Phone Coaching and Internet-delivered Weight Loss
Phase: NA
Conditions: Obesity
Sponsor: The Miriam Hospital

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DIAL Now Trial  
(Disseminating Internet-based Approaches for Lifelong change) 
 
Study Protocol: 4/4/20 
 
 
ClinicalTrials.gov: NCT03867981 
 
Grant funding: R01 DK117783-01 
 
 

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Background. 
Internet-based weight loss (WL) programs are effective for many, but a significant number of individuals fail to 
achieve a clinically significant WL and may require a more personalized treatment approach. One strategy for 
improving Internet-delivered WL (IDWL) treatment, while still limiting delivery costs, is to use a stepped-care 
intervention, in which all individuals receive a standardized Internet program and a more intensive intervention 
is reserved for those with suboptimal WL outcomes. Our research team has demonstrated that the provision of 
a brief period of individualized coaching to early non-responders enrolled in IDWL treatment significantly 
improved intervention adherence and post-treatment WL, when compared to early non-responders who 
received no coaching. The current study builds on these findings and examines whether WL can be further 
improved through the use of extended coaching, whether these effects are sustained once the phone coaching 
(PC) is removed, whether these interventions are effective from a cost perspective, and the mechanisms 
through which PC affects intervention engagement and WL.  
 
Study Design and Overview.  450 participants will be randomized at baseline to 1 of 3 groups: 1) IDWL only 
(‘Control’; n=150), 2) IDWL+Brief PC for early non-responders (‘Brief’; n=150), or 3) IDWL+Extended PC for 
early non-responders (‘Extended’; n=150).  Randomization will occur in equal numbers based on permuted 
block randomization procedure with small, random 
sized blocks. Randomization will be stratified by sex 
and race/ethnicity (non-Hispanic White vs. Other).   
      An overview of the study design is shown in 
Figure 4. Participants will be recruited in multiple 
cohorts and the study will be conducted over a 5-year 
period. All individuals will receive a 4-month IDWL 
program, followed by an 8-month IDWL maintenance 
program. Participants will report their weight weekly 
on the study website and 4-week WL will be used to 
classify individuals as initial responders (4-wk WL 
≥4%) or early non-responders (4-wk WL <4%). Initial 
responders will continue the IDWL program but will 
not receive any additional intervention, while 
treatment for early non-responders will be dependent upon randomization assignment. Early non-responders 
randomized to ‘Control’ will not receive PC while early non-responders randomized to ‘Brief’ will receive weekly 
PC for 3 weeks (weeks 5-8), and early non-responders randomized to ‘Extended’ will receive weekly PC for the 
remainder of the WL program (weeks 5-16). During the WL maintenance phase (months 5-12), monthly video 
lessons will be provided and participants will continue to receive automated feedback monthly; however no 
additional PC will occur during this time. Assessments will be performed at baseline, post WL treatment (4 
months) and following the 8-month, no-contact WL maintenance period (1 year). Body weight, intervention 
adherence, diet, physical activity, and psychosocial factors will be assessed.  
 
Study Aims. 
 
Primary aim:  To compare treatment effects on weight outcomes at 4 and 12 months. The primary weight 
outcome is percent weight change from baseline to 4 and 12 month follow-ups, and the secondary weight 
outcome is the percentage of participants achieving a clinically significant WL (≥5% WL). It is hypothesized that 
WL will be:  Extended > Brief > Control. We will also examine treatment effects on primary and secondary 
weight outcomes among early non-responders only.  
 
 
Secondary aims:  (1) To examine the incremental cost per kg of WL in Brief, Extended, and Control. (2) To 
compare Brief, Extended and Control on intervention engagement (e.g., diet quality, physical activity, self -
monitoring, video lessons viewed) and to examine whether intervention engagement mediates the effects of 
the intervention on WL. (3) To examine whether 4-week WL moderates the effect of the interventions on 
longer-term WL. By using a 4% WL threshold to classify early non-responders, we can both continuously and 

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categorically (e.g., <2% vs. 2-4%) examine whether there is an interaction between early WL and the efficacy 
of the interventions.  
 
Exploratory aim: To explore mechanisms through which PC may affect engagement and WL, including 
perceived support, self-efficacy and intrinsic/extrinsic motivation and consider other moderators (e.g., gender, 
race/ethnicity).   
 
 
Recruitment. Participants will be recruited through advertisements in local newspapers, direct mailings, 
Internet and television ads, and by using LifeChart through a generated Report. Individuals will be instructed 
to: 1) call the WCDRC to see if they are eligible to participate in this study and a member of the research staff 
will conduct a formal phone screen with them via the phone (see attached phone screen).  2) go to our study 
website to learn more about the study and to complete an initial online screener via RedCap (see attached for 
text describing the study and online screener). Those who appear to be eligible based upon the online 
screener will be called by a member of our research staff  in which the remaining questions from the phone 
screen will be asked by a member of our research staff. All eligible participants will be scheduled for an 
orientation session either in-person, via phone or video call where they will learn more about the study and if 
interested, informed consent will be obtained in-person or electronically using Redcap. 
 
Participants. 450 weight loss seeking men and women will be recruited for this study. Participants will be 
between the ages of 18 and 70, have a BMI between 25 and 45 kg/m2, and have regular (i.e., daily) access to 
the Internet, defined as owning a smartphone with Internet capabilities, and/or having a broadband or wi-fi 
connection at home or work. Additional exclusionary criteria can be found in the Protection of Human Subjects 
section and Clinical Trials Section 2.2. Eligibility Criteria. 
 
Internet-based weight loss program. All participants, independent of randomization assignment or early non-
responder status, will receive a 4-month, Internet-delivered behavioral WL program followed by an 8-month, 
minimally intensive, IDWL maintenance program. Prior to the start of the program, participants will be taught 
how to navigate the study website and will be given the opportunity to ask questions. The goal of the program 
is to induce a 1-2 lb WL per week. To assist in achieving this goal, individuals will be given a daily calorie 
intake goal of 1200-1800 kcal/day depending upon starting weight and a physical activity (PA) goal which 
progresses to 250 min/week of moderate-intensity PA. Using the self-monitoring platform on the website, 
participants will be instructed to record their body weight, calorie intake, and PA daily over the 16-week period. 
If participants do not own a scale, one will be provided. Computer-generated, personalized feedback will be 
provided weekly based upon these self-report data. Further, participants will be instructed to view a 10-15 min 
multimedia lesson weekly. These lessons are modeled after the Look AHEAD Trial80 and example lesson 
topics including strategies for increasing PA, eating out at restaurants, and problem solving. Moreover, the 
study website gives participants access to weekly recipes and additional tip sheets offering useful strategies for 
healthy eating and regular PA (e.g., strategies for meal planning, dealing with negative emotions, or exercisin g 
safely).  
 
Following the completion of the 16-week WL program, all participants will transition to a no-contact, 
minimally intensive WL maintenance program. During months 5-12, participants will have the opportunity to 
view monthly video lessons which focus on strategies for successful WL maintenance (e.g., relapse 
prevention, goal setting, overcoming barriers, etc.) and they will be instructed to continue to self -monitor their 
weight, dietary intake, and physical activity minutes on the study website for one week every month. 
Automated feedback will only be provided monthly and will be tailored based upon whether the participant lost, 
gained, or maintained WL. No phone coaching will occur beyond 4 months.  
 
Identification of early non-responders. Percent WL at the end of week 4 will be used to classify individuals 
as early non-responders (<4%) or initial responders (≥4%). This will be calculated using self -reported weight at 
baseline and weight at the end of the week 4. If a participant did not report a weight at week 4, an automated 
email will be sent prompting them to log their weight immediately. If after 3 email attempts a weight is still not 
recorded, the participant will receive a telephone call. Participants still missing 4-week weight data will be 
unable to be classified as an initial responder or early non-responder and thus will only be included in the 
analyses involving the aggregate sample. To reduce potential bias and enhance scientific rigor, participants will 

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not be informed of their randomization assignment or the criteria used to determine who will receive PC. 
Instead, all participants will be told that they will receive an IDWL program and have the possibility to receive a 
brief period of PC or PC for the entire duration of the WL portion of the program, and that they will be contacted 
if they were selected to receive the PC. 
 
Phone coaching for early non-responders. Early non-responders randomized to ‘Brief’ will receive weekly 
PC for 3 consecutive weeks (delivered during weeks 5-7), while early non-responders randomized to 
‘Extended’ will receive weekly PC for the remainder of the WL program (delivered during weeks 5-16). 
Coaches will be dieticians, exercise physiologists, or interventionists at the WCDRC with previous intervention 
experience in behavioral WL programs. All coaches will be trained and supervised by Dr. Pellegrini (Co-I). 
Training will be consistent with that proposed in the Supportive Accountability model and will include basic 
motivational interviewing and problem solving strategies, establishing trust and rapport with the participant, 
practical solutions for barriers common to early non-responders, and individualized meal planning methods. 
The initial PC session will be approximately 45 minutes in duration and all remaining sessions will be 
approximately 10-15 minutes. The content material of the coaching calls will be similar to that provided in our 
pilot study11 and is guided by the Supportive Accountability Model which posits that human support (via 
coaching) improves adherence to web-based treatment programs through accountability to a coach who is 
viewed as being trustworthy, benevolent, and having expertise developed by Mohr and colleagues39. The 
TeleCoach Manual38, which was developed within the context of the Supportive Accountability framework, will 
be adapted for WL and used in the proposed study.  
The overarching goal of the coach is to help the participant ‘jump start’ his or her WL through the 
provision of a supportive environment. Thus, a large portion of  the initial PC session will be spent establishing 
rapport and focusing on each of the following elements: understanding the context of the participant’s life, 
eliciting their coping and treatment history and hopes for treatment, providing feedback and brief 
psychoeducation, identifying potential barriers and problem solving, reviewing the program website, and 
eliciting commitment to the process of the coaching calls (see Clinical Trials 4.2.a for more details). The goal of 
the follow-up phone calls is to use motivational interviewing principles to keep the participant motivated, elicit 
commitment, and problem solve any barriers to intervention adherence or achievement of program goals. Prior 
to the phone call, coaches will review the participant’s website logins and self-monitoring data. These follow-up 
sessions will begin with a brief check-in and conclude by setting a SMART (Specific, Measurable, Achievable, 
Results-focused, Time-bound) goal for the upcoming week. During each PC session, participants will also be 
encouraged to continue to self-monitor on the study website and view weekly video lessons. Further, during 
the last week of PC for ‘Extended’ participants, a portion of the phone call will focus on strategies for 
successful WL maintenance and maintaining accountability and motivation following the cessation of PC.  
While the structure of the coaching calls will be similar across participants, the content will be tailored to 
the individual. Coaches will use goal setting, problem solving and motivational interviewing strategies to help 
participants adhere to the intervention and achieve program goals; thus having the ability to address both 
typical barriers as well as non-traditional barriers to WL. Our preliminary data highlight several common 
barriers among early non-responders. Some examples are frequent eating out, feelings of being overwhelmed 
(too busy), underestimation of caloric intake, and greater than normal effort required to stay on track. Thus, 
coaches will be provided with training and resources highlighting potential strategies for overcoming each of 
these barriers and they will be trained in how to convey this information with the participant (see C.1.d above).  
Coaches will also be trained in developing individualized meal plans. In our pilot study, coaches worked 
with the participants to develop an individualized meal plan for the upcoming week that relied heavily on pre -
packaged foods (e.g., meal replacement products, frozen entrees, single size portion snacks, etc) and fruit and 
vegetable consumption. Meal planning with a coach can reduce the amount of effort required when counting 
calories and self-monitoring, ensure that the participant achieves his/her calorie intake goal, save time for 
those who are busy, and reduce restaurant eating and/or lead to better food choices while eating out, thereby 
addressing many of the common barriers mentioned above. These meal plans will be tailored to each 
participant’s food preferences in order to promote adoption of this meal plan and revised weekly if needed. 
To ensure rigor and reproducibility of our PC sessions, coaches will be provided with standardized 
manual to ensure that critical intervention elements are discussed during each PC session, coaches will be 
trained by Dr. Pellegrini, and calls will be audio recorded and treatment fidelity will be assessed (see C.11.b). 
 

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Assessment components. Assessments of weight, intervention engagement (diet, physical activity, 
adherence), and psychosocial factors (perceived support, self -efficacy, motivation) will occur at baseline, 4, 
and 12 months. Brief descriptions of these measures are provided below.  
 
Weight, height, and body mass index. Objective measures of weight and height will be performed by a staff 
member. Calculations of body mass index, absolute weight change in kg, and percent weight change from 
baseline will be calculated. Further the percentage of participants in each treatment group achieving a clinically 
significant WL (≥5%) will be determined. Percent WL at the end of week 4 will be calculated using self -reported 
weight obtained from the study website at baseline and 4 weeks, and these data will be used to categorize 
participants as early non-responders or initial responders.  
 
Intervention engagement. Diet, physical activity (PA), and intervention adherence are important weight 
control behaviors which can influence body weight.   
 
• Physical activity will be objectively-measured for 1 week at baseline, 4, and 12 months using the newest 
generation of Actigraph accelerometers (Actigraph GT9X Link). Participants will receive the Actigraph at their 
scheduled assessment visit and will be instructed to wear the accelerometer on their waist during all waking 
hours, exclusive of bathing and swimming, for 7 consecutive days at each assessment period. This monitor 
uses a validated triaxial accelerometer and proprietary data filtering technology to estimate free-living PA and 
sedentary behaviors81-83. Accelerometer data will be processed and analyzed using Actigraph’s ActilLife 
software. Data will be considered valid if the monitor was worn for ≥10 hours on ≥4 days (including ≥1 
weekend day).  Intensity will be assessed as average counts per minute (cpm) and previously validated cut 
points will be used to identify bout-related moderate-to-vigorous intensity PA (≥1952 cpm accumulated in 
bouts ≥10 min) and sedentary time (<100 cpm). Minutes per day spent in moderate-to-vigorous intensity PA 
and sedentary behaviors will be calculated.  
 
• Diet will be assessed using the web-based Dietary Screener Questionnaire (DSQ) developed by NCI84.  This 
questionnaire was originally validated using recall data form the National Health and Nutrition Examination 
Survey. The DSQ is a 26-item screener that asks about the frequency of consumption in the past month of 
selected foods and drinks, such as fruits and vegetables, dairy/calcium, added sugars, whole grains/fiber, red 
meat, and processed meat.  The Dietary Screener will allow us to examine diet quality and changes in 
dietary factors targeted by the intervention and encompassed within healthy eating lesson material (e.g., 
reducing intake of sugar sweetened beverages, baked good and other refined carbohydrates and increasing 
intake of fruits, vegetables and fiber.  To assess for total energy intake, participants will report caloric intake 
via self-monitoring records.  
• Intervention adherence will be assessed separately during the 4-month WL program and 8-month WL 
maintenance period. Outcome measures include the number of website logins, video lessons viewed, and 
the frequency of self-monitoring, all of which are generated automatically by the study website. The number 
of coaching calls completed will also be assessed for ‘Brief’ and ‘Extended’ early non-responders.  
 
Psychosocial process measures. An exploratory aim of this trial is to examine psychosocial process 
measures which could mediate or moderate the effect of PC on adherence and WL.  
 
• Perceived support will be measured in two ways. First, all participants will complete the Important Others 
Questionnaire90 which measures the participants perception of the supportiveness of ‘important others’ which 
can be a family member, spouse, friend, or coach with respect to their diet and PA behaviors. This will allow 
for comparisons in perceived support between all three treatment groups which is important for meditational 
analyses. However, it is equally important to measure the strength of the coach-participant bond, as this is an 
important aspect of the Supportive Accountability model; thus those randomized to Brief or Extended will also 
complete the Helping Alliance Questionnaire91. This will allow for the exploration of whether the coach-patient 
bond differs between Brief and Extended, and whether the magnitude of alliance is associated with WL. 
 
• Self efficacy for diet will be assessed using the Weight Efficacy Lifestyle (WEL) Questionnaire92 which 
assesses one’s confidence in their ability to avoid overeating when faced with certain situations. Self-efficacy 
for PA will be assessed by the Self-Efficacy for Exercise Scale93 which evaluates an individual’s confidence 
to exercise when faced with a variety of barriers such as fatigue or a lack of time. 
 

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• Motivation will be assessed using the Treatment Self-Regulation Questionnaire for Weight Management94 
which assesses the degree to which an individual’s motivation for weight management behaviors is relatively 
autonomous or self-determined.   
 
Other weight-related factors: Self-compassion will be assessed using the Self-Compassion Scale which 
assesses the degree to which an individuals acts towards themselves when experiencing a difficult time. 
Perceived stress will be measured via the Perceived Stress Scale, which assesses the degree to which 
situations in one’s life are appraised as stressful. Restrained and disinhibited eating will be assessed using the 
Three-Factor Eating Questionnaire which measures three dimensions of eating behavior. Reasons why 
behaviors are engaged in to manage weight will be evaluated by the Reasons for Weight Management 
Questionnaire. Weight bias and weight stigma will be assessed using the Weight Bias Internalization Scale and 
Weight Stigma Questionnaire respectively. Important weight-control behaviors will be assessed using the 
Weight Control Strategies Questionnaire which consists of 4 subscales: dietary choices, self-monitoring 
strategies, physical activity, and psychological coping.  Weight loss goals will be evaluated using the Goals and 
Relative Weights Questionnaire and realistic weight loss will be evaluated using the Realistic Weight Loss 
Questionnaire. The Paffenbarger Activity Questionnaire (PAQ) will be used to assess leisure time physical 
activity and provides an estimate of minutes and calories expended per week in overall leisure time activity and 
in activities of light (5 kcal/min), medium (7.5 kcal/min), and high (10 kcal/min) intensity. All active participants 
will also be asked to complete a one-time questionnaire related to how their lives and weight loss efforts have 
been affected by the coronavirus. This questionnaire will be completed online by the participant using Redcap.  
 
Participants will receive $50 for completion of the 4 month assessment and $75 for completion of the 12 month 
assessment.  Cash will be distributed at an in-person visit, however, if those visits cannot occur participants 
can choose to either have a check mailed directly to them or have an amazon gift card emailed to them.   
 
Cost and cost-effectiveness analysis. This study seeks to inform future WL dissemination efforts into 
healthcare and community settings; thus in addition to examining differences in WL between the 3 early non-
responder treatment groups, it is also critical to evaluate the effectiveness of PC from a cost-perspective. All 
participants enrolled in this study will receive an identical IDWL and WL maintenance program. Once 
developed the cost of this automated program is minimal and the cost of implementing this program remains 
fixed, regardless of the number of individuals enrolled. Therefore, the current analyses focus on the absolute 
and relative costs of ‘Brief’ and ‘Extended’ PC for early non-responders, compared to ‘Control’ (no coaching).  
 
The cost-effectiveness of adding PC for early non-responders enrolled in IDWL treatment will be 
assessed from both an organizational perspective (as this will drive adoption and impact potential scalability) 
and a societal perspective95.The incremental cost-effectiveness ratio, defined as the difference in cost between 
the interventions, divided by the difference in their effect on WL, will be the primary cost-effectiveness outcome 
for this trial. This represents the average incremental cost associated with each additional kilogram lost in 
‘Brief’, ‘Extended’, and ‘Control’. We will also assess whether this cost differs by the degree of initial WL (e.g., 
4-wk WL <2% vs. 2-4%), as it is possible that the cost-benefit of the different doses of coaching are dependent 
upon the magnitude of weight lost within the first 4 weeks of treatment. Costs will reflect the full costs of 
implementation (including training costs) and delivery of the proposed PC intervention. This includes overhead 
costs, such as office space for coaches and access to telephone lines, and interventionist costs which take into 
account the cost of interventionist training, intervention preparation, scheduling, and the completion of phone 
calls. Interventionist time will be valued using payroll records. Participant costs (used only in the analyses 
which assess cost from a ‘societal’ perspective) equal the value of time spent on the phone calls. Time will be 
measured by the interventionist and valued at the median wage. In addition to calculating the cost/kg of WL, 
we will also assess the absolute cost of the PC (i.e., total cost to implement and deliver the intervention) and 
the cost of the coaching per participant for ‘Brief’ and ‘Extended’ treatment groups.  
 
 
Treatment fidelity. To ensure that the intervention is delivered as designed, phone coaches will adhere to 
treatment manuals and Drs Unick (PI) and Pellegrini (Co-I) will train the coaching staff. All PC sessions will be 
audio-recorded and 10% will be randomly selected and reviewed by a Dr. Pellegrini and her staff at the 
University of South Carolina using a session-specific fidelity checklist. Fidelity checks will occur on a quarterly 

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basis. Fidelity checks will ensure good coaching practices and intended session content (e.g., meal planning, 
SMART goals). Further, the length of all PC sessions will be recorded to ensure that the amount of contact 
time is within the guidelines. If at any time fidelity is <85%, coaches will be retrained via videoconference by 
Dr. Pellegrini. 
 
Data collection and management.  All assessment data will be entered into the data management program 
by a member of the research staff. Range checks will be built into the data entry procedure to alert staff to data 
that requires additional clarification. Dr. Unick will conduct error checking and preliminary analyses of all data 
to ensure accuracy. Questionnaire data will be collected using REDCap (Research Electronic Data Capture), 
which is a secure, web-based application designed to support data capture for research studies and is hosted 
by Lifespan. It provides an intuitive interface for validated data entry, audit trails for tracking data manipulation 
and export procedures, and automated export procedures for seamless data downloads to common statistical 
packages. Only IRB approved research staff will have access to the REDCap platform and staff members will 
be granted access through a secure login provided by the study PI. Finally, Mr. Daniello (WL Application 
Programmer) will be responsible for preparing and maintaining the electronic data collection and storage 
system of all intervention data.  
 
Statistical Analysis, Sample Size, and Power Estimation.  With a sample size of n=450, the proposed study 
is fully powered to detect between group differences in both primary and secondary weight outcomes (e.g. % 
WL and % achieving clinically significant WL). Further, we have >70% power for all secondary aims. Full 
details regarding the power analysis, statistical approach, and methods for handling missing data can be found 
in the Statistical Design and Power Section (Clinical Trials 4.4). Dr. Dunsiger, the study biostatistician will 
provide guidance and oversee all aspects of data analysis plan. 
 
STATISTICAL DESIGN AND POWER  
Sample Size Considerations  
The proposed study is fully powered for the Primary Aim which includes both primary and secondary weight 
outcomes (e.g. % WL and % achieving clinically significant WL). Consistent with expert opinion103,104, we 
integrated several sources of evidence to determine an expected effect size for the proposed study. Our goal 
was to be powered for both treatment effects among the aggregate sample of participants (all randomized 
participants), as well as among early non-responders only. Based upon unpublished data from our IDWL 
programs, we anticipate 75% of participants will be early non-responders. These data suggest a mean WL of 
3.7% (SD=3.8%) among early non-responders, and our pilot data11 suggest brief coaching among early non-
responders will correspond to an additional 2% WL (or mean of 5.7% WL). Further greater contact time is 
associated with greater WL40-45, thus we anticipate the Extended PC will result in an additional 2% WL among 
early non-responders (mean 7.7%). Similarly, for the aggregate sample (all randomized participants) we expect 
weight losses of 4.7% (Control), 6.2% (Brief), and 7.7% (Extended) at 4 months. These estimates are based 
upon our previous data suggesting that 25% of participants will be initial responders, and that mean WL among 
this subgroup will be 7.7%. Given the above estimates and a two-sided alpha=0.05, we would need N=360 
participants (120/group) to have 80% power to test the primary aim among both the aggregate sample and 
early non-responders only.  However, given the known risks of powering on pilot data, as well as the longer 
follow-up than our pilot work, we have chosen to inflate the proposed sample size to N=450 (150/arm). With 
the increased sample size of N=450, we have 80% power to detect a 1.8% WL difference between treatment 
groups for early non-responders only, and 1.25% WL for the aggregate sample. Although our goal was to 
power for the primary study aim, a sample size of 450 also allows us to be reasonably powered for secondary 
aims (>70% for all secondary aims, assuming small-medium effect sizes, f 2=0.08). Our exploratory aims are 
considered hypothesis generating, rather than hypothesis testing, and thus we do not present a priori power 
analysis. Inference in this aim will be based on the estimation of effect sizes and 95% confidence intervals 
Data Analysis 
As a preliminary step, demographics, baseline measurements (weight, height, BMI), physical activity, diet, and 
psychosocial measures will be summarized across the aggregate sample and compared between groups using 

8 
 
Analysis of Variance (ANOVA) for continuous variables, chi-squared analyses for categorical variables and 
non-parametric tests as appropriate. Any variables not balanced between randomization will be considered 
potential confounders in the subsequent models if these variables are correlated with the outcome under 
consideration (at a modest p<.30 level). The distribution of each of the primary and secondary study outcomes 
will be assessed using both parametric and graphical methods and transformed as necessary (e.g. Log 
transform towards normality). Potential distributions for the outcome variables include normal and binomial, 
and zero-inflated distributions. As a subsequent step, we will assess potential between-group differences in 
baseline variables between ‘initial responders’ and ‘early non-responders’ using the same approach as 
described above.  
        Primary Aim 1: We will compare treatment effects with respect to the primary outcome (% weight change 
from baseline) using a longitudinal mixed effects regression model. The model will simultaneously regress 
percent weight change at 4 and 12-month follow-up on treatment group, time, treatment x time and potential 
confounders of the treatment effect. Models will include a subject-specific intercept to adjust for repeated 
measurements within participant over time. Modeling is done using a likelihood-based approach and thus 
makes use of all available data without directly imputing missing outcomes, to produce consistent estimates of 
the regression parameters. Specification of contrasts for the treatment effect makes it possible to make all 2-
way comparisons between treatment groups using a single model (e.g., Extended vs. Brief, Extended vs. 
Control, Brief vs. Control).  Mixed models are flexible in that they allow for a wide range of specifications of the 
time effect (linear, non-linear) as well as distributions of the outcome (e.g., normal).  Next, using a longitudinal 
regression model implemented with generalized estimating equations (GEE) with robust standard errors, we 
will examine treatment differences in clinically significant WL (≥5% WL)105,106. Specifically, we will regress 
indicators of clinically significant WL at 4 and 12-month follow-ups on treatment, time, treatment x time and 
potential covariates (e.g., variables not balanced by randomization) using binomial errors, a logit link function, 
and a working unstructured correlation to accommodate within-subject correlation. Finally, using a similar 
modeling approach to that above, we will examine treatment effects among the subset of early non-responders 
only. 
 
Secondary Aim 1: We will estimate the incremental cost/kg WL in Brief and Extended, relative to 
Control. Costs will be compared using graphical methods, ANOVA and non-parametric methods as 
appropriate.        
Secondary Aim 2: We will examine intervention effects on engagement (e.g., diet quality, physical 
activity, self-monitoring, video lessons viewed) and test whether engagement mediates effects of treatment on 
WL outcomes.  First, using a series of mixed effects regression models, we will regress engagement over time 
on treatment group, time, treatment x time and potential confounders of the treatment effect.   Models will be 
run separately for each of the engagement outcomes.  Next. we will use a multiple mediation approach, in 
which all potential mediators (e.g., diet quality, physical activity, self-monitoring, video lessons viewed)  are 
tested simultaneously using a product of coefficients method 107 with bootstrapped standard errors (5000 
samples with replacement). We will estimate the path coefficients (a path: effects of treatment on changes in 
mediators over time and b path: effects of changes in the mediators on WL over time, controlling for baseline), 
as well as the indirect effect of treatment (ab path: effect of treatment on WL through the mediators). Models 
will be run separately for each of the primary and secondary WL outcomes.  
It should be noted that Secondary Aims 1 and 2 will be analyzed first among the aggregate sample, and 
then among early non-responders only. 
 
Secondary Aim 3: We will examine whether early non-responder status is a moderator of the 
treatment effect on WL outcomes using a similar analytic approach as that described for Primary Aim 1. 
Specifically, models for the primary and secondary WL outcomes will include main effects of treatment, time, 
potential moderator, as well as all two- and three-way interactions between these variables.  Non-responder 
status will be considered a moderator if the treatment x moderator effect is significantly different than zero.  
Models for the primary WL outcome (percent weight loss) will be run using a mixed effects regression model 
and for the secondary weight outcome (% achieving a clinically significant WL) a GEE will be used.  We will 
examine the moderating role of non-responder status both continuously (% WL at 4 weeks) and categorically 
(e.g., <2% vs. 2-4%).  
         Exploratory Aim: Analysis will be conducted among early non-responders only.  First, we will explore 
mechanisms through which PC may affect engagement and WL, including perceived support, self-efficacy and 

9 
 
intrinsic/extrinsic motivation.  First, we will consider potential mediators of PC effects on engagement, including 
self-efficacy and perceived support.  We will use a similar approach to that described in Secondary Aim 3 in 
which a series of multiple mediators models implemented with a product of coefficients approach with 
bootstrapped standard errors (one for each engagement outcome) will be explored in order to generate effect 
estimates for the path coefficients (a, b and indirect effect ab) and associated 95% CI’s.  We will then explore 
whether these same constructs (support, self-efficacy and motivation) are potential mediators of WL outcomes.  
Our goal is not to conduct formal mediator models but rather to estimate effects to generate hypotheses in 
support of (or against) the conceptual model (Figure 1).   
Next, we will explore additional potential moderators of the treatment effect (e.g. sex, race/ethnicity, 
self-efficacy, motivation) using a similar analytic approach as that described for Secondary Aim 2. Specifically, 
models for the primary and secondary WL outcomes will include main effects of treatment, time, potential 
moderator, as well as all two- and three-way interactions between these variables.  A variable will be 
considered a moderator if the treatment x moderator effect is significantly different than zero.  Models for the 
primary WL outcome (percent weight loss) will be run using a mixed effects regression model and for the 
secondary weight outcome (% achieving a clinically significant WL) a GEE will be used. 
         
        Missing data. Analyses will be on the intent-to-treat sample (everyone randomized will be included in the 
final analysis) under various assumptions about the missing data mechanism, apart from early non-responder 
analyses which will include only those participants who were able to be classified as initial responders or early 
non-responders at 4 weeks, which will not use an intent-to-treat approach (see Approach C.6). Sensitivity to 
these assumptions will be tested. Specifically, we will gather follow-up information and reasons for dropout 
regardless of protocol completion and censor at the point of loss. We will compare the robustness of our 
findings using two statistical approaches for handling missing data. First, we will use inverse probability 
weighting with propensity scores. This is a two-step method: 1) using logistic regression, the probability of 
missingness is modeled as a function of baseline covariates and baseline values of the outcome and 2) the 
inverse of the propensity scores (predicted probabilities of dropout from the first step) serve as weights in our 
regression model of the outcomes. Provided the data are missing at random (MAR) or that the probability of 
missingness can be fully explained by observable data, this approach produces asymptotically unbiased 
estimates. To allow for the possibility that the MAR assumption may not hold, we will also use a second 
approach, pattern mixture models, in which the distribution of the outcome is assumed to follow a mixture of 
two distributions: one for those who complete follow up and another for those who do not.     
 
PROTECTION OF HUMAN SUBJECTS 
 
1. Risks to Subjects  
 
Human Subject Involvement and Characteristics: Participants in this study will be a sample of 450 men and 
women, aged 18-70 years, with a body mass index (BMI) of 25-45 kg/m2, with regular Internet access. The 
lower age limit of 18 was selected to exclude children, given that children benefit from different types of dietary 
and physical activity interventions, particularly those with greater parental involvement. The upper age limit of 
70 was chosen because older adults have more medical co-morbidities and may require more medical 
supervision. Given that weight loss (WL) is recommended for those who are overweight or obese, 25 kg/m2 
was selected as the lower end of the BMI range since this is the threshold used to classify overweight. An 
upper BMI range of 45 kg/m2 was included, as individuals with a BMI >45 have additional medical co-
morbidities and may require more intensive weight loss programs or bariatric surgery. Participants must have 
regular (i.e., daily) Internet access (defined as owning a smartphone with Internet capabilities, and/or having a 
broadband or wi-fi connection at home or work) to be eligible for this study. However, according to recent Pew 
Research data, 88% of Americans use the Internet and this percentage is upwards of 98% among individuals 
≤49 years of age. Further, Internet usage was found to be similar across racial categories (Caucasian: 88%, 
Hispanic 88%, Black 85%) and 73% of adults have high-speed broadband service at home. Therefore, it is 
likely that very few individuals will be excluded from this study due to a lack of regular Internet access.  
 

10 
 
Listed below are additional exclusionary criteria. These inclusion/exclusion criteria were developed to ensure 
participant safety and limit the number of individuals who would be excluded for obesity-related medical 
conditions or comorbidities. Given that dissemination of this program is a broader goal of this study, we also 
wanted to ensure that the study sample was more inclusive and representative of the overweight and obese 
population. To ensure safety, individuals with a history of heart disease, diabetes, or cancer, will be required to 
provide physician consent prior to enrolling. 
 
Exclusionary criteria: 
1) Currently pregnant, <6 months post-partum, nursing, or planning to become pregnant within the next 12 
months.  
2) Current enrollment in a commercial WL program or other WL research study 
3) Currently taking WL medications or previously had bariatric surgery 
4) Inability to walk 2 blocks without stopping 
5) Any medical condition for which WL, dietary restriction, or physical activity is contraindicated 
 
Sources of Research Material: Data will be obtained specifically for research purposes via direct 
measurement and questionnaires. Height and weight will be directly measured, physical activity will be 
objectively-assessed using the Actigraph GT9X Link accelerometer, and demographic information, health 
history, and dietary and weight control practices will be assessed via questionnaire. Further, intervention 
adherence data, the number of phone coaching calls completed, the length of each phone call, and 
interventionist time will be obtained directly from the intervention platform and database. 
 
Potential Risks: The risks associated with this study are quite minimal. The intervention instructs participants 
to engage in moderate-intensity exercise which gradually progresses to 250 minutes/week. Although safety 
precautions will be taken (e.g., gradual exercise progression, information on exercise safety is provided), it is 
possible that an individual could experience some muscle soreness or an injury as a result of the exercise. 
Further, the risk of a sudden cardiac event occurring during exercise is very minimal and is estimated to be 
approximately 1 per every 36.5 million hours of moderate-to-vigorous exertion.  In addition, participants will be 
instructed to reduce calorie intake by 500 to 1000 calories per day. It is possible that participants may engage 
in unhealthy dietary practices, but this is not likely and precautions will be taken to minimize this risk. Finally, 
there is the risk that the participant will not lose weight as a result of this program. However, this is a potential 
risk for any weight loss program or treatment. 
 
2. Adequacy of Protection Against Risks 
 
Recruitment and Informed Consent: Participants will be recruited through advertisements in local 
newspapers, direct mailings, Internet postings, and through business and community contacts. Interested 
individuals will respond to study advertisements by calling the Weight Control and Diabetes Research Center 
(WCDRC) or by going to the study website. An overview of the study will be described either via text on the 
study website, or verbally via the phone and interested individuals will be screened for eligibility. Eligible 
participants will then be scheduled for an orientation session either in-person, via phone or video conferencing 
where the study will be explained in greater detail. Individuals interested in the study will sign the informed 
consent document approved by the Miriam Hospital’s Institutional Review Board either in-person or 
electronically via Redcap . 
 
Protection Against Risk: To minimize risk, participants will be initially screened for any health conditions that 
would limit participation in a weight loss program and physician consent will be required for individuals with a 
history of diabetes, cancer, or heart disease. Further, as part of the initial intervention session, participants will 
be advised about safe weight loss practices. A rate of weight loss of 1-2 pounds per week is recommended 
and has been shown in other studies to be a safe rate of weight loss. Moreover, participants will have their 
weight objectively-assessed at baseline, 4, and 12 month assessment visits. If the rate of WL is too severe, or 
if the participant reports unsafe weight control practices at these visits, the Principal Investigator will discuss 
these issues with the participant. Further, as a safety precaution, gradual progression of exercise will be 

11 
 
prescribed within the intervention. Finally, protection against the risk of a breach of confidentiality will be 
minimized through careful adherence to best practices for data collection and management. Dr. Unick and staff 
at the WCDRC have extensive history conducting clinical trials and management of identifiable data from 
participants randomized to a weight management program.  
 
3. Potential Benefits of the Proposed Research to Subjects and Others 
 
Participants will receive a behavioral weight loss intervention which teaches healthy eating and exer cise 
behaviors. This has the potential to result in clinically significant weight losses and improvements in various 
health outcomes. Thus, while the potential risks of this study are quite minimal, the potential benefits are quite 
significant.   
 
4. Importance of Knowledge to be Gained 
 
Effective weight loss programs are critical for combatting the current obesity epidemic. This study is significant 
because it seeks to develop and evaluate a weight loss program, tailored to non-responders, which can be 
delivered entirely remotely; thus having great dissemination potential. Findings for this study could have 
important implications for obesity treatment.  
 
5. Educational Training of Staff 
 
All investigators and staff will be required to obtain education regarding the protection of volunteers in research 
from their own institution. The Miriam Hospital follows this plan:  
In June, 2005, the Office of Research Administration contracted with CITI, a Collaborative Institutional 
(modular) Training Initiative program, for our Human Subjects protection and HIPAA training for all research 
personnel. Currently this program offers our researchers a basic human subject's protection course as well as 
a refresher course which we require every three years. Documentation of successful completion is 
automatically generated and should be printed directly by the researcher. For further inf ormation regarding 
Lifespan’s Human Subject’s Protection: http://www.lifespan.org/research/IRB/MandatoryEdguidance.asp  
Additional and continuing education opportunities for clinical researchers include the Office of Research 
Administration newsletter that is circulated to > 900 recipients every 6 weeks. Relevant information concerning 
research review is available on the ORA web page at www2.lifespan.org/research/. In addition to standard 
institutional research information, the web page contains links to other sites such as CenterWatch, NIH, 
PRIM&R/ARENA. 
DATA SAFETY MONITORING PLAN 
 
The purpose of this study is to examine whether the addition of phone coaching (PC) for early non-responders 
enrolled in an Internet-delivered weight loss (IDWL) program improves treatment outcomes. Participants in this 
study will be asked to decrease their calorie intake and increase their physical activity to reduce body weight. 
Healthy weight loss practices will be recommended using previously tested diet and exercise prescriptions 
which have been shown to be safe. Thus, the focus of the Data Safety Monitoring Plan (DSMP) will be on 
monitoring the progress of the study (this includes recruitment, data collection, data management/quality 
control, adverse events, etc.) and reporting any concerns to the IRB and NIH study sponsor. The timing, 
frequency of reporting, and frequency of review are outlined below.  
 
Monitoring 
Reporting Frequency 
Frequency of Review 
Subject Enrollment 
Monthly by Dr. Unick 
Bi-annually to Independent Safety Officer 
IRB Compliance 
Annually by Dr. Unick 
Annually to Independent Safety Officer 
and NIH 
Adverse Events 
Continuously (see below) 
Bi-annually to Independent Safety Officer 
and annually to IRB and NIH 

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Quality Control 
As needed by Dr. Unick 
Annually to NIH 
 
Independent Safety Officer 
Dr. Amy Gorin has agreed to serve as the Safety Officer for this trial. She is a Professor in the Department of 
Psychological Sciences at the University of Connecticut and is nationally recognized for her work in the area of 
behavioral weight control. She has been the PI or Co-I on numerous NIH-funded grants; thus Dr. Gorin is well 
qualified to monitor the progress and safety of this trial.  
 
As indicated in the above table, our proposed DSMP will require frequent reporting to the Safety Officer and 
NIH study sponsor, and both parties will review and approve this protocol prior to the start of the trial. Dr. Gorin 
will be provided with study progress reports in 6 month intervals. These reports will include information on 
recruitment, rate of subject enrollment, efforts to recruit minority participants, participant retention, 
demographic characteristics of study participants, reasons for dropout, and adverse events. After reviewing 
these data, Dr. Gorin will indicate to Dr. Unick and NIH whether the study is progressing appropriately or 
whether changes are needed. At any point during the trial the Safety Officer can recommend that a phone call 
be held to discuss any issues with the progress or safety of the trial.  
 
Adverse Events and Serious Adverse Events 
An adverse event is defined as any untoward or unfavorable medical occurrence in a human subject, including 
any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, 
temporally associated with the subject’s participation in the research, whether or not considered related to the 
subject’s participation in the research. At each assessment visit, participants will be queried regarding any 
adverse events using an Adverse Events Form. In addition, information about adverse events may be reported 
by the participant on a coaching call. All interventionists will be trained to identify adverse events and to report 
any AEs to Dr. Unick using an Interim Adverse Event Form. All AEs will be reported to the IRB, NIH, and 
Safety Officer as indicated above. The IRB at The Miriam Hospital is a fully authorized Institutional Review 
Board that provides oversight to research conducted at The Miriam Hospital, Rhode Island Hospital, and 
affiliated Brown Medical School. It functions in compliance with the congressional statutes governing 
Assurance of Compliance with Health and Human Services (HHS) Regulations for Protection of Human 
Research Subjects. This board will be providing oversight to the proposed study.  
 
Serious adverse events (SAEs) are defined as any adverse event that meets any of the following criteria: fatal 
or life-threatening, result in significant or persistent disability, require or prolong hospitalization, result in a 
congenital anomaly/birth defect, or are important medical events that investigators judge to represent 
significant hazards or harm to research subjects. Any adverse event that meets any of these criteria will be 
documented as an SAE and an SAE form will be completed by the study investigators. Serious adverse events 
will be reported to the NIH and The Miriam Hospital’s IRB within 24 hours of knowledge of the event.  
 
Participant Confidentiality.  Participant confidentiality is of utmost importance for this study and guidelines 
outlined by our IRB will be followed. Participant data confidentiality will be protected through a multi-tiered 
approach including data collection, data handling, and data distribution processes to ensure anonymity both 
during and after the study. Participant information collected by the research staff will contain only a non -
identifiable study ID. A separate form linking study ID and participant identifiers (name, address, contact 
names and addresses) will be maintained in a locked file.  
 
Quality Control. All staff involved in data collection will be trained by the investigators and must demonstrate 
competence in administering all measures.  The research assistant will review all assessment data for 
accuracy and completion.  The investigators will conduct error checking and preliminary analyses of all data to 
ensure accuracy.  Hard copies of data will be stored in a locked filing cabinet and electronic data file will be 
password protected and backed up.