PMID- 26379170 OWN - NLM STAT- MEDLINE DCOM- 20160609 LR - 20201215 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 10 IP - 9 DP - 2015 TI - Use of High-Frequency In-Home Monitoring Data May Reduce Sample Sizes Needed in Clinical Trials. PG - e0138095 LID - 10.1371/journal.pone.0138095 [doi] LID - e0138095 AB - BACKGROUND: Trials in Alzheimer's disease are increasingly focusing on prevention in asymptomatic individuals. This poses a challenge in examining treatment effects since currently available approaches are often unable to detect cognitive and functional changes among asymptomatic individuals. Resultant small effect sizes require large sample sizes using biomarkers or secondary measures for randomized controlled trials (RCTs). Better assessment approaches and outcomes capable of capturing subtle changes during asymptomatic disease stages are needed. OBJECTIVE: We aimed to develop a new approach to track changes in functional outcomes by using individual-specific distributions (as opposed to group-norms) of unobtrusive continuously monitored in-home data. Our objective was to compare sample sizes required to achieve sufficient power to detect prevention trial effects in trajectories of outcomes in two scenarios: (1) annually assessed neuropsychological test scores (a conventional approach), and (2) the likelihood of having subject-specific low performance thresholds, both modeled as a function of time. METHODS: One hundred nineteen cognitively intact subjects were enrolled and followed over 3 years in the Intelligent Systems for Assessing Aging Change (ISAAC) study. Using the difference in empirically identified time slopes between those who remained cognitively intact during follow-up (normal control, NC) and those who transitioned to mild cognitive impairment (MCI), we estimated comparative sample sizes required to achieve up to 80% statistical power over a range of effect sizes for detecting reductions in the difference in time slopes between NC and MCI incidence before transition. RESULTS: Sample size estimates indicated approximately 2000 subjects with a follow-up duration of 4 years would be needed to achieve a 30% effect size when the outcome is an annually assessed memory test score. When the outcome is likelihood of low walking speed defined using the individual-specific distributions of walking speed collected at baseline, 262 subjects are required. Similarly for computer use, 26 subjects are required. CONCLUSIONS: Individual-specific thresholds of low functional performance based on high-frequency in-home monitoring data distinguish trajectories of MCI from NC and could substantially reduce sample sizes needed in dementia prevention RCTs. FAU - Dodge, Hiroko H AU - Dodge HH AD - Department of Neurology, Layton Aging and Alzheimer's Disease Center, Oregon Health & Science University, Portland, Oregon, United States of America; Oregon Center for Aging and Technology (ORCATECH), Oregon Health & Science University, Portland, Oregon, United States of America; Department of Neurology, Michigan Alzheimer's Disease Center, University of Michigan, Ann Arbor, Michigan, United States of America. FAU - Zhu, Jian AU - Zhu J AD - Graduate School of Public Health, University of Michigan, Ann Arbor, Michigan, United States of America. FAU - Mattek, Nora C AU - Mattek NC AD - Department of Neurology, Layton Aging and Alzheimer's Disease Center, Oregon Health & Science University, Portland, Oregon, United States of America; Oregon Center for Aging and Technology (ORCATECH), Oregon Health & Science University, Portland, Oregon, United States of America. FAU - Austin, Daniel AU - Austin D AD - Department of Neurology, Layton Aging and Alzheimer's Disease Center, Oregon Health & Science University, Portland, Oregon, United States of America; Oregon Center for Aging and Technology (ORCATECH), Oregon Health & Science University, Portland, Oregon, United States of America. FAU - Kornfeld, Judith AU - Kornfeld J AD - Department of Neurology, Layton Aging and Alzheimer's Disease Center, Oregon Health & Science University, Portland, Oregon, United States of America; Oregon Center for Aging and Technology (ORCATECH), Oregon Health & Science University, Portland, Oregon, United States of America. FAU - Kaye, Jeffrey A AU - Kaye JA AD - Department of Neurology, Layton Aging and Alzheimer's Disease Center, Oregon Health & Science University, Portland, Oregon, United States of America; Oregon Center for Aging and Technology (ORCATECH), Oregon Health & Science University, Portland, Oregon, United States of America; Portland Veterans Medical Center, Portland, Oregon, United States of America. LA - eng GR - P30 AG024978/AG/NIA NIH HHS/United States GR - R01 AG024059/AG/NIA NIH HHS/United States GR - P30-AG008017/AG/NIA NIH HHS/United States GR - R01-AG033581/AG/NIA NIH HHS/United States GR - R01-AG024059/AG/NIA NIH HHS/United States GR - R01 AG033581/AG/NIA NIH HHS/United States GR - P30-AG024978/AG/NIA NIH HHS/United States GR - P30 AG008017/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20150917 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Amyloid beta-Peptides) RN - 0 (Biomarkers) SB - IM MH - Aged, 80 and over MH - Alzheimer Disease/*diagnosis/drug therapy/prevention & control MH - Amyloid beta-Peptides/metabolism MH - Biomarkers/analysis MH - Clinical Trials as Topic/*methods MH - Cognitive Dysfunction/diagnosis/*physiopathology MH - Disease Progression MH - Female MH - Humans MH - Male MH - Monitoring, Ambulatory/*methods MH - Neuropsychological Tests/*statistics & numerical data MH - Sample Size PMC - PMC4574479 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2015/09/18 06:00 MHDA- 2016/06/10 06:00 PMCR- 2015/09/17 CRDT- 2015/09/18 06:00 PHST- 2015/03/30 00:00 [received] PHST- 2015/08/25 00:00 [accepted] PHST- 2015/09/18 06:00 [entrez] PHST- 2015/09/18 06:00 [pubmed] PHST- 2016/06/10 06:00 [medline] PHST- 2015/09/17 00:00 [pmc-release] AID - PONE-D-15-13785 [pii] AID - 10.1371/journal.pone.0138095 [doi] PST - epublish SO - PLoS One. 2015 Sep 17;10(9):e0138095. doi: 10.1371/journal.pone.0138095. eCollection 2015.