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Table of Contents
Vol. 10, No. 1-4, 2012
Issue release date: April 2012
Section title: Paper
Free Access
Neurodegenerative Dis 2012;10:170–174

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

Atri A.a–c · Rountree S.D.d · Lopez O.L.e · Doody R.S.d
aDepartment of Neurology, Massachusetts General Hospital, Boston, Mass., bGeriatric Research, Education and Clinical Center, ENRM VA Medical Center, Bedford, Mass., cHarvard Medical School, Boston, Mass., dAlzheimer’s Disease and Memory Disorders Center, Department of Neurology, Baylor College of Medicine, Houston, Tex., and eDepartment of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pa., USA
email Corresponding Author

Alireza Atri, MD, PhD

MGH Memory Disorders Unit

15 Parkman St.

WACC 715, Boston, MA 02114 (USA)

Tel. +1 617 726 1728, E-Mail atri@nmr.mgh.harvard.edu

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Background: 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. Objective: To compare the nature of evidence regarding the combination of approved AD treatments from RCTs versus long-term observational controlled studies (LTOCs). Methods: Comparisons of strengths, limitations, and evidence level for monotherapy [cholinesterase inhibitor (ChEI) or memantine] and combination therapy (ChEI + memantine) in RCTs versus LTOCs. Results: 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 comparisons and randomization. Conclusions: Naturalistic LTOCs provide complementary long-term level II evidence to complement level I evidence from short-term RCTs regarding therapeutic effectiveness in AD that may otherwise be unobtainable. A coordinated strategy/consortium to pool LTOC data from multiple centers to estimate long-term comparative effectiveness, risks/benefits, and costs of AD treatments is needed.

© 2012 S. Karger AG, Basel

Article / Publication Details

First-Page Preview
Abstract of Paper

Received: September 29, 2011
Accepted: November 15, 2011
Published online: February 10, 2012
Issue release date: April 2012

Number of Print Pages: 5
Number of Figures: 1
Number of Tables: 0

ISSN: 1660-2854 (Print)
eISSN: 1660-2862 (Online)

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