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Vol. 10, No. 6, 1999
Issue release date: November–December 1999
Section title: Original Research Article
Dement Geriatr Cogn Disord 1999;10:534–540
(DOI:10.1159/000017201)

Key Methodological Features of Randomized Controlled Trials of Alzheimer’s Disease Therapy

Minimal Clinically Important Difference, Sample Size and Trial Duration

Burback D. · Molnar F.J. · St. John P. · Man-Son-Hing M.
aGeriatric Assessment Unit, Ottawa Hospital, Civic Campus, bSisters of Charity of Ottawa Health Services, Ottawa, Ontario, cSection of Geriatric Medicine, Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada

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Article / Publication Details

First-Page Preview
Abstract of Original Research Article

Published online: 11/4/1999

Number of Print Pages: 7
Number of Figures: 1
Number of Tables: 4

ISSN: 1420-8008 (Print)
eISSN: 1421-9824 (Online)

For additional information: http://www.karger.com/DEM

Abstract

Background: The results of clinical trials are routinely presented in terms of statistical significance, which may or may not indicate clinical significance. Analysis of the minimal clinically important difference (MCID) of cognitive scales has received little attention to date. Objectives: By reviewing the key methodological features (sample size, duration, statistical and clinical significance) of clinical trials examining the efficacy of tacrine in the treatment of Alzheimer’s disease (AD), we assessed their ability to detect clinically important changes in cognition. Design: The value for the MCID of the Mini-Mental State Examination (MMSE) was determined by surveying specialists in neurology and geriatric medicine. This value was then used to interpret the clinical significance of the results of published randomized controlled trials (RCTs) assessing the efficacy of tacrine in the treatment of AD and to retrospectively determine their optimal sample size and trial duration. Results: The mean survey MCID for the MMSE was 3.72 (95% confidence interval 3.50–3.95) points. Only 2 of 12 tacrine RCTs using the MMSE found a statistically significant difference in MMSE scores for patients taking tacrine compared with those taking placebo. These improvements were not clinically significant when compared with the survey MMSE MCID. For parallel trials of tacrine in AD, the smallest sample size and minimum trial duration required to demonstrate a clinically significant difference were calculated to be 53 subjects and 1 year, respectively. Five of the 7 parallel trials met the required sample size; however, none of them met the criteria for trial duration. Conclusions: When using the MMSE as an outcome measure, no tacrine trial reported results that were clinically significant as perceived by clinicians working with dementia patients. Application of a range of plausible MCIDs to the parallel design RCTs also demonstrated that 2 of 7 of these trials did not have sufficient sample size, and none had sufficient duration of treatment to reliably detect clinically meaningful changes in cognition. Future clinical trials in this area will need to incorporate the evolving knowledge of MCIDs in order to increase their chance of detecting clinically relevant results.


Article / Publication Details

First-Page Preview
Abstract of Original Research Article

Published online: 11/4/1999

Number of Print Pages: 7
Number of Figures: 1
Number of Tables: 4

ISSN: 1420-8008 (Print)
eISSN: 1421-9824 (Online)

For additional information: http://www.karger.com/DEM


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

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