A Patient-facing Tool to Reduce Opioid-Psychotropic Polypharmacy in People Living With Dementia
Phase: NA
Conditions: Polypharmacy, Dementia
Sponsor: University of Michigan

FULL PROTOCOL TITLE 
 
A Patient-facing Tool to Reduce Opioid-Psychotropic Polypharmacy in People Living with 
Dementia. 
 
NCT: NCT05628181 
Protocol: Pro00065204 
Date: January 27, 2023 
 
Study Chairman or Principal Investigator: 
Donovan T. Maust, M.D., M.S., Associate Professor of Psychiatry, Michigan Medicine 
Supported by: 
The National Institute on Aging 
U54AG063546 
FY22_Pilot3_Maust  
Study Intervention Provided by:  
National Institute on Aging (NIA) IMbedded Pragmatic Alzheimer's disease (AD) and AD-
Related Dementias (AD/ADRD) Clinical Trials (IMPACT) Collaboratory  
Sponsor of IND/IDE:  
n/a 
 
 
 

 
Protocol Changes: 
 
Version 2 
September 19, 2022 
 
• Updated recruitment and screening details to include contact with care partners in 
addition to people living with dementia for Aim 1 focus group participants.  
 
Version 3 
October 17, 2022 
• Updated focus group recruitment to include mailing to participants in addition to 
email recruitment  
• Removed irrelevant mention of care partners in section 10.1 page 22. 
 
Version 4 
January 27, 2023 
 
• Updated recruitment protocol to add that clinicians will be given the opportunity to 
identify potential participants appropriate for the study than an EHR search may 
have overlooked 
• Added draft of opt out letter to be shared with clinicians 
 
 

Protocol Template, Version 4.0  

Protocol Template, Version 4.0 
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TABLE OF CONTENTS 
Page 
PREFACE ......................................................................................... Error! Bookmark not defined. 
FULL PROTOCOL TITLE ...........................................................................................................   
TABLE OF CONTENTS ............................................................................................................. 1 
PRÉCIS .......................................................................................................................................... 4 
Study Title ................................................................................................................................... 4 
Objectives ................................................................................................................................... 4 
Design and Outcomes ................................................................................................................. 4 
Interventions and Duration ......................................................................................................... 4 
Sample Size and Population........................................................................................................ 4 
STUDY TEAM ROSTER............................................................................................................. 5 
Principal Investigator:  Donovan Maust, MD, MS .................................................................. 5 
Co-Investigators:   Frederic Blow, PhD ................................................................................... 5 
Myra Hyungjin Kim, ScD ........................................................................................................... 5 
Amanda Leggett, PhD ................................................................................................................. 6 
Sarah Vordenberg, PharmD, MPH ............................................................................................. 6 
Site Principal Investigator: Esther Akinyemi, MD .................................................................. 6 
1 
Study objectives ..................................................................................................................... 8 
1.1 
Primary Objective ........................................................................................................... 8 
1.2 
Secondary Objectives...................................................................................................... 8 
2 
BACKGROUND AND RATIONALE ................................................................................ 8 
2.1 
Background on Condition, Disease, or Other Primary Study Focus .............................. 8 
2.2 
Study Rationale ............................................................................................................... 8 
3 
STUDY DESIGN ................................................................................................................... 9 
4 
SELECTION AND ENROLLMENT OF PARTICIPANTS .......................................... 10 
4.1 
Inclusion Criteria .......................................................................................................... 10 
4.2 
Exclusion Criteria ......................................................................................................... 10 

Protocol Template, Version 4.0 
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4.3 
Study Enrollment Procedures ....................................................................................... 11 
5 
STUDY INTERVENTIONS .............................................................................................. 12 
5.1 
Interventions, Administration, and Duration ................................................................ 12 
5.2 
Handling of Study Interventions ................................................................................... 13 
5.3 
Concomitant Interventions ............................................................................................ 13 
5.3.1 Allowed Interventions ............................................................................................... 13 
5.3.2 Required Interventions .............................................................................................. 13 
5.3.3 Prohibited Interventions ............................................................................................ 13 
5.4 
Adherence Assessment ................................................................................................. 13 
6 
STUDY PROCEDURES .................................................................................................... 13 
6.1 
Schedule of Evaluations ................................................................................................ 14 
6.2 
Description of Evaluations ............................................................................................ 15 
6.2.1 Screening Evaluation ................................................................................................ 15 
6.2.2 Enrollment, Baseline, and/or Randomization ........................................................... 15 
6.2.3 Follow-up Visits........................................................................................................ 16 
6.2.4 Completion/Final Evaluation .................................................................................... 16 
7 
SAFETY ASSESSMENTS ................................................................................................. 17 
7.1 
Specification of Safety Parameters ............................................................................... 17 
7.2 
Methods and Timing for Assessing, Recording, and Analyzing Safety Parameters .... 17 
7.3 
Adverse Events and Serious Adverse Events ............................................................... 17 
7.3.1 Reporting Procedures ................................................................................................ 18 
7.3.2 Follow-up for Adverse Events .................................................................................. 19 
7.4 
Safety Monitoring ......................................................................................................... 20 
8 
INTERVENTION DISCONTINUATION........................................................................ 20 
9 
STATISTICAL CONSIDERATIONS .............................................................................. 20 
9.1 
General Design Issues ................................................................................................... 20 
9.2 
Sample Size and Randomization .................................................................................. 20 
9.2.1 Treatment Assignment Procedures ........................................................................... 21 
9.3 
Interim analyses and Stopping Rules ............................................................................ 21 
9.4 
Outcomes ...................................................................................................................... 21 
9.4.1 Primary outcome ....................................................................................................... 21 
9.4.2 Secondary outcomes ................................................................................................. 21 
9.5 
Data Analyses ............................................................................................................... 21 

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10 DATA COLLECTION AND QUALITY ASSURANCE ................................................ 22 
10.1 
Data Collection Forms .................................................................................................. 22 
10.2 
Data Management ......................................................................................................... 22 
10.3 
Quality Assurance ......................................................................................................... 23 
10.3.1 
Training ................................................................................................................. 23 
10.3.2 
Quality Control Committee................................................................................... 23 
10.3.3 
Metrics .................................................................................................................. 23 
10.3.4 
Protocol Deviations ............................................................................................... 23 
10.3.5 
Monitoring ............................................................................................................ 23 
11 PARTICIPANT RIGHTS AND CONFIDENTIALITY ................................................. 23 
11.1 
Institutional Review Board (IRB) Review .................................................................... 23 
11.2 
Informed Consent Forms .............................................................................................. 24 
11.3 
Participant Confidentiality ............................................................................................ 24 
11.4 
Study Discontinuation ................................................................................................... 26 
12 ETHICAL CONSIDERATIONS ....................................................................................... 26 
13 COMMITTEES................................................................................................................... 27 
14 PUBLICATION OF RESEARCH FINDINGS ................................................................ 27 
15 REFERENCES .................................................................................................................... 27 
16 SUPPLEMENTS/APPENDICES ...................................................................................... 29 
 
I. Procedures Schedule 
  
II. Informed Consent Form Template 
  
III. Other (add as many appendices as necessary) 
 
 

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PRÉCIS 
Study Title  
A Patient-facing Tool to Reduce Opioid-Psychotropic Polypharmacy in People Living 
with Dementia. 
Objectives  
 
Establish:  
1. Implementation feasibility: after sending the tool, the proportion of enrollees with 
documentation in the EHR of discussion regarding CNS-active medications with a 
prescribing clinician (or pharmacist).  
2. Pilot ascertainment of the primary clinical outcome for a future intervention trial: using 
EHR to measure change in the total standardized daily dosage (TSDD) of the medication 
classes contributing to CNS polyRx from baseline to 4 months after sending the adapted 
intervention.  
Design and Outcomes    
Aim 1: successive rounds of virtual focus groups conducted over Zoom to adapt the EMPOWER 
educational tool for people living with dementia (PLWD) receiving CNS polyRx and their care 
partners (CPs). Brief follow-up phone calls with select care partners who participated in the 
focus group discussion in order to reflect on and clarify any feedback and insight that emerged 
during the group discussion.   
Aims 2 and 3: use the electronic health record (EHR) to identify a list of PLWD experiencing 
CNS polyRx and (b) a randomized-controlled clinical trial implementing the adapted 
EMPOWER intervention in two primary care clinics using pragmatic methods at University of 
Michigan Health and Henry Ford Health (n=120 PLWD). We will also interview prescribing 
clinicians to obtain their perspectives on barriers and facilitators to the intervention.  
Interventions and Duration  
Participants (i.e., PLWD experiencing CNS polyRx) will be mailed the educational tool. Four 
months after sending the tool, we will do a final EHR query for all participants to assess the 
burden of CNS polyRx (i.e., total standardized daily dosage) and determine whether the 
prescribing regimen changed from the medications prescribed at baseline. Participation will be 
over after the 4 months.  
Sample Size and Population  
Our goal is to include 4 participating clinics with at least 30 PLWDs with active CNS polyRx per 
clinic, for a total of about 120 eligible PLWDs.  
 
 
 

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STUDY TEAM ROSTER  
Principal Investigator: 
 
Donovan Maust, MD, MS 
 
2800 Plymouth Rd Bld 016-226W 
 
Ann Arbor, MI 48109 
 
734-845-3649 
 
maustd@umich.edu 
 
Main responsibilities/Key roles:  
As the Principal Investigator, Dr. Maust will take primary 
responsibility for overall scientific direction and oversight of 
the project. Dr. Maust will: 1) lead the development of the 
educational tool for Aim 1; 2) work with Drs. Blow and 
Vordenberg to oversee quantitative data collection and analysis 
for all aims, supported by data analyst; 3) work with Dr. 
Leggett to oversee focus group and qualitative interviews and 
analysis, supported by study qualitative coordinator; 4) along 
with Co- Investigators, prepare research reports and 
manuscripts for peer-reviewed publication; 5) provide overall 
supervision of study staff.  
Co-Investigators: 
 
 
Frederic Blow, PhD 
 
2800 Plymouth Rd Bld 016-229W 
 
Ann Arbor, MI 48109 
 
734-845-3657 
 
fredblow@umich.edu 
 
Main responsibilities/Key roles:  
As a Co-Investigator on this project, Dr. Blow will: 1) assist 
with oversight of the development of the educational tool for 
Aim 1; 2) assist with research design and measurement issues; 
3) assist with interpretation of Aims 2 findings; 4) collaborate 
with other study team members on research reports and 
scientific manuscripts for peer-reviewed publication. Dr. Blow 
also has a VA appointment. Division of his time between the 
University and the VA is formally described in a written 
Memorandum of Understanding. All his time on this project 
will come from the University of Michigan component of his 
appointment. 
 
 
 
 
 
 
 
Myra Hyungjin Kim, ScD 
 
3560 Rackham 
 
Ann Arbor MI 48109-1070 
 
734-936-0998 
 
myrakim@umich.edu 
 
Main responsibilities/Key roles: 
For this study, Dr. Kim will: 1) provide input to Dr. Maust and 
study analyst as all quantitative analyses are planned and 

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implemented; 2) provide regular biostatistical consultation 
across the duration of the proposed study, specifically related 
to obtaining the necessary data for a subsequent R01 proposal; 
and 3) participate in final manuscript preparation. 
 
 
 
 
 
 
 
Amanda Leggett, PhD 
 
4250 Plymouth Rd 
 
Ann Arbor MI 48109 
 
734-232-0528 
 
leggetta@umich.edu 
 
Main responsibilities/Key roles: 
 As a Co-Investigator on this project, she will: 1) assist with the 
design and development of recruitment methods and materials 
for Aims 1 and 2; 3) participate in focus groups and qualitative 
analysis for the development of the educational tool; 4) assist 
Dr. Maust with the supervision of the Qualitative Coordinator; 
5) collaborate with other study team members on research 
reports and scientific manuscripts for peer-reviewed 
publication. 
 
 
 
 
 
 
 
Sarah Vordenberg, PharmD, MPH 
 
428 Church St 
 
Ann Arbor, MI 48109-1065 
 
734-763-6691 
 
skelling@umich.edu 
 
Main responsibilities/Key roles:  
As a Co-Investigator on this project Dr. Vordenberg will: 1) 
provide input into the development of the educational tool in 
Aim 1; 2) assist with sample design and selection for Aim 2; 3) 
collaborate with other study team members on research reports 
and scientific manuscripts for peer- reviewed publication. 
 
PARTICIPATING STUDY SITES  
 
Site Principal Investigator: Esther Akinyemi, MD 
 
2799 West Grand Blvd 
 
Detroit, MI 48202-2689  
 
313-916-2600 
 
eakinye2@hfhs.org 
 
Main responsibilities/Key roles:  
Research will collaborate to carry out the goals and objectives 
of this project including overseeing development of the 
EMPOWER brochure, identifying potential clinics for the 
project, oversee the ongoing EHR data pulls and data transfers 
and ensure other project tasks are completed.  Dr. Akinyemi 

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will assure that work is congruent with the desired objectives 
of the study. Dr. Akinyemi will participate in regular team 
meetings, contribute to analysis, reports, manuscripts, and 
dissemination of information 
 
Site Co-Investigator:               Brian Ahmedani, PhD 
 
 
Ste 3 A 
 
One Ford Place 
 
Detroit, MI 48202  
 
313-916-2600 
 
bahmeda1@hfhs.org 
 
Main responsibilities/Key roles:  
Dr. Ahmedani will oversee the work of the ongoing EHR data 
pulls and data transfer tasks to ensure these are completed in a 
timely manner and congruent with the desired objectives of the 
study. He will also participate in reviewing the analysis and 
dissemination of the result and he will participate in regular 
conference calls. 
 
 
 

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1 
STUDY OBJECTIVES 
1.1 Primary Objective 
The primary clinical outcome will be change in the total standardized daily dosage 
(TSDD) of the medication classes contributing to CNS polyRx as measured in the EHR, 
from baseline to 4 months after sending the adapted intervention. We hypothesize that the 
TSDD of the medication classes contributing to CNS polyRx will decline from baseline 
to 4 months in participants receiving the nudge intervention (though this pilot study is not 
designed [or powered] to detect a statistically significant change).  
1.2 Secondary Objectives 
• Adapt an educational nudge intervention to help motivate CNS polyRx 
deprescribing among PLWD 
• Establish mailing of the educational brochure within the clinic workflow by 
engaging clinicians and pharmacists at each of the identified clinics  
• Establish implementation feasibility: after sending the tool, the proportion of 
enrollees with documentation in the EHR of discussion regarding CNS-active 
medications with a prescribing clinician (or pharmacist).  
2 
BACKGROUND AND RATIONALE  
2.1 Background on Condition, Disease, or Other Primary Study Focus 
The number of people living with Alzheimer’s disease or a related dementia (PLWD) in the 
U.S. is projected to grow to 50 million people by 2050. Although cognitive impairment is the 
clinical hallmark of dementia, behavioral and psychological symptoms of dementia (BPSD) such 
as apathy, delusions, agitation, and sleep disturbances are exceedingly common, occur in all 
forms of dementia, and often dominate disease presentation.1-5 Nearly all patients will exhibit 
these symptoms at some point in the course of dementia.3,6 Such symptoms, as opposed to core 
cognitive symptoms, are particularly vexing and create the most difficulties for patients, 
caregivers, and clinicians, leading to earlier nursing home placement.7-13 Central nervous system-
active medications are widely prescribed to PLWD in the community to address these symptoms. 
In a recent JAMA publication by Dr. Maust’s team analyzing all traditional Medicare 
beneficiaries living with dementia who had Part D prescription drug coverage, 73.5% filled a 
prescription for at least one CNS medication, despite the minimal evidence of efficacy among 
PLWD while 13.9% of community-dwelling PLWD were exposed to CNS polyRx, defined as 
>30 days of concurrent exposure to ≥3 CNS medications.14 CNS medication use—singly and in 
combination—poses specific risks for older adults overall and PLWD specifically given the 
adverse impact on cognition and potential for harms including fall-related injury and death.  
2.2 Study Rationale 
The health care system is poorly equipped to deal with the growing number of persons living 
with dementia (PLWD) and their complex medical and psychosocial needs, which may help 
explain their high rate of potentially inappropriate psychotropic and opioid polypharmacy. 
However, there is potential for direct-to-patient education to promote deprescribing. The power 
of a direct-to-patient educational nudge approach has been highlighted by the EMPOWER 
intervention, which specifically focused on and successfully achieved sedative-hypnotic (e.g., 

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benzodiazepines) deprescribing in older adults. Critically for this proposal, a post hoc analysis 
found no difference in efficacy between participants with and without mild cognitive 
impairment. Based on the potential demonstrated by EMPOWER, a direct-to-patient approach 
may be a helpful mechanism to prompt CNS polyRx deprescribing among PLWD. Therefore, we 
will adapt direct-to-PLWD educational nudge to address such polypharmacy. This educational 
intervention poses minimal risks to participants, particular given that the “usual care” being 
targeted (CNS polyRx) in fact poses significant risks to PLWD.  
3 
STUDY DESIGN 
• 
Type/design of trial (e.g., placebo-controlled, double-mask, parallel design, open-label, dose 
escalation, dose-ranging) 
This is an educational nudge intervention with two intervention clinics and two control 
clinics. 
• 
Specific statement of the primary and secondary outcomes (must be consistent with Study 
Objectives) 
The primary clinical outcome will be change in the total standardized daily dosage (TSDD) 
of the medication classes contributing to CNS polyRx as measured in the EHR, from baseline 
to 4 months after sending the adapted intervention. We hypothesize that the TSDD of the 
medication classes contributing to CNS polyRx will decline from baseline to 4 months in 
participants receiving the nudge intervention (though this pilot study is not designed [or 
powered] to detect a statistically significant change).  
 
Secondary Objectives are: 
a. Adapt a patient- oriented educational nudge intervention to help motivate CNS 
polyRx deprescribing among PLWD 
b. Establish mailing of the educational brochure within the clinic workflow by 
engaging clinicians and/or pharmacists at each of the participating clinics  
c. Establish implementation feasibility: after sending the tool, the proportion of 
enrollees with documentation in the EHR of discussion regarding CNS-active 
medications with a prescribing clinician (or pharmacist).  
• 
Study population and groups/arms including sample size  (including a table, if appropriate) 
We will identify 120 PLWD experiencing CNS polyRx across participating clinics to receive 
the intervention.  
• 
Study location (e.g., in-patient or out-patient, clinic, community) 
A total of four primary care clinics at University of Michigan Health and Henry Ford Health; 
potentially more clinics will be engaged if necessary to reach the goal of N=120 PLWD. 
• 
Approximate duration of enrollment period and follow-up (specify individual participant vs. 
entire trial) 
Approximately 6 months accounting for EHR review, sending the nudge tool, and then 
allowing several months (4) afterwards for dyads to discuss with clinicians and make 
medication changes. 
• 
Description of intervention and administration 
An adapted EMPOWER brochure that will specifically be modified to address CNS polyRx 
(as opposed to the single-class focus of the original). The intervention will be adapted based 

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on input from successive rounds of focus groups and then administered by mail through the 
clinic. There is no direct interaction between the study team and PLWD 
• 
Randomization, blinding and any stratification 
There is no patient-level randomization. Within each health system (University of Michigan 
and Henry Ford), we will randomly select one of the clinics where patients will receive the 
nudge intervention. 
• 
Other protocol specific details, such as centralization of evaluations (e.g., central laboratory 
or central reading center for clinical scans). 
n/a 
 
 
4 
SELECTION AND ENROLLMENT OF PARTICIPANTS  
4.1 Inclusion Criteria  
Aim 1: Focus Group Research  
The inclusion criteria for the Person living with Dementia (PLWD) will be:  
(1) Individuals with a self-reported diagnosis of dementia of any type and experiencing no 
more than mild dementia;  
(2) Individuals that are able to read, speak and understand English;  
(3) Individuals that have a care partner (CP) 
(4) Individuals that are 50 years of age or older. 
 
The inclusion criteria for the care partner (CP) will be: 
(1) Individuals who are 18 years of age or older or considered legal adults in their state of 
residence; 
(2) who are able to read, speak and understand English; 
(3) Individuals who are identified as the CP to the PLWD. 
 
Aim 2 and 3: Intervention 
The inclusion criteria for the Person living with Dementia (PLWD) will be:  
(1) Individuals who are receiving care at the one of the selected primary care clinics at 
Michigan Medicine and Henry Ford Health System;  
(2) Individuals who have a diagnosis of dementia or mild cognitive impairment (MCI) of 
any type based on ICD-10 codes;  
(3) Individuals who have been prescribed ≥3  of the medications that contribute to CNS 
polyRx (e.g., antidepressants, antipsychotics, anti-epileptics, benzodiazepines, non-
benzodiazepine benzodiazepine receptor agonist hypnotics, or opioids) based on chart 
review;  
(4) Individuals that are 50 years of age or older. 
4.2 Exclusion Criteria  
Aim 1: Focus Group Research  
The exclusion criteria for PLWD will be:  
(1) Individuals who do not read, speak, or understand English;  
(2) Individuals with a diagnosis of dementia that is in severe stage; 
(3) Individuals with visual impairment that would prohibit viewing study materials; 

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(4) Individuals with hearing impairment sufficient to prohibit participation in a focus 
group. 
 
The exclusion criteria for CPs will be:  
(1) Individuals who do not read, speak or understand English;  
(2) Individuals with any visual impairment that would prohibit viewing study materials;  
(3) Individuals with any hearing impairment that would prohibit participation in a focus 
group. 
 
Aim 2 and 3: Intervention 
(4) After identifying potential participants through EHR at the intervention and control 
clinics, we will provide the list to their primary care clinicians to review and opt-out 
potential participants for whom they feel the intervention is not appropriate. (While the 
control clinics will not receive the intervention, we will still allow their clinicians to 
indicate PLWD for whom the think the intervention would be inappropriate in order to 
have the most comparable groups.) At intervention sites, clinicians will also be given 
the opportunity to suggest any additional patients at the clinic who meet the inclusion 
criteria and may have been missed by the EHR search. The opt out letter and responses 
will be sent by email to/from the research assistant or coordinator at each respective site 
and the clinic liaison. If doctors wish to suggest any additional patients, those patients 
will be added to REDCap by the health system’s own research team. Patients selected 
in this way will be noted in REDCap as having been selected through this alternate 
method.   
 
 
4.3 Study Enrollment Procedures  
Aim 1: Focus Groups 
Identifying and recruiting trial participants: Participants will be identified and recruited through 
various organizations including Michigan Medicine entities (e.g., the CTSA recruitment portal, 
Pepper Center, and ADRC, UMHealthResearch), the Henry Ford Health System (HFHS), and 
community dementia organizations with which Drs. Maust and Leggett have partnered with 
previously (Alzheimer’s Association and Dementia Minds). Study staff will distribute flyers via 
mail and/or email to the organizations and individuals with mild cognitive impairment/early-
stage dementia and care partners from an existing list of participants in our previous work who 
have indicated interest in being contacted again for future research to maximize exposure. 
Anyone who thinks they may qualify for the study can call or email a study team member to 
inquire. Staff will use a screening log to document participant contact information and any 
reasons for ineligibility. The screening log will be stored on a RedCap (Research Electronic Data 
Capture) database. Focus groups will be virtual and conducted over Zoom. Each participant will 
receive the focus group questions and the brochure ahead of time. The virtual format will ensure 
a diverse sample and reduce participant burden. Following the group discussion, the study team 
will conduct brief follow-up phone interviews with select, individual focus group participants. 
The purpose of these follow-up phone calls is to allow participants and researchers time to reflect 
on the discussion and clarify any insights that emerged. Not all focus group participants will be 
asked to participate in a follow-up phone call.  

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Eligibility and Ineligibility criteria: Focus group PLWD participants will have no more than mild 
dementia based on the CP and/or PLWD self-report. Eligibility will be based on self-report and 
the dyad’s availability and willingness to participate in the group discussion. Participation in the 
focus group will present no more than minimal risk to the participants and the probability of 
experiencing minimal risks associated with this project are not greater than risks encountered in 
daily life.  
Consent procedures: Please see section 11 for consent procedures. 
Aim 2: Pilot feasibility of (a) using the electronic health record (EHR) to identify PLWD 
experiencing CNS polyRx and (b) implementing the adapted EMPOWER intervention in 
two primary care clinics using pragmatic methods.  
Identifying and recruiting trial participants: Patients in Aim 2 and 3 will not be recruited directly 
to participate.  
Eligibility and Ineligibility criteria: We will use the electronic health record (EHR) to identify 
patients living with dementia prescribed these problematic medication combinations (2a). Team 
data analysts will use DataDirect—the portal for researchers into the Michigan Medicine and 
HFHS EHRs—to identify PLWD seen in primary care with CNS-active polyRx. ICD-10 codes 
will be used to identify PLWD (including MCI) with an ambulatory care encounter with a 
primary care clinician (internal medicine, family medicine, or geriatrics) during the preceding 12 
months. Within each system, we will identify a pair of clinics that have relatively similar panel 
characteristics (similar volume overall; PLWD with similar distributions of gender, 
race/ethnicity) to serve as the paired intervention-control sites. Among PLWD, we will use 
current outpatient medications data to identify those with ≥3 active prescriptions of the 
medications that contribute to CNS polyRx (e.g., antidepressants, antipsychotics, anti-epileptics, 
benzodiazepines, non-benzodiazepine benzodiazepine receptor agonist hypnotics, or opioids). 
We will contact the primary care clinicians of eligible PLWD once by email to offer them the 
opportunity to exclude potential PLWD participants for whom they think the intervention would 
be inappropriate; clinicians will have one week to opt potential participants out, or to suggest an 
eligible patient we may have missed (if they do not reply, we will assume that we can proceed).  
Randomization: We will randomly select one clinic (or more, as needed to meet the target dyad 
sample size) within each system as the intervention clinic; dyads in these clinics will receive the 
nudge intervention. Dyads within the other clinic in each system will serve as controls. 
Consent procedures: We will request a waiver of informed consent for PLWD participants in 
Aim 2 and 3.  See section 11.2 for details.  
 
5 
STUDY INTERVENTIONS  
5.1 Interventions, Administration, and Duration  
This project will adapt the EMPOWER educational brochure for PLWD receiving CNS polyRx. 
The educational brochure will be mailed to intervention participants identified through EHR at 
Michigan Medicine and Henry Ford Health System. Prior work utilizing the EMPOWER 
intervention specifically focused on sedative-hypnotic (e.g., benzodiazepines) deprescribing in 
older adults.15 In that EMPOWER trial, investigators developed an educational tool to “increase 
risk perception about benzodiazepines through knowledge acquisition and change in beliefs”16 

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(e.g., “The dose that I am taking causes no side effects;” [True/False]]); this tool (in the form of 
an 8-page brochure) was mailed to older adults on long-term benzodiazepine therapy. In the 
current study, this tool, to be delivered in the form of a brochure mailed to PLWD will describe 
what CNS polyRx is, present information about the associated risks, and suggest that they speak 
with their prescribing clinician or pharmacist about ways to potentially simplify their medication 
regimen. The tool will be adapted through three successive rounds of focus groups of PLWD and 
caregivers (n=5 PLWD-CP dyads per round for 15 dyads total). As part of Aim 2, we will 
identify eligible participants from the EHR and allow primary care clinicians to opt-out patients 
for whom they believe the intervention would be inappropriate. The educational tool will be 
mailed from the participating health systems with a cover letter from the respective clinic that 
includes the specific medication combination that made the PLWD eligible for the study. The 
goal of the educational nudge is to prompt a conversation with the PLWD’s clinician or 
pharmacist; the material will clearly state that individuals should not make any medication 
changes without discussing with their clinician. The EHR will be reviewed 4 months after the 
brochure is mailed to determine with there has been any change to the CNS polyRx. 
 
5.2 Handling of Study Interventions  
n/a 
 
5.3 Concomitant Interventions 
5.3.1 Allowed Interventions 
All usual interventions are allowed. 
5.3.2 Required Interventions  
None. 
5.3.3  Prohibited Interventions 
None. 
5.4 Adherence Assessment  
n/a 
 
6 
STUDY PROCEDURES 
 

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6.1 
Schedule of Evaluations 
 
Assessment 
Month 1-2  
Month 3-4 
Month 5-6 
Month 7-8 
Month 9-10 Month 11-12 
Draft adapted tool 
x 
 
 
 
 
 
Adapt content (focus 
groups x3) 
 
x 
x 
 
 
 
Follow-up phone calls 
 
x 
x 
 
 
 
Screen/Identify target 
PLWD in EHR 
 
 
x  
  
  
  
Allow clinician opt-out of 
participants  
 
 
x 
 
 
 
Clinic randomization 
 
 
x 
 
 
 
Mailing of educational tool 
 
 
  
x 
  
  
2-month chart review 
 
  
 
x  
  
  
4-month chart review  
 
  
  
  
x  
  
Clinician Interviews 
 
 
 
 
 
x 
Adverse Events  
  
 
 
x 
x 
x 

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6.2 Description of Evaluations  
6.2.1 Screening Evaluation 
Aim 1: Screening for focus groups will be based on subject’s self-reported diagnosis of 
early-stage dementia.  
 
Aim 2/3: Screening for the intervention will occur through electronic health record 
(EHR) chart review, this project does not require screening evaluations. 
 
Consenting Procedure 
Aim 1: For the focus group discussions, the consent process will be interactive and 
allow the participants with dementia to express understanding and interest. Before the 
focus groups, participants will be mailed the adapted brochure for previewing and a 
simplified consent form with key information about the project and their involvement. 
At the beginning of the focus group, which will be conducted over the Zoom 
teleconferencing platform, study staff will review the main tenets of the Consent 
Information Sheet with all participants using a comprehensive oral script and take 
time to answer questions. Participants will also be informed that they may be asked to 
participate in a brief follow-up phone call after the focus group (scheduled no later 
than 2 weeks following the focus group, at the selected participant’s convenience). At 
the beginning of the focus group when staff summarizes the Consent Information 
Sheet, participants will be informed that they can opt out of eligibility for the 
potential follow-up phone call.  
Aims 2/3: For the intervention we will request waiver of informed consent for PLWD 
intervention participants; see section 11.2.  
Screening   
Aim 1: Screening for focus groups will be based on subject’s  (PLWD and/or CP)self-
reported diagnosis of early-stage dementia.  
Aims 2/3: Screening to identify eligible participants will occur through electronic 
health record (EHR) chart. We will provide primary care clinicians the opportunity to 
opt-out their patients if they think the intervention is not clinically appropriate. The 
confirmed PLWDs will be the recipient of the nudge intervention. 
6.2.2 Enrollment, Baseline, and/or Randomization 
Enrollment 
Aim 1: Research staff will contact potential participants by telephone to collect basic 
demographic information to ensure a diverse sample and determine eligibility. 
Eligibility will be based on 1.) a diagnosis of dementia of any type with no more than 
mild dementia as reported by the PLWD and/or the care recipient and 2.) the dyad’s 
availability and willingness to participate in the virtual group discussion. 
Aim 2/3: Once a PLWD is deemed eligible based on chart review and mailed the 
educational tool, they are enrolled in the project.  

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Baseline Assessments 
Aim 1:  There are no baseline assessments for focus group participants.  
Aim 2/3: There are no baseline assessments of the participants. Baseline information 
will be collected from the EHR, including basic demographics (age, gender, 
race/ethnicity), diagnoses, and active medications include CNS-active.  
Randomization 
Aim 1: n/a 
Aim 2/3: We will randomly select one clinic (or more, as needed to meet the target 
sample size) within Michigan Medicine and Henry Ford Health System as the 
intervention clinics from which  PLWD will receive the nudge intervention. PLWD 
within the other clinic in each system will serve as controls. 
6.2.3 Follow-up Visits 
Aim 1: Participants in the group discussion may be asked to participate in a follow-up 
phone call 1-2 weeks after the group discussion is over. The follow-up will allow 
time for researchers to reflect on the discussion and to clarify any questions that may 
come up after the discussion. Not every focus group participant will be asked to 
participate in a follow-up. After the research team reviews transcripts, the research 
team will clarify any questions that come up after the discussion is over. Additionally, 
based on the teams’ previous experience in working with CP-PLWD dyads, some 
care participants may not be comfortable being frank with their PLWD present and 
the follow-up may allow care partners the opportunity to clarify anything without 
their PLWD present. The follow-up phone call will be brief (≤15 minutes) and not all 
participants will be asked to participate. Potential participants will be called or 
emailed after the focus group to determine if they are interested in participating and 
the call will be scheduled at their convenience.  
The intervention does not entail any follow-up visits. For evidence of implementation 
feasibility, we will do a 2-month chart review of PLWD primary care and pharmacy 
notes to determine if there is documented evidence of conversation related to the 
medications of interest (i.e., did the nudge intervention have the intended outcome). 
 
6.2.4 Completion/Final Evaluation 
We will repeat a final EHR review for evidence of documented conversation related 
to these medications. In addition, we will review the active medications to determine 
the primary outcome of changes to the CNS-active medication regiment. 
Additionally, we will conduct informant interviews with 10 primary care clinicians 
across intervention clinics from U-M and HFHS. The purpose of these interviews will 
be to explore potential barriers with experts and will explore whether: 
• PLWD discussed receiving the tool with the clinician; 
• Clinician perception of whether the tool motivated: 
o discussion related to prescribing that might not have occurred 
otherwise; 
o prescribing changes that might not have occurred otherwise; 

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• Clinician suggestions for modifications to the tool; 
• Clinician suggestions regarding their perceived barriers or facilitators to 
improving the appropriateness of CNS-active prescribing, e.g.: 
o Clinical uncertainty regarding which medications to address; 
o Lack of access to clinical pharmacists to facilitate medication changes; 
o Lack of psychosocial resources for the PLWD-CP dyad. 
 
 
 
7 
SAFETY ASSESSMENTS  
7.1 Specification of Safety Parameters 
n/a 
7.2 Methods and Timing for Assessing, Recording, and Analyzing Safety Parameters 
The intervention is presenting education, which has a benign safety profile. Should the 
participants, in consultation with their clinician, choose to make medication changes, then 
participants should be at lower risk of adverse events by minimizing the burden of these 
medications. In a recent study of deprescribing among PLWD (of any, not limited by 
medication class), there was no difference in hospitalization or mortality rates in 
intervention groups, and review of records did not “reveal any pattern of adverse drug 
withdrawal events associated with the intervention.”17 In the original EMPOWER 
intervention (deprescribing of sedative-hypnotics), “no major adverse effects requiring 
hospitalization were reported.”15 
Study participants will be identified using the EHRs and the intervention will consist of 
mailed materials to the participant—otherwise, the study team has no contact with study 
participants. Therefore, any potential adverse event reporting will come to the research 
team through clinics from which patients are identified. In the event of clinic staff 
notifying the study team  of a serious and unexpected adverse event, the PI will follow 
the required reporting protocols detailed below. 
 
7.3 Adverse Events and Serious Adverse Events  
AE Definition: AE is any untoward or unfavorable medical occurrence in a human 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. 
SAE Definition: SAEs consist of 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; requires or prolongs hospitalization; causes persistent or significant disability 
or incapacity; is another condition which investigators judge to represent significant 
hazards. 
Unanticipated Problem (UP) Definition: any incident, experience, or outcome that 
meets all of the following criteria: 

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• unexpected, in terms of nature, severity, or frequency, given (a) the research 
procedures that are described in the protocol-related documents, such as the IRB-
approved research protocol and informed consent document; and (b) the 
characteristics of the study population; 
• related or possibly related to participation in the research;  
• suggests that the research places participants or others at a greater risk of harm 
(including physical, psychological, economic, or social harm) than was previously 
known or recognized. 
AEs for this study include: 
 
AEs for this study include a PLWD making medication changes without first consulting 
with a treating clinician. This may be revealed during the 2-month and 4-month chart 
reviews or by the prescribing clinician. Given risks associated with usual care (e.g., risk 
of respiratory suppression and death from common psychotropic-opioid combinations), 
while we will consider self-directed medication change an AE, in fact PLWD risk of 
medication-related adverse events would likely be lower than the risk from usual care 
(i.e., without change). Overall, we consider the potential for AEs to be low. 
 
SAEs for this study include: 
SAEs are not related nor anticipated as a result of this study. The study activities pose 
minimal risks. Death or hospitalization can reasonably be expected considering the study 
population includes persons living with dementia and those experiencing CNS polyRx. 
However, the study activities will not contribute to the death of participants; in fact, 
reducing burden of CNS-active medication should lower the risk of death. Prior 
deprescribing intervention studies in older adults demonstrate no impact on 
hospitalization or death.1715 
7.3.1 Reporting Procedures 
Severity of Event 
All data and safety monitoring reporting will classify SAEs and AEs as to their severity, 
expectedness, and potential relatedness to the study intervention as per the definitions 
below: 
Severity 
• Mild: Awareness of signs or symptoms, but easily tolerated and are of minor 
irritant type causing no loss of time from normal activities. Symptoms do not 
require therapy or a medical evaluation; signs and symptoms are transient. 
• Moderate: Events introduce a low level of inconvenience or concern to the 
participant and may interfere with daily activities, but are usually improved by 
simple therapeutic measures; moderate experiences may cause some interference 
with functioning 
• Severe: Events interrupt the participant’s normal daily activities and generally 
require systemic drug therapy or other treatment; they are usually incapacitating 
 

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Relationship To Study Intervention 
Definitely Related: The adverse event is clearly related to the investigational 
agent/procedure – i.e. an event that follows a reasonable temporal sequence from 
administration of the study intervention, follows a known or expected response pattern to 
the suspected intervention, that is confirmed by improvement on stopping and 
reappearance of the event on repeated exposure and that could not be reasonably 
explained by the known characteristics of the subject’s clinical state. 
Possibly Related: An adverse event that follows a reasonable temporal sequence from 
administration of the study intervention follows a known or expected response pattern to 
the suspected intervention, but that could readily have been produced by a number of 
other factors. 
Not Related: The adverse event is clearly not related to the investigational 
agent/procedure - i.e. another cause of the event is most plausible; and/or a clinically 
plausible temporal sequence is inconsistent with the onset of the event and the study 
intervention and/or a causal relationship is considered biologically implausible. 
 
7.3.2 Follow-up for Adverse Events 
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  
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  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 Safety Officer, Dr. Madhuri Reddy  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 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 Safety Officer, Dr. Madhuri 
Reddy within 48 hours of the study’s knowledge of the event. 

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• 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 Safety Officer, Dr. Madhuri Reddy at a minimum every 6 months, 
or at a frequency requested by the Safety Officer or NIA IMPACT Collaboratory 
PO. 
7.4 Safety Monitoring 
The NIA Guidelines on Data and Safety Monitoring generally require that a NIA-
appointed Data and Safety Monitoring Board or Safety Officer monitor clinical trials. 
Please see the Data and Safety Monitoring Guidelines . 
8 
INTERVENTION DISCONTINUATION  
For this pragmatic intervention, there is no specific intervention discontinuation. The 
intervention consists of providing educational information on one occasion and it will be 
up to the dyad and clinician whether there are any resulting medication changes. 
9 
STATISTICAL CONSIDERATIONS  
9.1 General Design Issues  
 
For this nudge intervention, the primary clinical outcome will be change in the total 
standardized daily dosage (TSDD) of the medication classes contributing to CNS polyRx 
as measured in the EHR, from baseline to 4 months after sending the adapted 
intervention. We hypothesize a decline in the total standardized daily dosage (TSDD) 
following the nudge intervention. The presumed mechanism of the intervention is that the 
nudge educational tool will activate the dyad to discuss their current medication regimen 
with the prescribing clinician or a pharmacist. To determine whether the intervention has 
had this desired effect, as an implementation feasibility target, the team at each site will 
revisit intervention PLWD charts to complete an expedited chart review. We will 
complete initial reviews approximately two months after sending the tool and final 
review four months after sending the tool. 
9.2 Sample Size and Randomization 
Our goal of participants is a total of 120 PLWD (a total of 60 across 2 intervention 
clinics; 60 across 2 control clinics), after allowing for clinician opt-out. This will then 
allow us to obtain a reasonably precise estimate of the first feasibility outcome (i.e., 
documentation of a prescribing-related conversation in the EHR), allowing us to 
determine the number of clinics within each health care system needed for the future 
ePCT. We will also be able to estimate the lower limit of a 95% confidence interval 
around the implementation feasibility target (i.e., documented discussion regarding CNS 
polyRx) not to drop below the pre-determined target of 50%. With N=60 PLWD (i.e., the 
PLWD in the intervention clinics) and assuming 65% to 75% to show evidence of CNS-
medication discussions, the lower limits of a 95% confidence interval for implementation 

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feasibility target will be 51.6% to 62.1%, respectively. Meeting the implementation 
feasibility target will allow us to proceed to a full ePCT. 
9.2.1 Treatment Assignment Procedures 
We will randomly select one clinic (or more, as needed to meet the target sample 
size) within Michigan Medicine and Henry Ford Health System as the intervention 
clinic; PLWD in these clinics will receive the nudge intervention. PLWD within the 
other clinic in each system will serve as controls. 
9.3 Interim analyses and Stopping Rules 
No interim analyses are planned. 
9.4 Outcomes  
9.4.1 Primary outcome   
The primary clinical outcome will be change in the total standardized daily dosage 
(TSDD) of the medication classes contributing to CNS polyRx as measured in the EHR, 
from baseline to 4 months after sending the adapted intervention. 
9.4.2 Secondary outcomes   
n/a 
9.5 Data Analyses 
• Aim 1 will involve rapid and rigorous qualitative analysis. Focus group discussions and 
any follow-up phone calls will be audio recorded. Following transcription of focus 
groups, the transcripts will be used to create summaries for each focus group, which will 
then be reconciled through discussion. Summary data regarding tool refinement and 
recipient engagement will be transferred into a matrix for interpretation and comparison 
across groups. This matrix will be reviewed by all pilot investigators to select final 
refinements of the tool as well as to finalize the Aim 2 engagement strategy. If 
participants selected for a follow-up phone call agree to being recorded, the brief 
discussion will be audio recorded for accuracy purposes.  
• Aim 2: With N=120 PLWD, we expect to obtain a reasonably precise estimate of the first 
feasibility outcome, allowing us to determine the number of clinics within each health 
care system needed for the future ePCT.  
• 
Aim 3: Four months after sending the tool, we will do a final EHR query (Aim 3) for all 
participants to assess the burden of CNS polyRx (i.e., total standardized daily dosage) 
and determine whether the prescribing regimen changed from the medications prescribed 
at baseline. We will use each active outpatient prescription for a CNS-active medication 
and convert them to a standardized daily dose using the minimal effective geriatric daily 
dose, adding the total across all CNS-active medications at the patient level. This—
change in the total standardized daily dosage (TSDD) following the nudge intervention—
will be the primary outcome for the study and subsequent trial. With the expected sample 
size of 120 PLWD (60 per group and 30 per clinic-group), we expect to have a good 
estimate of the variability of the distribution of change in TSSD (clinical outcome 

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measure) from baseline in each group as well as within-clinic correlation of the changes 
in TSSD. 
Data analysis will be completed by a Maust team analyst, under supervision of the study 
biostatistician. Because the nature of the intervention is that any changes are made by the 
PLWD in consultation with their treating clinician, there are not trial results or 
information to provide to the clinician at completion of the pilot study (i.e., the 
intervention does not entail treatment changes other than those made by the treating 
clinician).  
10 
DATA COLLECTION AND QUALITY ASSURANCE 
10.1 Data Collection Forms 
To maintain the confidentiality of the intervention participants, the study team will follow 
strict procedures that protect subject information. Information necessary for eligibility 
and enrollment will be stored in REDCap. REDCap is a secure web application designed 
to support data capture for research studies. It provides user-friendly web-based case 
report forms, real-time data entry with branching logic and validation (e.g. for data types 
and range checks), audit trails, a de-identified data export mechanism to common 
statistical packages (SPSS, SAS, Stata, R/S-Plus), procedures for importing data from 
external sources, and advanced features such as a data quality check module. The system 
was developed by a multi-institutional consortium initiated at Vanderbilt University. 
REDCap servers are physically located in the University of Michigan Medical School 
Information Systems (MSIS) data center. Application and database servers are on virtual 
machines (VM). Surveys will capture focus group participant demographics, specific 
diagnosis information for PLWD including diagnosis type and date of diagnosis; this 
information will also be collected and stored in REDcap. Participants’ names and contact 
information will be stored in a secure, REDCap database, separate from their study data 
and only accessible to members of the research team for research purposes.  
 
Focus group discussions will be recorded and then transcribed with identifiers removed 
and audio recordings will be destroyed. Transcriptions will be stored in password 
protected files.  
 
Only data necessary for the intervention will be collected through EHR for subjects in 
aim 2 and 3 (demographics, medications, mailing address). Study participants will be 
identified using the EHR and data collected will be stored in REDCap. Outcome data will 
be collected from the EHRs and stored in REDCap, there will not be any further contact 
with study participants beyond the initial mailing of the intervention materials. 
 
10.2 Data Management  
Qualitative data from focus groups in Aim 1 will be stored in password protected files. 
All survey data from Aim 1 and EHR data from Aims 2 and 3 will be stored in REDCap. 
The system was developed by a multi-institutional consortium initiated at Vanderbilt 
University. REDCap servers are physically located in the University of Michigan 
Medical School Information Systems (MSIS) data center. The University of Michigan 

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team will sponsor REDCap accounts for each necessary member of the Henry Ford team.  
Only necessary study team members will have access. The Michigan Medicine team will 
lead data analysis.  
10.3 Quality Assurance  
10.3.1 
Training 
All staff have completed Program for the Education and Evaluation in Responsible 
Conduct of Research (PEERRS) and Good Clinical Practice trainings. Staff will 
follow quality assurance procedures to assure the accuracy and consistency of study 
data. Any adverse events that are serious and unexpected will be reported to study 
staff by participating clinics. Training on the importance of identifying any adverse 
events, including checklists, will be provided to clinic staff throughout the course of 
the study.  
10.3.2 Quality Control Committee  
The Principal Investigator, Dr. Maust, will be responsible for ensuring participants’ 
safety on a daily basis.  The study team will meet regularly to ensure safety and 
quality. In addition, the NIA IMPACT Collaboratory Safety Officer 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 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 DSMB chair, will make a determination regarding the level and format of data 
and safety monitoring this study requires, i.e., full DSMB oversight or monitoring by 
an independent SO. 
10.3.3 Metrics 
n/a 
10.3.4 Protocol Deviations 
Any unplanned deviations or departures from IRB approved protocol procedures will 
be reported to Dr. Maust and the Advara IRB.   
10.3.5 Monitoring 
Both the enrollment and implementation feasibility targets from Aim 2 will entail 
chart reviews for patients with dementia experiencing CNS-PolyRx. For each 
component, research assistants (RAs) will complete the first 20 chart reviews, which 
will then be reviewed by Drs. Maust and Akinyemi (the UM and Henry Ford PIs, 
respectively) to assure appropriate and accurate data abstraction. The RAs will then 
complete further reviews independently. 
11 
PARTICIPANT RIGHTS AND CONFIDENTIALITY  
11.1 Institutional Review Board (IRB) Review 
This protocol and any future modifications will be submitted to the Advara IRB for 

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approval. Study team members will strictly adhere to IRB guidelines and policies.  
11.2 Informed Consent Forms 
Aim 1: Focus groups PLWD participants will have no more than mild dementia and 
participation in the focus group will present no more than minimal risk to the participants 
and the probability of experiencing minimal risks associated with this project are not 
greater than risks encountered in daily life.  We will seek approval to waive 
documentation and include a comprehensive oral script for the PLWD-CP dyad. After 
completing the recruitment and screening procedures, interested and eligible individuals 
will have the option to receive a mailed and/or emailed a Consent Information Sheet (a 
simplified consent form with key information about the project and their involvement) 
before the focus group. At the beginning of the virtual focus group, study staff will 
review the main tenets of the Consent Information Sheet with all participants (PLWD-CP 
dyads) using a comprehensive oral script Participants will also be informed that they may 
be asked to participate in a brief follow up phone call after the focus group (1-2 weeks 
following the discussion, and scheduled at the selected participant’s convenience). The 
study team also allow participants to opt out of a follow-up phone call at the beginning of 
the focus group when staff summarizes the Consent Information Sheet. Participants will 
be encouraged to ask questions and verbal consent will be obtained. We have chosen this 
consent process to minimize participant burden and to ensure the cognitively impaired 
participants are not overwhelmed by information. This verbal consent process will make 
our recruitment processes more efficient. We will maintain a spreadsheet where we track 
participant IDs, we include a column for date of consent and consent provider. It should 
not be assumed that persons with mild cognitive impairment/early-stage dementia are 
unable to give consent. Our approach will make the consent process interactive and 
provide opportunities for the individual with dementia to demonstrate capacity to 
understand the study while not overwhelming with information. The research includes 
people living with dementia who will have capacity to provide informed consent. To 
ensure that the individuals understand their involvement in the research, our approach to 
informed consent will me pragmatic and interactive. We will use Talk Back to assess 
comprehension we will remind participants that their participation is voluntary and they 
are free to leave at any time. We will use the same approach (waiving documentation and 
using a comprehensive oral script) for obtaining informed consent for CP participants in 
the focus groups. 
Aims 2 and 3: We will request a waiver of informed consent for PLWD participants in 
for the following reasons: 
• The research involves no more than minimal risk: This is an educational intervention to 
prompt a discussion with the PLWD’s clinician or pharmacist. Given the inclusion 
criteria—these are PLWD exposed to CNS polyRx—the "probability and magnitude of 
harm or discomfort anticipated in the research are not greater in and of themselves than 
those ordinarily encountered in daily life” given the adverse outcomes associated with the 
usual care (i.e., CNS polyRx) that establishes study eligibility.  
• The research could not practicably be carried out without the requested waiver or 
alteration: Sending an informed consent document to PLWD describing the 

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deprescribing study could bias the control group by introducing them to the concept of 
deprescribing itself and interfere with the aims of this project.  
• If the research involves using identifiable private information or identifiable 
biospecimens, the research could not practicably be carried out without using such 
information or biospecimens in an identifiable format: In order to determine feasibility, 
implementation, and primacy outcomes, the information must be in an identifiable 
format. 
• The waiver or alteration will not adversely affect the rights and welfare of the subjects: 
The intervention is entirely comprised of education about appropriate medication use; 
generally providing additional, potentially actionable information to patients and families 
is a valuable goal in health care settings.  
• Whenever appropriate, the subjects or legally authorized representatives will be provided 
with additional pertinent information after participation:  At the conclusion of the study, 
we will send the intervention PLWD a one-page informational study summary. The 
summary will be written in accessible language and will include pertinent information 
and findings. 
11.3 Participant Confidentiality  
Aim 1: To minimize the violation of confidentiality for focus group participants, we will 
ensure that data are protected and cannot be linked to a particular person. It is not 
possible to guarantee confidentiality because focus group members may talk about their 
experience, however, participants will be asked to only disclose information that they are 
comfortable sharing in the group setting and we will ask that participants not disclose any 
information shared outside of the group. Unique identification numbers will be assigned 
to each participant and all forms are coded with this number, rather than by name. All 
data are stored in secure password protected files. Enrollment files and subject code/name 
sheets will be stored separately because they contain identifying information. Rigorous 
data security measures and staff training procedures will be put in place to minimize the 
risk of breach of confidentiality. The study team has considerable experience in 
maintaining the confidentiality of participant data and datasets, using established 
procedures to ensure data confidentiality. All investigators and research staff fulfill 
ongoing training requirements for handling protected health information as outlined by 
the Health Insurance Portability and Accountability Act (HIPAA). 
 
Aim 2 and 3: A full HIPAA waiver of authorization will be sought for the use of 
electronic health record data. In order to fulfill requirements for a HIPAA waiver of 
authorization, participant’s protected health information will not be disclosed unless 
necessary for certain individuals working on behalf of the study sponsor. 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 FDA, the NIA/NIH, 
and the OHRP. To maintain confidentiality of the intervention participants, the study 
team will follow strict procedures that protect the confidentiality of subject information; 
Subjects will be assigned study numbers, study records will be secured through the use of 
password protected files and coded by subject identification numbers so that participants 

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cannot be identified by their research record. Access to the EHR files will be limited to 
appropriate study personnel and only study team members who have completed 
appropriate training in the protection of human subjects will have access to the data. At 
the conclusion of the study, identifiers including subject tracking files will be deleted. It 
is necessary for the study team to access intervention participant’s EHR for research 
activities to occur and without a HIPAA waiver of authorization for the following 
reasons: 
• The research involves no more than minimal risk: This is an educational 
intervention to prompt a discussion with the PLWD’s clinician or pharmacist. 
Given the inclusion criteria—these are PLWD exposed to CNS polyRx—the 
"probability and magnitude of harm or discomfort anticipated in the research are 
not greater in and of themselves than those ordinarily encountered in daily life” 
given the adverse outcomes associated with the usual care (i.e., CNS polyRx) that 
establishes study eligibility.  
• The research could not practicably be carried out without the waiver: Without 
access to PHI the research cannot practicably be conducted. 
• If the research involves using identifiable private information or identifiable 
biospecimens, the research could not practicably be carried out without using 
such information or biospecimens in an identifiable format: In order to determine 
feasibility, implementation, and primacy outcomes, the information must be in an 
identifiable format. Only members of the research team will have access to PHI, 
all data will be stored in password protected files with limited access. Identifiable 
data will be deleted/destroyed at the completion of the project 
• The waiver will not adversely affect the rights and welfare of the subjects: The 
intervention is entirely comprised of education about appropriate medication use; 
generally providing additional, potentially actionable information to patients and 
families is a valuable goal in health care settings.  
 
 
 
11.4 Study Discontinuation  
The study may be discontinued at any time by the IRB, the NIA or other government 
agencies as part of their duties to ensure that research participants are protected.  
12 
ETHICAL CONSIDERATIONS 
 
All study team members have appropriate training in the protection of human subjects 
and study team members will strictly follow IRB rules and guidelines and will adhere to 
data management policies.  

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13 
COMMITTEES 
Provide a list of the committees (Steering Committee or Executive Committee, 
Publication Committee, Adjudication Committee, etc.) and describe their roles. 
 
Safety Officer 
Madhuri Reddy, MD, MSc 
Geriatric Medicine Specialist, Hebrew SeniorLife 
Dr. Reddy is a geriatric medicine specialist who specializes in chronic wound care and 
technology. She has a fellowship in chronic wound healing and uses evidence-based care to 
develop methods of prevention and management of pressure ulcers. Dr. Reddy previously served 
as the Chair of the Institutional Review Board at Hebrew SeniorLife. 
 
14 
PUBLICATION OF RESEARCH FINDINGS 
Publication of the results of this trial will be governed by the policies and procedures 
developed by the Steering Committee as well as by the IMPACT Collaboratory.  Any 
presentation, abstract, or manuscript will be made available for review by the IMPACT 
Collaboratory prior to submission. 
15 
REFERENCES 
Provide the citations for all publications and presentations referenced in the text of the 
protocol. 
 
1. Kaufer DI, Cummings JL, Christine D, Bray T, Castellon S, Masterman D, MacMillan A, 
Ketchel P, DeKosky ST. Assessing the impact of neuropsychiatric symptoms in alzheimer's 
disease: The neuropsychiatric inventory caregiver distress scale. J Am Geriatr Soc. 
1998;46(2):210-5. 
2. Lyketsos CG, Carrillo MC, Ryan JM, Khachaturian AS, Trzepacz P, Amatniek J, 
Cedarbaum J, Brashear R, Miller DS. Neuropsychiatric symptoms in alzheimer's disease. 
Alzheimers Dement. 2011;7(5):532-9. PMCID: PMC3299979. 
3. Geda YE, Roberts RO, Knopman DS, Petersen RC, Christianson TJ, Pankratz VS, Smith 
GE, Boeve BF, Ivnik RJ, Tangalos EG, Rocca WA. Prevalence of neuropsychiatric symptoms in 
mild cognitive impairment and normal cognitive aging: Population-based study. Arch Gen 
Psychiatry. 2008;65(10):1193-8. PMCID: PMC2575648. 
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16 
SUPPLEMENTS/APPENDICES 
16.1 Central Nervous System-Active Classes and Medications 
Class 
AHFS code 
Generic names 
Antidepressants 
28:16.04.20, 
28:16.04.16,  
28:16.04.28,  
28.16.04.92, 
Trazodone 
28:16.04.20: Citalopram, Escitalopram, Fluoxetine, 
Fluvoxamine, Paroxetine, Sertraline, Vilazodone 
28:16.04.16: Desvenlafaxine, Duloxetine, Levomilnacipran, 
Venlafaxine, Milnacipran 
28:16.04.28: Amitriptyline, Amoxapine, Clomipramine, 
Desipramine, Doxepin, Imipramine, Maprotiline, Nortriptyline, 
Protriptyline, Trimipramine 
28.16.04.92: Bupropion, Mirtazapine 
Misc: Trazodone 
Antiepileptics 
28.12.XX.XX 
except  
benzodiazepines  
28:12.04: Phenobarbital, Primidone, Methohexital 
28:12.12: Ethotoin, Fosphenytoin, Phenytoin 
28:12.16: Ethadione, Paramethadione, Trimethadione 
28:12.20: Ethosuximide, Methsuximide 
28:12.92: Brivaracetam, Carbamazepine, Eslicarbazepine, 
Felbamate, Gabapentin, Lacosamide, Lamotrigine, 
Levetiracetam, Magnesium Sulfate, Oxcarbazepine, 
Perampanel, Pregabalin, Rufinamide, Sultiame, Tiagabine, 
Topiramate, Valproate/Divalproex/Valproic Acid, Vigabatrin, 
Zonisamide, Acetazolamide 
Antipsychotics  
28.16.08.XX 
28:16.08.04: Aripiprazole, Asenapine, Brexpiprazole, 
Cariprazine, Clozapine, Iloperidone, Lurasidone, Olanzapine, 
Paliperidone, Pimavanserin, Quetiapine, Risperidone, 
Ziprasidone 
28:16.08.08: Haloperidol 
28:16.08.24: Chlorpromazine, Fluphenazine, Perphenazine, 
Prochlorperazine, Thioridazine, Trifluoperazine 
28:16.08.32: Thiothixene 
28:16.08.92: Loxapine, Molindone, Pimozide 
Benzodiazepines 
28:24.08 
Alprazolam, Chlordiazepoxide, Clorazepate, Diazepam, 
Estazolam, Flurazepam, Halazepam, Lorazepam, Midazolam, 
Oxazepam, Prazepam, Quazepam, Temazepam, Triazolam, 
Clobazam, Clonazepam 
Opioids 
28:08.08 and 
28:08.12 
Codeine, Fentanyl, Hydrocodone, Hydromorphone 
Levorphanol, Meperidine, Methadone, Morphine, Opium, 
Oxycodone, Oxymorphone, Remifentanil, Sufentanil, 
Tapentadol, Tramadol, Buprenorphine, Butorphanol, 
Nalbuphine, Pentazocine, Dihydrocodeine 
Z-drugs 
Subset of 
28:24.92 
Eszopiclone, Zaleplon, Zolpidem