Real World Observational Database for COVID-19 Treatment and Outcomes
Conditions: COVID-19
Sponsor: Hackensack Meridian Health

 
 
 
 
Real World   
 Observational Database  
for COVID-19  Treatment and Outcomes 
 
 
Principal 
Investigator: 
Andrew Ip MD 
Document type: 
Non-interventional study protocol 
Version number: 
05, Contains Amendment 4 
 
 
 
 
 
Release date: 
Amendment IV 
October 2-2020 
 
 
 
Confidential and Proprietary 
 
Not for Publication 
 
The information in this document contains information that are privileged or confidential and may not be 
disclosed unless such disclosure is required by federal or state law or regulations. In any event, persons to 
whom the information is disclosed must be informed that the information is privileged or confidential and 
may not be further disclosed by them. These restrictions on disclosure will apply equally to all future 
information supplied to you which is indicated as privileged or confidential.  

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Table of contents 
 
1 
Responsible Parties .............................................................................................................. 3 
2 
Brief Synopsis ..................................................................................................................... 4 
Amendments and Updates .......................................................................................................... 6 
3 
Rationale .............................................................................................................................. 7 
4 
Registry Objectives ............................................................................................................. 8 
5 
Research Methods ............................................................................................................... 8 
5.1 
Registry Design and Collection ............................................................................... 8 
5.2 
Analytic Design ....................................................................................................... 9 
5.3 
Registry Population ............................................................................................... 10 
5.4 
Site Responsibilities............................................................................................... 10 
5.5 
Registry Data Collection ........................................................................................ 10 
5.6 
Variables ................................................................................................................ 11 
5.7 
Data Analysis ........................................................................................................ 12 
5.8 
Quality Control ..................................................................................................... 12 
6 
Protection of Human Subjects ........................................................................................... 12 
7 
Disseminating and Communicating Registry Results ....................................................... 15 
8 
Data Ownership ................................................................................................................. 16 
9 
References ......................................................................................................................... 16 
 
 

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1 
Responsible Parties 
Table 1-1 
Main responsible parties 
 
 
 
Principal Investigator 
 
Andrew Ip MD 
John Theurer Cancer Center at Hackensack University Medical Center  
92 Second Street 
New Jersey, NJ 07601 
 
Principal Analytic Group 
 
 
 
 
 
Participating Centers 
 
COTA 
101 Arch Street, 15th Floor 
Boston, MA 02110 
Phone: (866) 648-3833 
 
 
Hackensack Meridian Health Network 
 
 
 

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2 
Brief Synopsis 
 
The principle objective of this observational database is to build research-grade real 
world data that will serve as platform to advance the scientific understanding and 
clinical care of patients with COVID-19.   
1. Demographic, diagnostic, treatment and outcome data from centers throughout the 
Hackensack Meridian Health Network will be abstracted from the electronic health 
records of patients with confirmed or suspected COVID-19.  This will be purely 
observational and no direction as to the care of the patient will be performed as part of 
this effort.  There will be no research intervention(s) with the exception of collection of 
data from subjects currently receiving treatment or will/ or have had treatment at 
Hackensack Meridian Health Network.  Data will be collected both retrospectively and 
prospectively.  
1a. Data points to be collected will include, but are not limited to: age, gender, zip code, 
prior evaluation for COVID-19, tobacco history, race, site of care, healthcare worker, 
nursing home care, visits to ER, presenting features of fever/ cough/ dyspnea/ 
gastrointestinal/ mental status changes, days of symptoms, comorbidities, uses of 
antihypertensives, duration of hospitalization/ ICU care, presenting laboratory 
functions, presenting vital signs, need for oxygen support, dialysis/ ecmo use, treatment 
with hydroxychloroquine/ azithromycin/ remdesevir/ tociluzimab/ anti-inflammatory 
agents, arrhythmias/ QTc prolongation, enrollment on clinical trial, positive cultures, 
survival and cause of death.  Additional data points may be added as needed however 
these points will only be collected related to their treatment and treatment related 
outcomes. 
2.  The data will be entered into a central HMH database hosted within the REDCap 
system (HIPAA compliant, secure)l) 
 
 

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3. A de-identified dataset will be sent to COTA for primary statistical analysis as 
requested by the research teams.  COTA will also make available a data/analytic 
visualization tool (hosted on Tableau) for analysis by primary investigators.  
4. De-identified data may also be sent directly to HMH investigators for their own 
analysis after appropriate Human Subject Protection Review. 
5. Data may be made available to governmental agencies as requested.  
 
 
 

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Amendments and Updates 
 
Amendment number: 04 
Date:   October 2, 2020 
 
 
Table 2-1 
Study protocol amendments and updates 
Number 
Date 
Section of 
study protocol 
Amendment or 
update 
Reason 
01             April 5, 2020 
Title Changed to 
capture RWD 
Outcomes for 
CoVID 
Population in 
HMHN. 
 
Protocol will now allow for 
RWD Outcomes.  This 
information will be utilized to 
determine best treatment 
options for CoVid 
Population. 
02 
April 23, 2020 
Section 7.3 
 
The HMH Biorepository 
(BioR) will be granted 
access to the database.  
03 
June 17, 2020 
Section 7.4 
 
The University of Miami will 
be granted access to only 
de-identified portions of the 
database. 
04 
August 20, 2020 
Section 7.3 
 
HMH Biorepository (BioR) 
collection clarification. 
05 
October 2, 2020 
Section 5.1 and 
7.3 
 
Adding BI as a source of 
data in addition to EPIC.  
 
 
 

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3 
Rationale  
3.1 Rationale for an Observational Database in COVID-19 
Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by SARS-CoV-
2 virus, a novel betacoronavirus discovered in Wuhan, China in December 2019. 
Subsequently, the disease has spread globally and outbreaks have been identified in over 
100 countries. In China, data extracted from medical records of 1099 hospitalized patients 
and outpatients with laboratory confirmed COVID-19, revealed a summary of clinical 
characteristics. The most common symptoms were fever (43% on admission and 88.7% 
during hospitalization), cough (67.8%) and diarrhea (3.8%). On admission, ground-glass 
opacity was the most common radiologist finding on CT scans (56.4%). According to 
another recent Chinese study evaluation of 72,314 cases, 80% of patients presented with 
mild disease and the overall case-fatality rate was about 2.3%. (1) 
A more complete understanding of the epidemiology,  presenting features, role of co-
morbidities in severity of illness, needs for and utilization of healthcare resources, 
effectiveness of therapeutic approaches including off-label use, and clinical outcomes is 
desperately needed.  Well-designed clinical trials, although helpful in gaining regulatory 
approval of new agents, enroll only a fraction of available patients and may not always 
mirror “real world” scenarios.  An outcome  atabase may be able to provide rapid 
indicators of effective strategies.  Collecting data from the electronic health records 
permits significantly detailed information to be analyzed while not interfering with the 
routine best medical care delivered by the treating physicians.    
 

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4 
Registry Objectives  
 
The principle objective of this Observation Outcomes Database is to build research-
grade real world data that will serve as a platform to advance the scientific 
understanding and clinical care of patients with COVID-19 in order to provide best 
clinical treatment options.   
 
4.1 Primary Objectives 
 
4.11 
Understand epidemiology including presenting features of the COVID-19 
 
 
pandemic within the Hackensack Meridian Network 
 
4.12  Explore the impact of co-morbidities and other patient factors on the  
 
 
severity of COVID-19  
 
4.13  Understand need for hospitalization, ICU support and other healthcare 
 
 
resources among patients with COVID-19 
 
4.14 
Explore efficacy and toxicity of various treatment strategies including “off-
 
 
label use” of medications in real world settings 
 
4.15  Measure clinical outcomes including hospital discharges and survival 
5 
Research Methods 
5.1 
Registry Design and Collection 
The Hackensack Meridian Health RWD Observational COVID-19, a descriptive 
observational database, is a multi-center initiative collecting data throughout the 
Hackensack Meridian Health Network (HMH).    
The database will be drawn from the electronic health records of patients with confirmed 
or suspected COVID-19.  HMH utilizes the EPIC system at most of the facilities, which will 
serve as the primary data source.  Additional data obtained via other HMH staff and 

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bioinformatics can be added to the database as available and permitted. This includes but 
is not limited to data obtained either directly from EPIC or provided by other sources such 
as the HMH Business Intelligence Office (BI) to facilitate data extraction. Reports provided 
by BI can be entered directly into the REDCap database or kept separately (as pre-data 
supplements that might be added at a later time).  
The database will be designed within the REDCap system.  REDCap is a secure web 
application for building and managing online surveys and databases. While REDCap can 
be used to collect virtually any type of data (including 21 CFR Part 11, FISMA, and HIPAA-
compliant environments), it is specifically geared to support online or offline data capture 
for research studies and operations.   
The REDCap hosted universal observational database can export HIPAA compliant files 
for external analysis as part of the secondary research usage clause defined by the OHRP.   
Data collection fields enumerating the common prognostic variables, treatment regimens 
and clinical outcomes have been designed by the principal investigator and the study team 
with input from the Centers of Disease Control and Prevention (CDC).   
The abstraction process into the database will be performed by members of HMH who are 
approved to have access to the EPIC system or provided by BI.   Outside abstraction, which 
would involve viewing of PHI, will not be permitted unless specifically granted by the IRB.  
5.2 
Analytic Design 
COTA, a data and analytic company headquartered in Boston MA, was founded by 
physicians at the John Theurer Cancer Center at Hackensack University Medical Center 
(an HMH site) in 2011.  The company is experienced in the handling of large observational 
databases.  Current shareholders of COTA include Hackensack Meridian Health and some 
of its physicians.  COTA currently has a business associate agreement with Hackensack 
University Medical Center and several additional HMH sites which would permit 
abstraction of PHI if required.    COTA will only receive de-identified data to perform 
secondary research analysis.  

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Governmental agency (including but not limited to the CDC and FDA) have been contacted 
about this observational database and will be given access to data as requested. 
5.3 
Registry Population 
 
5.31 Registry Population Inclusion Criteria 
 
5.311 Confirmed or suspected COVID-19  
 
5.312 Data available via the EPIC system 
 
5.313  NO age restriction  
 
5.314 NO pregnancy restrictions 
5.4 
 
 
Site Responsibilities  
5.41 
HMH  abstract of data from the EPIC system.  
5.42  
All eligible patients with COVID-19 will be included.  
 
5.5 
Registry Data Collection  
 
 
5.51 
Research personnel approved by HMH will extract and organize data from 
 
 
the electronic health  record into the database.   
 5.52 
Data will be entered into the REDCap approved database only.  All  
  
protected health information (PHI) will be handled to maintain HIPAA 
  
compliance.   The REDCap system will store PHI but this information will 
  
not be exported for any analysis unless specifically approved by the IRB. In  
the REDCap forms, all PHI will be parked as “identifiers” and only deidentified 
datasets will not be exported and shared with anyone but the study team.  
 
 
5.53 
Key prognostic diagnostic fields, demographics, treatments, and outcomes 
 
 
will be populated with data.  Structured and  
 
 
unstructured data in the patients’ electronic records will be reviewed to  
 
complete the population of the registry. The database however is not   

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intended to be an all-inclusive representation of the medical chart.  Daily  
 
laboratories of routine nature will not be collected.  
 
 
5.54 
Adverse events may be scored and recorded using the common toxicity 
 
 
criteria (CTC).  However, it will be the treating sites responsibility to  
 
 
report to the authorities/manufacturers any serious adverse events in 
 
 
accordance with standards of care for the institution and in compliance 
 
 
with local/national regulations.  
 
 
5.55 
This initiative is meant to be an observational database.  No additional 
 
 
testing or treatment will be required for enrollment of a patient.  All  
 
 
clinical care, including diagnostic and therapeutic decisions, will be at the 
 
 
sole discretion of the patient’s treatment team. 
5.6 
Variables 
Data points will be collected from the electronic medical record (or other HMH sources as 
available for patients with confirmed or suspected COVID-19.  A partial listing is detailed 
below: 
 
5.61 
Key demographic variables include age, gender, race,  zip code, past  
 
 
medical history documented co-morbidities, smoking history, etc.   
 
5.62 
Key diagnostic variables include date of diagnosis (COVID testing),  
 
  
blood count at time of hospitalization and/or entry to ICU care, chemistry 
 
 
panel,  ferritin, ddimer, c-reactive protein, IL-6 levels, etc.    
 
5.63 
Key therapeutic variables include use of hydroxycholaquine, azithromycin, 
 
 
ventilator support, dialysis support, pressor support, etc.  
 
5.64 
Key outcome variables include will include need for hospitalization,  
 
 
duration of hospitalization, need for icu/ventilator support, duration of icu 
 
 
support, and death. .  

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5.65 
Key treatment center variables include hospital type (academic/  
 
 
community), number of cases per hospital.  
Data Analysis 
 
 
5.71  COTA will provide basic descriptive analysis of the COVID-19 patients in a 
 
 
de-identified aggregated fashion.   Survival and healthcare utilization  
 
 
analysis with time variables will utilized censoring and the Kaplan-Meier 
 
 
methodology.  Multi-variable analysis for associations between  
 
 
demographic and/or treatment variables and key outcomes will be  
 
 
performed.  Additional analysis will be performed per review of the data.  
5.7 
Quality Control 
 
Unlike traditional data sources (ie, claims databases) the full medical record is analyzed 
by the abstractors allowing deep medical variables to be characterized.  The principal 
investigators and COTA will perform statistical reviews to uncover “obvious” 
inaccuracies.  However, the data will not undergo formal secondary reviews for accuracy.   
Investigators should understand the limitations of an observational database in drawing 
any conclusions.  
6 
Protection of Human Subjects 
 
This document is a study protocol for an observational database study. This study is to be 
conducted according to United States and international standards of Good Clinical 
Practice (CFR Title 21 parts 11, 50, 54, 56, 312, International Conference on 
Harmonization and the Declaration of Helsinki), applicable government regulations and 
Institutional research policies and procedures. 
 
 
 

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6.1 
Informed Consent 
The Principal Investigator believes that the elements for a full waiver of consent under 45 
C.F.R. §46.116 are met.  Specifically, in order to waive consent the following requirements 
must be met: 
(1) The research involves no more than minimal risk to the subjects; 
(2) The waiver or alteration will not adversely affect the rights and welfare of the subjects; 
(3) The research could not practicably be carried out without the waiver or alteration; as 
COVID-19 populations have  received treatment and have been discharged or deceased.    
The study protocol represents an observational review of patients with confirmed or 
suspected COVID-19. No interventions are required for enrollment of patients into this 
database.  There will be no direct contact any patient.  Protected health information (PHI) 
will not be made available (pursuant to the HIPAA Privacy Rule as described below) and 
only aggregate data will be disclosed.   The data collection will be conducted across HMH 
network drawing information from a variety of healthcare settings, with data drawn 
principally from the electronic health records utilized by the network.   It would not be 
practical (item 3) by the Investigators to obtain consent across the network (which 
includes multiple hospitals and clinics across the state) as no contact will occur between 
the study team and the potential subjects.  This is an observational study.  The subjects 
will be receiving standard of care therapy at multiple sites, with their consent for the care 
per usual practice, and will not be made aware of the collection of the data nor will their 
treating physicians as to keep the therapy unbiased by participation in this study.   
Furthermore, this study will involve only collection of data that has or will be obtained for 
care of the patient/subject.  Thus the study may be considered “secondary research” 
under the revised common rule that became effective January 2020.  Unlike the pre-2018 
rule exemption for secondary use of information and biospecimens, the Final Rule has no 
requirement that the information and biospecimens must be pre-existing at the time that 
the investigator begins the research; prospective collection is permitted. 

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Although the information will involve collection of the data from PHI and the REDCap 
database will need to have identifiers in place to permit data entry, the analysis will only 
be performed on de-identified datasets which will be exported to the research teams 
(COTA or other investigators).  The REDCap system is HIPAA compliant and requires 
study team access.  Identified datasets will not be shared.  Thus the identifiers are not 
available to the research analytic teams and will not be shared.  
Lastly, although not funded a governmental agency, the data may be shared with 
governmental agencies (including the CDC) as part of public health concerns.  
6.2 HIPAA Privacy Rule compliance 
The diagnostic evaluations and clinical outcomes of all patients with COVID-19 in HMH 
centers participating in this registry will be drawn from the EPIC system which contains 
PHI.  The collected data will be entered into the REDCap system which will contain PHI.   
Both systems are secure, meeting HIPAA compliance, and may only be accessed by 
authorized personnel.   
All data analysis will be conducted on exported de-identified data, under the secondary 
use clause.  NO PHI will be publically disclosed unless requested by governmental 
agencies.   
6.3 
IRB 
The Hackensack University Medical Center Institutional Review Board will serve as the 
IRB of record for this study for the Hackensack Meridian Network.     
 
 

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7 
Disseminating and Communicating Registry Results 
7.1 
 
HMH, the principal investigator, and/or HMH sub-investigators  may choose to publish 
information in the medical literature and/or at national  meetings based on this registry.   
Any investigator will be required to recognize the data source in compliance with the 
journal standard practice.  NO PHI may disclosed.  If PHI is to be shared with other HMH 
investigators regarding separate IRB retrospective projects, this will be identified and 
written in the separate IRB approved protocol. 
 7.2 
 
HMH, the principal investigator, and/or HMH sub-investigators may release data (de-
identified) or analytic findings to governmental agencies as requested.  
 
7.3 
 
The HMH Biorepository (BioR) will be granted access to the database and any pre data, 
supplements or queries provided to the RWD study as the BioR is collecting the same 
clinical information from patients who have either provided consent for this collection 
or for any other specimens that have been acquired as per the BioR’s protocol. The BioR 
will follow the internal SOP of the database and will not release personal health 
identifiers (PHI) to researchers. 
7.4 
The University of Miami will be granted access to only de-identified portions of the 
database as they are externally validating a risk score HMH has developed.  They also 
will be developing a separate risk score on predicting intubation in COVID-19 patients 
and we anticipate an ongoing collaboration of sharing data 
 

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8 
Data Ownership 
Data contributed to the HMH registry will become the property of HMH.  It may be utilized 
for commercial purposes by HMH in de-identified HIPAA compliant fashion.    
 
9 
References 
 
1. Z Wu, JM. McGoogan: Characteristics of and important lessons from the coronavirus disease 
2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese 
Center for Disease Control and Prevention. JAMA (2020 Feb 24), 10.1001/jama.2020.2648