Recruiting to preclinical Alzheimer's disease clinical trials through registries.
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ABSTRACT:
SUBMITTER: Grill JD
PROVIDER: S-EPMC5399544 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:We examined the use of clinical trials registries in published systematic reviews and meta-analyses from clinical neurology. A review of publications between January 1, 2008 and December 31, 2014 from five neuroscience journals (Annals of Neurology, Brain, Lancet Neurology, Neurology, and The Neuroscientist) was performed to identify eligible systematic reviews. The systematic reviews comprising the final sample were independently appraised to determine if clinical trials registries had been included as part of the search process. Studies acknowledging the use of a trials registry were further examined to determine whether trial data had been incorporated into the analysis. The initial search yielded 194 studies, of which 78 systematic reviews met the selection criteria. Of those, five acknowledged the use of a specific clinical trials registry: four reviewed unpublished trial data and two incorporated unpublished trial data into their results. Based on our sample of systematic reviews, there was no increase in the use of trials registries in systematic review searches over time. Few systematic reviews published in clinical neurology journals included data from relevant clinical trials registries.
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Project description:INTRODUCTION:We forecast the prevalence of preclinical and clinical Alzheimer's disease (AD) and evaluated potential impacts of primary and secondary preventions in the United States. METHODS:We used a multistate model incorporating biomarkers for preclinical AD with US population projections. RESULTS:Approximately 6.08 million Americans had either clinical AD or mild cognitive impairment due to AD in 2017 and that will grow to 15.0 million by 2060. In 2017, 46.7 million Americans had preclinical AD (amyloidosis, neurodegeneration, or both), although many may not progress to clinical disease during their lifetimes. Primary and secondary preventions have differential impact on future disease burden. DISCUSSION:Because large numbers of persons are living with preclinical AD, our results underscore the need for secondary preventions for persons with existing AD brain pathology who are likely to develop clinical disease during their lifetimes as well as primary preventions for persons without preclinical disease.
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Project description:BackgroundDevelopment of new therapies for Alzheimer's disease (AD) is increasingly focused on more mildly affected populations, and requires new assessment and outcome strategies. Patients in early stages of AD have mild cognitive decline and no, or limited, functional impairment. To respond to these assessment challenges, we developed a measurement approach based on established scale items that exhibited change in previous amnestic Mild Cognitive Impairment (aMCI) trials.MethodsPartial least squares regression with a longitudinal clinical decline model identified items from commonly used clinical scales with the highest combined sensitivity to change over time in aMCI and weighted these items according to their relative contribution to detecting clinical progression in patients' early stages of AD. The resultant AD Composite Score (ADCOMS) was assessed for its ability to detect treatment effect in aMCI/prodromal AD (pAD) clinical trial populations.ResultsADCOMS consists of 4 Alzheimer's Disease Assessment Scale-cognitive subscale items, 2 Mini-Mental State Examination items, and all 6 Clinical Dementia Rating-Sum of Boxes items. ADCOMS demonstrated improved sensitivity to clinical decline over individual scales in pAD, aMCI and in mild AD dementia. ADCOMS also detected treatment effects associated with the use of cholinesterase inhibitors in these populations. Improved sensitivity predicts smaller sample size requirements when ADCOMS is used in early AD trials.ConclusionsADCOMS is proposed as new standard outcome for pAD and mild AD dementia trials, and is progressing in a CAMD-sponsored qualification process for use in registration trials of pAD.
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Project description:INTRODUCTION:Practice effects are characteristic of nearly all standard cognitive tasks when repeated during serial assessments and are frequently important confounders in clinical trials. METHODS:We summarize evidence that gains in neuropsychological test performance scores associated with practice effects occur as artifactual changes associated with serial testing within clinical trials. We identify and emphasize such gains in older, non-cognitively impaired individuals and estimate an effect size of 0.25 for composite cognitive measures in older populations assessed three times in a 6- to 12-month period. RESULTS:We identified three complementary approaches that can be used to attenuate practice effects: (1) massed practice in a prebaseline period to reduce task familiarity effects; (2) tests designed to reduce practice-related gains so that item-specific driven improvements are minimized by using tasks that minimize strategy and/or maximize interitem interference; and (3) well-matched alternate forms. DISCUSSION:We have drawn attention to and increased awareness of practice effect-related gains that could result in type 1 or type 2 errors in trials. Successfully managing practice effects will eliminate a large source of error and reduce the likelihood of misinterpretation of clinical trials outcomes.
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