A Pilot Study of mDOT for Immunosuppressant Adherence in Solid Organ Transplant Recipients
Phase: NA
Conditions: Medication Adherence, Liver Transplantation, Kidney Transplantation
Sponsor: Johns Hopkins University

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A Pilot Study of mDOT for Immunosuppressant Adherence in Solid Organ 
Transplant Recipients 
Version 1.0 
Principal Investigator: 
 Dr. Douglas Mogul, MD, PhD. 
Johns Hopkins University 
Supported by: 
The National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK) 
NCT04587024

 
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TABLE OF CONTENTS 
Page 
TABLE OF CONTENTS ............................................................................................................. 2 
STUDY TEAM ROSTER........................................................................................................... 4 
PARTICIPATING STUDY SITES ............................................................................................ 4 
SYNOPSIS .................................................................................................................................. 4 
1. STUDY OBJECTIVES ............................................................................................................. 6 
1.1 
Primary Objective ........................................................................................................... 6 
1.2 
Secondary Objectives...................................................................................................... 6 
2. BACKGROUND AND RATIONALE .................................................................................... 6 
3. STUDY DESIGN ....................................................................................................................... 7 
4. SELECTION AND ENROLLMENT OF PARTICIPANTS ................................................ 8 
4.1 
Inclusion Criteria ............................................................................................................ 8 
4.2 
Exclusion Criteria ........................................................................................................... 8 
4.3 
Study Enrollment Procedures ......................................................................................... 8 
5. STUDY PROCEDURES .......................................................................................................... 9 
5.1 
Schedule of Evaluations ................................................................................................ 10 
5.2 
Description of Evaluations ............................................................................................ 11 
5.2.1 Enrollment, Baseline, and Randomization................................................................ 11 
5.2.2 Blinding..................................................................................................................... 12 
5.2.3 Follow-up Visits........................................................................................................ 12 
6. RISKS AND BENEFITS ........................................................................................................ 12 
6.1 
Risks .............................................................................................................................. 12 
6.2 
Benefits ......................................................................................................................... 13 
6.3 
Renumeration ................................................................................................................ 13 
6.4 
Costs .............................................................................................................................. 13 
7. SAFETY ASSESSMENTS ..................................................................................................... 13 
8. INTERVENTION DISCONTINUATION ........................................................................... 13 
9. STATISTICAL CONSIDERATIONS .................................................................................. 13 
10. DATA COLLECTION AND QUALITY ASSURANCE .................................................. 14 

 
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10.1 
Data Collection Forms .................................................................................................. 14 
10.2 
Coordinating Center Functions and Multi-site Study Plan ........................................... 15 
10.2.1 
Responsibilities ..................................................................................................... 15 
10.2.2 
IRB Document Management ................................................................................ 15 
10.2.3 
Screening and Enrollment Tracking ..................................................................... 15 
10.2.4 
Data Safety and Monitoring Plan .......................................................................... 15 
10.2.5 
Identifying Enrolling Sites .................................................................................... 16 
10.3  Data Management and Monitoring ............................................................................... 17 
10.3.1 
Source Documents ................................................................................................ 17 
10.3.2 
Data Management Plan ......................................................................................... 17 
10.3.3 
Data Capture Methods .......................................................................................... 17 
10.3.4 
Participant Confidentiality, Security and Storage ................................................. 17 
11. REFERENCES ...................................................................................................................... 18 
 

 
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STUDY TEAM ROSTER  
 
Lead Site: 
 
Johns Hopkins University 
 
Dorry Segev, MD, PhD 
 
dorry@jhmi.edu 
Dr. Douglas Mogul, MD, PhD 
dmogul1@jhmi.edu 
 
Macey Henderson, JD, PhD  
macey@jhmi.edu 
 
 
PARTICIPATING STUDY SITES 
 
Johns Hopkins University 
 
Douglas Mogul, MD, PhD, Principal Investigator 
 
Phone: 410-955-8769 
 
Email: dmogul1@jhmi.edu 
 
 
University of Miami 
Tamir Miloh, MD, Principal Investigator 
Phone: 305-355-5760 
Email: txm760@med.miami.edu 
 
 
University of Virginia 
 
Kenneth Brayman, MD, Principal Investigator 
Phone: 434-924-9370 
Email: klb9r@virginia.edu 
 
SYNOPSIS  
Study Aims:  
Primary Objective: To compare medication adherence of solid organ transplant 
recipients, specifically liver and kidney transplants, using the mobile DOT (mDOT) 
application (i.e., intervention) to those who did not use the mDOT application (i.e., 
control). We will compare medication adherence between intervention and control arms 
using the Medication Level Variability Index (MLVI), a validated measure of adherence 
derived from the standard deviation of measured drug levels (22-23).   
 
Secondary objectives:  
• Clinical endpoints including rejection and hospitalization 
• Patient reported adherence on immunosuppressant therapy instrument (ITAS) 
• Patient-reported QoL outcomes as measured by PedsQL and SF-36 
• Patient-reported self-efficacy using the Riekert Self-efficacy scale  
• Patient-reported usability using the PSSUQ (treatment arm only) 
• To examine the patterns of medication adherence in  transplant recipients in both 
groups to better understand baseline medication adherence 
• To understand the feasibility and acceptability of implementing such a system into the 
clinical workflow and patient follow-up care management 
 
Design and Outcomes: 

 
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In this multi-center study, patients >/= 13 years of age who receive a liver or kidney 
transplant at Johns Hopkins Hospital, University of Virginia Medical Center or 
University of Miami Medical Center will be recruited to participate in this randomized 
control trial (RCT).  
 
There will be 2 arms participants may be randomly assigned to: intervention and control 
arms. Participants in the intervention arm will receive the mDOT application, and 
participants in the control arm will not. Both arms will still receive standard of care post-
transplant.  
 
We will use block randomization to assign participants to the intervention or the control 
group using random block sizes ranging from 2 to 8. Block randomization will improve 
the probability of balanced groups over the course of the study as well as during shorter 
time horizons. A research data analyst, blind to the group allocations, will generate a list 
of sequential group assignments using this method. The list will be used to create 
sequentially numbered, sealed envelopes that will be used to allocate consenting 
participants to the control or intervention arms of our study. Each patient will have a 50% 
chance to be in the intervention arm of the study. 
 
Interventions and Duration: 
Participants will be enrolled in the study for 12 months.  All subjects will complete study 
assessments and have immunosuppressant levels and clinical outcomes followed for 12 
months.  This subjects randomized to the intervention group will use the app for the first 
3 months following enrollment.  Subjects randomized to the control group will not use 
the app and will follow routine standard of care. 
  
No study visits are required of research participants after enrollment, but they will 
complete surveys and an interview over the phone.  
 
Procedure 
Baseline 3 months 6 months 9 months 
12 months 
Baseline clinical/demographic/lab 
info/baseline survey 
X 
 
 
 
 
Immunosuppression levels and laboratory 
values collected from medical record 
X 
X 
X 
X 
X 
Interval health information collected 
 
X 
X 
X 
X 
Patient-reported outcomes* 
X 
X 
 
 
X 
Phone Interview 
 
 
 
 
X 
*these include ITAS, PedsQL <18 years at enrollment or SF-36 if >18 years at enrollment, Reikert self-
efficacy scale, PSSUQ (treatment arm only and only at 3 months) 
Sample Size and Population:  
Participant enrollment will continue until we have reached 25 participants in each arm by 
age (13-21 years and 22 years and older) for a total of 100 participants. We will follow all 
study participants for 12 months.  

 
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1. STUDY OBJECTIVES 
1.1 
Primary Objective 
To compare medication adherence of solid organ transplant recipients, specifically 
liver and kidney transplants, using the mobile DOT (mDOT) application (i.e., 
intervention) to those who did not use the mDOT application (i.e., control). We will 
compare medication adherence between intervention and control arms using the 
Medication Level Variability Index (MLVI), a validated measure of adherence 
derived from the standard deviation of measured drug levels (22-23).   
 
1.2 
Secondary Objectives 
• Clinical endpoints including rejection and hospitalization 
• Patient reported adherence on immunosuppressant therapy instrument (ITAS) 
• Patient-reported QoL outcomes as measured by PedsQL and SF-36 
• Patient-reported self-efficacy using the Riekert Self-efficacy scale  
• Patient-reported usability using the PSSUQ (treatment arm only) 
• To examine the patterns of medication adherence in  transplant recipients in both 
groups to better understand baseline medication adherence 
• To understand the feasibility and acceptability of implementing such a system 
into the clinical workflow and patient follow-up care management 
2. BACKGROUND AND RATIONALE 
In adolescent and adult solid organ transplant recipients, poor adherence to 
immunosuppressant medications carries the risk of graft rejection, short- and long-term 
post-transplant complications, and increased healthcare costs (1-8). In transplant 
recipients, adherence to immunosuppressive drugs, as well as general medical indications 
is imperative to overall outcomes (9). The rate of non-adherence to immunosuppressive 
medications in transplant patients varies vastly, with reports ranging from 15-40% in 
adults and much higher at 50-70% among adolescents (9-14). Additionally, medication 
adherence is a key concern in the transition from adolescent to adult-centered transplant 
care, and transition planning should be prioritized in these transplant patients (15-18). 
Because of lacking objective and accurate non-adherence measurements, both to 
immunosuppressive drugs and medical indications, the true implications and prevalence 
of non-adherence is not yet well understood (19-21). Therefore, we believe that mobile 
health (mHealth) technology has the potential to allow clinicians and researchers to more 
comprehensively address and understand non-adherence in adolescent and adult 
transplant recipients.  
 
emocha Mobile Health Inc. has developed an application that enables users to track dose-
by-dose medication adherence through asynchronous, video directly observed therapy 
(DOT). This helps patients take their medication as prescribed and gives providers the 
assurance that their patients are supported and successful in treatment. DOT is the 
practice of watching a patient take every dose of medicine in-person, and has typically 
only been done in extreme cases because it can be both costly and burdensome: DOT is 
the standard of care for Tuberculosis treatment and has proven high-adherence rates. 
Through mHealth technology, DOT can be used more broadly and without added burden; 
emocha’s technology allows this through enabling patients to use their mobile application 

 
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to view their regimen, record themselves taking every dose of their medication, report 
side effects or symptoms, visualize their treatment progress, and access educational 
content. This information is encrypted and transmitted to a HIPAA-secure web portal for 
providers to review. The aim of this study is to conduct a randomized control trial to 
compare medication adherence between patients who use the mHealth system against 
controls who do not.  
 
emocha has formally evaluated their mDOT platform across several disease states: 
tuberculosis, Hepatitis C virus, and opioid use disorder. The U.S. Centers for Disease 
Control and Prevention (CDC) recognizes emocha’s video modality as an acceptable 
form of DOT, according to their latest guidelines (24).  To date, emocha has partnered 
with Johns Hopkins and three Maryland health department tuberculosis programs to 
assess quantitative, qualitative, and cost outcomes associated with emocha video DOT 
implementation. Among all participants – with more than 1,400 videos submitted thus far 
– mean patient adherence was 94 percent (median adherence 96 percent, interquartile 
range 93 to 100 percent). Similar adherence rates were proven in independent studies 
using emocha performed by Harris County, TX and the Puerto Rico Department of 
Health. Additionally, emocha is conducting a trial on the feasibility of video DOT for 
patients undergoing the initiation phase of buprenorphine treatment through office-based 
opioid treatment programs, as well as conducting ongoing research on Hepatitis C 
medication adherence among injection drug users.  
3. STUDY DESIGN 
The purpose of this study is to understand how the use of an mHealth application, 
mDOT, changes medication adherence behaviors among liver or kidney transplant 
recipients. For the purpose of this research, the mobile app is a device of non-significant 
risk and exempt from the IDE requirement. emocha Mobile Health is the device 
manufacturer.  
 
In this multi-center study, patients >/= 13 years of age who receive a liver or kidney 
transplant at Johns Hopkins Hospital, University of Virginia Medical Center or 
University of Miami Medical Center will be recruited to participate in this randomized 
control trial (RCT). There will be 2 arms participants may be randomly assigned to: 
intervention and control arms. Participants in the intervention arm will receive the mDOT 
application, and participants in the control arm will not. Both arms will still receive 
standard of care post-transplant.  
 
Participants are followed for their compliance with standard of care recommendations. 
No additional care or procedures will be administered to study participants. Given the 
uncertainty in whether this mHealth intervention will improve rates of 
immunosuppression medication adherence in liver and kidney transplant recipients, a 
non-treatment group is necessary in order to identify whether an advantage exists.  
 
 

 
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4. SELECTION AND ENROLLMENT OF PARTICIPANTS  
4.1 
Inclusion Criteria 
Participants must meet all of the following inclusion criteria to participate in this 
study: 
• 
> 13 years old 
• 
Own a smartphone and are willing to receive information through it 
• 
Received a liver or kidney transplant at a participating study site during or 
prior to the study period. 
4.2 
Exclusion Criteria 
All candidates meeting any of the following exclusion criteria at baseline will be 
excluded from study participation:   
• Patients with cognitive impairments will not be eligible for enrollment due to 
inability to provide informed consent. 
• 
Inability or unwillingness of individual or legal guardian/representative to 
give consent.  
4.3 
Study Enrollment Procedures  
Participants will be approached by the following methods: 
For subjects ages 13-21 years old: either while they are an inpatient post-transplant or 
at any follow-up outpatient clinic visit by a study member to participate in this study.  
For subjects >21 years old: either while they are an inpatient post-transplant or at 
their first post-op outpatient clinic visit by a study team member to participate in this 
study. 
 
For all subjects:  
When feasible to conduct in-person consenting, written consent will be obtained 
explaining the purpose of the study, their part in it, and that they can withdraw from 
the study at any time. As much time as necessary will be allowed for obtaining 
consent. Assent will be obtained from participants age 13-17 years, along with 
parental consent. 
 
Additionally, we will make provisions for phone consent and enrollment if needed 
due to potential COVID-19 restrictions so that enrollment may proceed according to 
plan.   If unable to conduct in-person consenting and enrollment process, patients will 
be contacted by phone and the study team will conduct the appropriate oral 
consent/assent procedures and conduct the procedures listed below remotely. 
 
We will use block randomization to assign participants to the intervention or the 
control group using random block sizes ranging from 2 to 8. Block randomization 
will improve the probability of balanced groups over the course of the study as well 
as during shorter time horizons. A research data analyst, blind to the group 
allocations, will generate a list of sequential group assignments using this method. 
The list will be used to create sequentially numbered, sealed envelopes that will be 
used to allocate consenting participants to the control or intervention arms of our 
study. Each patient will have a 50% chance to be in the intervention arm of the study. 

 
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Participant enrollment will continue until we have reached 25 participants in each arm 
by age (13-21 years and 22 years and older) for a total of 100 participants and we will 
follow study participants for 12 months. No study visits are required of research 
participants after enrollment, but they will complete surveys and an interview over 
the phone.  
 
 
5. STUDY PROCEDURES  

 
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5.1 
Schedule of Evaluations 
Procedure 
Baseline 
3 months 
6 months 
9 months 
12 months 
Informed Consent 
X 
 
 
 
 
Randomization  
X 
 
 
 
 
Baseline clinical/demographic/lab info/baseline 
survey 
X 
 
 
 
 
Immunosuppression levels and laboratory values 
collected from medical record 
X 
X 
X 
X 
X 
Interval health information collected 
 
X 
X 
X 
X 
Patient-reported outcomes* 
X 
X 
 
 
X 
Phone Interview 
 
 
 
 
X 
*these include ITAS, PedsQL <18 years at enrollment or SF-36 if >18 years at enrollment, Reikert self-efficacy scale, PSSUQ (treatment 
arm only and only at 3 months) 

 
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5.2 
Description of Evaluations  
5.2.1 
Enrollment, Baseline, and Randomization  
Consenting Procedure: 
For all subjects:  
When feasible to conduct in-person consenting, written consent will be obtained 
explaining the purpose of the study, their part in it, and that they can withdraw from 
the study at any time. As much time as necessary will be allowed for obtaining 
consent. Assent will be obtained from participants age 13-17 years, along with 
parental consent. 
 
Additionally, we will make provisions for phone consent and enrollment if needed 
due to potential COVID-19 restrictions so that enrollment may proceed according to 
plan.   If unable to conduct in-person consenting and enrollment process, patients will 
be contacted by phone and the study team will conduct the appropriate oral 
consent/assent procedures and conduct the procedures listed below remotely. 
 
Enrollment and Baseline Assessments: 
Once consent and, when applicable, assent is obtained, participants will complete a 
baseline survey containing questions about basic demographic, health, and 
smartphone usage information. After completing the baseline survey, subjects will be 
randomized into either the control or intervention arm. Study personnel will assist 
participants assigned to the mHealth intervention (mDOT) with downloading the 
mDOT application and explain its functioning. Patients will be strongly discouraged 
from discussing which treatment they are receiving with their clinical team.  
 
In regard to using the mDOT app, a designated study team member will enter the 
medications prescribed and times to take the medications into the app for each 
participant in the intervention arm. As a second check, another member of the study 
team will ensure that medications entered into the app are consistent with what is in 
the patient’s EHR to reduce the risk of transcription error. The app will then remind 
participants when it is time to take their medication, and what to take. Participants 
will then take a video of themselves taking the prescribed immunosuppression 
medications. A designated study team member will then review the uploaded videos 
and either accept or reject them in regard to adherence. Participants can view their 
progress, adherence, and what days they are expected to take their medications in a 
calendar-like view.  
 
Randomization: 
We will use block randomization to assign participants to the intervention or the 
control group using random block sizes ranging from 2 to 8. Block randomization 
will improve the probability of balanced groups over the course of the study as well 
as during shorter time horizons. A research data analyst, blind to the group 
allocations, will generate a list of sequential group assignments using this method. 
The list will be used to create sequentially numbered, sealed envelopes that will be 
used to allocate consenting participants to the control or intervention arms of our 
study. Each patient will have a 50% chance to be in the intervention arm of the study. 
 

 
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5.2.2 
Blinding 
Research team members responsible for enrollment and reviewing emocha app 
submissions will not be masked to who is in the intervention or control arm. Patients 
will be aware of which arm they are randomized to as well. In this sense, the study 
will not be blinded to patients. Furthermore, patients/families will be strongly 
discouraged from discussing with their clinical team to which treatment arm they are 
enrolled. Data extraction (labs, drug levels) will be performed by study personnel that 
are blinded to the treatment arm. Individuals performing data analysis will receive de-
identified data that does not explicitly describe which group is intervention and which 
is control, but simply the code without a key. Only the PI at each site and necessary 
personnel performing data extraction will have the key for the code to minimize bias 
in data analysis. 
 
5.2.3 
Follow-up Visits 
After enrollment in the study, we will measure medication adherence in both arms at 
3 month intervals for 12 months. MLVI, the standard deviation of recorded drug 
levels, will be calculated for each subject.  Medication adherence will be ascertained 
through electronic health record (EHR) review of immunosuppression levels (i.e. 
tacrolimus, sirolimus, cyclosporine, prednisone, mycophenolate). Organ transplant 
recipients get labs post-transplant drawn frequently.  Included in these lab draws are 
immunosuppression levels. A significant change in trough levels (i.e. undetectable or 
supra therapeutic) signal an issue of adherence to the prescribed regimen (i.e. missing 
doses, taking extra doses, etc.). We will track lab values using EHR, and record these 
in the secure REDCap database.  
 
Participants in both arms will complete the immunosuppressant therapy instrument 
(ITAS), a validated tool to measure medication adherence at baseline for those 
subjects who have been on immunosuppressant therapy for at least 3 months at time 
of enrollment, at 12 weeks post enrollment for all subjects, and at 12 months post 
enrollment. Scores on the ITAS scale range from 0 (very poor adherence) to 12 
(perfect adherence), and scores will be compared between the control and 
intervention arms (25). Participants will complete age appropriate QOLs at matching 
intervals to the ITAS.  Follow-up questionnaires will be completed by phone with a 
designated study team member. Indicate treatment and followup visit assessments for 
each visit. List all measurements and procedures in bulleted format.  
 
6. RISKS AND BENEFITS 
6.1 
Risks 
The only risk to participants in using this mHealth application is the loss of 
confidentiality, which will be kept to a minimum. This application will comply with 
HIPAA regulations on how to handle PHI, including but not limited to secure 
encryption of data, access controls, and industry-standard best practices. All 
information gathered will be de-identified and only linked through a study-specific 
identification number.  
 
All study data except identifying information will be entered into a central access 
database (REDCap). These data will be accessible by only authorized study personnel 

 
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from the secure study database. User level authentication will be required to gain 
access to the REDCap account. A separate access database will be created which has 
patient identifiable information along with a unique identifier. All specific 
assessments will have labels (individual study ID number) affixed to them and the 
results will remain strictly confidential. Risks to confidentiality will be minimized by 
separating identifiers from the results of the questionnaires. 
6.2 
Benefits 
Participants may or may not benefit directly from participation in this study. 
Participation in the study could help providers, transplant centers, and liver transplant 
recipients in the future from the information gathered in this study. 
6.3 
Renumeration 
Subject will receive $100 after completion of participation. 
6.4 
Costs 
There is no cost to patients for participating in this study. 
7. SAFETY ASSESSMENTS  
This is a minimal risk study. However, there is a slight risk of loss of confidentiality. To 
minimize this risk, hard copies of all study materials, including consent forms, will be 
stored in locked cabinets that are only accessible to the study team. Electronic copies of 
all study materials will be kept on a secure, password-protected server that is only 
accessible to the study team. All study data except participants' identifying information 
will be entered into a central access database. These data will be accessible by only 
authorized study personnel from the secure study database. User level authentication will 
be required to gain access to the central database. A separate access database will be 
created which has patient identifiable information along with a unique identifier. All 
specific assessments will have labels (individual study ID number) affixed to them and 
the results will remain strictly confidential. Risks to participants' confidentiality will be 
minimized by separating identifiers from the results of the survey responses. 
8. INTERVENTION DISCONTINUATION  
Participants may withdraw from the study at any time without penalty. This would not 
preclude participants from obtaining regular medical care or follow-up care related to 
their transplant. If participants choose to withdraw, the study team will use the data 
collected prior to withdrawal and mark the remaining data as censored. 
Upon study completion or if study participation ends prematurely, those who were 
randomized to mDOT app will return to their usual standard of care.  Those who were 
randomized to standard of care will continue in that manner.   
 
9. STATISTICAL CONSIDERATIONS  
Primary outcome variables:  
12-week immunosuppression medication adherence:  
We will measure medication adherence in both arms at 12 weeks. The Medication 
Level Variability Index (MLVI) will be used to analyze immunosuppression lab 

 
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values to determine adherence with a relative risk noted for standard deviation >2. 
 
Secondary outcome variables: 
Hospitalization days 
Biopsy-proven rejection 
Clinician-assigned rejection 
 
We will recruit 100 liver and kidney transplant recipients (50/arm), and compare 
recipients who received the mHealth intervention to controls that did not receive it. 
The Medication Level Variability Index (MLVI) will be used to analyze 
immunosuppression lab values to determine adherence with a relative risk noted for 
standard deviation >2.  Descriptive statistics will be performed to compare 
frequencies of secondary outcomes (e.g., hospitalization, rejection, etc). Patient 
reported outcomes will be scored as appropriate and differences compared between 
treatment arms.  Additionally, we will perform subgroup analyses for younger 
transplant recipients (age at transplant <40), older transplant recipients, men, and 
women. 
 
In addition to understanding the efficacy of this technology in a transplant patient 
population, we will also evaluate the feasibility of implementing such a system into 
clinical workflow. We will examine time spent by reviewers each week using mDOT, 
most ideal time post-transplant to consent and educate participants on using the 
application, and streamlining the workflow involved in the application. In order to 
ensure acceptability among the patients who will be using the app, we will survey all 
participants in the intervention arm at the end of the study period on their overall 
satisfaction in using the app. This survey will be administered with the ITAS scale 
over the phone. In addition, we will also examine consent rate and use of the mDOT 
app by participants over time to understand acceptability of using the application. 
 
Feasibility will also be measured through phone interviews with all study participants 
at 12 months. We will contact all patients who consented to be in the study to 
participate in the phone interviews. The interviews will be semi-structured, with a set 
of pre-written questions as the guide. All interviews will be audio recorded. 
Transcription of the interviews will be conducted by Production Transcripts, Inc. 
 
10. DATA COLLECTION AND QUALITY ASSURANCE 
10.1 
Data Collection Forms  
All study data except identifying information will be entered into a central access 
database (REDCap). These data will be accessible by only authorized study personnel 
from the secure study database. User level authentication will be required to gain 
access to the REDCap account. A separate access database will be created which has 
patient identifiable information along with a unique identifier. All specific 
assessments will have labels (individual study ID number) affixed to them and the 
results will remain strictly confidential. Risks to confidentiality will be minimized by 
separating identifiers from the results of the questionnaires. 

 
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10.2 
Coordinating Center Functions and Multi-site Study Plan 
10.2.1 Responsibilities 
A Clinical Coordinating Center (CCC) will be responsible for overall recruitment and 
retention, data management, monitoring and communication among the enrolling 
sites, and the general oversight of the conduct of this human subject research project. 
The CCC for this trial is the Epidemiology Research Group in Organ Transplantation, 
located at 2000 E. Monument Street, Baltimore, MD 21202.  
   
10.2.2 IRB Document Management 
There is a plan in place for reviewing site approval documents. An sIRB coordinator 
oversees the process of reviewing site approval documents and consent forms prior to 
sIRB review. The coordinator collaborates with the JHM IRB and conducts web calls 
with each enrolling site to promptly and adequately pre-review site documents prior 
to site-specific JHM IRB submissions. The sIRB specialists confirm that each 
participating site has on file an FWA with OHRP. Throughout the study, the sIRB 
specialists and CCC site managers will assure that all centers have the most current 
version of the protocol, which will be stored in the electronic trial management file 
(eTMF). Site managers will communicate protocol amendments to enrolling site PIs 
and lead study coordinators via receipt-confirmed email and telephone contact 
follow-up. 
 
10.2.3 Screening and Enrollment Tracking 
Recruitment and retention at the sites will be supported by a centrally managed 
electronic data collection (EDC) system in REDCap where data will be entered on 
every screening and enrollment, including inclusion and exclusion criteria met, and 
demographics needed for reporting. Enrollment reports will be generated monthly and 
reported annually as part of the renewal process. 
 
10.2.4 Data Safety and Monitoring Plan 
This is a minimal risk study. However, there is a slight risk of loss of confidentiality. 
To minimize this risk, hard copies of all study materials, including consent forms, 
will be stored in locked cabinets that are only accessible to the study team. Electronic 
copies of all study materials will be kept on a secure, password-protected server that 
is only accessible to the study team. All study data except participants' identifying 
information will be entered into a central access database. These data will be 
accessible by only authorized study personnel from the secure study database. User 
level authentication will be required to gain access to the central database. A separate 
access database will be created which has patient identifiable information along with 
a unique identifier. All specific assessments will have labels (individual study ID 
number) affixed to them and the results will remain strictly confidential. Risks to 
participants' confidentiality will be minimized by separating identifiers from the 
results of the survey responses.   
Although this study is deemed minimal risk, any unanticipated problems or study 
deviations will first be reported to the site investigator, study principal investigator 
and then the sIRB. 

 
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Events meeting the sIRB prompt reporting guidelines will be reported to the lead site 
IRB within 72 hours and will be reported to the relying IRBs per their guidelines.  
10.2.5 Identifying Enrolling Sites 
The lead study team will be responsible for notifying JHM IRB of sites added using 
the template below. Final approval will be withheld until the JHM IRB and the OHSR 
have all required documentation on file. The protocol will be amended, as a change in 
research if additional sites are added to the project. Johns Hopkins will be an 
enrolling site. If any problems arise with enrolling sites, IRB specialists will 
communicate with the site contact person named in the application, if necessary. 
  
Site 
Identification 
Template 
Site name and address 
PI name and contact (phone and email) 
Confirmation that the research can be conducted at that site, has an IRB, and 
that the IRB has completed its approval of the research 
Site FWA number 
An executed agreement to rely on the JHM IRB 
 
Participating Sites: 
1. Johns Hopkins University 
Department of Pediatric Gastroenterology, Hepatology and Nutrition 
600 N. Wolfe Street 
CMSC 2-116 
Baltimore, MD 21287 
PI: Douglas Mogul, MD, PhD 
Phone: 410-955-8769 
Email:  dmogul1@jhmi.edu 
 
2. University of Virginia 
 
 
Department of Surgery, Transplantation 
 
 
1300 Jefferson Park Ave. 
Fourth Floor 
Charlottesville, VA 22903 
 
 
PI: Kenneth Brayman, MD, PhD, FACS 
 
 
Phone: 434-924-9370 
 
 
Email: klb9r@virginia.edu 
 
3. University of Miami 
 
 
Department of Pediatric Transplant 
1801 NW 9th Ave 3rd Floor Miami, FL 33136 
PI: Tamir Miloh, MD 
Phone: 305-355-5760 
Email: txm760@med.miami.edu 
 

 
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10.3  Data Management and Monitoring 
10.3.1 
Source Documents 
Source documents for this study will include the subjects’ medical records and study 
record documents. If the investigators maintain separate research records, both the 
medical record and the research records will be considered the source documents for 
the purposes of auditing the study. The local site investigator will retain a copy of 
source documents. The local site investigator will permit monitoring and auditing of 
these data, and will allow the sponsor, IRB and regulatory authorities access to the 
original source documents. The local site investigator is responsible for ensuring that 
the data collected are complete, accurate, and recorded in a timely manner. Source 
documentation (the point of initial recording of information) should support the data 
collected and entered into the study database/case report form and must be signed and 
dated by the person recording and/or reviewing the data. All data submitted should be 
reviewed by the site investigator and signed as required with written or electronic 
signature, as appropriate. Data entered into the study database will be collected 
directly from subjects during study visits or will be abstracted from subjects’ medical 
records.  
 
10.3.2 Data Management Plan 
Study data will be collected at the study site(s) and entered into the study database. 
Data entry is to be completed on an ongoing basis during the study.  
 
10.3.3 Data Capture Methods 
Clinical data will be entered into a secure REDCap database. The data system 
includes password protection and internal quality checks to identify data that appear 
inconsistent, incomplete, or inaccurate. 
 
10.3.4 Participant Confidentiality, Security and Storage 
Coded identifiers, password-protected data files, and locked file cabinets kept in a 
secure building will be used to protect against breaches of confidentiality. 
emocha Mobile Health’s plan is to store the data for a minimum of 7 years according 
to HIPAA requirements, and provide Johns Hopkins with accessibility to the raw data 
submitted by participants in the intervention arm through the mDOT app and its audit 
logs. emocha only accesses the data on a need-to-know basis, in order to support any 
issues that may come up. All data access is logged and accessible to study 
administrators. All emocha applications comply with HIPAA regulations on how to 
handle protected health information, including but not limited to secure encryption of 
data, access controls, and industry-standard best practices. A robust role-based 
permission system limits system access to only authorized, authenticated users to 
ensure the need-to-know basis of PHI. All PHI is encrypted both in-flight and at-rest, 
and all access to, or modification of, patient data and system configuration is logged. 
The server infrastructure is secured from both physical and remote access. 
 
In-flight encryption refers to the encryption of all data while being transmitted. Data 
is sent over a secure HTTPS connection secured by a 2048-bit SSL certificate. The 
SSL configuration is audited regularly, ensuring that system configuration is as up-to-
date as possible. All connections between the database and application servers are 

 
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made over SSL/TLS, using the same 2048-bit certificate. At-rest encryption means 
that all PHI in the database and disk is always stored encrypted. This includes any 
record of a user, anything in the error log or audit log tables, and any patient data. The 
encryption scheme uses the Advanced Encryption Standard (AES) algorithm of at 
least 256 bits, with the ability to revoke and issue new keys as needed. Data being 
sent from mobile devices is encrypted on the device as soon as it has been collected. 
Data is then transmitted to the server over a secure HTTPS channel and deleted from 
the device as soon as receipt of the transmission is confirmed. Encryption/decryption 
keys are housed on a separate server and only accessible through a highly-restrictive 
API, which is not directly reachable from the database server. Keys are only stored in 
memory on the application server and never in permanent files written to a disk. 
Effectively, the database cannot decrypt its own data; even in the event of the server 
being compromised and a malicious party acquiring an export of the data, PHI will 
remain secure. 
 
Any viewing or modification of the system or patient data is logged in a persistent 
and unmodified database. Audit trail records include but are not limited to the action 
being taken, the date and time, and, in the case of modifications, both the old and new 
values. These logs are available to be searched with numerous sorting and filtering 
options on the administrative interface. In addition, nothing is ever deleted in the 
system; data is “soft-deleted” via marking with a flag that will hide the record during 
normal operations, but leave it easily recoverable if needed. 
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