translating observational and lab- based trials to
TRANSCRIPT
Translating Observational and Lab-based Trials to Community-based
Interventions: Why and How Michelle C. Carlson, PhD
Johns Hopkins Bloomberg School of Public Health Department of Mental Health, Center on Aging and Health
Workshop on Understanding Pathways to Successful Aging:
Behavioral and Social Factors Related to Alzheimer’s Disease National Academy of Sciences, Engineering and Medicine
June 12-13, 2017
1
Overview • Why do community interventions? • Any movement is good (Revenge of the Sit I & II)
• Building Metrics Around Movement- incorporating wearable devices to develop indices that inform evaluation, mechanism and intervention design
• Why do people move? Social, purposeful and other motivations to tap into
• Why don’t people move? Barriers related to the individual’s health and to the environment
• Environment as key intervention design factor- includes safety, available infrastructure, community partners
• Challenges & Opportunities- engaging & building trust with stake holders, sustaining & growing a community-based intervention post study
Why Do Interventions in the Community?
• Translating Beneficial Behaviors into Everyday Life styles=> Behavior change – Physical activity/exercise – Cognitive activity – Retain/regain social purpose
• Reaching at risk populations in their communities
• Scaling up from clinic/lab to generalize to real-world environments
2.5
33.
54
4.5
0 5000 10000 15000 20000 25000avg_steps
Fitted values Lhippocampus
1000 more steps/ day is associated with a larger hippocampus, a brain region important to memory and dementia risk
Varma, Chuang, Harris, Tan, & Carlson, 2014, Hippocampus
Even small increases in daily walking activity may matter
Lifestyle Physical Activity and Brain Health
PA associated with subiculum in women Varma, Tang, & Carlson, 2015 Hippocampus
Physical Activity (PA) Guidelines for Older Adults: Determined by Environment
• Current Guidelines: 30 minutes/day of moderate-intensity PA ; 20 minutes/day of vigorous-intensity PA three days/week
• Difficulties in reaching PA targets for older adults; particularly those of low socioeconomic status (SES)
• Benefits of low-intensity physical activity in enriched, daily environments?
Sources: HHS: Health People 2020; Tudor-Locke & Basset, 2004; PAG Report, 2008; Marshall, et al. 2007; Parra-Medina, 2010
Linking Physical Activity to Social Engagement with a Purpose: Volunteering -Desire to remain generative & productive -Harnessing one’s lifetime of accumulated wisdom • Volunteers 60 and older
• Serve in public elementary schools: K-3 • Multiple roles to exercise executive function,
memory – Reading literacy – Library support – Math support – Behavioral support
• >15 hours per wk • Travel to & from schools; walking within schools • Sustained dose: full school year
Freedman & Fried, 1997; Fried et al., 2004; Fried et al., 2013; Glass et al., 2004
Baltimore Experience Corps Trial • Evaluation funded by NIA BSR: 2006-
2013 • Randomized:
– 702 60 yrs. and older to EC or low-activity control
– Matched 25 public elementary schools with EC to control
• Exposure: 2 years of high-intensity service
• Outcomes: – Physical: Disability, mobility, walking
speed – Cognitive: Memory, executive function – Psychosocial well-being
• Nested Brain Health Substudy(N=120)
Brain plasticity; Executive function
MESSAGE:
Generative Service
Intervention Primary Pathways Mechanisms Performance-based outcomes
Strength, balance
Social Integration & Support
Generativity
Physical Activity
Cognitive Activity
Social Activity, Engmnt. Psycho-Social
Well-being
Memory
Walking Speed
Frailty
Recruitment Message & Mechanisms: Causal Pathway
IADLs
Falls
Women in Experience Corps maintained average steps/day over 24 months post-Intervention while Controls declined.
5000
6000
7000
8000
9000
Ave
rage
ste
ps/d
ay
Baseline 12-months 24-months
Control
Intervention
Varma, Tan, Gross, Harris, Romani, Fried, Rebok, Carlson, 2015 AJPM
Men had significantly higher baseline levels of daily physical activity than women and maintained these levels.
Did We Increase Daily Physical Activity Following Program Participation? Step Activity (N=115):
Women EC= red; Control= blue
Does Experience Corps Lead to Changes in Brain Health?
• 2-year improvement in memory related to 2-year increase in whole brain volume in EC (blue.
5000
5500
6000
6500
7000
7500
Baseline 12 month 24 month
Volu
me
(mm
3 )
Men: Hippocampal Volume (mm3)
Intervention
Control
Carlson, Kuo, Chuang, Varma, et al., 2015 Alz & Dementia
• Men in the Experience Corps arm showed a 0.8-1.6% increase in total cortical and hippocampal brain volumes v. declines in controls.
• Women in Experience Corps also tended to exhibited modest gains of 0.3-0.54% by 24 months of exposure.
-4 -2 0 2 42-year change in Whole-Brain volume
InC
11
Experience Corps also impacts the amygdala, a region important to socially salient information and a biomarker for AD risk (Miller et al., 2013) (see nice meta-review by Bruhl et al., 2014)
• Using shape diffeomorphometry, we see specific patterns of change
Only the left amygdala shows significant group differences post-intervention, after correction for multiple-comparisons (p=0.0052)
Con
trol
Inte
rven
tion
Gro
up D
iff
Carlson, Varma, Miller, & Tang, under review
From School to Community: Building Metrics to Identify Opportunities for Purposeful Activity in Daily Life
• Measure real-time contexts in daily life when it occurs by expanding use of real-time mobile assessment in the community – Are there “hot spots”? – Are there diurnal patterns when individuals are most
able to exercise? – Is meaningful vs. any social engagement a magic
ingredient? • Create opportunities, particularly in low-
resourced neighborhoods
Using GPS+ accelerometers to determine where the greatest amounts of outdoor activity occur in daily life
Carlson, Varma, Adam, Crainiceanu, & Zipunnikov, under review
Environmental Barriers to Physical and Social Activity Distribution of BECT participants across Baltimore City (n=535)
HotSpot analysis of participants with poor global cognition (MMSE scores <26) (left panel) and with poor memory (right panel)
Adam, Varma, Harris, & Carlson, under review
Double Jeopardy- At risk individual in at-risk environment Community interventions can target both
Place Matters • Location where intervention takes place
– Is accessible, in members’ neighborhoods – capitalizes on existing school & other community
infrastructures – Schools & senior centers offer safe access in & around
(e.g., side walks) (Tan et al., 2010 Am J. Public Health)
• Examples of Community-based Interventions:
– Community Choirs (Johnson, UCSF; NIA 2012-17) conducted in partnership with San Francisco Community Music Center & SF Dept. of Aging & Adult Services
– SYNAPSE Project (Park et al., 2014) – Senior Odyssey of the Mind (Stine-Morrow et al., 2008) – Theatre acting (Noice & Noice, 2004, 2014)
Identifying & Engaging Stake Holders in Research-Community Partnerships
• Identify all stake holders’ needs: – Older adults: cognition, physical function, disease
management – Children & young adults: literacy, obesity, bullying,
substance abuse • Identify community partners
– local gov’t & non-profit agencies, senior centers, etc. • Listen & share in intervention design =
collaboration…Build trust! • Challenges & opportunities
– Sustainability beyond research enterprise – Cost effectiveness
It Takes a Village: Research Team and Collaborators
• Jeremy Barron - JHU • Michelle Carlson - JHU • Yi-Fang Chuang - Natl Yang Ming U • Kay Dickersin - JHU • Kirk Erickson - U Pittsburgh • Constantine Frangakis - JHU • Linda Fried - Columbia U • Kevin Frick – JHU • Alden Gross - JHU • Tara Gruenewald – USC • Jin Huang - JHU • Arthur Kramer - Northeastern U • Sylvia McGill - EC Baltimore • Jeanine Parisi - JHU
• Christine Ramsey – VA CT • George Rebok - JHU • William Romani – AARP • David Roth - JHU • Roberta Scherer - JHU • Teresa Seeman - UCLA • Erwin Tan – AARP • Elizabeth Tanner – JHU • Vijay Varma – NIA, LBN • Keith Whitfield – Wayne State U • Paul Willging - JHU • Qian-Li Xue - JHU
Funding Acknowledgments Experience Corps Trial • Alzheimer’s Drug Discovery
Foundation • NIA BSR Grant #
P01AG027735-03 supplement • Greater Homewood
Community Corporation • Johns Hopkins OAIC Pepper
Center Grant #P30AG021334 • Johns Hopkins
Neurobehavioral Research Unit
• S.D. Bechtel Award
Geo-Coded Activity • Johns Hopkins ADRC Pilot
Grant • Johns Hopkins OAIC
Pepper Center Grant #P30AG021334
Trial Methods: Analysis of Older Adults
• Intention-to-treat (ITT): Intervention vs. Control ignoring compliance (i.e., N1+N2 vs.
N3+N4) • Complier average causal effect (CACE): Intervention vs. Control among compliers (i.e., N1 vs. N3)
CACE
Complier Non-Complier
ITT Intervention N1 N2
Control N3 N4
Some Terms • Active Control: Control condition is the principal method of removing the
influence of unwanted variables to determine the effectiveness of the Intervention condition in a randomized, controlled trial (RCT)
• Community-based Intervention: interventions embedded within community settings and infrastructures
• Equipoise: Ethical considerations, including assurances of receiving the best available standard therapy (clinical) and non-maleficence
• Generalizability: as applied to outcomes, the impact of an intervention on outcomes beyond those abilities and systems trained or exercised. May also be described as near and far transfer.
• Prevention: interventions designed to delay and reduce the risk of onset of clinical disease(s)
• Randomized Controlled Trial: provides critical evidence for the efficacy or effectiveness of behavioral interventions
• Risk/Protection Factor: behavioral, health, demographic, and/or environmental factors that may increase/reduce one’s risk for an adverse health outcome
• Sustainability: program maintenance independent of research funding, often done in collaboration with community stakeholders