Remote Monitoring of Symptoms and Cognitive Function Using Telehealth
Phase: NA
Conditions: End Stage Liver Disease
Sponsor: Albert Einstein Healthcare Network

V Navarro/ M Verma                                                                                                                               1 
 
I. Research Project Title, Purpose, Anticipated Project Duration and Inclusion of Proprietary Information 
Protocol Version: May 8 2017 
Investigators: Victor Navarro, Manisha Verma, Richard Kalman 
Title:   
Remote monitoring of symptoms and cognitive function using Telehealth: T- Liver project 
 
Purpose:  
End-Stage Liver Disease (ESLD) is one of the ten leading causes of death in US. It is marked by 
episodic acute exacerbations of the underlying liver disease which often leads to severe 
symptoms, poor quality of life, mental deterioration and repeated hospitalizations.  The overall 
purpose of this project is to introduce a telehealth based intervention (involving remote 
monitoring of symptoms and cognitive function assessment) initiated during the time of hospital 
admission of ESLD patients. This will support enhanced clinical care and improve self-
management in ESLD population. In addition, it will reduce healthcare utilization, improve 
medication adherence and overall health outcomes.    
 
 
II. Research Project Overview  
 
The primary goal is to develop and implement a systematic clinical approach for remote 
monitoring of symptoms and cognitive function in ESLD patients, through developing a 
telehealth based intervention. The intervention includes assembling specific apps on an 
ipad/smartphone/tablet through a web based secured system, having patients respond to periodic 
assessments and transmission of results instantly to providers, who will follow specified clinical 
pathways stratified by severity scores.  
 
Methods:  This is a single arm study to assess the effectiveness of an experimental telehealth 
intervention within the treatment of ESLD, and compare it with a historic cohort.  All inpatients 
with advanced liver diseaseand at least 1 complication will be eligible to participate. the study 
group receives the Telehealth intervention and will be given an ipad/smartphone preloaded with 
the instruments used for symptom monitoring and cognitive function assessment during the 
hospital admission. A research coordinator will consent the patients and conduct a 30-minute 
introduction to use of device on the day of enrollment (within 24-48 hours of admission). The 
second assessment will be done on day 2, and third assessment on day of discharge. After that, 
the patient will be told to do the study assessments daily at home.  The study assessment results 
will be reviewed by the providers on the same day, and based on the severity scores clinical 
actions will be taken and documented.  
 
IV. Expected Research Outcomes and Benefits - 
Primary Outcomes:   
1) Healthcare utilization (30 and 90-day readmission) 
2) Changes in severity scores of symptoms and quality of life over time. 

V Navarro/ M Verma                                                                                                                               2 
 
3) Patient experience/satisfaction.  
Benefits of the research: Applying telehealth intervention (inclusive of remote monitoring of 
symptoms and cognitive function) with a well-defined clinical algorithm at the time of discharge 
of patients with ESLD, who are prone to impaired quality of life, adds a new dimension to the 
care delivery model. This new post-hospital discharge algorithm is expected to have positive 
effects on many parameters, including readmission rates, patient satisfaction, and above all on 
the health outcomes.  Arguably, these improvements will reduce health care costs among a group 
of patients with ESLD, who are high utilizers of healthcare services. Benefits to individual 
patients include monitoring of their own symptoms, and cognitive function, which will allow 
early detection of hepatic encephalopathy and/or other complications. 
 
VII. Evaluation Component and Research Evaluative Procedures - Oversight and Statistical Tests  
 
Oversight: The PI will be overseeing the implementation of the project along with the Co-
Investigator. Since the study involves patients who are admitted to the hospital, and offers them a 
device to improve their own care, the likelihood of participation is high. We will assess the 
attrition rates and other technical issues during the project. Higher rates of no response to timed 
assessments from enrolled patients will trigger an alert to the research coordinator, who will then 
call the patients to make sure device is working appropriately and explore the reasons for 
missing responses. Furthermore, a detailed discussion at the time of enrollment about the project 
and expected responsibilities from patients will reduce the missing data points.  
 
Statistical Tests: The data for study group will be described using both graphic and summary 
statistics. Process data on participation, usage and satisfaction with telehealth intervention will be 
collected and summarized to assess intervention fidelity. We will assess the change in percent 
readmissions at 30 days and 90 days in the study groupfrom baseline to 3 months.  The average 
rate of change in the defined outcomes in longitudinal (overtime) analyses using paired t tests 
and 95%CIs of the differences in the two groups will be conducted. The trajectories of symptom 
and quality of life scores will be illustrated by graphing individual patient values over time 
course of the study for the intervention group. We will test whether the relationship between 
study outcome and study arm differ with the severity of disease as assessed by MELD (Model 
for End Stage Liver Disease) score using two-way analysis of variance for repeated measures. 
 
 
 
(B) Performance Measures  
B) Performance measures: 
 
1) Number of patients enrolled in the study. 
2) Completion of 7, 28 days and 3 months assessment of symptoms and cognitive function by 
the patients. 

V Navarro/ M Verma                                                                                                                               3 
 
3) Attrition rates of enrolled patients. 
4) Efficiency of the technical device provided to patients as assessed from ease of use by 
patients and providers.  
5) Scholarly activities (publications and presentations) resulting from study data. 
 
VIII. Health Disparities  
This project will target the patient population at Einstein, which is largely underserved, and 
minority. No racial/ethnic or gender group will be excluded from the proposed study. 
Furthermore as the study involves providing an ipad/smartphone to patients, it eliminates any 
existing disparity of access for anyone who participates.  
 
XI. Research Plan  
(1) Specific Aims  
 
The specific aims are: 
1. To develop and implement a systematic clinical approach for remote monitoring of 
symptoms and cognitive function in ESLD patients, through assembling specific apps on 
an ipad/smartphone using web based cloud technology (referred to as telehealth 
intervention). 
2. To evaluate the impact of our telehealth intervention on health care utilization (30/90 day 
readmissions) 
3. To assess prospectively the comparative efficacy of telehealth intervention within the 
treatment of ESLD, in improving i) symptom scores, ii) patient reported quality of life, 
and iii) satisfaction with device and questionnaire. We hypothesize that Telehealth 
intervention will show improvement in these domainsover time [a 10% improvement in 
scores from baseline to 3 months will be considered clinically significant]  
 
 
(2) Background and Significance  
 
End-Stage Liver Disease (ESLD) is one of the ten leading causes of death in US. i 
Hospitalization rates due to ESLD and its complications have skyrocketed by 93% (due to 
hepatorenal syndrome), 62% (due to portal hypertension), and 190% due to Hepatitis C and its 
complications from 2004-05 to 2010-11.ii   Developing interventions which can potentially 
reduce readmissions and healthcare utilization are a national priority according to the Affordable 
Care Act.iii  Telehealth offers a unique platform to remotely monitor individual patients and 
offer enhanced care at the time of need, and has shown success in congestive heart failure, lung 
disease and diabetes.iv  There is no research demonstrating its utilization or efficacy for liver 
disease patients. Hence, we propose to develop and test the effectiveness of a T-Liver 
intervention to remotely monitor the symptoms  (pain, shortness of breath) weight, temperature, 
and cognitive function (using symptom questions and a stroop test) to reduce healthcare 
utilization,  improve patient satisfaction and health outcomes.  
 

V Navarro/ M Verma                                                                                                                               4 
 
“HGE healthcare solutions” is a group of experts who have pioneered some work in telehealth, 
and created a smartphone based COPD app (Chronic Obstructive Pulmonary Disease), which 
assesses daily symptoms and triggers alerts to providers for immediate treatments. This app has 
shown to improve health outcomes and reduce hospitalizations by changing the approach of 
health care to proactive than reactive. v  vi We will be partnering with this company in creating 
and delivering our telehealth intervention. The company operates on a HIPAA secured platform, 
which maintains confidentiality and security of the data. They also offer technical assistance to 
end users during normal business hours.  
 
 
(3) Research Design, Methods and Activities -  
 
Methods:  This is a single arm trial to assess the effectiveness of an experimental telehealth 
intervention within the treatment of ESLD, and compare it with a historic control.  The study 
patients continue to receive the routine standard of care, which may involve addressing 
symptoms based on individual needs and circumstances. All participants will be given an 
ipad/smartphone preloaded with the instruments used for symptom monitoring and cognitive 
function assessment. A research coordinator will consent the patients and conduct a 30-minute 
introduction to use of device on the day of enrollment. Repeat assessments will be done as 
shown in Table 1 above. All patients will receive the standard of care discharge planning, 
including discharge instructions and a confirmed follow-up ambulatory visit within 2-4 weeks.  
Inclusion Criteria: All patients being discharged from the inpatient liver practice of the Einstein 
Healthcare Network (EHN) who meet the following criteria will be eligible. 
 Patients must be age 18 years or older 
 Ability to provide informed consent, and must be able to cognitively answer 
questionnaires  
 Patients who received a diagnosis of Advanced Liver Disease with at least 1 of the 
complications (Hepatorenal Syndrome, Portal Hypertension, Ascites, Hepatic 
Encephalopathy)  
 Patient must be able to read/ speak English 
 Patient must have a support person 
 
Exclusion Criteria:  
 Cognitive impairment which precludes participation 
 Projected survival, in the opinion of the provider, of less than six months 
 Current psychosis or confusion, precluding a patient from being consented 
 Patients being discharged to nursing homes 
 Patients with red green color blindness (as they will not be able to respond to stroop test 
questions). 
 
Telehealth Intervention: 
Patients will receive a 30-minute introduction to the use of ipad/smartphone, and instructions to 
respond to the following assessments. Initial assessments will be performed on the day of 
enrollment, and all of them will be repeated periodically (Table 1), for a total of 3 months study 

V Navarro/ M Verma                                                                                                                               5 
 
participation. The assessments include the following:  Pain (severity, location), shortness of 
breath (at rest or with mild activity), cognitive function assessment (drowsy, hard time 
concentrating, irritable, trouble remembering things, slurred speech, unsteady gait), and stroop 
test (color matching test, one cycle lasts 45 seconds).  
 
 
Weight monitoring: Monitoring weight will allow assessment of fluid retention in ESLD 
patients, and help detect any development/ worsening of ascites.  Patients will be instructed to 
enter their daily weights for the first month, and then every week for next 2 months. Any weight 
gain of more than 2 lbs within 1-2 days for 3 consecutive days will trigger a phone call by the 
providers.  
 
A simplified step by step guide summarizing the instructions will be included with the device. 
Patients will be given a toll-free number that will be available during work hours (9am to 5pm) 
for any technical issues, and will be urged to complete assessments by 11 am on a daily basis.  
 
Site: Levy 7 is the home of the “Liver Care Center at Einstein”, a 15 bed inpatient unit dedicated 
to the care of patients with liver disease.  This inpatient unit is the site of identification and 
recruitment of patients in this project.  
 
Recruitment methods: The research coordinator will contact eligible patients within 24-48 
hours of admission and conduct informed consent. All patients who consent will be then 
randomized to either of the 2 groups. We assume 3-4 patients will be enrolled per week, for 7 
months of enrollment period.  
 
Sample size and power: Assuming a baseline risk of readmission in the historic control of 40% 
and 10% attrition rates, a sample size of 50 patients will be sufficient to detect a difference of 
35% or greater in the intervention group. Accepting a type I error rate of no more than .05, and a 
Type II error rate of .20, we will have 80% statistical power to detect a difference of this 
magnitude or larger.   
Retention strategies: Patients will be informed about the purpose of the study and their 
responsibilities at the time of consent by the research coordinator. All patients with a support 
person will be eligible. Strategies (i.e. education about value of study participation) will be added 
if recruitment rates fall within 20% of target. 
Analysis plan:  Medical records will be utilized to capture the disease severity, diagnosis, 
duration of liver disease and presence of comorbidities. Patients enrolled into the study will be 
followed up for 6 months. Descriptive and analytics statistics will be done using linear 
correlation and regression.  We will compare the clinical markers at baseline with 3 month value 
using unpaired t test..  . 
 
 
Limitations:  

V Navarro/ M Verma                                                                                                                               6 
 
Patient Attrition: this is an anticipated problem, as physical and cognitive deterioration may 
make the completion of questionnaires difficult. This limitation will be minimized by the short 
interval assessments and completion of study at 3 months.  
 
 
 
 
(4) Protection of Human Subjects -  
 
  
(a) Risks to subjects:  There is no medical risk to any participant and no sharing of 
protected health information in this project. It is completely up to the participants to 
agree for this study. Refusal for participation will not impact their health care in the 
office. There are minimal risks to participants related to their completion of survey 
questionnaires. There may be some emotional distress as they complete the symptom 
and quality of life questions, but this will influence and enhance their own care. 
Patients may have technical difficulties, which will be addressed through availability 
of a help desk and the research coordinator during work hours. 
(b) Adequacy of protection against risks:  There are no known risks in this study. All 
study personnel have completed the IRB required CITI training, and will be trained 
appropriately. Confidentiality is maintained through Einstein’s secured system and 
the secure administration through HGE. The PI and Co-Investigator will be available 
to answer any of the patient’s concerns. The research coordinator will conduct an in-
depth informed consent explaining the purpose of the project, and the expectations 
from patients to respond to the assessments in a timely way. All the information 
collected is through a secured password protected system, which allows encrypted 
data transmission to the providers 
(c) Recruitment of subjects:  All patients discharged from the Inpatient liver unit who 
meet the eligibility criteria will be approached for consent. Once the patients agree to 
participate, the details of the study and device operations will be discussed. If the 
patient needs more time to decide, we will allow them to take the information home 
and get back to the research coordinator within 1-2 days.  
(d) Informed consent:  An in-depth informed consent will be conducted in person using 
paper version. The IRB approval will be attached.  
(e) Data confidentiality and provision of medical or professional intervention, if needed:  
Einstein Healthcare Network’s Human Research Protection Program (HRPP) is a 
comprehensive system to ensure the protection of the rights and welfare of subjects in 
Human Research. It is comprised of the EHN leadership, Office of Research and 
Technology Development (ORTD), Institutional Review Board (IRB), investigators 
and their study staff and relevant departments and units. The HRPP not only promotes 
compliance with relevant laws, regulations and professional and ethical standards at 
all levels, it addresses the needs and concerns of researchers and enhances support of 
their endeavors. The HGE has a secured system through which the patients will 

V Navarro/ M Verma                                                                                                                               7 
 
complete the study assessments and communicate with providers. All data collected 
will be completely confidential, and will not be shared with anyone outside of this 
project. 
(f) Potential benefits of the research to subjects:  Since this study involves close 
monitoring of symptoms and development of any hepatic encephalopathy, it will 
enhance patient centered care through timely management of symptoms, and early 
detection of complications of ESLD.   
(g) Importance of knowledge to be gained:  The knowledge gained from this project 
will enable the use of technology in care of liver disease patients in a meaningful 
way, and allow early detection of symptoms/ problems which will trigger clinical 
actions as needed and thereby make the approach to care more proactive than 
reactive. This will potentially engage patients in their own care, and improve the 
healthcare service delivery model for ESLD.  
 
(h) Inclusion of women, children and minorities in the research:   All eligible candidates 
more than 18 years of age are included in this study, irrespective of any specific race / 
sex, etc.  
 
Data Safety Monitoring Plan: During this study medical history and other lab values will be 
assessed at baseline, 4 weeks and 3 months from the medical records. Only the study personnel 
will have access to this information, and is not shared with any third party including the HGE 
company. All the data collected is for research purposes only. The data will be saved in a 
password protected format within Einstein’s secured network drive. The PI and Co-Investigator 
will review the data on an ongoing basis for data completeness and accuracy including patient 
accrual, compliance with inclusion/ exclusion criteria, patient adherence to intervention. Study 
progress and safety will be reviewed monthly.  
 
 
 
 
 
 
 
REFERENCES 
                                                             
i Lim, Y. S., & Kim, W. R. (2008). The global impact of hepatic fibrosis and end-stage liver 
disease. Clinics in liver disease, 12(4), 733-746. 
ii Xu, F., Tong, X., & Leidner, A. J. (2014). Hospitalizations and costs associated with hepatitis C and 
advanced liver disease continue to increase. Health Affairs, 33(10), 1728-1735. 

V Navarro/ M Verma                                                                                                                               8 
 
                                                                                                                                                                                                    
iii  Pub. L. 111-148: Patient Protection and Affordable Care Act. Washington, DC: Government Printing 
Office. http://www.gpo.gov/fdsys/pkg/PLAW-111publ148/content-detail.html 
iv Darkins, A., Ryan, P., Kobb, R., Foster, L., Edmonson, E., Wakefield, B., & Lancaster, A. E. (2008). 
Care Coordination/Home Telehealth: the systematic implementation of health informatics, home 
telehealth, and disease management to support the care of veteran patients with chronic 
conditions.Telemedicine and e-Health, 14(10), 1118-1126. 
v Cordova, F. C., Ciccolella, D., Grabianowski, C., Gaughan, J., Brennan, K., Goldstein, F., ... & Criner, 
G. J. (2015). A Telemedicine-Based Intervention Reduces the Frequency and Severity of COPD 
Exacerbation Symptoms: A Randomized, Controlled Trial. Telemedicine and e-Health. 
vi Smith, H. S., Criner, A. J., Fehrle, D., Grabianowski, C. L., Jacobs, M. R., & Criner, G. J. (2015). Use 
of a SmartPhone/Tablet-Based Bidirectional Telemedicine Disease Management Program Facilitates 
Early Detection and Treatment of COPD Exacerbation Symptoms. Telemedicine and e-Health.