combination of the probability and magnitude of harm in average total QALYs/year lost to harm in treated patients. This parameter was truncated at a value of 0.2 (one QALY lost for every five patient-years) so that the distribution in beneficial trials could be more clearly seen.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0114339-g006: Multi-way sensitivity analysis: Distribution of Intervention Parameters in Beneficial vs. Non-beneficial trials.Box plots of the distribution of intervention parameters across the range of parameters studied. X-axis for each individual plot represents the range of parameter values. Total harm represents the combination of the probability and magnitude of harm in average total QALYs/year lost to harm in treated patients. This parameter was truncated at a value of 0.2 (one QALY lost for every five patient-years) so that the distribution in beneficial trials could be more clearly seen.
Mentions: Out of 10,000 simulations, 318 resulted in a net societal benefit. Parameter distributions in the trial simulations that resulted in net societal benefit are compared to those that did not in Figure 6. Across the speculative range of parameters included in this analysis, the total harm in QALYs per year (probability of harm * magnitude of harm) was the most important parameters as 75% of beneficial trials had a total harm of less than 0.007 QALYs per year and 95% had total harm less than 0.02 QALYs/year. Treatment effect was also an important parameter as the mean relative risk reduction in beneficial trials was 0.55 vs. 0.41 in non-beneficial trials. Discontinuation rates were lower in beneficial trials (mean rate 5.4% vs. 10.1%) and specificity was higher (mean spec 81% vs. 75%). Sensitivity was only modestly higher in beneficial vs. non-beneficial trials (76% vs. 75%). For mean relative risk reduction, discontinuation rates, sensitivity and specificity, simulations with net societal benefit existed across nearly the entire range of parameters explored.

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