Presentation on theme: "Physical Activity to Improve CV Health in Women: a Pragmatic Trial Women’s Health Initiative Strong & Healthy The WHISH Trial CCC-lead PI: Marcia Stefanick,"— Presentation transcript:
Physical Activity to Improve CV Health in Women: a Pragmatic Trial Women’s Health Initiative Strong & Healthy The WHISH Trial CCC-lead PI: Marcia Stefanick, Ph.D Behavioral Science Director: Abby King, Ph.D. Stanford University School of Medicine DCC Multiple-PI: Andrea LaCroix, Ph.D.(lead) Charles Kooperberg, Ph.D., FHCRC (Fred Hutchinson Cancer Research Center) Clustered R01s ≥ $500K/yr PAR-13-128 (Investigator Initiated Multi-Site Clinical Trials - Collaborative RO1).
WHISH Trial Primary Hypothesis An intervention designed to improve levels of aerobic physical activity based on national (DHHS*) recommendations for older U.S. adults, combined with muscle strengthening, balance and flexibility exercises, and reduced sedentary behavior, will reduce major CV events (CV death, MI, stroke) in older (WHI) women, compared to “usual activity” controls over ~4 years of follow-up Physical Activity Guidelines Advisory Committee(2008). Report of the Physical Activity Guidelines Advisory Committee, 2008. Washington, DC: U.S. Department of Health and Human Services. http://www.health.gov/paguidelines/guidelines/chapter5.aspx http://www.health.gov/paguidelines/guidelines/chapter5.aspx *
WHISH Trial Primary Aim Conduct a pragmatic trial in approximately 52,500 women enrolled in the WHI Extension Study, for whom CV outcomes are available, randomized to a centralized, tailored physical activity intervention or “usual activity” (observational control comparison). Primary Safety Aim Evaluate whether an intervention based on DHHS- recommended levels of physical activity for older American adults increases the risk of total clinical fracture, hip fracture, falls, or non-CVD mortality over ~4 years
WHISH Trial Secondary Aim Evaluate whether this tailored, PA intervention reduces risk of selected PA-linked secondary outcomes, potentially ameliorable through regular physical activity, of importance to maintaining independence in older women Secondary Hypotheses Women randomized to the WHISH PA intervention (compared to observational control) will have: Lower rates of venous thromboembolic events (VTE) and peripheral artery disease (PAD); Less loss of physical function including higher rates of ongoing mobility (and independence) Secondary Safety Aim Evaluate whether increased PA increases CABG or PCI
WHISH Trial Eligible based on existing data Follow, per original protocol no yes no yes Based on Zelen. N Eng J Med 1979 Randomized Consent Design for the WHISH trial Follow, per original protocol Inclusion: Alive; WHI MRC or linked to CMS (Medicare administrative data) Exclusions: recent (past 6 months) CV event; dementia; living in a nursing home; self-reported inability to walk
WHISH Trial Assumptions in randomized consent design Existing data are adequate for primary eligibility determination Original consent and protocol covers Re-approach for additional studies All outcome ascertainment procedures Control arm represents “standard of care” Randomization is ethical Power calculations account for Lack of adherence/cross-over Dilution of effect from non-consenters Fraction consenting to intervention expected to be high Primary analysis based on ITT principle, includes: non-consenters those found to be ineligible after randomization
WHISH Trial Pragmatic Trial considerations Randomized Consent Design* in well-characterized cohort (WHI infrastructure creates tremendous efficiencies**) Scientific Advantages: Increases external validity (no/limited Hawthorne effect in control arm) Provides estimates of effectiveness, rather than efficacy Practical advantages Avoids resentful demoralization in control group Simplifies recruitment/consent and reduces associated costs Intervention based on National Recommendations (DHHS) and Publicly Available Resources (NIA Go4Life®) to be delivered by widely used Technology ( interactive voice response, IVR + telephone ) – pilot tested in small WHI sample; will offer two levels of consenting Outcomes collected in WHI: ~20,000 in Medical Records Cohort (MRC) + additional 32,500 linked to CMS records; NDI searches * Adamson et al, Contemporary Clin Trials 2006;27:305-319. **
WHISH Trial WHISH Intervention – in brief Goals per DHHS (2008) PA Guidelines for older adults Consent mailings to women assigned to Intervention will include basic recommendations/goals and Go4Life® pamphlet (exercises) Go4Life® Written Materials, DVD, Website publicly available evidence-based exercise and physical activity materials developed by the National Institute on Aging “Full Consent” reinforced and individualized by means of an algorithm-driven telephone- delivered interactive voice response (IVR) system managed centrally at Stanford, with “light (human) touch” (telephone and mailed materials), as needed Weekly for 6 weeks, Bi-monthly for 6 weeks, then Monthly “Mailings Only” consent option (2-4x/yr) – may become “Full” Special materials for women who use walkers, canes, wheelchairs, and to deal with injuries & rehabilitation National (& Regional) Community Facilities/Resources, e.g. Senior Centers, Ys (Silver Sneakers), Special Programs
WHISH Trial http://go4life.nia.nih.gov/ On Go4Life website: can watch exercise videos, submit personal exercise success stories, print educational tip sheets, use interactive tools in MyGo4Life section to make an exercise plan and track progress over time. Exercise & Physical Activity: Your Everyday Guide from the National Institute on Aging 120-page guide describes the benefits of exercise and physical activity for older adults Workout to Go: A Sample Exercise Routine from the National Institute of Aging at NIH Featured exercises include: Hand Grip Wall Push-Up Overhead Arm Raise Back Leg Raise Side Leg Raise Toe Stand Stand on One Foot Heel-to-Toe Walk Balance Walk Ankle Stretch Back Stretch Thigh Stretch Shoulder and Upper Arm Stretch Go4Life DVD—Everyday Exercises from the NIA How to set exercise goals and stick to them. Includes sample exercises for endurance, strength, balance, flexibility & list of resources.
WHISH Trial Background: The use of interactive voice response (IVR) technology for healthcare applications and for medical and psychological research is growing. Health-related IVR examples include: Follow up of patients after hospital discharge Peer support to patients with chronic heart failure Increase of medication adherence Weight loss promotion in pre-diabetic patients Physical activity in older adults (CHAT, King et al, 2007) Physical activity in WHI participants – WHISH pilot
WHISH Trial 218 Community-dwelling Under-active Adults ages ≥ 55 yrs, randomized to: Community Health Advice by Telephone: CHAT Project Telephone Advice by (IVR) COMPUTER Attention- Control arm Telephone Advice by HUMAN Assessments at 0, 6, 12, & 18 mos. King, Friedman, Marcus, et al., Health Educ Res, 2002
WHISH Trial MVPA ( kcal/kg -1 /day -1 ) Baseline 6 mo. 12 mo. * Intervention > control, p control, p =.05 0.80.95 1.10 1.25 1.40 1.55 1.70 1.85 * Control Automated Advice Human Advice † CHAT Trial Moderate-Vigorous PA (7-day PAR) * * King AC et al., Health Psychol, 2007 18 mo. (N.S.) Mean age 61 + 6 yrs (range:53-78) 67% women 86% white
WHISH Trial WHISH Pilot Study Design 27 WHI former Diet Trial participants - average age: 75 years (66 – 92) Baseline Physical Activity (by telephone interview*) F34: walking outside home ≥ 10 min w/o stopping; moderate/strenuous exercise Q: Strengthening exercises and Balance/Flexibility ≥ 2x/wk (Y/N) Welcome Packet: NIA Go4Life®, Omron Pedometer, IVR instructions
Participants increased PA significantly between baseline and follow-up (mean change (min/week): 79 ± 116, p<.001).
WHISH Trial WHISH PA Monitoring Intervention Arm Mailings Only (+website)- simple calendars (pre-paid postcards). “Full” - IVR phone contact (PA type & amount, pedometer steps) based on Adherence, tailored behavioral augmentations are built into intervention Vanguard cohort will be studied with SMART trial design, for optimization of intervention Both Arms (self-report) short OPACH PA questionnaire mailed to WHISH participants in annual WHI Form 33 (WHI outcomes) mailings; first mailing prior to initiating the intervention (baseline) and then annually. Subset of Both Arms (Objective PA Monitoring) ~1000 from each arm, randomly selected among OPACH/WHISH participants for 7-day accelerometry (B, 6-, 18- and 24-months)
WHISH Trial Outcomes, Events needed Intention to Treat (ITT) comparison of clinical events Expect ~52,500 to meet eligibility criteria In MRC or linked to CMS at trial outset (i.e. Outcomes/Data being collected as a fn. of enrollment in WHI Extension Study) Exclusions: recent (past 6 months) CV event; dementia; living in a nursing home; self-reported inability to walk Expect 80% of Intervention arm to consent 60% to “full” intervention; 20% to “mailings only” Anticipating 10-12% effect size observational studies suggest 25-30% reduction in CV events WHI: currently observed annualized rates: 0.90%/yr, suggests a ~ 4 year follow-up is needed
WHISH Trial WHISH Outcomes Collected within the Scope of the Ongoing WHI Extension Study
WHISH Trial Outcomes, Events (continued) WHI Analyses have demonstrated reliability of CMS data for MI and stroke (kappa~0.75), and other CV events (Hlatky et al; Burwen et al) We have ~80% power for finding a significant treatment effect if true effect size is ~12.5% and 90% if true effect size is ~14.5% If trial were extended one year (using a no cost extension): ~80% power for ~11% true effect size, and 90% if the effect size is a little under 13%. With 44 months follow up (2019) Expected number of CV Events With 56 months follow up (2020) Expected number of CV Events Effect ControlIntervention Power ControlIntervention Power 10%94084760.9%1191107371.1% 11%94083869.4%1191106279.2% 12%94082977.0%1191105085.8% 13%94082083.4%1191103991.0% 14%94081088.6%1191102794.5% 15%94080192.5%1191101596.9%
WHISH Trial Anticipated timeline for proposed trial Activity Yr 1 0-6 mo Yr 1 6-12 Yr 2 Yr 3 Yr 4 Yr 5 Finalize IVR and Intervention MaterialsX IRB approvals (FHCRC, Stanford)X Screening, Randomization, Consenting (DCC) X Initiate Intervention in Vanguard cohortX Intervention Adoption Phase (3 months) X X Intervention Optimization and Maintenance XXXXX Study closeout X Analyses/publication of final manuscripts X