Deprescribing to Reduce Injurious Falls Among Older Adults With Dementia
Phase: NA
Conditions: Dementia
Sponsor: University of Washington

1 
 
DEPRESCRIBING TO REDUCE INJURIOUS FALLS AMONG OLDER ADULTS WITH DEMENTIA 
 
 
Principal Investigator: 
Elizabeth A. Phelan, MD, MS 
Professor, Medicine/Gerontology and Geriatric Medicine, School of Medicine 
Adjunct Professor, Health Systems and Population Health, School of Public Health 
University of Washington  
 
 
Kaiser Permanente Washington Site Investigator: 
Benjamin Balderson, PhD 
 Senior Collaborative Scientist 
Kaiser Permanente Washington Health Research Institute 
Kaiser Permanente Washington 
 
 
 
 
Supported by: 
 
The National Institute on Aging 
 
IMPACT Collaboratory (U54AG063546) Pilot Grants Program 
 
FY22_Pilot4_Phelan 
 
 
 
 
 
 
 
 
 
 
Version 2 
Approved November 17, 2022 
 
 

2 
 
 
 
TABLE OF CONTENTS 
TABLE OF CONTENTS ............................................................................................................. 2 
PRÉCIS ................................................................................................................................ .. 5 
STUDY TEAM ROSTER ............................................................................................................ 6 
PARTICIPATING STUDY SITES ................................................................................................. 7 
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 ........................................................... 9 
4.1 
Inclusion Criteria ............................................................................................................. 9 
4.2 
Exclusion Criteria........................................................................................................... 10 
4.3 
Study Enrollment Procedures ....................................................................................... 10 
5 
STUDY INTERVENTIONS ................................................................................................ 11 
5.1 
Interventions, Administration, and Duration ............................................................... 11 
5.2 
Handling of Study Interventions ................................................................................... 13 
5.3 
Concomitant Interventions ........................................................................................... 13 
5.4 
Adherence Assessment ................................................................................................. 13 
6 
STUDY PROCEDURES .................................................................................................... 14 
6.1 
Schedule of Evaluations ................................................................................................ 14 
6.2 
Description of Evaluations ............................................................................................ 14 
7 
SAFETY ASSESSMENTS .................................................................................................. 15 

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7.1 
Specification of Safety Parameters ............................................................................... 15 
7.2 
Methods and Timing for Assessing, Recording, and Analyzing Safety Parameters ...... 15 
7.3 
Adverse Events and Serious Adverse Events ................................................................ 15 
7.3.1 Reporting Procedures ............................................................................................... 16 
7.3.2 Follow-up for Adverse Events ................................................................................... 17 
7.4 
Safety Monitoring ......................................................................................................... 17 
8 
INTERVENTION DISCONTINUATION .............................................................................. 17 
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 ...................................................................................................... 18 
9.4.2 Secondary outcomes ................................................................................................. 18 
9.5 
Data Analyses ................................................................................................................ 18 
10 DATA COLLECTION AND QUALITY ASSURANCE.............................................................. 19 
10.1 
Data Collection Sources ................................................................................................ 19 
10.2 
Data Management ........................................................................................................ 21 
10.3 
Quality Assurance ......................................................................................................... 21 
11 PARTICIPANT RIGHTS AND CONFIDENTIALITY ............................................................... 21 
11.1 
Institutional Review Board (IRB) Review ...................................................................... 21 
11.2 
Informed Consent ......................................................................................................... 22 
11.3 
Participant Confidentiality ............................................................................................ 23 
11.4 
Study Discontinuation ................................................................................................... 23 
12 ETHICAL CONSIDERATIONS ........................................................................................... 23 
13 COMMITTEES ............................................................................................................... 24 
14 PUBLICATION OF RESEARCH FINDINGS ......................................................................... 24 
15 REFERENCES ................................................................................................................. 25 

4 
 
16 SUPPLEMENTS/APPENDICES ........................................................................................ 27 
16.1 
Intervention announcement email 
16.2 
EBPO text 
16.3 
Participant questionnaire 
 
 

5 
 
PRÉCIS 
Study Title:  Deprescribing to Reduce Injurious Falls among Older Adults with Dementia 
 
Objectives 
The overarching objective of this project is to assess the feasibility and acceptability of 
implementing STOP-FALLS, an evidence-based, deprescribing intervention that targets central 
nervous system (CNS)-active medications, with older persons with dementia (OPWD) and their 
care partners, including those from diverse backgrounds. To accomplish this objective, we have 
the following aims: 
Aim 1. Adapt STOP-FALLS for OPWD and their care partner(s). Stakeholder (primary care 
provider and care partners of OPWD) perspectives will be elicited to inform and guide 
adaptations. These activities are considered “not human subjects research,” and have been 
reviewed and determined to be IRB exempt by Kaiser Permanente Washington (KPWA) IRB. 
Aim 2. Conduct a one-arm pilot trial of the adapted STOP-FALLS intervention to determine 1) 
feasibility of reaching OPWD and their care partners, 2) acceptability of the intervention, and 3) 
whether the intervention was implemented as intended (implementation success). 
Aim 3. Establish feasibility of using pragmatic methods to ascertain the following outcomes: 1) 
medically treated falls (primary outcome), 2) all-cause emergency department visits and 
hospitalizations (secondary outcome), and 3) nursing home placement (secondary outcome).  
Design and Outcomes 
The study design for Aims 2 and 3 is a one-arm, health-system embedded pragmatic pilot trial. 
Outcomes are described above and will be obtained from the virtual data warehouse (VDW) of 
the health system. 
 
Interventions and Duration 
The intervention consists of patient-facing, written brochures on six classes of CNS-active 
medications and provider decision support in the form of pharmaceutical aids (evidence-based 
pharmaceutical opinions, or EBPOs). Patient participants will receive a one-time mailing of a 
brochure, and PCP will receive decision support materials synchronous with the patient 
participant mailing. Subsequent actions around deprescribing (discussion, tapering) of the 
medication will be at the discretion of the patient participant and the PCP. 
 
 
Sample Size and Population 
The target sample size is 120 older adults with diagnosed dementia. 
 
 

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STUDY TEAM ROSTER 
Principal Investigator: 
Elizabeth A. Phelan, MD, MS 
 
 
 
 
University of Washington 
Harborview Medical Center 
325 9th Ave 
Box 359755 
Seattle, WA 98104 
 
 
 
 
Telephone: (206) 744-9112 
 
 
 
 
Fax: (206) 744-9976 
 
 
 
 
Email: phelane@uw.edu 
Dr. Phelan will provide overall leadership and oversee all operational 
issues for the project, including management of the research team, 
intervention refinement and implementation, data collection, analysis 
and interpretation, IRB and Data and Safety Monitoring Board reporting, 
and report and manuscript preparation and results dissemination. 
 
Co-Investigators:  
 
Benjamin Balderson, PhD 
 
 
 
 
Kaiser Permanente Washington Health Research Institute 
 
 
 
 
1730 Minor Ave 
 
 
 
 
Ste 1600 
 
 
 
 
Seattle, WA 98101 
 
 
 
 
Telephone: (206) 326-2568 
 
 
 
 
Fax: (206) 287-  
 
 
 
 
Email: Benjamin.h.balderson@kp.org 
 
 
 
 
Site Principal Investigator, Kaiser Permanente 
Dr. Balderson will provide overall administrative and scientific oversight 
of the project at KPWA. Dr. Balderson will be heavily involved in data 
collection, preliminary analyses/ interpretation of results, and 
presentations. He will play a key role in the study intervention by being 
the liaison with primary care and will work with Kaiser Permanente 
leaders. 
 
 
 
 
 
 
 
 
 
 
Shelly Gray, PharmD 
 
 
 
 
University of Washington 
 
 
 
 
Health Sciences Building, H-361D 
 
 
 
 
Box 357630 
 
 
 
 
Seattle, WA 98195 
 
 
 
 
Telephone: (206) 616-5061 
 
 
 
 
Fax: (206) 543-3835 
 
 
 
 
Email: slgray@uw.edu 
 
 
 
 
Co-Investigator, University of Washington  
Dr. Gray will help guide all scientific decisions, participate actively in 
project team meetings, lead refinement of patient-facing intervention 

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materials, assist with finalizing the research evaluation, assist with 
interpretation of study data, and engage in preparation of reports, 
presentations, and manuscripts. 
 
 
 
 
 
Sascha Dublin, MD, PhD 
 
 
 
 
Kaiser Permanente Washington Health Research Institute 
 
 
 
 
1730 Minor Ave 
 
 
 
 
Ste 1600 
 
 
 
 
Seattle, WA 98101 
 
 
 
 
Telephone: (206) 287-2870 
 
 
 
 
Fax: (206) 287-2871 
 
 
 
 
Email: Sascha.Dublin@kp.org 
 
 
 
 
Co-Investigator, Kaiser Permanente 
Dr. Dublin will provide expertise as a practicing KPWA provider to 
inform intervention strategies and the integration of the study into 
KPWA clinics.  
 
 
 
 
 
Andrea Cook, PhD 
 
 
 
 
Kaiser Permanente Washington Health Research Institute 
 
 
 
 
1730 Minor Ave 
 
 
 
 
Ste 1600 
 
 
 
 
Seattle, WA 98101 
 
 
 
 
Telephone: (206) 287-4257 
 
 
 
 
Fax: (206) 287- 2871 
 
 
 
 
Email: Andrea.J.Cook@kp.org 
 
 
 
 
Co-Investigator, Statistician, Kaiser Permanente 
Dr. Cook will be involved in all issues related to study design and 
statistical analyses.  
 
PARTICIPATING STUDY SITES 
We anticipate submitting 1 site application, for Kaiser Permanente Washington, where the 
research will be conducted. 
 
 
 
 
Benjamin Balderson, PhD 
 
 
 
 
Kaiser Permanente Washington Health Research Institute 
 
 
 
 
1730 Minor Ave 
 
 
 
 
Ste 1600 
 
 
 
 
Seattle, WA 98101 
 
 
 
 
Telephone: (206) 326-2568 
 
 
 
 
Fax: (206) 287- 2871 
 
 
 
 
Email: Benjamin.h.balderson@kp.org 
 
 
 
 

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1. STUDY OBJECTIVES  
 
1.1. Primary Objective  
To assess the feasibility and acceptability of implementing STOP-FALLS, an evidence-
based, deprescribing intervention that targets central nervous system (CNS)-active 
medications, with older persons with dementia (OPWD) and their care partners. 
 
1.2. Secondary Objective 
To determine the feasibility of using pragmatic methods to ascertain the primary and 
secondary outcome measures. These outcomes are:  1) medically treated falls (primary 
outcome), 2) all-cause emergency department visits and hospitalizations, and nursing 
home placement (secondary outcomes). 
 
2. BACKGROUND AND RATIONALE 
 
2.1. Background on Condition, Disease or Other Primary Study Focus  
 
Falls among older adults are a major public health concern given their multiple adverse 
consequences including severe injury, functional decline, nursing home placement, and 
mortality.1 Older people with dementia (OPWD) have eight to ten times more incident 
falls compared to age-matched peers without dementia.2, 3 OPWD are also less likely 
than those without dementia to make a full functional recovery after a fall-related 
injury,4 and falls increase burden on care partners.5, 6  
 
 
Medications and particularly those that affect the central nervous system (CNS) are a 
key modifiable risk factor for falls.7 Research has found that reducing CNS-active 
medications can reduce falls.8 CNS-active medications are considered potentially 
inappropriate for older adults, especially for OPWD, and guidelines recommend 
avoiding their use.9 However, use remains common and is increased among OPWD.10, 11  
 
2.2. Study Rationale 
STOP-FALLS-D seeks to address the guideline-practice gap described under 2.1., above. 
Our research team adapted a set of best practices12, 13 for reducing use of CNS-active 
medications and is currently testing it with older adults without dementia in a 
pragmatic, cluster-randomized trial in primary care clinics of Kaiser Permanente 
Washington (KPWA). The intervention, called STOP-FALLS, (PI: Phelan, 1 U01CE002967) 
is a nudge intervention designed to activate patients and providers.14 It delivers direct-
to-patient education and provider decision support about the risks of five classes of 
CNS-active medications: opioids, sedative-hypnotics, skeletal muscle relaxants, tricyclic 
antidepressants, and first-generation antihistamines. The intervention is delivered via 
mail (to patients) and via the electronic medical record (to PCPs). Care partners are not 
an intervention target, and dementia is one of the exclusion criteria. From the health 

9 
 
equity perspective, given that OPWD are more susceptible to the side effects of CNS-
active medications, and also given that they are more likely to be prescribed these 
medications, it seems reasonable and indeed imperative to attempt to reach them with 
the proposed intervention. 
 
3. STUDY DESIGN   
 
This study consists of three aims. 
 
The study design for Aim 1 is qualitative, one-on-one interviews with stakeholders. This 
aim was reviewed and determined to be IRB exempt by KPWA’s IRB. The purpose of 
this aim is to adapt STOP-FALLS intervention materials for older adults living with 
dementia by conducting interviews with stakeholders (KPWA primary care providers 
and care partners of OPWD receiving care within KPWA).  
 
The final intervention materials, revised based on the input obtained from stakeholders 
who participate in Aim 1 interviews, will be submitted in a modification to Advarra to 
be used for Aims 2 and 3. 
 
Aims 2 and 3 will be reviewed by Advarra. The remainder of the protocol thus pertains 
to Aims 2 and 3 only.  
 
The study design for Aim 2 is a one-arm, pragmatic, health-system-embedded pilot trial 
to determine 1) feasibility of reaching OPWD and their care partners, 2) acceptability of 
the intervention, and 3) whether the intervention was implemented as intended 
(implementation success). 
Aim 3 involves data collection for the pilot trial to establish the feasibility of using 
pragmatic methods to ascertain the following outcomes: 1) medically treated falls 
(primary outcome), 2) all-cause emergency department visits and hospitalizations 
(secondary outcome), and 3) nursing home placement (secondary outcome).  
 
4. SELECTION AND ENROLLMENT OF PARTICIPANTS  
 
4.1. Inclusion Criteria 
 
Participants must meet the following inclusion criteria to participate: 1) KPWA enrollees 
aged 60 years or older, 2) diagnosed dementia, based on either a dementia diagnosis 
code or prescription for a cholinesterase inhibitor or memantine, 3) receiving primary 
care at a KPWA integrated group practice outpatient clinic, and 4) taking at least one 

10 
 
CNS-active medication on a chronic (≥3 month) basis, as determined by KPWA 
prescription fill records. The classes of CNS-active medications targeted by the 
intervention will be: antipsychotics, opioids, sedative-hypnotics, skeletal muscle 
relaxants, tricyclic antidepressants, and first-generation antihistamines. 
 
Care partners will be identified as individuals aged 18 years or older who self-identify as 
a care partner for the person with dementia and return a completed research 
questionnaire. 
 
4.2. Exclusion Criteria 
 
Participants meeting any of the following criteria will be excluded from study 
participation: a) residing in a skilled nursing facility; b) cancer diagnosis in the prior 12 
months; c) receiving hospice or palliative care; d) legally blind (unable to see print 
materials.  
 
4.3. Study Enrollment Procedures 
 
1. This project will request a waiver of consent to send out the educational brochure 
and collect data from the electronic medical record (EMR), because mailed 
educational material could reasonably be sent to patients from their healthcare 
home as part of routine care, and because decisions about any changes to 
medications will rest with the patient, their care partner, and their PCP. Therefore, 
there will not be a process for the participant to opt-out of the study. See section 
11.2 for details. The project will request a waiver of documentation of consent for 
the questionnaire; completing and returning the questionnaire indicates permission 
to use responses for research.  
 
2. Before commencing data pulls, the study team will email the Medical Chief at each 
intervention clinic to alert them that this pilot intervention is going to commence. 
Because the intervention and implementation are very comparable to that of STOP-
FALLS, which these clinicians are already familiar with due to having been based in 
intervention clinics for the STOP-FALLS trial, a more in-depth clinic presentation to 
providers is not deemed necessary. 
 
3. Using KPWA automated data under a waiver of HIPAA authorization, the study 
programmer will identify all potential participants who meet inclusion criteria. The 
programmer will oversample participants who are of Hispanic ethnicity and whose 
race is not white. Of this potential participant pool we will identify a total study 
sample of 120 participants to whom we will mail the study materials.  
 

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5. STUDY INTERVENTIONS 
 
5.1. Interventions, Administration and Duration 
 
Aim 2 
The study design is a one-arm, pragmatic pilot trial. The intervention will be 
implemented with up to four clinics and up to 120 OPWD and their care partners. The 
intervention consists of an educational brochure about a CNS-active medication that 
the OPWD has been prescribed along with decision support for that individual’s PCP. To 
assess the acceptability of the intervention, a brief questionnaire will be mailed to the 
OPWD shortly after mailing of the intervention materials. Follow-up for outcomes 
ascertainment will start at the time of mailing of intervention materials to eligible 
participants.  
 
1. After the sample has been identified, the study team will send a packet to all eligible 
participants containing: 
a. A cover letter addressed to the participant and any care partner they may have. The 
letter will also contain a study phone number with voicemail to call if either 
participant or care partner has questions. This voicemail line will be monitored by 
study staff; 
b. Educational brochure for the medication class that the participant has been 
prescribed on a chronic (3 months or longer) basis; 
c. For most drug classes, a corresponding non-pharmacological self-care sheet, 
previously approved for STOP FALLS that has been modified based on dementia care 
partner input (Aim 1 interviews).   
 
2. At the same time, the study team will use the Epic (electronic medical record) “staff 
message” functionality to send a message letting the PCP know that their patient is 
included in the study and a link to the EBPO of the relevant medication class.  The 
purpose of this message is to enable the PCP to be prepared to have conversations 
with participants about their medication use and for these conversations to be 
guided by the evidence and talking points in the EBPO. The timing of these messages 
is not aligned with an upcoming clinic visit; it is anticipated that a participant/care 
partner may initiate the conversation with the provider on their own time schedule.  
 
3. When the participant/care partner receives the mailed packet, they can choose to 
read the materials or not. Reading all the materials in the packet should take 
approximately 10 minutes. If they choose, they can discuss the information in the 
brochure with their PCP. 
 

12 
 
4. Approximately 1-3 weeks after brochure mailing, the study team will send a brief 
questionnaire to OPWD and their care partners to ascertain intervention 
acceptability including the perceived usefulness of the educational materials and the 
likelihood of starting conversations about their medications with their providers. 
Care partner sociodemographics will also be obtained via this questionnaire for 
descriptive purposes. If the participant/care partner choose to complete and return 
the questionnaire, that activity should take approximately 5 minutes. (see 
Supplements/Appendices: Participant questionnaire) 
 
5. Returned questionnaires will be data-entered, and a survey response dataset will be 
created.  
 
Aim 3 
The automated data pulls and chart review associated with Aim 3 involve data 
collection for the pilot trial to establish the feasibility of using pragmatic methods to 
ascertain the following outcomes: 1) medically treated falls (primary outcome), 2) all-
cause emergency department visits and hospitalizations (secondary outcome), and 3) 
nursing home placement (secondary outcome).  
 
Automated data pull  
1. The study programmer will modify existing code from STOP-FALLS to pull data 
from KPWA automated data sources for the following three outcomes: 
1) medically treated falls (primary clinical outcome), 2) all-cause emergency 
department visits and hospitalizations (secondary outcome), and 3) nursing 
home placement (secondary outcome). 
2. An analytic dataset will be created and outcomes data summarized. We 
anticipate this will take 3-6 months. 
Medication taper ascertainment from medical records 
1. The study programmer will modify existing code from STOP-FALLS to create flags 
indicating which participants’ medical records have deprescribing text in the “sig 
field” (i.e., prescribing instructions) for each CNS-active medication. 
2. The KPWA study team members (Dr. Balderson and Ms. Fujii) will review up to a 
20% random sample of records to adjudicate whether or not the flags correctly 
identified evidence of a medication taper, completing the following shell table 
for each record: 
 
Field 
Description  
Notes: 

13 
 
Study ID 
Pre-populated study ID 
 
ConsumerNo 
Pre-populated Consumer Number 
PHI 
Medication class 
Pre-populated med class (e.g. 
opioid, TCA, benzo) 
 
Date 
Pre-populated date 
PHI 
Taper flag 
Pre-populated (yes/no) 
Did the program identify a 
potential deprescribing plan 
for the sig field? 
KPWA_sig 
Pre-populated text 
Actual text from sig field 
Taper flag correct? 
Yes/No/Not sure 
Does the adjudicator find 
information in the medical 
record to support the 
“Taper flag”? 
Notes: 
Text box 
Any additional information 
to support decision making 
of “taper flag correct” 
score. 
 
 
5.2. Handling of Study Interventions 
 
Due to the nature of the intervention, participants cannot be masked.  
 
There is no “training fidelity” plan given the nature of this intervention.  
 
There is no “intervention fidelity” plan given the nature of this intervention. 
 
5.3. Concomitant Interventions 
 
We do not have any concomitant interventions.  
 
5.4. Adherence Assessment  
 
There is no “adherence assessment” plan given the nature of this intervention.  
 
 

14 
 
 
6. STUDY PROCEDURES 
 
6.1. Schedule of Evaluations  
 
Measure 
Baseline 
1-3 month 
follow-up 
3-6 month 
follow-up 
Aim 2 
 
 
 
Feasibility (Participants meeting eligibility criteria are 
identified and mailed intervention materials) 
X 
 
 
Acceptability (Participants find the intervention 
acceptable) 
 
X 
 
Implementation Success (Taper plans for CNS-active 
medications are documented in the participants’ medical 
records) 
 
X 
X 
Aim 3 
 
 
 
Feasibility of obtaining outcomes data from the medical 
records (e.g., falls, nursing home placement, etc.) 
 
 
X 
 
 
6.2. Description of Evaluations  
The pilot study evaluation (Aim 2) will assess 1) feasibility of reaching the target 
population, 2) acceptability of the intervention, and 3) success of intervention 
implementation. 
 
Intervention feasibility will be measured by the ability to pull baseline data such as 
participant contact information, eligibility/ineligibility criteria, and demographics.  If no 
more than 30% of intervention materials are “returned to sender,” we will deem it 
feasible to reach the target population.   
 
Intervention acceptability will be measured by responses on returned questionnaires.  
If at least 65% of returned questionnaires indicate the intervention is acceptable and [if 
applicable] open-ended comments are positive >50% of the time, we will deem the 
intervention to be acceptable to the target population. 
 
Intervention implementation success will be measured by documentation of a plan to 
taper in the “sig” field in the participant’s medical record; if at least 35% of participants 
have a documented taper plan, we will consider the intervention to have been 
successfully implemented. 

15 
 
 
Feasibility of obtaining outcomes data from the medical record will be assessed in Aim 
3. Outcomes (clinical and utilization) data will be summarized and presented as percent 
of the study sample with the event (e.g., percent with a medically treated fall; percent 
with any ED visit or hospitalization, percent with a skilled nursing facility stay). Time to 
first medically treated fall will also be recorded. 
 
7. SAFETY ASSESSMENTS  
 
7.1. Specifications of Safety Parameters  
 
Comprehensive medication management is part of the KPWA standard of care, and any 
medication changes will be made by the participant and their PCP. This is consistent 
with usual care. There is no requirement for participants, care partners or PCPs to 
engage in discussion about medication safety or deprescribing. The intervention is 
education and designed to offer participants and their care partners information to 
understand the risks of CNS-active medications for older adults with dementia. The 
intervention does not alter a participant’s medication prescriptions.  
 
There is still the possibility for adverse effects from the intervention. These are 
described under 7.3., below. 
 
7.2. Methods and Timing for Assessing, Recording and Analyzing Safety Parameters  
 
This research involves testing an educational intervention, and therefore the main risk is 
breach of confidentiality. For more detail on the steps we will take to ensure patient 
confidentiality, see section 11.3.  
 
To allow for the possibility that adverse events may result from the intervention, we 
define adverse events and reporting procedures in the following section.  
 
Throughout the study period, any clinic champion or PCP will be able to report safety 
concerns via the study’s project manager’s voicemail.  
 
7.3. Adverse Events (AE) and Serious Adverse Events (SAE) 
AEs for this study include:   
 
 Medication withdrawal symptoms (e.g., for opioids – nausea, vomiting, diarrhea) 

16 
 
 Worsening of underlying condition for which medication was prescribed (e.g., for 
antipsychotics – behavioral and psychological symptoms of dementia (BPSD) (e.g., 
agitation, aggression, psychosis) 
 
The severity of AE is likely to be moderate and would be expected as a result of reduction 
in medications especially if the medication were withdrawn rapidly or abruptly. 
 
SAEs for this study include: 
 
 Emergency department visit or hospitalization for management of medication 
withdrawal symptoms 
 Emergency department visit or hospitalization for management of BPSD or re-
emergence of other symptoms for which the medication was prescribed 
 Hospitalization due to any cause 
 Death due to any cause 
 
The above events would be expected given the nature of the intervention and the 
population under study (i.e., older adults with dementia). 
 
7.3.1. Reporting Procedures  
 
Contact information (telephone / voicemail) for the study’s project manager will be 
provided to intervention clinics, and clinic champions and PCPs will be invited to report 
any possible adverse events resulting from the trial. For each report, the site PI and 
study PI will review the potential concern. Review of the electronic medical record for 
adverse events will be restricted to SAE.  
 
Adverse events that are serious and unexpected will be reported to the IMPACT 
Collaboratory Regulatory and Data Team Leader, the NIA IMPACT Collaboratory 
Program Officer, and the project’s Safety Officer and, if related to the intervention, to 
the Advarra IRB, within 48 hours of the study team’s knowledge of the event. 
 
All deaths will be reported to the IMPACT Collaboratory Regulatory and Data Team 
Leader, the NIA IMPACT Collaboratory Program Officer, and the project’s Safety Officer 
within 24 hours of the study team’s knowledge of death.  
All unanticipated problems (UPs) will be reported to the IMPACT Collaboratory 
Regulatory and Data Team Leader, Advarra IRB, NIA IMPACT Collaboratory Program 
Officer, and the project’s Safety Officer within 48 hours of the study’s knowledge of the 
problem. 

17 
 
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, Advarra IRB, NIA IMPACT Collaboratory PO, and the project’s 
Safety Officer at a minimum every 6 months, or at a frequency requested by the IMPACT 
Collaboratory. 
7.3.2. Follow-up for Adverse Events  
 
Adverse events will be reviewed by the Safety Officer for the study as described above, 
who will determine the need for any follow-up actions and define the exact nature of 
those actions.  
 
7.4. Safety Monitoring  
 
An independent Safety Officer has been appointed by the NIA IMPACT Collaboratory to 
serve as the data safety monitor.  
 
8. INTERVENTION DISCONTINUATION  
 
For this pilot study of a one-time, pragmatic, educational intervention, we do not have 
intervention discontinuation criteria.  
 
9. STATISTICAL CONSIDERATIONS 
 
9.1. General Design Issues  
This is a one-arm pilot study to inform a future full-scale, stage 4 embedded pragmatic 
clinical trial (ePCT). The one-arm design is justified because the primary objective is to 
establish feasibility and acceptability of the intervention. We hypothesize that the 
intervention will be feasible to implement, acceptable to patients and clinicians, and that 
outcomes will be feasible to assess via pragmatic methods. 
 
9.2. Sample Size and Randomization 
 
For Aims 2 and 3, our sample size calculations are based on the framework of “green”, 
“yellow” and “red” lighting for pilot feasibility trials.39 Based on our primary endpoint, which 
is implementation success,17 assuming the upper boundary of the “red” zone is 20% and the 
lower boundary of the “green” zone is 35%, the sample size required for analysis given 90% 
power and one-sided 5% alpha is n=78 (intervention arm only). Specifically, if the true rate 
is in the “green” zone with a sample size of 78, we have 90% power for the study to not be 
defined as “red” lighted. We will increase the sample size to 120 to be able to have 90% 
power across all secondary endpoints as well. 

18 
 
 
9.2.1. Treatment Assignment Procedures  
This is a one-arm pilot trial, and as such all participants will receive the 
intervention.  
 
9.3. Interim analyses and Stopping Rules  
No interim analyses are planned. There are no stopping rules. 
 
9.4. Outcomes  
 
9.4.1. Primary outcome 
 
The primary outcome is medically treated falls, defined as falls for which medical care is 
 
received. Our measure of the primary outcome will be time to first medically treated 
 
fall. The time window of observation for the primary outcome will be 6 months 
 
subsequent to the patient-facing materials being distributed to study participants. 
 
We will ascertain this outcome from health plan utilization files using International 
 
Classification of Disease-10 injury diagnosis and fall-related (V-code or W-code) external 
 
cause of injury codes.20-22 We will describe fall events according to sex and 
 
race/ethnicity.  
 
9.4.2. Secondary outcomes  
Secondary outcomes are 1) all-cause emergency department visits and 
hospitalizations, and 2) nursing home placement. Secondary outcomes will be 
ascertained from utilization files of the health plan. 
 
9.5. Data Analyses 
We will summarize measures of feasibility and acceptability using binary outcomes and 
calculating proportions and 95% confidence intervals using simple descriptive analysis. 
For our primary endpoint of implementation success, following the framework 
proposed for pragmatic pilot trials,39 if 35% have a documented taper plan, the trial will 
be “green” lighted to move forward to a confirmatory study; if 20%-<35% have a 
documented taper plan, it will be “yellow” lighted, meaning that the intervention needs 
be modified if to move forward; and if <20% have a documented taper plan, it will be 
“red” lighted, meaning that the intervention is a “no go”. The same framework will be 
applied across secondary endpoints. We will examine differences by relevant 
sociodemographic characteristics (e.g., race, ethnicity, sex) for each outcome using the 
same criteria. 
 
 

19 
 
10. DATA COLLECTION AND QUALITY ASSURANCE  
 
10.1. 
Data Collection Sources  
There will be two sources of data collection for this research project: 1) KPWA 
automated data sources and 2) a mailed questionnaire. 
1) KPWA automated data sources and electronic medical records: KPWA automated 
data sources will be used to complete both Aims 2 and 3. Automated data sources 
such as demographics, prescription medication fills, and diagnoses will be used to 
identify and mail to eligible participants for Aim 2.  In order to ascertain the 
occurrence of deprescribing, we will look at the electronic medical records of 
participants to determine whether a plan to taper the target medication was 
documented. For Aim 3, we will use automated data sources to collect and 
summarize the following outcomes of interest: 1) medically treated falls (primary 
clinical outcome), 2) all-cause emergency department visits and hospitalizations, and 
3) nursing home placement. 
 
       Table 1: Data from KPWA to identify potential study participants 
Source (specify) 
(i.e., from KPWA, or an 
existing or previous study, 
etc.) 
List of electronic data that will be used to identify potential 
participants 
KPWA electronic data sources 
Healthcare Utilization: all outpatient visits, dates, provider id 
KPWA electronic data sources 
Pharmacy Dispensing Data: drug name, NDC, strength, quantity, 
days supply, prescriber id, and date dispensed for all medications 
of interest (antipsychotics, opioids, benzodiazepines, tricyclic 
antidepressants, Z-drugs, other sedative hypnotics, muscle 
relaxants, antihistamines) and medications to treat 
Alzheimers/dementia 
KPWA electronic data sources 
Diagnosis Codes:  all fall and fracture related diagnoses and dates 
of diagnoses, all opioid use diagnoses codes and dates (exclusion 
criteria)  
KPWA electronic data sources 
Demographics: age, sex, race, and ethnicity  
KPWA electronic data sources 
Tumor Registry: dates of all cancer diagnosis (exclusion criteria)  
KPWA electronic data sources 
Procedures:  all fall and fracture related procedure codes and 
dates of procedure 
KPWA electronic data sources 
Enrollment: enrollment in KPWA (start and stop dates) 
KPWA electronic data sources 
Provider table: provider id, specialty, provider type 
KPWA electronic data sources 
Referral for nursing homes and/or hospice (Exclusion Criteria) 

20 
 
KPWA electronic data sources 
Hospice admissions database (Exclusion Criteria to confirm that 
these patients are not receiving hospice care) 
KPWA electronic data sources 
Provider ID, Specialty, Provider Type, primary practice clinic. Data 
collected so that we can determine who the patients’ PCP is for 
Epic Staff Messaging the EBPO to the correct provider). 
 
       Table 2: Data from KPWA to ascertain study outcomes 
Source 
(i.e., from KPWA, or an 
existing or previous study, 
etc.) 
Key Information/Description of Variables 
KPWA electronic data 
sources 
Diagnosis codes: 
 
For outcomes including: 
 
Injury diagnostic codes 
 
Fall-related diagnostic codes 
 
For chronic conditions associated with falls, e.g.: 
arthritis, back pain, knee pain, alcohol use disorder, chronic lung 
disease, congestive heart failure, diabetes, heart disease, hip 
fracture, hypertension, obesity, peripheral neuropathy, 
osteoporosis, Parkinson’s disease, stroke, urinary incontinence, 
impaired vision, impaired hearing, memory problems, non-
melanoma cancers, frailty 
 
For other diagnoses related to medication prescription for the 
following conditions:  anxiety, depression, insomnia, chronic pain 
KPWA electronic data 
sources 
All healthcare utilization for the primary outcome (falls) such as 
primary care visits, specialty visits, emergency department visits, 
inpatient stays, nursing home admissions 
KPWA electronic data 
sources 
All emergency department visits, inpatient stays, and nursing 
home admissions 
KPWA electronic data 
sources 
Pharmacy dispensing data (drug name, date of dispensing, 
strength, quantity, days supply, provider id, NDC) for the 
following intervention target prescription medication classes:  
antipsychotics, benzodiazepines, z-drugs, opioids, muscle 
relaxants, antihistamines, tricyclic antidepressants.  
In addition, the following medication classes are needed to 
examine whether target medications were substituted with 
equally unsafe medications as a result of the intervention: 
Gabapentinoids, other sedative hypnotics, other antidepressants, 
NSAIDs. 

21 
 
KPWA electronic data 
sources 
KP’s Center for Effectiveness and Safety Research (CESR) Med 
Order Table information (e.g. instruction for usage, prescription 
date, medication type) 
KPWA electronic data 
sources 
Demographics (e.g., age, sex, race, marital status) 
 
2) Questionnaire: We will assess acceptability of the intervention (Aim 2) via a brief, 
mailed questionnaire. The questionnaire will be anonymous; it will not contain any 
identifiable information such as PHI or a study ID. Thus, this information cannot be 
linked to any other study data. 
 
10.2. 
Data Management  
KPWA automated data sources and electronic medical records: All automated data will 
be extracted from KPWA automated data sources. Data will be stored on KPWA 
password protected computers. Medication deprescribing information will be 
ascertained by looking at the “sig” field under the “Medication tab” of the KPWA 
electronic medical record. The results of that chart review, whether or not deprescribing 
information is indicated and the wording used, will be data-entered into a MS Excel 
spreadsheet stored on a KPWA password protected computer.  
Questionnaires: The responses of the returned questionnaires will be data-entered into 
a MS Excel spreadsheet stored on a KPWA password protected computer.   
10.3. 
Quality Assurance  
 
For Aim 2, to ensure accuracy of the data, we will double input data from the mailed 
questionnaires. For sig field data, up to 20% of charts will be reviewed to determine if 
the sig data pulls are accurate. 
 
For Aim 3, the data pulled will be verified as being within the follow-up time window 
and pertinent to the given study participant by hand-review of the data returned. 
 
11. PARTICIPANT RIGHTS AND CONFIDENTIALITY 
 
11.1. 
Institutional Review Board (IRB) Review  
 
This protocol and patient/care partner-facing materials will be reviewed and approved 
by the IRB responsible for oversight of the study. 
 
 
 

22 
 
 
11.2. 
Informed Consent   
 
Waiver of informed consent. We request a waiver of informed consent for the research 
to be conducted in Aims 2 (pilot trial) and 3 (outcomes ascertainment). This research 
meets the five criteria for a waiver of informed consent, as follows: 
1) the research is minimal risk by virtue of its educational nature; participants are not 
required to engage in discussions about deprescribing; study materials provide 
guidance about how to safely taper and stop medications; 
2) the research could not practicably be carried out without a waiver, because 
obtaining written informed consent would be highly burdensome to the target 
population (OPWD) and outweigh the minimal risks of the intervention; obtaining 
surrogate consent would be likely to render otherwise eligible participants ineligible 
if a surrogate were not available or identifiable and thus compromise recruitment 
and threaten achievement of sufficient sample size; 
3) the research could not practicably be carried out without the use of identifiable 
data; these data are needed to identify the eligible sample of OPWD and send study 
materials to them and to their PCP, and to extract research measures including 
outcomes data from the KPWA virtual data warehouse (VDW). With regard to 
outcomes data extraction specifically, in prior research that we have conducted that 
focused on the same target medication classes, in which we initially provided 
participants an opportunity to opt out of use of automated data for outcomes 
assessments, we experienced a higher proportion of opt-outs among those who 
were on opioids. This imbalance represents a threat to internal validity that can be 
avoided through a waiver of consent; 
4) the waiver will not adversely affect the rights or welfare of participants; the cover 
letter accompanying the educational brochure will encourage the participant to 
discuss their use of the medication with their PCP and share the brochure with 
family members and/or friends who help them with their health care but explain 
that they are under no obligation to do so; 
5) whenever appropriate, participants or legally authorized representatives will be 
provided with additional pertinent information after participation; a summary of key 
findings from the research can be written up for publication in a patient-facing 
KPWA newsletter that goes out to KPWA enrollees on a periodic basis.  
Alteration and waiver of documentation of consent. An alteration and waiver of 
documentation of informed consent is requested for the Aim 2 questionnaire. This brief 
questionnaire will be the source of information on intervention acceptability and care 
partner sociodemographic characteristics. The questionnaire will contain a statement 
explaining that by completing and sending the questionnaire back to the study staff, the 

23 
 
participant is giving us permission to use their anonymous responses for research. A 
cover letter containing most, but not all of the components of informed consent will be 
included with the questionnaire.  
Waiver of HIPAA Authorization. A full waiver of HIPAA authorization is requested for 
study sample identification and collecting study outcomes. The use of protected health 
information (PHI) for this purpose involves no more than minimal risk to the privacy of 
individuals, because the PHI will be protected from improper use and disclosure by 
virtue of its being accessed only by the KPWA-based study staff. No PHI will be 
transmitted beyond the KPWA-based programmer, Research Specialist, and Project 
Manager, and any linking files created for participant tracking, extraction of data from 
electronic health records, and data analysis will be destroyed as soon as the research 
has been completed and the study findings published. The research could not 
practicably be conducted without the waiver and without access to and use of the PHI, 
as obtaining consent directly from participants for this purpose would be unnecessarily 
burdensome.  
 
11.3. 
Participant Confidentiality 
All data will be stored on the KPWA secure network folders accessible only to research 
study team members. Only the KPWA study programmer will have access to the linking 
file. The KPWA study programmer, KPWA Research Specialist, and KPWA Project 
Manager will have access to identifiers so that they can recruit participants, mail out 
study materials, and let providers know that their patient is participating in the study. 
Computer files will be password protected with access restricted to staff using this 
information to perform study-related activities. All analytic data files will be password 
protected. Data tables with any identifiers needed for mailing the patient brochures 
(i.e., name, address)) will be kept separate from all other study data tables. All 
employees at KPWA routinely sign a confidentiality form that covers access to all data 
encountered. 
 
11.4. 
Study Discontinuation 
The study may be discontinued at any time by the IRB, the NIA, the OHRP, the FDA, or 
other government agencies as part of their duties to ensure that research participants 
are protected. 
 
12. ETHICAL CONSIDERATIONS 
All research conducted at KPWA complies with the Department of Health and Human Services 
requirements for safeguarding the rights and welfare of human subjects, regardless of the 
source of funding. KPWA and UW each have approved Federal-wide Assurance Compliance filed 
with the Office for Human Research Protections (OHRP). Both institutions have agreed to cede 
to Advarra for IRB oversight and study approval. Advarra will also serve as the Research Privacy 

24 
 
Board, and ensures that the privacy and confidentiality or protected health information is 
maintained, as required by the Health Insurance Portability and Accountability Act (HIPAA). 
 
 

25 
 
 
13. COMMITTEES  
NIA Program Officer 
Partha Bhattacharyya 
Program Director  
National Institute on Aging 
bhattacharyyap@nia.nih.gov  
(301) 496-3131 
 
14. PUBICATION OF RESEARCH FINDINGS 
 
Publication of the evaluation of the pilot study will be determined by the study team. Our 
primary purpose is to inform the development of a full-scale, stage IV effectiveness 
embedded pragmatic clinical trial. Publication of the results of this pilot study will be 
governed by the policies and procedures developed by the IMPACT Collaboratory.   
 
 

26 
 
 
15. REFERENCES 
1. 
Centers for Disease C, Prevention. Fatalities and injuries from falls among older adults--
United States, 1993-2003 and 2001-2005. MMWR Morb Mortal Wkly Rep. Nov 17 
2006;55(45):1221-4.  
2. 
Allan LM, Ballard CG, Rowan EN, Kenny RA. Incidence and prediction of falls in 
dementia: a prospective study in older people. PLoS One. 2009;4(5):e5521. 
doi:10.1371/journal.pone.0005521 
3. 
Casey CM, Caulley J, Phelan EA. The Intersection of Falls and Dementia in Primary Care: 
Evaluation and Management Considerations. Med Clin North Am. Sep 2020;104(5):791-806. 
doi:10.1016/j.mcna.2020.06.003 
4. 
Shaw FE. Falls in cognitive impairment and dementia. Clin Geriatr Med. May 
2002;18(2):159-73. doi:10.1016/s0749-0690(02)00003-4 
5. 
Kamiya M, Sakurai T, Ogama N, Maki Y, Toba K. Factors associated with increased 
caregivers' burden in several cognitive stages of Alzheimer's disease. Geriatr Gerontol Int. Apr 
2014;14 Suppl 2:45-55. doi:10.1111/ggi.12260 
6. 
Leggett AN, Polenick CA, Maust DT, Kales HC. Falls and Hospitalizations Among Persons 
With Dementia and Associated Caregiver Emotional Difficulties. Gerontologist. Mar 19 
2018;58(2):e78-e86. doi:10.1093/geront/gnx202 
7. 
Seppala LJ, Wermelink A, de Vries M, et al. Fall-Risk-Increasing Drugs: A Systematic 
Review and Meta-Analysis: II. Psychotropics. J Am Med Dir Assoc. Apr 2018;19(4):371 e11-371 
e17. doi:10.1016/j.jamda.2017.12.098 
8. 
Campbell AJ, Robertson MC, Gardner MM, Norton RN, Buchner DM. Psychotropic 
medication withdrawal and a home-based exercise program to prevent falls: a randomized, 
controlled trial. J Am Geriatr Soc. 1999;47(7):850-3.  
9. 
American Geriatrics Society 2019 Updated AGS Beers Criteria® for Potentially 
Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. Apr 2019;67(4):674-694. 
doi:10.1111/jgs.15767 
10. 
Maust DT, Strominger J, Bynum JPW, et al. Prevalence of Psychotropic and Opioid 
Prescription Fills Among Community-Dwelling Older Adults With Dementia in the US. JAMA. 
Aug 18 2020;324(7):706-708. doi:10.1001/jama.2020.8519 
11. 
Growdon ME, Gan S, Yaffe K, Steinman MA. Polypharmacy among older adults with 
dementia compared with those without dementia in the United States. J Am Geriatr Soc. Sep 
2021;69(9):2464-2475. doi:10.1111/jgs.17291 

27 
 
12. 
Martin P, Tamblyn R, Benedetti A, Ahmed S, Tannenbaum C. Effect of a Pharmacist-Led 
Educational Intervention on Inappropriate Medication Prescriptions in Older Adults: The D-
PRESCRIBE Randomized Clinical Trial. JAMA. Nov 13 2018;320(18):1889-1898. 
doi:10.1001/jama.2018.16131 
13. 
Tannenbaum C, Martin P, Tamblyn R, Benedetti A, Ahmed S. Reduction of inappropriate 
benzodiazepine prescriptions among older adults through direct patient education: the 
EMPOWER cluster randomized trial. JAMA Intern Med. Jun 2014;174(6):890-8. 
doi:10.1001/jamainternmed.2014.949 
17. 
Proctor E, Silmere H, Raghavan R, et al. Outcomes for implementation research: 
conceptual distinctions, measurement challenges, and research agenda. Adm Policy Ment 
Health. Mar 2011;38(2):65-76. doi:10.1007/s10488-010-0319-7 
20. 
Moreland BL, Burns ER, Haddad YK. National rates of non-fatal emergency department 
visits and hospitalisations due to fall-related injuries in older adults 2010-2014 and 2016: 
transitioning from ICD-9-CM to ICD-10-CM. Inj Prev. Mar 2021;27(S1):i75-i78. 
doi:10.1136/injuryprev-2019-043516 
21. 
Hedegaard H, Johnson RL. An Updated International Classification of Diseases, 10th 
Revision, Clinical Modification (ICD-10-CM) Surveillance Case Definition for Injury 
Hospitalizations. Natl Health Stat Report. Jul 2019;(125):1-8.  
22. 
Slavova S, Costich JF, Luu H, et al. Interrupted time series design to evaluate the effect 
of the ICD-9-CM to ICD-10-CM coding transition on injury hospitalization trends. Inj Epidemiol. 
Oct 1 2018;5(1):36. doi:10.1186/s40621-018-0165-8 
39. 
Lewis M, Bromley K, Sutton CJ, McCray G, Myers HL, Lancaster GA. Determining sample 
size for progression criteria for pragmatic pilot RCTs: the hypothesis test strikes back! Pilot 
Feasibility Stud. Feb 3 2021;7(1):40. doi:10.1186/s40814-021-00770-x 
 
 

28 
 
16. SUPPLEMENTS/APPENDICES  
Participant questionnaire 
 
The first question lets us know who is filling out this questionnaire. Is the person filling out this 
questionnaire: 
 
Someone who assists a Kaiser Permanente enrollee who may have memory difficulties with 
their medical care 
 
A Kaiser Permanente enrollee who may have memory difficulties 
 
Other; _______________________________ 
 
The next question is about the medication information packet that you received in the mail recently. 
Please choose the response that best describes your impression of the medication information packet. 
The medication information packet...
  
Completely 
disagree 
Disagree 
Neither 
agree nor 
disagree 
Agree 
Completely 
agree 
Meets my approval
Is appealing to me
Is likeable
Is welcome to me
 
Please tell us about yourself 
1.  Which of the following describes your race? Please select all that apply 
 American Indian/Alaskan Native 
 Asian 
 Black or African American 
 Native Hawaiian/Other Pacific Islander 
 White 
 You describe yourself as;______________________ 
 
2. Do you consider yourself to be: 
 Hispanic or Latino 
 Not Hispanic or Latino 
 
3. What is your age?    

29 
 
 Less than 65 
 65-74 
 75-84 
 85-94 
 95 and older 
 
4. Sex 
 Female 
 Male 
 You describe yourself as;____________