Clinical trial NCT06046560
Conditions: Cardiovascular Diseases Diabetes
Keywords: Digital Health Remote Care Delivery Team-based Care Model
Sponsor: Brigham and Women's Hospital
Start date: 2021-03-22; Completion date: 2023-07-25
Enrollment: 200 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
A randomized remote, implementation trial in the Mass General Brigham network was performed on 200 patients with T2D at high CV or kidney risk. The study's primary objective was to create a remote diabetes management platform that improved the initiation and adherence to glucose-lowering medications with CV and kidney benefit and was evaluated by the primary outcome: increasing the proportion of patients with prescriptions for GDMT therapy by 6 months.

Detailed description:
A randomized remote, implementation trial in the Mass General Brigham network performed on 200 patients with T2D at high CV or kidney risk. Patients eligible for, but not prescribed, SGLT2i or GLP-1 RA were randomly assigned to 1) simultaneous patient education and medication initiation "simultaneous" arm or 2) 2-months of education followed by medication initiation "education-first" arm. A multi-disciplinary team provided education and prescribed GDMT using a treatment algorithm. The study's primary objective was to create a remote diabetes management platform that improved the initiation and adherence to glucose-lowering medications with CV and kidney benefit and was evaluated by the primary outcome: increasing the proportion of patients with prescriptions for GDMT therapy by 6 months. Secondary objectives included the primary outcome by randomization arm, prescribed therapy by 2 months, and patients taking prescribed therapy.

Arms: arm 1: Patient will immediately begin participation in a remote, pharmacist-driven heart failure clinic that will initiate and titrate medications according to a standardized medical algorithm. arm 2: Patient will first receive curated patient education, an alert to providers, and provider education, and then after 2 months begin participation in the remote clinic.
Interventions: intervention 1: SGLT2 inhibitor, GLP-1 RA intervention 2: Education-First
Intervention descriptions: intervention 1: Immediate initiation of guideline-directed medical therapy. Will also immediately receive the same educational services provided in the "Education-First" intervention. intervention 2: For the first 2-months of their participation, patients in this arm will receive curated patient education, an alert to providers, provider education, and then after 2 months, be invited to participate in the remote clinic. The patient education would consist of curated video content and informational worksheets provided by email or secure patient messaging. Provider alerts would happen through notifying of a patient's eligibility for therapy.

Protocol documents:
SAP_002.pdf: 
1 
 
 
 
DRIVE Program: Diabetes Remote Intervention to 
improVe use of Evidence-based medications 
 
 
Statistical Analysis Plan 
November 16, 2023 
 
 


2 
 
 Study Information 
 
Title 
DRIVE Program: Diabetes Remote Intervention to improVe use 
of Evidence-based medications 
Principal Investigator 
Benjamin M. Scirica, MD, MPH 
 
Cardiologist, Brigham and Women’s Hospital 
Associate Professor, Harvard Medical School 
 
70 Francis St.  
Boston, MA 02115 
 
Phone: (857) 307-4000  
Email: bscirica@bwh.harvard.edu 
Date of last version of 
protocol 
November 9, 2021 
 
Research question and 
objectives 
● Create a remote diabetes management platform to improve 
adherence to new guidelines regarding use of glucose-
lowering medications with cardiovascular and renal benefit 
for patients with type 2 diabetes and high cardiovascular 
and/or renal risk. 
● Increase patient disease knowledge, activation, and 
engagement. 
● Evaluate optimal timing of patient education within the 
program. 
 
 


3 
 
Research Question and Objectives 
The overarching goal of the DRIVE Program is to partner with and support physicians to 
overcome the well-recognized therapeutic inertia that delays the adoption of new evidence-based 
therapy and prevents patients from achieving recommended care targets.  
In this project, we will use a collaborative drug therapy management (CDTM) agreement to 
allow a pharmacist, in collaboration with a patient navigator, to initiate, discontinue, and titrate 
SGLT2i, GLP-1 RA, and other diabetes medications based on an algorithm developed by 
physicians.  
Importantly, medication selection and recommendations in this program are based on guideline 
recommendation and standard of care. In this project, the patient will be provided with education 
and therapeutic recommendations and will then decide whether to start a new medication and 
which medication to start if there is equipoise between medications. Patients are not “assigned” 
to take a specific medication in any of the navigator-CDTM interventions, if there is equipoise.  
Roughly 50% of patients enrolled into this quality improvement program will be allocated into 
an “education first” pathway, which will provide 4 weeks of digital, paper, and customized video 
resources to explain the medical rationale and anticipatory guidance regarding diabetes care and 
therapeutics with proven benefit prior to becoming eligible for medical therapy prescription. In 
addition to looking at uptake and adherence, we will be measuring baseline and end-of-study 
Patient Activation Measures for each participant. Patient Activation Measures have been shown 
to correlate with increased self-care behaviors, medication adherence, and diabetes monitoring 
(11). 
Primary Aim 
The primary objective of this study is to create a remote diabetes management platform that 
compared to baseline, will improve initiation and adherence to contemporary guidelines 
regarding the use of glucose-lowering medications with cardiovascular and renal benefit for 
patients with type 2 diabetes and high cardiovascular and/or renal risk. 
Secondary Aim(s) 
● Evaluate optimal timing of patient education within the program. (measured as prescriptions 
by randomization arm, prescriptions at 2 months, and patients on therapy at end of study) 
● Increase patient disease knowledge, activation, and engagement (as measured with short-
form Patient Activation Measure) 
Exploratory Aim(s) 
Weight and HbA1c 
We will compare age, socioeconomic demographics (where available), baseline characteristics 
and medical history, HbA1c, and demonstrate that they are evenly distributed in the population 
and between groups. We will report subgroup-specific rates if there are significant differences 
(e.g., evidence of heterogeneity).  


4 
 
Data Sources 
Data will be collected from the electronic health record (HER) and directly from patients. All 
data will be stored in an encrypted, secure database within the Mass General Brigham firewall 
and using HIPAA-compliant applications. 
Study Sample Size 
Primary Outcome: By design, no patients will be on SGLT2i or GLP-1 RA therapy at baseline. 
We are excluding patients who are on the drugs of interest at baseline, so our primary outcome is 
the proportion of prescription therapy provided at 6 months. Our null hypothesis is that with we 
would expect with our education only (control) arm to increase rate of prescription from 0% to 
5% based on secular trends and from 0% to 20% increase in SGLT2i or GLP-1 RA therapy in 
our intervention group utilizing navigators. 100 patients per arm will allow a 25% dropout rate to 
maintain power > 80% to maintain an alpha level of 0.05. As we are comparing the timing of 
education in the A/B allocated groups, we expect that our sample size will provide ~80% power 
to detect an absolute rate of prescription difference of 15% between our immediate titration and 
education prior to titration groups (i.e., at 3 months) 
Secondary Outcomes: With a mean HbA1c of 7.2% and a standard deviation of 1%, to obtain 
80% power to detect a 0.5% difference in HbA1c, we would need to enroll 63 patients per arm 
(preliminary data.) To account for dropout, (expecting 25% dropout) we will calculate N1= n/(1-
dropout rate) => 63/0.75 = 84 patients per arm.  
Data Management 
Mass General Brigham will create a data collection instance within the patient-management 
application. All data will be collected and stored within the Mass General Brigham firewall in a 
HIPAA-compliant, encrypted server, key variables data will be randomly sampled and verified 
for accuracy in 40 patients representing 20% of the study population. Data will be stored for at 
least 5 years after project completion. 
Data Analysis 
We will utilize SAS software, version 9.4 (SAS Institute) to conduct our statistical analysis. 
There will be ongoing quality checks of the data. Before final analysis, the data will be queried 
for outliers and missing data. The primary analysis will not impute any missing data though 
sensitivity analysis may use imputation methods such as last observation carried forward 
(LOCF).  
Definition of Analysis Sets 
For the Full Analysis Set (FAS) Patients will be included all patients enrolled (intention-to-treat 
analysis.) 
The Per protocol Set (PPS) will include patients that did not drop out or become unreachable and 
completed the entire quality improvement program. 


5 
 
Statistical Methods 
For our primary outcome, the percent of patients on either an SGLT2i or GLP-1 RA from 
baseline to conclusion of the study at 6 months post-enrolment, we will perform a Chi-Square 
test to determine a difference in the terminal rates at the end of the study to determine treatment 
effects between groups.  
We will develop a cumulative incidence curve displaying patients both prescribed and taking 
DRIVE medications for the duration of the program. 
We will perform t-tests and Fisher’s exact test for the baseline univariate analysis. As we will be 
utilizing A/B allocation there should be no bias or confounding at baseline, however if any 
significant differences are found, we will correct for these utilizing logistic regression. A/B 
allocation with 200 patients should cause any confounders to balance between the groups. We 
will also perform a longitudinal model for binary outcome at 6 months. For our co-secondary 
outcomes, the change in the HbA1c, and PAM from baseline to the end of the 6-month study, 
these will be analysed with a paired t-test and we will report a mean and standard deviation. A 
secondary analysis will be to conduct linear regression models with two variables (baseline 
HbA1c and baseline weight) to control for any confounders. 
We will conduct our analysis via the intention-to-treat principle with two-sided type I error with 
an alpha of 0.05. For participants with missing outcome data, we will perform a sensitivity 
analysis with missing outcomes excluded or included as an event.  
A priori sub-analyses will be performed based on zip code, baseline HbA1c, race, insurance 
status, and sex with a p-value threshold of 0.1 for these secondary analyses and we will account 
for multiple testing. A cox proportional hazards model will be performed to assess time-to-
prescription between groups. 
After the final data was reviewed, a series of subsequent hypotheses were identified for 
additional analysis. These analyses are, by definition, post hoc and, therefore, considered 
hypothesis-generating. A p-value of 0.05 will be considered significant without any correction 
for multiple comparisons. 
 
Interim Analysis 
N/A 
 
Quality Control 
Data will be collected from our EHR, the MGB Electronic Data Warehouse (EDW), and 
patients. Clinical laboratories within MGB system have laboratory certificates available upon 
request. 

Prot_001.pdf: 
PARTNERS HUMAN RESEARCH COMMITTEE 
PROTOCOL SUMMARY 
Partners Human Subjects Research Application Form  
 
Filename: Protocol Summary 
Version Date:  October 15, 2014 
 
  
1 
 
Answer all questions accurately and completely in order to provide the PHRC with the relevant 
information to assess the risk-benefit ratio for the study.  Do not leave sections blank. 
 
PRINCIPAL/OVERALL INVESTIGATOR 
 
Name: Benjamin Scirica, MD, MPH 
Phone: (857) 307-4000  
Email: bscirica@bwh.harvard.edu 
 
Address: 
70 Francis St.  
Boston, MA 02115 
 
Name of Organization: 
Brigham and Women’s Hospital 
 
PROTOCOL TITLE 
 
DRIVE Program: Diabetes Remote Intervention to improVe use of Evidence-based medications 
 
 
FUNDING 
 
Novo Nordisk, Inc. 
 
VERSION DATE 
 
November 9, 2021 
 
SPECIFIC AIMS 
Concisely state the objectives of the study and the hypothesis being tested. 
 
The aim of this program to: 
 
1.) Create a remote, or “virtual” diabetes management platform to improve adherence to new guidelines 
regarding use of glucose-lowering medications with cardiovascular and renal benefit for patients with 
type 2 diabetes and high cardiovascular and/or renal risk. 
  
2.) Increase patient disease knowledge, activation, and engagement. 
 
3.) Evaluate optimal timing of patient education within the program. 
 


Partners Human Subjects Research Application Form 
  
Filename: Protocol Summary 
Version Date:  October 15, 2014 
 
  
2 
BACKGROUND AND SIGNIFICANCE 
Provide a brief paragraph summarizing prior experience important for understanding the 
proposed study and procedures. 
 
Patients with type 2 diabetes mellitus are at markedly increased risk of cardiovascular disease when 
compared to patients without diabetes. SGLT2 inhibitors (SGLT2i) and GLP1 receptor agonists (GLP1-
RA) are glucose-lowering medications that have also demonstrated improved cardiovascular and renal 
outcomes in patients with cardiovascular disease, at high risk for cardiovascular disease, and with chronic 
kidney disease (CKD). However, to date, there has been slow clinical uptake of these medications, even 
in patients at high cardiovascular and renal risk. Utilizing a navigator-driven approach with a 
collaborative practice agreement-based clinical algorithm will allow for a cost-effective and scalable 
approach to medication optimization in patients with diabetes and cardiovascular disease, increased risk 
of cardiovascular disease, and/or CKD.  
 
A navigator-driven, pharmacist led, remote disease management approach has been shown to be efficient 
and effective in patients who suffer from hypertension, hyperlipidemia, and heart failure (HF) with 
reduced ejection fraction within multiple MGB settings. To date, we have enrolled almost 10,000 MGB 
patients into our programs over the past 4 years. The goal of the proposed program is to expand to 
patients with diabetes who are at increased risk of poor clinical outcomes. The overarching goal of these 
programs is to partner with and support primary care physicians to help overcome the well-recognized 
therapeutic inertia that often delays adoption of new evidence-based therapy and prevents patients from 
achieving recommended care targets. Our programs utilize collaborative drug therapy management 
(CDTM) agreements, statutory legislation that allows pharmacists to start, titrate, and optimize therapy 
when using treatment algorithms designed by physicians. These CDTM agreements are approved by the 
BWH Pharmacy and Therapeutics Committee. 
 
In this project, we will use a CDTM agreement to allow a pharmacist, in collaboration with a patient 
navigator, to initiate, discontinue, and titrate SGLT2i, GLP1-RA, and other diabetes medications based on 
an algorithm developed by physicians.  
 
Importantly, medication selection in this program is guided by shared decision-making. In this project, the 
patient will decide whether to start a new medication and which medication to start if there is equipoise 
between medications. Patients are not “assigned” to take a medication in any of the navigator-CDTM 
interventions.  
 
RESEARCH DESIGN AND METHODS 
Briefly describe study design and anticipated enrollment, i.e., number of subjects to be enrolled 
by researchers study-wide and by Partners researchers.  Provide a brief summary of the 
eligibility criteria (for example, age range, gender, medical condition).  Include any local site 
restrictions, for example, “Enrollment at Partners will be limited to adults although the sponsor’s 
protocol is open to both children and adults.”
 
Eligible patients will be identified prospectively utilizing a search paradigm previously described in Phase 
1 of this project (Reference Protocol 2020E000255). Eligible patients will be selected from several 
sources, including the EHR and the Digital Care Transformation (DCT) cohorts, which are groups of 
patients who previously participated or are currently participating in medication titration for management 
of hypertension, hyperlipidemia, and HF with reduced ejection fraction. These patients will be screened 
for eligibility for inclusion in this program.  
 
Inclusion Criteria: Patient is eligible if they meet ALL the following criteria. 


Partners Human Subjects Research Application Form 
  
Filename: Protocol Summary 
Version Date:  October 15, 2014 
 
  
3 
• 
Type 2 diabetes currently on, or intolerant to, metformin (treated with diet,  DPP4 inhibitor, 
sulfonylurea, pioglitazone, glinides, and/or basal insulin); 
• 
Age 27-79 years; 
• 
Hemoglobin A1c (HbA1c) 6.5-8.9% at the time of screening; 
o Participants whose baseline HbA1c after enrollment is 5.7-6.4% or 9.0-9.9% will remain 
in the program.  
• 
At elevated cardiovascular and/or renal risk defined as any atherosclerotic cardiovascular 
disease (ASCVD)¹, estimated ASCVD risk >10%, HF, estimated glomerular filtration rate (eGFR) 
<60 mL/min/1.73m2, urine albumin-to-creatinine ratio greater than 300 mg/g,  or non-alcoholic 
fatty liver disease, and those aged 60 years or older with at least two of: tobacco use, 
dyslipidemia, hypertension, or abdominal obesity. 
 
Exclusion Criteria: Patient is ineligible if they meet any ONE of the following criteria. 
• 
Type 1 diabetes, type 3c diabetes (pancreatogenous), maturity onset diabetes of the young 
(MODY) 
• 
Currently prescribed an SGLT2i or GLP1-RA;  
• 
Currently prescribed basal and bolus insulin; 
• 
History of diabetic ketoacidosis (DKA) 
• 
History of hypoglycemia²; 
• 
Frequent hypoglycemia (as defined as >2 episodes in 1 week)², OR 
• 
Prior liquid or solid organ transplant 
• 
Limited life expectancy, difficulty managing one’s medications, or any competing medical 
condition that, in the opinion of the investigator would diminish their ability to participate in the 
trial (i.e., active malignancy) 
• 
Pregnancy, breastfeeding, or without adequate birth control utilization 
• 
eGFR below 15 ml/min/m2 
• 
eGFR below 30 ml/min/m2 with a history of pancreatitis 
 
¹ ASCVD for this project is defined as history of myocardial infarction, angina, unstable angina, coronary 
revascularization, percutaneous coronary intervention, transient ischemic attack (TIA) stroke, peripheral 
artery disease, carotid artery disease (>50% luminal obstruction) 
² Hypoglycemia for this project is defined as a blood sugar < 70 mg/dL 
 
Patients recruited into the program will enter either 1) a gradual education period for 2 months followed 
by pharmacist and navigator-based medication titration, or 2) rapid education in conjunction with 
pharmacist and navigator-based medication titration via a Collaborative Drug Therapy Management 
(CDTM) algorithm designed to improve medical therapy for the treatment of type 2 diabetes with 
cardiorenal comorbidities. The CDTM will be approved by the BWH Pharmacy and Therapeutics 
committee. We will use A/B testing to optimize the timing of the educational program. Outcomes will 
include percentage of patients prescribed SGLT2i or GLP1-RA, percentage of prescriptions filled, 
HbA1c, change in the diabetes treatment satisfaction questionnaire short (DTSQs) score, and Patient 
Activation Measure (PAM) at enrollment and completion of the program. 
 
Participants whose HbA1c rises to 9.0-9.9% following enrollment as part of their program baseline labs 
will automatically be assigned to immediate pharmacist and navigator-based medical titration and rapid 
education. As a result, participants with baseline HbA1c between 9.0-9.9% will remain in the program but 
will not be part of the A/B testing. 
  
We will generate prototype software to guide DM medication changes based on patient-specific 
information and to longitudinally monitor each participant's progress through the algorithm and document 


Partners Human Subjects Research Application Form 
  
Filename: Protocol Summary 
Version Date:  October 15, 2014 
 
  
4 
clinical and laboratory information. Basic patient demographic, laboratory, medication, and medical 
history data will be housed in a secure platform database for clinical management and communication. 
Briefly describe study procedures.  Include any local site restrictions, for example, “Subjects 
enrolled at Partners will not participate in the pharmacokinetic portion of the study.”  Describe 
study endpoints.
 
Potential participants will be screened for eligibility through CardioCompass – an application housing 
medical data currently in use at DCT – as well as the EHR as described in protocol 2020E000255. If 
eligible, the patients will be contacted by navigators trained to describe the study procedures, who will 
ask them whether they would be willing to participate. 
 
Participants who agree to participate will enter either early pharmacist and navigator-led medical titration 
and concurrent education, or a gradual titration, through which patients will undergo 2 months of diabetes 
self-management education followed by pharmacist and navigator-led program of medication 
optimization. Navigators will contact the patient at regular intervals and monitor symptoms and 
laboratory tests will be obtained per protocol to ensure safety of the prescribed medications. Any 
symptoms will be evaluated by the program nurse practitioner or physician and managed per standard of 
care.  
 
The education program for all patients will follow standard diabetes self-management education curricula, 
focusing on medication adherence, the role and benefit of medical therapy for the treatment of type 2 
diabetes, and other self-management behaviors. We will offer written materials of current guideline 
recommendations and an online web portal with short educational videos about diabetes, cardiovascular 
risk, and lifestyle and medical interventions. Educational videos produced by study staff will be made 
available to participants through the Mytonomy (www.mytonomy.com) web-based portal. In addition, 
materials from https://knowdiabetesbyheart.org/ – a collaboration between the American Heart 
Association and the American Diabetes Association – will be shared with patients virtually. We will also 
offer live webinar, question/answer sessions for patients and providers to gain education and ask 
questions regarding the medications and program. 
 
Once each participant has been followed for six months, the intervention will conclude with formal 
written handoff to the patient’s primary care provider (PCP), and the ongoing monitoring of labs, disease 
management, health care utilization, health outcomes, and medications will continue beyond the program 
period as per the patient’s PCP. 
 
If an enrolled participant decides that they no longer want to take the medication prescribed within the 
program, they will be asked whether they can be contacted one final time to answer a few questions about 
their current health and the program. This contact would take place at the same time they would have 
completed the program had they remained on the prescribed medication. 
 
For studies involving treatment or diagnosis, provide information about standard of care at 
Partners (e.g., BWH, MGH) and indicate how the study procedures differ from standard care.  
Provide information on available alternative treatments, procedures, or methods of diagnosis.
 
Current standard of care at Mass General Brigham (MGB) includes an individual’s PCP, endocrinologist, 
nephrologist, or cardiologist being aware of the available treatment options, the benefits of the 
medications as demonstrated by medical research, recognizing the patient’s eligibility for the medication, 
the risks and benefits of utilizing and not utilizing the medication, prescribing the medication, and 
following up laboratory and symptoms to assess for efficacy and further medication titration. 
 


Partners Human Subjects Research Application Form 
  
Filename: Protocol Summary 
Version Date:  October 15, 2014 
 
  
5 
Our innovation creates an organized, protocolized manner in which to screen patients, determine 
eligibility for medication initiation, and educate, prescribe, and monitor the effects of these medications 
over the initiation period, when education, monitoring, and titration are required.  
 
Describe how risks to subjects are minimized, for example, by using procedures which are 
consistent with sound research design and which do not unnecessarily expose subjects to risk or 
by using procedures already being performed on the subject for diagnostic or treatment purposes.
 
Risks are minimized with pharmacist and physician oversight, a rigorous medication prescription and 
monitoring protocol, and frequent patient engagement, contact, and laboratory monitoring. Moreover, all 
medications in this program are FDA-approved and being used according to the prescribing instructions 
and guidelines. 
 
Describe explicitly the methods for ensuring the safety of subjects.  Provide objective criteria for 
removing a subject from the study, for example, objective criteria for worsening disease/lack of 
improvement and/or unacceptable adverse events.  The inclusion of objective drop criteria is 
especially important in studies designed with placebo control groups.
 
The program requires that particular prescriptions and titrations be accompanied by an appropriately 
timed laboratory test. In parallel with the laboratory draws, navigators will routinely ask participants to 
report potential adverse events. Program pharmacists carry out all prescribing decisions per standardized 
protocol, and physicians oversee the process and are available for consultation on any patient as needed. 
All dosing information as well as reported medication side effects and/or intolerances will be entered into 
the EHR. Moreover, all medications in this program are FDA-approved and being used according the 
prescribing instructions and guidelines. 
 
FORESEEABLE RISKS AND DISCOMFORTS 
Provide a brief description of any foreseeable risks and discomforts to subjects.  Include those 
related to drugs/devices/procedures being studied and/or administered/performed solely for 
research purposes.  In addition, include psychosocial risks, and risks related to privacy and 
confidentiality.  When applicable, describe risks to a developing fetus or nursing infant.
 
All digital health technologies containing participant data will be secure according to MGB standards. 
Patient-identifying data will be accessible only to those assigned to the protocol who require this data to 
ensure patient safety. All health information is stored on MGB encrypted computers.  
 
EXPECTED BENEFITS 
Describe both the expected benefits to individual subjects participating in the research and the 
importance of the knowledge that may reasonably be expected to result from the study.  Provide 
a brief, realistic summary of potential benefits to subjects, for example, “It is hoped that the 
treatment will result in a partial reduction in tumor size in at least 25% of the enrolled subjects.”  
Indicate how the results of the study will benefit future patients with the disease/condition being 
studied and/or society, e.g., through increased knowledge of human physiology or behavior, 
improved safety, or technological advances. 
 
Clinical trials have demonstrated that SGLT2i and GLP1-RA can improve cardiovascular and renal 
outcomes. The EMPA-REG OUTCOME, DECLARE-TIMI 58, CANVAS, and VERTIS-CV trials 
demonstrated, in aggregate, a reduction in mortality, major adverse cardiovascular events, HF events, and 
renal adverse events for patients with type 2 diabetes and ASCVD and CKD (1, 2, 3, 4). The LEADER, 


Partners Human Subjects Research Application Form 
  
Filename: Protocol Summary 
Version Date:  October 15, 2014 
 
  
6 
EXSCEL, Harmony Outcomes, and REWIND trials, in aggregate, similarly demonstrated a reduction in 
mortality and major adverse cardiovascular events for patients with type 2 diabetes and ASCVD (5, 6, 7, 
8). With these benefits, the American Diabetes Association (ADA) and European Association for the 
Study of Diabetes (EASD), American College of Cardiology (ACC), and Kidney Disease: Improving 
Global Outcomes (KDIGO) guidelines have recommended these two classes of medication for patients 
with ASCVD, HF, or CKD (9, 10, 11, 12, 13). Registries, however, have found low utilization of these 
classes of medications, including in the MGB health system (14, 15).  
 
EQUITABLE SELECTION OF SUBJECTS 
The risks and benefits of the research must be fairly distributed among the populations that stand 
to benefit from it.  No group of persons, for example, men, women, pregnant women, children, 
and minorities, should be categorically excluded from the research without a good scientific or 
ethical reason to do so.  Please provide the basis for concluding that the study population is 
representative of the population that stands to potentially benefit from this research.
 
The study population will be drawn from the EHR and/or the BWH Innovation database of patients, and 
eligible patients will be consecutively contacted for potential participation with no bias. We will focus on 
enrolling patients at high cardiovascular and renal risk (based on the presence of ASCVD, high ASCVD 
risk score, and/or a known diagnosis of HF or CKD) in whom these medications have FDA indication and 
the support of society guidelines for their use. 
 
When people who do not speak English are excluded from participation in the research, provide 
the scientific rationale for doing so.  Individuals who do not speak English should not be denied 
participation in research simply because it is inconvenient to translate the consent form in 
different languages and to have an interpreter present.
 
Our navigators are fluent in English. For patients who do not speak English, MGB’s interpreter services 
will be used for both the initial enrollment call and all future verbal communications. A written consent 
form will not be used, as detailed in the Consent Procedures section. 
 
For guidance, refer to the following Partners policy: 
          Obtaining and Documenting Informed Consent of Subjects who do not Speak English
          https://www.partners.org/Assets/Documents/Medical-Research/Clinical-
Research/Non-English-Speaking-Subjects.pdf 
 
 
 
RECRUITMENT PROCEDURES 
Explain in detail the specific methodology that will be used to recruit subjects.  Specifically 
address how, when, where and by whom subjects will be identified and approached about 
participation.  Include any specific recruitment methods used to enhance recruitment of women 
and minorities.
 
• 
The study population will be recruited through both A) an algorithm designed specifically for this 
protocol that identifies eligible patients within the MGB EHR and B) the existing BWH 
Innovation cohort defined earlier. 


Partners Human Subjects Research Application Form 
  
Filename: Protocol Summary 
Version Date:  October 15, 2014 
 
  
7 
• 
Through email or the Epic in-basket, the navigator will notify each potential participant’s PCP of 
their patient’s eligibility and the program details. The PCP can choose to tell the study team not to 
contact their patient. 
• 
The navigator will then send a Patient Gateway or email message to the patient informing them of 
the program details, requesting they take a brief Intake Survey, and notifying them that they will 
contact them by phone if they do not opt out. 
o Prior to sending program information via an email message, the navigator will first send 
the IRB-approved Email Consent email message. 
• 
Lastly, the navigator will call the patient. 
 
 
Provide details of remuneration, when applicable.  Even when subjects may derive medical 
benefit from participation, it is often the case that extra hospital visits, meals at the hospital, 
parking fees or other inconveniences will result in additional out-of-pocket expenses related to 
study participation.  Investigators may wish to consider providing reimbursement for such 
expenses when funding is available
 
Participants will not be paid or receive any type of remuneration / compensation for their time and 
expenses. Participants will pay for laboratory draws in accordance with their personal health 
insurance plans. 
 
 
For guidance, refer to the following Partners policies: 
          Recruitment of Research Subjects 
          https://www.partners.org/Assets/Documents/Medical-Research/Clinical-
Research/Recruitment-Of-Research-Subjects.pdf
 
          Guidelines for Advertisements for Recruiting Subjects
          https://www.partners.org/Assets/Documents/Medical-Research/Clinical-
Research/Guidelines-for-Advertisements.pdf 
 
          Remuneration for Research Subjects
          https://www.partners.org/Assets/Documents/Medical-Research/Clinical-Research/Remuneration-for-
Research-Subjects.pdf 
 
 
CONSENT PROCEDURES 
Explain in detail how, when, where, and by whom consent is obtained, and the timing of consent 
(i.e., how long subjects will be given to consider participation).  For most studies involving more 
than minimal risk and all studies involving investigational drugs/devices, a licensed physician 
investigator must obtain informed consent.  When subjects are to be enrolled from among the 
investigators’ own patients, describe how the potential for coercion will be avoided.
 
Potential participants will be notified by letter or Patient Gateway message that they will soon receive a 
call from a navigator about possible enrollment into the program. 
 
The navigator will review the program details with the participant over the phone. The participant can 
agree to participate during this initial phone call but will also be given the opportunity to ask questions, 
review written materials, and/or separately speak to their PCP prior to enrollment. There is no time 


Partners Human Subjects Research Application Form 
  
Filename: Protocol Summary 
Version Date:  October 15, 2014 
 
  
8 
constraint within which the patient must agree to participate. However, enrollment will be capped at the 
first 200 patients who agree to participate. The patient’s decision to participate or not to participate in this 
program will be documented in the EHR. The patient will be informed that the decision to participate or 
not will not affect the care they receive from other providers. 
 
As this project is using FDA-approved medications prescribed according to guideline recommendations 
and therefore the primary risk to subjects is no more than minimal and no different from standard of care, 
the study will be conducted with a waiver of consent/authorization. 
 
NOTE: When subjects are unable to give consent due to age (minors) or impaired decision-
making capacity, complete the forms for Research Involving Children as Subjects of Research 
and/or Research Involving Individuals with Impaired Decision-making Capacity, available on 
the New Submissions page on the PHRC website: 
      https://partnershealthcare.sharepoint.com/sites/phrmApply/aieipa/irb 
 
For guidance, refer to the following Partners policy: 
     Informed Consent of Research Subjects:
     https://www.partners.org/Assets/Documents/Medical-Research/Clinical-
Research/Informed-Consent-of-Research-Subjects.pdf
 
 
 
DATA AND SAFETY MONITORING 
Describe the plan for monitoring the data to ensure the safety of subjects.  The plan should 
include a brief description of (1) the safety and/or efficacy data that will be reviewed; (2) the 
planned frequency of review; and (3) who will be responsible for this review and for determining 
whether the research should be altered or stopped.  Include a brief description of any stopping 
rules for the study, when appropriate.  Depending upon the risk, size and complexity of the 
study, the investigator, an expert group, an independent Data and Safety Monitoring Board 
(DSMB) or others might be assigned primary responsibility for this monitoring activity.        
 
NOTE: Regardless of data and safety monitoring plans by the sponsor or others, the principal 
investigator is ultimately responsible for protecting the rights, safety, and welfare of subjects 
under his/her care. 
 
The study team  will review laboratory results and potential adverse event data, as needed, within 3  
weeks of initiation or titration, and for the period the program is responsible for the medication and until 
diabetes care is handed back to his/her PCP. Participants will also be encouraged and asked to report any 
side effects that they experience while in the program. The principal investigator will determine whether 
the research should be altered or stopped. 
 
Describe the plan to be followed by the Principal Investigator/study staff for review of adverse 
events experienced by subjects under his/her care, and when applicable, for review of sponsor 
safety reports and DSMB reports.  Describe the plan for reporting adverse events to the sponsor 
and the Partners’ IRB and, when applicable, for submitting sponsor safety reports and DSMB 
reports to the Partners’ IRBs.  When the investigator is also the sponsor of the IND/IDE, include 
the plan for reporting of adverse events to the FDA and, when applicable, to investigators at 
other sites.   


Partners Human Subjects Research Application Form 
  
Filename: Protocol Summary 
Version Date:  October 15, 2014 
 
  
9 
 
NOTE: In addition to the adverse event reporting requirements of the sponsor, the principal 
investigator must follow the Partners Human Research Committee guidelines for Adverse Event 
Reporting
 
Clinical outcomes will be monitored periodically as per standard of care with regular and appropriate 
laboratory and clinically reported events. For those taking SGLT2i, we expect DKA ~0.2%, 
hypoglycemia ~3%, UTI, and/or mycotic infections at a rate of ~6% and will prospectively collect and 
monitor clinical data related to this program. We will also review the EHR for hospitalizations. GLP1-RA 
are known to cause gastrointestinal side effects in ~20% of users; these are mitigated by slow titration. 
More serious AEs such as gallbladder events are rarer and occur at a frequency lower than may be 
observed in a sample of this size. The details of the management protocol, including monitoring for 
safety, will be based on existing guidelines. This will be submitted separately to the P&T committee. 
HbA1c will be checked at 3 and 6 months after the initiation of therapy per ADA guidelines for usual care 
after diabetes medication change. 
 
MONITORING AND QUALITY ASSURANCE 
Describe the plan to be followed by the principal investigator/study staff to monitor and assure 
the validity and integrity of the data and adherence to the IRB-approved protocol.  Specify who 
will be responsible for monitoring, and the planned frequency of monitoring.  For example, 
specify who will review the accuracy and completeness of case report form entries, source 
documents, and informed consent.   
 
NOTE: Regardless of monitoring plans by the sponsor or others, the principal investigator is 
ultimately responsible for ensuring that the study is conducted at his/her investigative site in 
accordance with the IRB-approved protocol, and applicable regulations and requirements of the 
IRB.
 
The study data will be monitored regularly by the principal investigator and clinical leads, supported by 
data analysts for quality assurance. 
 
For guidance, refer to the following Partners policies: 
          Data and Safety Monitoring Plans and Quality Assurance
         https://www.partners.org/Assets/Documents/Medical-Research/Clinical-Research/DSMP-in-
Human-Subjects-Research.pdf 
 
          Reporting Unanticipated Problems (including Adverse Events)
          https://www.partners.org/Assets/Documents/Medical-Research/Clinical-
Research/Reporting-Unanticipated-Problems-including-Adverse-Events.pdf
 
 
 
PRIVACY AND CONFIDENTIALITY 
Describe methods used to protect the privacy of subjects and maintain confidentiality of data 
collected.  This typically includes such practices as substituting codes for names and/or medical 
record numbers; removing face sheets or other identifiers from completed 
surveys/questionnaires; proper disposal of printed computer data; limited access to study data; 


Partners Human Subjects Research Application Form 
  
Filename: Protocol Summary 
Version Date:  October 15, 2014 
 
  
10 
use of password-protected computer databases; training for research staff on the importance of 
confidentiality of data, and storing research records in a secure location.   
 
NOTE: Additional measures, such as obtaining a Certificate of Confidentiality, should be 
considered and are strongly encouraged when the research involves the collection of sensitive 
data, such as sexual, criminal or illegal behaviors.
 
All digital health technologies containing participant data will be secure according to MGB standards. 
Patient-identifying data will be accessible only to those assigned to the protocol who require these data to 
ensure patient safety. All health information is stored on MGB encrypted computers. 
 
SENDING SPECIMENS/DATA TO RESEARCH COLLABORATORS OUTSIDE 
PARTNERS 
Specimens or data collected by Partners investigators will be sent to research collaborators 
outside Partners, indicate to whom specimens/data will be sent, what information will be sent, 
and whether the specimens/data will contain identifiers that could be used by the outside 
collaborators to link the specimens/data to individual subjects.
 
Identifiable information will not be shared with persons or entities outside of MGB. Research 
collaborators will be provided with high-level tables that do not include any patient identifiable 
information.  
 
Specifically address whether specimens/data will be stored at collaborating sites outside 
Partners for future use not described in the protocol.  Include whether subjects can withdraw 
their specimens/data, and how they would do so.  When appropriate, submit documentation of 
IRB approval from the recipient institution.
 
No specimens or data will be stored at collaborating sites outside of MGB for future use. 
 
Participants can withdraw their participation from the study. However, since the study is done in 
collaboration with patients’ PCPs and all data is entered within the EHR, their data will not be removed. 
 
RECEIVING SPECIMENS/DATA FROM RESEARCH COLLABORATORS OUTSIDE 
PARTNERS 
When specimens or data collected by research collaborators outside Partners will be sent to 
Partners investigators, indicate from where the specimens/data will be obtained and whether the 
specimens/data will contain identifiers that could be used by Partners investigators to link the 
specimens/data to individual subjects.  When appropriate, submit documentation of IRB 
approval and a copy of the IRB-approved consent form from the institution where the 
specimens/data were collected.
 
Specimens will not be obtained from outside MGB.