Validity, significance, strengths, limitations, and evidentiary value of real-world clinical data for combination therapy in Alzheimer's disease: comparison of efficacy and effectiveness studies.

Neuro-degenerative Diseases
Alireza AtriRachelle Smith Doody

Abstract

Randomized controlled efficacy trials (RCTs), the scientific gold standard, are required for regulatory approval of Alzheimer's disease (AD) interventions, yet provide limited information regarding real-world therapeutic effectiveness. To compare the nature of evidence regarding the combination of approved AD treatments from RCTs versus long-term observational controlled studies (LTOCs). Comparisons of strengths, limitations, and evidence level for monotherapy [cholinesterase inhibitor (ChEI) or memantine] and combination therapy (ChEI + memantine) in RCTs versus LTOCs. RCTs examined highly selected populations over months. LTOCs collected data across multiple AD stages in large populations over many years. RCTs and LTOCs show similar patterns favoring combination over monotherapy over placebo/no treatment. Long-term combination therapy compared to monotherapy reduced cognitive and functional decline and delayed time to nursing home admission. Persistent treatment was associated with slower decline. While LTOCs used control groups, adjusted for multiple covariates, had higher external validity, and favorable ethical, practical and cost considerations, their limitations included potential selection bias due to lack of placebo co...Continue Reading

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Citations

Oct 9, 2012·Journal of the International Neuropsychological Society : JINS·Meghan B MitchellAlireza Atri
Oct 31, 2015·Neurodegenerative Disease Management·Radoslaw Magierski, Tomasz Sobow
Oct 11, 2013·Dementia and Geriatric Cognitive Disorders·David WilkinsonClaus Goebel
Jan 24, 2014·Brain Pathology·Diego IaconoMargaret Gatz
Oct 28, 2019·Alzheimer's & Dementia : Translational Research & Clinical Interventions·Marwan N SabbaghJohn E Harrison
Aug 11, 2018·Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring·Lindsay WallaceMelissa K Andrew
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Jun 3, 2015·Drugs & Aging·William James DeardorffGeorge T Grossberg
Feb 2, 2019·The Medical Clinics of North America·Alireza Atri

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