Veterans Affairs Pharmacist Heart Failure Medication Titration Project 2
Phase: NA
Conditions: Quality Improvement, Pharmacotherapy, Heart Failure
Sponsor: Stanford University

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Randomized Evaluation of Audit and Feedback and Referral Nudges to Increase Heart Failure 
Medication Optimization Among Primary Care Pharmacists in the Veterans Affairs Healthcare 
System (PHARM-HF-2) 
 
Protocol V-1.1 
 
July 10, 2025 
 
 

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PROJECT SUMMARY  
Title 
Randomized Evaluation of Audit and Feedback and Referral Nudges 
to Increase Heart Failure Medication Optimization Among Primary 
Care Pharmacists in the Veterans Affairs Healthcare System 
(PHARM-HF-2) 
Study Objectives 
The co-primary objectives are to determine whether either (1) a 
education and feedback (E+F) intervention providing pharmacists 
with HF education and feedback of their heart failure (HF) 
medication titration encounter rates or (2) primary care referral 
nudges increase the frequency of primary care pharmacist heart 
failure medication management encounters.  
Study Design 
The PHARM-HF-2 is a multi-site pragmatic randomized quality 
improvement project that evaluates two different interventions. 
First, the education and feedback intervention will be randomized 
at the level of the clinical site in a stepped wedge design. A total of 
22 VHA sites will be randomized to different time points at which 
they begin receiving the intervention. In the initial phase, all sites 
will receive education only. At intervals of 2 months, 4 sites will 
transition from education only to education and feedback in a 
randomized order. By the end of the project, all sites will be 
receiving the education and feedback intervention.  
 
Second, primary care referral nudges will studied with a two-arm 
parallel design with randomization at the level of the primary care 
team (PACT team) with 1:1 allocation stratified by site. This nested 
evaluation will start four months into the study. 
Number of Participants 
N ~22 sites with ~400 pharmacists and ~400 PACT teams 
Trial Location 
United States: Veterans Health Administration VISN 6 sites (n=7), 
VISN 10 sites (n=7), and VISN 19 sites (n=8) 
Inclusion Criteria 
Pharmacists and primary care clinicians employed within the VHA 
VISN and providing Patient Aligned Care Team (PACT) care 
Exclusion Criteria 
Lack of site alignment with this quality improvement initiative   
Intervention 1: Audit 
and 
Feedback 
+ 
Education vs. Education 
Only 
VHA Sites will be randomly assigned to Education + Feedback vs. 
Education Only groups. 
At sites randomized to the Education+Feedback group, PACT 
pharmacists with prior HF actions will receive data monthly via 
email including their total medication titration encounters. They 
will also receive invitations to monthly educational sessions and 
access to shared resources on HF medication management.  
At sites randomized to Education only, PACT pharmacists will 
receive access to the monthly educational sessions and access to 

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shared resources on HF medication management. They will not 
receive monthly emails or other reminders. 
Intervention 2: Primary 
Care Pharmacy Referral 
Nudges vs. Usual Care 
VHA sites will be randomly assigned to primary care pharmacy 
referral nudges (Referral Nudges) vs. Usual Care.  
For sites randomized to primary care pharmacy referral nudges, 
primary care clinician will receive a weekly Teams message with 
Veterans being seen that week with HF that are on suboptimal 
medication therapy with a suggestion to consider discussing PACT 
pharmacy referral.  
 
For PACT teams randomized to usual care, there will be no referral 
nudges. 
Randomization 
For the education and feedback intervention, we will randomize 
PACT teams via a stepped wedge design stratified by VISN using 2-
month intervals. There will be 4 sites that transition from Education 
Only to Education and Feedback every 2 months. 
For the primary care pharmacy referral nudges,  we will use 
permuted block 1:1 randomization with block sizes of 2 to primary 
care pharmacy referral nudges vs. usual care. 
Co-Primary Endpoint 
Number of monthly heart failure medication adjustment 
encounters for pharmacists in the Education+Feedback vs. 
Education Only arms. 
Co-Primary Endpoint 
Number of monthly heart failure medication adjustment 
encounters for pharmacists in PACT teams with Referral Nudges vs. 
Usual Care.  
Secondary Endpoints 
• Number of HF encounters with pharmacists 
• For the primary care referral intervention, the rate of GDMT 
utilization (beta-blocker, ACE-I/ARB/ARNI, MRA, SGLT-2) among 
patients without documented contraindications based on vitals, 
allergies, and laboratory values. 
• For the primary care referral intervention, the percentage of HF 
patients at greater than 50% target dose of each GDMT 
category among patients without documented 
contraindications based on vitals, allergies, and laboratory 
values 
Study Timeline 
• Sites and PACT teams will be randomized at the study start for 
each VISN. 

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• Following randomization, monthly educational sessions will 
start, and educational resources will be available. 
• Starting month 5, primary care clinicians will receive weekly 
messages regarding patients with upcoming visits on 
suboptimal GDMT. 
Assessment 
Heart failure medication actions and heart failure medications will 
be assessed via the VHA Corporate Data Warehouse at the end of 
the study. 
Duration 
The overall study duration will be 12 months. This will include 6 
study intervals.   
Statistical 
Considerations 
For the education and feedback intervention, we assumed there 
are at 4 sites randomized during each of 5 steps with a mean 
number of pharmacists of 21 per site. With a moderate coefficient 
of variation of 0.3 for sites, a mean number of HF medication 
adjustment encounters of 0.4 and a standard deviation of 0.8, we 
have 90% power for identifying a change in HF medication 
adjustment encounters of 0.2. 
 
For the primary care pharmacist referral intervention, we assumed 
there will be 11 sites randomized to referral nudges and 11 to usual 
care. With a mean number of 0.8 monthly pharmacist HF 
medication adjustment encounters in the usual care arm and a 
standard deviation of 0.8, we have 90% power for identifying a 
change in HF medication adjustment encounters of 0.8.  
 
 
 

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1. BACKGROUND AND RATIONALE  
 
HF causes >1.2 million hospitalizations and 300 thousand deaths annually.  This occurs despite 
effective GDMT for HFrEF.1  With SGLT2i, there is now also therapy for improving quality of 
life and reducing hospitalizations for HF with preserved ejection fraction (HFpEF).2  While 
prior quality improvement efforts have focused on inpatient care, there is a critical need to 
improve outpatient care. GDMT escalation in the outpatient setting is rare.3  This inertia leads 
to persistent GDMT gaps with <2% of outpatients on optimal therapy.3,4 
 
Nurse or pharmacist led GDMT management programs have been shown to effectively 
increase GDMT rates.5 The VHA has a pharmacist-based HF remote management program 
that uses an online, real-time, patient dashboard to optimize HF therapy. However, only 10% 
of VHA patients with recent-onset HF received HF care from pharmacists, with many of the 
encounters being limited to monitoring and education. Expanding the pharmacist program is 
a national VHA goal, but how to successfully implement this is unclear. Prior studies at single-
center academic VAs have shown that utilization of the VHA pharmacist management 
program significantly increases GDMT rates.6–11  
 
The PHARM-HF 2 study is testing an implementation strategy for pharmacist HF care across 
three VHA regions to evaluate if combined pharmacist education and monthly feedback 
messages increases VHA pharmacist HF management. Simultaneously, the project will 
evaluate if primary care nudges for pharmacist referral increase pharmacist HF management. 
 
 

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2. HYPOTHESIS 
Our primary hypotheses are the following: (1) Education with feedback messages increase the 
frequency of pharmacist HF medication management compared with education alone and (2) 
Primary care pharmacist referral nudges increase the frequency of pharmacist HF medication 
management compared with usual care. 
 
 

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3. PROJECT DESIGN 
This is a multisite randomized quality improvement project. The project evalues two separate 
interventions to increase pharmacist HF medication adjustment. First, in a stepped wedge 
randomized design,  we will compare education and feedback messages with education versus 
education alone.  The education and feedback intervention will be randomized at the level of 
the clinical site. A total of 22 VHA sites will be randomized to different time points at which they 
begin receiving the intervention. In the initial phase, all sites will receive education only. At 
intervals of 2 months, 4 sites will transition from education only to education and feedback in a 
randomized order. By the end of the project, all sites will be receiving the monthly education 
and feedback intervention. The figure below displays the randomization.  The figure below 
displays the site randomization over time.  
 
All pharmacists will receive access to educational material. The educational material will include 
monthly Teams webinars and sharepoint resources with titration protocols, frequently asked 
questions documents, and other HF educational information. Following randomization to the 
education and feedback arm, the pharmacists will receive a monthly Teams message containing 
the intervention. Data for the intervention will be obtained from the VHA national HF 
dashboards. The frequency of pharmacist HF medication actions will be assessed at the end of 
the 12-month study.  
 
 
 
The second component of the project will be a parallel randomized project comparing primary 
care pharmacist referral nudges with usual care. This second project will be nested within sites 
randomized to education and feedback above in months 5 and later. Sites will be block 
randomized  1:1 with block sizes of 2. 
 
 
Site 1
Education
Education
E&F
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Site 5
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Site 6
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Site 7
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Site 8
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Site 9
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Site 10
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Site 11
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Site 12
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Site 13
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Site 17
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Site 18
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Site 19
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Site 20
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Site 21
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Site 22
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Month 1 
Month 2
Month 3
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Month 12
7/16-8/15
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10/16-11/15 11/16-12/15 12/16-1/15
1/16-2/15
2/16-3/15
3/16-4/15
4/16-5/15
5/16-6/15
6/16-7/15

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4. PROJECT PROCEDURES 
 
Randomization  
The sequence generation process will be performed using a secure password-protected 
computerized randomization algorithm on REDCap. Site randomization for education and 
feedback intervention crossover will occur at the start of the study for all sites.  
Randomization of PACT teams will occur at the time each site crosses over to the education and 
feedback arm. Sites will be randomized with block sizes of 2. 
 
 
 

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5. 
TREATMENT ARMS 
5.1  
Educational Only 
All pharmacists will be informed regarding the educational material on a VHA Sharepoint site. 
The educational information will include suggested titration protocols, education about heart 
failure medications, a frequently asked questions document, guideline documents, patient 
educational material, and recordings of Teams webinars on heart failure management. The 
pharmacists will be invited to a regular webinar regarding heart failure medication 
management. 
 
5.2  
Education and Feedback (E+F) 
For sites randomized to education and feedback, all PACT pharmacists with a heart failure 
action within the last year will receive a monthly Teams message. The monthly Teams message 
will contain information including their heart failure medication actions over the prior 3 month 
period. This data will be obtained from VHA pharmacy data. The message will also include 
reminders regarding the monthly educational sessions and access to the educational 
sharepoint. They will also receive a Teams calendar hold for the monthly educational meeting. 
 
5.3 
Primary Care Pharmacist Referral Nudges 
For sites randomized to the referral nudges, primary care clinicians will receive a weekly email 
that lists potential patients with HF with reduced ejection fraction with upcoming clinic visits 
that are not on optimal medication therapy. These patients will be eligible for, but not 
prescribed, at least 50% of the target dose of one of four classes of guideline-recommended 
heart failure therapy: beta-blockers, renin angiotensin system inhibitors, mineralocorticoid 
receptor antagonists, or sodium glucose cotransporter 2 inhibitors. The message will suggest 
referral to PACT pharmacists for medication optimization.  
 
 
 

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6.  
STATISTICAL CONSIDERATIONS AND ANALYSIS PLAN 
6.1  
Sample Size Assumptions 
For the education and feedback intervention, we assumed there are 4 sites randomized during 
each of 5 steps with a mean number of pharmacists of 21 per site. With a moderate coefficient 
of variation of 0.3 for sites, a mean number of HF medication adjustment encounters of 0.4 and 
a standard deviation of 0.8, we have 90% power for identifying a change in HF medication 
adjustment encounters of 0.2. 
 
For the primary care pharmacist referral intervention, we assumed there will be 22 sites with 
400 PACT teams randomized to referral nudges or usual care. With a mean number of 0.8 
monthly pharmacist HF medication adjustment encounters in the usual care arm and a 
standard deviation of 0.8, we have over 90% power for identifying a change in HF medication 
adjustment encounters of 0.8.  
 
6.2  
Statistical Analysis Plan 
To be finalized.