eFramingham Heart Study Randomized Controlled Trial #2
Phase: NA
Conditions: Cardiovascular Diseases
Sponsor: Boston University

 
 
 
eFramingham Heart Study Randomized Controlled Trial #2 
NCT04752657 
Joanne M Murabito, MD ScM 
   Phone:   508-935-3461 
   Email:   murabito@bu.edu 
October 2020   
Statistical Analysis Plan- pages 4-5   

eFHS Offspring/Omni Protocol 
October, 2020 
 
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The objective is to test the effect of administering half of survey modules every 2 weeks versus 
all survey modules every 4 weeks on improving participants’ response rates. 
Methods 
We prepared the protocol for this randomized factorial trial in compliance with the SPIRIT 
checklist and plan to register the trial on clinicaltrials.gov. 
Study setting and Eligibility criteria 
Our randomized controlled trial will include participants of the electronic Framingham Heart 
Study (eFHS). Participants in eFHS are invited to enroll from the FHS Offspring and Omni 
Group 1 Cohorts during the in-person examination 10/5 at the FHS Research Center in 
Framingham, MA, USA or remotely from home after the in-person examination. In order to be 
eligible in the eFHS, individuals have to meet the additional following criteria: English-speaking 
individual who owns an iPhone with compatible iOS (version 10.0 or higher) or Android (version 
5.0 or higher); residence in the United States; provision of permissions for notifications and data 
sharing with the Research Center; provision of signed and dated informed consent (within the 
eFHS mobile app). Enrollment in the randomized controlled trial will start once approved by IRB. 
Surveys and Interventions 
All eFHS participants have the eFHS myDataHelps mobile app (developed by FHS investigators 
with CareEvolution our industry partner) installed on their smartphone. The eFHS app allows 
communication with participants through notifications and data collection. Participants are asked 
to answer health surveys administered through the app.  
Survey assessments will include 6 modules: cognition, pain, mood, physical function and 
performance, physical activity, and events (table 1). The interventions are defined by the 
patterns of administration of survey modules to the experimental and control groups as 
described in Table 2. The administration of the cognition, pain, mood, and psychosocial 

eFHS Offspring/Omni Protocol 
October, 2020 
 
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modules follow the same pattern for both groups. However, the administration of the physical 
function, physical activity, and events modules is shifted for the experimental group as 
compared to the control group.  
The cognition and gait tasks are currently not available on android phones. Thus, we will not 
administer these modules to participants who have an android phone instead of an iphone and 
these participants will contribute data only to the other survey modules. 
Table 1: survey modules 
Cognition 
 
Trails 
Task 
Stroop 
Task 
Tapping 
Task 
Cognitive function 
4-items 
Cognitive abilities 
4-items 
Pain  
 
Pain Q (past 7 days)  
5 items 
Body Map (past 3 months) 
 
Mood 
 
Depression (past 7 days)  
4 items 
Anxiety (past 7 days)  
4 items 
Loneliness (no timeframe)  
3 items 
Psychosocial parameters (loneliness, social 
support, resilience) 
3-items, 8-items, 11-items, 6-
items 
Physical function/performance 
 
Gait 
Task 
Mobility no timeframe 
4 items 
Sleep (past 7 days) 
4 items 
Fatigue (past 7 days) 
4 items 
Mobility outside home (past 4 weeks) 
5 items (with more if yes) 
Physical activity 
 
RAPA (no timeframe) 
9 items 
Events 
 
Falls/hospitalzn (past month) 
2 items (with more if yes) 
 

eFHS Offspring/Omni Protocol 
October, 2020 
 
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Table 2: pattern of administration of survey modules in the experimental and control groups 
Participants will be able to complete a survey module from its administration until the next wave. 
This time varies across survey modules given the frequency and timing of administration. For 
example, participants will be able to complete the first pain module between week 0 and week 4 
post-randomization and they will be able to complete the last pain module between week 24 and 
week 28. For the physical function module, the first survey can be completed between week 0 
and 8 in the control group and between week 2 and 10 for the experimental group; while the last 
survey can be completed between week 24 and 32 in the control group and between week 26 
and 34 in the experimental group.   
All participants will periodically receive notifications through the eFHS app to remind them to 
answer the surveys on the eFHS app. Based on our previous work, we will send personalized 
notifications, that include the name of participants and account for the number of surveys 
already completed, to improve response rate to surveys.1 One week after randomization, we 
also will contact all participants by telephone to inquire about any technical issue with the app. 
Week
0
2
4
6
8
10
12
14
16
18
20
22
24
26
Cognition

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Pain
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Body map
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Mood
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Psychosocial

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Physical function
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Physical activity
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Events
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# modules
Exp. group
7
3
5
5
5
3
7
Control group
4
3
2
1
3
2
3
2
3
2
2
1
4
3
Administration to both groups
Administration to control group
Administration to experimental group

eFHS Offspring/Omni Protocol 
October, 2020 
 
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Duration of trial  
We will conduct the trial over 32 weeks.  
Outcomes 
We define 4 survey periods. Period 1 encompasses all survey modules administered from 
baseline up to week 8 (19 surveys/tasks per participant); period 2 from week 8 up to week 16 
(18 surveys/tasks per participant); period 3 from week 16 up to week 24; period 4 from week 24 
(16 surveys/tasks per participant).  
The primary outcome is the proportion of surveys/task returned per participant (partially or fully 
completed). The secondary outcome is the proportion of questions/task completed per 
participant. For both the primary and secondary outcomes, we will compare the mean 
proportions assessed longitudinally across the 4 periods between the experimental and control 
groups.  
Random allocation  
We will randomly allocate each participant to one of the 2 groups. A statistician will generate 
randomization lists with the use of randomly permuted blocks of varying sizes, with stratification 
according to participant’s age (≤75 years vs. >75 years) and type of phone (android vs. iphone). 
Randomization will be implemented centrally through the app.  
eFHS researchers and statistician will be masked to the group assignment. As part of eFHS, 
support staff help participants complete their remote monitoring and data transmission. The 
support staff uses standardized scripts to interact with participants over the phone to address 
technical questions.  
Sample size 
We calculated the sample size for the comparison of the mean proportion of surveys returned 
between the two groups across time. We assumed consistent difference over time and that the 

eFHS Offspring/Omni Protocol 
October, 2020 
 
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distribution of the sample proportions are approximately normally distributed. We account for 4 
time periods. We very conservatively assumed a correlation of the repeated measures of 0.6 
and a standard deviation on the proportion of survey returned of 20%. A sample size of 300 
participants per group guarantees 95% power to detect a mean difference of 5% between 
groups, for example between a mean of 50% of surveys returned per participants in the control 
group vs. a mean of 55% of surveys returned per participants in the experimental group.  
Statistical methods 
We will use a mixed-effects regression model to compare the mean proportions between groups 
across time. Analyses will be in intention-to-treat. We will fit random-intercept models as well 
random-intercept and random-trend models. 
We will perform the following a priori subgroup analyses. We will assess and compare the 
primary and secondary outcomes in subgroups defined according to age (> vs. ≤75 years), sex 
(female vs. male), type of phone (iphone vs. android), cognitive status (impaired or not) and 
whether participants have an apple watch or not. The cognition and gait tasks are currently not 
available on android phones. 
 
 
 

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References 
1. 
Trinquart L, McManus, D.D., Nowak, C., et al. Abstract 13084: Increasing 
Engagement in the Electronic Framingham Heart Study (eFHS): A Factorial 
Randomized Trial. Circulation. 2019;140(Suppl_1):A13084-A84. doi: 
doi:10.1161/circ.140.suppl_1.13084.