Building Electronic Tools To Enhance and Reinforce CArdiovascular REcommendations - Heart Failure (BETTER CARE-HF)
Phase: NA
Conditions: Heart Failure, Heart Failure With Reduced Ejection Fraction
Sponsor: NYU Langone Health

 
 
Official Title: 
Building Electronic Tools To Enhance and Reinforce CArdiovascular 
REcommendations - Heart Failure (BETTER CARE-HF)   
NCT Number: 
NCT05275920 
Study Number: 
21-00644 
Document Type:  
Study Protocol and Statistical Analysis Plan 
Date of the 
Document: 
• 
February 14, 2023 
 
  

 
 
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Study Title:  
 
 
BETTER CARE - HF: Building Electronic Tools To Enhance and 
Reinforce CArdiovascular REcommendations – Heart Failure 
 
 
NYULH Study Number: 
 
 
S21-00644 
 
Principal Investigator: 
 
 
Saul Blecker, MD 
NYU Langone Health 
Department of Population Health 
Saul.blecker@nyulangone.org 
 
 
Additional Investigator: 
 
 
Amrita Mukhopadhyay, MD 
NYU Langone Health 
Department of Medicine, Division of Cardiology 
amrita.mukhopadhyay@nyulangone.org 
 
 
Funding Sponsor:  
 
 
2021 CTSI Pilot Project Award 
 
Initial version: 5/21/2021  
Amended:  2/7/2023 
 
 

Study number: s21-00644 
 
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Statement of Compliance 
 
This study will be conducted in accordance with the Code of Federal Regulations on the Protection of 
Human Subjects (45 CFR Part 46), any other applicable US government research regulations, and 
institutional research policies and procedures. The Principal Investigator will assure that no deviation from, 
or changes to the protocol will take place without prior agreement from the sponsor and documented 
approval from the Institutional Review Board (IRB), except where necessary to eliminate an immediate 
hazard(s) to the study participants. All personnel involved in the conduct of this study have completed 
Human Subjects Protection Training. 
 
 

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Table of Contents 
 
PROTOCOL SUMMARY .............................................................................................................................. 1 
SCHEMATIC OF STUDY DESIGN ............................................................................................................... 2 
1 
INTRODUCTION, BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ....................... 3 
1.1 
BACKGROUND INFORMATION AND RELEVANT LITERATURE ................................................................ 3 
1.2 
RATIONALE .................................................................................................................................... 3 
1.3 
POTENTIAL RISKS & BENEFITS ........................................................................................................ 4 
1.3.1 
Known Potential Risks ............................................................................................................. 4 
1.3.2 
Known Potential Benefits ........................................................................................................ 4 
2 
OBJECTIVES AND PURPOSE ........................................................................................................... 4 
2.1 
PRIMARY OBJECTIVE ...................................................................................................................... 4 
3 
STUDY DESIGN AND ENDPOINTS .................................................................................................... 4 
3.1 
DESCRIPTION OF STUDY DESIGN .................................................................................................... 4 
3.2 
INTERVENTION ............................................................................................................................... 4 
3.3 
STUDY ENDPOINTS......................................................................................................................... 5 
4 
STUDY POPULATION ......................................................................................................................... 5 
4.1 
TOTAL NUMBER OF PARTICIPANTS AND SITES .................................................................................. 5 
4.2 
INCLUSION CRITERIA ...................................................................................................................... 5 
4.3 
EXCLUSION CRITERIA ..................................................................................................................... 5 
4.4 
VULNERABLE SUBJECTS ................................................................................................................. 6 
5 
STRATEGIES FOR RECRUITMENT .................................................................................................. 6 
5.1 
DURATION OF STUDY PARTICIPATION .............................................................................................. 6 
5.2 
PARTICIPANT WITHDRAWAL OR TERMINATION .................................................................................. 6 
6 
STUDY SCHEDULE............................................................................................................................. 6 
7 
STUDY PROCEDURES / EVALUATIONS .......................................................................................... 7 
8 
SAFETY AND ADVERSE EVENTS ..................................................................................................... 7 
8.1 
DEFINITIONS .................................................................................................................................. 7 
8.1.1 
Investigator reporting: notifying the IRB .................................................................................. 8 
9 
STATISTICAL CONSIDERATIONS .................................................................................................... 9 
9.1 
STUDY HYPOTHESES ...................................................................................................................... 9 
9.2 
SAMPLE SIZE DETERMINATION ........................................................................................................ 9 
9.3 
STATISTICAL METHODS .................................................................................................................. 9 
10 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS ................................... 9 
11 
ETHICS/PROTECTION OF HUMAN SUBJECTS ............................................................................. 10 
11.1 
ETHICAL STANDARD ..................................................................................................................... 10 
11.2 
INSTITUTIONAL REVIEW BOARD ..................................................................................................... 10 
11.3 
INFORMED CONSENT PROCESS .................................................................................................... 10 
11.3.1 
Research Use of Stored Data ........................................................................................... 10 
11.4 
FUTURE USE OF STORED DATA .................................................................................................... 11 
12 
DATA HANDLING AND RECORD KEEPING ................................................................................... 11 
12.1 
DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES .............................................................. 11 
12.2 
STUDY RECORDS RETENTION ....................................................................................................... 11 
12.3 
PUBLICATION AND DATA SHARING POLICY ..................................................................................... 11 

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13 
STUDY FINANCES ............................................................................................................................ 11 
13.1 
FUNDING SOURCE ........................................................................................................................ 11 
13.2 
COSTS TO THE PARTICIPANT ......................................................................................................... 11 
13.3 
PARTICIPANT REIMBURSEMENTS OR PAYMENTS ............................................................................ 11 
14 
STUDY ADMINISTRATION ............................................................................................................... 12 
14.1 
STUDY LEADERSHIP ..................................................................................................................... 12 
15 
CONFLICT OF INTEREST POLICY .................................................................................................. 12 
16 
REFERENCES ................................................................................................................................... 13 
17 
ATTACHMENTS ................................................................................................................................ 13 
 
 
 

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List of Abbreviations 
 
ACE-I 
Angiotensin converting enzyme-inhibitor 
AE 
Adverse event 
ARB 
Angiotensin receptor blocker 
BB 
Beta-blocker 
BPA 
Best Practice Alert 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
CSOC 
Clinical Study Oversight Committee 
DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
EF 
Ejection Fraction 
EHR 
Electronic Health Record 
FFR 
Federal Financial Report 
FWA 
Federalwide Assurance 
HIPAA 
Health Insurance Portability and Accountability Act 
HFrEF 
Heart Failure with Reduced Ejection Fraction 
ICF 
Informed Consent Form 
IRB 
Institutional Review Board 
MOP 
Manual of Procedures 
MRA 
Mineralocorticoid Receptor Antagonist 
N 
Number (typically refers to participants) 
NIH 
National Institutes of Health 
NYULH 
New York University Langone Health 
OHRP 
Office for Human Research Protections 
OHSR 
Office of Human Subjects Research 
PI 
Principal Investigator 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SOP 
Standard Operating Procedure 
US 
United States 
 
 
 
 
 

Study number: s21-00644 
 
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authorized in writing by the study sponsor 
Drug/Device Template Version: 13 JUN 2016 
Protocol Summary 
Title 
BETTER CARE – HF: Building Electronic Tools To Enhance and Reinforce 
CArdiovascular REcommendations – Heart Failure 
Short Title 
BETTER CARE – HF: Building Electronic Tools To Enhance and Reinforce 
CArdiovascular REcommendations – Heart Failure 
Brief Summary 
This study will test two types of electronic health record (EHR)-based alerts to 
improve guideline-adherent care for patients with heart failure and reduced 
ejection fraction (HFrEF). Alerts will be triggered for patients with ejection 
fraction (EF) ≤ 40% who are not on guideline-recommended medical therapy. 
The two types of alerts tested will be a Best Practice Alert (BPA) and an 
electronic message. 
Objectives 
To test two types of EHR-based alerts that promote appropriate medical 
therapy for patients with HFrEF. 
Methodology 
Prospective cohort study 
Endpoints 
Primary endpoint: medication prescribing patterns  
Secondary endpoint: hospitalization and mortality 
Study Duration 
Eighteen months 
Participant Duration 
Eighteen months 
Population 
Patients with EF ≤ 40% 
Study Sites 
One single health system, NYULH, consists of approximately 60 outpatient 
cardiology practices.  
Number of participants 
Up to 2000 participants 
Statistical Analysis 
We will begin all analyses with descriptive summary statistics and graphical 
displays of all variables. Primary analyses will utilize McNemar’s tests for 
medication prescriptions and patient outcomes of hospitalization and 
mortality. We will adjust for patient demographics and clinical characteristics, 
as well as provider-level characteristics, such as demographics, panel size, 
insurance mix, and sub-specialty training.  
 
 
 

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Schematic of Study Design 
 
 
Prior to  
Enrollment 
 
 
 
 
 
Intervention 
 
 
 
 
Evaluation 
 
 
 
 
 
 
 
 
 One single health system, NYULH, consists of approximately 60 outpatient 
cardiology practices.  
Distribute evenly in a 1:1:1 ratio to install either Best Practice Alert (BPA), electronic 
message, or neither alert in the electronic health record. 
Evaluate prescribing rates of medical therapy in patients meeting eligibility seen at 
participating practices 
 
Through a survey sub-study, evaluate provider perceptions on the acceptability, 
usefulness, and ease of use of the BPA and electronic message.   

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1 
Introduction, Background Information and Scientific Rationale 
1.1 
Background Information and Relevant Literature 
 
For patients with heart failure and reduced ejection fraction (HFrEF), the cornerstone of evidence-based 
care includes several medications that have been found to significantly reduce morbidity and mortality, 
which include: 1) mineralocorticoid antagonists (MRA), 2) angiotensin converting enzyme inhibitors, 
angiotensin receptor blockers, angiotensin receptor neprilysin inhibitors (ACE-I/ARB/ARNI), and 3) beta-
blockers (BB). Current guidelines give these medications a class I recommendation,1 and recently 
published performance measures2 also strongly recommend these agents.  However, despite their well-
accepted benefits, several prior studies have revealed significant gaps in medical therapy for HFrEF 
patients.3-5 Using number-needed-to-treat estimates based on data from randomized trials, these gaps in 
medical therapy account for an estimated 68,000 deaths per year nationwide, with the largest proportion 
being from lack of appropriate MRA therapy.6  
In prior studies, successful interventions for improvement have often included multidisciplinary approaches 
with nurses, pharmacists, or other trained individuals.7-9 However, the need for dedicated staff can be costly, 
and electronic health record (EHR)-based interventions could be a potential cost-effective solution. Prior 
studies assessing the efficacy of EHR-based interventions to improve medical therapy for HFrEF have 
mainly been conducted in the inpatient setting.10-12 Inpatient algorithms may be limited as they reflect one 
instance in time. Additionally, acute hospitalization may restrict the ability to add multiple agents due to 
renal dysfunction or hypotension. Therefore, we propose the development of an outpatient EHR-based 
system to target patients with HFrEF who are not on the appropriate therapy. 
Outpatient provider-facing EHR-based interventions could include best practice alerts (BPA) or electronic 
messages. While limited data exist for both types of interventions, some studies have observed significant 
improvements in health outcomes.13-15 Potential adverse effects have also been described, such as 
increased alert frequency with BPAs14 and physician burnout with electronic messages.16 Given the 
potential for benefit and/or harm, it is imperative to study such interventions with rigor. Currently, no study 
directly compares different types of EHR-based alerts. 
In this study, we aim to test a BPA and an electronic message for HFrEF patients who are not on guideline-
recommended therapy. This work is significant because it aims to reduce gaps in medical therapy for HFrEF 
patients, which we hope will reduce mortality, decrease hospitalizations, and improve symptoms. 
We will not be directly recruiting or enrolling patients. However, we will be monitoring patients for clinical 
outcomes using EHR data and are requesting a waiver of authorization and consent. 
We will also conduct a survey to assess provider acceptability and perceived usefulness and ease of use 
of the BPA and electronic messages. This survey will be sent to the cardiologists at NYULH who received 
the BPA and electronic messages. 
1.2 
Rationale 
This study aims to evaluate EHR-based alerts to improve adherence to guideline-recommended medical 
therapy among patients with HFrEF.  
Understanding provider feedback on the BPA and electronic messages is necessary to understanding 
why these EHR tools may or may not work to improve care. For example, the BPA may be more effective 
at improving prescribing, and the surveys could help us understand if this was because cardiologists 
thought that they were easier to use. Moreover, there may be drawbacks, such as increased time needed 
during visits due to the BPAs or electronic messages. The only way to obtain this type of information is 
from the cardiologists at NYULH who received the BPAs and electronic messages, as they are the only 
ones who can comment on the acceptability, usefulness, and ease of use of the EHR tools. 

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1.3 
Potential Risks & Benefits 
1.3.1 
Known Potential Risks 
The risk is not greater than minimal risk (i.e., risk encountered in daily life or in the course of usual 
clinical practice). Individual case determinations of potential safety gaps will never be released to 
supervisors of any clinicians whose charts are being reviewed. 
The principal risk of the study, as for any medical record review, is inadvertent release of confidential 
patient information. We will avoid such inadvertent disclosure by storing all identifiable information on a 
secure server and restricting access to the data to authorized study personnel. 
 
For provider surveys, we expect the level of risk due to this study to be minimal. Potential risks to 
providers may include the following issues listed. 
• 
Coercion/Undue Influence: The study will include NYULH employees. Participants may feel 
coerced or under pressure to participate in the survey or provide positive remarks about their 
work activities. Staff will be informed that participation is solely voluntary and has no bearing on 
their employment status or salary. Additionally, employee’s will be informed that their decision 
to participate in the research study may not affect (favorably or unfavorably) performance 
evaluations, career advancement, or other employment-related decisions made by peers or 
supervisors. 
• 
Discomfort:  Participants may feel uncomfortable answering some of the study questions. They 
will be informed that they can refuse to answer any questions they wish. The information that 
we are retrieving is not sensitive in nature and we do not expect it to be of concern to the 
participant. 
1.3.2 
Known Potential Benefits 
There may be benefit to individual patients for whom alerts may be triggered in this pilot study if their care 
is improved to comport with guidelines. The research will contribute critically to our knowledge of EHR-
based alerts.  
 
For the provider surveys, the information gained will put the effectiveness results into context (for 
example, help explain why one type worked better than another). Additionally, from an institutional quality 
improvement perspective, this will allow us to inform plans for next steps. The information gained from 
these surveys may also be beneficial to the providers themselves, as the feedback from this could impact 
next steps for the institution and future workflow within the EHR. 
 
2 
Objectives and Purpose 
2.1 
Primary Objective 
The primary objective of the study is to evaluate EHR-based alerts to promote appropriate medical 
therapy for patients with HFrEF. 
 
3 
Study Design and Endpoints 
3.1 
Description of Study Design 
NYU Langone Health has ambulatory care sites in the five boroughs of New York City (NYC) as well as in 
suburbs of New York and New Jersey. All have the NYU Epic EHR.  
3.2 
Intervention 
The two types of EHR-based alerts include: 1) BPA and 2) electronic message. 

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Best Practice Alert (BPA) – BPAs are alerts that appear at the time of the visit, allowing for real-time 
intervention while the provider is with a patient, but also potentially interrupting provider workflow. The 
BPA appears at the beginning of a visit/encounter and includes 1) a tailored advisory, 2) educational link 
to guidelines, 3) medication information, 4) vital sign and pertinent lab results, and 5) options for next 
steps (i.e. ordering medication, providing reasons for not prescribing). 
Electronic Message – Unlike the BPA, the electronic message is not necessarily seen at the time of the 
visit, and is more likely to be seen between visits. The electronic message is similar to the BPA in terms 
of information provided, but can include information on multiple patients in the same message, and 
overall prescribing metrics. 
3.3 
Study Endpoints 
Outcomes measured at the prescription encounter level include whether there is a prescription for BB, 
ACE-I/ARB/ARNI, and/or MRA. Secondary patient outcomes include hospitalization, hospitalization for 
HF, and mortality. 
3.4 
Provider Surveys 
We will conduct surveys of cardiology providers after the implementation of the EHR-based 
alerts across all NYULH Cardiology locations.  The survey will aim to obtain further 
understanding of provider real-world experiences with, and perception of the clinical decision 
support tools. We will use a mix of likert-scale, multiple-choice, and open-ended questions to 
assess the alerts based on previously reported implementation science frameworks, specifically 
focusing on acceptability, usefulness, and ease of use of the two EHR-based alerts.   
 
The goal for this survey is to obtain an overall assessment of the EHR-based alerts’ usefulness as 
a long-term strategy for health system-wide quality improvement.  Past evidence suggests that 
physicians dislike clinical decision support tools, believing they have minimal utility and result in 
general inefficiency, increased time required for care, and contribute to a sense of alert 
fatigue.  We seek to determine whether these perceived downsides of EHR-based alerts were a 
factor in providers’ impressions of the alerts used in this study. . The final survey is attached. 
4 
Study Population   
4.1 
Total Number of Participants and Sites  
This is a single site study involving NYULH outpatient cardiology clinics serving a total of approximately 
2000 participants. 
4.2 
Inclusion Criteria 
• 
Patient with an encounter visit at NYULH cardiology practice during the study period 
• 
Patient with EF ≤ 40% on most recent echocardiogram 
• 
Patient ages 18-100 
4.3 
Exclusion Criteria 
• 
Pregnancy 
• 
Ventricular assist device 
• 
In order to give providers time to add and up-titrate medications, we will exclude patients who had 
a newly reduced EF in the last 3 months. 
• 
Medication-specific exclusion for MRA: most recent systolic blood pressure less than 105 mm Hg, 
most recent potassium < 5.1, any potassium > 5.5, most recent glomerular filtration rate < 30 
(using MDRD equation), or a documented MRA allergy. 

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4.4 
Vulnerable Subjects 
No vulnerable patients will be enrolled. 
 
For the survey, we will recruit NYULH cardiologists who received the BPAs or messages. The only way to 
obtain feedback on the BPAs and electronic messages is from the cardiologists at NYULH who received 
the BPAs and electronic messages, as they are the only ones who can comment on the acceptability, 
usefulness, and ease of use of these EHR tools. Cardiologists will be informed that their decision to 
participate or not, and their responses, will in no way affect their employment, salary, or performance 
evaluations and they will be reminded that they can stop participating whenever they want. Their 
information will be de-identified and completely anonymous. No identifiable PII or health information will 
be collected.   
 
5 Strategies for Recruitment  
 
Eligible patients from the chosen practice sites will be identified electronically within EPIC using an 
algorithm developed by the study team and NYULH’s DataCore. This algorithm reviews patient records 
for EF ≤ 40% on most recent echocardiogram, and exclusion criteria listed above. Patients meeting 
eligibility will be automatically included, and all data collection will take place passively via the NYULH 
EHR system, EPIC. An EPIC reporting analyst will extract the relevant parameters from EPIC into a 
report. Patients from the selected practice sites will undergo their usual interactions with their providers 
and no study-specific activities will take place. 
5.1 
Duration of Study Participation 
Patients’ clinical outcomes will be monitored through EHR data for 18 months. 
5.2 
Participant Withdrawal or Termination 
Not applicable as the subjects are recruited at the clinic level. 
5.3 Provider Survey Recruitment 
For the provider survey, we will recruit cardiologists who received the BPA or electronic message through 
emails (see attachment). They will be made aware that completing the survey is completely anonymous 
and will in no way impact their employment. The recruitment emails will be sent via listservs of 
cardiologist who received the BPAs and electronic messages. These listservs are specific for those 
cardiologists who received BPAs or electronic messages and the survey does not require cardiologists to 
self-select whether they received a BPA or a message. Only cardiologists who received a BPA or 
electronic message will be contacted. We will send an initial recruitment email and a subsequent follow 
up email. 
 
The consent form will be attached to the email. It will also be available via link within the first question in 
Qaltrix. The first question in Qaltrix asks the provider to review the consent document and requires the 
provider to click a button stating that they are consenting to participate before being shown the remaining 
survey questions. If the provider does not click this button, they will not be able to move forward or complete 
the survey. 
6 Study Schedule 
 
Participants will be included in this study by virtue of meeting eligibility criteria and having a patient 
encounter during the study period. There are no study-specific visits.  Any patient meeting criteria who 
has one or more patient encounters during the study period will be included.  Therefore, no study-specific 
visits are relevant for this study, so there is no schedule of visits. 
 

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7 Study Procedures / Evaluations 
 
There are no study-specific procedures that patients will undergo. They will receive care as usual by their 
outpatient providers.  The EHR algorithm developed by the study team identifies eligible patients with EF ≤ 
40% on most recent echocardiogram, and exclusion criteria listed above. The EHR algorithm will also 
capture information on demographics, diagnoses in the patient’s problem list, prescription history, allergies, 
EF, and relevant lab results.  
 
For patients meeting the eligibility criteria, a message in the EHR will automatically be sent to the provider. 
The provider will receive either a Best Practice Alert (BPA) or electronic message indicating that their heart 
failure patient is not on guideline-recommended therapy. The message will offer guidance for physician 
decision-making regarding HFrEF care. The study team presented the proposed project to the NYULH 
MCIT Project Portfolio Review Committee on February 11, 2021 and was approved to work with MCIT to 
build the electronic messages. Providers will be notified through the Weekly Epic Update and in 
presentations to medical directors that they may see the alert prior to the start of the study. 
 
Patients’ clinical outcomes will be monitored through EHR data collection for 18 months. Data collection 
will include elements of protected health information including patient name, medical record number, 
address zip code, and service dates. These will be necessary for data linkages and in order to track patients 
for receipt of intervention and clinical outcomes. All PHI data will be kept on a secure NYULH server and 
destroyed at the earliest possible point. Data on the patient’s medication prescription, hospitalization, 
hospitalization for HF, and mortality will be recorded as study outcomes. The study team members will not 
collect this information directly; data will be collected in NYULH’s EHR system, EPIC, and an EPIC 
Reporting analyst from DataCore will extract the relevant parameters from the EHR into a report.   
 
 
Data points that will be collected for research purposes  
Medication prescription 
Hospitalization 
Hospitalization for HF 
Mortality 
Name 
Medical record number 
Address zip code 
Service dates 
 
Provider survey data will be anonymously collected via Qaltrix. No identifiable information, PII, or health 
information will be collected. The URLs for the survey are below: 
 
BPA version = https://nyumc.yul1.qualtrics.com/jfe/preview/previewId/f42fb1cb-b997-4fb8-8f60-
9e311e6b6320/SV_7P3UhfvSH6KgpuK?Q_CHL=preview&Q_SurveyVersionID=current 
  
IBM version =  https://nyumc.yul1.qualtrics.com/jfe/preview/previewId/c97ab951-3feb-478a-8af8-
a53e9abbe02d/SV_7PQoQunPLM8l8ZU?Q_CHL=preview&Q_SurveyVersionID=current 
8 
Safety and Adverse Events 
8.1 
Definitions 
Unanticipated Problems Involving Risk to Subjects or Others 
Any incident, experience, or outcome that meets all of the following criteria:  
• Unexpected in nature, severity, or frequency (i.e., not described in study-related documents such 
as the IRB-approved protocol or consent form, the investigators brochure, etc) 

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• Related or possibly related to participation in the research (i.e., possibly related means there is a 
reasonable possibility that the incident experience, or outcome may have been caused by the 
procedures involved in the research) 
• Suggests that the research places subjects or others at greater risk of harm (including physical, 
psychological, economic, or social harm). 
 
Adverse Event 
An adverse event (AE) is any symptom, sign, illness or experience that develops or worsens in severity 
during the course of the study.  Intercurrent illnesses or injuries should be regarded as adverse events.  
Abnormal results of diagnostic procedures are considered to be adverse events if the abnormality: 
• results in study withdrawal 
• is associated with a serious adverse event 
• is associated with clinical signs or symptoms 
• leads to additional treatment or to further diagnostic tests 
• is considered by the investigator to be of clinical significance 
 
Serious Adverse Event 
Adverse events are classified as serious or non-serious.  A serious adverse event is any AE that is:  
• fatal 
• life-threatening 
• requires or prolongs hospital stay 
• results in persistent or significant disability or incapacity 
• a congenital anomaly or birth defect 
• an important medical event 
 
All adverse events that do not meet any of the criteria for serious should be regarded as non-serious 
adverse events.  
 
8.1.1 
Investigator reporting: notifying the IRB 
Federal regulations require timely reporting by investigators to their local IRB of unanticipated problems 
posing risks to subjects or others.  The following describes the NYULMC IRB reporting requirements, 
though Investigators at participating sites are responsible for meeting the specific requirements of their 
IRB of record.  
 
Report Promptly, but no later than 5 working days: 
Researchers are required to submit reports of the following problems promptly but no later than 5 working 
days from the time the investigator becomes aware of the event: 
• 
Unanticipated problems including adverse events that are unexpected and related 
– Unexpected: An event is “unexpected” when its specificity and severity are not accurately 
reflected in the protocol-related documents, such as the IRB-approved research protocol, any 
applicable investigator brochure, and the current IRB-approved informed consent document 
and other relevant sources of information, such as product labeling and package inserts.  
– Related to the research procedures: An event is related to the research procedures if in the 
opinion of the principal investigator or sponsor, the event was more likely than not to be 
caused by the research procedures.  
– Harmful: either caused harm to subjects or others, or placed them at increased risk 
 
Other Reportable events: 
The following events also require prompt reporting to the IRB, though no later than 5 working days: 
• Complaint of a research subject when the complaint indicates unexpected risks or the complaint 
cannot be resolved by the research team. 

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• Protocol deviations or violations (includes intentional and accidental/unintentional deviations 
from the IRB approved protocol) for any of the following situations:  
– one or more participants were placed at increased risk of harm  
– the event has the potential to occur again 
– the deviation was necessary to protect a subject from immediate harm 
• Breach of confidentiality 
• Incarceration of a participant when the research was not previously approved under Subpart C 
and the investigator believes it is in the best interest of the subject to remain on the study. 
• New Information indicating a change to the risks or potential benefits of the research, in 
terms of severity or frequency. (e.g. analysis indicates lower-than-expected response rate or a 
more severe or frequent side effect; Other research finds arm of study has no therapeutic value; 
FDA labeling change or withdrawal from market) 
 
Reporting Process 
The reportable events noted above will be reported to the IRB using a Reportable New Information 
submission and will include a description of the event with information regarding its fulfillment of the 
above criteria, follow-up/resolution, and need for revision to consent form and/or other study 
documentation. Copies of each report and documentation of IRB notification and receipt will be kept in the 
Clinical Investigator’s study file. 
 
9 
Statistical Considerations 
9.1 
Study Hypotheses 
Patient in clinics receiving the EHR-based alerts will have higher rates of adherence to guideline 
recommended medical therapy. 
Providers will like the EHR-based alerts and will want to continue to use them in their practice. 
9.2 
Sample Size Determination 
In order to have 80% power to detect a 10% improvement in prescribing for each intervention 
arm vs. control, we will require a total of at least 1503 patients (501 per arm).  Based on prior 
data, we estimate that alerts will trigger for a sample between 1500-2000 patients, but are 
unable to accurately control the specific number of patients due to fluctuating clinical volume at 
practices. 
9.3 
Statistical Methods 
We will begin all analyses with descriptive summary statistics and graphical displays of all variables. 
Primary analyses will utilize McNemar’s tests for medication prescriptions and patient outcomes of 
hospitalization and mortality. We will adjust for patient demographics and clinical characteristics, as well 
as provider-level characteristics, such as demographics, panel size, insurance mix, and sub-specialty 
training. 
9.4 Provider Survey Assessment 
Answers from surveys will be tabulated with descriptive statistics.  
10 Source Documents and Access to Source Data/Documents 
 

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The EPIC electronic health record is the primary data collection instrument for the study.  Study-specific 
case report forms will not be used. 
 
Access to study records will be limited to IRB-approved members of the study team. The investigator will 
permit study-related monitoring, audits, and inspections by the IRB/EC, the sponsor, government 
regulatory bodies, and University compliance and quality assurance groups of all study related 
documents (e.g., source documents, regulatory documents, data collection instruments, study data etc.).  
The investigator will ensure the capability for inspections of applicable study-related facilities (e.g., 
pharmacy, diagnostic laboratory, etc.). 
 
11 Ethics/Protection of Human Subjects 
11.1 Ethical Standard 
The investigator will ensure that this study is conducted in full conformity with Regulations for the 
Protection of Human Subjects of Research codified in 45 CFR Part 46. 
11.2 Institutional Review Board 
A request for waiver of informed consent, and request for waiver of HIPAA authorization will be submitted 
to the IRB for review and approval. Approval of the protocol, the waiver of consent, and the waiver of 
HIPAA authorization must be obtained before any participant is enrolled. Any amendment to the protocol 
will require review and approval by the IRB before the changes are implemented to the study.  
11.3 Informed Consent Process 
We will obtain a waiver of informed consent and a waiver of HIPAA authorization for patients seen in the 
participating clinics to acknowledge their participation at a clinic level. The risks to subjects are exactly 
equivalent to the risks experienced in the standard setting of patient care. The new module to be 
activated in EPIC relates only to guidance for physician decision-making regarding HFrEF care, and has 
no impact on disclosure or treatment of PHI. Patients will receive care from their providers in the usual 
way.  The only difference is the interface with the electronic health record that is used by the physician 
during the course of the patient encounter.  The autonomy of the provider to make decisions about patient 
care will not be affected. It is impracticable to obtain consent from patients for receipt of standard medical 
care by their usual providers.  It is unclear what they would be providing consent for, since they will 
receive care as usual from their providers. Patients will not be provided with additional information.  They 
will be treated as usual by their providers and the providers’ experience with the module is irrelevant to 
their patient experience. 
 
For provider surveys, we are requesting a waiver of documentation of consent. These surveys present no 
more than minimal risk to providers. Prior to beginning survey questions, providers will be given consent 
form that contains all pertinent study and contact information. The consent form will be attached to the 
recruitment email and also will be available via link in Qaltrix prior to the survey. The providers will be asked 
to acknowledge consent through clicking a button within Qaltrixbefore they are able to participate in the 
survey questions. Providers will be informed that they may agree not to participate and that this will have 
no bearing on their employment status. 
11.3.1 Research Use of Stored Data 
• Intended Use: Data collected under this protocol may be used to study the effectiveness of the 
EHR-based alerts.  
• Tracking: Data will be tracked using Epic reports generated by study team members.  
o 
Disposition at the completion of the study.  Data will be retained in de-identified electronic 
form on secure, password-protected digital storage media in the NYULH MCIT-managed 
shared network drive, under the supervision of Drs. Blecker and Mukhopadhyay. 
•  Storage: Data with identifiable information will be stored on an MCIT-shared network drive, a 
secure, firewall-protected university server in a location with restricted access. Anti-virus software 

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writing by the study sponsor 
 
is installed and current. Electronic access to the server will be through unique ID and complex 
password login and will only be granted to authorized researchers approved through this proposal. 
Login sessions can be individually monitored and tracked. All computer workstations require 
password login and have up-to-date virus software. Identifiable data will never be stored on 
moveable electronic media. Identifiable data will never be transmitted outside NYU. Only group-
level information without personal identifiers will be included when presenting results or submitting 
manuscripts for publication.  
o 
 
 
If any information is shared with external interested site(s), dataset agreements with NYU LANGONE will 
be established. 
 
11.4 Future Use of Stored Data 
Access to the dataset for any future research will require separate IRB approval. 
 
12 Data Handling and Record Keeping 
12.1 Data Collection and Management Responsibilities 
 
Data collection is the responsibility of the study staff at NYULH under the supervision of Dr. Blecker. The 
investigator is responsible for ensuring the accuracy, completeness, and timeliness of the data reported. 
12.2 Study Records Retention 
Study documents and data will be retained for the longer of 3 years after close out or 5 years after final 
reporting/publication. These documents should be retained for a longer period, however, if required by 
local regulations. No records will be destroyed without the written consent of the sponsor, if applicable. It 
is the responsibility of the sponsor to inform the investigator when these documents no longer need to be 
retained. 
12.3 Publication and Data Sharing Policy 
This study will comply with the NIH Public Access Policy, which ensures that the public has access to the 
published results of NIH funded research. It requires scientists to submit final peer-reviewed journal 
manuscripts that arise from NIH funds to the digital archive PubMed Central upon acceptance for 
publication. 
 
13 Study Finances 
13.1 Funding Source 
This study is financed through a grant from the NYU CTSI (Clinical and Translational Sciences Institute) 
Pilot Project Award. 
13.2 Costs to the Participant 
There are no costs to participants in this study. 
13.3 Participant Reimbursements or Payments 
There are no participant reimbursements or payments. 
 

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writing by the study sponsor 
 
14 Study Administration 
14.1 Study Leadership 
Not applicable 
15 Conflict of Interest Policy 
 
The independence of this study from any actual or perceived influence, such as by the pharmaceutical 
industry, is critical. Therefore, any actual conflict of interest of persons who have a role in the design, 
conduct, analysis, publication, or any aspect of this study will be disclosed and managed. Furthermore, 
persons who have a perceived conflict of interest will be required to have such conflicts managed in a 
way that is appropriate to their participation in the study. The study has established policies and 
procedures for all study group members to disclose all conflicts of interest and will establish a mechanism 
for the management of all reported dualities of interest.  
 
Any investigator who has a conflict of interest with this study (patent ownership, royalties, or financial gain 
greater than the minimum allowable by their institution, etc.) must have the conflict reviewed by the NYU 
Langone Conflict of Interest Committee with a Committee-sanctioned conflict management plan that has 
been reviewed and approved by the study sponsor prior to participation in this study.  All NYULH 
investigators will follow the applicable conflict of interest policies. 
 

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writing by the study sponsor 
 
16 References 
1. 
Yancy, C.W., et al., 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for 
the Management of Heart Failure: A Report of the American College of Cardiology/American 
Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of 
America. Circulation, 2017. 136(6): p. e137-e161. 
2. 
Heidenreich, P.A., et al., 2020 ACC/AHA Clinical Performance and Quality Measures for Adults 
With Heart Failure: A Report of the American College of Cardiology/American Heart Association 
Task Force on Performance Measures. J Am Coll Cardiol, 2020. 76(21): p. 2527-2564. 
3. 
Fonarow, G.C., et al., Improving evidence-based care for heart failure in outpatient cardiology 
practices: primary results of the Registry to Improve the Use of Evidence-Based Heart Failure 
Therapies in the Outpatient Setting (IMPROVE HF). Circulation, 2010. 122(6): p. 585-96. 
4. 
Greene, S.J., et al., Medical Therapy for Heart Failure With Reduced Ejection Fraction: The 
CHAMP-HF Registry. J Am Coll Cardiol, 2018. 72(4): p. 351-366. 
5. 
Chin, K.L., et al., The treatment gap in patients with chronic systolic heart failure: a systematic 
review of evidence-based prescribing in practice. Heart Fail Rev, 2016. 21(6): p. 675-697. 
6. 
Fonarow, G.C., et al., Potential impact of optimal implementation of evidence-based heart failure 
therapies on mortality. Am Heart J, 2011. 161(6): p. 1024-30.e3. 
7. 
Desai, A.S., et al., Remote Optimization of Guideline-Directed Medical Therapy in Patients With 
Heart Failure With Reduced Ejection Fraction. JAMA Cardiol, 2020. 5(12): p. 1-5. 
8. 
Driscoll, A., J. Currey, and A.M. Tonkin, Nurse-Led Titration of Angiotensin-Converting Enzyme 
Inhibitors, β-Adrenergic Blocking Agents, and Angiotensin Receptor Blockers in Patients With 
Heart Failure With Reduced Ejection Fraction. JAMA Cardiol, 2016. 1(7): p. 842-843. 
9. 
Lowrie, R., et al., Pharmacist intervention in primary care to improve outcomes in patients with left 
ventricular systolic dysfunction. Eur Heart J, 2012. 33(3): p. 314-24. 
10. 
Blecker, S., et al., Interrupting providers with clinical decision support to improve care for heart 
failure. Int J Med Inform, 2019. 131: p. 103956. 
11. 
Riggio, J.M., et al., Effectiveness of a clinical-decision-support system in improving compliance 
with cardiac-care quality measures and supporting resident training. Acad Med, 2009. 84(12): p. 
1719-26. 
12. 
Qian, Q., et al., ACEi/ARB for systolic heart failure: closing the quality gap with a sustainable 
intervention at an academic medical center. J Hosp Med, 2011. 6(3): p. 156-60. 
13. 
Lee, J., et al., Cluster Randomized Trial Examining the Impact of Automated Best Practice Alert 
on Rates of Implantable Defibrillator Therapy. Circ Cardiovasc Qual Outcomes, 2019. 12(6): p. 
e005024. 
14. 
Powers, E.M., et al., Efficacy and unintended consequences of hard-stop alerts in electronic 
health record systems: a systematic review. J Am Med Inform Assoc, 2018. 25(11): p. 1556-1566. 
15. 
Kirby, A.M., et al., Using Clinical Decision Support to Improve Referral Rates in Severe 
Symptomatic Aortic Stenosis: A Quality Improvement Initiative. Comput Inform Nurs, 2018. 
36(11): p. 525-529. 
16. 
Tai-Seale, M., et al., Physicians' Well-Being Linked To In-Basket Messages Generated By 
Algorithms In Electronic Health Records. Health Aff (Millwood), 2019. 38(7): p. 1073-1078. 
 
17 Attachments 
These documents are relevant to the protocol, but they are not considered part of the protocol.  They are 
stored and modified separately. As such, modifications to these documents do not require protocol 
amendment.

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Drug/Device Template Version: 13 JUN 2016