Reducing Inappropriate Medication Use for BPSD and Improving Health Outcomes for PLWD
Phase: NA
Conditions: Dementia
Sponsor: University of California, Davis

Protocol Template, Version 3.0  
Clinical Interventional Study  
Protocol (CISP) 
 
 

Protocol Template, Version 3.0 
 
 
FULL PROTOCOL TITLE 
 
Reducing Inappropriate Medication Use for BPSD and Improving Health Outcomes in 
PLWD Principal Investigator: 
Helen C. Kales, MD 
Joe P. Tupin Endowed Professor and Chair of the Department of Psychiatry and Behavioral 
Sciences at University of California, Davis  
Supported by: 
The National Institute on Aging 
FY22_Pilot2_Kales  
Study Intervention Provided by: N/A 
Sponsor of IND/IDE: N/A 
(Any modification to the protocol should be annotated on the coversheet or in an appendix.  The 
annotation should note the exact words that are changed, the location in the protocol, the date 
the modification was approved by the Executive Committee, and the date it became effective.)  
Version 1  
 
November 15, 2022 
 
 
 
 
 

Protocol Template, Version 3.0 
 
 
 
PROTOCOL VERSION TRACKING 
When making changes to an approved and “final” protocol, please provide a summary of the 
changes, with the date, at the front of the protocol. Update the version number and date with each 
change.  
 
Date 
Version # 
Summary of changes to protocol 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Protocol Template, Version 3.0 
 
 
TABLE OF CONTENTS 
Page 
PREFACE ......................................................................................... Error! Bookmark not defined. 
FULL PROTOCOL TITLE .......................................................................................................... i 
TABLE OF CONTENTS ............................................................................................................. 3 
PRÉCIS .......................................................................................................................................... 6 
Study Title ................................................................................................................................. vii 
Objectives ................................................................................................................................. vii 
Design and Outcomes ................................................................................................................. ii 
Interventions and Duration ........................................................................................................ iii 
Sample Size and Population ....................................................................................................... iii 
STUDY TEAM ROSTER ............................................................................................................ 1 
Principal Investigator: Name .................................................................................................... 1 
Co-Investigators: Name ............................................................................................................ 1 
PARTICIPATING STUDY SITES ............................................................................................. 3 
1 
Study objectives ..................................................................................................................... 3 
1.1 
Primary Objective ........................................................................................................... 3 
1.2 
Secondary Objectives ...................................................................................................... 3 
2 
BACKGROUND AND RATIONALE ................................................................................ 3 
2.1 
Background on Condition, Disease, or Other Primary Study Focus .............................. 4 
2.2 
Study Rationale ............................................................................................................... 5 
3 
STUDY DESIGN ................................................................................................................... 7 
4 
SELECTION AND ENROLLMENT OF PARTICIPANTS ............................................ 8 
4.1 
Inclusion Criteria ............................................................................................................ 9 
4.2 
Exclusion Criteria ........................................................................................................... 9 
4.3 
Study Enrollment Procedures ......................................................................................... 9 
5 
STUDY INTERVENTIONS ................................................................................................ 9 

Protocol Template, Version 3.0 
 
 
5.1 
Interventions, Administration, and Duration .................................................................. 9 
5.2 
Handling of Study Interventions ................................................................................... 11 
5.3 
Concomitant Interventions ............................................................................................ 11 
5.3.1 Allowed Interventions ................................................ Error! Bookmark not defined. 
5.3.2 Required Interventions ............................................... Error! Bookmark not defined. 
5.3.3 Prohibited Interventions ............................................. Error! Bookmark not defined. 
5.4 
Adherence Assessment ................................................................................................. 11 
6 
STUDY PROCEDURES .................................................................................................... 11 
6.1 
Schedule of Evaluations ................................................................................................ 12 
6.2 
Description of Evaluations ............................................................................................ 13 
6.2.1 Screening Evaluation ................................................................................................ 13 
6.2.2 Enrollment, Baseline, and/or Randomization ........................................................... 13 
6.2.3 Follow-up Visits ....................................................................................................... 13 
6.2.4 Completion/Final Evaluation .................................................................................... 13 
7 
SAFETY ASSESSMENTS ................................................................................................. 13 
7.1 
Specification of Safety Parameters ............................................................................... 13 
7.2 
Methods and Timing for Assessing, Recording, and Analyzing Safety Parameters .... 13 
7.3 
Adverse Events and Serious Adverse Events ............................................................... 14 
7.3.1 Reporting Procedures ................................................................................................ 14 
7.3.2 Follow-up for Adverse Events .................................................................................. 15 
7.4 
Safety Monitoring ......................................................................................................... 15 
8 
INTERVENTION DISCONTINUATION ....................................................................... 15 
9 
STATISTICAL CONSIDERATIONS .............................................................................. 17 
9.1 
General Design Issues ................................................................................................... 17 
9.2 
Sample Size and Randomization .................................................................................. 17 
9.2.1 Treatment Assignment Procedures ........................................................................... 18 
9.3 
Interim analyses and Stopping Rules ............................................................................ 18 
9.4 
Outcomes ...................................................................................................................... 18 
9.4.1 Primary outcome ........................................................ Error! Bookmark not defined. 
9.4.2 Secondary outcomes .................................................. Error! Bookmark not defined. 
9.5 
Data Analyses ............................................................................................................... 19 
10 DATA COLLECTION AND QUALITY ASSURANCE ................................................ 20 
10.1 
Data Collection Forms .................................................................................................. 20 

Protocol Template, Version 3.0 
 
 
10.2 
Data Management ......................................................................................................... 20 
10.3 
Quality Assurance ......................................................................................................... 20 
10.3.1 
Training ................................................................................................................. 20 
10.3.2 
Quality Control Committee ................................................................................... 20 
10.3.3 
Metrics .................................................................................................................. 20 
10.3.4 
Protocol Deviations ............................................................................................... 20 
10.3.5 
Monitoring ............................................................................................................ 20 
11 PARTICIPANT RIGHTS AND CONFIDENTIALITY ................................................. 20 
11.1 
Institutional Review Board (IRB) Review .................................................................... 20 
11.2 
Informed Consent Forms .............................................................................................. 20 
11.3 
Participant Confidentiality ............................................................................................ 22 
11.4 
Study Discontinuation ................................................................................................... 22 
12 ETHICAL CONSIDERATIONS ....................................................................................... 23 
13 COMMITTEES .................................................................................................................. 23 
14 PUBLICATION OF RESEARCH FINDINGS ................................................................ 23 
15 REFERENCES .................................................................................................................... 23 
16 SUPPLEMENTS/APPENDICES ...................................................................................... 23 
 
I. Procedures Schedule 
  
II. Informed Consent Form Template 
  
III. Other (add as many appendices as necessary) 
 
 

Protocol Template, Version 3.0 
 
 
PRÉCIS 
Intervention Structure, Implementation Protocol, Fidelity/Adherence Monitoring Plan:  
In this study, we will refine and pilot the application of DICE in 4 primary care clinics by: (a) 
leveraging existing clinic staff to deliver DICE to care partner-PLWD dyads; (b) using 
electronic resources to identify and recruit PLWD-care partner dyads based on clinically 
relevant and minimum inclusion/exclusion criteria; and c) evaluating clinically relevant 
outcomes using the electronic medical record (EMR).  DICE will be implemented in four large 
primary care clinics within the UCD Health System over a 6-month period (n=100 PLWD-care 
partner dyads; 25 dyads per site, allowing comparison of implementation and outcomes by site 
characteristics). Key “study champions” at each of the four primary care clinics will be the 
licensed practical nurse assigned to each clinic who will serve as the Onsite DICE Coordinator 
(ODC).  
 
As a minimal risk study embedded in primary care practices, we plan to obtain a waiver of 
informed consent for PLWD, care partners and clinic staff in order to reduce introduction of 
artificial care resources or biases wherever possible. Additionally, a HIPAA waiver will be 
obtained for subject identification (see a. below) and outcome ascertainment from the EMR. 
There will be minimal PHI data collected. At the time the agreement is finalized, the IRB of 
Record to make the HIPAA determinations, or if necessary UC Davis IRB will make the HIPAA 
determinations before releasing the acknowledgment of a reliance on an external IRB. 
 
 
We have arranged with University of California Davis LVN supervisors (Ms. Elder and Ms. 
Skillsky) to do a 6-hour training for all of the LVNs on a single day. This will be a hybrid of in 
person (kick off session and ending brainstorming session) and watching the online modules 
together in a campus auditorium. ODCs will then use the approach in a “test” case in study 
months 2-3 during which they will engage in as needed coaching with a DICE trainer (a 
geriatric psychiatrist and education specialist) to ensure they are using the approach with 
fidelity.  The DICE trainer will also be available as needed for coaching during the remainder 
of the study for approach related questions. Manualization and training with follow-up 
coaching have been shown to be effective implementation strategies that can enhance fidelity 
of implementation of an evidence-based program.  Other clinic personnel (social workers and 
PCPs) will also receive the manual, an email overview of the study, and be invited to train 
using the website or at the on-site training. Following training and case consultation, the ODCs 
will then use the DICE Approach for any PLWD they encounter during the 6-month study 
period (months 4-9). Primary outcome metrics will be collected using the electronic medical 
record and by estimating time spent in the approach and strategies extracted from clinic notes.  
 
The ODC will meet with the PLWD-Care partner dyad by phone to determine if any BPSD are 
present. If no BPSD are currently present, the ODC will educate the care partner about DICE, 
including minimizing risk factors to prevent behaviors, and plan to continue monitoring (26) 
for BPSD during the 6-month study period. If BPSD are occurring, then the “Describe” and 
“Investigate” Steps of DICE will be triggered. 
 
Each step of DICE will be documented by the ODC in their clinic note within the EMR. In the 
“Describe” step, the ODC will obtain an accurate characterization of the behavior and the 

Protocol Template, Version 3.0 
 
 
context in which it occurs as well as quantify the frequency and severity of the most 
troublesome behavior (as defined by the care partner) using the one-item question we have used 
in prior trainings (16, 17): “Please rate from 0 to 4 the severity and frequency of the behavior 
(0=none or never; 1=mild and/or occasionally; 2=moderate and/or sometimes; 3=severe and/or 
frequently; and 4=very severe and/or daily). If the severity and frequency are different, pick the 
higher score (e.g. a behavior that is daily but mild should be scored as a 4)”. In the 
“Investigate” step, the ODC will identify possible underlying and modifiable causes of the 
behavior. 
 
With information obtained in the “Describe” and “Investigate” steps, the ODC will work with 
the care partner to create and implement a treatment plan to manage BPSD. The ODC will 
brainstorm with the care partner (e.g. what are activities the PLWD enjoys) and instruct the 
care partner in behavioral and environmental strategies. These approaches could include 
enhancing effective communication with the PLWD, creating meaningful activities, dealing 
with environmental challenges including ensuring safety, and simplifying tasks and creating 
structured routines. The ODC will also consult with other relevant clinic personnel on the 
Create treatment plan as needed; for example, a plan may involve having the provider assess 
and manage infection, constipation or pain. From prior experience with DICE, these first three 
steps (Describe, Investigate, Create) can be accomplished in 30 minutes. 
 
Following the “Create” step, and in a 2-week follow-up contact by telephone, the ODC will 
engage in the “Evaluate” step with the care partner, during which the ODC will determine if 
recommended strategies were used and their effectiveness. Effectiveness will be measured by 
repeating the frequency/severity question asked of the care partner in Describe so that the 
impact of the strategy can be assessed quantitatively comparing the pre- and post-strategy 
scores at 2 weeks’ time; any downward movement of the score will be categorized as effective. 
, If the DICE generated strategies were effective, the ODC will monitor and surveil for BPSD 
with monthly contact. If the DICE generated strategies were not effective, the ODC will 
problem-solve with the care partner and other team members to determine if a) strategies were 
used and if so correctly; or b) if strategies are not effective and additional “Create” 
recommendations are needed. Additionally, the DICE trainer (MB) will be available to ODC 
for coaching regarding the DICE Approach as needed during the study period. 
 
 
Study Title  
Training Dementia Care Professionals to Help Care Partners Improve the Management of 
BPSD Using the DICE Approach 
Objectives  
Primary: To pilot a clinical implementation of The DICE Approach to not only provide 
clinicians tools to address behavioral issues with PLWD patients via their caregivers but also 
to determine the feasibility of ascertaining and analyzing the primary (psychotropic 
medication use) and secondary clinical outcomes (hospitalizations, ED visits and nursing 
home placement of PLWDs), including whether they differ for participants of color. 
 

Protocol Template, Version 3.0 
ii 
Secondary: To inform the design of a future large-scale ePCT, including its relevance to 
people from diverse racial, ethnic, socio-economic, and educational backgrounds who are 
living with dementia and their care partners. DICE is centered around reducing the “knee-
jerk” use of psychiatric medications for sedation among PLWD, particularly when the 
underlying causes of BPSD (e.g. infection; pain; stressful environment) have not been 
explored.  
Design and Outcomes   
In this study, we will refine and pilot the application of DICE in 4 primary care clinics by: 
(a) leveraging existing clinic staff to deliver DICE to care partner-PLWD dyads; (b) using 
electronic resources to identify and recruit PLWD-care partner dyads based on clinically 
relevant and minimum inclusion/exclusion criteria; and c) evaluating clinically relevant 
outcomes using the electronic medical record (EMR). DICE will be implemented in four 
large primary care clinics within the UCD Health System over a 6-month period (n=100 
PLWD-care partner dyads; 25 dyads per site, allowing comparison of implementation and 
outcomes by site characteristics). Key “study champions” at each of the four primary care 
clinics will be the licensed practical nurse (LVN) assigned to each clinic who will serve as 
the Onsite DICE Coordinator (ODC).  
 
Aim 1:  
Feasibility measures will include: 1) rate of enrollment of PLWD-care partner dyads; 2) 
number of contacts between ODCs and dyads; and 3) time requirements for ODCs 
implementing DICE (as estimated by the ODCs and corroborated by clinic notes).   
 
Acceptability will be measured by the acceptance rates of the ODC’s recommendations of 
strategies for BPSD (generated by use of DICE) among dyads, as well as by other providers 
within the primary care practice. Exit interviews of participants (ODCs, other providers and 
care partners) will be conducted to further deepen the knowledge of intervention 
acceptability and implementation challenges. 
 
Clinical outcomes: all UCD clinical sites (inpatient and outpatient) use the same EMR 
(EPIC), so ascertaining clinical outcomes will be uniform across clinics. The primary clinical 
outcome is the feasibility of measuring psychotropic medication use. Mean PLWD 
participant psychotropic medication use during the intervention period will be compared to 
historical controls (mean rate of medication use among PLWD for the four participating 
clinics in the 6 months prior to the intervention).  
 
Aim 2: Secondary clinical outcomes will be the feasibility of measuring rates of 
hospitalizations, ED visits and nursing home placement ascertained from the EMR. Mean 
PLWD participant health care utilization during the intervention period will be compared to 
historical controls (mean rate in the 6 months prior to the intervention). The feasibility of 
obtaining the nursing home placement variable from the EMR will be established during this 
pilot study by ascertaining nursing home placement from care partners and then determining 
if it subsequently is recorded in the EMR.  
 

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iii 
Interventions and Duration  
The DICE Approach intervention will be piloted for 6 months during the study period. As 
above, mean PLWD participant psychotropic medication use during the intervention 
period will be compared to historical controls (mean rate of medication use among 
PLWD for the four participating clinics in the 6 months prior to the intervention). 
Secondary clinical outcomes(Aim 2) will be the feasibility of measuring rates of 
hospitalizations, ED visits and nursing home placement ascertained from the EMR. Mean 
PLWD participant health care utilization during the intervention period will be compared 
to historical controls (mean rate in the 6 months prior to the intervention). 
Sample Size and Population  
Study aim 1: We will examine data across 4 clinics to assess the feasibility of a multi-site 
study. We selected 25 dyads per clinic as our sample size (total n=100) to have the ability 
to examine feasibility measures within clinic as well as across clinic with some accuracy. 
For example, the degree of accuracy around an enrollment rate of 75% overall is 18% 
(width of the 95% confidence interval), allowing us a tighter margin of error overall. 
Within clinic, accuracy is larger (width of 95% confidence interval 36%), suggesting more 
uncertainty, but allowing us to examine clinic-specific enrollment to ensure that there is 
consistency across clinics.  
An exploratory analysis will the subjects enrolled in the study (n= 100 PLWD) as described 
above, will be compared on [measures] with historical controls (n=100 PLWD) . 

Protocol Template, Version 3.0 
1 
STUDY TEAM ROSTER  
Principal Investigator: 
Helen C. Kales, MD – Joe P. Tupin Endowed Professor and Chair of 
the Department of Psychiatry and Behavioral Sciences at University 
of California, Davis (UC Davis) 
2230 Stockton Blvd. Suite 212 
Sacramento, CA 95817 
Office (916) 703-3143 
Main (734) 680-9981 
hckales@ucdavis.edu 
 
Main responsibilities/Key roles: Dr. Kales will be responsible for 1) 
overall scientific direction and oversight; 2) resolving methodological 
questions; 3) contributing to study analyses, and 4) preparing research 
reports and manuscripts for peer-reviewed publication and 
dissemination. She will execute these functions through regular 
contact with the other investigators and staff. Human subjects 
research will be conducted at the UC Davis site in the health system 
clinics. All data will be stored at UCD on our secure servers and data 
sharded with DU or sponsors will be de-identified data only.  
 
Co-Investigators: 
Leslie McClure, PhD – Professor & Chair, Department of 
Epidemiology & Biostatistics, Drexel University (DU) 
3215 Market Street 
Nesbitt Hall 535 
Philadelphia, PA 19141 
Office (267) 359-6218 
Lam439@drexel.edu 
 
Main responsibilities/Key roles: Dr. McClure will provide statistical 
and study design expertise to the project, including generating the 
randomization scheme, assisting with data management with a de-
identified dataset provided to her by the UC Davis team, and cleaning, 
analysis and dissemination.  
 
 
Laura N. Gitlin PhD, - Distinguished University Professor and 
Dean, Drexel University 
 
 College of Nursing and Health Professions 
Drexel University 
1601 Cherry Street, Mail Stop 10501 
10th Floor Room 1092 

Protocol Template, Version 3.0 
2 
Philadelphia, PA 19102 
Main (215) 260-0968 
Lng45@drexel.edu  
 
Main responsibilities/Key roles: Dr. Gitlin is a close collaborator of 
Dr. Kales having worked on two NIH (NINR and NIA) R01 clinical 
trials together as well as a partner in the development of The DICE 
Approach. She will work closely with Dr. Kales on key aspects of 
study methodology (design, implementation), interpretation of results 
and manuscript preparation. 
 
Project Manager: 
 
Vince Kern, Project Analyst 4, University of California Davis 
3267 Shawnee Tr. 
Pinckney, MI 48169 
(734) 245-5858 
vkern@ucdavis.edu 
 
Main responsibilities/Key roles: Mr. Kern will work under the 
direction of Dr. Kales to: 1) assist in general management and 
objectives of the study, including day-to-day management of project 
activities; 2) troubleshoot and assist with the website for ODC and 
other clinic staff training; 3) oversee the RA (including submitting 
and maintaining regulatory documentation subject ascertainment from 
the EMR, coordinating clinic staff DICE trainings and consultation 
with Dr. Blazek, facilitating clinic DICE rollout, data collection and 
data cleaning); and 4) coordinate and participate in all study meetings 
related to operations, site updates, study supervision and assessment 
reliability. 
 
Consultant:  
 
 
Mary Blazek, MD  
4260 Plymouth Rd.  
Ann Arbor, MI 48109 
(734) 764-6831 
mblazek@med.umich.edu 
 
Main responsibilities/Key roles: Dr. Blazek will assist with the 
planning and implementation of DICE training in the UC Davis 
primary care sites as well as serve as consultant to the Onsite DICE 
Coordinators (ODCs) for cases in the months post-training. She will 
also contribute to manuscripts for peer-reviewed publication and 
dissemination. 
 
 
 

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3 
Research Assistant: TBD 
 
 
PARTICIPATING STUDY SITES  
University of California, Davis: Helen C. Kales, MD – Joe P. Tupin Endowed Professor and  
Chair of the Department of Psychiatry and Behavioral Sciences at 
University of California, Davis 
All non-exempt human subjects activities will occur at UC Davis. 
 
Drexel University:   
 Leslie McClure, PhD – Professor & Chair, Department of 
Epidemiology & Biostatistics, Drexel University 
Laura Gitlin, PhD - Distinguished University Professor and Dean, 
Drexel University 
 
Drexel’s activity falls in an exempt category and as such they will 
seek an exemption from their IRB and will not need to cede to 
Advarra. 
 
 
 
1 
STUDY OBJECTIVES 
1.1 Primary Objective: To assess the feasibility and acceptability of the ePCT protocolized 
version of DICE that will guide the subsequent evaluation of the effectiveness of the 
intervention in a full-scale ePCT. DICE will be implemented in four large primary care 
clinics within the UCD Health System over a 6-month period (n=100 PLWD-care partner 
dyads; 25 dyads per site, allowing comparison of implementation and outcomes by site 
characteristics). Feasibility measures will include: 1) rate of subject enrollment (PLWD-
care partner dyads); 2) number of contacts between ODCs and dyads; and 3) time 
requirements for ODCs implementing DICE.  Acceptability will be measured by the 
acceptance rates of the ODC’s recommendations of strategies for BPSD (generated by use 
of DICE) among dyads, as well as other providers within the primary care practice. Exit 
interviews of participants (ODCs, other providers and care partners) will be conducted to 
further deepen the knowledge of intervention acceptability and implementation challenges. 
Secondary Objectives: To determine the feasibility of ascertaining and analyzing the 
primary (psychotropic medication use) and secondary clinical outcomes (hospitalizations, 
ED visits and nursing home placement of PLWDs) from the existing health system-wide 
electronic medical record (EMR) which will subsequently be used in a full-scale 

Protocol Template, Version 3.0 
4 
effectiveness ePCT. Clinical outcomes for PLWD participants will be measured after the 6-
month DICE implementation period using the EMR and compared to corresponding 
outcomes for the four participating clinics in the 6 months prior to the intervention 
(“historical control”; all PLWD in the four participating clinics): 
2a) To determine the feasibility of measuring psychotropic medication use (primary 
outcome) within the EMR. Mean participant psychotropic medication use during the 
intervention period will be compared to historical controls (mean rate of medication use for 
participating clinics in the 6 months prior to the intervention). 
2b) To determine the feasibility of measuring hospitalizations, ED visits and nursing home 
placement (secondary outcomes) using the EMR. Mean participant health care utilization 
during the intervention period will be compared to historical controls (mean rate in the 6 
months prior to the intervention). 
 
2 
BACKGROUND AND RATIONALE  
2.1 Background on Condition, Disease, or Other Primary Study Focus 
Managing behavioral and psychological symptoms (BPSD) is one of the most challenging 
aspects of caring for a person living with dementia (PLWD), causing intense care partner 
(family and formal provider) burden and upset, and posing threats to their health and well-
being. Importantly, PLWD with BPSD are at risk for increased hospitalization rates, emergency 
department (ED) visits and nursing home placement. Potentially preventable hospitalization 
(PPH) encompasses hospitalizations for conditions that, with optimal access to outpatient care 
and management, should be unnecessary (e.g. urinary tract infection). Notably, dementia has 
been associated with the greatest additional PPH risk in patients with less medical comorbidity, 
belying the notion that patients with dementia are at increased risk for hospitalization simply 
because they are more medically ill. 
A key factor in increased PPH risk is thought to be the presence of BPSD. The potential 
influence of BPSD on healthcare outcomes is conceptually depicted in Figure 1, which suggests 
that modifiable patient, environmental and care partner factors impact this relationship/ PWLD 
typically live in the community and are followed in primary care settings. However, Primary 
Care Physicians (PCP’s) largely lack the time, training, and access to dementia care expertise 
and delivery care systems to effectively manage the nearly ubiquitous BPSD. Although the FDA 
has not approved any medications to treat BPSD, it is common clinical practice to use psychiatric 
medications such as antipsychotics to try to control them. However, antipsychotics show only 
limited efficacy in improving behavioral symptoms and have significant risks including side 
effects and mortality resulting in FDA black box warnings regarding their use for this purpose. 
Moreover, care partners frequently manage multiple BPSD simultaneously, and that can be a 
“moving target”—aggression may co-occur with or be replaced with wandering, and so on. Thus, 
the very nature of BPSD makes a simple “magic bullet” medication solution impossible, 
ineffective and inappropriate. 

Protocol Template, Version 3.0 
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2.2 Study Rationale 
Nonpharmacologic strategies are recommended by multiple medical organizations and expert 
groups as the preferred first-line treatment approach to reduce inappropriate medication use in 
managing BPSD, except in emergency situations such as when behaviors could lead to imminent 
danger. Unfortunately, effective nonpharmacological strategies for BPSD have not been 
translated into real-world clinical management and standard care. Through a process of expert 
consensus and review of the existing evidence, we previously developed a low-cost, pragmatic, 
patient-centric, evidence-informed algorithm approach (“DICE”), to manage BPSD. DICE 
protocolizes an approach that has been tested in various randomized trials. 
The DICE Approach systematically guides care partners and clinicians alike through the 
assessment and management of BPSD and teaches new transferrable problem-solving skills 
(Figure 2).  We have manualized and developed both in-person and online care partner module-
driven training in DICE. The trainings have now been delivered to hundreds of care partners 
nationally (Michigan, California, North Carolina, Pennsylvania, Wisconsin) and internationally 
(UK) where they have shown positive impact (18,19). The manual (20) has sold over 500 copies 
to date since 2017 and the training website released in 2020 (21) has over 500 subscribers.  
The training approach was created with an eye towards wide-spread implementation and 
dissemination. The goal was to create a short training (6 hours, as opposed to weeks or months in 
other trainings) to minimize the time spent learning the approach. Given that prior studies have 
shown that brief mental health training programs can be effective for producing new skills in 
both professional providers (22) and family care partners (23), we created a training program 
aimed broadly at anyone (provider, family or professional care partner) caring for PLWD. 

Protocol Template, Version 3.0 
6 
 
The training uses a modular format comprised of 8 sections:  
1. What is dementia? 
2. Behaviors in dementia 
3. Describe step (learning to create a complete symptom description to guide assessment and 
management of behaviors) 
4. Investigate step (identifying, examining and ruling out possible underlying and modifiable 
causes of behavior) 
5. Create step (learning how to use behavioral and environmental strategies to manage 
behavioral symptoms; strategies based upon those nonpharmacologic approaches with the 
strongest evidence base, family caregiver interventions, which include caregiver education 
and support, training in stress reduction/cognitive reframing and specific skills in problem 
solving) 
6. Evaluate step (assessing whether recommended strategies were or were not effective) 
7. Learning about medications 
8. Caring for the caregiver 
The companion manual follows the modular format of the trainings. Training has been designed 
to be interactive, incorporating videos and hands-on learning and systematically moves trainees 
through a problem-solving approach to identify appropriate and tailored strategies to address the 
presenting BPSD (18). DICE has been designed to be algorithmic, easy to remember and helpful 
to create good habits and problem-solving. Strategies generated are based on patient and care 
partner profiles and the environmental context of behavioral occurrences. The approach includes 
guidance on the most judicious and appropriate use of psychotropics for BPSD, and expands the 
discussion of medications beyond psychotropics to other medications for the underlying causes 

Protocol Template, Version 3.0 
7 
of BPSD (e.g. pain, infection, constipation). Thus, in the approach, pharmacologic, non-
pharmacologic strategies or their combination may be recommended (1). Given that in-person 
trainings are both time and personnel intensive, we subsequently used the lessons learned from 
the in-person trainings to create a training website that is accessible 24/7 while retaining the 
interactive format (via e-simulations of various clinical situations both to teach the approach and 
test knowledge following training). 
The DICE approach is ready for a pilot embedded pragmatic trial: it is manualized; there is a 
brief, tested, and accessible training program; it is designed for use by clinicians from any 
discipline; and its outcomes (mitigating negative effects of BPSD) reflect what matters to all 
stakeholders, including reduced inappropriate medication use.  Figure 2 describes the DICE 
Approach in more detail. 
 
3 
STUDY DESIGN 
There are no public-facing marketing materials for this study.  
In this study, we will refine and pilot the application of DICE in 4 primary care clinics by: (a) 
leveraging existing clinic staff to deliver DICE to care partner-PLWD dyads; (b) using electronic 
resources to identify and recruit PLWD-care partner dyads based on clinically relevant and 
minimum inclusion/exclusion criteria; and c) evaluating clinically relevant outcomes using the 
electronic medical record (EMR). DICE will be implemented in four large primary care clinics 
within the UCD Health System over a 6-month period (n=100 PLWD, care partner n= 100) 
dyads; 25 dyads per site, allowing comparison of implementation and outcomes by site 
characteristics). Key “study champions” at each of the four primary care clinics will be licensed 
practical nurse assigned to each clinic who will serve as the Onsite DICE Coordinator (ODC).  
Secondary outcomes: EMR data collection: To determine the feasibility of ascertaining and analyzing 
the primary (psychotropic medication use) and secondary clinical outcomes (hospitalizations, ED visits 
and nursing home placement of PLWDs) from the existing health system-wide electronic medical record 
(EMR) which will subsequently be used in a full-scale effectiveness ePCT. Clinical outcomes for PLWD 
participants will be measured after the 6-month DICE implementation period using the EMR and 
compared to corresponding outcomes for the four participating clinics in the 6 months prior to the 
intervention (“historical control” n=100; compared to the sample of PLWD n=100. The total study sample 
size N= 100.  
As a minimal risk study embedded in primary care practices, we plan to obtain a waiver of 
informed consent for PLWD, care partners and clinic staff in order to reduce introduction of 
artificial care resources or biases wherever possible. Additionally, a HIPAA waiver will be 
obtained for subject identification (see a. below) and outcome ascertainment from the EMR. 
There will be minimal PHI data collected. 
We will work with each clinic site to allow ODC’s the dedicated time (at least 6 hours) to engage 
in the online training during month one of the study. Because we want to have the least impact 

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on clinic schedules, ODCs will be permitted to do the training at their own pace asynchronously 
(e.g. all ODCs need not do the training at the same time). ODCs will then use the approach in a 
“test” case in study months 2-3 during which they will engage in as needed coaching with a 
DICE trainer (a geriatric psychiatrist and education specialist) to ensure they are using the 
approach with fidelity.  The DICE trainer will also be available as needed for coaching during the 
remainder of the study for approach related questions. Manualization and training with follow-up 
coaching have been shown to be effective implementation strategies that can enhance fidelity of 
implementation of an evidence-based program.  Other clinic personnel (nurse care navigators 
and PCPs) will also receive the manual, an email overview of the study, and be invited to train 
using the website. Following training and case consultation, the ODCs will then use the DICE 
Approach for any PLWD they encounter during the 6-month study period (months 4-9). Primary 
outcome metrics will be collected using the electronic medical record and by estimating time 
spent in the approach and strategies extracted from clinic notes. 
 
4 
SELECTION AND ENROLLMENT OF PARTICIPANTS  
Study Population: English-speaking (as discerned from the EMR) PLWD-Care partner dyads 
from the 4 participating clinics will be recruited. Dyads in the participating clinics will be 
identified in the following way:  
• via warm handoff from a clinic provider to the ODC via the current standard of care for 
working with caregivers of PLWD regarding behavioral concerns, ODCs will be 
notified of the potential study participant by either of the two methods of 
ascertainment by the study RA. The ODC will then contact the care partner who is 
identified in the EMR as the responsible person or family member for the PLWD by 
telephone participation in the DICE program. We will also track the proportion of 
PLWD without a caregiver listed for study tracking. 
 
Setting: Participants will be recruited from four primary care clinics in the Primary Care 
Network (total of 13) at University of California Davis. Clinics have been selected for the 
number of PLWD seen annually in each clinic. Below is preliminary information obtained on 
the potential subject population for the four study clinics from FY 1/1/2021-12/31/2021: 
 
 
Midtown 
Elk Grove 
ACC 
FCC 
>65 years old 
Dementia 
63 
67 
66 
76 
Race/ethnicity 
 
 
 
White 
40 (63.55) 
35 (52.2%) 
40 (63.5%) 
27 (35.5%) 
Black 
11 (17.5%) 
14 (20.9%) 
11 (17.5%) 
11 (14.5%) 
Asian 
8 (12.7%) 
10 (14.9%) 
8 (12.7%) 
25 (32.9%) 
Other 
4 (6.4%) 
8 (11.9%) 
4 (6.3%) 
13 (17.1%) 
 

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4.1 Inclusion Criteria  
Participants must meet all inclusion criteria to participate in the study: 
DICE participants 
1) Person living with dementia (as defined by chart diagnosis) and their care partner 
2) Care partner age >18 as defined in the EMR 
3) Care partner English speaking 
Historical controls 
1) Person living with dementia (as defined by chart diagnosis) 
 
4.2 Exclusion Criteria  
1) Age of care partner <18 (this age group is rarely the responsible or legal party for PLWD) 
2) Non-English speaking 
 
4.3 Study Enrollment Procedures  
PLWD-Care partner dyads from the 4 participating clinics will be recruited via warm handoff 
from a clinic provider. The ODC will then contact the care partner who is identified in the EMR 
as the responsible person or family member for the PLWD by telephone to discuss participation 
in the DICE Program. Participants will be recruited from four primary care clinics in the Primary 
Care Network (total of 13) at University of California Davis. Clinics have been selected for the 
number of PLWD seen annually by clinic social workers who are embedded in each clinic. As a 
minimal risk study embedded in primary care practices, we plan to obtain a waiver of informed 
consent for PLWD, care partners and clinic staff in order to reduce introduction of artificial care 
resources or biases wherever possible. There will be minimal PHI data collected. 
 
5 STUDY INTERVENTIONS  
5.1 Interventions, Administration, and Duration  
This is a single group intervention. We have arranged with University of California Davis LVN 
supervisors to do a 6-hour training for all the LVNs on a single day. This will be a hybrid of in 
person (kick off session and ending brainstorming session) and watching the online modules 
together in a campus auditorium. ODCs will then use the approach in a “test” case in study 
months 2-3 during which they will engage in as needed coaching with a DICE trainer (a 

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geriatric psychiatrist and education specialist) to ensure they are using the approach with 
fidelity.  Manualization and training with follow-up coaching have been shown to be effective 
implementation strategies that can enhance fidelity of implementation of an evidence-based 
program.  Other clinic personnel (social workers and PCPs) will also receive the manual, an 
email overview of the study, and be invited to train using the website or at the on-site training. 
Following training and case consultation, the ODCs will then use the DICE Approach for any 
PLWD they encounter during the 6-month study period (months 4-9). Primary outcome metrics 
will be collected using the electronic medical record and by estimating time spent in the 
approach and strategies extracted from clinic notes.  
 
As part of the DICE program, the ODC will meet with the PLWD-Care partner dyad by phone 
to determine if any BPSD are present. If no BPSD are currently present, the ODC will educate 
the care partner about DICE, including minimizing risk factors to prevent behaviors, and plan 
to continue monitoring (26) for BPSD during the 6-month study period. If BPSD are occurring, 
then the “Describe” and “Investigate” Steps of DICE will be triggered. 
 
Each step of DICE will be documented by the ODC in their clinic note within the EMR as is 
part of usual practice. In the “Describe” step, the ODC will obtain an accurate characterization 
of the behavior and the context in which it occurs as well as quantify the frequency and severity 
of the most troublesome behavior (as defined by the care partner) using the one-item question 
we have used in prior trainings (16, 17): “Please rate from 0 to 4 the severity and frequency of 
the behavior (0=none or never; 1=mild and/or occasionally; 2=moderate and/or sometimes; 
3=severe and/or frequently; and 4=very severe and/or daily). If the severity and frequency are 
different, pick the higher score (e.g. a behavior that is daily but mild should be scored as a 4)”. 
In the “Investigate” step, the ODC will identify possible underlying and modifiable causes of 
the behavior. 
 
With information obtained in the “Describe” and “Investigate” steps, the ODC will work with 
the care partner to create and implement a treatment plan to manage BPSD. The ODC will 
brainstorm with the care partner (e.g. what are activities the PLWD enjoys) and instruct the 
care partner in behavioral and environmental strategies. These approaches could include 
enhancing effective communication with the PLWD, creating meaningful activities, dealing 
with environmental challenges including ensuring safety, and simplifying tasks and creating 
structured routines. The ODC will also consult with other relevant clinic personnel on the 
Create treatment plan as needed; for example, a plan may involve having the provider assess 
and manage infection, constipation or pain. From prior experience with DICE, these first three 
steps (Describe, Investigate, Create) can be accomplished in 30 minutes. 
 
Following the “Create” step, and in a 2-week follow-up contact by telephone, the ODC will 
engage in the “Evaluate” step with the care partner, during which the ODC will determine if 
recommended strategies were used and their effectiveness. Effectiveness will be measured by 
repeating the frequency/severity question asked of the care partner in Describe so that the 
impact of the strategy can be assessed quantitatively comparing the pre- and post-strategy 
scores at 2 weeks’ time; any downward movement of the score will be categorized as effective.  
If the DICE generated strategies were effective, the ODC will monitor and surveil for BPSD 
with monthly contact. If the DICE generated strategies were not effective, the ODC will 

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problem-solve with the care partner and other team members to determine if a) strategies were 
used and if so correctly; or b) if strategies are not effective and additional “Create” 
recommendations are needed. Additionally, the DICE trainer (MB) will be available to ODC 
for coaching regarding the DICE Approach as needed during the study period. 
 
5.2 Handling of Study Interventions  
See above. 
5.3 Concomitant Interventions  
Not applicable. 
5.4 Adherence Assessment  
Rather than adherence, in this pilot study, we will be examining feasibility and acceptability. 
Feasibility measures will include: 1) rate of enrollment of PLWD-care partner dyads; 2) number 
of contacts between ODCs and dyads; and 3) time requirements for ODCs implementing DICE 
(as estimated by the ODCs and corroborated by clinic notes).   
Acceptability will be measured by the acceptance rates of the ODC’s recommendations of 
strategies for BPSD (generated by use of DICE) among dyads, as well as by other providers 
within the primary care practice. 
 
6 STUDY PROCEDURES 
 

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6.1 Schedule of Evaluations 
 
 
Assessment 
Screening:  
Baseline, 
Enrollment,  
Visit 1 (Day 0) 
Followup, 
Visit 2 (Day 
14) 
Followup 
Visit 3 
(Day44) 
Followup 
Visit 4 (Day 
74) 
Followup 
Visit 5 (Day 
104) 
Followup 
Visit 6 (Day 
134) 
Followup 
Visit 7 (Day 
164) 
Verification of dementia 
diagnosis and eligibility  
via inclusion/exclusion 
criteria 
X 
  
  
  
  
  
  
  
Demographics 
X 
  
  
  
  
  
  
X 
Current Medications 
X 
X 
 X 
X  
 X 
 X 
 X 
X  
Hospitalizations 
 
 
 
  
  
 
  
X 
Nursing Home Placement 
 
 
 
 
 
 
 
X 
ED Visits 
 
 
 
  
  
 
  
X 
Adverse Events  
  
X 
X 
X 
X 
X 
X 
X 

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6.2 Description of Evaluations  
Please refer to Section 3. 
6.2.1 Screening Evaluation 
Consenting Procedure 
Not applicable. A waiver of informed consent will be sought as DICE will be part of any contact 
by the ODC with care partners about behavioral concerns in the PLWD.  A waiver of 
information consent will also be requested for access to the EMR for the historical controls.  
6.2.2 Enrollment, Baseline, and/or Randomization 
Enrollment 
Enrollment will follow identification and meeting of inclusion and exclusion criteria. 
6.2.3 Follow-up Visits  
Visits will be flexible and tailored to the needs of each care partner and PLWD as part of usual 
care. However, in general, Visit 1 will consist of meeting with the care partner over the phone to 
determine if any behavioral or psychological symptoms of dementia (BPSD) are present. If none 
are present, the ODC will educate the care partner about BPSD and the DICE Approach and 
create a plan for monitoring during the 6-month study period. If BPSD are present, the 
“Describe” and Investigate” steps of the DICE intervention will be triggered. Using this 
information during the same visit, the ODC will work with the care partner to create and 
implement a treatment plan. This visit will be accomplished in 30 minutes. Visit 2 will occur 
approximately 2 weeks after the first visit. The ODC will engage in the “Evaluate” step to 
determine if the treatment plan was implemented and its effectiveness. If effective, the ODC will 
monitor and surveil for BPSD with monthly contact. If not effective, the ODC will work with the 
care partner to create additional treatment strategies and then follow up at intervals between 2 
weeks and 1 month as needed. 
6.2.4 Completion/Final Evaluation 
At the final visit, an evaluation of the current effectiveness of DICE strategies will be performed. 
Exit interviews of participants (ODCs, other providers and care partners) will be conducted to 
further deepen the knowledge of intervention acceptability and implementation challenges. We 
will seek a waiver of informed consent for these interviews which will be conducted by study 
team members. 
 
7 SAFETY ASSESSMENTS   
The anticipated risks are very minimal given that this is a non-pharmacologic intervention being 
implemented to enhance usual care. 
7.1 Specification of Safety Parameters 
NA 
7.2 Methods and Timing for Assessing, Recording, and Analyzing Safety Parameters 
NA 

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7.3 Adverse Events and Serious Adverse Events  
Adverse Event (AE): Any untoward or unfavorable medical occurrence in a clinical research 
study participant, including any abnormal sign (e.g. abnormal physical exam or laboratory 
finding), symptom, or disease, temporally associated with the participants’ involvement in the 
research, whether or not considered related to participation in the research. 
Serious Adverse Event (SAE): Any adverse event that: 
• 
Results in death 
• 
Is life threatening, or places the participant at immediate risk of death from the event as it 
occurred 
• 
Causes persistent or significant disability or incapacity 
• 
Results in congenital anomalies or birth defects 
• 
Is another condition which investigators judge to represent significant hazards 
 
No AE’s or SAE’s are expected based upon the study intervention. Hospitalizations and ED 
visits are secondary outcomes in the study and not considered adverse events. However, we will 
collect data on such events from the medical chart and caregiver report during visits and report 
them as needed.  
 
7.4 Reporting Procedures 
The primary investigator will be responsible for determining the severity and whether any AE or 
SAE is study related. 
Severity of Event 
For adverse events (AEs), the following guidelines will be used to describe severity.  
• 
Mild – Events require minimal or no treatment and do not interfere with the 
participant’s daily activities.  
• 
Moderate – Events result in a low level of inconvenience or concern with the 
therapeutic measures. Moderate events may cause some interference with functioning. 
• 
Severe – Events interrupt a participant’s usual daily activity and may require systemic 
drug therapy or other treatment. Severe events are usually potentially life-threatening or 
incapacitating.  Of note, the term “severe” does not necessarily equate to “serious”. 
These terms should match those collected on the Adverse Event Form.  
Relationship To Study Intervention 
Given the nature of the intervention, a binary assessment (related/not related) will be used. No 
AE’s or SAE’s are expected based upon the study intervention. Hospitalizations and ED visits 
are secondary outcomes in the study and not considered adverse events. 
AEs for this study include:  Mild inconvenience due to the time taken for the intervention.  
SAEs for this study include:  Given the nature of the participant population based on age and 
comorbidities, death can reasonably be expected (unrelated to the intervention) in some PLWD.    

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7.5 Follow-up for Adverse Events 
The occurrence of an adverse event (AE) or serious adverse event (SAE) may come to the 
attention of study personnel during visits with the ODC or study team review of the medical 
record. 
We will distinguish between alerts and adverse events as developed by the NIH REACH 
initiative. Alerts refer to events occurring independently of the study and place the PLWD or 
care partner at risk. These could include a care partner medical emergency, PLWD driving, 
aggression in the dyad, suicidal ideation in a care partner or PLWD, etc. The Project Manager 
will keep a running record of alerts and dates of resolution. We will seek resolution of an alert 
within 48 hours of being notified of such and define resolution as the participant being 
contacted and informed of actions to resolve the presenting issue. Alert forms will be 
reviewed by Dr. Kales weekly during research administration meetings. Adverse events 
include hospitalization. ED visit, nursing home placement or death of a caregiver or PLWD. 
There are two levels of monitoring of adverse events. For AEs attributed to the 
study/intervention, notification of the PI, IRB, Safety Officer (SO) and NIA occurs within 24 
to 48 hours of identification of the event, as per the DSMP and as noted in Section 7.7 below. 
For AEs not attributed to the study/intervention, the first level of monitoring occurs on a 
weekly basis and involves the following; a) the PI are notified of all non-emergency events at 
staff meetings with project directors at their respective sites; b) events are reviewed at weekly 
interviewer meetings at respective sites to assure that each has been managed appropriately 
and follow-up and resolution obtained); c) all events will be entered in a secure on-line data 
management system developed, and monitored at DU. The second level of review involves 
generating aggregate data reports that are provided to both PIs and SO twice yearly for review 
(or more frequently if they so choose). Data entry and an aggregate review facilitate a double 
check that events are resolved and assist in monitoring of the trial. Resolution of events is 
defined as the participant having been contacted and informed of actions to resolve the 
presenting issue. 
7.6 Safety Monitoring 
Given the minimal risk nature of the study embedded in usual care, NIA determined that a 
DSMB is not required. Rather, the IMPACT Collaboratory Safety Officer (SO) will be appointed 
to evaluate all study protocols and enrollment rates to ensure conformity to human subject 
procedures and patient safety in the trial. The SO will also review the study design, the IRB 
protocols, any adverse events, and interim reports of the ongoing study. Dr. Kales will be 
responsible for overseeing the preparation of data and data analyses for the SO.  The Principal 
Investigator (PI) will be responsible for ensuring participants’ safety on a daily basis. In addition, 
the NIA IMPACT Collaboratory SO will oversee all data and safety monitoring activities for this 
study. The SO will act in an advisory capacity to the NIA Director to monitor participant safety, 
to evaluate the progress of the study, and to review procedures for maintaining the 

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confidentiality of data, the quality of data collection, management, and analyses. Advarra IRB 
will conduct the ethical review required for the protection of human subjects.  NIA PO, in 
consultation with SO, will make a determination regarding how often data safety monitoring 
reporting is needed.   
 
7.7 Reporting schedule: 
• 
All adverse events that are serious (SAE) and unexpected (i.e., have not been 
previously reported for the study’s intervention) will be reported to the IMPACT 
Collaboratory Regulatory and Data Team Leader (Dr. Julie Lima), NIA IMPACT 
Collaboratory PO (Dr. Partha Bhattacharyya), and the IMPACT Collaboratory project’s 
Safety Officer (SO) within 48 hours of the study’s knowledge of SAE. 
o Only those adverse events that are serious (SAE), unexpected, and related to the 
intervention must also be reported to Advarra IRB. Unexpected and unrelated 
SAEs will be reported to Advarra IRB on a case-by-case basis if requested by the 
IMPACT Collaboratory project’s Safety Officer (SO) or NIA IMPACT 
Collaboratory PO. 
 
• 
All deaths will be reported to IMPACT Collaboratory Regulatory and Data Team Leader 
(Dr. Julie Lima), NIA IMPACT Collaboratory PO (Dr. Partha Bhattacharyya), and the 
IMPACT Collaboratory project’s Safety Officer (SO) within 24 hours of study’s 
knowledge of death. 
o Advarra IRB does not require the specific reporting of death outside of the 
SAE reporting requirement above, but they will be notified on a case-by-case 
basis if requested by the IMPACT Collaboratory project’s Safety Officer (SO) 
or NIA IMPACT Collaboratory PO. 
 
• All unanticipated problems (UPs) will be reported to the IMPACT Collaboratory 
Regulatory and Data Team Leader (Dr. Julie Lima), Advarra IRB, NIA IMPACT 
Collaboratory PO (Dr. Partha Bhattacharyya), and the IMPACT Collaboratory project’s 
Safety Officer (SO) within 48 hours of the study’s knowledge of the event. 
 
• The summaries of all previously reported unexpected and related SAEs, deaths, and UPs, 
as well as all other SAEs and AEs will be reported to IMPACT Collaboratory Regulatory 
and Data Team Lead (Dr. Julie Lima), Advarra IRB, NIA IMPACT Collaboratory PO (Dr. 
Partha Bhattacharyya), and the IMPACT Collaboratory project’s Safety Officer (SO) at a 
minimum every 6 months, or at a frequency requested by the IMPACT Collaboratory 
project’s Safety Officer (SO) or NIA IMPACT Collaboratory PO. 
 

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8 INTERVENTION DISCONTINUATION  
 As a minimal risk study embedded in primary care practices, we plan to obtain a waiver of 
informed consent for PLWD, care partners and clinic staff in order to reduce introduction of 
artificial care resources or biases wherever possible. The DICE Approach will be delivered as 
part of routine care. It is possible that PLWD/care partners may drop out of routine outpatient 
care. If this occurs, we will continue to monitor and evaluate PLWD data. 
 
9 STATISTICAL CONSIDERATIONS  
9.0 General Design Issues  
The overarching goal of this proposal is to refine and pilot the application of DICE in primary 
care clinics by: (a) leveraging existing clinic staff to deliver DICE; and (b) using electronic 
resources to identify and recruit PLWD-care partner dyads based on clinically relevant and 
minimum inclusion/exclusion criteria.  We maximize a pragmatic approach and minimize a 
separate study infrastructure to evaluate feasibility and acceptability in order to prepare for a 
larger embedded pragmatic trial (ePCT). Licensed practical nurses embedded in four primary 
care practices at University of California Davis (UCD), whom we will refer to as “Onsite DICE 
Coordinators” (ODC), will coordinate behavioral management using DICE with care partner-
PLWD dyads and other clinic providers. We will accomplish this goal through the following 
specific aims: 
Aim 1.  To assess the feasibility and acceptability of the ePCT protocolized version of DICE that 
will guide the subsequent evaluation of the effectiveness of the intervention in a full-scale ePCT. 
DICE will be implemented in four large primary care clinics within the UCD Health System over 
a 6-month period (n=100 PLWD-care partner dyads; 25 dyads per site, allowing comparison of 
implementation and outcomes by site characteristics). Feasibility measures will include: 1) rate 
of subject enrollment (PLWD-care partner dyads); 2) number of contacts between ODCs and 
dyads; and 3) time requirements for ODCs implementing DICE.  Acceptability will be measured 
by the acceptance rates of the ODC’s recommendations of strategies for BPSD (generated by use 
of DICE) among dyads, as well as other providers within the primary care practice. Exit 
interviews of participants (ODCs, other providers and care partners) will be conducted to further 
deepen the knowledge of intervention acceptability and implementation challenges. 
Aim 2. To determine the feasibility of ascertaining and analyzing the primary (psychotropic 
medication use) and secondary clinical outcomes (hospitalizations, ED visits and nursing home 
placement of PLWDs) from the existing health system-wide electronic medical record (EMR) 
which will subsequently be used in a full-scale effectiveness ePCT. Clinical outcomes for PLWD 
participants will be measured after the 6-month DICE implementation period using the EMR and 

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compared to corresponding outcomes for the four participating clinics in the 6 months prior to 
the intervention (“historical control”; all PLWD in the four participating clinics): 
2a) To determine the feasibility of measuring psychotropic medication use (primary 
outcome) within the EMR. Mean participant psychotropic medication use during the 
intervention period will be compared to historical controls (mean rate of medication use for 
participating clinics in the 6 months prior to the intervention). 
2b) To determine the feasibility of measuring hospitalizations, ED visits and nursing home 
placement (secondary outcomes) using the EMR. Mean participant health care utilization 
during the intervention period will be compared to historical controls (mean rate in the 6 
months prior to the intervention). 
9.1 Sample Size and Randomization 
We will examine data across 4 clinics in order to assess the feasibility of a multi-site study. We 
selected 25 dyads per clinic as our sample size (primary study sample- total n=100 PLWD), and 
their caregiver (n=100) in order to have the ability to examine feasibility measures within clinic 
as well as across clinic with some accuracy. For example, the degree of accuracy around an 
enrollment rate of 75% overall is 18% (width of the 95% confidence interval), allowing us a 
tighter margin of error overall. Within clinic, accuracy is larger (width of 95% confidence 
interval 36%), suggesting more uncertainty, but allowing us to examine clinic-specific 
enrollment to ensure that there is consistency across clinics. 
To determine the feasibility of ascertaining and analyzing the primary (psychotropic medication 
use) and secondary clinical outcomes (hospitalizations, ED visits and nursing home placement of 
PLWDs) from the existing health system-wide electronic medical record (EMR) participants (the 
primary study sample of PLWD n=100) will be measured after the 6-month DICE 
implementation period using the EMR and compared to corresponding outcomes for the four 
participating clinics in the 6 months prior to the intervention (historical controls n=100); all 
PLWD in the four participating clinics), (N=300).  
9.2 Treatment Assignment Procedures  
Not applicable 
9.3 Interim analyses and Stopping Rules  
Not applicable 
9.4 Outcomes  
Clinical outcomes: all UCD clinical sites (inpatient and outpatient) use the same EMR (EPIC), 
so ascertaining clinical outcomes will be uniform across clinics. The primary clinical outcome 
is the feasibility of measuring psychotropic medication use. Mean PLWD participant 

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psychotropic medication use during the intervention period will be compared to historical 
controls (mean rate of medication use among PLWD for the four participating clinics in the 6 
months prior to the intervention). Secondary clinical outcomes will be the feasibility of 
measuring rates of hospitalizations, ED visits and nursing home placement ascertained from the 
EMR. Mean PLWD participant health care utilization during the intervention period will be 
compared to historical controls (mean rate in the 6 months prior to the intervention). The 
feasibility of obtaining the nursing home placement variable from the EMR will be established 
during this pilot study by ascertaining nursing home placement from care partners and then 
determining if it subsequently is recorded in the EMR. 
 
 
9.5 Data Analyses 
Data will be summarized with descriptive statistics to allow us to review the demographics and 
clinical characteristics of our enrolled participants, as well as to review implausible values. The 
extent of missing data will also be assessed as a key indicator of feasibility of collecting data 
from clinic notes and the EMR; additionally, we will ascertain whether baseline characteristics 
are associated with missingness in order to modify study procedures for the larger trial. 
Feasibility will be characterized by rate of enrollment (# enrolled/# invited to enroll), number of 
contacts between ODCs and dyads (summarized as averages/SDs across dyads), and time 
requirements (summarized as averages/SDs). We will examine these overall and by clinic, to 
ensure consistency across clinics. We will summarize data on medication use (binary: 
psychotropic use or not) for the four clinics overall prior to the study and for enrolled PLWD 
post-intervention and will compare them using mixed models with a logit link to analyze these 
pre-post data, accounting for correlation within clinic. Models will first be fitted in a crude 
fashion, secondarily we will include covariate adjustment as a means to inform design 
characteristics in the ePCT, recognizing we have limited power to make definitive conclusions 
from these analyses. We will similarly examine healthcare utilization (counts of hospitalizations 
and ED visits; binary measure of nursing home placement) once we ensure that these data are 
feasibly collected from the EPIC EHR. 
Models will first be fitted in a crude fashion, secondarily we will include covariate adjustment 
to inform design characteristics in the ePCT, recognizing we have limited power to make 
definitive conclusions from these analyses. We will similarly examine healthcare utilization 
(counts of hospitalizations and ED visits; binary measure of nursing home placement) once we 
ensure that these data are feasibly collected from the EPIC EHR. In order to go on to the ePCT, 
we must meet two criteria. First, the primary feasibility outcome (enrollment rates) must be 
greater than 75%. Second, we must be able to show that the lower limit of the 90% confidence 
interval for testing the pre-post medication use is greater than a 25% decrease in the pre-study 
proportion. The former criteria is based on the observed enrollment rate in the pilot from the 
WeCareAdvisor study (17) of PLWD-care partner dyads; the latter is based on what is 
reasonable to assume will change in the shorter 6-month pilot and is clinically relevant. 
 

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10 DATA COLLECTION AND QUALITY ASSURANCE 
10.2 Data Collection Forms 
Data will be collected from the electronic medical record. ODCs will put information about the 
use of the DICE Approach into their routine clinical notes. Exit interviews will be collected on 
paper and uploaded into secure study files.  
10.3  Data Management  
The UCD study team will be responsible for data collection. Data from the clinical notes as well 
as outcomes will be downloaded onto a secure server. A waiver of authorization for PHI data 
will be completed by the study team. The Drexel CO-I will be responsible for data management 
and analysis of a deidentified data set that is transferred from UCD and securely stored at Drexel. 
10.4 Quality Assurance  
10.3.1 
Training 
The study will take place in usual clinic care. The only added training will be the training in the 
DICE approach as described above. PIs and study personnel will be trained in Good Clinical 
Practice and HIPAA for research purposes. 
10.3.2 Quality Control Committee  
Not applicable 
10.3.3 Metrics 
Not applicable 
10.3.4 Protocol Deviations 
Will be submitted as applicable.  
10.3.5 Monitoring 
Not applicable 
 
11 PARTICIPANT RIGHTS AND CONFIDENTIALITY  
11.1 Institutional Review Board (IRB) Review 
This protocol and any subsequent modifications will be reviewed and approved by the IRB or 
ethics committee responsible for oversight of the study.   
11.2 Informed Consent Forms 
We request a waiver of informed consent for the use of electronic medical records for 
recruitment purposes and outcome ascertainment, enrollment, and participation in the program 
for the study subjects.  We also request a waiver of informed consent through the use of 

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electronic medical records for historical controls.  We offer the following justifications for the 
waivers of informed consent: 
• 
the research involves no more than minimal risk to the subjects. This is an augmentation 
of usual care.  The anticipated risks are minimal given that this is a non-pharmacologic 
intervention being implemented to enhance usual care by educating clinical staff on The 
DICE Approach. The training is done via The DICE Approach web-based training and its 
companion printed manual. 
• 
The research could not practicably be carried out without the requested waiver. As part 
of usual care, it would be impossible to consent every dyad. As a minimal risk study 
embedded in primary care practices, we are requesting a waiver of informed consent for 
PLWD, care partners and clinic staff in order to reduce introduction of artificial care 
resources or biases wherever possible. Also, requiring consent would introduce artificial 
care resources and bias which would compromise scientific validity.  
• 
the research could not practicably be carried out without using such information; 
collecting data on this augmentation of usual care is essential for this research. The 
knowledge to be gained is critical. Rates of psychotropic use are at all-time highs post-
pandemic, putting PLWD at risk for morbidity, mortality and reduced quality of life. .  
We require identifiable information for recruitment purposes and for access to the EMR 
for the historical controls. 
• 
The waiver or alteration will not adversely affect the rights and welfare of the subjects. 
This is an augmentation of usual care that is being adopted clinic wide.  The main 
purpose of this study is to assess the feasibility and usability of this intervention in 
primary care and anticipate that it will benefit PLWD and their care partners.  
• 
There will be minimal PHI data collected and the HER data will be de-identified prior to 
sending the data to the data analyst in the study. Requiring consent will introduce 
artificial care resources and bias which would compromise scientific validity.  
• 
The clinicians and/or caregivers who will be applying the strategy post-training will be 
seeking outcomes and the PLWD will not be trained in The DICE Approach but rather be 
the recipient of the non-pharm behavioral strategies. 
• 
Whenever appropriate, the subjects will be provided with additional pertinent information 
after participation. At the end of the study; no information will be provided directly to 
subjects.  However, we plan to provide information about the results through 
departmental/HS electronic newsletters, through our CTSC study pages and we will 
utilize UCD CTSC resources to disseminate the findings to the community at large.  
Finally, please note that we do not consider the exit interviews to be a human subjects research 
activity requiring consent. They consist of Exit interviews of participants (ODCs, other providers 
and care partners) and will be conducted to further deepen the knowledge of intervention 
acceptability and implementation challenges. 
 

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11.3 Participant Confidentiality  
In using the EMR data for subject identification and outcome ascertainment, we will request a 
full waiver of HIPAA authorization since we are not planning on getting direct authorization 
from the PLWD themselves. The HIPAA waiver is needed for the release or use of identifiable 
PHI by a covered entity for the purposes of research. The HIPAA authorization/waiver criteria 
that must be met are similar to, but distinct from the consent waiver requirements, and each 
criteria (provided below) must be stated and justified. Exit interviews will be linked to study ID 
only and no PHI will be collected.  
Use or disclosure involves no more than minimal risk to the privacy of individuals because of the 
presence of at least the following elements: 
• We will protect health information identifiers from improper use or disclosure.  Any data 
that leave the site will be identified only by a participant identification number 
(Participant ID, PID) to maintain confidentiality.  All records will be kept in a locked file 
cabinet.  All computer entry and networking programs will be done using PIDs only. 
Information will not be released without written permission of the participant, except as 
necessary for monitoring by IRB, the sponsor or persons working on behalf of the 
sponsor (i.e. IMPACT research study staff, the DSMB and/or Safety Officer), the NIA, 
and the OHRP. 
• 
We will destroy identifiers at the earliest opportunity absent a health or research 
justification or legal requirement to retain them, and 
• 
The PHI will not be used or disclosed to a third party except as required by law, for 
authorized oversight of the research study, or for other research uses and disclosures 
permitted by the Privacy Rule; Information will not be released without written 
permission of the participant, except as necessary for monitoring by IRB, the sponsor or 
persons working on behalf of the sponsor (i.e. IMPACT research study staff, the DSMB 
and/or Safety Officer), the NIA, and the OHRP. 
• 
Research could not practicably be conducted without the waiver or alteration;  As a 
minimal risk study embedded in primary care practices, we are requesting a HIPAA 
waiver for PLWD, care partners and clinic staff in order to reduce introduction of 
artificial care resources or biases wherever possible. 
• 
Research could not practicably be conducted without access to and use of PHI. We 
require PHI information for recruitment purposes and outcome ascertainment, 
enrollment, and participation in the program and for access to the EMR for the historical 
controls. 
 
11. 4 Study Discontinuation  
The study may be discontinued at any time by the IRB, the NIA, the OHRP, or other government 
agencies as part of their duties to ensure that research participants are protected.  

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11.5 Ethical Considerations 
All ethical principles as listed in the Belmont Report will be followed. 
11.6 Committees  
Not applicable. 
11.8 Publication Of Research Findings 
Publication of the results of this trial will be governed by the policies and procedures developed 
by the Steering Committee.  Any presentation, abstract, or manuscript will be made available for 
review by the sponsor and the NIA prior to submission.  We will adhere to the IMPACT 
Collaboratory Publication and Acknowledgment Policy and Resource and Data Sharing Plan 
available on the IMPACT Investigator’s Portal. 
 
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SUPPLEMENTS/APPENDICES - NONE