Align: Aligning Medications With What Matters Most
Phase: NA
Conditions: Polypharmacy, Alzheimer Disease and Related Dementias
Sponsor: Johns Hopkins University

Protocol Template, Version 3.0, February 17, 2021 
 
 
 
 
 
 
PILOT STUDY OF ALIGN: A PRAGMATIC DEPRESCRIBING TRIAL 
FOR PATIENTS WITH DEMENTIA IN PRIMARY CARE 
ClinicalTrials.gov ID: NCT04938648 
Principal Investigator: 
Ariel Green, MD, MPH, PHD 
Assistant Professor of Medicine 
Division of Geriatric Medicine and Gerontology 
Johns Hopkins University School of Medicine 
 
Kaiser Permanente Colorado Site Principal Investigator: 
Rebecca Boxer, MD, MS 
Medical Director of Clinical Trials 
Institute for Health Research 
Kaiser Permanente Colorado 
Supported by: 
The National Institute on Aging 
IMPACT Collaboratory (U54AG063546) Pilot Grants Program  
 
 

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TABLE OF CONTENTS 
Page 
PREFACE ......................................................................................... Error! Bookmark not defined. 
FULL PROTOCOL TITLE ............................................................ Error! Bookmark not defined. 
TABLE OF CONTENTS .............................................................................................................. i 
PRÉCIS .......................................................................................................................................... v 
Study Title ................................................................................................................................... v 
Objectives ................................................................................................................................... v 
Design and Outcomes ................................................................................................................. v 
Interventions and Duration ......................................................................................................... v 
Sample Size and Population ....................................................................................................... vi 
STUDY TEAM ROSTER ............................................................................................................ 7 
Principal Investigator: ................................................................................................................. 7 
Ariel Green, MD, MPH, PhD 
Co-Investigators: ......................................................................................................................... 7 
Rebecca Boxer, MD, MS 
Cynthia M. Boyd, MD, MPH 
Jennifer Wolff, PhD 
Qian-Li Xue, PhD 
Elizabeth A. Bayliss, MD, MSPH  
 
PARTICIPATING STUDY SITES ............................................................................................. 8 
1 
Study objectives ..................................................................................................................... 9 
1.1 
Primary Objective ........................................................................................................... 9 
1.2 
Secondary Objectives ...................................................................................................... 9 
2 
BACKGROUND AND RATIONALE ................................................................................ 9 
2.1 
Background on Condition, Disease, or Other Primary Study Focus .............................. 9 
2.2 
Study Rationale ............................................................................................................... 9 
3 
STUDY DESIGN ................................................................................................................. 10 
4 
SELECTION AND ENROLLMENT OF PARTICIPANTS .......................................... 12 

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4.1 
Inclusion Criteria .......................................................................................................... 12 
4.2 
Exclusion Criteria ......................................................................................................... 12 
4.3 
Study Enrollment Procedures ....................................................................................... 12 
5 
STUDY INTERVENTIONS .............................................................................................. 13 
5.1 
Interventions, Administration, and Duration ................................................................ 13 
5.2 
Handling of Study Interventions ................................................................................... 14 
5.3 
Concomitant Interventions ............................................................................................ 14 
5.4 
Adherence Assessment ................................................................................................. 15 
6 
STUDY PROCEDURES .................................................................................................... 15 
6.1 
Schedule of Evaluations ................................................................................................ 15 
6.2 
Description of Evaluations ............................................................................................ 16 
6.2.1 Screening Evaluation ................................................................................................ 18 
6.2.2 Enrollment, Baseline, and/or Randomization ........................................................... 19 
6.2.3 Follow-up Visits ....................................................................................................... 20 
6.2.4 Completion/Final Evaluation .................................................................................... 20 
7 
SAFETY ASSESSMENTS ................................................................................................. 20 
7.1 
Specification of Safety Parameters ............................................................................... 20 
7.2 
Methods and Timing for Assessing, Recording, and Analyzing Safety Parameters .... 21 
7.3 
Adverse Events and Serious Adverse Events ............................................................... 21 
7.3.1 Reporting Procedures ................................................................................................ 21 
7.3.2 Follow-up for Adverse Events .................................................................................. 22 
7.4 
Safety Monitoring ......................................................................................................... 22 
8 
INTERVENTION DISCONTINUATION ....................................................................... 22 
9 
STATISTICAL CONSIDERATIONS .............................................................................. 22 
9.1 
General Design Issues ................................................................................................... 22 
9.2 
Sample Size and Randomization .................................................................................. 23 
9.2.1 Treatment Assignment Procedures ........................................................................... 23 
9.3 
Interim analyses and Stopping Rules ............................................................................ 23 
9.4 
Outcomes ...................................................................................................................... 23 
9.4.1 Primary outcome ....................................................................................................... 24 
9.4.2 Secondary outcomes ................................................................................................. 24 
9.5 
Data Analyses ............................................................................................................... 25 

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10 DATA COLLECTION AND QUALITY ASSURANCE ................................................ 26 
10.1 
Data Collection Forms .................................................................................................. 26 
10.2 
Data Management ......................................................................................................... 26 
10.3 
Quality Assurance ......................................................................................................... 27 
11 PARTICIPANT RIGHTS AND CONFIDENTIALITY ................................................. 27 
11.1 
Institutional Review Board (IRB) Review .................................................................... 27 
11.2 
Informed Consent Forms .............................................................................................. 27 
11.3 
Participant Confidentiality ............................................................................................ 30 
11.4 
Study Discontinuation ................................................................................................... 30 
12 ETHICAL CONSIDERATIONS ....................................................................................... 30 
13 COMMITTEES .................................................................................................................. 31 
14 PUBLICATION OF RESEARCH FINDINGS ................................................................ 31 
15 REFERENCES .................................................................................................................... 31 
16 SUPPLEMENTS/APPENDICES ...................................................................................... 34 
 
 
 

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PRÉCIS 
Study Title 
ALIGN: Aligning Medications with What Matters Most 
Objectives  
The overarching goal of this proposal is to refine and pilot a workflow in which a clinical 
pharmacist makes deprescribing recommendations to the primary care provider (PCP) to 
reduce medication regimen complexity for people living with dementia (PLWD) and 
their care partners. To accomplish our main objective above, we propose the following 
specific aims: 
 
1) To assess the feasibility and acceptability of ALIGN in two different health care 
systems, to guide the subsequent evaluation of the effectiveness of the intervention in an 
embedded pragmatic trial (ePCT). 
 
2) To determine the feasibility of the primary and secondary outcome measures for the 
subsequent ePCT: 
2a) To determine the feasibility of measuring the primary outcome, the patient-level 
Medication Regimen Complexity Index (pMRCI)1-4, within the existing EHR 
systems, and to compare it with a more pragmatic measure, chronic medication count, 
as the primary outcome measure for the ePCT. 
2b) To determine the feasibility of measuring the secondary outcome, the Family 
Caregiver Medication Administration Hassles Scale (FCMAHS)5, a caregiver-
reported outcome measure. 
Design and Outcomes   
This is a pilot study of a pragmatic intervention consisting of the following strategies: 1) 
direct-to-consumer deprescribing educational materials designed to activate the care 
partner and PLWD; 2) a telehealth visit in which a clinical pharmacist discusses benefits 
and harms of the patient’s medications with the patient and care partner in the context of 
their goals and preferences; and 3) pharmacist-PCP communication in which the 
pharmacist provides tailored deprescribing recommendations designed to be useful and 
actionable for the PCP. The study will assess the feasibility and preliminary efficacy of 
the intervention in two healthcare systems, to guide the subsequent evaluation of the 
intervention in an ePCT. 
 
Patient eligibility criteria will be: age ≥65 years with a diagnosis of Alzheimer’s disease 
or related dementia (ADRD) from ICD-9 or ICD-10 visit codes or from the electronic 
health record (EHR) problem list and ≥5 chronic medications. Patients and care partners 
will be enrolled as dyads and randomized to the intervention group and a delayed 
intervention control group that will receive the pharmacist-led component 3 months after 
the educational mailing.  

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Interventions and Duration  
Dyads at each pilot site will be randomly assigned to receive the pharmacist-led 
intervention immediately after the educational mailing or to a delayed intervention 
control group that will receive the pharmacist-led component 3 months after the mailing. 
Piloting with a delayed intervention control group will allow for a more realistic 
examination of the differential effect of a low-touch control arm (educational mailing 
only) vs. the pharmacist-led process. Each participant will be on study (intervention 
period and additional follow-up) for 3 months. 
Sample Size and Population  
The eligible patient population for the pilot study will be all patients at the two pilot 
clinics who are age 65 or greater with a diagnosis of Alzheimer’s disease and related 
dementias (ADRD) from either ICD visit codes or documentation on the problem list. 
Patients must also be taking 5 or more chronic medications, and active patients, defined 
as having >1 visit to the primary care clinic within the past year. We will enroll 60 
patient-care partner dyads (15 dyads per arm at each site). 

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STUDY TEAM ROSTER  
Principal Investigator: 
Ariel Green, MD, MPH, PhD 
 
Johns Hopkins University School of Medicine 
 
5200 Eastern Ave, Mason F. Lord Bldg, Suite 7000 
 
Baltimore, MD 21224 
 
Telephone: 410-550-6733 
 
Fax: 410-550-8701 
 
afrank2@jhmi.edu 
 
 
Co-Investigators: 
Rebecca Boxer, MD, MS 
 
Institute for Health Research, Kaiser Permanente Colorado 
 
2550 South Parker Rd., Suite 200 
 
Aurora, CO 80014 
 
Telephone: 303-636-2479 
 
Fax: 303-636-2944 
 
rebecca.s.boxer@kp.org 
 
Site Principal Investigator, Kaiser Permanente 
 
 
Cynthia M. Boyd, MD, MPH 
 
Johns Hopkins University School of Medicine 
 
5200 Eastern Ave, Mason F. Lord Bldg, Suite 7000 
 
Baltimore, MD 21224 
 
Telephone: 410-550-8676 
 
Fax: 410-550-8701 
 
cyboyd@jhmi.edu 
 
Co-Investigator 
 
 
Jennifer Wolff, PhD 
 
Johns Hopkins Bloomberg School of Public Health 
 
624 N. Broadway, Hampton House 692 
 
Baltimore, MD 21205 
 
Telephone: 410-502-0458 
 
Fax: 410-955-0470 
 
jwolff2@jhu.edu 
 
Co-Investigator 
 
 
Qian-Li Xue, PhD 
 
Johns Hopkins Center on Aging and Health 
 
2024 E. Monument Street, Room 2-722 
 
Baltimore, MD 21205 
 
Telephone: 410-614-9625 
 
Fax: 410-614-9625 
 
qxue1@jhu.edu 
 
Co-Investigator, Statistician 
 
 
Elizabeth A. Bayliss, MD, MSPH  
 
Institute for Health Research, Kaiser Permanente Colorado  

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2550 S. Parker Road, Suite 200 
 
Aurora, CO 80014 
 
Telephone: 303-636-2472 
 
Fax: 303-636-2944 
 
Elizabeth.Bayliss@kp.org 
 
Co-Investigator 
 
PARTICIPATING STUDY SITES  
 
 
Ariel Green, MD, MPH, PhD 
 
Johns Hopkins University School of Medicine 
 
5200 Eastern Ave, Mason F. Lord Bldg, Suite 7000 
 
Baltimore, MD 21224 
 
Telephone: 410-550-6733 
 
Fax: 410-550-8701 
 
afrank2@jhmi.edu 
 
 
Rebecca Boxer, MD, MS 
 
Institute for Health Research, Kaiser Permanente Colorado 
 
2550 South Parker Rd., Suite 200 
 
Aurora, CO 80014 
 
Telephone: 303-636-2479 
 
Fax: 303-636-2944 
 
rebecca.s.boxer@kp.org  
 
 
 

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1 
STUDY OBJECTIVES 
1.1 Primary Objective 
To assess the feasibility and acceptability of ALIGN in two different health care systems, 
to guide the subsequent evaluation of the effectiveness of the intervention in an embedded 
pragmatic trial (ePCT).  
1.2 Secondary Objectives 
To determine the feasibility of the primary and secondary outcome measures for the 
subsequent ePCT: 
a) To determine the feasibility of measuring the primary outcome, the patient-level 
Medication Regimen Complexity Index (pMRCI)1-4, within the existing EHR systems, and 
to compare it with a more pragmatic measure, chronic medication count, as the primary 
outcome measure for the ePCT. 
b) To determine the feasibility of measuring the secondary outcome, the Family Caregiver 
Medication Administration Hassles Scale (FCMAHS)5, a caregiver-reported outcome 
measure. 
 
2 
BACKGROUND AND RATIONALE  
2.1 Background on Condition, Disease, or Other Primary Study Focus 
PLWD use more medications and have more complex medication regimens than people 
without dementia. Medication regimen complexity is a major source of burden for family 
caregivers of PLWD in the community.6-9It has been associated with adverse drug events,10 
poor adherence,11 hospital discharge to non-community settings,12 and hospital 
readmission,10 suggesting that “the cure may have become the disease.”13,14 Regimen 
complexity strains patients, caregivers, and healthcare systems due to the time and stress 
associated with administering medications (eg, due to swallowing difficulties or 
confusion), monitoring and direct medication costs. The key principle of person-centered 
care is that people should be on the medicines that will help them achieve their goals – but 
not medicines that are either likely to be harmful or unhelpful.15 
 
Few prior deprescribing studies have targeted caregivers of PLWD, despite the enormous 
strain caregivers face due to medication-related tasks16 and their specific informational and 
decisional needs and conflicts.17 Most deprescribing interventions have focused on specific 
drug classes or the number of medications only, not addressing dosing schedule and 
additional directions for medication use – critical factors that determine regimen 
complexity and caregiver burden. Furthermore, interventions to reduce medication regimen 
complexity have primarily occurred in hospitals,18 long-term care facilities,19 or skilled 
home healthcare,20 not in primary care – typically the first point of contact with the health 
care system for PLWD and their caregivers. Another knowledge gap is that health systems 
rarely collect data on outcomes that reflect the lived experience of dementia caregivers.21 
Both the Alzheimer’s Association and the 2017 NIA National Research Summit on 
Dementia Care identified the development and use of patient/caregiver-reported outcome 
measures (PCROs) as a priority for dementia research.21 

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2.2 Study Rationale 
In preliminary work by our team and others, PCPs cite time pressure during office visits 
and lack of published guidance of when and how to stop medications as barriers to 
optimizing prescribing.22-24 Deprescribing statins, antihypertensives, and psychotropic 
medications in older adults has been shown to be safe, and may lead to improved quality of 
life, reductions in falls, and improvements in cognitive and psychomotor function.25-28 
Pharmacists are ideally suited to help address the barriers to deprescribing by lessening 
demands on PCP time and providing concrete, individualized deprescribing 
recommendations. Previous research has shown that providers have high acceptance rates 
for medication therapy management services provided by community pharmacists.29,30 Our 
qualitative research has revealed that patients, caregivers and PCPs have a high degree of 
trust in clinical pharmacists embedded within primary care clinics.31 
 
ALIGN: Aligning Medications with What Matters Most is informed by learnings from 
OPTIMIZE, our team’s patient-centered, pragmatic deprescribing intervention for PLWD 
in primary care that is currently being prospectively evaluated with a cluster-randomized 
trial at 18 clinics within KPCO.32  OPTIMIZE is based on the Chronic Care Model, in 
which patients and families are empowered through approaches such as education and self-
management support, and practice teams are bolstered by tools such as decision support 
and clinical information systems.33 OPTIMIZE consists of two components: A patient-level 
intervention comprised of a deprescribing educational brochure, and a PCP-level 
intervention comprised of an in-person deprescribing educational session, deprescribing 
“tip sheets” and tailored feedback at the level of the clinic on rates of potentially 
inappropriate medication (PIM) prescribing in PLWD. Although OPTIMIZE materials 
encourage patients and caregivers to discuss deprescribing with PCPs, the intervention does 
not require such conversations. ALIGN builds on OPTIMIZE by more explicitly 
addressing the informational and decisional needs of caregivers through a shared decision 
making process facilitated by clinical pharmacists, who are already embedded in both 
pilot clinics and throughout their parent healthcare systems. ALIGN leverages existing 
pharmacist-led comprehensive medication management programs in both healthcare 
systems. The goal of the pharmacist-led process in ALIGN is to optimize prescribing and 
reduce medication regimen complexity by focusing on what matters most to the patient and 
caregiver, beyond rigid adherence to clinical practice guidelines. ALIGN is responsive to 
the COVID-19 outbreak in that it can be delivered entirely via telephone. 
3 
STUDY DESIGN 
The proposed pragmatic intervention consists of the following strategies: 1) direct-to-
consumer deprescribing educational materials designed to activate the care partner and 
PLWD; 2) a telehealth visit in which a clinical pharmacist discusses benefits and harms of 
the patient’s medications with the patient and care partner in the context of their goals and 
preferences; and 3) pharmacist-PCP communication in which the pharmacist provides 
tailored deprescribing recommendations designed to be useful and actionable for the PCP. 
The study will assess the feasibility and preliminary efficacy of the intervention in two 
healthcare systems, to guide the subsequent evaluation of the intervention in an ePCT. 
 
We will enroll 60 patients and their care partners as dyads (15 dyads per arm at each site). 
Patient eligibility criteria will be: age ≥65 years with a diagnosis of ADRD from ICD-9 or 
ICD-10 visit codes or from the EHR problem list and ≥5 chronic medications. In 

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Baltimore, the study site will be 1-4 clinics that are part of Johns Hopkins Community 
Physicians (JHCP). In Denver, the study sites will be KPCO greater Denver metro primary 
care practices. Dyads at each pilot site will be randomly assigned to receive the pharmacist-
led intervention immediately after the educational mailing or to a delayed intervention 
control group that will receive the pharmacist-led component 3 months after the mailing. 
(Please see the Consent section for a discussion of consent options for consenting patients 
as part of pragmatic trials.) 
 
This protocol employs a pragmatic design. The intervention is delivered by clinical 
pharmacists who are already integrated in primary care clinics at JHCP and KPCO. 
The pharmacists are trained in complex geriatric medication management and 
routinely provide comprehensive medication management to Medicare beneficiaries. 
 
Aim 1 is to assess the feasibility and acceptability of ALIGN in two different health care 
systems, to guide the subsequent evaluation of the effectiveness of the intervention in an 
ePCT. Data to measure feasibility will be acquired from the EHR, checklists completed by 
the pharmacists, and audiorecordings of pharmacist phone calls with care partners. We will 
collect the following measures: 
• Proportion of dyads that opt out of the intervention; 
• Proportion of pharmacist messages to the PCP that receive an acknowledgement or 
response; 
• Number of contacts between pharmacist and PCP and between pharmacist and dyad; 
• Time required by the pharmacist to complete the intervention; 
• Proportion of dyads who complete 2 of 2 pharmacist phone calls based on documented 
status reports. 
 
To evaluate intervention acceptability, we will track the following: 
• Type of recommendations made by the pharmacist and acceptance rates for those 
recommendations (we will look in the chart for notation of patient/care partner and PCP 
acceptance). 
 
Aim 2 is to determine the feasibility of the primary and secondary outcome measures for 
the subsequent ePCT: 
In Aim 2a, we will determine the feasibility of measuring the primary outcome, the patient-
level Medication Regimen Complexity Index (pMRCI)1-4, within the existing EHR 
systems, and compare it with a more pragmatic measure, chronic medication count, as the 
primary outcome measure for the ePCT. 
 
In Aim 2b, we will determine the feasibility of measuring the secondary outcome, the 
Family Caregiver Medication Administration Hassles Scale (FCMAHS)5, a caregiver-
reported outcome measure. 
 
We will develop the procedures for collecting both outcomes for the full trial. 
 
In Aim 2a, feasibility will be measured as follows: 
• Proportion of participants with data elements available vs. unavailable to calculate the 
pMRCI. 

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To compare it with chronic medication count as the primary outcome measure for the 
ePCT, we will measure: 
• Change in chronic medication count; and 
• Change in pMRCI from baseline to 3 months. 
Chronic medication count will be obtained from the EHR using algorithms refined in 
OPTIMIZE. 
 
In Aim 2b, feasibility will be measured as follows: 
• Response rate and completion time for the FCMAHS using each mode of administration. 
 
4 
SELECTION AND ENROLLMENT OF PARTICIPANTS  
4.1 Inclusion Criteria  
Participants must meet all of the following inclusion criteria to participate in this study: 
 
• Care partners will be defined as family or other companions >21 years who regularly 
help the patient with managing medications. We will ask patients to identify the person 
who helps them the most with tasks such as picking up medications at the pharmacy, 
requesting refills, filling the pill box and administering medications. 
• Patient eligibility criteria will be: age ≥65 years with a diagnosis of ADRD from ICD-9 
or ICD-10 visit codes or from the EHR problem list and ≥5 chronic medications. We 
will include only active patients, defined as having ≥1 visit to the primary care clinic 
within the past year. 
 
4.2 Exclusion Criteria  
Candidates meeting any of the following exclusion criteria at baseline will be excluded 
from study participation: 
• As both the pilot and the planned pragmatic trial will be based in primary care, 
individuals residing in long term care facilities or enrolled in hospice will be excluded. 
• Individuals who cannot converse comfortably in English will be excluded because the 
FCMAHS has not been validated in other languages. 
  
4.3 Study Enrollment Procedures  
1) Using clinical and claims data under a waiver of HIPAA Authorization, the data 
analytics team at each institution will identify all patients at each of the two clinics who 
meet inclusion criteria. This list will be routed to the project assistant via a HIPAA-
compliant method. 
 
2) The project assistant will perform administrative roles for the study. This includes:  
Mailing study materials with opt-out provisions to the homes of 30 randomly selected 
patients from this list. Patients will be entered into a study database for tracking and to 
avoid repeated mailings. Study materials will include a phone number that patients or 
care partners can call to opt out. We will continue mailing materials to eligible patients 
until 30 have been recruited at each clinic. Materials will also provide dyads the 
opportunity to opt in by calling the phone number. To emphasize that the study is for 

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care partners, the envelope and introductory letter will be addressed to the patient and 
family (eg, “Mr. John Smith and family”). 
 
Scheduling virtual visits with the clinical pharmacist. Dyads who do not opt out (and 
those who opt in) within 14 days of the study mailing will be randomized using 
computer-generated random numbers to either the intervention group or the delayed 
intervention control group, and called by the project assistant.  
 
If the patient and care partner do not opt out, the project assistant will call the patient’s 
phone number listed in the EHR and use an IRB-approved script (attached) to identify the 
care partner: 
• The project assistant will briefly explain that they are calling about “a program for 
family members and friends who are caring for someone with memory problems.” 
o If the patient answers the phone, the project assistant will say, “I’m calling 
about your medicines. Many people have someone who helps them manage 
their medicines on a daily basis.” They will then ask to speak with the care 
partner. 
o If the care partner answers the phone, the project assistant will ask, “Are you 
the person who helps [PATIENT] the most to manage their medicines?” 
This is the standard approach that clinic staff use to call patients with 
dementia on the phone and identify their care partners during the 
course of clinical care. As the intervention is designed to address the needs 
of care partners and requires their participation, the project assistant will ask 
to speak with the care partner first. Because some patients with mild or 
moderate dementia may be interested in hearing about the program, the 
project assistant will offer to describe it to the patient as well. 
• Patients who are unwilling or unable to identify a care partner who helps them 
manage their medicines will be excluded. The project assistant will document the 
reasons for ineligibility in a REDCap Screening Log. 
• The project assistant will briefly describe the pharmacist consult to the care partner. If 
the care partner agrees, the project assistant will schedule the pharmacist call, which 
will occur immediately (within 4 weeks) for the intervention group and at 
approximately 3 months for the delayed intervention control group. 
 
4) If patients or care partners opt out during the phone call, the project assistant will 
document the reason (eg, no time to participate, not interested) in a REDCap Screening 
Log. 
 
5) Dyads randomized to the delayed intervention group will be told that they will receive 
another phone call from the project assistant in approximately 3 months to remind them of 
their appointment with the clinical pharmacist. 
 
6) After scheduling the pharmacist consult, project assistants will offer care partners in 
both groups the option of completing the secondary outcome measure, the Family 
Caregiver Medication Administration Hassles Scale (FCMAHS). For care partners who are 
interested in completing the FCMAHS, project assistants will obtain verbal consent when 
administering the measure over the phone (see script). If the care partner does not wish to 
complete the FCMAHS over the phone during the scheduling phone call, the project 

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assistant will offer to call back before the pharmacist visit (up to 28 days) or to later e-mail 
the care partner a link to an electronic version. 
 
5 
STUDY INTERVENTIONS  
5.1 Interventions, Administration, and Duration 
1) The mailing sent to patients’ homes will be no more than 3 pages and will consist of an 
informational brochure introducing the idea of discontinuing unnecessary or potentially 
inappropriate medications. This approach is based on an established model of patient-
centered deprescribing and is adapted from a direct-to-consumer deprescribing intervention 
for older adults on benzodiazepines.34,35 Materials are designed to engage care partners and 
invite them to discuss medication-related concerns with the pharmacist. The informational 
brochure will include mention of how to plan for a telehealth visit with a clinical 
pharmacist to discuss medication optimization and reasons why some people may benefit 
from taking fewer medicines. It will encourage care partners to discuss their key health 
outcome goals for the patient, and medication-related activities that the dyad finds helpful 
and feasible vs. unhelpful or difficult. The brochure will include instructions NOT to 
discontinue any medications without talking to the clinical pharmacist or the patient’s 
primary care clinician. 
 
2) As described in Section 4.3, dyads who do not opt out (and dyads who opt in) will be 
called by the project assistant to assess interest and schedule the pharmacist consult 
approximately 14 days after mailing the intervention materials. 
 
Intervention group: 
3) The project assistant will schedule the telehealth visit with the clinical pharmacist to 
occur within the next 4 weeks. 
 
4) After scheduling the pharmacist consult, the project assistant will offer care partner the 
option of completing the secondary outcome measure, the Family Caregiver Medication 
Administration Hassles Scale (FCMAHS). They will obtain verbal consent for the 
FCMAHS when administering it over the phone (see script). If the care partner does not 
wish to complete the FCMAHS over the phone during the scheduling phone call, the 
project assistant will offer to call back before the pharmacist visit (up to 28 days) or to later 
e-mail the care partner a link to an electronic version. The FCMAHS will be administered 
again 3 months after the enrollment phone call. 
 
5) Using comprehensive medication management (CMM) as a foundation, the pharmacist 
will call the patient-care partner dyad to assess for medication-related problems, such as 
issues with adherence, potential adverse effects and caregiver strain related to medication 
management. Clinical pharmacists are already embedded in both pilot clinics and 
throughout their parent healthcare systems, and are conducting CMM phone calls 
with patients. The clinical pharmacists in ALIGN have considerable experience doing 
medication reviews with older adults, patients with dementia and care partners. They 
will use a script that was closely adapted from templates that are currently being used 
by embedded clinical pharmacists in both healthcare systems. The pharmacists will use 
these guiding questions to elicit the dyad’s goals and priorities for the patient’s health in 

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order to align medications with goals of care (see attached template). We anticipate that the 
intervention phone call will take up to 1 hour. 
 
6) The pharmacist will then develop an evidence-based deprescribing communication, 
which will be routed to the PCP via the EHR using a standardized template (see attached). 
The pharmacist will contact the PCP as per usual clinical practice. The template will 
encourage the PCP to respond to the pharmacist either to accept the recommendations, to 
ask questions or to raise concerns. 
 
7) With the PCP’s approval, the pharmacist will call the dyad to implement the 
recommendations and document the changes in the EHR. An updated medication list will 
be mailed to the dyad. All decisions about discontinuation or continuation of medications 
will be made by the PCP and patient/ care partner. 
 
Delayed intervention group: 
Steps 1-2 will be identical to the intervention group. For participants randomized to the 
delayed intervention control group, the project assistant will schedule the pharmacist 
consult in approximately 3 months. 
 
After scheduling the pharmacist consult, project assistants will offer care partners in the 
delayed intervention group the option of completing the Family Caregiver Medication 
Administration Hassles Scale (FCMAHS). They will obtain verbal consent for the 
FCMAHS when administering it over the phone (see script). If the care partner cannot 
complete the FCMAHS over the phone during the scheduling phone call, the project 
assistant will offer to call back before the pharmacist visit (up to 28 days) or to later e-mail 
them a link to an electronic version. The FCMAHS will be administered again 3 months 
after the enrollment phone call. 
 
The project assistant will call the care partner again closer to the date of the pharmacist 
visit to remind them of the appointment. Steps 4-6 will be identical the intervention group 
but will occur 3-4 months after study enrollment. 
 
5.2 Handling of Study Interventions  
Due to the nature of the intervention, participants, pharmacists and PCPs cannot be 
masked. Project assistants will enter data into a REDCap database so that the researchers 
can analyze it without having access to group assignment. 
We will use multiple strategies to implement and measure fidelity in the study: 
Training Fidelity: Training materials for pharmacists will consist of guiding questions to 
help elicit patient/care partner health outcome goals, communicate about deprescribing 
with patients and care partners, and align medications with goals of care, and an Epic 
template for communicating deprescribing recommendations to the PCP (attached). This 
document was developed in collaboration with 3 clinical pharmacists at JHCP and 
KPCO and closely adapted from the approach and language they use when calling 
patients with dementia and their care partners on the phone. 
Intervention Fidelity: 

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1. Intervention adherence will be measured using a REDCap survey, which will enable us 
to monitor in real time and address issues immediately. The survey will be sent to 
pharmacists electronically together with the appointment information for each 
intervention telehealth visit. It will consist of a checklist that pharmacists will use to 
report which intervention elements occurred, any protocol deviations beyond their control 
(eg, dyads canceling a meeting), and the time required to complete each task in the 
intervention. We will calculate intervention fidelity as the proportion of dyads who 
participate in 2 of 2 pharmacist phone calls based on documented status reports. 
2. We will calculate the proportion of eligible dyads that opt out of the intervention, and 
the proportion of pharmacist messages to the PCP that receive an acknowledgement or 
response (captured in the EHR). 
3. To evaluate the content of the intervention being delivered, we will analyze a random 
sample of audiorecorded phone calls between pharmacists and dyads. We will use a 
fidelity checklist to determine the extent to which the pharmacists deliver the key 
elements of the intervention: 1) Assessing for medication-related problems (adherence 
issues, potential adverse effects, care partner strain); 2) Eliciting the dyad’s key health 
outcome goals for the patient’s health; and 3) Aligning medications with goals of care. 
We will also review the pharmacist-physician communication in the EHR to calculate the 
proportion of templates that are properly completed. This will enable us to provide 
feedback to the pharmacists in real time to address barriers to achieving high fidelity. 
5.3 Concomitant Interventions 
We do not have any concomitant interventions. All medical care will proceed in 
according to the decisions of the patient, care partner and primary care provider.   
5.4 Adherence Assessment  
There is no planned adherence assessment given the nature of the intervention. 
6 
STUDY PROCEDURES 
6.1 
Schedule of Evaluations 
Assessment 
Identify 
eligible 
population 
Baseline: 
scheduling phone 
call (Day 0 + 28 
days) 
3 months post 
enrollment (Day 
90 + 45 days) 
Inclusion/Exclusion Criteria  
X 
 
  
Patient demographics and 
diagnoses 
X 
  
  
Care partner demographics 
 
X 
 
Chronic medication count 
 
X 
 X 
Patient-level Medication Regimen 
Complexity Index (pMRCI) 
 
X 
 X 
Family Caregiver Medication 
Administration Hassles Scale 
(FCMAHS) 
 
X 
 X 

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Feasibility measures 
 
 
 
Proportion of dyads that opt out 
X 
 
 
Proportion of participants with data 
elements available to calculate 
pMRCI 
 
 
 
 
 
Throughout intervention 
Response rate and completion time 
for FCMAHS 
 
X 
X 
Proportion of pharmacist messages 
to PCP that receive 
acknowledgement or response 
 
 
 
 
Throughout intervention  
Number of contacts between 
pharmacist and PCP and between 
pharmacist and dyad 
 
 
 
 
 
Throughout intervention  
Time required by pharmacist to 
complete intervention 
 
 
X 
Type of recommendations made by 
pharmacist, acceptance rates for 
recommendations 
 
 
X 
Fidelity measures 
 
 
 
Proportion of intervention elements 
successfully completed by 
pharmacist 
 
 
X 

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6.2 Description of Evaluations  
Pilot study evaluations will consist of: 1) assessing baseline eligibility criteria; 2) assessing the 
intervention for feasibility and acceptability; 3) assessing outcomes of the future pragmatic trial 
for measurement feasibility; and 4) assessing intervention fidelity. 
Definitions of the data elements and sources are itemized below. Unless otherwise mentioned, all 
data at JHCP will be extracted from the EHR. All data at KPCO will be extracted from the 
KPCO Virtual Data Warehouse, a quality controlled, common data model that includes data 
from multiple KPCO data sources covering enrollment, utilization, pharmacy, demographics, 
mortality, problem list diagnoses, and social history, among other domains.36 
Inclusion/ exclusion criteria: As previously described (section 4.1). Data elements will include 
age, diagnosis codes, current medications on the date of enrollment (see definition “chronic 
medication count” below). Chronic diagnoses will be from a list of 86 chronic conditions 
itemized in the Multiple Chronic Conditions Chartbook.37 We have developed a method of 
counting chronic medications that uses a consensus-based list of Generic Product Index (GPI) 
categories to be included for polypharmacy estimates.  
Patient demographics and diagnoses: Age, gender, and race/ethnicity will be collected from 
the EHR. ICD-10 codes will be used to identify diagnoses from visit billing codes, hospital and 
emergency department claims diagnoses, and problem list diagnoses. 
Care partner demographics: Age, gender, race/ethnicity, relationship to patient, and health 
literacy (“How confident are you filling out medical forms by yourself?”) will be asked by the 
project assistant during the scheduling phone call. 
Chronic medication count: We will use the approach refined in Optimize to define chronic 
medication use as any prescription medication for which the patient had at least a 28-day supply 
on the assessment date.32 We selected a 28-day supply (rather than a supply for a longer time 
period) because some medications (such as opioid medications) are mostly dispensed in 28-day 
supplies. Chronic medications exclude the following domains identified by 2-digit GPI codes: 
vaccines, toxoids, allergenic extracts, oxytocics, local anesthetics—parenteral, general 
anesthetics, antiseptics and disinfectants, antidotes, diagnostic products, chemicals, and medical 

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devices. We are examining different methods of identifying chronic medications in the Johns 
Hopkins EHR. 
Patient-level Medication Regimen Complexity Index (pMRCI): Scores are derived from 
weighted values of regimen components (eg, dosage formulations, frequencies, and specific 
instructions).2 We will adapt an algorithm developed and tested by Dr. Boyd’s team to extract 
pre-specified variables from the EHR and calculate pMRCI scores in REDCap.20 The data 
analytics teams at both institutions will determine the steps necessary to further adapt the pMRCI 
for use within the existing EHR systems. In doing so, we will build on methods developed by 
JHU researcher, Dr. Hadi Kharazzi, who automated the pMRCI within an EHR and calculated 
pMRCI scores for 70,000 patients.3,38 Similar EHR adaptations of the pMRCI by other 
researchers will also serve as a foundation for our work.109 
Family Caregiver Medication Administration Hassles Scale (FCMAHS): Collected from 
family care partners at baseline by the project assistant and again at approximately 3 months 
after enrollment. For care partners who are unable to complete the FCMAHS by phone, we will 
examine the feasibility of administering it electronically by e-mailing them a link. See attached 
patient intervention materials. Project assistants will record administration time when the 
FCMAHS is administered over the phone. Care partners will be asked to record administration 
time when it is self-administered electronically. 
Feasibility measures: 
Proportion of dyads that opt out: Will be assessed from the patient recruitment/ tracking log 
completed by project assistants. 
Proportion of participants with data elements available to calculate pMRCI: Will be 
calculated based on the algorithm developed above. 
Response rate and completion time for FCMAHS: Completion time will be collected by 
project assistants when they administer the FCMAHS on the telephone, and via self-report when 
it is administered electronically. The response rate using both modes of administration will be 
assessed. 

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Proportion of pharmacist messages to PCP that receive an acknowledgement or response; 
number of contacts between pharmacist and dyad; number of contacts between pharmacist 
and PCP: Project assistants will extract these data from the EHR at 3 months. 
Time required by pharmacist to complete the intervention: Pharmacists will be asked to 
complete a REDCap survey. The link will be sent to them via e-mail to complete after each 
patient-care partner telehealth visit. 
Fidelity measures: 
Proportion of intervention elements successfully completed by pharmacist: A sample of 
audiorecorded telehealth visits between pharmacists and dyads will be scored by project 
assistants using a fidelity checklist. 
6.2.1 Screening Evaluation 
Consenting Procedure 
As described in section 4.3, initial eligibility will be determined based on available 
clinical and claims data under a waiver of HIPAA Authorization. 
Project assistants will serve as scheduling coordinators for the pilot study. Dyads who do 
not opt out (and those who opt in) will be called by the project assistant approximately 14 
days after the study materials are mailed. Using the same approach that clinic staff use to 
call patients with dementia on the phone and identify their care partners during the course 
of clinical care, the project assistant will use an IRB-approved script (attached) to 
describe the pharmacist consult and assess interest. If the patient declines to identify a 
care partner and does not have a care partner listed in the EHR, the dyad will not be 
eligible. This phone call is described in section 4.3. 
Participation in the pharmacist consult is not contingent on completion of the secondary 
outcome measure, FCMAHS. After scheduling the pharmacist consult, project assistants 
will offer care partners the option of completing the FCMAHS. They will obtain verbal 
consent for the FCMAHS when administering it over the phone (see script). If the care 
partner cannot complete the FCMAHS over the phone during the scheduling phone call, 

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the project assistant will offer to call back before the pharmacist visit (up to 28 days) or 
to later e-mail them a link to an electronic version. 
6.2.2 Enrollment, Baseline, and/or Randomization 
Enrollment 
Project assistants will mail study materials with opt-out provisions to the homes of 60 
patients (30 at each site). Dyads who do not opt out (or who opt in) will be called by the 
project assistant approximately 14 days later to describe the pharmacist consult and 
assess interest. Enrollment will be defined as the date of this phone call. 
Baseline Assessments 
The baseline point will be defined as the date of the enrollment phone call, whether or not 
dyads are randomized to the intervention or delayed intervention control group. 
Randomization 
Dyads who do not opt out (or who opt in) will be randomized to the immediate or 
delayed intervention group prior to the enrollment/scheduling phone call using computer-
generated random numbers. The intervention group will be scheduled to have the 
pharmacist telehealth visit immediately (within 4 weeks) after enrollment. The delayed 
intervention group will receive the pharmacist-led component 3-4 months after 
enrollment. For dyads randomized to the delayed group, the project assistant will say, “I 
will call you back in about 3 months to remind you of the call with the pharmacist.” 
6.2.3 Follow-up Visits 
As described in the Evaluations Table, dates for follow up measurements will be relative 
to baseline/enrollment. This is defined as the date of the enrollment phone call. Data will 
be extracted from the EHR and VDW as described above. There will be one follow up 
call/e-mail to administer the FCMAHS 3 months after enrollment for care partners who 
have opted to complete it. 
6.2.4 Completion/Final Evaluation 
As described above, there will be one follow up phone call/e-mail to administer the 
FCMAHS 3 months after enrollment. Care partners who do not wish to complete the 
FCMAHS by phone will be offered an electronic version and will be e-mailed a link. All 

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other data will be extracted from the EHR and VDW. If participants discontinue the 
intervention early (eg, by opting out during the pharmacist phone call), we will still 
extract their data from the EHR and VDW but will not offer the FCMAHS. 
 
7 
SAFETY ASSESSMENTS  
7.1 Specification of Safety Parameters 
Comprehensive medication management is already part of the KPCO and JHCP standard of 
care, and any changes in medication regimens will be made by the pharmacist, PCP and 
patient/care partner through shared decision making. This is consistent with usual care. 
There is no requirement for patients, care partners, or PCPs to engage in discussions about 
medication optimization upon receipt of intervention materials. The intervention is 
educational and designed to offer care partners the opportunity to discuss optimal 
medication use. The intervention does not in itself alter patient medication prescribing. 
There is still the potential for adverse effects or unintended consequences from the 
intervention including: inadvertent stopping of necessary medications by patients or care 
partners and associated effects of those potential discontinuations, longer patient-PCP visit 
encounters devoted to medication discussions or clarifying misunderstandings, and lower 
satisfaction of patients/ care partners about medication management. If PCPs and patients 
or care partners elect to discontinue specific medications, there is the potential for recurrent 
symptoms, adverse drug withdrawal events, and anxiety about the deprescribing process. 
Potential risks can be minimized or prevented by using a patient-centered, pharmacist-led, 
structured deprescribing process, such as ALIGN. The intervention brochure and template 
for the pharmacist visit will include language that instructs the dyad not to stop any 
medications without talking to the pharmacist or PCP. 
7.2 Methods and Timing for Assessing, Recording, and Analyzing Safety Parameters 
Throughout the study period any physician, pharmacist or health care staff member will be 
able to report concerns about a safety issue that arises via a dedicated, monitored study 
email address and phone number as well as via contacting the PIs at each site (Green at 
Johns Hopkins; Boxer at KPCO). In addition, during the pilot study, study staff will review 
medical records of all patient participants who have ED visits, hospitalizations, or 

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observation admissions to assess whether any emergency services were likely to have 
resulted from medication discontinuation. We will also assess whether emergency services 
were likely to have resulted from adverse effects of non-discontinued medications.  
Information on use of emergency services will inform the development of safety 
procedures for the future pragmatic trial. 
7.3 Adverse Events and Serious Adverse Events  
We define adverse events as any new negative diagnosis or symptom during the study 
period that results in seeking medical care. Serious adverse events will be those requiring 
the use of emergency hospital services. In the ADRD-MCC population we anticipate a 
baseline hospitalization rate of approximately 30% due to morbidity burden. As described 
above, we will review medical records of all patients who use emergency hospital services 
during the pilot study period and use this information to inform adverse event monitoring 
for the future pragmatic trial. Each month, project assistants will also review the list of 
enrolled patients who have received intervention materials for any uses of hospital 
emergency services. These cases will be targeted for record review by the site PI. 
7.3.1 Reporting Procedures 
We will provide contact information for the JHU and KPCO Project Managers (TBD) and the 
JHU and KPCO PIs (Green and Boxer) to all clinical pharmacists and PCPs at the pilot study 
sites and ask them to report any perceived adverse events resulting from the trial.  
7.3.2 Follow-up for Adverse Events 
For each report, the JHU and KPCO PI will contact the clinical pharmacist and/or PCP to review 
the potential concern. All potential concerns will be noted and discussed with the Safety Officer 
as part of reviewing pilot study results and will be reported to the IRB. Duration of follow-up 
will extend until discharge from the hospital for hospitalizations or completion of any acute care 
services associated with an adverse event.     
7.4 Safety Monitoring 
An independent Safety Officer will be appointed to serve as the data safety monitor. 

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8 
INTERVENTION DISCONTINUATION  
For this pilot study of a pragmatic intervention, we do not have intervention discontinuation 
criteria.  
9 
STATISTICAL CONSIDERATIONS  
9.1 General Design Issues  
This is a pilot of a future pragmatic, cluster randomized trial. The pilot aims to assess feasibility 
and acceptability of the intervention. There are no statistical hypotheses. Our conceptual 
hypotheses are that the pilot intervention will be acceptable to patients and clinicians and feasible 
to conduct. In Aims 1 and 2a, our focus will be on descriptive statistics (counts and proportions). 
In Aim 2b, the primary analyses will rely on intention-to-treat analysis to present the 
comparative results of the trial. All events following randomization will be counted. Analyses 
using post-randomization data (eg, intervention compliance) will be discussed as secondary 
analyses. We will distinguish non-compliance with intervention from non-compliance with 
follow-up (ie, missing data). 
For our primary outcome measure, pMRCI, we will first perform correlation analyses between 
chronic medication count and pMRCI scores at baseline. We will analyze changes in pMRCI 
before and after intervention and evaluate the impact of intervention assignment on the change 
scores using linear regression. The cluster by health system effect will be accounted for in the 
calculation of robust standard errors. Given the pilot nature of this trial, we will focus on 
estimates of precision in detecting treatment effects that will aid in the planning of a larger, 
sufficiently powered ePCT. We will also explore treatment effects by gender, age strata and 
race/ethnicity, again focusing on estimates of with-stratum variabilities instead of statistical 
significance. We will use multiple imputation to account for missing data. 
For our secondary outcome measure, FCMAHS, we will first construct summary scores of the 
FCMAHS subscales using principal components analysis. We will then analyze changes in 
FCMAHS before and after intervention and evaluate the impact of intervention assignment on 
the change scores using linear regression.  

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9.2 Sample Size and Randomization 
Sample size calculation: With an attrition rate of 10%, a sample size of 30 dyads per arm will 
produce a 2-sided 95% confidence interval with a width equal to 0.4 standard deviation (SD) when 
the SD of the study outcome (ie, based on normalized score) is 1. 
9.2.1 
Treatment Assignment Procedures 
Enrolled dyads will be randomized prior to the scheduling phone call using computer-generated 
random numbers to either the intervention group or the delayed intervention group. The 
intervention group will then be scheduled to have the pharmacist telehealth visit immediately 
(within 4 weeks) after enrollment. The delayed intervention group will be scheduled to receive 
the pharmacist-led component 3-4 months after enrollment. For dyads randomized to the delayed 
group, the project assistant will say, “I will call you in about 3 months to remind you of your 
appointment with the pharmacist.” Due to the nature of the intervention, participants, 
pharmacists and PCPs cannot be masked. Project assistants will enter data into a REDCap 
database so that the researchers can analyze it without having access to group assignment. 
9.3 Interim analyses and Stopping Rules 
There are no interim analysis planned or stopping rules.  
9.4 Outcomes  
Aim 1 is to assess the feasibility and acceptability of ALIGN in two different health care 
systems, to guide the subsequent evaluation of the effectiveness of the intervention in an 
embedded pragmatic trial. Data to measure feasibility will be acquired from the EHR, REDCap 
surveys completed by the pharmacists, and audiorecordings of pharmacist phone calls with care 
partners. We will collect the following measures: 
• Proportion of dyads that opt out of the intervention; 
• Proportion of pharmacist messages to the PCP that receive an acknowledgement or response; 
• Number of contacts between pharmacist and PCP and between pharmacist and dyad; 
• Time required by the pharmacist to complete the intervention; 

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• Proportion of intervention elements, including pharmacist phone calls, successfully completed. 
To evaluate intervention acceptability, we will track the following: 
• Type of recommendations made by the pharmacist and acceptance rates for those 
recommendations (project assistants will review the EHR for notation of patient/care partner and 
PCP acceptance). The pharmacists will document each phone call with the dyad in the EHR and 
will record whether the patient and care partner have agreed to the recommendations. The 
template for the pharmacist message to the PCP (attached) includes a routing comment that asks 
the PCP to respond via secure chat or staff message – either to indicate acceptance or ask 
questions about the recommendations. 
Aim 2 is to determine the feasibility of the primary and secondary outcome measures for the 
subsequent ePCT: 
Aim 2a is to determine the feasibility of measuring the primary outcome, the patient-level 
Medication Regimen Complexity Index (pMRCI)1-4, within the existing EHR systems, and to 
compare it with a more pragmatic measure, chronic medication count, as the primary outcome 
measure for the ePCT. 
Aim 2b is to determine the feasibility of measuring the secondary outcome, the Family Caregiver 
Medication Administration Hassles Scale (FCMAHS)5, a caregiver-reported outcome measure. 
As described in Section 6.2, we will develop the procedures for collecting the pMRCI and 
FCMAHS. In Aim 2a, feasibility will be measured as follows: 
• Proportion of participants with data elements available vs. unavailable to calculate the pMRCI. 
To compare it with chronic medication count as the primary outcome measure for the ePCT, we 
will measure: 
• Change in chronic medication count; and 
• Change in pMRCI from baseline to 3 months. 

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Chronic medication count will be obtained from the EHR using algorithms refined in 
OPTIMIZE. 
In Aim 2b, feasibility will be measured as follows: 
• Response rate and completion time for the FCMAHS using each mode of administration. 
• Change in FCMAHS from baseline to 3 months. 
9.5 Data Analyses 
In Aims 1 and 2a, our focus will be on descriptive statistics (counts and proportions). In Aim 2b, 
the primary analyses will rely on intention-to-treat analysis to present the comparative results of 
the trial. All events following randomization will be counted. Analyses using post-randomization 
data (eg, intervention compliance) will be discussed as secondary analyses. We will distinguish 
non-compliance with intervention from non-compliance with follow-up (ie, missing data). 
 
For our primary outcome measure, pMRCI, we will first perform correlation analyses between 
chronic medication count and pMRCI scores at baseline. We will analyze changes in pMRCI 
before and after intervention and evaluate the impact of intervention assignment on the change 
scores using linear regression. The cluster by health system effect will be accounted for in the 
calculation of robust standard errors. Given the pilot nature of this trial, we will focus on estimates 
of precision in detecting treatment effects that will aid in the planning of a larger, sufficiently 
powered ePCT. We will also explore treatment effects by gender, age strata and race/ethnicity, 
again focusing on estimates of with-stratum variabilities instead of statistical significance. We will 
use multiple imputation to account for missing data. 
 
For our secondary outcome measure, FCMAHS, we will first construct summary scores of the 
FCMAHS subscales using principal components analysis. We will then analyze changes in 
FCMAHS before and after intervention and evaluate the impact of intervention assignment on the 
change scores using linear regression.  

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10 
DATA COLLECTION AND QUALITY ASSURANCE 
10.1 Data Collection Forms 
The majority of the study data will be collected from the Johns Hopkins EHR and the KPCO 
VDW as described in Evaluation Section 6. Demographic, health and medication data will be 
automatically merged into REDCap on enrolled patients or will be manually entered by the 
project assistant (there will be some site-specific differences). Patient interactions will be 
documented in the EHR and data from those interactions will be entered into REDCap for 
descriptive analyses. 
Responses from care partners to the FCMAHS will be collected by a project assistant on the 
telephone or electronically (self-administered) via a link sent through e-mail. 
Intervention fidelity measures will be collected from clinical pharmacists via a REDCap survey 
that will be e-mailed to them, and from audiorecordings of telehealth visits between pharmacists 
and patient-care partner dyads.  
10.2 Data Management  
Unless otherwise mentioned, all data will be extracted from the Johns Hopkins EHR and the 
KPCO Virtual Data Warehouse, a quality controlled, research common data model that includes 
data from multiple KPCO data sources and includes the following domains: Pharmacy data, 
demographics, problem list diagnoses, and social history. Two identical instances of the 
REDCap database will be used for data collection – one at each site. Data from VDW will be 
pulled directly into REDCap; data from EHR will be manually entered into REDCap, 
downloaded and cleaned; data from pharmacist fidelity measures will be manually entered. 

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10.3 Quality Assurance  
Multiple strategies will be used to ensure accuracy of the data, including (but not limited to) the 
following: 
• The REDCap database will incorporate field validation (eg, format type, valid range) 
whenever possible to increase accuracy of data entry. 
• After every 3rd dyad is enrolled, the project assistants will download data from the REDCap 
database into Excel or SAS to assess for missingness. 
• We will use double input for any key variables that are manually entered. These variables 
will be re-entered into an empty database by someone other than the individual who 
completed the first data entry. The reliability of the entered data will then be assessed by 
comparing the first and second round of data entry so that any errors can be identified and 
corrected. 
11 
PARTICIPANT RIGHTS AND CONFIDENTIALITY  
11.1 Institutional Review Board (IRB) Review 
This protocol and patient/care partner-facing materials will be reviewed and approved by the 
IRB responsible for oversight of the study.  
11.2 Informed Consent Forms 
This pragmatic intervention adheres to standard clinical practice for older adults with 
dementia. The intervention is delivered by clinical pharmacists who are already integrated 
in primary care clinics at JHCP and KPCO and have considerable experience doing 
medication reviews with older adults, patients with dementia and care partners. The 
pharmacists are trained in complex geriatric medication management and routinely provide 
comprehensive medication management to Medicare beneficiaries. ALIGN provides structured 
templates for these existing comprehensive medication management phone calls, to focus them 
around dementia and to align medications with goals of care. 
 

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Options for pragmatic trial consent range from 1) full individual level recruitment and written 
informed consent, to 2) recruitment information sent to all eligible candidates with an ‘opt out’ 
clause, to 3) general information on the intervention provided to all eligible patients with an 
option for further inquiry. We request a waiver of informed consent (option 2) as an acceptable 
approach for the intervention, audio-recording of the pharmacist visit, and data collection from 
the EHR. This is based on the following factors: 
 
(i) The research involves no more than minimal risk to the subjects. 
- Any changes in medication regimens will be made by the pharmacist, PCP and patient/care 
partner through shared decision making. This is consistent with usual care. 
- Comprehensive medication management is already part of the KPCO and JHCP standard of 
care. 
- There is no requirement for patients/ care partners or PCPs to engage in discussions about 
medication optimization upon receipt of intervention materials. 
- Potential risks of deprescribing can be minimized or prevented by using a patient-centered, 
pharmacist-led, structured process, such as ALIGN. Any medication believed to have increased 
potential for physiologic withdrawal, such as benzodiazepines, will undergo a prescribed drug 
taper under the clinical pharmacist’s supervision according to standard clinical procedure. In 
addition, patients and care partners will be told that they can contact the pharmacist with any 
concerns about drug withdrawal effects or medical condition exacerbation. Further, medications 
can be restarted or increased at any time should concerns arise on the part of the patient, care 
partner or PCP. The intervention brochure and template for the pharmacist visit will include 
language that instructs the dyad not to stop any medications without talking to the pharmacist or 
PCP. 
 
(ii)  The research could not practicably be carried out without the requested waiver or alteration. 
Requiring full individual level recruitment and written informed consent would be highly 
burdensome to the target population, older adults with dementia, and would outweigh the 
minimal risks of the intervention itself. The standard procedures for assessing capacity, 
identifying a legally authorized representative and obtaining surrogate consent would likely 
cause many patients to opt out or become ineligible, which would compromise the scientific 

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validity of any evaluation of the intervention. Even if we consented care partners, the research 
cannot practicably be carried out without enrolling patients and care partners as dyads. 
 
(iii)  If the research involves using identifiable private information or identifiable biospecimens, 
the research could not practicably be carried out without using such information or biospecimens 
in an identifiable format: 
The intervention is pragmatic and designed to test a scalable process that can be implemented 
across multiple clinics to improve care for PLWD. For this reason, our initial eligibility criteria 
and our primary outcome, the patient-level Medication Regimen Complexity Index, are derived 
from the EHR data under a waiver of HIPAA Authorization. The data need to be identifiable in 
order to recruit individual patients and care partners and to link subject data over time. 
 
(iv)  The waiver or alteration will not adversely affect the rights and welfare of the subjects: 
Intervention materials will include an informational cover letter that will indicate that dyads may 
wish to discuss medication discontinuation with the pharmacist but are under no obligation to do 
so. It will explain that because this is a new clinical program, appointments are limited and the 
pharmacist consult may be scheduled up to 3 months out. This is consistent with usual care, in 
which non-urgent appointments are typically made at least 3 months out. 
 
(v) Whenever appropriate, the subjects or legally authorized representatives will be provided 
with additional pertinent information after participation. 
We do not currently have plans to provide study subjects with information after the study ends. 
However, we could provide a summary of the study and its main findings to the individual 
clinics and they may distribute it through patient newsletters if they wish. We may also share the 
key findings with both health care systems and they may disseminate the information to their 
patients as they see fit. 
 
For Aim 2b, we will obtain verbal informed consent to administer the Family Caregiver 
Medication Administration Hassles Scale (FCMAHS). After scheduling the pharmacist consult 
with interested care partners, project assistants will offer the FCMAHS. They will explain that 
the pharmacist consult is not contingent on completion of the questionnaire. If the care 

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partner is interested in completing the FCMAHS, the project assistant will obtain verbal 
informed consent for either the telephone or web version, according to the care partner’s 
preference (see attached script). The project assistant will offer to administer the FCMAHS as 
part of the same phone call or to call back before the pharmacist visit (up to 28 days later). They 
will tell care partners that they will call back to administer the FCMAHS once more about 3 
months after enrollment, defined as the date of the scheduling phone call. 
 
11.3 Participant Confidentiality  
Data Management 
EHR data: Eligible patient/ care partner participants will be identified by the data analyst at each 
site using EHR data under a waiver of HIPAA Authorization. The study staff have successfully 
completed HIPAA and human subjects research trainings. We will comply with our institutions’ 
policies regarding data sharing, data protection, and data file destruction at the earliest date. 
For all sources of data, names and other identifiers will be kept in REDCap, a secure, HIPAA 
complaint web-based application for clinical data collection with secure authentication options 
for multi-site projects. Statistical analyses will be performed on de-identified data; participants 
will never be individually named. All computerized data will be kept on secured computers or 
networks at KPCO and Johns Hopkins. Once the data are cleaned and verified, there will be no 
further changes to the dataset. We will merge our de-identified data sets and Johns Hopkins will 
be responsible for analysis. These data will be accessible only to the research team, using 
confidential usernames and passwords. 
11.4 Study Discontinuation  
The study may be discontinued at any time by the IRB, the NIA, the OHRP, the FDA, or other 
government agencies as part of their duties to ensure that research participants are protected.  
12 
ETHICAL CONSIDERATIONS 
All research conducted at Johns Hopkins and KPCO complies with the Department of Health and 
Human Services requirements for safeguarding the rights and welfare of human subjects, 
regardless of the source of funding. Johns Hopkins and KPCO each have approved Federal-wide 

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Assurance Compliance filed with the Office for Human Research Protections (OHRP). Both 
institutions have agreed to cede to Advarra for IRB oversight and study approval. Advarra will 
also serve as the Research Privacy Board, and ensures that the privacy and confidentiality or 
protected health information is maintained, as required by the Health Insurance Portability and 
Accountability Act (HIPAA). 
13 
COMMITTEES 
NIA Program Officers: 
Partha Bhattacharyya, PhD 
National Institute on Aging 
Division of Behavioral and Social Research 
Gateway Building 
  
7201 Wisconsin Avenue    
Bethesda MD 20892-9205 
  
Phone: (301) 496-3131 
Fax: (301) 402-0051 
bhattacharyyap@mail.nih.gov 
Stakeholder Panel: ALIGN builds off OPTIMIZE, our team’s ongoing cluster-randomized 
deprescribing pragmatic trial at KPCO. OPTIMIZE has two stakeholder panels comprised of 
patients/care partners and clinicians. We will extend these panels and develop similar ones at 
JHCP to provide insight on study design, intervention materials, implementation, results 
interpretation and dissemination. Their contributions will ensure that the intervention is relevant 
to patients and care partners, generalizable across health systems and culturally-tailored to 
promote health equity. Stakeholder panels will meet quarterly by teleconference. Dr. Green will 
lead these efforts.  
14 
PUBLICATION OF RESEARCH FINDINGS 
Publication of the evaluation of the pilot study will be determined by the study team. Our 
primary purpose is to inform a subsequent cluster randomized controlled trial.  Publication of the 
results of this pilot study will be governed by the policies and procedures developed by the study 
team.   
15 
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16 
SUPPLEMENTS/APPENDICES 
Items in this list are not included in this document, but are external documents included in the 
application. 
A. Patient/care partner intervention materials 
 
a. Cover letter for intervention materials 
 
b. Patient/care partner brochure 
c. Web-based Family Caregiver Medication Administration Hassles Scale 
d. Template for pharmacist telehealth visit and pharmacist-PCP communication 
B. Recruitment materials 
a. Telephone script for scheduling phone call 
 
b. Oral consent script for FCMAHS