Interpreting the results of Parkinson's disease clinical trials: Time for a change
Identifieur interne : 000718 ( Main/Corpus ); précédent : 000717; suivant : 000719Interpreting the results of Parkinson's disease clinical trials: Time for a change
Auteurs : Nick H. G. Holford ; John G. NuttSource :
- Movement Disorders [ 0885-3185 ] ; 2011-03.
English descriptors
Abstract
Randomized clinical trials testing putative disease‐modifying agents in Parkinson's disease (PD) have yielded controversial results that have not influenced evidence‐based recommendations for the treatment of PD. We argue that the failure of these clinical trials may be linked to end point‐based statistical analyses that must make prior assumptions about the magnitude and the time course of wash‐in and wash‐out of drug effects. Many of these shortcomings may be avoided with quantitative modeling of the entire time course of the clinical trial and examining evidence for three concomitant processes, disease progression, symptomatic drug effects and disease modifying effects. The power of this approach is illustrated by modeling of DATATOP and ELLDOPA trial data. © 2010 Movement Disorder Society
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DOI: 10.1002/mds.23555
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We argue that the failure of these clinical trials may be linked to end point‐based statistical analyses that must make prior assumptions about the magnitude and the time course of wash‐in and wash‐out of drug effects. Many of these shortcomings may be avoided with quantitative modeling of the entire time course of the clinical trial and examining evidence for three concomitant processes, disease progression, symptomatic drug effects and disease modifying effects. The power of this approach is illustrated by modeling of DATATOP and ELLDOPA trial data. © 2010 Movement Disorder Society</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Nick H. G. Holford MBChB, FRACP</name><affiliations><json:string>University of Auckland, Auckland, New Zealand</json:string></affiliations></json:item><json:item><name>John G. 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G.</namePart><namePart type="family">Holford</namePart><namePart type="termsOfAddress">MBChB, FRACP</namePart><affiliation>University of Auckland, Auckland, New Zealand</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">John G.</namePart><namePart type="family">Nutt</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Oregon Health & Science University, Portland, Oregon, USA</affiliation><description>Correspondence: Oregon Health & Science University, Mail Code OP32, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, USA</description><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="editorial" displayLabel="editorial"></genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2011-03</dateIssued><dateCaptured encoding="w3cdtf">2010-04-05</dateCaptured><dateValid encoding="w3cdtf">2010-11-01</dateValid><copyrightDate encoding="w3cdtf">2011</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">2</extent><extent unit="tables">3</extent><extent unit="references">54</extent><extent unit="words">7438</extent></physicalDescription><abstract lang="en">Randomized clinical trials testing putative disease‐modifying agents in Parkinson's disease (PD) have yielded controversial results that have not influenced evidence‐based recommendations for the treatment of PD. We argue that the failure of these clinical trials may be linked to end point‐based statistical analyses that must make prior assumptions about the magnitude and the time course of wash‐in and wash‐out of drug effects. Many of these shortcomings may be avoided with quantitative modeling of the entire time course of the clinical trial and examining evidence for three concomitant processes, disease progression, symptomatic drug effects and disease modifying effects. The power of this approach is illustrated by modeling of DATATOP and ELLDOPA trial data. © 2010 Movement Disorder Society</abstract><note type="additional physical form">Author Roles and Disclosures</note><note type="content">*Relevant conflict of interest/financial disclosures: Nothing to report. Portions of this study were supported by the Michael J. Fox Foundation, VA Parkinson's Disease Research, Education and Clinical Center (PADREDD), and NIH NINDS RO1‐NS21062 (to J.G.N.). Full financial disclosures and author roles may be found in the online version of the article.</note><subject lang="en"><genre>Keywords</genre><topic>clinical trials</topic><topic>disease‐modifying therapies</topic><topic>modeling clinical trials</topic><topic>Parkinson's disease</topic></subject><relatedItem type="host"><titleInfo><title>Movement Disorders</title></titleInfo><titleInfo type="abbreviated"><title>Mov. 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