SteadyRx: Smartphone ART Adherence Intervention for Drug Users
Phase: NA
Conditions: HIV, Medication Adherence
Sponsor: Johns Hopkins University

 
STUDY TITLE: SteadyRx: Smartphone ART Adherence Intervention for Drug Users 
 
NCT: 02317614 
 
PI: Michael Fingerhood  
 
DATE: July 17, 2017 

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ABSTRACT 
Purpose 
The primary purpose of the “SteadyRx” protocol is to evaluate the SteadyRx 
Smartphone-based intervention as a means of promoting and maintaining 
antiretroviral adherence in people living with HIV who are struggling with 
addiction. 
Participants & Inclusion/Exclusion Criteria 
Study participants will be selected from adults who are receiving care at the 
Comprehensive Care Practice on the Johns Hopkins Bayview Medical Campus. 
Applicants will be eligible to participate in the study if they: a) are 18 to 100 years 
old; are HIV positive; c) have a primary care physician who is providing their HIV-
related care including prescribed ART; d) meet criteria for substance use disorder; e) 
speak fluent English; f) can operate a smartphone. Applicants will be excluded if they 
a) report current suicidal or homicidal ideation; b) report active hallucinations; or c) 
are enrolled in another HIV/AIDS-related or medication adherence-related study. 
 
Design 
This randomized controlled pilot study features a parallel group design. Participants (N 
= 50) will be randomly assigned to one of the two groups: Treatment as usual (TAU) or 
the SteadyRx-supported antiretroviral adherence group (SteadyRx). We will randomize 
using urn stratification to promote equal numbers of individuals in each group and 
balanced distributions within a dichotomized covariate expected to be associated with 
the outcome. Stratification variables are current depression (Y/N); self-report of problem 
drug use in the last 30 days (Y/N); and TOFHLA score ≤ the rolling median (Y/N). Study 
participation will last for six months from the date of randomization. 
 
 

5 
 
Standard Services 
Participants will be receiving care for their HIV at CCP. This will include ART. 
 
Assessments 
An intake assessment (e.g., ASI-Lite) will be collected prior to randomization. 
Additional assessments will be conducted at 30-day intervals throughout the 6-month 
intervention period. All assessment forms are listed in the List of Manual Forms. 
Complete descriptions of each assessment and the schedule of delivery for each 
assessment is provided below. 
 
Primary Outcome Variable 
The primary outcome measures for intervention effectiveness will be (1) the 
percent of participants who take 95% of prescribed doses of their antiretroviral 
medication(s) within three hours of their scheduled dosing time each month as 
measured by MEMS, and (2) the percent of participants who achieve a viral load <400 
HIV-RNA/mL at each of the two assessments collected during the active intervention 
period. 
 
Secondary Outcome Variables 
Secondary Measures. (1) Monthly percentage of on-time (i.e., within three hours 
of the scheduled time set by patient-physician agreement) bottle openings as measured 
by MEMS and self-report, respectively. Note that this is different from the primary 
measure which dichotomizes adherence (Y/N) with a 95% threshold. The primary 
measure is the measure of greatest clinical significance. The secondary measure is more 
sensitive to changes in behavior; (2) CD4 counts and HIV-1 RNA levels obtained at 
primary care visits. 
Exploratory Measures. (1) MOS-HIV physical health and mental health summary 
scores (0-100) across the study period; (2) self-reported days of opiate and cocaine use. 
Usage, Acceptability, and Cost Measures. Outcomes related to the usage and 
acceptability of the Smartphone application will include Acceptability Questionnaire 
total score, SUMI global scale score, average uses per day, and average duration of use 
per day. Outcomes related to the cost of the intervention will include total cost of the 
intervention per person, and the incremental cost-effectiveness ratio (ICER). To 
calculate ICER, we will divide the costs of the intervention by the difference between the 
two groups in terms of the percent of participants who take 95% of prescribed doses of 
their antiretroviral medication. The ICER can be interpreted as dollars spent per unit of 
desired outcomes gained. In addition, a more complete cost/benefit analysis conducted 
by academic economists will be included in a future large-scale study. 
 
 

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INVESTIGATORS 
The following is a list of the responsible investigators for the study and their 
contact information. 
 
Western Michigan University 
 
Department of Psychology 
 
Anthony DeFulio, Ph.D. (Principal Investigator)  
Department of Psychology 
Western Michigan University  
Kalamazoo, MI 49008-5439 
P: (269)387-4459 
C: 410-340-3524 
 
Johns Hopkins University  
Department of Medicine: 
Dr. Michael Fingerhood, MD  
Chemical Dependency Unit  
Baltimore, MD 21224 
5200 Eastern Ave. West Tower  
P: 410-550-2999 
C: 410-218-8190 
 
Department of Psychiatry and Behavioral Sciences: 
 
Kenneth Silverman, Ph.D.  
5200 Eastern Ave. Ste 142W  
Baltimore, MD 21224 
P: 410-550-2694 
 
 

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RECRUITMENT 
Responsible Staff 
The Outreach Coordinator and Student Investigators will be responsible for 
conducting the screening interviews. Only approved staff members will be responsible 
for obtaining informed consent to participate in this research. The Outreach 
Coordinator will coordinate the recruitment process and will supervise all recruitment 
activities. All aspects of the recruitment process are detailed in the Intake Assessment 
Checklist, which should be used to guide the entire process from the first time we are 
introduced to a potential participant to the time when they are randomly assigned to a 
study condition. 
Rate of Recruitment 
We will need to randomly assign five people per month to the study conditions. 
This may require obtaining consent for more than five people per month. We can begin 
by obtaining initial consent from a minimum of two people per week, and then reducing 
this number if the rate of random assignment greatly exceeds our target. It is 
acceptable to have a rate of recruitment that is higher than the target, but it is a 
problem to have a rate of recruitment that is lower than the target for an extended 
period of time. 
Identifying Participants 
Overview of initial screening procedures. It is possible that all participants will be 
patients at the Comprehensive Care Practice (CCP). CCP is located in the Mason F. 
Lord Building at the Johns Hopkins Bayview Medical Center in Baltimore, MD. CCP 
provides primary medical care to ~450 HIV+ adults and will serve as the primary 
recruitment site. However, over the course of this research we will attempt to identify 
possible recruitment sites within the State of Michigan. If we identify sites within 
Michigan, we will seek WMU IRB approval for those sites prior to initiating 
recruitment from those sites. Recruitment procedures across the sites will be as similar 
as possible given local resource constraints. Any differences will be specified 
concurrently with seeking approval for the new site(s). 
Participants will be recruited from their regularly scheduled HIV care 
appointments at which current viral load and CD4 counts are evaluated. Anyone who is 
HIV positive who meets the criteria for substance use disorder will be told by their 
doctor about our research study and given a recruitment flyer that explains the nature 
of participation. 
Script for physician: I am conducting a research study with my 
colleagues that may be of interest to you. The research study is 
testing a way to help people living with HIV take their antiretroviral 
medicines according to their prescriptions. The study provides $50 per 
month for participating in an interview and showing the interviewer 
your pill bottle. Some people in the study will also get money for 
taking their medication. Here is a flyer about the research study. If it 
seems like something that might interest you, then you can talk to the 
outreach coordinator today. She can tell you more about the study and 
will ask you a few questions to determine if the study is right for you. I 
want to stress that participating in this 

8 
 
research is optional, and that your care at Johns Hopkins will not be 
affected in any way by your decision to participate or not participate. 
Would you like to talk to the outreach coordinator to learn more about it? 
 
If they express interest in learning more, the doctor will contact the staff 
member at the doctor’s office who is in charge of study recruitment and 
assessment (hereafter, outreach coordinator). The person who is currently 
serving in this role is Tyesha Karume. Tyesha has a bachelor’s of science in 
nursing and a masters of education. She regularly consults with 
Comprehensive Care Practice patients regarding the importance of medication 
adherence and helps them address barriers to adherence and access to care. 
Tyesha is a JHU employee who is listed on the JHU IRB protocol as a study 
team member, has completed all training required by the JHU IRB, and is 
approved by the JHU IRB as a consent designee for this study. The outreach 
coordinator will go upstairs to CCP and wait for the patient to finish their 
appointment. Once the appointment is complete, the outreach coordinator will 
escort the patient to their office. The outreach coordinator will briefly explain 
the intake interview process and basic purpose of the study. 
 
Script for outreach coordinator: As you know, I am recruiting 
participants for a research study. This study is about a smartphone- 
based intervention for medication adherence that makes it easier for 
users to contact their care providers, provides users with reminders to 
take their medicine, and pays users money when they submit videos of 
themselves taking their pills each day. Half of the people who join this 
study will be randomly selected to receive the smartphone-based 
intervention, which we call SteadyRx. All of the people who join this 
study will get paid $30 per month for participating in interviews and $20 
for bringing me a special electronic pill bottle that we will use to hold your 
medicine that tracks when you open the bottle, a total of $50 per month. If 
you are interested in joining this study, then I will help you to do that. We 
will need to schedule another appointment in order to move forward. 
During this appointment, we will go through a study consent form 
together that explains the study in detail. Then I will ask you questions 
that will allow me to assess whether you qualify to take part in this 
study. The whole process will take about two hours. Since it includes an 
interview, you will be paid $50 if you complete this process, whether or 
not it turns out you qualify for the study. Would you like to proceed? 
 
If the patient agrees to move forward they will schedule an appointment 
for 10:00 AM or 1:00 PM on the next day or as soon as possible. Participants will 
be instructed to bring their pill bottles to the appointment. 
Intake Interview 
Reminder Calls Participants who have not returned for their assessment will 
be given reminder calls related to their scheduled intake interview by the 
student investigators. They will also receive follow up calls if they fail to show 
up for their 

9 
 
scheduled appointment time. Reminder calls will be given one day before their 
scheduled appointment. The calls will be between 10AM – 6PM Monday through 
Thursday and 1PM – 5PM on Sunday. 
If the participant does not answer, the student investigator will wait one hour and 
then call again. This process is repeated if they do not answer again. If they do not 
answer a third time, the student investigator will leave the following voicemail: 
 
“Hi (PERSON's NAME), my name is *First Name* and I am calling on behalf 
of Tyesha Karume at the Comprehensive Care Practice at Johns Hopkins 
Bayview. I just wanted to remind you that you have an appointment 
scheduled for (APPOINTMENT TIME) tomorrow and confirm that you will 
be coming. Thank you and have a nice day.” 
 
If someone other than the participant answers the phone, follow the following 
script: 
 
"Hi, I'd like to speak to (PERSON'S NAME)." If the person on the phone asks 
who you are or why you are calling then say, "My name is *First Name* and 
I am calling to remind them about an appointment they have at Johns 
Hopkins tomorrow." If they ask for further details tell them "I'm sorry, but I 
am only allowed to discuss details with (PERSON'S NAME)." 
 
Once the participant is one the phone, follow the following script: 
 
"Hi (PERSON'S NAME), my name is *First Name* and I am calling on behalf 
of Tyesha Karume at the Comprehensive Care Practice at Johns Hopkins 
Bayview. I just wanted to remind you that you have an appointment 
scheduled for (APPOINTMENT TIME) tomorrow and confirm that you will be 
coming.” If they say yes, say "Okay, great, remember that your appointment 
is at (APPOINTMENT TIME) and that you need to bring your pill bottle and 
will be paid $30 for completing the interview and if you qualify for the study, 
then you will receive an additional $20 for bringing your pill bottle. That 
means you will be paid up to $50 tomorrow for bringing your pill bottle and 
completing the interview." Once they respond, then say "Okay, see you at 
(APPOINTMENT TIME) tomorrow, have a great day, Bye." 
 
If they indicate that they are unsure, or do not know what you are talking about, 
follow the following script: 
 
“Tyesha asked me to call you because I am helping her recruit participants for 
a research study and you are scheduled for an appointment with her 
tomorrow. If you'd like, I can remind you what the study is all about." 
 

10 
 
If they wish to be reminded, follow the following script: 
"This study is about a smartphone-based intervention for medication 
adherence that makes it easier for users to contact their care providers, 
provides users with reminders to take their medicine, and pays users money 
when they submit videos of themselves taking their pills each day. Half of 
the people who join this study will be randomly selected to receive the 
smartphone-based intervention, which we call SteadyRx. All of the people 
who join this study will get paid $30 per month for participating in 
interviews and $20 for bringing me a special electronic pill bottle that we 
will use to hold your medicine that tracks when you open the bottle, a total 
of $50 per month. The whole process will take about two hours. Since it 
includes an interview, you will be paid $30 if you complete this process 
tomorrow, whether or not it turns out you qualify for the study, and $20 for 
bringing your pill bottle if you qualify for the study." 
Reminder calls will be discontinued immediately upon request of the participant, 
will not exceed three per week, and will be discontinued after one month from the 
originally scheduled intake interview or appointment time. 
Calling No-Shows. Any participant who does not show up for the randomization 
appointment at their scheduled time should be contacted via phone by outreach 
staff, reminded of their appointment, reminded of the possibility of entering the 
study, and rescheduled if necessary. A record of all attempts to call no-shows 
should be kept on a separate contact log. 
Transportation to the Intake Appointment. Should the participant be unable to 
immediately attend the intake appointment following the initial screening, the 
participant should be assisted in developing a plan to attend the appointment. We 
cannot provide financial assistance to make this happen, but we do provide a 
reloadable gift card with an initial value of $50 to everyone who completes their 
intake interview, independent of whether they qualify or choose to continue and 
be randomly assigned to one of the study groups. If a participant is unable to 
complete the intake assessment through no fault of their own (e.g., technical 
malfunction) and must return, they will be compensated $20 for the return trip. 
Procedures for Initiating the Intake Assessment. Once the participant has 
arrived for the intake assessment, the outreach coordinator will obtain the 
CD4/RNA counts, substance abuse history, and depression diagnosis from the 
participant’s primary physician. The outreach coordinator will print out the 
following materials: 
1) Inclusion/Exclusion Checklist; 2) Smartphone Assessment; 3) Study Consent 
Form; 4) HIPAA form; and 5) Material Acknowledgement Form. The outreach 
coordinator will contact the WMU staff to inform them that the participant has 
arrived and give them the CD4/RNA counts, the substance abuse history, and 
depression diagnosis of the participant. The outreach coordinator will then 

11 
 
initiate the Smartphone Assessment. If the participant meets inclusion criteria, 
the outreach coordinator will escort him/her to the assessment station on the 
second floor of CLH. If the participant is excluded, the outreach coordinator 
should ask if the participant needs bus tokens and dismiss them. The outreach 
coordinator will set the participant up at the assessment computer to begin the 
informed consent process. The assessment computer is under the control of the 
WMU staff using TeamViewer remote control software. 
Informed Consent Process. The consent process will require that participants are 
seated at a computer that will run a presentation that plays a recording of staff 
reading the consent form aloud and also displays the corresponding consent form 
text on the screen. Participants will be given their own paper copy of the consent 
form, and a staff member will then begin the computerized presentation. If the 
computerized presentation is not available, a study team member will read the 
consent form aloud to the subject. The study team member will answer any 
questions posed by the participant during the reading of the consent form. At the 
end the study team member will ask, “Do you have any questions?” or if the 
participant asked questions during the reading, “Do you have any more 
questions?” If the participant asks a question that is directly related to the 
consent process or the intake interview that cannot be answered by referencing 
the consent form, then the study team member should immediately call the 
principal investigator and consult with him prior to answering the question. After 
the consent form has been presented to the participant, they will be given a brief 
quiz that will address the major points of the consent form to ensure that they 
understand the details of the consent form. Any errors will be explained and 
corrected by the study team member. An investigator will be consulted if a person 
scores less than 70% correct, or if the subject has any questions that the person 
administering the consent cannot address. If the participant scores more than 
70%, the study team member will ask, “Would you like to participate in the 
interview?” Participants will be given as much time as they need to give initial 
consent. If the participant declines, the study team member will thank them for 
their time and see the participant out of the research space. If the participant 
accepts, the study team member say, “Please sign and date the initial consent 
form,” and indicate where to do so on the form. The staff member should also sign 
and date the form as indicated. The participant should be told to retain their copy 
of the consent form. At this point, the initial consenting procedure is complete 
and the intake interview can begin. 
Inclusion/Exclusion Criteria and Checklist. The Inclusion/Exclusion Checklist 
lists the inclusion/exclusion criteria for the study and the location where the 
relevant information can be obtained to determine whether or not a participant 
meets each criterion. At no time should any study team member disclose to the 
participant the requirements for eligibility into the study. If a participant asks a 
question related to the eligibility criteria, immediately consult with the principal 
investigator about what action to take. During the intake interview, the 

12 
 
Inclusion/Exclusion checklist should be updated and reviewed. If the participant 
has either failed to meet an inclusion criterion or has met an exclusion criterion, 
then the participant should be dismissed. Of course, participants can stop the 
interview at any time and for any reason. A participant who chooses to stop the 
interview permanently prior to the completion of the interview will be considered 
dismissed and will not be further evaluated for study participation. If a 
participant is excluded following the informed consent, they should be paid $50 for 
participating in the intake assessments. 
Inclusion/Exclusion Criteria: 
Applicants will be eligible to participate in the study if they: 
a) Are 18 to 100 years old 
b) Are HIV positive 
c) Have a primary care physician who is providing their HIV-
related care including prescribed ART 
d) Meet criteria for substance use disorder 
e) Speak fluent English 
f) Can operate a smartphone 
 
Applicants will be excluded if they: 
a) Report current suicidal ideation. Immediately initiate suicide 
prevention protocol in accordance with CCP policy/practices. 
b) Report auditory or visual hallucinations. Immediately alert study 
doctor if a participant has active hallucinations. 
c) Are currently participating in any other HIV/AIDS related or 
medication adherence related research studies. 
Informing Participants of Eligibility/Ineligibility. The applicants should never be 
told why they are eligible or ineligible. This policy will prevent the community 
from learning about the eligibility criteria. This is imperative, since knowledge of 
the study criteria could result in applicants either falsely self-reporting 
characteristics in an effort to get admitted to the study. All staff members should 
be intimately familiar with the policies related to eligibility described in this 
treatment manual. 
The Intake Interview. The interview will be conducted by using the SteadyRx 
Intake Assessment Checklist – Outreach Coordinator and the Intake Assessment 
Checklist – WMU Staff. This interview includes the Smartphone Assessment 
Protocol, the Testing of Functional Health Literacy in Adults (TOFHLA), the Beck 
Depression Inventory (BDI-II), the Visual Analog Scale for self-reporting ART 
adherence, the Medical Outcomes Study HIV Health Survey, Addiction Severity 
Index – Lite (ASI- Lite), and the Patient Reactions Assessment. 

13 
 
The Smartphone Assessment Protocol assesses whether participants can 
operate a smartphone. 
The Test of Functional Health Literacy in Adults (TOFHLA) – a 
standard measure of health literacy which has been shown to predict 
ART adherence. 
The Visual Analog Scale for self-reporting ART adherence which has 
been recommended as providing the highest quality self-reports of ART 
adherence in several recent studies. 
The Medical Outcomes Study HIV Health Survey is a widely used 
assessment of quality of life for HIV/AIDS patients that assesses perceived 
physical and mental health. 
The Addiction Severity Index-Lite which assesses drug use and related 
problem severity 
The Patient Reactions Assessment is a 15-item validated instrument for 
assessing a patient’s perceived ability to initiate communication about their 
illness. This will allow us to determine whether the consult element of 
SteadyRx has an effect on patient’s perceptions of the quality of their 
communication with their provider. 
After the intake interview is completed, the staff member should review 
and complete the Inclusion/Exclusion checklist. If the participant is eligible, then 
he/she should be informed that he/she is a candidate for diversion to treatment 
and he/she is invited to participate in a research study. 
Any participant who is ineligible should be informed that they are not 
eligible to participate in the study. Upon notification of ineligibility, some 
participants may be saddened or angered. See the section on study eligibility for 
further details describing how to handle ineligible participants. Be sure to retain 
all completed assessments, independent of whether a participant was eligible for 
the study. Assessments completed by ineligible participants will be collected and 
stored separately from assessments completed by eligible participants. 
CD4 counts and HIV-1 RNA levels. The participants will sign a separate consent 
form granting their care provider (i.e., Comprehensive Care Practice) permission 
to share their test results with the study team. Thus, we anticipate that we will 
have a baseline measure and two study period measures of CD4 and HIV-1 RNA 
levels for pilot study participants. We will also maintain a record of scheduled 
appointments and whether the participant attended each appointment (Y/N; 
coded yes for any appointment attended within one week of the originally 
scheduled date). Importantly, we will be collecting our monthly assessments on 
the same day as the patient is scheduled to have their CD4 and HIV-1 RNA levels 
checked in the same building. Note that we do not plan to interface directly with 

14 
 
the existing medical records systems used by care providers. Instead, care 
providers will submit the information to the outreach coordinator, who will relay 
the information to the study team in Kalamazoo via the phone. 
 
 

15 
 
RANDOM ASSIGNMENT TO STUDY CONDITIONS 
Overview 
The random assignment process is the collective responsibility of student 
investigators and the outreach coordinator. The separate roles of these staff 
members in this process are described in separate sections below. The day of 
random assignment must occur within two weeks of the first meeting. If a 
participant has not completed the necessary procedures for randomization by the 
two-week time point, then that participant should be permanently discharged 
from the study. 
Procedures 
Overview. All staff will be prepared for the intake assessment. After the informed 
consent is signed by the participant, the Outreach Coordinator notifies the WMU 
staff and brings the participant to the computer terminal. Student investigators 
will have the primary responsibility for randomly assigning participants to one of 
the two study conditions. After completing the randomization procedure, the 
Outreach Coordinator and WMU staff should train participants how to use the 
SteadyRx app and PillWatch function (if in SteadyRx group), distribute CTPayer 
card, and update relevant data logs. 
Randomization Variables. The proposed pilot study will feature a 2 group, 
randomized controlled, parallel group design. In order to assess the effectiveness 
of the proposed intervention as a whole, participants will be assigned to receive 
usual care (Control Group) or the SteadyRx smartphone intervention. A 
computerized urn randomization procedure will be used to randomize participants 
and balance groups on three baseline characteristics that may independently 
influence the main outcome measures of ART adherence and viral load. 
Specifically, depression, active drug use, and low health literacy have all been 
shown to be associated with reductions in ART adherence. Thus, we will use 
presence of current depression (Y/N); self-reported recent Cocaine or Opiate use 
(Y/N); and TOFHLA (a health literacy measure; see Assessments) score ≤ the 
rolling median (Y/N) as the stratification variables in the present study. While it 
might be desirable to stratify on additional variables, increasing the number of 
variables is not practical given the study’s sample size. 
Procedure. After obtaining informed consent, the student investigator will 
complete the intake interview. First, the ASI-Lite will be administered to finish 
determining eligibility. If the participant is eligible for the study, the TOFHLA 
will be administered. While the participant is completing the ASI-Lite and the 
TOFHLA, the student investigator will call the Outreach Coordinator to obtain 
depression status, CD4 count, HIV-1 RNA levels, and drugs of abuse history 
information. Once the participant has completed the TOFHLA and information 
regarding recent drug use and depression status, group assignment can be 
determined. The student investigator will then call the principal investigator, 

16 
 
Anthony DeFulio, and give the answers to the stratification variables. The 
principal investigator will then run the urn randomization procedure and relay 
the group assignment to the student investigator. The participant will then 
complete the rest of the surveys (Visual Analog Scale for self-reporting ART 
adherence, MOS-HIV, Patient Reactions Assessment, SteadyRx Reminder 
Enrollment Form, and Contact Information Sheet). 
Notifying Outreach Coordinator. After the participant has been randomized and is 
completing the rest of the assessments (see above), the student investigator will 
inform the Outreach Coordinator of the group assignment. The Outreach 
Coordinator will bring the necessary materials to complete the intake to the 
participant (MEMS cap, CT Payer card, and smartphone (if in SteadyRx group). 
After the Outreach Coordinator is notified of study condition, and the assessments 
are finished, the student investigator will inform the participant of study 
condition. 
Notifying Participant of Study Condition. The student investigator will notify the 
participant of the result of the randomization procedure. 
 
If the result is the SteadyRx group, the student investigator will say the following: 
“You have been assigned to the SteadyRx group. This means that you are 
able to be paid $30 each month for coming here and completing an interview 
with our outreach staff. This also means that you will be provided with a cell 
phone for 6 months. You will be provided with a medicine cap that will go on 
top of your prescription HIV medication bottle. You are responsible for 
keeping track of both of these items. If either of these items are lost, stolen, 
or sold, you will be penalized. If you keep your cell phone for the whole 
study, you will receive $100 at the end of the study. Instead of receiving 
$100 for returning the cellphone, you may choose to keep it. Each time you 
bring your medicine cap back to an interview, you will receive $20. On the 
cell phone, you will find an app called SteadyRx, which we will teach you 
how to use now. Do you have any questions?” 
 
If the result is the control group, then the student investigator will say the 
following: 
“You have been assigned to the control group. This means that you are able 
to be paid $30 each month for coming here and completing an interview with 
our outreach staff. Each month, we’ll set up an appointment for the 
following month and our outreach staff will be calling you from time to time 
to remind you about your appointments and the money you can make. You 
will be provided with a medicine cap that will go on top of your prescription 
HIV medication. Each time you bring the medicine cap to an assessment 
interview, we will pay you $20. We will make an appointment with you for 
our next meeting today before you leave. I’d also like to provide you with $50 
for coming here today, and you may also have two bus tokens if you’d like. 
Do you have any questions?” 

17 
 
If the participant was found ineligible for the study due to answers given in the 
ASI-Lite, then the student investigator will read the following script: 
“Unfortunately, you did not qualify for the study.  The good news is that we 
are paying you $50 for your time today. Tyesha should be down any 
moment with the card. We want to emphasize that we thank you for coming 
out and taking time to complete these assessments. This also is a very 
important part of our study. We also wanted to note that this will not 
change your care at the CCP or at Johns Hopkins. Thank you again for 
your time.” 
MEMS Cap. All participants will receive a MEMS cap which is to be placed on the 
cap of their prescription HIV medication. The intake assessment cannot take place 
if the participant did not bring their pill bottle. The student investigator is 
responsible for initiating a participant into the MEMS database located at 
http://www.mwvaardex.com/. The student investigator should use their own 
personal login information to access the database. 
Assigning Materials. All participants will be assigned a CTPayer card which will 
be loaded with $50 for completing the intake assessment, regardless of study group 
assignment. All participants will sign a SteadyRx Material Acknowledgement 
Form that specifies what materials they received. A log will also be updated with 
this information. 
CT Payer. All debit cards will be issued and loaded through CTPayer. The 
outreach coordinator will be responsible for issuing the debit card. Prior to giving 
the debit card to the participant, the outreach coordinator will call the student 
investigator in Kalamazoo and inform them of the specific card being issued to the 
participant. The principal investigator and student investigators will be 
responsible for assigning the debit card to participants and paying participants 
through the CTPayer system. Immediately after being informed of the debit card 
information, the student investigator will login to the CTPayer system with the 
lab account through their website https://partners.payoneer.com/ and change the 
Payee ID of the specific debit card to the participant’s assigned participant ID. 
SteadyRx Group Only. Participants in the SteadyRx group will receive a 
Smartphone with the SteadyRx application downloaded onto it. Participants 
will be required to complete PillWatch protocol. 
Creating Participant SteadyRx accounts. The responsibility of creating Motiv8 
Systems accounts for participants in the SteadyRx group will be the student 
investigators’ in Kalamazoo. In order to access the backend of the SteadyRx, the 
student investigators will create an admin account for themselves using the 
credentials given by the principal investigator. The student investigators will then 
navigate to the following URL: http://steadyrx.red5hift.com. 

18 
 
The Clients tab should be the default start page. Click “Add Client” in order 
to begin the process. Both their login and their alternate ID will be the 
participants’ PTID. The password will be selected from the list of passwords 
created by the principal investigator on the shared Google Drive. Once a password 
has been assigned to a participant, cross that password out on the list. After 
creating the account, the student investigator must then assign participant to 
either the OnePerDay or TwoPerDay program. This will correspond to whether 
the participant must take their antiretroviral medication once or twice per day. 
The student investigator will create either one or two dose windows accordingly 
entering the participants’ cellphone number followed by “@myboostmobile.com” 
where it asks for an email address. Finally, the student investigator will add the 
participants’ healthcare contacts to the InTouch contacts. 
Preparation for the First 30-Day Assessment and Participant Departure. After the 
participant has been informed of their study condition, outreach staff should then 
set up the first 30-day assessment appointment, provide the participant with an 
appointment card, confirm their contact information and release the participant. 
The student investigator should make a $50 payment to the participant, update 
the Materials Assignment records, and set up a new data sheet. 
 
 

19 
 
GENERAL PROCEDURES 
Overview 
The rest of the study manual from this point onward describes how 
participants who have been randomly assigned to one of the two study conditions 
(i.e., Control or SteadyRx) are handled throughout the main portion of the study 
(i.e., the post- randomization period). This section on general procedures covers 
procedures that are applied to all randomized participants, independent of their 
group assignment. The subsequent sections apply only to participants who have 
been assigned to the SteadyRx group. Thus, the focus of this section is on the 
monthly assessments. 
Monthly Assessments 
Reminder Calls. Participants will be given reminder calls related to their scheduled 
monthly assessment by the student investigators. They will also receive follow up 
calls if they fail to show up for their scheduled appointment time. Reminder calls 
will be given one day before their scheduled appointment. The calls will be between 
10AM – 6PM Monday through Thursday and 1PM – 5PM on Sunday. 
 
If the participant does not answer, the student investigator will wait one hour and 
then call again. This process is repeated if they do not answer again. If they do not 
answer a third time, the student investigator will leave the following voicemail: 
 
“Hi (PERSON's NAME), my name is *First Name* and I am calling on behalf 
of the SteadyRx research team. I just wanted to remind you that you have 
your monthly assessment scheduled for (APPOINTMENT TIME) tomorrow 
and confirm that you will be coming. Thank you and have a nice day.” 
 
If someone other than the participant answers the phone, follow the following 
script: 
 
"Hi, I'd like to speak to (PERSON'S NAME)." If the person on the phone asks 
who you are or why you are calling then say, "My name is *First Name* and I 
am calling to remind them about an appointment they have at Johns Hopkins 
tomorrow." If they ask for further details tell them "I'm sorry, but I am only 
allowed to discuss details with (PERSON'S NAME)."  
 
Once the participant is one the phone, follow the following script: 
 
"Hi (PERSON'S NAME), my name is *First Name* and I am calling on behalf 
of the SteadyRx research team. I just wanted to remind you that you have a 
monthly assessment scheduled for (APPOINTMENT TIME) tomorrow and 
confirm that you will be coming.”  If they say yes, say "Okay, great, remember 
that your appointment is at (APPOINTMENT TIME) and that you need to 

20 
 
bring your pill bottle and will be paid $30 for completing the interview and 
you will receive an additional $20 for bringing your pill bottle. That means 
you will be paid up to $50 tomorrow for bringing your pill bottle and 
completing the interview." Once they respond, then say "Okay, see you at 
(APPOINTMENT TIME) tomorrow, have a great day, Bye." 
 
If they indicate that they are unsure, or do not know what you are talking about, 
follow the following script: 
 
“Tyesha asked me to call you because you are scheduled to come in for your 
monthly assessment interview tomorrow for the SteadyRx research study you 
are participating in.” 
 
Reminder calls will be discontinued immediately upon request of the participant, 
will not exceed three per week, and will be discontinued after one month from the 
originally scheduled intake interview or appointment time. 
Collection Schedule. Scheduling monthly assessments is the responsibility of the 
outreach coordinator and the student investigators in Kalamazoo. Both are 
responsible for different aspects of the monthly assessment protocol. Monthly 
assessments should be scheduled to occur every 30 days over the course of 180 
days (for a total of six monthly assessments after random assignment). The first 
monthly assessment is scheduled for 30 days after the day of random assignment. 
During the Monthly Assessment Interview, the outreach coordinator should review 
and update the Monthly Assessment Checklist-Outreach Coordinator, and the 
student investigator should update the Monthly Assessment Checklist-WMU staff. 
The outreach coordinator should keep a record of all scheduled assessments, which 
should include their PTID, the scheduled date for all assessments, whether or not 
the assessment was collected for all planned assessments to date, the date that 
each collected assessment was actually conducted, the number of days that passed 
between the planned collection date and the actual collection date, and summary 
data indicating the overall percentage of planned assessments that have been 
collected to date and the average days from planned collection to actual collection 
for all collected assessments to date. 
Contacting No-Shows. The student investigators are responsible for contacting 
participants who do not show up for monthly assessments. Any participant who 
does not show up for a monthly assessment at their scheduled time should be 
contacted via phone by student investigators reminded of their appointment, 
reminded of the $50 they can earn, and rescheduled if necessary. Participants can 
also be contacted by using the information on the participant contact information 
sheet that was completed as part of the intake or most recent monthly assessment. 
Any updates that occur to the contact information should be noted on the most 
recent contact sheet. If necessary and if time allows, then the outreach coordinator 
can travel to the participant’s residence to conduct the monthly assessment. A 

21 
 
record of all attempts to call no-shows should be kept on a separate log. 
Elements of the monthly assessments. The outreach coordinator will be 
responsible for: 
• Attaching the MEMS reader to the assessment computer 
• Obtaining CD4 and HIV-1 RNA levels from medical record 
• Scheduling the next monthly assessment 
Reading a participant’s MEMS cap. Upon a participant’s arrival, the outreach 
coordinator will place the MEMS cap on the reader and initiate the reading. 
Tutorials for reading a MEMS cap will be made available to the outreach 
coordinator from the student investigators as well as from the help section located 
within the database. They will obtain CD4 and HIV-1 RNA levels from the medical 
record or from printed labs given by the participants. The outreach coordinator 
will inform WMU staff of the participant’s arrival and any new lab information. 
Conducting Monthly Assessments. The remainder of the monthly assessment will 
take place over the phone with one of the student investigators located in 
Kalamazoo. The student investigator is responsible for reading each assessment 
question aloud to the participant and filling in the answers accordingly. Upon the 
completion of both the MEMS reading and phone assessments, the participant 
should be paid $50. If the participant brought in recent CD4 and RNA lab 
readings and have an undetectable viral load, they should be paid $100, up to 
twice during the study. All relevant data logs should be updated (see Monthly 
Assessment Checklist – WMU Staff). 
 
The student investigator is solely responsible for conducting the 
following assessments: 
 
● Visual Analog Scale for self-reporting ART adherence 
● Medical Outcomes Study HIV Health Survey 
● Addiction Severity Index-Lite 
● Patient Reactions Assessment 
 
In addition to the previous assessments, student investigators are also 
responsible for conducting the following assessments for participants in the 
SteadyRx group: 
 
● SteadyRx Satisfaction Questionnaire 
● Software Usability Measurement Inventory 
 
 
 
 

22 
 
MAIN STUDY: STEADYRX PROCEDURES 
 
Overview 
 
The SteadyRx procedures are the primary responsibility of the student 
investigators in Kalamazoo, who will be overseen by the principal investigator. It 
is critical that all student investigators are familiar with the SteadyRx Treatment 
Manual in addition to the policies and procedures specified in this study manual. 
 
Assessing Videos in SteadyRx 
 
The responsibility of assessing the videos submitted by participants to 
PillWatch will be the student investigators’ in Kalamazoo. Videos will be assessed 
once per day for all participants by one of the student investigators. The student 
investigators will create a schedule to equally share this task over the course of 
the entire study. The student investigators will only use the computers whose IP 
addresses have been approved by the CTPayer system. 
The student investigators will then login using the admin account used to 
create SteadyRx participants’ Motiv8 accounts. Then the student investigators 
will navigate to the videos tab. All videos marked as unattended should be 
attended to and then either approved or rejected according to the criteria in the 
PillWatch training module. 
Two of the student investigators will assess each video independently. They 
will be assigned to be the first or the second appraiser. A schedule has been 
created in order to split this responsibility evenly. The first appraiser will input 
their decision in the first appraiser’s google sheet in the study google drive. They 
will then notify the second appraiser that they have done so. The second appraiser 
will then input their decision in the second appraiser’s google sheet. This will 
automatically update the first appraiser’s google sheet. The second appraiser will 
then open the first appraiser’s google sheet to check for agreement. If there is 
agreement, the second appraiser will log in to the Motiv8 systems website and 
either accept or reject the video submission. If there is not agreement, the second 
appraiser contacts the first appraiser to deliberate whether or not to accept or 
reject the video. If they are unable to reach agreement, they ask the third student 
investigator to independently review the video submission. The team will either 
accept or reject the video according to the third student investigator’s decision. 
The first week that the participant is in the study will be considered a 
training week. During this time, video submissions will be reviewed by the 
student investigators, who will provide feedback to the participant to insure that 
they are submitting videos that meet all of the criteria specified in the PillWatch 
protocol.  
Once all videos have either been approved or rejected, the client’s account 
will automatically update with the $2 credit for one day of full medication 

23 
 
adherence. Full medication adherence for the day is defined as one accepted video 
for the OnePerDay group in the allotted dose time window or two accepted videos 
for the TwoPerDay group in the allotted dose time windows. 
A $6 bonus credit should be given for full medication adherence three days 
in a row. At the end of every 30-day study period, each participant that has at 
least 29 days of full medication adherence should be credited $20. The first two 
times that a participant has an undetectable viral load at their appointment with 
their primary care physician at CCP, they will receive an incentive bonus of $100. 
All bonus credits should be manually entered into the client’s account information 
via the client’s tab in Motiv8. This includes the intake and monthly assessment 
payments. The student investigators will specify the reason in addition to the 
amount in order for the client to have a full record. 
Only when the participant is due more than $10 will the student 
investigators credit their CTPayer card. 
SteadyRx Video Submission Feedback 
 
All participants in the SteadyRx group will obtain feedback on their 
video submissions. The level and detail of feedback is determined by how 
close the video submissions are to meeting all criteria for acceptance. 
Week One Training. Participants will be instructed that the first week of 
participation is a training week, during which videos may be accepted that do not 
meet all criteria. Participants will receive feedback the day after their first 
submission, and every other day after the first submission until the end of 
training week. Feedback will be given by a student investigator calling the 
smartphone given to them for the study. Student investigators are to identify 
specific inadequacies in the submissions (e.g., not opening the pill bottle on 
screen), explain them to the participant, and check for understanding. 
Retraining. If, after feedback has been delivered twice and there has been no 
improvement, the student investigator will contact the Outreach Coordinator 
to schedule an appointment for the participant to come in for retraining. At 
the appointment, the Outreach Coordinator will go through the training 
materials and instruct the participant on submitting a video that meets all 
criteria for acceptance. Participants will be compensated $20 for returning to 
Johns Hopkins for retraining. 
Adverse Events & Study Notes 
*** Tracking and reporting adverse events is a *** critical 
responsibility of all CLH staff. 
The primary policies and procedures on adverse events and study notes 
are described below. All staff should review the Study Manual to be sure that 
they are following the procedures appropriately. 

24 
 
Tracking & Reporting Adverse Events. An adverse event is any bad thing that 
happens to a participant. This could include feeling sick or chronically tired, 
getting mugged on the streets of Baltimore, or any other bad thing you can 
imagine, even shark attacks and hang glider accidents. 
If any member of the research team learns of an adverse event, it is their 
responsibility to file an adverse event report and bring the event to the attention 
of the Outreach coordinator and Principal Investigators. 
Incarceration. The investigator and outreach coordinators must be immediately 
notified if a participant becomes jailed or otherwise imprisoned, is enrolled in a 
halfway house, or enters a constant monitoring procedure managed by any part of 
a criminal justice system. Under any of these conditions, an Adverse Event Report 
must be written. The IRB must be notified of any incarcerations at the time of 
continuing review. In order to avoid a reset, an incarcerated participant must 
supply a urine sample within two days of release, and then resume a normal 
testing schedule thereafter. Incarceration will not have any effect on discharge 
date or any aspect of study procedures except as specified above. 
Study Notes. ALL RESEARCH STAFF ARE RESPONSIBLE FOR WRITING 
STUDY NOTES. Any adverse events should also be entered into the SteadyRx 
Study Note System. To access this system, open the SteadyRx folder in the BERC 
folder on Google Drive and click on the Google Sheet with the filename “Study 
Notes.” In addition to writing a study note for any and all adverse events, study 
notes should be written for ANY deviation from the standard protocol of this study, 
and for ANY important information not entered elsewhere. If any decision had to be 
made that was not already specified this Study Manual, then a study note should be 
made. 
The basic rule of creating a study note is this: If you think there is any 
chance that a study note should be created, then a study note should be created. 
Specific examples of reasons to write a study note include any study-wide or 
participant-specific changes in contingencies or policies; any unintentional 
changes in procedure due to computer or staff error; any alteration in pay not 
specified in the protocol, or accidental payments or underpayments made to any 
participant. Once you are done writing the study note, notify the principal 
investigator. 
Data Management 
Data management is the responsibility of the student investigators and the 
outreach coordinator. The key outcome measures are all recorded automatically 
and electronically. This includes pill bottle openings and SteadyRx use measures. 
All participants will be trained to the point of skill mastery on all aspects of using 
the electronic pill bottles and the SteadyRx system. The data for all ACASI 
assessments will be stored in the Qualtrics database. The data for all MEMS caps 
readings will be stored within the medAmigo database. The data for all PillWatch 

25 
 
assessments will be stored in the backend of the SteadyRx application. All data 
will be stored on the SteadyRX server. With respect to the SteadyRX system 
servers, these Servers have been hardened against attack over the network and 
an intrusion detection system is in place. Administrative access to servers is by 
encrypted, private key-secured channels only. Servers are physically secured in a 
locked cabinet in a locked room in a secure facility accessible by photo ID only. 
The computer services provided under this project include daily system-wide on-
site and encrypted offsite backups with incremental database backups in 15 
minute intervals. All data transfer will be encrypted using 256- bit SSL 
encryption, the standard level of encryption used to secure eCommerce and 
banking transactions on the Internet. HIV serostatus and viral load measures, 
and drug use history will be provided by the participants’ doctor and transmitted 
over the phone by the outreach coordinator to the WMU staff. A log of the 
materials assigned to the participants and a discharge log will also be kept on 
Google Drive. 
All video submission data from those in the SteadyRx group will be 
recorded on individual google sheets. Submissions (y/n), time of submission, 
submission acceptances, money earned and when payments are made are 
included in the Google Sheets. Videos are independently accepted or rejected by 
two student investigators (see Assessing Videos in SteadyRx). 
ALL of these databases will be transcribed to a master Google Sheet 
excel file on a regular basis. In order to ensure accuracy in transcription of 
paper based data (e.g., HIV serostatus and viral load), two investigators will 
transcribe the data separately and it will only be recorded on the master data 
sheet upon agreement. The responsibility of updating these excel files will be 
shared between the student investigators and the outreach coordinator. Data 
will be backed up on one of two external hard drives on a weekly basis. Hard 
drives used will be alternated and the responsibility will be shared across 
student investigators. 
 
 

26 
 
MAIN STUDY DISCHARGE 
Main Study Discharge will occur for all participants irrespective of group 
assignment upon completion of the 6th Main Study Assessment and should be 
scheduled for study day 180. Outreach staff are responsible for Main Study 
Discharge and should follow the Discharge Checklist. The Main Study Discharge 
interview is identical to the monthly assessment interview aside from collecting 
the participant’s smartphone and MEMS cap. The participant is entitled to a $100 
incentive for keeping the same smartphone for the entire study period and 
returning it during this interview. Alternatively, they can forego the $100 and keep 
the smartphone. They will be told of this choice during the intake interview and 
reminded at study discharge. If they choose to keep the phone, immediately remove 
payment and contact information from the Boost Mobile account. Also change the 
pin to their participant ID and make a note in the phone number records log. 
 
 
 
 
 
 
 

Analytic plan for SteadyRx study 
 
Descriptive statistics (means and standard deviations or proportions) will be calculated 
for demographics, baseline participant factors (e.g., quality of life, substance use), treatment 
history, health literacy, and application ratings and engagement. All analyses will be intent to 
treat; all participants who are randomized will be included. All analyses will be adjusted for the 
pre-specified covariates used for stratification.77 All hypothesis tests will be two-sided, α will be 
set at 0.05, and p-values for secondary analyses will be corrected to maintain α=0.05. Based on 
our past research and the automated collection of our primary outcome measure, we expect 
relatively little missing data and little difference in the rates of missing data across groups. We 
plan to conduct analyses in which missing samples are assumed to represent the adverse 
outcome (e.g., missing = drug positive) and in which missing data will be ignored (missing = 
missing). The “missing positive” method is more conservative and will be considered the primary 
method.    
Primary Outcomes. The effects of the intervention relative to the control group on the 
dichotomous monthly adherence measure will be analyzed with a longitudinal logistic regression 
model with treatment group and time as covariates. The group term, representing the between-
group difference averaged over time, will be the primary coefficient of interest. Correlation 
among outcomes over time within individuals will be handled using the method of Generalized 
Estimating Equations (GEE).78 The dichotomous viral load variable (<400 HIV-RNA/mL, y/n) will 
be modeled with an analogous model but with only two follow-up measures.  
Secondary and Exploratory Analyses. Continuous measures assessed repeatedly over 
time (bottle openings, CD4, HIV-1 RNA, and MOS-HIV) will be analyzed using a longitudinal 
linear regression model, analogous to that used for the primary outcomes. We will control for 
baseline values in the CD4, viral load, and MOS-HIV models. Measures assessed only at intake 
will be analyzed via linear or logistic regression as appropriate. Baseline predictors of response 
to treatment, including positive urine screen for cocaine or opioids, health literacy (TOFHLA), 
depression (BDI), psychological factors (SCL-90), job and educational history (VEA), and 
executive function (Wisconsin Card Sorting) will be assessed by fitting regression models with 
interactions between treatment assignment and each predictor variable, to determine if the 
effect of treatment on outcome varies as a function of each of these predictors. Similar models, 
with an interaction between treatment group and drug use, adherence to buprenorphine/ 
methadone, and attendance to primary care, respectively, (as time-varying covariates) will allow 
us to determine whether these variables affects response to treatment. 
Usage, Acceptability, and Cost. Acceptability and SUMI global scale scores, app uses 
per day, daily duration of use, and cost of the app and incentives and ICER will be summarized 
via descriptive statistics (mean, SD, medians, histograms).  
 
Data Analysis to be reported in future publication 
Groups were compared on intake variables using Fisher’s exact tests for dichotomous 
variables, chi-square tests for categorical variables with more than two categories, and t-tests 
for continuous variables. Outcome measures were analyzed using generalized estimating 
equations (GEE) (Zeger, Liang, & Albert, 1988), including and excluding the stratification 
variables as covariates. GEE results presented use the covariate model unless otherwise 
specified. Planned comparison t-tests were used to compare between and within groups on 
outcome measures at time points 1 and 6. Analyses were intent-to-treat and conducted using 
SAS version 9.3. Missing data were treated as missing-missing. Analyses were two-tailed with 
statistical significance set at alpha of .05. Due to the error in the collection of biometric data, 
analyses for these variables are not included.