{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T21:17:20Z","timestamp":1761513440338,"version":"build-2065373602"},"reference-count":13,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,3,1]],"date-time":"2014-03-01T00:00:00Z","timestamp":1393632000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>The February 2013 Food and Drug Administration (FDA) draft guidance for developing drugs for early\u2010stage Alzheimer's disease (AD) creates certain challenges as they guide toward the use of one cognitive outcome to gain accelerated marketing approval for preclinical AD drugs, and a composite clinical scale \u2013 the Clinical Dementia Rating Scale in particular \u2013 for the primary outcome for prodromal AD clinical trials.<\/jats:p><jats:p>In light of the developing knowledge regarding early stage diagnoses and clinical trials outcomes, we recommend that FDA describe its requirements for validating preclinical AD diagnoses for drug development purposes, maintain the principle for requiring coprimary outcomes, and encourage the advancement of outcomes for early stage AD trials. The principles for drug development for early stage AD should not differ from those for clinical AD, especially as the diagnoses of prodromal and early AD impinge on each other. The FDA should not recommend that a composite scale be used as a sole primary efficacy outcome to support a marketing claim unless it requires that the cognitive and functional components of such a scale are demonstrated to be individually meaningful. The current draft guidelines may inadvertently constrain efforts to better assess the clinical effects of new drugs and inhibit innovation in an area where evidence\u2010based clinical research practices are still evolving.<\/jats:p><\/jats:sec>","DOI":"10.1016\/j.jalz.2013.12.002","type":"journal-article","created":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T02:50:29Z","timestamp":1396320629000},"page":"247-250","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Rethinking the Food and Drug Administration's 2013 guidance on developing drugs for early\u2010stage Alzheimer's disease"],"prefix":"10.1002","volume":"10","author":[{"given":"Lon S.","family":"Schneider","sequence":"first","affiliation":[{"name":"Keck School of Medicine University of Southern California Los Angeles CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,3]]},"reference":[{"key":"e_1_2_6_2_2","unstructured":"U.S. Food and Drug Administration.Guidance for industry Alzheimer's disease: developing drugs for the treatment of early stage disease (FDA\u20102013\u2010D\u20100077) DRAFT.February 2013 [accessed 2013 June 30]. 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