Slowing the progression of Alzheimer disease: methodologic issues.
The evidence to support a claim that a new drug will slow the progression of Alzheimer disease (AD) must derive from epistemologically valid research methods. Although agency regulations do not specify the magnitude of an effect that a drug must possess to be granted a claim as a treatment for AD, the evidence to support any claim must be adduced in adequate and well-controlled clinical investigations and must meet the standard of "substantial evidence." Because a claim presented in drug product labeling may not be false or misleading in any particular, a distinction must be made between treatments that provide a "symptomatic" benefit and those that alter the course of dementia. Examples of some of the difficulties likely to be encountered by sponsors seeking to develop evidence to support a claim that a new drug slows the progression of dementia are presented. A suggestion is made for a clinical trial design, designated as the "randomized start design," that may be useful in such a question. Why this design might overcome many of the difficulties, both practical and ethical, present in the "discontinuation" design, the design ordinarily proposed to assess a drug's effect on disease progression, is discussed.
Leber
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Division of Neuropharmacological Drug Products, Food and Drug Administration, Rockville, Maryland, USA.
D000544:Alzheimer Disease / Q000188:drug therapy*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D017277:Drug Approval / Q000331:legislation & jurisprudence / Q000379:methods; D004341:Drug Evaluation / Q000379:methods; D006801:Humans; D018697:Nootropic Agents / Q000592:standards*; D017063:Outcome Assessment, Health Care / Q000379:methods; D016032:Randomized Controlled Trials as Topic / Q000379:methods* / Q000592:standards; D012107:Research Design / Q000592:standards; D013997:Time Factors; D014481:United States
D018697:Nootropic Agents