Music & MEmory: A Pragmatic TRial for Nursing Home Residents With ALzheimer's Disease_part1
Phase: NA
Conditions: Dementia
Sponsor: Brown University

Protocol, Version 3.0  
Protocol 
 
 
MUSIC & MEMORY: A PRAGMATIC TRIAL FOR NURSING HOME RESIDENTS WITH ALZHEIMER'S 
DISEASE (METRICAL) 
 
Principal Investigator: 
 
Vincent Mor, PhD 
Professor of Health Services, Policy & Practice and the Florence Pirce Grant University Professor in the 
Brown University School of Public Health 
Supported by: 
The National Institute on Aging 
NIA R33AG057451 
 
 

Protocol, Version 1.0 
 
Version 3 
November 17, 2021
TABLE OF CONTENTS 
Music & MEmory: A Pragmatic TRIal for Nursing Home Residents with ALzheimer's Disease 
(METRIcAL) ....................................................................................................................................   
TABLE OF CONTENTS .............................................................................................................. i 
PRÉCIS ......................................................................................................................................... iv 
Study Title ................................................................................................................................. iv 
Objectives ................................................................................................................................. iv 
Design and Outcomes ............................................................................................................ iv 
Interventions and Duration ...................................................................................................... v 
Sample Size and Population .................................................................................................. v 
STUDY TEAM ROSTER ............................................................................................................. 6 
Principal Investigator: .............................................................................................................. 6 
Co-Investigators: ...................................................................................................................... 6 
Role: co-Investigator, measurement lead ............................................................................ 7 
Nursing Home Corporation Contacts: ................................................................................... 7 
Research Team Members: ..................................................................................................... 7 
PARTICIPATING STUDY SITES .............................................................................................. 8 
1 
Study objectives ................................................................................................................. 9 
2 
BACKGROUND AND RATIONALE ................................................................................. 9 
2.1 
Background on Condition, Disease, or Other Primary Study Focus .................... 9 
2.2 
Study Rationale .......................................................................................................... 10 
3 
STUDY DESIGN................................................................................................................. 10 
4 
SELECTION AND ENROLLMENT OF PARTICIPANTS ............................................ 11 
4.1 
Resident Inclusion & Exclusion Criteria .................................................................. 11 
4.2 
Facility Inclusion & Exclusion Criteria ..................................................................... 12 
4.3 
Study Enrollment Procedures .................................................................................. 12 
4.3.1 
Facility Recruitment Procedures: ......................................................................12 
4.3.2 
Facility Recruitment Estimates: .........................................................................13 
4.3.3 
Facility Randomization and Stratification Procedures: ..................................13 
5 
STUDY INTERVENTIONS ............................................................................................... 13 

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5.1 
Interventions, Administration, and Duration ........................................................... 13 
5.2 
Concomitant Interventions ........................................................................................ 14 
6 
Data sources and Elements .......................................................................................... 15 
6.1 
Data Sources .............................................................................................................. 15 
6.2 
Data Linkages ............................................................................................................. 16 
7 
SAFETY ASSESSMENTS ............................................................................................... 17 
7.1. 
Minimal Risk Determination: ..................................................................................... 17 
7.2. 
Serious Negative Reactions and Serious Adverse Events .................................. 17 
7.3. 
Followup for Serious Negative Reactions .............................................................. 18 
7.4. 
Protection Against Risks ............................................................................................ 19 
7.5. 
Safety Monitoring ....................................................................................................... 19 
8 
INTERVENTION DISCONTINUATION .......................................................................... 19 
9 
STATISTICAL CONSIDERATIONS ............................................................................... 19 
9.1 
General Design Issues .............................................................................................. 19 
9.2 
Sample Size and Randomization ............................................................................ 20 
9.3 
Interim analyses and Stopping Rules ..................................................................... 20 
9.4 
Outcomes .................................................................................................................... 20 
9.4.1 
Primary outcome .................................................................................................20 
9.4.2. Secondary Outcomes: .............................................................................................21 
9.4.3. Process Measures for Implementation Analysis: ................................................21 
9.5 
Data Analyses ............................................................................................................. 22 
10 
DATA COLLECTION AND QUALITY ASSURANCE ............................................. 23 
10.1 
Onsite Data Collection ............................................................................................... 23 
10.2 
Data Confidentiality .................................................................................................... 24 
10.3 
Data Management ...................................................................................................... 25 
10.4 
Data Use Agreements ............................................................................................... 25 
11 
PARTICIPANT RIGHTS AND CONFIDENTIALITY................................................. 25 
11.1 
Institutional Review Board (IRB) Review ................................................................ 25 
11.2 
Participant Confidentiality ......................................................................................... 25 
12 
ETHICAL CONSIDERATIONS .................................................................................... 27 
13 
COMMITTEES ................................................................................................................ 27 
14 
PUBLICATION OF RESEARCH FINDINGS ............................................................. 27 

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15 
REFERENCES ............................................................................................................... 27 
16 APPENDICES ..................................................................................................................... 32 
 
 

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PRÉCIS 
Study Title  
METRIcAL: Music & MEmory: A Pragmatic TRIal for Nursing Home Residents with ALzheimer's Disease   
Objectives  
To conduct a repeat parallel, pragmatic cluster randomized control trial (RCT) of personalized music for 
nursing home (NH) residents with moderate to severe dementia cared for in 81 NHs within four NH health care 
systems: PruittHealth, Good Samaritan Society, Vetter Senior Living, and CommuniCare (Terrapins Division).  
Design and Outcomes   
Aim 1 of this study is to use a train-the-trainer model to implement M&M in 27 facilities with ongoing monitoring 
of the program’s adoption and acceptance by long-stay NH residents with Alzheimer’s disease-related 
dementias (ADRD). Using the implementation guide developed during the R21, corporate leadership will 
provide step-by-step training and support to facilities in the intervention arm to include: setting achievable 
milestones, reviewing progress, and assisting with mid-course corrections. Implementation will be closely 
monitored by Brown through monthly conference calls with the corporations and the leadership at the 
participating NHs.  
 
Aim 2 of this study is to estimate the impact of M&M on agitated and aggressive behaviors in NH residents with 
moderate to severe dementia. Agitated and/or aggressive behaviors are measured three ways: by interviewing 
staff about resident behaviors over time (primary outcome); through direct observation of residents when using 
and not using M&M (secondary outcome); and using available administrative data (secondary outcome). Other 
secondary outcomes include: other emotional states directly observed while the resident is using and not using 
M&M (anger, pleasure, alertness, sadness), antipsychotic use, antidepressant use, anxiolytic use, and 
depression. In this cluster RCT, the unit of random assignment is the facility, but the unit of analysis is the 
patient, clustered within the facility. The analytic approach we propose is based upon the cumulative likelihood 
of reductions in agitated and aggressive behaviors in a long-stay population with moderate to severe dementia, 
conditional upon survival to at least one post-intervention observation. Outcomes will be evaluated using a 
repeat parallel design, comparing wave 1 (intervention) and wave 2 (control) NHs (n=54) in the first study year, 
and wave 2 (intervention) and wave 3 (control) NHs (n=54) in the second study year. The repeat design allows 
for modification of the intervention delivery between waves to increase adherence. Since we do not expect the 
intervention to affect mortality, the comparison will be based on the last observed total agitation score among 
residents meeting eligibility criteria in the treated and control groups. All deaths among exposed and control 
populations will be routinely controlled and reported to the data safety and monitoring board for monitoring 
purposes. Facilities will be stratified by corporation, and balanced on baseline agitated and aggressive 
behaviors and number of eligible residents, prior randomization. Because we are interested in the effect of the 
intervention among those who use it, we will also conduct an as-treated analysis, using a technique described 
by multilevel-mixture analysis for analyzing cluster randomized data with non-compliance.  
 
Aim 3 of this study is to examine factors associated with variation in providers’ adherence to the 
implementation of M&M. We will adopt six distinct approaches to documenting implementation adherence: 1) 
research staff will survey NHs at baseline to assess the quality improvement infrastructure and performance 
improvement practices; 2) using a user-defined assessment, NH staff will document aspects of the process by 
which potentially-eligible residents are assessed for their ability to listen to the music, their music preferences, 
and the results of their initial trial of the music; 3) NH staff (with the help of research staff) will capture metadata 
about each song played, including a count of the replays, which will yield estimates of the degree of exposure 
to the intervention; 4) research staff will document NH staff participation and attendance at all training 
sessions; 5) research staff will conduct interviews with NH staff to identify barriers, facilitators, and best 
practices related to implementation; and 6) research staff will conduct an environmental scan while on-site to 
capture observable characteristics of implementation variation, such as storage and use of equipment and staff 
familiarity with intervention. Our analysis will quantitatively and qualitatively characterize facility variation in 
implementation measures based on the consolidated framework for implementation research (CFIR) 

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constructs.  
Interventions and Duration  
M&M is a personalized music program that uses portable music players to deliver individualized music to 
people with dementia. NH staff provide cognitively-impaired people with music playlists tailored to their 
personal history of music preferences. The program assumes that musical memories remain present and that 
personalized music can quell the anxiety and agitation stimulated by the confusion secondary to dementia. 
NHs randomized to the first wave will receive the intervention in the first study year and end participation in the 
study; NHs randomized to the second wave will serve as controls in the first study year and receive the 
intervention in the second study year; and NHs randomized to the third wave will serve as controls in the 
second study year and receive the intervention in the third study year. During the first and second study years, 
we will collect primary data (repeat parallel design). In the third study year, we will only rely upon secondary 
data to conduct outcome analyses.  
Sample Size and Population  
Eligible facilities will have at least 15 long-stay residents with moderate to severe dementia, defined as a 
diagnosis of dementia and either a Brief Interview for Mental Status score ≤12 or moderately or severely daily 
decision-making. Preliminary research and pilot data informs our estimates of the potential effect of M&M on 
any improvement in agitated and aggressive behaviors. Assuming an intra-class correlation (ICC) of 0.12 and 
6 points reduction in the outcome variable of interest (staff reporting of resident agitated and/or aggressive 
behaviors), we need 24 NHs in each arm to be able to test our primary outcome with power of .8 with a two-
tailed alpha of .05. Since we plan on recruiting 27 facilities per arm, we will have adequate power even if we 
encounter unforeseen circumstances. 
 

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STUDY TEAM ROSTER  
Principal Investigator: 
 
Vincent Mor, PhD 
Professor of Health Services, Policy & Practice  
Florence Pirce Grant University Professor 
Center for Gerontology and Healthcare Research 
Brown University, School of Public Health 
Providence, RI 02912 
(401) 863-3211 
vincent_mor@brown.edu 
Co-Investigators: 
 
Ellen McCreedy, PhD 
Assistant Professor 
Center for Gerontology and Healthcare Research 
Health Services, Policy & Practice 
Brown University, School of Public Health 
121 South Main Street, Suite 6 
Providence, RI 02903 
(401) 863-7345 
ellen_mccreedy@brown.edu 
Role: project director, co-Investigator 
 
Roee Gutman, PhD 
Associate Professor of Biostatistics 
Brown University, School of Public Health 
121 South Main Street, Suite 7 
Providence, RI 02912 
(401) 863-2682 
roee_gutman@brown.edu 
role: co-Investigator, statistical design and analysis lead 
 
Rosa Baier, MPH 
Associate Director, Center for Long-Term Care Quality & Innovation 
Associate Professor of Practice, Department of Health Services, Policy & Practice 
Center for Gerontology and Health Care Research 
Brown University, School of Public Health 
Providence, RI 02912 
(401) 863-3818 
rosa_baier@brown.edu 
Role: co-Investigator, intervention committee lead, corporate liaison, supervises consultants 
 
James Rudolph, MD 
Director of the Center of Innovation in Long Term Services and Supports (LTSS COIN) 
Associate Professor of Medicine 
Associate Professor of Health Services, Policy and Practice 
Brown University & Providence VA Medical Center 
james_rudolph@brown.edu 
Role: co-Investigator, implementation science lead 
 
Kali Thomas, PhD, MA 
Associate Professor of Health Services, Policy and Practice 

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Center for Gerontology and Health Care Research 
Brown University, School of Public Health 
Providence, RI 02912 
(401) 863-9036 
kali_thomas@brown.edu 
Role: co-Investigator, measurement lead 
 
Nursing Home Corporation Contacts: 
 
Michelle Kutner 
Good Samaritan Society 
4800 W. 57th St. 
Sioux Falls, SD 57108 
605-362-3166 
mkutner@good-sam.com 
 
Crystal Evans 
PruittHealth 
1626 Jeurgens Court  
Norcross GA 30093 
770-279-6240 
CryEvans@pruitthealth.com 
 
Courtney Schmitz  
Vetter Senior Living 
20220 Harney Street 
Elkhorn, NE 68022 
402-895-3932 
cschmitz@vhsmail.com 
 
Amy Maxwell 
CommuniCare (Terrapins Division) 
1302 Concourse Drive, Suite 200 
Linthicum Heights, MD 21090 
443-270-9462 
amaxwell@chs-corp.com  
Research Team Members: 
Jeffrey Hiris 
Systems Manager/Senior Programmer 
Center for Gerontology and Health Care Research  
Brown University 
Providence, RI 02912 
(401) 863-3317 
jeffrey_hiris@brown.edu 
Role: Coordinates all data transfer and data file storage and linkages at Brown. 
 
Julie Lima, MPH, PhD 
Investigator 
Center for Gerontology and Health Care Research  
Brown University 
Providence, RI 02912 
(972) 355-7814 
julie_lima@brown.edu 
Role: responsible for DUAs and IRB activities within Brown 

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Annie Yang, MS 
Biostatistician 
Center for Gerontology and Health Care Research  
Brown University 
Providence, RI 02912 
annie_yang@brown.edu 
Role: supports Roee Gutman, statistical design and analyses 
PARTICIPATING STUDY SITES  
The study is being conducted at 81 NHs owned by PruittHealth, Good Samaritan Society, Vetter Senior Living, 
and CommuniCare corporations. Corporate leadership for each corporation are listed above.  
 
 
 

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1 
STUDY OBJECTIVES 
Over 80% of people with Alzheimer’s disease-related dementias ADRD exhibit behavioral and 
psychological symptoms of dementia (BPSD)(1, 2) that can adversely affect their experiences and 
outcomes.(3) BPSD are a heterogeneous group of symptoms ranging from agitation and anxiety to apathy, 
depression, delusions, and sleep or appetite changes.(2) BPSD not only adversely affects people’s 
experiences and outcomes,(3) but also contributes to burden and stress for family caregivers(4-7) and 
healthcare providers.(8, 9) Use of antipsychotic medications to mitigate BPSD in ADRD increases the risk of 
serious complications,(10, 11) including extrapyramidal symptoms,(12-14) serious cardiovascular events,(14, 
15) and even death.(16-18)(19) For this reason, existing guidelines recommend exhausting non-
pharmaceutical options for treating these symptoms before initiating medications.(20, 21) Indeed, decreasing 
the use of antipsychotics for NH residents with dementia is a Centers for Medicare & Medicaid Services (CMS) 
goal.(22) 
Eliciting musical memories using familiar or preferred music may decrease feelings of isolation and 
anxiety,(23, 24) as musical memories are encoded in areas of the brain affected later in the ADRD process 
than areas of the brain involved in verbal memory and executive functioning.(25, 26)(27-29) Studies have 
demonstrated that individualized music can reduce anxiety,(30-32) decrease negative affect or depression,(30, 
31) and mitigate physically-agitated behaviors(33, 34) in people with ADRD. One specific music intervention, 
MUSIC & MEMORYSM (M&M), provides people with ADRD with iPods populated with music playlists tailored to 
their personal history of music preferences.(35) The purpose of METRIcAL is to test the impact of 
implementing M&M on NH residents’ BPSD outcomes during a four-year R33, by undertaking a pragmatic trial 
in four multi-facility NH corporations caring for residents with ADRD. We will conduct two parallel, cluster 
randomized controlled trial (RCT) with 81 facilities. The Specific Aims of the R33 are to:  
 
Aim 1. Use a train-the-trainer model to disseminate M&M to 81 NHs, with ongoing monitoring of the program’s 
adoption and acceptance by long-stay NH residents with ADRD. 
 
Aim 2. Estimate the impact of M&M on agitated and aggressive behaviors, observed emotional states, 
antipsychotic use, antidepressant use, anxiolytic use, and depression for long-stay NH residents with ADRD. 
 
Aim 3. Examine factors associated with variation in NHs’ implementation of the implementation of M&M.   
2 
BACKGROUND AND RATIONALE  
2.1 Background on Condition, Disease, or Other Primary Study Focus 
ADRD(36-38) is the sixth leading cause of death and the only one in the top 10 that cannot be prevented, 
cured, or slowed.(39) Its prevalence is increasing with population aging and is expected to reach 7.1 million 
people by 2025—a 40% increase.(39) The Aging, Demographics, and Memory Study, a nationally 
representative sample of older adults, estimates ADRD prevalence at 5% for adults aged 71-79 years of age, 
rising to 24% for adults aged 80-89 years, and 37% for adults aged ≥90 years.(40) 
Because of its effect on memory and other cognitive functions, ADRD leads to a loss of independent 
function that profoundly impacts patients, caregivers, and the healthcare system as a whole.(40) A significant 
number of people with ADRD require long-term services and supports (LTSS): the Centers for Disease Control 
and Prevention estimates that ADRD patients comprise nearly one-third of people receiving adult day (32%) or 
home health services (30%) and half of those living in assisted living (40%), hospice (44%), or NHs (49%).(41) 
Analyses of Medicare data, made publicly available through Brown’s Long-term Care Focus website 
[http://ltcfocus.org/] suggest that 60% of long-stay NH residents have ADRD. Moreover, almost all people with 
ADRD exhibit BPSD over the course of their illness.(2, 3) The prevalence of BPSD is nearly 2.5 times as high 
among those in NHs (80%-96%)(1, 2) vs. the community (33%).(42) BPSD are a heterogeneous group of 
symptoms ranging from agitation and anxiety to apathy, depression, delusions, and sleep or appetite 
changes.(2) The pathogenesis is not well understood, although likely due to multifactorial causes.(2) BPSD not 
only adversely affects people’s experiences and outcomes,(3) but also contribute to burden and stress for 
family caregivers(4-7) and healthcare providers.(8, 9) 
BPSD-related problems contribute to high use of antipsychotic medications among NHs. CMS data reveal 
that, on average, 20% of long-stay NH residents are prescribed antipsychotics for BPSD symptoms.(43) A 

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2011 Office of the Inspector General (OIG) report found that 83% of NH antipsychotic use was off-label, and 
88% of off-label use targeted residents with ADRD.(44) While antipsychotic use in NHs has decreased since 
2012, likely as a result of the OIG report,(44) national efforts,(45, 46) and quality improvement (QI) 
campaigns,(47) prevalence remains high in light of the well documented adverse effects. Indeed, a 2011 
systematic review documented the fact that antipsychotics increase the risk of cerebrovascular adverse events 
and death in this population.(48) 
2.2 Study Rationale 
Using antipsychotic medications to control agitation and aggression among people with ADRD increases 
the risk of complications,(11) including extrapyramidal symptoms,(12, 14) serious cardiovascular events,(14, 
15, 49-51) and even death.(16)(17, 18, 20) For this reason, existing guidelines recommend exhausting non-
pharmacological options;(20, 21) indeed, decreasing the use of antipsychotics for NH residents with ADRD is a 
CMS goal.(22) Unfortunately, as ADRD progresses, behavioral symptoms, including agitation and aggression, 
worsen, perhaps due to an inability to modulate responses as a direct effect of damage to the brain as well as 
sensory deprivation that can induce fear, anxiety, and confusion.(52-55) Eliciting musical memories using 
familiar music may decrease feelings of isolation and anxiety(23, 24) since musical memories are encoded in 
areas of the brain affected later than are areas of the brain governing verbal memory and executive 
functioning.(25-29) Individualized music has been shown to reduce anxiety,(30-32) decrease negative affect or 
depression,(30, 31) and to control physically agitated behaviors(33, 34) in people with ADRD. Further 
supporting the neurological pathway of eliciting musical memory, individualized music selections are more 
effective at reducing agitation compared to playing “relaxing” or classical music.(56) Several systematic 
reviews highlight the potential for music therapy to reduce agitation,(57-60) aggression,(58) anxiety,(61) 
behavioral symptoms,(61, 62) and mood.(62)This proposed pragmatic trial will not test the neurological 
premise on which individualized music is based, which would require complex imaging studies along with 
detailed behavioral monitoring. Rather, its significant contribution is testing the effectiveness of individualized 
music as a non-pharmacological treatment for BPSD. 
MUSIC & MEMORY (M&M) is a music program that builds upon an evidence-based protocol(63) by using 
easily-operated iPods to deliver individualized music to people with ADRD. The program was developed by a 
social worker, Dan Cohen, with experience leveraging technology to benefit those who would otherwise have 
no access. Caregivers (providers, family, or others) provide cognitively-impaired people with music playlists 
tailored to their personal history of music preferences.(35) The program assumes that musical memories 
remain present and that personalized music can quell the anxiety and agitation stimulated by the confusion 
secondary to brain disease. Its potential is illustrated powerfully in the 2014 documentary, Alive Inside, which 
shows people with severe dementia begin to move, sing, and even describe memories.(64) Thousands of 
provider sites across the world have become certified in M&M, including hundreds of NHs in the U.S. NH staff 
participate in MUSIC & MEMORY, Inc.-led certification and training webinars that offer suggestions for 
choosing residents to receive iPods, identifying music preferences, and sustaining the use of the iPods. The 
M&M website offers materials and ongoing support to participating facilities. Twelve states have M&M NH 
demonstration projects underway. However, to date demonstration evaluations have revealed wide variation in 
the level, approach and sustainability of implementation of M&M. For example, there has been variation in 
which residents receive an iPod, where the iPods are stored, and how often residents have access to 
them.(65) Rigorous evaluation of a uniformly-implemented intervention is necessary to definitively establish the 
program’s efficacy and to characterize factors associated with effective implementation. 
3 
STUDY DESIGN 
We will conduct two parallel, cluster RCTs of M&M for people with ADRD in 81 NHs; the unit of random 
assignment will be the facility and the unit of analysis the resident, clustered within the facility (see Table 1, 
next page). The primary study outcome is agitated and aggressive behaviors, as measured by interviewing a 
staff member who knows the resident well. Secondary study outcomes include: agitated and aggressive 
behaviors measured through direct observation of the resident when s/he is using and not using the music, 
agitated and aggressive behaviors as reported in available administrative data, emotional states observed 
while the resident is using and not using the music, antipsychotic use, antidepressant use, anti-anxiolytic use, 
and depression. First, using MDS data obtained from each corporation’s EHR and centralized corporate 
knowledge about their facilities’ capabilities and constraints, we will identify eligible facilities and contact facility 

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leadership to ensure that they want to, and have the necessary staffing resources to participate. Second, 
stratifying by corporation and prevalence and balancing on other key study variables at baseline, we will 
randomize facilities within corporation to one of three intervention waves. Third, we will use the most recent 
MDS data to identify eligible residents within each facility from the pool of long-stay residents with ADRD. At 
the same time, we will use knowledge gained from the R21 pilot phase to develop train-the-trainer materials 
and make any needed revisions to the step-by-step protocol. Fourth, we will train corporate trainers and 
support them as they train staff in participating facilities and mentor sites during implementation. Finally, we will 
obtain primary and secondary data for evaluation, using Research Assistant (RA) obtained observation and 
data from NHs’ EHRs, merged with MDS and Medicare enrollment records. Obtaining, merging, and cleaning 
these data will occur throughout implementation phase. 
 
Table 1. Repeat Parallel Design 
 
Period 1 
(June, 2019 - 
January, 2020) 
Period 2 
(April, 2020 - 
November, 2020) 
Period 3 
(February 2021 - 
September, 2021) 
Sequence 1 
(27 Nursing Homes) 
Intervention*† 
(405 residents) 
Coronavirus 
Pandemic† 
Intervention† 
(405 residents) 
Sequence 2 
(27 Nursing Homes) 
Control*† 
(405 residents) 
Coronavirus 
Pandemic† 
Intervention*† 
(405 residents) 
Sequence 3 
(27 Nursing Homes) 
Control† 
(405 residents) 
Coronavirus 
Pandemic† 
Control*† 
(405 residents 
*Primary data collection conducted in Sequence 1 and Sequence 2 nursing homes during Period 1, and Sequence 2 and Sequence 3 
nursing homes during Period 3 
†Secondary data collection including Minimum Data Set (MDS) and medication order data collected in all periods for all sequences, 
even during the coronavirus. 
 
4 
SELECTION AND ENROLLMENT OF PARTICIPANTS  
4.1 Resident Inclusion & Exclusion Criteria  
Eligible residents must be long-stay and have ADRD. Long-stay residents include anyone who had a 
quarter or annual assessment in the past four months. ADRD is defined by the presence of a dementia 
diagnosis and either a Brief Interview for Mental Status score ≤12 or moderately or severely daily decision-
making. Resident exclusion criteria include being deaf or not liking music. Figure 2 describes the process for 
identifying eligible residents using Minimum Data Set (MDS) data. 
 
 
 

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Figure 2. Steps for Identifying Eligible Residents Using the Minimum Data Set 
  
4.2 Facility Inclusion & Exclusion Criteria  
Using the Minimum Data Set (MDS), Brown will identify facilities which have at least 15 eligible residents. 
Brown staff will provide a list of facilities who are likely to have enough residents meeting eligible criteria to 
corporate leadership. From the list of potentially eligible facilities, corporate leadership will eliminate any facing 
other significant threats to implementation (e.g., recent leadership changes, recent poor regulatory survey 
performance such as immediate jeopardy or monetary penalties). Corporate leadership will reach out to 
potentially eligible facilities to allow for an opt-out of participation and to verify that they are not currently using 
M&M. 
4.3 Study Enrollment Procedures  
4.3.1 Facility Recruitment Procedures:  
Once eligible facilities are identified, they will be contacted by the Brown project leadership for a baseline 
telephone interview. The purpose of this call is to describe the study and provide a final opportunity for the 
facility to opt-out, without corporate leadership present. While senior corporate leaders strongly endorse the 
project, the final decision to participate in the intervention arm will be the individual facility’s administrator. 
All residents in NH 
STEP 1. 
Long-stay residents (quarterly or 
annual in last 120 days) 
Not long-stay residents  
(NOT ELIGIBLE) 
STEP 2. 
Select the most recent quarterly 
or annual MDS report 
STEP 3. 
Alzheimer's disease  
(MDS I4200) 
Other Dementia  
(MDS I4800 or I8000) 
Have neither  
(NOT ELIGIBLE) 
DEMENTIA 
(POTENTIALLY ELIGIBLE FOR M&M) 
STEP 4. 
BIMS ≤ 12 (MDS C0500 ≤12) 
Moderately or severely impaired daily 
decision making  
(MDS C1000=2 or C1000=3) 
Have neither  
(NOT ELIGIBLE) 
DEMENTIA AND EVIDENCE OF MODERATE TO SEVERE COGNITIVE 
IMPAIRMENT  
(POTENTIALLY ELIGIBLE FOR M&M) 
STEP 5. 
Completely deaf  
(MDS B0200=3)  
Completely deaf or dislikes music 
per staff knowledge  
(NOT ELIGIBLE) 
Not deaf and likes music 
ELIGIBLE FOR M&M! 

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Once the NHs are recruited, they will be randomly assigned (see Section 4.3.3. for randomization procedures) 
to one of three intervention waves by Brown statisticians.  
 
4.3.2 Facility Recruitment Estimates:  
Based upon our sample size calculations (see Section 9.2), we require 24 facilities per arm (72 facilities 
total). To account for the fact that some facilities may not successfully implement the intervention post-
randomization, we increased our facility recruitment targets to 27 facilities in each study arm (81 facilities total) 
Table 2 provides the key characteristics of eligible facilities by corporation. 
 
Table 2. Key Characteristics of Eligible Nursing Homes by Partnering Corporation 
 
Corporations 
 
A 
B 
C 
D 
Eligible Nursing Homes (#) 
69 
12 
25 
76 
Geographic Region 
Mid-West 
Mid-West 
Mid-Atlantic 
South 
Black Residents (%) 
1% 
<1% 
53% 
42% 
CMS Overall Quality Star Rating (Mean) 
3.4 
4.5 
2.0 
3.1 
Ownership Type 
Non-Profit 
Non-Profit 
For-Profit 
For-Profit 
Residents with any antipsychotic Use in Last 7 days (%) 
23% 
18% 
25% 
26% 
Residents with any agitated or aggressive behaviors (%) 
27% 
14% 
15% 
17% 
 
4.3.3 Facility Randomization and Stratification Procedures:  
Facilities will be randomized within NH health care system strata. Within each health system, sites will be 
partitioned into triplets based on the Mahalanobis distance from the overall mean on the following key 
variables: percentage of eligible nursing home residents with any agitated or aggressive behavior (MDS 
Aggressive Behavior Scale > 0) on their most recent quarterly or annual assessment and number of eligible 
long-stay residents. The rationale for this additional balancing is that agitated and aggressive behaviors, a 
study outcome of interest, are known to vary considerably at the facility-level due to nursing home resident 
composition, staffing, and the degree of “ascertainment” and documentation of behaviors. It was also important 
to balance on the number of eligible residents in a nursing home, because nursing homes with more eligible 
residents can be more selective in who receives the program, possibly picking “better” candidates. Within 
balanced triplets, one facility will be randomly chosen for each of three periods (Table 1).  
5 
STUDY INTERVENTIONS  
5.1 Interventions, Administration, and Duration 
The M&M personalized music program will be implemented for at least 8 months in each intervention 
facility. (Obviously, facilities are encouraged to continue to use the music devices with patients long after this 
8-month period and the devices will remain at the facility for use among appropriate patients). The intervention 
consists of: 1) identifying the music a resident with ADRD preferred when she was between the ages of 18 and 
24, either by consulting family members or through trial and error; 2) creating a personalized playlist for each 
resident; 3) loading this personalized playlist on the resident’s music player (iPod); and 4) using the iPod with 
the resident twice a day for approximately 30 minutes to 1 hour per use, at times when residents with ADRD 
tend to experience BPSD. Recommended times are when the resident gets up in the morning (during daily 
personal care) and in the late afternoon, when sundowning is common. In addition to these set times, NH staff 
are encouraged to use the music at other times when an individual resident is likely to experience BPSDs. In 
the first parallel trial, NH staff will be responsible for completing all four steps. In the second parallel trial, 
research staff will create personalized playlists (step 2) and load music players (step 3). For the second 
parallel trial, staff will provide Brown with 15 eligible residents’ “preferred” music genre and resident age. 
Brown research staff will preload iPods with popular music in the resident’s preferred genre from when they 
were between the ages of 16 and 26 (current best practice recommendation). This process is similar to 
playlists generated by Spotify and other streaming services. Additionally, we will be using playlists from the first 
trial to culturally and regionally tailor music selections. This is particularly important for the current study as we 
have four regionally and racially diverse corporations: two NH corporations serving predominately white, rural 

Protocol, Version 3.0 
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residents in the Midwest, one NH corporation serving mostly African American residents in the DC metro area; 
and one NH corporation serving southern African American and white residents. Based on our extensive 
population experience and large music database from the R21 and R33 phases we are able to observe 
differences in music preferences between a majority African American NH in rural Georgia and a majority 
African American NH in urban Maryland. Approximately 15% of all NH residents are African American; 
approximately 25% of the study sample is African American. This over-representation allows for cultural and 
regional tailoring of music playlists and has implications for the uptake of the Music & Memory program beyond 
the current study. By preloading devices with music, the program can be led by nursing staff from the 
beginning (step 4). We will compare the effects of these two processes on targeted use of the music to 
address clinical agitation.   
In our preliminary work, funded by the Research and Retirement Foundation, Brown (in partnership with 
B&F Consulting) identified facilitators and barriers to implementing the M&M program in six, high-performing 
NHs in the northeast. Important findings from this preliminary work include the need to: align the intervention to 
priorities of individual facilities; pilot the intervention with a few residents before expanding to an entire unit or 
NH; and integrate M&M into routine care planning and quality improvement activities to sustain use. During the 
R21, Brown and B&F translated these lessons learned into a step-by-step Implementation Guide (Appendix A). 
The Implementation Guide addresses logistics and process steps, including:  
• 
Identifying a computer to house an iTunes library,  
• 
Charging and storing iPods,  
• 
Researching resident playlist preferences, 
• 
Downloading personalized playlists, 
• 
Piloting the intervention with the first resident, 
• 
Scaling the intervention across a unit / within a nursing home, 
• 
Incorporating the intervention into care planning and data tracking, and 
• 
Sustaining the program after the 8-month intervention period. 
The Implementation Guide also provides checklists for tracking monthly progress towards successful 
implementation. 
Each participating NH receives two types of intervention trainings. First, NH staff will participate in 
standard M&M training and certification. Standard M&M training and certification is offered as a two, 1.5-hour 
live webinars, covering the benefits of M&M and a basic introduction to the equipment. After completing these 
two webinars, NHs become certified in M&M and receive a certificate to display in their facility.  
The second intervention training will be administered by the corporations for their participating facilities. 
This training will follow the steps outlined in the Implementation Guide. During the R33, B&F consulting will 
train and mentor corporate trainers in how to introduce and then disseminate M&M. This pragmatic approach 
mimics real-world diffusion and allows us to efficiently deliver the intervention to the 27 treatment NHs in each 
trial. In keeping with a pragmatic trial, implementation will be tailored to the needs of individual corporations 
and their facilities. However, at a minimum, corporate trainers will lead monthly coaching calls with the project 
team in the intervention facilities to track progress and set goals. Corporate trainers will help identify the “right” 
NH staff to participate in each NH’s M&M team and will mentor teams throughout the process, helping them to: 
set milestones, identify and track process data, review progress, and make mid-course corrections. The project 
team must include: the NH administrator, DON, activities staff, a nurse manager, and a certified nursing 
assistant. Other team members may be added, as appropriate. Corporate trainers will visit each NH at least 
twice during the intervention (launch and mid-implementation) to provide technical assistance and support.  
The research team has established serval ways to monitor adherence to the intervention protocol which 
are described in 9.4.3 Process Measures for Implementation Analysis. 
5.2 Concomitant Interventions 
Many eligible facilities are likely to have periodic, or even daily, music-based activities for residents. 
Facilities may also be testing other non-pharmaceutical options for addressing BPSD in ADRD while 
participating in the current study. However, facilities that are already systematically using personalized music, 
delivered through headphones or personal speakers, with multiple residents (whether M&M certified or not) will 
be excluded from the current study. 

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6 
DATA SOURCES AND ELEMENTS 
We seek to assess the effect of M&M on agitated and aggressive behaviors in NH residents with moderate 
to severe dementia. Agitated and/or aggressive behaviors are measured three ways: by interviewing staff 
about resident behaviors over time (primary outcome); through direct observation of residents when using and 
not using M&M (secondary outcome); and using available administrative data (secondary outcome). Other 
secondary outcomes include: other emotional states directly observed while the resident is using and not using 
M&M (anger, pleasure, alertness, sadness), antipsychotic use, antidepressant use, anxiolytic use, and 
depression. We would also like to understand best practices for integrating the Music and Memory program 
into existing care processes, facilitators and barriers of using the music, and how the intervention is 
implemented for each eligible patient (e.g. dose, reason for use, time of day) that might contribute or detract 
from its effectiveness.  
6.1 
Data Sources 
Secondary Data 
Electronic Health Records (EHRs): Three of our partners use PointClickCare (PCC); the other, has two 
vendors AmeriTec and Matrix Care. We are currently working with these EHR vendors on the PROVEN trial. 
Thus, we already have procedures in place to extract and link these EHR data with national Medicare 
repository data and ultimately to Medicare enrollment records. We will use the NHs’ EHR to obtain “real-time,” 
individual patient-level data for MDS assessments, user-defined assessments (UDAs), and medication order 
data. 
Minimum Data Set (MDS): The MDS has nearly 400 data elements, including cognitive function, 
communication / hearing problems, physical functioning, behavioral problems, continence, mood state, 
diagnoses, health conditions, special treatments, and medication use. Staff complete assessments for all 
individuals admitted to Medicare and Medicaid-certified NHs, including enrollees in both traditional Medicare 
and Medicare Advantage. Staff are required to submit MDS data to CMS regularly(66-69) and complete 
assessments upon admission, quarterly, and with changes in status or transfer from the building. Repeated 
evaluations of the reliability of the MDS reveal adequate to good values on most data items and scales. Brown 
investigators found that missing data are scarce.(66-69) Research using MDS data has made major 
contributions to our understanding of how policy, fiscal, and clinical factors influence the quality of NH care,(68, 
70-80) and much of this work has been conducted by Brown investigators participating in this proposed project. 
Medicare Enrollment, Vital Status, and Chronic Condition Warehouse Data: Brown investigators have 
decades of experience working with Medicare files linked to MDS and provider-specific data. The Medicare 
enrollment file provides demographic information as well as Medicaid eligibility, HMO status, and mortality 
data. The Chronic Condition Warehouse data elements include a summary of the past presence of over 20 
unique diagnoses present on any Medicare claim. Because we will obtain real-time MDS data from the 
facilities, we will also request the quarterly updates to the Vital Status and Chronic Condition Warehouse file 
from CMS; this will allow us earlier access to date of death than the enrollment file. These data allow us to 
track mortality even in the event that a resident is hospitalized and does not return to their original NH. 
Certification and Survey Provider Enhanced Reporting (CASPER): CASPER are publicly-available data 
from the Medicare/Medicaid certification and inspection process that all NHs undergo. Brown investigators 
have assembled a three-decade data panel on all certified U.S. facilities including data on ownership, size, 
staffing, services, patient acuity, and quality inspection results.(81, 82) 
Primary Data 
Primary data collection tools can be found in Appendices B-H. These data will be collected by independent 
data collectors during three site visits (baseline, four, and eight months).  
iPod Metadata: The iPod shuffle retains limited data about use. Information about the songs played (e.g., 
artist, album, track title, duration of track, genre) and the number of times a song is played are available and 
will be downloaded. 
Staff Interviews: the RAs will interview the NH caregiver most familiar with the resident using the Cohen 
Mansfield Agitation Inventory (CMAI), a validated 29-item tool for measuring agitation in people with ADRD 
living in NHs.(83, 84) We will use the CMAI to assess the frequency and severity of eligible residents’ 
behaviors over the previous week. 
Resident Observation (Trial 1 Only): The Agitated Behaviors Mapping Instrument (ABMI) will be used to 
observe resident behaviors at the point of intervention. Using independent, trained observers, we will observe 

Protocol, Version 3.0 
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the frequency of residents’ agitated behaviors over short intervals, when they are using and not using the M&M 
intervention. We will also use the Lawton Observed Emotion Rating Scale (OERS),(85) which was designed to 
measure pleasure, anger, anxiety/fear, sadness, and general alertness. Reactions to music will be captured, 
when observations include the use of M&M. 
Implementation Observation Checklist: The Implementation Observation Checklist is completed by data 
collectors while on-site. It describes adherence to specific aspects of the study protocol (e.g., are the playlists 
individualized, are the iPods labeled, are frontline staff involved in delivering intervention to residents, etc).  
Key Informant Interviews: Key informant interviews with the administrator and nursing lead in each 
intervention facility will be completed by Brown research team members at 4- and 8-months (mid- and full-
implementation). These interviews will identify facilitators, barriers, and best-practices related to implementing 
the M&M program, and feedback on corporate trainings.   
6.2 
Data Linkages 
During the R21, we developed and tested procedures for linking primary data, collected on-site at the 
nursing homes, to existing secondary data sources at the resident-level (Figure 2). Data linkage techniques are 
described in the paragraphs below. 
Figure 3. Linking Primary and Secondary Data at the Resident-Level  
 
As described in Section 6.1 Data Sources, there are four types of data that will be collected on-site: staff 
interview, resident observation, implementation observation, and iPod metadata. These data will be linked to 
secondary data obtained directly from NHs (MDS, UDA, and medication order data) and secondary data 
obtained directly from CMS (Medicare Enrollment, Vital Status, Chronic Condition Warehouse Data, and 
Certification and Survey Provider Enhanced Reporting). Data collected on-site will be entered using tablets 
through data entry systems developed in Qualtrics, the secure web-based survey tool supported by Brown’s 
Computing & Information Services. Data will be uploaded to the Qualtrics central servers using a secure 
channel. When entering the study data in Qualtrics, the patient data will only be identified by a pre-assigned 
Brown study ID; no personally identifying information (PII) or existing IDs (e.g., medical record number, social 
security number) will be entered. In preparation for analyses, the primary data will be downloaded from 
Qualtrics and stored on a secure server at Brown. Using a secure crosswalk of Brown study IDs to real person 
identifiers, the primary data will be linked to the secondary data (the collection of which was already approved 
by the IRB) for analyses. All analytic files released by the Systems Manager to analysts will be stripped of PII 
and will include only the Brown study ID. 
Brown University investigators and database management staff already receive national MDS, Medicare, 
and CASPER data semi-annually or quarterly under several CMS data use agreements (DUAs). There is a 
well-established database management structure for linking these files. Brown University also has experience 

Protocol, Version 3.0 
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integrating EMR data from with CMS Medicare enrollment records and Medicare claims. Using algorithms 
based on standard patient identifiers including Heath Insurance Claim (HIC) numbers, date of birth, gender, 
and Social Security Numbers (SSNs), matching rates generally exceed 98%. The new activity for METRIcAL is 
linking primary data collected on-site to secondary data. In the R21 pilot study, secure data transfer and 
linkage of primary and secondary data for all four corporations were successfully accomplished.  
7 
SAFETY ASSESSMENTS  
7.1. Minimal Risk Determination: 
There are special informed consent considerations for individual residents in the study. The intervention is 
of relatively low risk, and it will be implemented facility-wide as part of the intervention facilities’ standard 
operating procedures for addressing agitated and aggressive behaviors in dementia. Thus, we received a 
waiver of individual informed consent as set forth by the four criteria found in HHS 45 CFR 46:116 (Brown 
University IRB #1705001793): 
1. The research involves no more than minimal risk;  
2. The waiver will not adversely affect the rights and welfare of the subjects ‐ we are merely asking the 
staff about resident behaviors and observing residents from afar with no direct contact; 
3. The research could not practicably be carried out without the waiver this study involves evaluative 
measures of different types (observations, metadata from the music device, and MDS assessments) 
which need to be linked but are individually otherwise exempt or, due to their unobtrusive nature, readily 
waiver consent. These secure data linkages, necessary for the full evaluation, would not be possible 
without a waiver of individual consent; and 
4. Whenever appropriate, subjects will be provided with additional pertinent information after participation  
7.2. Serious Negative Reactions and Serious Adverse Events 
Please refer to the Data Safety and Monitoring Plan and Data Safety Monitoring Board Charter for complete 
safety assessment information. 
     Adverse Events: An adverse event (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. The potential AEs that could occur during this trial are: distress or 
strong negative emotional reactions in response to listening to the music delivered via the M&M intervention; 
and distress or strong negative emotional reactions in response to being observed (Trial 1 Only). Distress or 
strong negative emotional reactions to the music may include screaming / calling out, crying (not always a 
negative response), or attempting to remove headphones. Distress or strong negative emotional reactions to 
being observed may include screaming or becoming agitated / aggressive. Distress resulting from the music 
and the distress of being observed by a data collector would be classified as mild because the distress is easily 
tolerated and/or remediated, requires no medical evaluation, and has signs and symptoms that are transient. 
An immediate, negative reaction to the music would fit the study relatedness category “Definitely Related.” A 
negative reaction to being observed would fit the study relatedness category “Possibly Related,” as it will likely 
be difficult to precisely determine the origins of behaviors and reactions in residents with advanced dementia, 
and it is unclear the extent to which the resident might be aware that s/he is being observed. AEs resulting 
from negative reactions to the music are expected but likely rare. AEs resulting from negative reactions to the 
data collectors are not expected. 
     Serious Adverse Events: The potential serious adverse event (SAE) that could occur during this trial is a 
fall secondary to spontaneous ambulation (e.g., dancing) while listening to the music. Falls during spontaneous 
ambulation while listening to music could be classified as moderate or severe, depending on the presence of 
related injury and/or need for tertiary care. A fall during spontaneous ambulation while listening to the music is 
“Possibly Related” to the intervention, as this population of NH residents with moderate to severe dementia is 
prone to falls (independent of the intervention). This SAE is not expected, as falls are not consistent with 
available information about the intervention. 
     Unanticipated Problems: Unanticipated problems (UPs) are defined by DHHS 45 CFR part 46 as any 
incident, experience, or outcome that meets all of the following criteria: 

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1. 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; 
2. related or possibly related to participation in the research (possibly related means there is a reasonable 
possibility that the incident, experience, or outcome may have been caused by the procedures involved 
in the research); and 
3. 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. 
     Deaths: This study involves NH residents with advanced dementia. Death is expected in this population. In 
one of our ongoing, large cluster-randomized trials, which enrolls a similar population of NH residents with 
advanced dementia, we are observing a 60% annual mortality rate. There is no anticipated relationship 
whatsoever between the intervention (personalized music) and death.  
 
7.3. Followup for Serious Negative Reactions 
Adverse Events, Serious Adverse Events, Unanticipated Problems, and Deaths have specific reporting 
procedures. 
 
     As part of NH staff training, instructions will be given as to what constitutes an AE / SAE / UP. NH staff will 
be instructed to stop the music if an event occurs in which resident distress seems to result from the music 
(AE). NH staff are already trained in fall response (SAE). The NH staff should report any AE / SAE / UP to 
his/her immediate supervisor as soon as possible, but not exceeding 4 hours after the event. If deemed by the 
supervisor to be a true AE / SAE / UP, the NH supervisor will complete a Nursing Home Event Reporting Form, 
which will be submitted to the research project director via email within 24 hours of the event. The project 
director will report the event to the PI via email or telephone immediately upon becoming aware of the event. 
     Similarly, as part of the observer training, data collectors will be given instructions as to what constitutes an 
AE / SAE / UP. Data collectors will be instructed to terminate an observation if an event occurs in which 
resident distress seems to result from being observed (AE). Data collectors will report events to the NH 
supervisor as soon as possible, but not exceeding 4 hours after the event. If deemed by the supervisor to be a 
true AE / SAE / UP, the NH supervisor will complete a Nursing Home Event Reporting Form, which will be 
submitted to the research project director via email within 24 hours of the event. The project director will report 
the event to the PI via email or telephone immediately upon becoming aware of the event. 
     Upon receipt of the Nursing Home Event Reporting Form, the project director and Dr. James Rudolph will 
contact the NH supervisor and complete the Event Verification Form. Dr. Rudolph is a co-investigator on the 
project and a board-certified geriatrician with NH medical experience. Specifically, the project director and Dr. 
Rudolph will review the details of the event with the NH supervisor, confirm that the event meets criteria for a 
true AE / SAE / UP, and classify the severity, expectedness, and relatedness of the event.  
     During verification, if it is determined that the event does not meet the criteria for a true AE/ SAE/ UP, the 
Nursing Home Event Reporting Form and the Event Verification Form will be retained by the study team, and 
no further action will be taken. 
     During verification, if it is determined that the event is a true AE (and not a SAE or UP), the Nursing Home 
Event Reporting Form and the Event Verification Form will be retained for quarterly reporting of AEs to the 
Data Safety Monitoring Board (DSMB), the NIA Program Officer, and the IRB. A summary of AEs will be 
included in the semi-annual DSMB report. 
     During verification, if it is determined that the event is a true SAE, the PI will notify the DSMB, the NIA 
Program Officer, and the IRB within 24 hours of the research team becoming aware of the event (within 48 
hours of the event occurring). The Event Verification Form will also be used to capture the follow-up status of a 
resident who has experienced a SAE. The Nursing Home Event Reporting Form and the Event Verification 
Form will be retained and a summary of SAEs will be included in the semi-annual DSMB report.   
     During verification, if it is determined that the event is a true UP, the PI will notify the DSMB, the NIA 
Program Officer, the Office for Human Research Protections, and the IRB within 24 hours of the research team 
becoming aware of the event (within 48 hours of the event occurring). The Event Verification Form will also be 
used to capture the follow-up status of a resident who has experienced a UP. The Nursing Home Event 
Reporting Form and the Event Verification Form will be retained and a summary of UPs will be included in the 
semi-annual DSMB report. 

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     We will receive information on deaths occurring within the nursing home monthly, based on administrative 
data sent from participating NH corporations to Brown University. Deaths among residents exposed to the 
intervention will be reported within 24 hours of study’s knowledge of death. The report of death will be 
submitted via email to NIA Program Officer and to the DSMB Chair.  
 
7.4.  Protection Against Risks 
     Procedures to minimize against risks include: training NH staff on how to choose appropriate candidates to 
receive the intervention and how to deliver the intervention to minimize risk of negative reactions; training data 
collectors to conduct resident observations as unobtrusively as possible; and extensive data safety protocols. 
     Training NHs: There are several levels of ongoing training and monitoring. NH corporate leadership will 
receive a two-day initial training on how to help their participating NHs select residents who are likely to 
respond positively to the intervention. During this training, leadership will also be taught the best way to 
approach the residents with the music, in order to minimize negative reactions related to startling them. For 
example, the training details how to initially hold the headphones away from the resident’s ears to allow the 
resident to hear and get used to the music before experiencing the sensory pressure of the headphones. 
Corporate leadership will then repeat this training with each of their participating NHs before the intervention 
begins. Once the intervention begins, monthly phone calls will be made to NH staff by corporate leadership 
and Brown University staff in order to reinforce these best practices for minimizing negative reactions and to 
monitor for any events that have not been otherwise reported. In addition, corporate leadership will visit each 
site twice during the study to make sure the intervention is being administered consistent with best practices.  
     Training Data Collectors: Data collectors will attend a three-day training at Brown University before the start 
of the intervention. During this training, data collectors will visit a NH to become familiar with the setting and to 
practice conducting observations unobtrusively. During the actual study, a maximum of four observations will 
be conducted for each resident during a data collector visit, with two data collector visits per resident over the 
course of the study. Each observation will be a maximum of five minutes in duration. The data collector will 
neither be left alone with the resident nor interact directly with the resident. Whenever possible, the observation 
will be done when the resident is in a common area, but this may not always be feasible. If the observation is 
done while the resident is in his or her room, the data collector will remain outside of the room and observe as 
discreetly as possible through an open door. The goal is for the data collector to be as inconspicuous as 
possible. This protocol has been approved by the Brown University IRB. 
 
7.5. Safety Monitoring 
A DSMB for METRIcAL will act in an advisory capacity to the National Institute on Aging (NIA) Director to 
monitor participant safety, data quality, and progress of the study. External DSMB members will be specified 
by the funding agency. Members of the METRIcAL team who will participate in the open sessions of the DSMB 
include the PI (Mor), the lead biostatistician (Gutman), and project director (McCreedy). The NIA project officer 
for METRIcAL, Partha Bhattacharyya, will attend DSMB meetings and serve as the liaison between the DSMB 
and NIA. 
8 
INTERVENTION DISCONTINUATION  
The study may be discontinued at any time by the IRB, the NIA, the OHRP, or other government agencies 
as part of their duties to ensure that research participants are protected. Individual facilities in the intervention 
may withdraw from study participation at any time at the discretion of their senior management or corporate 
supervisors. Individual residents or their proxies can refuse the intervention and/or the observation of the 
implementation of the intervention.  
9 
STATISTICAL CONSIDERATIONS  
9.1 General Design Issues  
We will conduct two parallel, cluster-randomized control trials (RCTs) of personalized music for nursing 
home (NH) residents with moderate to severe dementia cared for in 81 NHs within four NH health care 
systems: PruittHealth, Good Samaritan Society, Vetter Senior Living, and CommuniCare (Terrapins Division). 
Twenty-seven facilities will receive the intervention in each trial. 

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9.2 Sample Size and Randomization 
The primary outcome for this study is agitated and aggressive behaviors, as measured by the Cohen-
Mansfield Agitation Inventory (CMAI). We have three ways of measuring agitation and aggression – the 
Minimum Data Set (MDS), the Cohen-Mansfield Agitation Inventory (CMAI), and the direct observation of 
residents while using and not using the music. Prior research suggests that agitated behaviors are under-
ascertained in the MDS, due to staff normalizing these behaviors when exhibited by the residents.(86) For this 
reason, we chose the CMAI as our primary study outcome. We based our sample size estimates and analytic 
plan on the CMAI (staff interview). 
Sample size estimates are based on the primary trial outcome: total score on the CMAI among long-stay 
residents with dementia. Based on data from the first trial, We conducted a post hoc power calculation to 
estimate the required sample size for different effect sizes. We used the formula proposed by Teerenstra et al 
(2012) and imputed values from the trial data. For significance level α and power 1-β, the formula for the 
required number of residents is: 
𝑛𝑟𝑒𝑠=
2 (𝑍1−𝛼
2 + 𝑍1−𝛽)
2
𝜎2
𝛿2
(1 + (𝑛−1)𝜌)(1 −𝑟2), 
where 𝑍𝑥 is the critical value from a normal distribution at 𝑥, 𝜎2 is the variance of the outcome CMAI, 𝛿 is the 
effect size, 𝜌 is the intra-class correlation, 𝑛 is the number of residents per cluster and 𝑟 is the correlation 
between a cluster means at baseline and at follow-up. To obtain the number of clusters required per arm we 
would need 𝑛𝑟𝑒𝑠/𝑛. In our parallel design experiment completed just before the pandemic, we found that 𝜎=
20, 𝜌= 0.12 and 𝑟= 0.5. Assuming an alpha level of 0.05 and power of 80%, we need 24 NHs per study arm 
to detect a 6-point reduction in the total CMAI score. We recruited 27 NHs per study arm which will allow us to 
address possibly higher ICC values, non-participation and lower correlation between the baseline and outcome 
scores. 
 
9.2.2. Treatment Assignment Procedures: Please refer to section 4 for a detailed description of the treatment 
assignment procedures.  
 
9.2.3. Blinding: Our partner health care systems will know which facilities are designated intervention facilities. 
Brown University statistician and data management staff will present aggregated post-random assignment 
comparisons of intervention and control facilities’ baseline characteristics, but these preliminary analyses will 
be not generated at the individual facility level. Dr. Mor, the study PI, will be blinded to the identity of both the 
control and intervention facilities. Facility assignment will be unblinded to the DSMB members at their request. 
9.3 Interim analyses and Stopping Rules 
We do not include stopping rules in the METRIcAL trial protocol for two reasons.  First, this is a minimal risk 
study for which serious negative reactions will be extremely rare (see Section 7.1). Indeed, the Brown IRB has 
concurred with this interpretation, having allowed a waiver of consent specifically because they view the study 
as minimal risk.  Second, a stopping rule would not be very feasible since the implementation period is only 8 
months in each facility, meaning that interim data analyses will be difficult, if not impossible, to perform.  
9.4 Outcomes  
9.4.1 Primary outcome   
The primary outcome for this study is the frequency of agitated and aggressive behaviors, as measured by 
the CMAI. The CMAI has 29 items organized under three domains: aggressive behavior, physically 
nonaggressive behavior, and verbally agitated behavior.(83) For each item, a staff member familiar with the 
resident’s behavior is asked how often each behavior occurred in the past week. Response choices are: never 
(1); less than once a week (2); once or twice a week (3); several times a week (4); once or twice a day (5) 
several times a day (6); or several times an hour (7). For NH residents with dementia the inter-observer 
reliability of the CMAI was: .62 for physically aggressive behaviors (reliable change index, RCI = 7.54), .73 for 
physically non-aggressive behaviors (RCI = 7.09), and .61 for verbally agitated behaviors (RCI = 5.80).(87) 

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Test-retest reliability was: .82 for physically aggressive behaviors (reliable change index, RCI = 2.59), .83 for 
physically non-aggressive behaviors (RCI = 5.44), and .86 for verbally agitated behaviors (RCI = 3.22).(87) 
During the R21 phase, the average total CMAI score for eligible residents at baseline was 60.98 (SD:15.37). 
Average total CMAI scores were similar across nursing home corporations (Table 3).  
 
Table 3. Total CMAI Scores for Eligible Residents at Baseline During R21 
Obs 
Mean 
SD 
Min 
Max 
Kurtosis 
Overall 
42 
60.98 
15.37 
30 
95 
2.41 
Good Sam 
10 
63.90 
20.23 
38 
95 
1.65 
Vetter 
12 
59.58 
13.79 
38 
89 
3.10 
Pruitt 
10 
58.20 
10.35 
42 
77 
2.39 
CommuniCare 
10 
62.50 
17.44 
30 
86 
2.44 
9.4.2. Secondary Outcomes:  
Secondary outcomes are obtained from primary and secondary data sources.  
 
Primary Data  
Agitated and aggressive behaviors. The Agitated Behaviors Mapping Instrument (ABMI). The ABMI has 14 
items which can be collapsed into total agitation, verbal agitation, and physical agitation.(90) Interrater 
reliability (IRR) for identification of behavior exceeds 90% in Cohen-Mansfield’s publications (93%, 96%); 
reported intraclass correlations coefficient (ICC) .90.(90-92) Cohen-Mansfield also reports high ICCs between 
videotaped (blinded) coding of behaviors and direct observation of behaviors (not blinded): .94 for verbal 
agitation, .93 for physical nonaggressive agitation, and .94 for total agitation.(90) Pearson correlation 
coefficients for identical items on the ABMI and CMAI are: .317 for verbal agitation (requests for attention .372, 
screaming .432, cursing .168, and complaining .442); .389 for physical agitation (pacing .542, repetitions .555, 
and exit seeking .322); .203 for combined agitation; .411 for physical aggression and .400 for 
disruptiveness.(93) 
Mood. Mood states are also observed using the Lawton Observed Emotion Rating Scale (OERS),(85) 
which was designed to measure pleasure, anger, anxiety/fear, sadness, and general alertness in nursing home 
residents with ADRD.  
 
Secondary Data 
Agitated and aggressive behaviors. In addition to the CMAI and the ABMI, we will also measure agitation 
and aggressive behavior using the MDS. The Aggressive Behavior Score (ABS) is derived from four items in 
MDS, Section E, which describe the frequency of: 1) physical behaviors (hitting kicking, pushing, etc.); 2) 
verbal behaviors (threatening, screaming, cursing, etc.); 3) other behaviors (scratching self, pacing, throwing, 
smearing food, etc.); and 4) rejection of care. Each behavior problem is rated in its frequency, ranging from 0 
(never) to 3 (daily), and the ABS is constructed by summing these four items. It has an alpha reliability 
between 0.79 and 0.93.(95) 
Receipt of antipsychotic medications and their substitutes. We have two data sources for receipt of 
antipsychotic, antidepressant, and anxiolytic medications: electronic medication orders and the MDS. The MDS 
assessment includes a count of the number of days in the last 7 in which an antipsychotic, antidepressant, and 
anxiolytic medication was received. We are also receiving standing medication orders from all four 
corporations. This data includes drug name and class, order date, ordering physician, and number of pills.  
Mood. The MDS includes the Patient Health Questionnaire (PHQ-9) a validated measure of depressed 
mood asked of the residents or if unable to respond to the interview, rated by staff.(96) 
 
9.4.3. Process Measures for Implementation Analysis:  
We will adopt five distinct approaches to assessing implementation: 1) a user-defined assessment (UDA) 
by which potentially eligible residents are assessed for their ability to listen to music, their music preferences, 
and the results of the initial trial of the iPod; 2) iPod metadata about each song that is played, including a count 
of the times played (and therefore the sum of all plays per unit time); 3) documentation of NH staff participation 
and attendance in M&M training and monthly corporation calls; 4) key informant interviews of NH staff during 
and after implementation; and 5) implementation observation checklist, completed on-site by data collectors, to 

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describe adherence to specific aspects of the study protocol (e.g., are the playlists individualized, are the iPods 
labeled, etc).  Table 4 describes the relationship between primary and secondary data sources and study 
outcomes. 
 
Table 4. Relationship of Data Sources to Study Outcomes 
 
Agitation / 
Aggression 
Mood 
Antipsychotic 
Mediation 
Anxiolytic 
Medications 
Antidepressant 
Medications 
Implementation 
Secondary Data 
 
 
 
 
 
 
   Minimum Data Set 
X 
X 
X 
X 
X 
 
   User Defined Assessment 
 
 
 
 
 
X 
   Medication Order Records 
 
 
X 
X 
X 
 
Primary data 
 
 
 
 
 
 
   Staff Interview 
X 
 
 
 
 
 
   Resident Observation 
X 
X 
 
 
 
 
   iPod Metadata 
 
 
 
 
 
X 
   Key Informant Interview 
 
 
 
 
 
X 
   Implementation observation 
 
 
 
 
 
X 
9.5 Data Analyses 
     The analytic approach in the second parallel trial is based on the minimum observed frequency of agitated 
and aggressive behaviors after intended exposure to the intervention (treatment) or after 8-months (control), 
conditional upon survival to at least one post-intervention observation (up to 4 months after baseline 
measurement). Our primary analysis is based upon an intent-to-treat principle, and we estimate complier 
average causal effect as a secondary analysis. The compliers analysis estimates the effects of the intervention 
for residents who received the music or would have received the music.  
     Our primary ITT analysis model is based on the model described by Murray & Blistein (2003)  and 
Teerenstra et al (2012). Let 𝑌𝑖𝑗𝑘 be the staff interview for resident 𝑖∈{1, … , 𝑛} from NH 𝑗∈{1, … , 𝐽} at time 𝑘∈
{𝑏𝑎𝑠𝑒𝑙𝑖𝑛𝑒, 𝑝𝑜𝑠𝑡−𝑒𝑥𝑝𝑜𝑠𝑢𝑟𝑒}, 𝐼𝑖𝑗 be an indicator that is equal to 1 if resident 𝑖 in facility 𝑗 is in the treatment 
group and 𝑇𝑖𝑗 is an indicator that is equal to 1 if this is the baseline score for resident 𝑖 in facility 𝑗. We assume 
that 𝑌𝑖𝑗𝑘= 𝜇𝑖𝑗𝑘+ 𝜖𝑖𝑗𝑘, where 𝜖𝑖𝑗𝑘~𝑁(0, 𝜎𝜖2), and 𝜇𝑖𝑗𝑘= 𝜇+ 𝛾𝑇𝑖𝑗𝐼𝑖𝑗+  𝜏(1 −𝑇𝑖𝑗)(1 −𝐼𝑖𝑗) + 𝛼(1 −𝑇𝑖𝑗)𝐼𝑖𝑗+ 𝑢𝑗+
(𝑢𝜏)𝑗,𝑘+ 𝑠𝑖𝑗. We define 𝑢𝑗~𝑁(0, 𝜎𝑢2) as the deviation of cluster 𝑗 from the overall mean, (𝑢𝜏)𝑗,𝑘~𝑁(0, 𝜎𝑢𝜏
2 ) 
represent the variation of each cluster at different time points, 𝑠𝑖𝑗~𝑁(0, 𝜎𝑠2) is the variation of individuals, 𝛾 is 
the difference at baseline between the mean of the intervention and control clusters, 𝜏 is the change from 
baseline to follow-up of the control clusters means, and α is the conditional treatment effect. Individual level 
covariates comprise of baseline variables including baseline CMAI. The estimate of interest would be the 
difference in marginal means. 
     To estimate the effects among participants that would comply with the intervention we used a technique 
described by Jo et al. Let 𝑐𝑖𝑗 be an indicator that is equal to 1 if resident 𝑖 in NH 𝑗 would use the music if 
provided. We assume that residents who would not be offered the music will not attempt to obtain it on their 
own. Eligible residents who do not receive the intervention who and receive care in an intervention NH are 
referred to as “non-compliers.” The effects of the intervention would be estimated using,  𝜇𝑖𝑗= 𝛽0 + 𝛽𝑐𝑐𝑖𝑗+
𝛼𝑐𝑐𝑖𝑗𝐼𝑖𝑗+ ∑
𝛾𝑖𝑗𝑙𝑋𝑖𝑗𝑙
𝐿
𝑙=1
+ 𝑢𝑛𝑏𝑗(1 −𝑐𝑖𝑗) + 𝑢𝑛𝑤𝑖𝑗(1 −cij) + 𝑢𝑐𝑤𝑖𝑗𝑐𝑖𝑗+𝑢𝑐𝑏𝑗𝑐𝑖𝑗, where the macro-unit residuals 
𝑢𝑛𝑏𝑗 (non-compliers) and 𝑢𝑐𝑏𝑗 (compliers) represent cluster-specific effects given 𝐼𝑖𝑗𝑘 and 𝑋𝑖𝑗𝑙, which are 
assumed to be normally distributed with zero mean and the between-cluster variances σ2nb (noncompliers) 
and σ2cb (compliers), respectively. The micro-unit residuals 𝑢𝑛𝑤𝑖𝑗 (non-compliers) and 𝑢𝑐𝑤𝑖𝑗 (compliers) are 
assumed to be normally distributed with zero mean and the within-cluster variance σ2nw (non-compliers) 
and σ2cw (compliers), and are equal across clusters. The following model for compliance status was assumed: 

Protocol, Version 3.0 
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𝑃(𝐶𝑖𝑗= 1) =
𝑒𝑥𝑝 (∑
𝜋𝑖𝑗𝑙𝑋𝑖𝑗𝑙
𝐿
𝑙=1
+𝜏𝑗)
1+𝑒𝑥𝑝 (∑
𝜋𝑖𝑗𝑙𝑋𝑖𝑗𝑙
𝐿
𝑙=1
+𝜏𝑗)  
Where 𝜋𝑖𝑗𝑙 are unknown parameters and 𝜏𝑗~𝑁(0, 𝜎𝜏2) so that the proportion of compliers may vary across 
clusters. Compliance status is only known in the intervention arm. Thus, a mixture model for compliance status 
in the control arm would be applied. Using the full likelihood, parameter estimates of the effect among 
compliers are estimated 
𝛿̂ = (𝛿̂1 −𝛿̂0)/𝜌𝑐 
where 𝛿̂𝑡 are the average CMAI among compliers in treatment group 𝑡 and where 𝜌𝑐 is the proportion of 
compliers. 𝛿̂𝑡 can be obtained from the above models across NHs. The variance of this estimate can be 
obtained via the delta method or using Markov chain Monte Carlo techniques. 
10 DATA COLLECTION AND QUALITY ASSURANCE 
10.1 Onsite Data Collection (Trial 1 Only) 
Procedures for onsite data collection are detailed in the Manual of Procedures. Briefly, on-site data 
collection will be used to capture primary study outcomes of frequency of agitated and aggressive behaviors, 
as well as secondary quality of life and engagement outcomes. Data collectors will also capture responses to 
music, collect metadata from iPods, and conduct an environment scan for observable characteristics of 
implementation. Data collectors will be flown to Providence, RI for a three-day intensify training for on-site data 
collection. During data collection months (baseline, 4-, and 8-months), Brown staff will have weekly phone calls 
with data collectors and supervisors. Visits will occur at baseline (pre-implementation), four months (mid-
implementation), and eight months (full implementation). Each visit will be two days in duration. There are 
several activities to be completed before, during, and after the on-site data collection visits. The following is an 
overview of these activities. 
 
Before Arrival: Site visit dates should be arranged approximately one month in advance of the visit by the 
project manager. In addition to the dates for the visit (2 consecutive days), the site should be made generally 
aware of the staff needed for the interview portion of the data collection. Approximately one week in advance of 
the on-site visit, the project director should reach out again to remind the NH of the upcoming site visit and 
request the facilities do the following in preparation: 
1. Prepare a list of the people who are currently using the program, or, in the case of baseline and 4-month 
visits, are likely to use the music during the intervention.   
2. Schedule time with nursing staff who are able to directly speak to the behaviors of these residents. The 
interviews take approximately 15 minutes per resident. If possible, these interviews should be scheduled 
for the first day of the site visit. 
3. Ensure the person most familiar with the technology (iTunes, iPods) will be available during the visit. In 
this email, the project director should also ask the preferred time for the data collector to arrive and the 
person s/he should ask for upon arrival. This information needs to be communicated to the evaluator. 
 
On-Site (Day 1): When the data collector arrives, she should first meet with the identified contact (often the 
administrator). The following tasks should be completed on the first day: 1) Obtain schedule for staff interview; 
2) Interview staff at designated times; and 3) With assistance of staff, download metadata from personal music 
players.  
The following information needs to be pre-populated in a secure tracking form to ensure the on-site data 
can be properly merged with the other administrative data used in this evaluation: resident last name, resident 
first name, birth month (MM), birth day (DD), birth year (YYYY), social security number (XXX-XX-XXXX), Point-
Click-Care Enterprise ID (if available), and whether or not the resident has been exposed to the intervention 
(Y/N). The tracking form will have unique study identifiers. These unique identifiers cannot be traced to specific 
individuals without the tracking form, and will be used to link the staff interviews and direct observations to 
other administrative data integral to the study evaluation.  
The data collector will interview NH staff members identified by the administration as being most familiar 
with the agitated and/or aggressive behaviors of the residents we will be observing during the second day of 
the visit. The purpose of interviewing the staff is to help us understand the frequency of behaviors. The staff 
member will be asked to approximate frequencies of specific resident behaviors over the past week and 

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estimate the amount of time staff spend attending to these behaviors. We will also ask staff to respond to items 
asking about the quality of life for this resident. 
At the four- and eight-month site visits, the evaluator will assist staff in downloading the iPod metadata. 
iPod metadata refers to the information captured in iTunes when an iPod is synced via the designated M&M 
computer. Specifically, we are interested in capturing the following for each resident’s playlist: song titles, song 
genres, song length, number of times a song has been played, and last time each song was played. By 
capturing the song length and the number of times a song has been played, we can better understand the 
amount of time the resident has received the intervention (approximate dose). By capturing last time the player 
was used, we can monitor attrition. 
 
Off-Site (Day 1): All on-site data collection is completed assuming internet at NHs is not available or reliable. In 
the evening, between the first and second days, the data collector needs to: upload completed staff interviews 
in Qualtrics, and upload metadata to server. 
 
On-Site (Day 2):  The second day is dedicated to systematic observation of the residents, while using and not 
using the music. When the data collector returns the second day, she should notify the administrator or contact 
person that she is on-site and asked to be introduced to the nursing staff on the unit(s) where the observations 
will take place. Each of the residents will be observed at least 4 times during the day. 
During the baseline visit none of the residents will have received the intervention. All observations will be 
of residents without the iPods. At the 8 month visit, all of the residents should have received the intervention 
and observations will be of residents while using and not using the iPods. At least four observations will be 
conducted for each resident: one in the morning; one mid-day; one in the late afternoon; and one with music (if 
music is being used for resident, else at a time chosen by data collector). At least one of the observations has 
to be during a meal. Residents will not be observed during any activities in which personal modesty is 
compromised (e.g., dressing or bathing). Whenever possible, residents will be observed in common areas, but 
may also be observed in their rooms with the door open or ajar. The evaluator should stand at an 
inconspicuous distance from the resident (minimum 5 feet from resident). 
 
Off-Site (Day 2): All on-site data collection is completed assuming internet at NHs is not available or reliable. In 
the evening, after the second day, the data collector needs to: upload completed observations in Qualtrics and 
complete the implementation observation. The implementation observation captures direct observations of how 
the equipment is being stored and used by staff, and gestalt impressions of staff familiarity and buy-in. The 
implementation observation will be completed by the evaluator immediately after leaving the site on the second 
day. 
 
All other data are derived from existing data. Please see Section 6 which details these sources. 
10.2 Data Confidentiality  
Brown University’s Center for Gerontology and Health Care Research will receive EMR patient-level data 
from partnering nursing home corporations. All four NH corporations have integrated sophisticated EMR 
systems in their facilities. The NH networks already have experience extracting MDS from their EMR systems 
for purposes of submitting mandatory, regular MDS reports to CMS. To protect patient confidentiality, the two 
corporations will place their data in a SSH secure server and will provide login information to Brown University. 
Data transfer to Brown University secure servers will be via SFTP protocol with password protection. Once the 
files have been uploaded to Brown University's servers they will be stored, unmodified, in a secure file location 
specific to these uploads. They will then be read into SAS datasets, one per file type. Brown University will 
then notify the facilities that the data was successfully downloaded and extracted, at which point the facilities 
will remove the data from their servers. All data files will be accompanied by a manifest detailing the number of 
distinct persons and records expected in them. Brown University will connect to the corporation servers on a 
monthly basis. Identifiers such as HICs and SSNs, will be included in order to be able to merge these person-
level data to the data received from CMS. Brown University’s information systems manager will be in charge of 

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the data transfer, and he will replace the HICs and SSNs fields with a Brown University-generated identification 
number (throughout our different data sources) to allow linkage of data for analytic purposes. 
10.3 Data Management 
Brown University’s Center for Gerontology and Health Care Research will serve as the Data 
Management/Statistical Center for the METRIcAL trial. The Center will be responsible for: receiving all data 
from CMS (Medicare, MDS), receiving all EMR data from study facilities, linking all secondary data with 
primary data collected onsite, and creating an analytic file and conducting analyses. Brown University 
investigators and database management staff already receive national MDS, Medicare, and OSCAR data 
semi-annually or quarterly under several CMS DUAs. There is a well-established data base management 
structure to linking these files. Brown also has experience linking EMR data from facilities with CMS Medicare 
claims and the MDS. The integration will be easily achieved thanks to the availability of HIC and SSN personal 
identifiers in both the EMR data from facilities and in the CMS Medicare claims and MDS data. 
10.4 Data Use Agreements 
The Brown University Center for Gerontology has an extensive history of working with ResDac to obtain 
DUAs to use CMS MDS and Medicare data for NIH funded projects, which will be obtained for this project. Our 
team will ensure all DUAs are compliant with NIH requirements.  
11 
PARTICIPANT RIGHTS AND CONFIDENTIALITY  
11.1 Institutional Review Board (IRB) Review 
The METRIcAL protocol was reviewed and approved by the Brown University Institutional Review Board (IRB).  
 
Informed Consent Forms 
The Brown IRB approved two waivers of individual consent. The Brown Institutional Review Board (IRB) 
approved a waiver of informed consent for secondary data under 45 CFR 46.116. This waiver covered the 
obtainment and linkages of EHR, MDS, Medicare Enrollment and Vital Status Data, and iPod metadata. The 
Brown IRB also approved a waiver of informed consent for the proposed primary data collection under 45 CFR 
46.116. This made it possible to collect primary data for all eligible residents, and to link staff interview and 
direct observation data to the available secondary data.  
11.2 Participant Confidentiality  
The main risk to participant confidentiality is a breach of confidentiality with the use of identifiable data. All 
research staff involved in the study will receive training in the protection of human subjects. The procedures 
described here address our efforts to minimize the risk of breach of confidentiality. All data management and 
analyses will be conducted by the Brown Center for Long-Term Care Quality & Innovation (Q&I Center), which 
is administratively housed within the Center for Gerontology & Healthcare Research and which leverages 
Gerontology’s administration and computing infrastructure. Researchers and staff have many years of 
experience working with identifiable data files on a large scale and have numerous security measures in place 
to ensure the integrity and confidentiality of the data. CMS data will be covered under the strict terms of a data 
use agreement (DUA). The CMS DUA will ultimately cover MDS, enrollment, and Vital Status File data. 
Though not required since HIPAA waivers cover the release of the resident data from the NH corporations to 
Brown University, if requested, we will also enter into DUAs with each of the NH corporations detailing the 
appropriate use of data. We will submit all executed DUAs to the IRB.  
At the conclusion of this study, or by the date of retention identified in the DUA, a CMS “Certificate of 
Disposition” certifying the proper destruction of all data obtained from CMS will be sent to CMS. All non-CMS 
data will be handled in a similar restrictive manner. In addition, all output containing individual identifiable 
information is treated as confidential data. This information is never transferred electronically via email. 
Shredders are used on any printed material containing individual identifiers. We will ensure that systems are in 
place to minimize the risk of breach of confidentiality for all data in this trial. Brown maintains numerous 
confidential databases, including MDS and Medicare files, and has a high level of security built into its 
computing systems. We will work closely with NH corporate leadership to develop protocols to maintain a high 

Protocol, Version 3.0 
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level of data confidentiality for extracting and merging data from their EHRs. As mentioned above, the Q&I 
Center leverages Gerontology’s administration and computing infrastructure. Gerontology maintains numerous 
confidential databases and has a high level of security built into its computing system. All data received at the 
Center will be stripped of any HIPAA personal identifiers and assigned unique identifiers. Access to the 
crosswalk between personal identifiers and new unique identifiers is restricted to the systems manager, Mr. 
Hiris, and this information is maintained in very high-security data files. No analytic files will contain personal 
identifiers.  
The procedures described here address our efforts to minimize the risk of breach of confidentiality. First, 
all staff involved in the study receive training in the protection of human subjects. Second, Brown University 
researchers and staff have many years of experience working with data files on a large scale and have 
numerous security measures in place to ensure the integrity and confidentiality of the data. We treat all output 
containing individual identifiable information as confidential data. This information is never transferred 
electronically via email or other protocols. Shredders are used on any printed material containing individual 
identifiers.  
We maintain numerous confidential databases and have a high level of security built into our computing 
system. The computing infrastructure consists of a VMS cluster, which houses all substantial data, a group of 
Windows servers that provide computing services and infrastructure support for client systems, and client 
Windows PCs through which all users access our systems. Network security is provided by a combination of 
firewalls, local network access controls, and continuous auditing and monitoring for security breaches. All 
access from systems external to the LAN is limited to encrypted channels (e.g., SSL for VMS terminal sessions 
or VPN connections for LAN file sharing access). Unencrypted access is provided only for the CGHCR external 
Web site and general e-mail support functions. The VMS cluster acts as a file server for Windows clients, and 
file access controls are consistently applied whether access is from the VMS or Windows environment.  
Security within the system is applied via Access Controlled Entries (ACEs) attached to all files on all 
systems. Security is applied uniformly to all files within a subtree of any file system, with the general rule that 
groups of users sharing a common task may read each other’s files but, in most cases, not write to each 
other’s files. VMS provides a highly-secure programming environment with ACEs applied to all objects and 
extremely controlled access to the larger system for individual users, as well as a versioning file system, 
secure batch queues and distributed processing, and efficient backup and recovery procedures. Windows 
clients are limited to a subset of these services (e.g., there is no way for file version information to be shown to 
Windows clients), but otherwise access is secured as for any other method of accessing data. 
Personally- and partially-de-identified data are housed in files that are restricted to systems management 
or to programmers who have been identified as custodians. No data are ever moved to more "public" spaces 
without identification information being stripped or non-reversibly encoded. Encoding is generally done via 
fairly large Roman cyphers applied iteratively to the original character string. No reverse encoding is ever 
generated nor maintained. Any matching between personally-identified data sources is done within a secured 
area prior to any data being exported. Windows servers that house partially de-identified data have matching 
ACEs applied so that access restrictions are applied consistently with VMS-based data. 
Since we use demographic covariates for many of our analyses, even the encoded data are best 
considered partially de-identified. ACEs restrict access to all data housed by CGHCR, such that access to any 
data elements on the servers is limited to those staff authorized to make such access. Authorizations are, in 
turn, granted by the core system's support staff upon request from a PI or other appropriate data owner. All 
users authorized to access CGHCR systems have access to some storage that is considered "general file 
sharing" but, by convention and policy, all individual or otherwise restricted data is prohibited from being stored 
on such space. Desktop systems are authorized to specific users, and it is assumed that they will store data 
they are authorized to work with on such local systems. The LAN is switched, yielding a reasonable amount of 
security between clients and servers within the LAN. Desktop systems are required to run current anti-virus 
software and are prohibited from running local file-sharing software. External analyses are run periodically to 
verify the security of systems within the LAN. 
Similarly, the Windows servers which support the LAN are configured as a local, isolated, secure, 
collapsed AD forest local to our LAN. DNS, DHCP, and other critical services are secured within the context of 
the local forest and are not accessible externally (with the exception, of course, of VPN or RDP access from 
authorized client systems). Extensive monitoring is done from the VMS cluster to ensure the health and 
stability of the Windows forest structure, and the individual servers within it. 

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In summary, CGHCR’s VMS computer system is highly secure and accessible only to authorized users. 
Within the group of authorized users, access to project data is restricted to individuals who are authorized to 
work on that specific research project. Access to identifiers is further restricted to the systems manager alone. 
Furthermore, CGHCR employees have signed an oath of confidentiality, and its violation is sufficient grounds 
for immediate termination.  
12 ETHICAL CONSIDERATIONS 
Ethical consideration for the METRIcAL trial will be in accordance with the Federal Policy for the 
Protection of Human Subjects (HHS Human Subjects Research 45 Code of Federal Regulations (CFR) 
46).(99) 
13  COMMITTEES 
We have three standing committees: steering, intervention and training, and data and measurement. No 
adjudication is necessary since this is a pragmatic trial and the measured outcomes are not adjudicated. 
The steering committee, consisting of the PI, the project director, and the project manager will have 
ultimate responsibility for all aspects of the study. Dr. Mor will serve as the primary liaison for the project to the 
NIH. The project's Steering Committee will oversee overall project direction, ensure timely submission of all 
requested project materials to the NIA, serve as the primary liaison between the project and the NH 
corporations, coordinate tasks among individual working groups, ensure project milestones are met, and 
review and approve all publications. The steering committee will also serve as the primary vehicle for decision-
making and help resolve conflicts or divergent approaches amongst team members. 
The intervention and training committee, consisting of the PI, project director, project manager, 
implementation lead, implementation consultants, and corporation representatives (as needed), are 
responsible for all aspects of implementation including: developing train-the-trainer materials; revising the 
Implementation Guide; training corporate staff; ensuring equipment delivery; monitoring and troubleshooting 
barriers to implementation; monitoring data collection activities; and conduct implementation evaluation. The 
implementation committee is largely responsible for the successful completion of the first and third study aims 
(see “Specific Aims”). The implementation team will meet twice a month or as needed. 
The data and measurement committee, consisting of the PI, project director, project manager, 
measurement lead, statistical design and analysis lead, research team members, and intervention science 
lead, are responsible for: obtaining IRB approval for study; securing data use agreements and IRB approvals; 
identifying facilities which meet eligibility criteria; identifying and providing intervention facilities with lists of 
eligible residents; executing monthly transfers of EHR data; training research assistants for on-site data 
collection; collecting iPod, interview, and direct observation data while on-site; merging all data into a secure 
project database, and analyzing data. The data and measurement committee is largely responsible for the 
second study aim (see “Specific Aims”) The data and measurement committee will meet twice and month, or 
as needed. 
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.  Any presentation, abstract, or manuscript will be made available for review by the NIA 
prior to submission. 
15 REFERENCES 
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16 APPENDICES 
Appendix A. Center Implementation Guide 
Appendix B. Staff Interview - CMAI 
Appendix C. Resident Observation - ABMI 
Appendix D. Implementation Observation Tool 
Appendix E. Key Informant Interview Guide - Administrator - Month 4 
Appendix F. Key Informant Interview Guide - Administrator - Month 8  
Appendix G. Key Informant Interview Guide - Director of Nursing - Month 4 
Appendix H. Key Informant Interview Guide - Director of Nursing - Month 8  
Appendix I. User-Defined Assessment