A Universal Medication Schedule to Promote Adherence to Complex Drug Regimens
Phase: NA
Conditions: Adherence
Sponsor: Northwestern University

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PROTOCOL TITLE: 
A Universal Medication Schedule to Promote Adherence to Complex Drug Regimens  
 
PRINCIPAL INVESTIGATOR: 
Michael Wolf, PhD, MPH 
Department of Medicine, Northwestern University  
750 N. Lakeshore Drive, 10th Floor 
Chicago, IL 60611 
(312) 503-5592 
mswolf@northwestern.edu  
 
VERSION NUMBER: 
Version 19 
 
VERSION DATE: 
 
May 27, 2021 
 
 
 
 
 
 
 
 

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Table of Contents 
 
Objectives ............................................................................................................................ 3 
 
Background .......................................................................................................................... 3 
 
Inclusion and Exclusion Criteria .......................................................................................... 7 
 
Study-Wide Number of Subjects ......................................................................................... 8 
 
Study-Wide Recruitment Methods ...................................................................................... 8 
 
Multi-Site Research ............................................................................................................. 9 
 
Study Timelines ................................................................................................................... 9 
 
Study Endpoints ................................................................................................................. 10 
 
Procedures Involved........................................................................................................... 12 
 Data and Specimen Banking .............................................................................................. 20 
 Data and Specimen Management....................................................................................... 22 
 Provisions to Monitor the Data to Ensure the Safety of Subjects ...................................... 26 
 Withdrawal of Subjects ...................................................................................................... 26 
 Risks to Subjects ................................................................................................................ 26 
 Potential Benefits to Subjects ............................................................................................ 26 
 Vulnerable Populations ...................................................................................................... 27 
 Community-Based Participatory Research ........................................................................ 27 
 Sharing of Results with Subjects ....................................................................................... 27 
 Setting ................................................................................................................................ 27 
 Resources Available........................................................................................................... 27 
 Prior Approvals .................................................................................................................. 28 
 Recruitment Methods ......................................................................................................... 28 
 Local Number of Subjects ................................................................................................. 31 
 Confidentiality ................................................................................................................... 31 
 Provisions to Protect the Privacy Interests of Subjects ...................................................... 31 
 Compensation for Research-Related Injury ....................................................................... 32 
 Economic Burden to Subjects ............................................................................................ 32 
 Consent Process ................................................................................................................. 32 
 Process to Document Consent in Writing .......................................................................... 34 
 Drugs or Devices................................................................................................................ 34 
 

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Objectives 
1.1 Specific Aims: 
1. 
Compare the effectiveness of the UMS EHR tools, with or without 
SMS and/or Portal interventions. 
2. 
Evaluate the ‘fidelity’ (reliability) of each strategy and explore patient, 
staff, physician, and health system factors influencing the delivery of 
the interventions, alone and in combination  
3. 
Assess the costs required to deliver each of the interventions from a 
health system perspective  
1.2 Hypotheses:  
H1-2. Compared to enhanced usual care, patients in the SMS only arm [H1] and 
in the Portal only arm [H2] will have greater adherence to their Rx 
regimen. 
H3. Compared to SMS only arm, patients receiving both the SMS and Portal, 
will have greater adherence to their Rx regimen [H3]. 
H4. Compared to the Portal only, patients receiving both the SMS and Portal will 
demonstrate greater adherence to their Rx regimen [H4]. 
 
 
Background 
2.1        Disease Background 
Effective, practical, and scalable approaches are needed to help patients safely use complex 
Rx regimens.1-3  We will leverage available technologies and test strategies to impart the 
Universal Medication Schedule (UMS) in primary care to help patients understand, 
consolidate, safely use, and adhere to their medications. 
 
The Challenge of Managing Complex Drug Regimens.  
In ambulatory care, patients assume primary responsibility for safely and appropriately 
administering Rx regimens.1 Yet the expectations placed on patients by the healthcare 
system for medication-related tasks are considerable. In order for patients to gain the 
benefits of drug therapy while minimizing risks of adverse drug events (ADEs), they must: 
1) have a functional understanding of medications and their proper dosing, 2) consolidate 
their regimen to the most efficient daily schedule, 3) problem-solve around regimen use as 
changes occur, and 4) continue the behaviors over time. Studies have repeatedly 
documented that patients have problems performing these routine tasks.4-7 This is alarming, 
as adults are being prescribed increasingly complex medication regimens.8 Over the past 
decade, the percentage of Americans taking ≥ 5 Rx drugs daily has doubled to nearly 40% 
of older adults.8 While long-term adherence is essential to reap health benefits, all forms 
of non-adherence - failure to fill new prescriptions, incomplete use, and premature 
discontinuation - are common.9-14  Non-adherence has been linked to greater morbidity and 
mortality from chronic conditions. Complex drug regimens also raise the risk for errors 
and ADEs, many of which are preventable or ameliorable.15-20 Nearly 10 million outpatient 
physician visits and 4 million emergency department admissions are attributed to ADEs or 
side effects annually.21 These are more likely to occur in primary vs. specialty care, among 
older patients and those with multi-morbidity.21-23  
 

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 Vulnerable Populations. Older age poses a significant risk for medication safety and 
adherence concerns for obvious reasons. The prevalence of multi-morbidity increases with 
age; approximately 17% of younger adults ages 20-39 live with 2 or more chronic 
conditions compared to a third of middle-aged adults (40-59), and nearly two thirds of 
individuals over 60 years old. This, in turn, often translates to a greater number of 
prescribed medications. As part of the aging process, the challenge of managing complex 
drug regimens is made ever more difficult by higher rates of cognitive decline and limited 
health literacy.24-26     
 
Literacy. Numerous studies have found limited literacy skills to be significantly 
associated with patients’ poorer recall of medication names and indications, inadequate 
understanding and demonstrated use of Rx instructions and precautions.5,6,27-32 Our team 
found that patients also may overcomplicate multi-drug regimens by taking medicine more 
times a day than necessary.4 Lower literate patients were at greater risk for not 
consolidating regimens [M=6.1 times/daily (SD=1.8); adequate literacy M=5.8 (SD=1.6) 
vs. low literacy M=6.5 (SD=2.4), p=0.03]. While studies have been inconclusive as to 
whether lower literacy is associated with non-adherence,33-36 the evidence clearly suggests 
that patients with lower literacy are more likely to misunderstand Rx instructions, putting 
them at greater risk for poor adherence.7,37  
 
Language. In addition, limited English proficiency (LEP) presents a formidable 
barrier in healthcare.38-43  Interpreters are rarely available to aid physicians and pharmacists 
in counseling LEP patients on safe Rx use, instructions are frequently unavailable in non-
English languages, and multilingual materials are often inaccurate and poorly translated.44-
47 These barriers have been shown to have a deleterious effect on LEP patients’ Rx use.48-
50 Wilson, et al. studied 1,200 LEP adults in California.50 Nearly half encountered 
difficulties interpreting Rx instructions and 16% experienced an adverse reaction as a 
result. Similarly, Sleath et al. found that 58% of LEP adults reported difficulty 
understanding English Rx instructions as a barrier to safe use.51  
 
 Health System Barriers. Individual barriers such as older age, limited literacy, and 
LEP are exacerbated by health system barriers.52 Multiple studies have shown physicians 
often fail to discuss with patients basic information around the safe use of prescribed 
medicines, let alone other relevant concerns (i.e. cost of medications).53-57 Furthermore, 
print Rx information is rarely distributed at the point of prescribing. Evidence also suggests 
that pharmacists equally fail to counsel patients on safe and appropriate Rx use.53,55,56 
While print materials (Rx labels, warning stickers, Medication Guides, patient leaflets) are 
provided by pharmacies, most are poorly written and confusing.58-61 In addition, 
considerable variability has been identified across this process.62-64 Bailey et al. found Rx 
instructions written by physicians to be highly variable;63 Wolf et al. reviewed Rx 
instructions printed by multiple pharmacies and also found that pharmacy translations often 
deviated from physicians’ instructions.64 Variable, poor quality physician prescriptions and 
pharmacy translations and lack of appropriate counseling complicate the task of organizing 
and properly dosing multi-drug regimens. 
 
2.2        Rationale 
An Evidence-Based Solution: A Universal Medication Schedule (UMS).  
The IOM 2008 report Standardizing Medication Labels recognized the need for setting 
standards within prescribing and dispensing practices to promote safe and accurate 

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medication use for patients.65 Members of our research team (Wolf, Wood) presented the 
concept of the UMS in this report. As approximately 90% of prescriptions are taken four 
times a day or less, the UMS specifically proposed to establish four standard time intervals 
(morning, noon, evening, bedtime) for the prescribing and dispensing of medicine. This 
would remove current variability in the manner in which prescriptions are written by 
physicians and transcribed by pharmacists.62-64 All prescriptions would instruct patients to 
take their medicine at one or more of these specified times; this would be described in a 
single, standardized fashion. UMS instructions also use health literacy best practices, like 
simplified text, numeric characters instead of words to detail dose (1 instead of ‘one’), and 
‘carriage returns’ (placing each dose on a separate line) to clearly identify every time a 
medicine is to be taken.4 
 
There is strong evidence supporting the UMS.4,65-70 Among a multi-site sample of 500 
primary care patients, Wolf et al. found those receiving UMS instructions versus a current 
standard were 33% more likely to accurately interpret Rx instructions.66  Lower literate 
adults were more likely to correctly comprehend the UMS instructions. These findings 
were replicated among 94 patients in Cork, Ireland, and also among 203 LEP patients in 
Chicago and San Francisco.68,69,71 Earlier studies also found the use of more explicit time 
intervals, such as those used in the UMS approach, improved patient understanding and 
reduced medication errors.67,72  
 
 
In January 2014, our team completed two parallel, 5-year clinical trials testing the UMS as 
an embedded standard in pharmacy practice [R01HS017687; R01HS016435]. 845 English 
and Spanish-speaking, low-income patients with type 2 diabetes and hypertension being 
cared for by one of 8 community health centers in the Washington D.C. area received 
reduced-cost medications from a collaborating non-profit, central-fill pharmacy. Patients 
were randomized to receive their bundled medications with UMS label instructions or a 
current standard modeled after a leading national pharmacy chain (no orientation to UMS 
provided). Over 9 months, both English and Spanish-speaking patients improved their 
proper use of multi-drug regimens (OR 1.98, 95% CI 1.02-3.85) with benefits extending to 
a near two-fold increased adherence rate as measured by pill count (OR 0.58, 95% CI 0.35-
0.98). Exploratory analyses also found a non-significant trend with glycemic control 
between arms (tight control (HbA1c <7.0%: 55.6% (UMS) vs. 46.3% (Standard), p=0.15). 
As with prior studies, these benefits were greatest for lower literate adults and those taking 
>5 Rx drugs. The IOM has repeatedly highlighted this concept, the US Pharmacopeia, 
American College of Physicians, and National Council for Prescription Drug Programs 
recommend it as a standard, and California passed legislation in 2011 stating the UMS as 
a best practice for Rx labeling, also supported by the National Board of Pharmacy.65,73,74 
 
Shifting Upstream: Implementing the UMS at Prescribing vs. Dispensing Medication. 
The above AHRQ/NIH-funded trials revealed several obstacles: 1) over half of patients 
routinely use multiple pharmacies resulting in their continued receipt of variable Rx label 
instructions; 2) imparting the UMS only on drug labels was not a sufficient signal to 
patients to consolidate multi-drug regimens; 3) patients need comprehensive views of the 
UMS applied to their entire Rx regimen vs. individual Rx labels only; 4) additional 
reminders may be beneficial to reinforce UMS prescribing after medical encounters, 
helping patients remember and simplify daily Rx use, and support adherence; 5) the UMS 

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alone may be insufficient at addressing multifaceted concerns that may warrant more 
intensive counseling and monitoring (issues with costs, side effects, regimen fatigue, 
motivation, etc.). Both the pharmacy and patients also expressed a need for improved, plain 
language Rx information that provides general knowledge to support safe Rx use. Our 
proposal is based on evidence from the field, extensive experience with EHRs, mobile 
technology, patient portals, and funded development work [R18HS17220, R21CA132771, 
R01NR011300, R01NR012745, U19HS021093]. We will shift the implementation of the 
UMS to primary care, leveraging technologies that are becoming increasingly prevalent 
per federal mandates (Health Information Technology for Economic and Clinical Health 
(HITECH) Act), particularly among community health centers.75 We respond to the Office 
of the National Coordinator (ONC) ‘Meaningful Use’ criteria by leveraging an EHR to 
deliver standard, patient-centered information supporting safe Rx use, as well as by 
extending the utility of a patient web-based portal.76  
 
Leveraging Increasingly Available Technologies to Support Medication Use. There are 
increasingly available technological solutions that can be leveraged to help patients learn 
how to safely and appropriately take prescribed medications at a cost that is not prohibitive, 
including electronic health records (EHRs) with corresponding ‘patient portals’ and cell 
phone applications (SMS text messaging).75,77-80 
 
 ‘Meaningful Use’ of EHRs. Our team has successfully field tested the UMS strategy 
at two academic centers using different EHR platforms (EpicCare: R18HS17220, 
R21CA132771; Cerner: U19HS021093).77 This included: 1) UMS-mapped standard 
physician instructions (a.k.a. ‘sigs’) that were e-prescribed to pharmacies (Epic only), 2) 
plain language medication information sheets (‘MedSheets’) incorporating the UMS sig 
given to patients upon checkout, and 3) a redesigned EHR medication list (‘MedList’) that 
organized a patient’s entire Rx regimen according to UMS intervals (Cerner only). These 
tools are in English and Spanish; we will now export all of these tools into a new EHR 
platform (GE Centricity) and Epic for this study. 
 
 Mobile Technologies to Promote Health Behavior Change. While EHRs can be 
leveraged to provide tools to support appropriate medication use in primary care, additional 
measures may be necessary to promote safe medication use outside of healthcare 
settings.77,81,82 Mobile technologies, specifically SMS text messages, have been used to 
provide health-centered messages to patients in their daily lives.83-86 Recent estimates 
indicate mobile technologies are useful tools for reaching low-income populations and 
racial/ethnic minorities; 92% of African-American and Latino adults own cell phones.87 
Text messaging capabilities are also commonly used; 81% of cell phone users send or 
receive text messages.87 While use of this technology is more common among younger 
adults, the number of older adult cell phone (even smart phone and tablet) users is 
increasing exponentially (89% ages 50-64; 77% ≥65), including those who actively receive 
and send text messages.87 Multiple studies have been conducted to evaluate text messaging 
as a means of promoting behavior change. 81,83,88 A 2010 systematic literature review by 
Cole-Lewis and Kershaw evaluated 12 interventions that utilized text messaging as a 
platform for disease management or prevention.83 Eight studies in this review reported 
positive changes in behavioral or clinical outcomes among individuals receiving text 
messages; outcomes included greater weight loss, smoking cessation, increased blood 
glucose monitoring and decreased hemoglobin A1c. Recent studies have found text 

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reminders increased Rx adherence, yet causal mechanisms and implementation ‘best 
practices’ remain unclear.89,90  
 
 Web-Based, EHR Patient Portal. Increasingly, EHR systems are incorporating 
‘patient portals’; these are web-based tools that allow patients encrypted access to their 
medical record.91-98 A variable list of functions may be offered to allow for self-
management support and enhanced communication between patients and healthcare 
providers (i.e. email physician, schedule appointments, reconcile and refill medicines). 
Improving access to and use of portals is important for ONC Meaningful Use stages 2-3 
criteria that emphasize greater health information exchange, patient-controlled data and 
patient involvement in decision making. 
 
While the potential value of patient portals is undeniable, actual evidence on their 
acceptability, usability, and effectiveness in benefitting patient care remains limited 
(Goldzweig et al, 2013).92 A few studies have found a diverse set of adults (young, old, 
veterans) to perceive these tools to be valuable. In specific circumstances they have been 
repeatedly used by patients, and a couple of trials have found portals to significantly 
improve patients’ adoption of recommended health behaviors.99,100 Nagykaldi et al. found 
that use of a patient portal among 422 adults at two primary care practices increased patient 
activation, perceptions of patient-centered care, and compliance with recommended 
preventive services (uptake of low-dose aspirin, pneumovax, children’s immunizations).101 
Little evidence is available specific to use of the patient portal for medication self-
management purposes. McInnes et al. examined data from the Veterans Aging Cohort 
Study and found that HIV+ veterans who used an electronic personal health record were 
nearly twice as likely to be ≥ 90% adherent to their antiviral regimens (OR 1.80, 95% CI 
1.35-2.38).102  Specific web portal functions used by veterans that aided adherence could 
not be identified, yet we still view the ability to review medication lists and lab values, to 
contact providers via secure messaging, and to seek additional Rx information as viable 
mechanisms for improvement.  Intensifying the challenge of how to make best use of the 
portal technology, system designers must account for age, race/ethnic, and literacy barriers. 
 
 
Inclusion and Exclusion Criteria 
3.1 Methods of screening for eligibility. Patients will be screened for eligibility by 
phone after they have had a regularly scheduled doctor appointment. The screener 
document details the series of questions that will be asked.  
3.2 Inclusion and Exclusion criteria.  
Patient Inclusion Criteria. Patients must meet the following eligibility criteria: 
1) Patient is age 50 and older  
2) Patient is English or Spanish speaking 
3) Patient has 5 or more Rx medications listed in the EHR list (we exclude 
‘as needed’ (PRN) medicines from all analyses and will not apply the 
UMS to these medicines) and self-reports being prescribed 3 or more Rx 
medications during the screener call. 
4) Patient owns a cell phone and is able to receive text messages 
5) Patient has access to the internet, and has or is willing to obtain a 
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Patient Exclusion criteria.  Adults with severe, uncorrectable vision, hearing or 
cognitive impairments or who are unable to consent, as well as prisoners will be 
excluded from this research.   
 
COVID-19 Survey Eligibility 
Wave 1: We will include any participant who has consented to participate in the 
main study and who has indicated that they were willing to be contacted for future 
studies run by Dr. Wolf on the consent form.  
 
Waves 2 – 4: We will include any participant who has consented to participate in 
the main study, who has indicated that they were willing to be contacted for future 
studies by Dr. Wolf on the consent form, and who completed at least Wave 1 of the 
COVID-19 survey. 
 
Waves 5-9:  
We will include any participant who has consented to participate in the main UMS 
Portal study, who has indicated that they were willing to be contacted for future 
studies by Dr. Wolf on the UMS Portal consent form, and who completed at least 
Wave 1 of the COVID-19 survey.  
 
 
Patient Inclusion Criteria: Any provider or staff that works at Erie Family Health Center 
or Lavin Primary Care, Northwestern University will be eligible to complete the 
provider/staff survey.  
 
 
Study-Wide Number of Subjects 
4.1 A total of 1505 patients will be enrolled in the study across all sites.   
4.2 We expect around 50 providers and staff will be enrolled for the 
provider/staff survey but we will not limit responses. All providers and staff 
that may have been exposed to the study will receive a link to complete the 
survey. 
 
 
Study-Wide Recruitment Methods 
5.1 Patient Interviews. 
Recruitment will be done by phone by trained Northwestern RAs.  
For patients recruited from Erie Family Health Center: first, Alliance will send Erie 
providers an encrypted file of a list of eligible patients from Erie Family Health Center who 
have an upcoming doctor appointment scheduled. Providers will indicate if any eligible 
patients should not be contacted. Providers will be reminded via email to reply with their 
list of approved patients. Providers will be informed that if they do not respond within two 
weeks they are giving Northwestern permission to contact all patients on the list. 
Northwestern will then mail a letter to patients on the list, notifying them that a research 
coordinator (RC) will be telephoning to invite them to participate in a study. Patients will 
be given the opportunity to opt out of being contacted by calling a hotline number and 
leaving a message. RCs will monitor the messages and send Alliance a list of patients who 
have chosen to opt out. Seven days after the letters have been sent, an RC will call patients 

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who did not opt out to ask screener questions to determine eligibility and, if eligible and 
interested, schedule their baseline. Due to COVID-19 restrictions, the study team may not 
be able to mail letters to all patients. If a letter mailing is not possible, the study team will 
still obtain permission from the provider to contact their patients but not send recruitment 
letters.  
 
For patients recruited from Northwestern Medicine Primary Care: potential participants 
will be identified through reports generated by the Enterprise Data Warehouse (EDW) for 
patients who have an upcoming appointment scheduled.  Per clinic protocol, all eligible 
patients can be contacted and providers will not receive a list of their patients to indicate 
who should not be contacted. Research staff will then mail a letter to patients on the list, 
notifying them that a research coordinator (RC) will be telephoning to invite them to 
participate in a study. Patients will be given the opportunity to opt out of being contacted 
by calling a hotline number and leaving a message. RCs will monitor the messages of 
patients who have chosen to opt out. Seven days after the letters have been sent, an RC will 
call patients who did not opt out to ask screener questions to determine eligibility and, if 
eligible and interested, schedule their baseline. Due to COVID-19 restrictions, the study 
team may not be able to mail letters to all patients. If a letter mailing is not possible, the 
study team will contact patients by phone after their doctor’s visit but not send recruitment 
letters.       
 
For providers and staff: To investigate healthcare provider and/or healthcare system-level 
barriers to implementation, we will conduct brief online interviews (n ∼25-50) with clinic 
providers and staff to explore barriers and facilitators to implementing the various 
intervention strategies. The practice manager, academic manager, or clinician partner at 
Erie Family Health Center and Northwester Medicine will email providers and staff that 
may have been involved in some aspects of the study a Redcap link to an online consent. 
If the provider or staff member consent and click next, they will be taken to a brief online 
survey. Survey responses will be anonymous.  
 
5.2 Data Abstraction from the Erie EHR.  
Mr. Hamilton (Quality Informatics), working under the supervision of Dr. Rachman, will 
write Structured Query Language (SQL) programs to extract data periodically from the 
EHR database. Also, lists of potentially eligible patients will be generated for recruitment 
and periodic medication lists will be updated in order to measure medication reconciliation. 
Data sets containing study identification numbers only will be prepared for sharing with 
the team. 
 
 
Multi-Site Research 
6.1 This study is a single-centered study. 
  
 
Study Timelines 
Timeline: We are anticipating the project to be completed in 4.5 years. The image below 
describes the timeline of events for this proposed study.   

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7.1 Study Duration. 
1. 
The anticipated duration of participation will be 6 months.  Patients will 
complete an in-person or phone baseline interview after having a regularly 
scheduled doctor appointment. They will then complete a 6-8 week phone 
interview, and a 6-month post baseline, in-person interview or phone interview 
(if unable to complete in person due to NU COVID-19 in-person interview 
restrictions).   
2. 
We have allotted 36 months to recruit and enroll all participants. 
3. 
We anticipate 9 additional months to finish preliminary analysis.  The estimated 
date to complete analysis is May 2021.  
 
 
Study Endpoints 
8.1 Covariates.  
Patient characteristics: Socio-demographic characteristics, language, country of 
origin, time in US, comorbidities, social support, cognition (the cognitive assessment 
will not be completed if the baseline interview is completed over the phone), and 
health status will be collected.  A literacy assessment using the Newest Vital Sign 
(NVS) and brief health literacy screener, and the Consumer Health Activation Index 
(CHAI) will be administered.   
 
Regimen characteristics: Rx drugs will be collected and grouped into drug class. 
Regimen complexity will be calculated via the Medication Regimen Complexity 
Index (MRCI).   
 
Provider-Patient Prescription Communication: We will ask questions adapted from 
the Consumer Assessment of Health Providers Survey (CAHPS-modified only as 

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necessary) to evaluate the extent and quality of provider verbal counseling on 
prescription medications. 
 
Fidelity (Process) Measures:  
- 
Receipt of UMS materials. We will collect EHR data on prescriptions and end-
of-visit summaries to assess whether the UMS sigs were actually prescribed and 
whether the MedSheets and Medlists were printed. Similarly, we will review 
patients’ actual medication bottles to determine if the labels reflect the UMS 
instructions and ask whether they received the MedSheets and Medlists (yes/no).  
- 
Receipt of SMS text reminders. At each follow-up, the RC will ask whether 
patients received text reminders. We also will have texting opt out data from the 
text message provider. 
- 
Use of Patient Portal. At each follow-up, the RC will inquire whether patients 
used the Patient Portal and if clinic staff followed-up with the patient. We also 
will obtain data through the EHR on who has accessed the portal and the number 
of portal logins each participant did during the study.  
  
8.2 Primary Endpoints. 
Effectiveness Outcomes. For the outcomes described below, we only include Rx 
chronic medications. Though we document them, we exclude PRN, as adherence 
concerns are different.   
 
Treatment knowledge. Patients will be asked to identify drug indication; binary 
classifications will be applied per drug. 
 
Medication adherence. The ASK-12 Adherence Barrier Survey assesses patients’ 
general adherence behaviors and barriers to treatment adherence.  Adherence will 
also be measured for each Rx medication using: 1) Self-report of how many pills and 
how often each medicine was taken over the last 24 hours.  The RC will record how 
many pills were taken at each time for each medicine.  Correct dosing will be 
measured as yes/no per drug, based on having properly demonstrated dose (# pills), 
spacing (hours between doses), frequency (times per day), and total pills/day, 2) in-
person/phone pill counts of all chronic, pill form medicines, using established 
guidelines employed by our team [R01HS00167; PI Wolf], 3) the proportion of days 
covered (PDC), a measurement of days covered with medication, based on pharmacy 
claims. This is calculated by summing the number of days’ supply obtained by a 
patient during a given time period and dividing by the number of days for which the 
medication was prescribed. For each patient, we will assess adherence within drug 
class. If a patient fills a prescription for a drug and switches to another drug within 
the same class, all prescriptions will be summed in the numerator. Adherence will be 
treated both continuously (PDC) and dichotomously (yes/no - PDC ≥80%).  Patients 
will be asked to sign a release at their first and/or last interview allowing us to obtain 
fill information from pharmacies used during the study. We will request information 
from pharmacies 6 months prior to baseline to a year post baseline. If the interview 
is completed over the phone, patients may receive a pharmacy release form by mail 
to sign and return to the research team. For the pill count during phone interviews, 
RCs will read a standardized script to ask patients to count study pills using a 
standardized procedure. If able, participants will be asked to join a video call so the 

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RC can take a screen shot of the patient’s remaining pills-per bottle. The RC will save 
the screen shot/photograph to the study project folder within the secure GIM server 
only using the patient’s studyid to identify the photograph. No PHI will be captured 
in the photograph. If the participant does not have video capabilities, the RC will 
proceed to explain how the patient can count their pills and relay the number to the 
RC. This script is outlined in the interview script. For patients consented before May 
19, 2020 that complete a phone 6 month, a brief script will be read informing patients 
of the change in the consent in regards to the pill count. The RC will ask the 
participant to provide verbal consent to allow the study team to take a screen 
shot/photograph of the patient’s pills during a video call in order for the RC to count 
the pills after the interview. The patient will be notified that no PHI will be captured 
in the photograph.  
 
Medication reconciliation.  Chart reviews will determine whether any discrepancies 
are present between patient self-report and the chart medication list. Nature of the 
discrepancy (omission vs. commission) will be recorded. 
 
Clinical Outcomes. Systolic/diastolic blood pressure will be collected on all patients 
during the baseline and 6 month interview. Low-density lipoprotein cholesterol 
(LDL) will be obtained from patients’ electronic health records.    Chart review of 
hemoglobin A1c (hbA1c) will be reviewed for all diabetic patients.  Differences will 
be measured between the last clinical measurement prior to baseline assessment and 
the last measured value during the study period (closest to 6 month assessment).     
 
 
Procedures Involved 
9.1 We will conduct a randomized trial using a 2x2 factorial design to test the 
effectiveness of UMS interventions to improve safe use and adherence to complex 
prescription (Rx) regimens. The research will be performed at Erie Family Health 
Center clinics and Northwestern Memorial HealthCare (NMHC) in Chicago. 
 
9.2 Research Coordinator Training. The RCs and the project manager will contact and 
consent participants, conduct interviews, perform retention and follow-up activities 
and quality assurance. All have completed human subjects training (CITI) and 
intensive training from Dr. Wolf in interview protocols and safe data transfer. They 
also have multiple years of patient interviewing and data management experience.  
Simulations will be used to monitor interviewer proficiencies. Our staff has ample 
experience conducting surveys measuring medication-related outcomes.  
 
9.3 Computer Programming. We will be using RedCap to collect all data. This allows 
for straightforward electronic entry of participant responses by the RC and generation 
of data files compatible with statistical programs. The database is both encrypted and 
password protected, and is only accessible by approved study personnel at 
Northwestern. Dr. Kwasny (analyst) will oversee the database structure and quality 
assurance activities. 
 
9.4 Data Safety and Monitoring Board (DSMB).  The DSMB will be formed early in 
the project and be given responsibility to review and approve the methods and 
analysis plan. It will be organized by Drs. Wolf and Bailey and include 4 health 
services researchers with related expertise. Meetings will be via video/tele-

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conference to review protocols, procedures, and concerns related to research 
integrity.  
 
9.5 Trial Registration. This study is registered at ClinicalTrials.gov (NCT02820753). 
 
9.6 Implementation and e-bugging of EHR, Portal Tools.  Dr. Wolf will plan the 
implementation of the EHR tools within the GE Centricity EHR with Dr. Rachman 
(Alliance CEO), Mr. Hamilton and Ms. Kaleba. All have considerable experience 
implementing changes to this system. Dr. Wolf has implemented the same processes 
to be tested in this study within Epic and Cerner platforms. Alliance’s informatics 
analysts will implement the EHR and portal tools, assist with piloting in the electronic 
test environment, troubleshoot and communicate with GE Centricity if necessary, and 
roll out tools to Alliance sites. Drs. Wolf, Bailey and Rachman and Ms. Herman will 
work together to impart the specific functionality (portal survey and electronic views 
of Medlist, Medsheet) on the Alliance portal, as well as ensuring functionality of the 
lab reports to the clinic containing the portal survey results. Dr. Wolf will also work 
with Epic programmers at NMHC to refine the build in Epic for Northwestern clinics. 
While all functions have already been programmed at Northwestern, some functions 
may need to be tweaked and turned on accordingly.  
 
9.7 Randomization. Randomization will occur at the patient level. Patients will be 
randomized to 1 of 4 arms (1:2:2:2). Because all arms receive the EHR tools, we are 
able to ‘turn on’ those features at all participating clinics. The other interventions 
occur outside of the clinic setting, so we are able to assign patients to those arms at 
an individual level.  
 
9.8 Clinic Space, Orientation and Workflow. Prior to implementation, Dr. Wolf will 
meet with physicians and staff at each of the sites to familiarize them with the planned 
study activities, answer questions, provide a printed synopsis of the protocol per site, 
and give contact information. They will work closely with Dr. Buchanan to 
coordinate activities at the sites and plan space needs for interviews and study visits. 
 
9.9 Spanish Translation. All of the measures identified already have Spanish versions. 
We will employ Dr. Schoua-Glusberg, from Research Support Services, to translate 
remaining components (introduction prompts, item probes, surveys, etc.), as well as 
the consent and recruitment materials into Spanish. Dr. Schoua-Glusberg has 
specialized in research studies with Hispanic populations, including topics such as 
methodology for instrument translations and qualitative pretesting of survey 
instruments in Spanish, since 1984 and we have worked with her extensively. Dr. 
Bailey (Spanish) will review all materials and facilitate any discussion to reach an 
agreement on the best words and phrases for the final product.   
 
9.10 Pilot-testing and Refinement of Study Materials and Protocol. We will pilot-test 
the study battery, protocol and patient materials among English and Spanish-speaking 
patients at Alliance sites. Cognitive interviews will be conducted among a 
convenience sample of 30 patients (n=15 per language) that meet eligibility criteria 
to refine and standardize the study materials. We will 1) obtain average completion 
times for the interview and 2) elicit patient comprehension and acceptability of the 
interview and patient materials through a set of targeted questions. If problems are 

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identified, the root cause(s) will be analyzed and modifications made to the interview 
and materials as appropriate prior to full-scale implementation.  
 
9.11 Interviews. The initial interview will be conducted in person or over the phone at the 
time of patient consent and enrollment. Following the baseline interview, RCs will 
conduct one telephone interview 6-8 weeks later. Assessments at this interview are 
aimed to closely track any change in the most proximal outcomes of Rx understanding 
and behavioral outcomes (self-report adherence). A final in-person interview or 
phone interview (if unable to complete in person due to NU COVID-19 in-person 
interview restrictions) will then be conducted 6 months post baseline. Patients will 
receive financial incentives to attend study visits ($40 for baseline interview, $60 at 
6 months). In addition, patients will receive reimbursement for text messaging costs 
if they do not have unlimited texting = (estimated costs based on greatest possible 
incurred charge). Patients will be provided $10 for transportation costs or a parking 
pass.  
 
 COVID-19 Waves 5-9 Patient Interviews.  Participants will complete up to five 
telephone interviews in total, with one interview taking place every 4 months. New, 
supplement-specific data collection related to COVID-19 will be collected via 
telephone interviews. See section 9.20 for more information 
 
 
9.12 Obtaining Clinical Markers Data. At in-person baseline and 6 months, trained RCs 
will use a blood pressure monitor to measure systolic/diastolic blood pressure on all 
participants. RCs will use an automated, validated device (Omron HEM-907XL) and 
procedures used in the National Health Examination and Nutrition Survey 
(NHANES). RCs will ask patients to sit quietly with feet and back supported for 5 
minutes before blood pressure is obtained. Three recordings will be taken per visit, 
spaced at least 5 minutes apart, and the mean of the 2nd and 3rd readings will be used 
to indicate blood pressure for that visit. Patient positioning, arm selection, cuff size 
selection and other techniques will follow NHANES procedures. Baseline and 6-
month interviews that are completed over the phone will not obtain in-person blood 
pressure values. 
 
In the event that a patient has a high blood pressure screening (systolic >180 
or diastolic >110): For patients with a high blood pressure screening, the RC 
will proceed to the following Hypertensive Emergency Screening Questions: 
Hypertensive Emergency Screening Questions: 
Are you currently experiencing… 
• Severe pain in the chest and/or upper back? 
• Nausea or vomiting? 
• New vision changes? 
• Severe trouble breathing? 
• A headache? (Must say yes to both sub-questions to count as a yes) 

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 Is it different from prior headaches? 
 Is it severe? 
The RC will then instruct the patients based on the following for Erie patients: 
• For interviews done at an Erie site, and patient has a systolic >180 or 
diastolic >110: Patient should be transferred in real time to the on-
site nurse for a full assessment and provider consultation regardless 
of responses to screening questions. The RC will provide the patient 
with their blood pressure values on a piece of paper. 
• For interviews done at Northwestern, and patient has a systolic >180 
or diastolic >110: 
 Patient should be advised to go to the Northwestern 
Emergency Department regardless of responses to screening 
questions before leaving the interview. The RC will provide 
the patient with their blood pressure values on a piece of paper. 
 The RC should notify Erie Family Health Centers of the 
patient’s blood pressure screening and that the patient was 
advised to go to the Emergency Department 
o The RC should call Erie directly and follow the phone tree 
to speak with a Patient Access Representative, 312-666-
3494 
 Erie Staff will notify the patient’s Primary Care Provider 
  
The RC will then instruct the patients based on the following for Northwestern 
patients: 
• If yes to any screening questions above, patient should either call their PCP’s 
office from the interview room to speak to a healthcare provider for advice, 
or proceed to the ER. 
• If no to all screening questions above, patient should be instructed to call their 
primary care doctor.  
 
For diabetic patients, a chart review or EDW pull will be done to examine 
Hemoglobin A1c (hbA1c) levels at their regularly scheduled primary care 
appointments closest to baseline and 6 month interviews. This is to decrease the 
burden on the participant – alternatives include taking a blood sample at our interview 
or asking participants to go to Quest Diagnostics. We felt that was excessive and 
unnecessary, so will use the EHR data provided by Erie or the EDW report for 
Northwestern patients.    
 
9.13 Study Arms. 
Enhanced Usual Care. Current usual care includes variable physician prescribing 
and/or nurse counseling, and no active SMS or surveillance of medication use post-
visits.  
 

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We are enhancing this usual care by adding UMS materials as a clinic standard, per 
Erie’s request following their current experience with these materials. All patients at 
Erie or NMHC, thus all patients in this study, will begin to receive UMS-related tools 
at their primary care visit to support Rx use. These materials have previously been 
successfully piloted in multiple NIH-funded studies.  These include:  
1. UMS Rx Instructions (‘Sigs’). The UMS is defined in Section 2.2. We have 
already successfully replaced existing EHR default sigs for 305 Rx drugs in 
primary care with UMS instructions [R21CA132771], and tested use of UMS 
sigs in pharmacy practice [R01HS017687, R01HS019435], in English and 
Spanish.  
 
2. MedSheets. As an additional measure funded by AHRQ [R18HS17220], we 
created single-page, plain language Rx information sheets following health 
literacy best practices with content appropriately sequenced from a patient’s 
perspective (drug name, indication, purpose/benefit, how to take, for how 
long, when to call your doctor, when to stop taking and call your doctor, 
important information). These sheets pull in the UMS sig to tailor content and 
serve as a tangible, ‘patient-friendly’ addition to the after-visit summary. 
Medsheets for a total of 305 Rx drugs have been embedded within the Epic 
EHR at NMFF and are automatically generated and distributed at check out 
to patients with new Rx prescriptions. Lexile analyses were performed on 
these sheets, confirming each to meet a < 8th grade readability standard. The 
content was developed by two pharmacists, performing an environmental 
scan of existing tools. Patients, physicians, and health literacy experts 
reviewed the material and guided revisions. 
 
3. MedList. We re-designed the EHR medication list to impart the UMS to an 
entire Rx regimen (R18HS17220; U19HS021093). All medicines are listed 
and instructions consolidated in UMS form (requiring e-confirmation by 
doctor to ensure patient safety and flagged by clinical decision support tools 
if harmful interactions exist in regimen – supervised by Dr. Wood) to visually 
depict patients’ morning, noon, evening, and bedtime medicine.  
 
The UMS EHR tools have been piloted in Epic and Cerner, and are now being 
implemented in GE Centricity for this proposal now. Among 144 patients at the 
NMFF General Medicine clinic, nearly all (91%) patients received their MedList, 
UMS sigs, and MedSheets for new medications; 85% reviewed it with their doctor. 
Feedback from 20 physicians offered unanimous positive feedback on the tools.77 
[R18HS17220]. 
 
9.14 
SMS Text Reminders. For those patients receiving text reminders (SMS; 
SMS+Portal), daily text reminders will be sent post baseline following the UMS 
intervals. The texts will continue daily, with the option to opt out at any time. 
Stopping the texts will not impact their continuance in the study. Texts will 
automatically stop after 6 weeks, with an option at that time for patients to opt back 
in to the service. Those who opt back in will get the texts all 6 months of the study, 
or until they decide to stop. In past studies we have sent texts for one week, but recent 
studies have shown patients may benefit from longer text interventions. A covariate 
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as whether or not people opted out. Participants without unlimited texting plans will 
be reimbursed the total cost of receiving the texts. Patients will receive uniform, 
generic messages around UMS time intervals such as, “Good Morning! Please 
remember to take your medicines today.” and, “Hope you had a great day and 
remembered to take all your medicine!”  
 
We will use EZ Texting, a safe, economical, premium Internet SMS text service plan, 
to program and schedule discrete UMS-centered text messages. These will be sent at 
standard intervals for all patients based on their regimen, with a maximum of two 
times a day (i.e. 1 or 2 times daily depending on regimen). Because these reminders 
are sent daily, we have limited the number of times sent per day so as not to burden 
and overwhelm the patient. Generic reminders are used due to the complexity of 
patient regimens and the SMS text message itself sent around the general time of 
behavior is a memory support. The premium plan ensures patients do not receive 
promotional messages with the text. A trained RC will orient and confirm patients 
can retrieve text messages. The RC will also instruct patients to abstain from reading 
text messages while driving and instead read messages and take medicines once they 
can safely concentrate on the task. 
 
9.15 
EHR Web-Based Patient Portal. The addition of the patient portal will 
provide opportunities to have ongoing communications with their clinic, real-time 
reconciliation and updating of medication lists, access to regimen-specific 
medication information, and to provide a feedback loop informing healthcare 
providers of adherence-related behaviors and concerns. The encrypted patient portal 
website will be managed by the Alliance HIT team and the MyChart team, under Dr. 
Wolf’s supervision. Secured instant messaging and email features to communicate 
with clinic staff are already available within the portal. The additional build out above 
these informational and communication features will be a periodic requests for 
patients to (1) identify if they missed taking any of the medicine in their regimen in 
the past 3 days, and (2) list any concerns or problems related to refill, cost, side 
effects, or management of their medicines. This process has previously been piloted 
with patients and can be performed in three minutes or less. Patients in this arm will 
be asked to fill this survey out 2 weeks, 1, 2, 3, 4, and 5 months post baseline. An 
email will be sent to patients at these time points, requesting that they access the 
portal and complete the regimen adherence assessment (embedded in the portal). The 
information submitted back by the patient will be sent back to the EHR and directed 
to the responsible doctor or nurse. Identified ‘champions’ at Erie and NMHC will be 
trained to review the files and identify patients with regimen-related concerns. 
Patients who do not complete the assessment within 48 hours will be sent a second 
email reminder. If they still do not fill out the survey, a third and final reminder will 
be sent. Patients who self-report any concerns or who demonstrate incorrect or missed 
doses will also trigger nurse follow-up.  The RC will create a MyChart or 
MyErieHealth account for patients that do not already have a patient portal account, 
depending on the clinic they attend. For Erie patients, a MyErieHealth account will 
be created through the MyErieHealth admin page. For Northwestern patients, the RC 
will obtain a MyChart activation code by accessing a patient’s chart through Epic. 
Erie staff will send encrypted emails weekly or as needed to NU RC’s with a list of 
patients that have completed the portal survey. For Northwestern patients, RC’s will 

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determine if a survey was completed by accessing a patient’s chart through Epic to 
see a record of a completed UMS Portal MyChart survey.  
 
9.16 Nurse Training. Nurses will be educated on health literacy and health 
communication best practices, barriers to medication self-management, and how to 
briefly counsel patients via face-to-face and telephone using teach-to-goal and 
implementation intention approaches. Our team has used these techniques in prior 
studies that tested a low literacy diabetes education strategy in FQHCs. Patients at 
the time of enrollment will also be extensively oriented to the patient portal and use 
of the EHR and portal tools. The clinic nurse phone number and email will be 
provided for technical support. 
 
9.17 Pharmacy Release.  
To calculate PDC, we will need to collect pharmacy claims data for each patient that 
grants permission.  For each patient, we will assess adherence within drug class. If a 
patient fills a prescription for a drug and switches to another drug within the same 
class, all prescriptions will be summed in the numerator. Once the patients have 
signed the informed consent, patients will be asked which pharmacies they use to fill 
their prescriptions.  They will be asked to sign the appropriate release(s) allowing us 
to obtain fill information from pharmacies used during the study. We will request to 
obtain information for any medicine that was filled 6 months prior to baseline to 1 
year post baseline. If the interview is completed over the phone, a pharmacy release 
form may be mailed to the participant to be filled out and returned to the study team.  
 
 COVID-19 Waves 5-9 Pharmacy fill data. For participants that complete 
COVID Wave 5-9, participants will be asked if they use Walgreens or CVS to fill 
their prescriptions. During the COVID consent process, participants will be informed 
that Walgreens and CVS Pharmacy may access, receive, or use their personal 
information, based on the pharmacies they utilize. 
 
 
9.18 Data Sources. Data sources for this study will include in-person interviews or phone 
interview with participants (see attached surveys), blood pressure machine readings 
during in-person visits, Electronic Health Record chart review, and pharmacy data.   
 
9.19 Data Collection. In order for the researchers to evaluate the intervention and how 
well it is being utilized, we will ask the Alliance to provide some data to Northwestern 
for Erie patients. For consented patients, the Alliance/Erie Family Health Center will 
provide data, including basic demographics, current medication lists and clinical 
outcomes from the patients’ medical record. The Alliance/Erie Family Health Center 
will also provide the above detailed information in the form of de-identified, 
aggregate data (i.e. frequencies and means (SD) per arm) for all patients, regardless 
of whether or not the patient consented to participate in the study. All data will be 
transferred 
via 
secure 
Sharepoint 
site.                        
 
Specifically: 
• Alliance will send contact information for identified eligible patients 
o Study ID 
o Patient’s medical number 

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o Patient name 
o Clinic and provider name 
o Home and cell phone number 
o Address 
o Sex 
o Date of Birth 
o Primary language 
o Date of last primary doctor appointment at Erie 
o All drugs prescribed (name, dose, form, GPI, instruction, date prescribed, 
number of refills, pharmacy, quantity) 
 
• NU will send Alliance/Erie Family Health Center Study IDs and baseline 
interview dates, linked by patient ID 
 
• Alliance will send the following information to Northwestern for consented 
patients: 
o Study ID 
o All values 6 months prior to baseline & 12 months post 
 Blood pressure  
 HbA1c  
 Cholesterol levels 
o Information on all prescribed medicines baseline to 12 months post 
(name, dose, form, GPI, instruction, date prescribed, number of refills, 
pharmacy, quantity) 
o Current at baseline and 12 months post 
 Chronic conditions 
 COVID-19 diagnosis and/or results of antibody test 
o All clinic visits/appointments 6 months prior to baseline and 12 months 
post (date, provider, meds prescribed, visit type) 
o Patient portal survey results, date completed, and possible clinic contact 
for patients in either of the portal arms 
o Patient portal use 6 months prior to baseline and 36 months post baseline 
 how many times patient logged on to portal 
 what portal was used for  
 when and how often portal was used 
 
For Northwestern patients, the same data that was requested above will be obtained 
through an additional EDW report, including patient medications, chronic 
conditions, COVID-19 diagnosis and/or results of antibody test, and healthcare 
utilization (ED, hospitalization, primary care appointments) as well as hypertension, 
diabetes and cholesterol clinical values.     
 
For Participants that complete COVID Wave 5-9. 
 EHR Data. Medical record data will be again collected via the Electronic Health 
Record (EHR) from January 1, 2019 - present. EHR data will confirm comorbidities 
and medications. We will also extract clinical outcomes (HbA1c, diastolic and 
systolic blood pressure, cholesterol (LDL, HDL, total, triglycerides), GFR, COVID-

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19 lab tests and results, COVID-19 diagnosis, COVID-19 vaccine type and dates,  
and antibody results), preventive services utilization (cancer screening, 
immunizations), and health services use (clinic visits (including telehealth), medical 
subspecialty visits, emergency department visits, hospitalizations). Lastly, we will 
collect patient portal usage.  
 
9.20 COVID-19 Survey. We are proposing an optional sub-study to be contacted from a 
pool of existing studies conducted by Dr. Michael Wolf (LitCog (STU00026255), 
REMinD (STU00203777), COPD Multimorbidity (STU00201640), UMS Portal 
(STU00201639), and TAKE IT (STU00204465). Participants will be invited to 
participate in an optional one-time brief (5-10 minute) telephone survey to capture 
one additional outcome pertaining to their knowledge, attitudes, and beliefs about the 
COVID-19 outbreak in March 2020. This new data will be linked with participant 
characteristics from the parent study. They will also be asked a series of patient-
reported health literacy items. Participants who complete to COVD-19 survey will 
receive a $10 gift card in the mail.  
 
Recruitment will be done by phone by trained Northwestern RAs. We will contact 
any who has indicated that they were willing to be contacted for future studies run by 
Dr. Wolf on the consent form. Verbal consent will be obtained prior to completing 
the one time brief (5-10 minute) telephone survey. 
 
Waves 2-4:  
From the same pool of existing studies included in Wave 1, any participants who 
completed the Wave 1 COVID-19 survey will be contacted and invited to participate 
in up to 3 additional telephone surveys (10-30 minutes each) over the course of 4 
months to continue to evaluate knowledge, attitudes, and beliefs over time about the 
ongoing COVID-19 pandemic. Participants who complete the follow-up interviews 
will receive a $10 gift card in the mail for wave 2 and a $15 gift card for waves 3 and 
4 (per survey), for a total of up to $40 for the follow-up activities. For wave 3 and 4, 
we increased the participant compensation from $10 to $15 due to the longer survey 
administered at this time point. 
Recruitment will be done by phone by trained Northwestern RAs. We will invite 
anyone who has indicated that they were willing to be contacted for future studies 
run by Dr. Wolf on the consent form and who completed the Wave 1 survey. Verbal 
consent for the follow up waves will be obtained prior to completing the Wave 2 
telephone survey (initiated 2 weeks after Wave 1). Participants who consent to these 
follow-up activities will be re-contacted for completion of Waves 3 and 4 at 1 month 
and 3 months post-wave 2. 
 
Waves 5-9 
In March 2020, we recruited a subset of the UMS Portal cohort (n=215), and patients 
enrolled in four other studies (n=458; Total N=673) to form the Chicago COVID-19 
Comorbidities (C3) cohort study. We initially completed four phone interviews 

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(described above) with them to better understand how older adults with underlying 
health conditions, at greater risk for COVID-19 complications, were responding and 
taking action (or not) to prevent infection and disease spread.  
 
We will now continue our investigation to better understand the longer-term impact 
of COVID-19. From the same pool of existing studies, any participants who 
completed the Wave 1 COVID-19 survey will be contacted and invited to participate 
in up to 5 additional telephone surveys occurring every 4 months. Interviews will 
collect information on participants’ responses to COVID-19 and changes in lifestyle 
behaviors, healthcare utilization, physical and mental health, access and adherence to 
treatment, socioeconomic circumstances and clinical outcomes. We will also collect 
data from the medical record and pharmacy record abstractions. 
 
Participants who complete additional telephone surveys will receive compensation in 
the mail. See section 22.2 for further details.  
 
Data from all waves of the COVID-19 telephone surveys will be captured in 
REDCap. 
 
9.21 
Post-trial investigations 
To investigate patient, healthcare provider, and/or healthcare system-level barriers to 
implementation, we will conduct brief online survey (n ∼25-50) with clinic providers 
and staff to explore barriers and facilitators to implementing the various intervention 
strategies. The practice manager, academic manager, or clinician partner at Erie 
Family Health Center and Northwester Medicine will email providers and staff that 
may have been involved in some aspects of the study a Redcap link to an online 
consent. If the provider or staff member consent and click next, they will be taken to 
a brief, anonymous online survey.  
 
We will also compare the cost-effectiveness of each strategy. Specifically, we will 
estimate the incremental cost of interventions over the cost of usual care from the 
perspective of AllianceChicago, Erie Family Health Center, and Northwestern 
Medicine. The primary operational costs of the intervention strategies include texting 
related costs and the programming and maintenance costs of the Epic/GE Centricity 
EHR and the patient portal. We will separately track development costs of the 
interventions, conditional on having an EHR and portal, which are primarily 
comprised of software generation and other programming requirements based on 
programmer hours. Staff/programmer costs will be measured using tracked time 
spent on developing and running the intervention and converted to dollars using 
current wages. 
 
 
Data and Specimen Banking 
10.1 Upon completion of all study activities, a final de-identified dataset will be created. 
This dataset will be stored indefinitely on the GIM server for secondary analyses. 

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Only authorized personnel will have access to the dataset. Data will be stored on 
Northwestern encrypted servers and access will be granted through the PI.   
 
 
Data and Specimen Management 
11.1 Analysis Plan. 
Aim 1.  
The proposed trial uses patient 1:2:2:2 randomization with random block size to 
achieve group comparability and balance. Stratified by clinic, each participant will 
be randomized to one of the four arms. The four arms are the result of a 2x2 factorial 
design, where SMS text reminder and portal are the two-level factors with all four 
arms receiving the EHR tools. We conservatively anticipate at least 80% retention 
for follow-up at six months. This will result in 1505 participants recruited to the study 
with an anticipated minimum of 1204 (172 participants in EHR arm and 344 per the 
other arms) available after six months, contributing to primary data analysis. Due to 
an NIA administrative hold, the interventions were not implemented as planned. 
Hence it was determined that the primary analysis would be “per-protocol” rather 
than intent-to-treat to assess the effect of the interventions under optimal conditions. 
Participants who received the initial 6 weeks of SMS messaging continuously will be 
considered as receiving the SMS intervention, and participants who logged on to the 
patient portal and completed at least one survey will be considered as receiving the 
patient portal.   
 
To ensure adequate balance across treatment arms, baseline outcomes and potential 
confounders including socio-demographic characteristics, comorbidities, regimen 
complexity (i.e. # of medications, total pills taken daily), health literacy level, and 
language will be examined. Variables found to have clinically meaningful differences  
across treatment groups will be entered as covariates in the generalized linear mixed 
models (GLMMs) used for formal analyses as described below.  
 
Prescription medication adherence at 6 months is the primary outcome of interest for 
Aim 1, with treatment knowledge regimen consolidation, and clinical outcomes being 
relevant to hypotheses of secondary interest. We will use generalized linear mixed-
effects models (GLMMs) to test for the effects of SMS text reminder and Portal, 
specifying the proper link functions based on the distribution of the outcome variable. 
Analyses will be performed using PROC GENMOD in SAS (v.9.4). SMS text 
reminder and Portal (both binary) and an interaction term for SMS and Porta are the 
three variables included in the model to denote the intervention groups and the 
enhanced usual care group (H1-6). Since adherence will be assessed for each 
medication, 2-level GLMM will be used with medications nested in participants. We 
will test for differences in the outcomes between each of the groups and the enhanced 
usual care arm to determine benefits of SMS texting or portal use, or both by 
constructing contrasts.  
 
Aim 2. 
We will determine the extent to which the interventions were implemented as planned 
(a process evaluation) across each of the sites and for all four study arms. We will 
collect EHR data on prescriptions and end of visit summaries to assess whether 
patients actually received new prescription orders (in after visit summaries) with the 

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UMS sigs, and review pharmacy records to determine if they were translated 
accordingly onto patients’ drug container labels. We will also observe during patient 
interviews (that occur after medical encounters) which patients received the 
MedSheets and MedList. For those receiving SMS text reminders (SMS and 
SMS+Portal arms), we will ask patients at all follow-up intervals whether they 
received the text messages. For those electing to turn off the service, we will 
qualitatively explore and code reasons why. For patients who receive the Portal 
(Portal and SMS+Portal), we will track usage data, rate of entry errors, review 
technical support logs for the frequency and nature of calls, and also investigate at 
each follow-up patient satisfaction, acceptability and usability of the portal.   
 
Aim 3.  
We will directly measure and assess the perspective costs of developing and running 
UMS interventions, alone and in combination. Specifically, we will estimate the 
incremental cost of interventions relative to usual care from the perspective of the 
Alliance, Erie, and Northwestern. The primary costs of running UMS technologies 
involves the limited expenses around printing (printer ink, paper, staff time) as a 
result of generating new Rx information with after-visit summaries. SMS monthly 
costs will be easily documented as well as usage. However, we will include estimates 
for programming maintenance, for both GE Centricity EHR/Epic and the patient 
portal, and will test the sensitivity of results to changes in the maintenance 
requirements in terms of programmer hours. We also will separately track 
development costs for software and other programming requirements based on 
programmer hours. Staff/programmer costs will be measured using tracked time 
spent on the intervention and wage estimates. We will test the sensitivity of 
operational costs to different assumptions about the potential use of variable staff 
using different salaries but assuming the same proficiency in terms of time 
required. Further, we will assess the sensitivity of estimates to different proficiency 
levels that could arise from learning by doing.   
 
Exploratory Analyses. In addition to the primary per-protocol analysis, we will 
investigate if there is a “dose response” of either intervention. Specifically, we will 
look at the total weeks participating in SMS text messages and the total number of 
portal surveys completed. Additionally, we will repeat all GLMM analyses described 
for Aim 1 to explore whether differences in interventions vary by relevant covariates 
representing patient and regimen characteristics known to impact outcomes, 
specifically adherence. Interaction terms will be included in models accordingly. 
Statistical significance for a tested interaction (p<0.05) will indicate that intervention 
groups differ in outcomes by the studied variable (i.e. age, literacy level, regimen 
complexity, drug class, language, activation, comfort with texting or portal, etc.). As 
adherence has its many measurement challenges, experts recommend triangulating 
with multiple measures. We will fully investigate and compare results across each 
adherence measure (24-hour recall, pill count, PDC) and create a general estimate of 
adherence via single factor score using maximum likelihood estimation. Exploratory 
analyses will examine HbA1c and blood pressure from baseline to 6 months, although 
power may be limited.  
 

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COVID-19 Survey: By extending each of these studies (LitCog (STU00026255), 
REMinD (STU00203777), COPD Multimorbidity (STU00201640), UMS Portal 
(STU00201639), and TAKE IT (STU00204465)) to capture an additional patient-
reported outcome related to one’s knowledge, attitudes and behaviors related to 
COVID-19, we can link participants’ responses to this longitudinal survey to a 
minimum data set of participant characteristics that include demographic, 
socioeconomic, cognitive (including health literacy) and health behavioral 
characteristics. We will then be able to investigate determinants of COVID-19 
knowledge, attitudes and behaviors without duplicating data collection efforts for 
these variables. 
 
Dr. Peipert will be analyzing data from the Wave 1 health literacy items. 
 
RCs will conduct interviews by telephone using REDCap survey software. Ms. 
Opsasnick (analyst) will oversee database structure & quality assurance.  Participants 
will complete 5 phone interviews with RCs. 
 
Statistical analyses will be led by Dr. Kwasny, and all analyses will be conducted 
with SAS 9.4 (Cary, NC). Using data from the C3 cohort, participants’ perceived 
levels of stress has been assessed from the initial onset of the outbreak (March 13-
20; C3 W1), through its rapid acceleration (March 27-April 3; C3 W2) and apex 
phases (May 1-22; C3 W3), and the flattening phase (July 15- August 15; C3 W4) of 
the COVID-19 pandemic. The additional surveys provides the opportunity to 
continually assess persistent stress over a span of time that likely will include the 
pandemic’s expected, slow recovery, an anticipated second wave in the fall/winter of 
2020/2021, and its eventual recovery as well. Also during this time, there may be new 
treatments available, as well as a vaccine for COVID-19. Initial models will examine 
associations between perceived stress as a result of COVID-19 and health and 
healthcare outcomes over time among C3 participants. As perceived stress, health 
and lifestyle behaviors are expected to change over time, we will use GLMMs to 
examine the relationship between stress, and outcomes (diet, alcohol use, smoking, 
physical activity, diet, weight gain, sleep, social isolation, treatment adherence, self-
reported health status) using stress as a time-varying covariate. For data from the 
EHR, we will assess routine health care use.  
 
11.2 Power Considerations. Study sample size was based on pairwise comparisons of the 
primary outcome of medication adherence, measured by 24-hour recall, at six months 
between both the SMS texting arm and the Portal arm compared to enhanced usual 
care (Aim1, H1-3) and the interactive effect of both SMS and Portal compared to 
either intervention alone (Aim1, H4-6). We expect 69% of enhanced usual care 
participants to be adherent at six months. Enrolling 1505 participants from 1 health 
center and conservatively estimating 80% retention at six months (n=1204; 172 EHR 
and 344 per other arms), we will have 80% power to detect a minimum absolute 
difference between study arms of 12% using a Type 1 error rate of 2.5%.  
 
With the sample size set by the primary outcome of 24-hour recall at 6 months, we 
also show detectable effects for pill count and regimen consolidation, and for all 

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outcomes comparing additional intervention effects of SMS texting and patient portal 
to EHR alone (i.e. SMS text reminders vs. enhanced usual care, Portal vs. enhanced 
usual care, SMS text reminders + Portal vs. SMS text reminders only, SMS text 
reminders + Portal vs. Portal only). Estimates for the enhanced usual care arm were 
calculated based on the minimum detectable differences calculated for H1-H3 and a 
Type 1 error rate of 2.5% was used for these comparisons between each of the three 
additional arms and enhanced usual care. Note: the minimum detectable differences 
for consolidation reflect a conservative 25% reduction in sample size; we will remove 
patients from analyses who misunderstand the dose frequency for any of their 
medicines (i.e. 2 times daily vs. 3 times daily).   
 
11.3 Protocol to ensure confidentiality. 
Each subject will be tracked using the RedCap, which is encrypted, password 
protected and only accessible by approved Northwestern personnel. Identifiers and 
other related information for coordinating research activities (recruitment outcome, 
research interview call log and interview visit schedule, etc.) will be in RedCap until 
it is de-identified.  
 
Several methods will be employed to reduce the risk of breach of confidentiality. A 
study identification number will be assigned to each subject in the study. The research 
data collected and stored will have the study identification number and no other 
identifying information on it. The consent forms and the de-identified study data will 
be kept in a separate locked file cabinet. Using this method, if someone were to gain 
illegal access to the locked filing cabinet with study data, they would have no way to 
link this data to any identifying information.  
 
11.4 Quality Assurance. 
Training will begin after surveys and interview protocols have been refined and 
standardized. The project manager will lead sessions to orient the research staff to the 
surveys and study protocols (e.g., interview process, use of laptops, data security). 
The training will include tailored discussion of 1) roles and responsibilities; 2) 
HIPAA and IRB mandates (completion of Human Subjects Training Program - CITI; 
3) effective recruitment communication and interviewing with attention paid to 
health literacy and culture; and 4) gathering and recording data including 
administering the structured survey electronically.  Role playing will be used to fine 
tune training for obtaining informed consent and interviewing patients.  Institutional 
Review Board (IRB) approval will be attained prior to any active recruitment efforts.  
All interviewers will be required to demonstrate competence in survey 
administration. Training the entire research staff at once will ensure uniform 
administration of the study protocols and interviews.  
 
11.5 Study-wide data management. 
Data Access.  The Data Custodian is the Principal Investigator, Dr. Michael Wolf.  
Only authorized personnel listed on this IRB will have access to the data.  Any 
information that could allow identification of individual participants, including the 
master list, will be kept strictly confidential 
 
Local Data Storage. Data will be stored in REDCap, a secure, web-based application, 
and on the Northwestern secure servers for the length of the study. The Project 

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Manager or Data Analyst will download the data from REDCap monthly and save to 
the “Analytic” folder within the UMS Portal project folder on the FSM department 
servers which are located in a HIPAA compliant data center.  These data files do not 
contain any identifiable information, and are identified by project staff by an assigned 
study ID. All identifiable information for Northwestern patients will remain in the 
secure REDCap system.  Upon completion of all study activities, a final de-identified 
dataset will be created. This dataset will be stored indefinitely on the GIM server for 
secondary analyses. Only authorized personnel will have access to the dataset. All 
identifiable information will be deleted upon completion of the study 
 
Data Coordination Center (Northwestern). The project manager and data analyst at 
NU will combine the data and maintain the master data file containing all data, create 
a data dictionary, and be responsible for data cleaning and providing updated data to 
study investigators when requested. 
 
Data Storage.  Data will be stored on the Northwestern server for the length of the 
study.  All identifiable information will be deleted upon completion of the study.   
 
 
Provisions to Monitor the Data to Ensure the Safety of Subjects 
12.1 Data Safety and Monitoring Board (DSMB). The DSMB will be formed early in 
the project and be given responsibility to review and approve the methods and 
analysis plan. It will be organized by Drs. Wolf and Bailey and include 4 health 
services researchers with related expertise. Meetings will be via video/tele-
conference to review protocols, procedures, and concerns related to research 
integrity. 
 
 
Withdrawal of Subjects 
13.1 In the case that subjects are unresponsive for 6 months past the date their follow up 
interview was due, they will be labeled as ‘lost to follow up.’  
13.2 Participants can choose to withdraw from the study at any time.  If a participant 
chooses to withdraw from the research, any data collected up until the point of 
withdrawal will still be utilized as it will not include identifying information.  They 
will then not be contacted for further interviews or visits.   
 
 
Risks to Subjects 
14.1 Participation in the study poses minimal risk of psychological, social and economic 
harm.  Informing subjects in advance that they may decline to answer any questions 
asked during the interview and discussion group will mitigate any risks associated 
with expressing their opinions (e.g., feeling uncomfortable).  They will also be 
assured they can terminate their participation in the study at any time without penalty.  
The risk/benefit ratio is low.  Minimal to no risk is expected for subjects in this study.    
   
 
Potential Benefits to Subjects 
15.1 It is possible that subjects enrolled in the intervention study arms may directly benefit 
in that they may have, as a result of this study, a better functional understanding of 
their medication. The results of this study may provide important information 
regarding how strategies can be implemented via the EHR and mobile and computer 
technologies to support safe and appropriate medication use. 

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Vulnerable Populations 
N/A 
 
 
Community-Based Participatory Research 
N/A 
 
 
Sharing of Results with Subjects 
18.1 Study results will not be shared with participants or anyone else.  
 
 
Setting 
19.1 The Alliance of Chicago will identify potential participants who are patients at Erie 
Family Health Center. Northwestern RCs will identify and recruit potential 
participants who are patients at NMHC.  RCs will recruit and screen participants. In-
person interviews will take place in a private space at Northwestern, at Erie clinics, 
or in community sites in the participant’s neighborhood (i.e. private study rooms in 
libraries). Baseline or follow-up interview that take place over the phone will be 
completed in a private space/private offices. For interviews that are not able to be  
  
 
Resources Available 
20.1 Team. The research team is comprised of 5 PhD level researchers, 3 Physician-
researchers, 2 master’s degree level researcher, 1 project manager, and 2 bilingual 
research coordinators, all of whom have extensive research experience.  The co-PIs 
represent institutions with proven track records in health literacy, medication safety 
and adherence, and the use of health technologies. All team members have extensive 
knowledge on health literacy in the context of medication management and health 
technologies.  Co-Investigators on this project include the Chief Operating Officer 
and Director of Clinical Informatics and Chief Executive Officer of Alliance, as well 
as the Director of the Health Literacy and Learning Program (HeLP), which seeks to 
advance the study of limited health literacy and interventions that could improve 
one’s ability to obtain, process, and understand basic information needed to make 
appropriate health decisions.  The investigators have successfully collaborated on 
numerous previous projects. The project manager has 4 years of experience managing 
complex research studies and supervising research staff.  The research coordinators 
receive extensive training on research methods, interviewing techniques and the 
consent process. We have significant experience in recruiting patients from FQHCs 
(Alliance clinics specifically), conducting studies related to medications, consenting 
patients to follow-up, and conducting multi-part follow-up with both in-person and 
telephone interviews. Additionally, the team has experience in managing data in 
accordance with the best-practices of the IRB to protect patients’ confidentiality. 
 
20.2 Erie Family Health Center. Performance sites will be clinics from the Alliance of 
Chicago, an electronic health record (EHR) system user community composed of 
safety net providers in eight states. The network is an innovator and leader in using 
health information technology (HIT) among community health centers. Founding 
members are in Chicago and have a long history of collaboration with Northwestern 
researchers, and Drs. Wolf and Bailey specifically. The Alliance links 67 community 

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health center practices in the metropolitan Chicago area alone serving more than 
153,000 unique patients. All of these clinics are Public Health Service 330-funded 
FQHCs with federal mandates to provide care to medically underserved U.S. areas. 
Patients receiving care at Alliance sites are mostly African American, Latino and low 
income. We will work specifically at Erie Family Health Center (33,350 patients, 
85% Latino). Alliance FQHCs share a common EHR (GE Centricity®) to promote 
quality improvement. Erie Family Health Center will rely on Northwestern’s IRB 
(IRB Authorization Agreement letter included).  The Alliance has an IRB of Record 
with Chicago Department of Public Health, so will not rely on NU’s IRB.     
 
NMHC. NMHC serves a diverse patient population and represents the entire 
spectrum of socioeconomic status. The practice employs more than 30 attending 
physicians. 
 
20.3 Facilities. The RCs will have access to a private space to consent and interview 
patients. All follow up calls and data recording will be done from a closed 
office/private space.  
 
20.4 Training protocols. Northwestern staff training. The Northwestern project manager 
and bilingual RCs have completed Human Subjects Training (CITI) and have 
received intensive training, led by Drs. Wolf, in interview protocols and safe data 
transfer. Any new research staff will go through the same rigorous training 
requirements. 
 
 
Prior Approvals 
21.1 We have received funding from the National Institute on Aging.  
 
 
Recruitment Methods 
22.1 For patients from Erie:  
Recruitment will be done by phone by trained Northwestern RAs. First, Alliance will 
send Erie providers an encrypted file of a list of eligible patients from Erie Family 
Health Center who have an upcoming doctor appointment scheduled. Providers will 
indicate if any eligible patients should not be contacted. Providers will be reminded 
via email to reply with their list of approved patients. Providers will be informed that 
if they do not respond within two weeks they are giving Northwestern permission to 
contact all patients on the list. Northwestern will then mail a letter to patients on the 
list, notifying them that a RC will be telephoning to invite them to participate in a 
study. Patients will be given the opportunity to opt out of being contacted by calling 
a hotline number and leaving a message. RCs will monitor the messages and send 
Alliance a list of patients who have chosen to opt out. Seven days after the letters 
have been sent, a RC will call patients who did not opt out to ask screener questions 
to determine eligibility and, if eligible and interested, schedule their baseline. Due to 
COVID-19 restrictions, the study team may not be able to mail letters to all patients. 
If a letter mailing is not possible, the study team will still obtain permission from the 
provider to contact their patients, but not send a recruitment letter. 
 
For patients recruited from Northwestern Medicine Primary Care: potential 
participants will be identified through reports generated by the Enterprise Data 

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Warehouse (EDW) for patients who have an upcoming appointment scheduled.  Per 
clinic protocol, all eligible patients can be contacted and providers will not receive a 
list of their patients to indicate who should not be contacted. Research staff will then 
mail a letter to patients on the list, notifying them that a research coordinator (RC) 
will be telephoning to invite them to participate in a study. Patients will be given the 
opportunity to opt out of being contacted by calling a hotline number and leaving a 
message. RCs will monitor the messages of patients who have chosen to opt out. 
Seven days after the letters have been sent, an RC will call patients who did not opt 
out to ask screener questions to determine eligibility and, if eligible and interested, 
schedule their baseline. Due to COVID-19 restrictions, the study team may not be 
able to mail letters to all patients. If a letter mailing is not possible, the study team 
will contact patients by phone after their doctor’s visit without sending letters.            
 
If requested by the patient, the RC may text or email the patient confirming their 
interview date, time, and address. At their baseline interview, the RC will proceed 
with obtaining their written or verbal consent and administer the baseline interview. 
The patient will then be eligible to receive the remaining components of the 
intervention depending on study arm (SMS, portal, SMS+Portal) and to participate 
in evaluation activities, Participants will give written informed consent or verbal 
consent using procedures approved by Institutional Review Boards at Northwestern 
University prior to completing the baseline interview.   
 
COVID-19 Surveys Recruitment Waves 1 and Waves 2-4: Recruitment will be 
done by phone by trained Northwestern RAs. We will contact anyone who has 
indicated that they were willing to be contacted for future studies run by Dr. Wolf on 
the consent form and who completed the Wave 1 survey. Verbal consent for the 
follow up waves will be obtained prior to completing the Wave 2 telephone survey 
(initiated 2 weeks after Wave 1). Participants who consent to these follow-up 
activities will be recontacted for completion of Waves 3 and 4 at 1 month and 3 
months post-wave 2). 
 
COVID-19 Surveys Recruitment Waves 5-9: All methods of recruitment will be 
done by trained Northwestern RCs.  
 
We will first mail a recruitment letter introducing the study to all eligible patients 
prior to contacting them by telephone. If the participant is not interested in 
participating or being contacted by the researcher, he/ she can opt out by calling the 
toll-free number within 7-10 days and the RC will not contact the participants. Due 
to COVID-19 restrictions, the study team may not be able to mail letters to all 
patients. If a letter mailing is not possible, recruitment will be done by phone by 
trained Northwestern RCs and will let the patient know about the opportunity to 
continue their participation and see if they are interested in learning more about it.  
 
If they are interested in participating, the RC will engage patients in the informed 
online or verbal consent process and HIPAA Authorization, as approved by the 

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Northwestern University Institutional Review Board. After obtaining consent, RCs 
will conduct the telephone interview or schedule it to be completed at a later date.  
 
For providers and staff: To investigate healthcare provider and/or healthcare system-
level barriers to implementation, we will conduct brief online interviews (n ∼25) with 
clinic providers and staff to explore barriers and facilitators to implementing the 
various intervention strategies. The practice manager, academic manager, or clinician 
partner at Erie Family Health Center and Northwester Medicine will email providers 
and staff that may have been involved in some aspects of the study a Redcap link to 
an online consent. If the provider or staff member consent and click next, they will 
be taken to a brief online survey.  
 
22.2 Participant Payment. 
 
Research Interview 
Payment 
Form of Payment 
baseline 
 $ 40 
cash at close of in-person interview or 
money order or gift card mailed if phone 
interview completed 
6-8 week 
 $ 0 
(very brief, included in other interviews) 
6 month 
 $ 60 
cash at close of in-person interview or 
money order  or gift card mailed if phone 
interview completed 
 
COVID-19 Survey: Participants who complete the wave 1 COVID-19 survey will 
receive a $10 gift card in the mail. Any participants who completed wave 2 will 
receive a $10 gift card; participants who complete wave 3 will receive a $15 gift 
card for their time; participants who complete wave 4 will receive a $15 gift card 
for their time (for up to $40 for all follow-up activities). All participants who 
verbally consent and complete any portion of the telephone interviews will be 
compensated. 
 
COVID-19 Waves 5-9: Participants will receive the following compensation for 
each interview they complete:  
 
Timepoint 
Compensation 
Wave 5 
$20 gift card 
Wave 6 
$20 gift card or 
money order 
Wave 7 
$30 gift card or 
money order 
Wave 8 
$30 gift card or 
money order 
Wave 9 
$40 gift card or 
money order 
 

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Money orders may issued for subject compensation for COVID-19 
supplement surveys if Visa gift cards are problematic for the subject. 
 
 
Local Number of Subjects 
23.1 A total of 1505 participants will be recruited from Erie Family Health Center clinics 
and NMHC. 
 
 
Confidentiality 
Only authorized research personnel will have access to study related data. Each 
participant will be tracked using Access and RedCap.  Identifiers and other related 
information for coordinating research activities (recruitment outcome, research 
interview call log and interview visit schedule, etc.) will be kept on the secure FSM 
network drive. Only the PI, project manager, and RCs will have access this database.  
Identifiers included in the database include: name, MRN, address, phone number, 
DOB. Upon completion of all study-related data collection the database with 
identifiable information will be deleted. Study generated data will be collected and 
stored in RedCap and SharePoint and will be download (void of all identifiers) into 
the project’s Analytic folder on the FSM server. Upon completion of the study, a final 
dataset, void of all identifiers will be created, and stored indefinitely for secondary 
analyses.   
 
 
Provisions to Protect the Privacy Interests of Subjects 
25.1 Information about study subjects will be kept confidential and managed according 
to the requirements of the Health Insurance Portability and Accountability Act of 
1996 (HIPAA). In order to preserve participants’ confidentiality rights, research 
subjects will be assigned code numbers that will be used to identify all the 
information collected. Using these codes, none of the collection forms will contain 
the names of the participants. All electronic data will be stored in on a password-
protected computer. A master study tracking database via Microsoft Access will 
contain information linking participants to their study id numbers. This database will 
be encrypted and password protected, kept on a secure server and only accessible by 
study personnel. Survey data will be stored in a REDCap. The data will not contain 
any identifiable information. Individual study identification numbers will be 
assigned to each participant and only this number will appear on the survey. 
Subjects will be informed that participation in any part of this research study may 
result in a loss of privacy, since persons other than the investigators may view their 
study records if deemed necessary for oversight purposes.  However; they will be 
identified by a unique identification number (“study id”), not by name, and any other 
identifying information (e.g. personal and/or contact information) will be kept 
separate from the other data; all information will be kept in secure, password-
protected files.  Personal information will be encrypted and linked to the study 
number. Further, subjects will be told that unless required by law, only the study 
investigators, members of the project staff, and representatives of the Northwestern 
University and local Institutional Review Boards will have the authority to review 
any study records.  In such case, they too will be required to maintain confidentiality. 
 

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25.2 Participation in the study poses minimal risk of psychological, social and economic 
harm.  Informing subjects in advance that they may decline to answer any questions 
asked during the interview and discussion group will mitigate any risks associated 
with expressing their opinions (e.g., feeling uncomfortable).   
 
25.3 All enrolled participants will provide written or verbal consent, include HIPAA 
authorization for the collection of all data, including review of the patient’s medical 
records.   
 
 
Compensation for Research-Related Injury 
N/A 
 
 
Economic Burden to Subjects 
N/A 
 
 
Consent Process 
28.1 Written consent will be obtained for all participants, prior to their participation.  The 
consent process will take place in a private room at NMHC, Erie clinic, in community 
sites in the participant’s neighborhood (i.e. private study rooms in libraries), or over 
the phone (RC will be in a private space).  For patients unable to complete the in-
person interview/in-person written consent due to COVID-19, we request a waiver 
of documentation of informed consent and an alteration to obtain verbal HIPPA 
Authorization. Due to restrictions to in-person interviews during the COVID-19 
pandemic, in-person interviews will not be able to be completed in-person to protect 
patients’ safety and to follow Northwestern guidelines. Research can not practicably 
be conducted without the waiver or alteration. After verbal consent and HIPPA 
Authorization is obtained, the consent date and the name of the research coordinator 
that obtained the consent will be recorded in Redcap prior to starting the baseline 
interview. Participants will be provided a consent form in their preferred language 
(English or Spanish). A bilingual (English/Spanish) research coordinators will work 
with participants who prefer Spanish language, and will communicate in Spanish 
with potential participants.  Informed consent and verbal consent will be viewed as a 
process, i.e. at several times during review of the IRB approved consent document, 
the subject will be asked to explain in his/her own words what his/her understanding 
of the consent. This will enable the research personnel to enter into a dialogue with 
the subject and ensure that the subject understands that he/she is free to withdraw at 
any time without penalty. Information will be provided to the subjects in terms that 
they can fully understand. There will be no exertion of any overt or covert coercion. 
They will be encouraged to ask questions prior to giving consent.  
 
28.2 Verbal consent process for COVID-19 survey:  
Subjects will be informed about the nature of the study by a CITI-certified RC and 
asked to provide verbal consent.  They will be informed that they may withdraw from 
the study at any time and given contact information for the PI and RC. A verbal 
consent, or a waiver of documentation of consent, is deemed appropriate because the 
nature of the study involves minimal risk and no PHI will be collected. If a patient 
agrees to participate after the RC reads the consent, the RC will record the patient’s 

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name on the consent form and the RC will sign their own name on the form. These 
consent forms will be locked in a file cabinet only accessible to necessary research 
staff. Patients will be given the option to receive a blank consent form for reference 
if they request it.   
 
For the follow-up waves of the COVID-19 survey, the same verbal consent process 
will be followed as above prior to wave 2. 
 
28.3 Online and verbal consent process for COVID-19 Waves 5-9:  
 
Subjects will be informed about the nature of the study by a CITI-certified RC and 
asked to provide online consent with HIPPA authorization and complete the wave 5 
interview after consent is obtained. If interested, the RC will send patients a link to 
Redcap either by email or SMS text to be able to read through the consent with the 
RC following the protocol below. If the patient agrees to participate, they will be 
asked to enter their first and last name, signature, date of birth, and date of consent to 
complete the online consent. 
 
If a patient is unable to complete the online consent due to inability to use technology 
for online consent, we request a waiver of documentation of informed consent and an 
alteration to obtain verbal HIPPA Authorization. After verbal consent and HIPPA 
Authorization is obtained, the consent date and the name of the research coordinator 
that obtained the consent will be recorded in Redcap by the RC prior to starting the 
first phone interview. 
 
Informed, online and verbal consent will be viewed as a process, i.e. at several times 
during review of the IRB approved consent document, the subject will be asked to 
explain in his/her own words what his/her understanding of the consent. This will 
enable the research personnel to enter into a dialogue with the subject and ensure that 
the subject understands that he/she is free to withdraw at any time without penalty. 
Information will be provided to the subjects in terms that they can fully understand. 
There will be no exertion of any overt or covert coercion. They will be encouraged 
to ask questions prior to giving consent. 
 
Once online consents are filled out, they will get an automatic email with the signed 
version of the consent. Patients will also be informed that they may print their screen 
to keep a copy of the consent. For patients that complete a verbal consent, they will 
be offered a copy of the consent document to be sent via email or mail for their 
records according to their preference. 
 
28.4 Online consent process for Provider/Staff survey 
We will ask providers and staff to consent to complete a brief online survey to obtain 
feedback about the trial.  Providers and staff will be informed of the nature and details 
of the survey via email.  They will be asked to complete an online consent to complete 
the brief survey. We request a waiver of documentation of consent for the 
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because the nature of the survey involves minimal risk and no PHI will be collected. 
In order to complete the online consent, participants will be asked to click if they 
agree or disagree before moving forward to the online survey. 
 
 
Process to Document Consent  
29.1 
Written or verbal consent will be obtained for all participants, prior to their 
participation.  The consent process will take place in a private room at NMHC, Erie 
clinic, in community sites in the participant’s neighborhood (i.e. private study rooms 
in libraries), or by phone (RC will be in a private space).  Participants will be provided 
a consent form in their preferred language (English or Spanish). A bilingual 
(English/Spanish) research coordinators will work with participants who prefer 
Spanish language, and will communicate in Spanish with potential participants.  
Informed consent will be viewed as a process, i.e. at several times during review of 
the IRB approved consent document, the subject will be asked to explain in his/her 
own words what his/her understanding of the consent. This will enable the research 
personnel to enter into a dialogue with the subject and ensure that the subject 
understands that he/she is free to withdraw at any time without penalty. Information 
will be provided to the subjects in terms that they can fully understand. There will be 
no exertion of any overt or covert coercion. They will be encouraged to ask questions 
prior to giving consent.  If the participant agrees to participate in the study, they will 
be asked to sign and date the consent form before proceeding with the interview.  The 
research coordinator guiding the consent process will then sign and date the consent 
form.  If a written consent is obtained, participants will receive a copy of the signed 
consent form.  After the interview, signed consent forms will be stored in locked 
cabinets in General Internal Medicine. For phone interviews, the patient will 
complete a verbal consent and verbal HIPPA Authorization. Patients will be emailed 
or mailed a blank copy of the consent document for their records. 
29.2 
Provider/Staff survey. Online consent will be obtained from providers and 
staff. All participants will be told that their participation is voluntary; they can stop 
at any time, and whether they participated or not will not be disclosed to their 
superiors.  If the provider/staff  does not want to participate or decides to stop before 
completing the survey, this will not be disclosed to any superiors.   
 
 
Drugs or Devices 
N/A