Automated Medication Platform With Video Observation and Facial Recognition to Improve Adherence to Antiretroviral Therapy in Patients With HIV/AIDS
Phase: NA
Conditions: HIV Infections
Sponsor: Charles Gellman

Automated Medication Platform with Video 
Observation and Facial Recognition to Improve 
Adherence to Antiretroviral Therapy in Patients with 
HIV/AIDS  
   
Principal Investigator: Charles Gellman 
Sponsor: HiDO Technologies 
Funded by: HiDO Technologies 
Version Number:  2.2 
20 July 2021 
 
 

  
Table of Contents 
STATEMENT OF COMPLIANCE ............................................................................................................................ 1 
1 
PROTOCOL SUMMARY .............................................................................................................................. 1 
1.1 
Synopsis ............................................................................................................................................... 1 
1.2 
Schema ................................................................................................................................................ 3 
1.3 
Schedule of Activities (SoA) .............................................................................................................. 4 
2 
INTRODUCTION ........................................................................................................................................... 4 
2.1 
Background Information ..................................................................................................................... 4 
2.2 
Rationale .............................................................................................................................................. 5 
2.3 
Risk/Benefit Assessment ................................................................................................................... 8 
2.3.1 
Known Potential Risks .................................................................................................... 8 
2.3.2 
Known Potential Benefits ............................................................................................... 8 
2.3.3 
Assessment of Potential Risks and Benefits ............................................................... 8 
3 
OBJECTIVES AND ENDPOINTS ............................................................................................................... 9 
4 
STUDY DESIGN ............................................................................................................................................ 9 
4.1 
Overall Design ..................................................................................................................................... 9 
4.2 
Scientific Rationale for Study Design ............................................................................................. 11 
4.3 
Justification for Dose ........................................................................................................................ 11 
4.4 
End of Study Definition ..................................................................................................................... 11 
5 
STUDY POPULATION ............................................................................................................................... 11 
5.1 
Inclusion Criteria ............................................................................................................................... 12 
5.2 
Exclusion Criteria .............................................................................................................................. 12 
5.3 
Lifestyle Considerations ................................................................................................................... 12 
5.4 
Screen Failures ................................................................................................................................. 12 
5.5 
Strategies for Recruitment and Retention ..................................................................................... 13 
6 
STUDY INTERVENTION ........................................................................................................................... 14 
6.1 
Study Intervention(s) Administration .............................................................................................. 14 
6.1.1 
Study Intervention Description .................................................................................... 14 
6.1.2 
Dosing and Administration ........................................................................................... 15 
6.2 
Preparation/Handling/Storage/Accountability ............................................................................... 16 
6.2.1 
Acquisition and accountability ..................................................................................... 16 
6.2.2 
Formulation, Appearance, Packaging, and Labeling ............................................... 16 
6.2.3 
Product Storage and Stability ...................................................................................... 16 
6.2.4 
Preparation ..................................................................................................................... 16 
6.3 
Measures to Minimize Bias: Randomization and Blinding .......................................................... 16 
6.4 
Study Intervention Compliance ....................................................................................................... 16 
6.5 
Concomitant Therapy ....................................................................................................................... 16 
6.5.1 
Rescue Medicine ........................................................................................................... 16 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ................................................................................................................... 17 
7.1 
Discontinuation of Study Intervention ............................................................................................ 17 

  
7.2 
Participant Discontinuation/Withdrawal from the Study .............................................................. 17 
7.3 
Lost to Follow-Up .............................................................................................................................. 17 
8 
STUDY ASSESSMENTS AND PROCEDURES ..................................................................................... 18 
8.1 
Efficacy Assessments ...................................................................................................................... 18 
8.2 
Safety and Other Assessments ...................................................................................................... 18 
8.3 
Adverse Events and Serious Adverse Events .............................................................................. 18 
8.3.1 
Definition of Adverse Events (AE) .............................................................................. 18 
8.3.2 
Definition of Serious Adverse Events (SAE) ............................................................. 18 
8.3.3 
Classification of an Adverse Event ............................................................................. 18 
8.3.4 
Time Period and Frequency for Event Assessment and Follow-Up ...................... 20 
8.3.5 
Adverse Event Reporting ............................................................................................. 20 
8.3.6 
Serious Adverse Event Reporting ............................................................................... 21 
8.3.7 
Reporting Events to Participants ................................................................................. 21 
8.3.8 
Events of Special Interest ............................................................................................ 21 
8.3.9 
Reporting of Pregnancy ................................................................................................ 21 
8.4 
Unanticipated Problems ................................................................................................................... 21 
8.4.1 
Definition of Unanticipated Problems (UP) ................................................................ 21 
8.4.2 
Unanticipated Problem Reporting ............................................................................... 22 
8.4.3 
Reporting Unanticipated Problems to Participants ................................................... 22 
9 
STATISTICAL CONSIDERATIONS .......................................................................................................... 23 
9.1 
Statistical Hypotheses ...................................................................................................................... 23 
9.2 
Sample Size Determination ............................................................................................................. 24 
9.3 
Populations for Analyses ................................................................................................................. 24 
9.4 
Statistical Analyses ........................................................................................................................... 24 
9.4.1 
General Approach ......................................................................................................... 24 
9.4.2 
Analysis of the Primary Efficacy Endpoint(s) ............................................................ 24 
9.4.3 
Analysis of the Secondary Endpoint(s) ...................................................................... 24 
9.4.4 
Safety Analyses ............................................................................................................. 25 
9.4.5 
Baseline Descriptive Statistics .................................................................................... 25 
9.4.6 
Planned Interim Analyses ............................................................................................ 25 
9.4.7 
Sub-Group Analyses ..................................................................................................... 25 
9.4.8 
Tabulation of Individual participant Data .................................................................... 25 
9.4.9 
Exploratory Analyses .................................................................................................... 25 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .............................. 25 
10.1 
Regulatory, Ethical, and Study Oversight Considerations .......................................................... 25 
10.1.1 
Informed Consent Process .......................................................................................... 25 
10.1.2 
Study Discontinuation and Closure ............................................................................ 26 
10.1.3 
Confidentiality and Privacy ........................................................................................... 27 
10.1.4 
Future Use of Stored Specimens and Data ............................................................... 27 
10.1.5 
Key Roles and Study Governance .............................................................................. 27 
10.1.6 
Safety Oversight ............................................................................................................ 28 

  
10.1.7 
Clinical Monitoring ......................................................................................................... 28 
10.1.8 
Quality Assurance and Quality Control ...................................................................... 28 
10.1.9 
Data Handling and Record Keeping ........................................................................... 28 
10.1.10 
Protocol Deviations ....................................................................................................... 29 
10.1.11 
Publication and Data Sharing Policy .......................................................................... 29 
10.1.12 
Conflict of Interest Policy .............................................................................................. 29 
10.2 
Additional Considerations ................................................................................................................ 29 
10.3 
Abbreviations ..................................................................................................................................... 30 
10.4 
Protocol Amendment History .......................................................................................................... 31 
11 
REFERENCES ............................................................................................................................................ 32 
12 
Appendix A: HiDO Product Brochure ....................................................................................................... 34 
 

Protocol: Automated Medication Platform…To Improve Adherence to ART 
 
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STATEMENT OF COMPLIANCE 
 
The trial will be conducted in accordance with International Conference on Harmonisation Good Clinical 
Practice (ICH GCP), applicable United States (US) Code of Federal Regulations (CFR), and the National 
Institute of Mental Health Terms and Conditions of Award. The Principal Investigator will assure that no 
deviation from, or changes to the protocol will take place without prior agreement from the 
Investigational New Drug (IND) or Investigational Device Exemption (IDE) sponsor, funding agency and 
documented approval from the Institutional Review Board (IRB), except where necessary to eliminate an 
immediate hazard(s) to the trial participants. All personnel involved in the conduct of this study have 
completed Human Subjects Protection and ICH GCP Training. 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the IRB for review and approval.  Approval of both the protocol and the consent form must 
be obtained before any participant is enrolled.  Any amendment to the protocol will require review and 
approval by the IRB before the changes are implemented to the study.  All changes to the consent form 
will be IRB approved; a determination will be made regarding whether a new consent needs to be 
obtained from participants who provided consent, using a previously approved consent form.] 
1 
 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS  
Title: 
Automated Medication Platform with Video Observation and Facial 
Recognition to Improve Adherence to Antiretroviral Therapy in Patients 
with HIV/AIDS 
  
Study Description: 
This is an unblinded study of the HiDO automated medication adherence 
platform in patients ages 18 to 55 who are currently taking ART. From this 
population, 24 participants will be recruited to use the HiDO medication 
adherence platform for a 90-day intervention period. Medication 
adherence and device usability will be measured by various means.  It is 
hypothesized that: a) use of HiDO will result in ≥95% medication 
adherence over 90 days; b) usability scores for the HiDO platform (as 
measured by Time on Task values and error rates) will be equal to or 
better than published benchmark rates for similar platforms; c) System 
Usability Scale (SUS) value will be >68; d) greater than 80% of participants 
will indicate that they are Likely or Strongly Likely to recommend the HiDO 
device to a friend or colleague.  
  
Objectives: 
 
Primary Objective:  Determine the effect of automated medication 
adherence platform (HiDO) on medication compliance.  
 
 
Secondary Objective: Determine usability of automated medication 
adherence platform (HiDO), as indicated by user ease of adoption (Time on 
Task, error rates), standardized user experience metric (SUS), and user 
endorsement (Net Promoter Score).  
  

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Endpoints: 
Primary Endpoint: Medication adherence as assessed by remote 
observation through the HiDO device at 90 days.  
Secondary Endpoints: Time on Task for initial registration, “first click” 
testing, facial recognition setup, medication administration, number and 
type of critical and non-critical errors and error-free rate, System Usability 
Scale (SUS), Net Promoter Score. 
  
Study Population: 
Sample of 24 participants from U.S. population of individuals ages 18 and 
older who are currently taking antiretroviral therapy (ART).  
  
Phase: 
1 
  
Description of 
Sites/Facilities Enrolling 
Participants: 
HiDO Technologies 
2191 Frascati Dr. 
El Dorado Hills, CA  95762-3970 
  
Description of Study 
Intervention: 
HiDO is an automated Artificial Intelligence driven direct observation 
medication adherence platform. The platform is a 510K exempt Class I 
medical device (890.5050) that integrates medication dispensing, dose 
administration time, pill count and front facing video cameras to validate 
the right medications, at the right time to the right patient. The device 
dispenses up to 7 different types of medications simultaneously. The 
camera logs every dose using facial recognition and provides real time 
consumption logs. Investigators have access to video observation logs, 
patient dose time, adherence trends, and study level adherence measures. 
For this study, the HiDO medication adherence platform will be delivered 
to the residence of each participant by the researcher, who will provide 
instructions for performing device setup that includes linking the HiDO 
device to the participant’s smartphone and filling the device with ART. The 
participant receives a smartphone alert when it is time to take a 
medication, and then pushes the button on the device to receive the 
correct medicine at the given time. If the patient does not respond, 
additional reminders are sent via phone and SMS. Medication adherence 
will be measured over 90 days using the HiDO device. Additionally, 
participants will participate in a semi-structured interview following the 
90-day period to assess system usability.   
  
Study Duration: 
12 months 
  
Participant Duration: 
104 days 
 
 

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1.2 
SCHEMA 
 
Figure 1. Study Schema for, “Automated Medication Platform with Video Observation and Facial Recognition to 
Improve Adherence to Antiretroviral Therapy in Patients with HIV/AIDS 
 
 
 
 

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1.3 
SCHEDULE OF ACTIVITIES (SOA) 
 
Procedures 
Screening / baseline 
measurement 
Day -14 to -1 
Week 1, Day 1 
(Completion of 
platform setup) 
Week 2, Day 14  
 +/-1 day 
Week 4, Day 28 
 +/-1 day 
Week 6, Day 42 
 +/-1 day 
Week 8, Day 56 
 +/-1 day 
Week 10, Day 70 
 +/-1 day 
Week 12, Day 84 
 +/-1 day 
Week 13, Day 90 
 +/-1 day 
Week 14, Day 97 
 +/-7 days 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
Medication adherence self-
report 
X 
 
 
 
 
 
 
 
 
 
Delivery of HiDO platform 
X 
 
 
 
 
 
 
 
 
 
Assisted platform setup 
X 
 
 
 
 
 
 
 
 
 
Time on Task  
X 
X 
X 
 
 
 
 
 
X 
 
Error rate  
X 
X 
X 
 
 
 
 
 
X 
 
Automated medication 
adherence 
 
X-------------------------------------------------------------------------------X 
 
Device log audit 
 
 
 
X 
 
X 
 
X 
 
X 
Usability assessment (semi-
structured interview)  
 
 
 
 
 
 
 
 
 
X 
Adverse event review and 
evaluation 
 
X---------------------------------------------------------------------------------------X 
Complete Case Report Forms 
(CRFs) 
X-------------------------------------------------------------------------------------------------X 
 
2 
INTRODUCTION 
 
2.1 
BACKGROUND INFORMATION 
 
HIV drug treatment saves lives. Antiretroviral therapy (ART) has directly and irrefutably reduced the 
death rate of people with HIV/AIDS. Because of public health measures including the administration of 
ART, AIDS-related deaths declined by 38% from 2000 to 2017—saving more than 11 million lives 
worldwide. 1 A high degree of adherence to ART is an essential part of this success. People living with 
HIV (PLWH) who strictly follow their ART regimens can control the disease. For example, 102 patients 
with acute or early HIV-1 infection were prospectively followed; 97% of those who strictly followed ART 
had undetectable viral levels at a median of 11 weeks and 92% had continued viral suppression at 18 
months.2  When HIV is suppressed in this way, the risk-of developing an AIDS-defining condition is 
greatly reduced.3 In fact, the immune system can even reconstitute itself.4 Moreover, patients who 
achieve viral suppression do not transmit HIV to others.5-7 Likewise, people at high risk who consistently 
take daily pre-exposure prophylaxis (PrEP) can substantially reduce their risk of acquiring HIV infection.7 
The same protective effect has been observed for post-exposure prophylaxis (PEP); however, the key to 
the success of ART, PrEP and PEP is strict adherence. 
 
Nonadherence in clinical trials has profound economic and societal costs. Medication adherence is 
critically important during clinical trials. Investigators insist on (or assume) adherence rates of ≥95%, 
however, substantial evidence exists that actual adherence in trials is far less than that.8,9 Gossec et al. 
performed a meta-analysis of 192 publications of RCTs in six chronic conditions and observes a median 
compliance of 93% through pill count adherence measures.10 However, when bodily fluid measurements 

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were used to assess adherence in this same population, the values were substantially lower, 54% to 
68%.9 This means that pill count is an inaccurate measure of adherence and true medication adherence 
rates are below 70%.9 High levels of medication adherence are perhaps no more important than they 
are in HIV clinical trials. Considering that patients with adherence rates of <95% are 3.5 times as likely to 
have treatment failure as defined as HIV-1 RNA >50 copies/ml than those with 95% adherence or 
greater.11 While recent work using real world data has suggested that HIV viral suppression may be 
possible with adherence rates as low as 80%, this appears to be ART regimen-dependent.12 Since we 
know that viral suppression is now possible with ART and interrupting transmission is possible with PrEP 
and PEP, the FDA will almost assuredly require viral suppression as an endpoint in anti-HIV medication 
trials. Compliance of less than 68% will cause IMPs to fail. If participants in a placebo-controlled trial are 
taking less than 70% of their study medication doses, the effect in active arm will be underestimated. 
Poor actual adherence during clinical trials skews data, confounds statistical analyses, increases 
participant discontinuation rates, lengthens recruitment periods and extends the total duration of 
clinical trials.13 Non-adherence is directly responsible for longer and more costly clinical trials.13 These 
costs are estimated to be in excess of $1.5 billion capitalized over the time required to develop a single 
new investigational medicinal product (IMP).9 This not only costs clinical trial sponsors substantial sums 
of money, but it slows the development of new therapies and decreases the pool of eligible study 
participants in future trials (e.g. most trials exclude potential participants who recently participated in a 
clinical trial). Timeline expansion translates to $600,000 per day in lost revenue opportunity for products 
with focused indications and up to $8 Million per day for broadly used medications.13 
 
Efforts to improve adherence are only modestly successful. Multiple factors contribute to 
nonadherence.14 These factors include the complexity of taking medications, time burden on the 
patient, the patient's perception of benefits and risks. Several measures have been proposed and 
deployed to improve adherence. These include behavioral skills training, medication adherence training, 
phone reminders, text reminders, smart pill caps, and various combinations thereof. Kanters and 
colleagues systematically reviewed 85 medication adherence trials comprising 16,271 participants and 
after conducting a network meta-analysis concluded, “Several interventions can improve adherence and 
viral suppression; generally, their estimated effects were modest and waned over time.” 15 The usual 
methods for monitoring adherence in clinical trials are self-reported medication adherence, pharmacy 
refill data, Medication Event Monitoring Systems, and therapeutic drug monitoring. Each of these 
methods has its strengths and weaknesses; but none can be considered a gold standard because of their 
inherent limitations. Direct observation could be the gold standard, but it is prohibitively expensive and 
impractical. 
 
Directly observed therapy could be a solution. Directly observed therapy is a means of encouraging 
strict medication adherence in which a health-care worker or other competent individual physically 
watches a patient consume their medication. Given the importance of strict medication adherence in 
HIV/AIDS, there have been efforts to institute directly observed therapy adherence measures.16,17 A 
systematic review and meta-analysis showed that directly-observed therapy of ART “had a significant 
effect on virologic, immunologic, and adherence outcomes.”18 In-person, directly observed therapy has 
its critics, however. They suggest it is coercive, dehumanizing, and hinders autonomy.19-21  
 
 
 
2.2 
RATIONALE 
 

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Directly observed therapy could be the gold standard for HIV, but the process must eliminate the 
burden of travel, the loss of autonomy and the high cost of direct observation. Poor medication 
adherence is an ongoing problem in clinical trials, especially in medications to treat HIV/AIDS. Even high 
potency, low genetic resistance ART regimens require adherence above 80% (and recommended 
adherence is greater than 95% regardless of agents). This means they fail to achieve viral suppression, 
are a source of drug-resistance strains of HIV, are more difficult to treat, can advance to AIDS, and 
acquire opportunistic infections and develop AIDS-related cancers. In clinical trials, poor adherence 
skews data, making the active arm seem less potent than control. Drug development programs may be 
scuttled due to poor and unrealized poor adherence. 
 
The purpose of the current study is to test the effectiveness of HiDO, an automated medication 
adherence platform, in both improving medication adherence among HIV/AIDS patients and providing a 
better user experience compared to existing medication adherence devices. 
 
Hypothesis 1:  Use of the HiDO automated medication adherence platform will result in ≥95% 
medication adherence over 90 days. 
Hypothesis 2:  Usability scores for the HiDO platform (as measured by Time on Task for initial 
registration, “first click” testing, facial recognition setup, and medication administration, number 
and type of critical and non-critical errors, and error-free rate) will be equal to or better than 
published benchmark rates for similar platforms.  
Hypothesis 3: The System Usability Scale (SUS) value for the HiDo platform will be equal to or 
better than published benchmark rates for similar platforms (>68).  
Hypothesis 4: Greater than 80% of participants will indicate that they are Likely or Strongly 
Likely to recommend the HiDo device to a friend or colleague.  
 
HiDO is an automated AI (Artificial Intelligence)-driven, direct observation medication adherence 
platform. The platform is a 510K exempt Class I medical device that integrates medication dispensing, 
dose administration time, pill count and a front-facing video and infrared cameras to validate the right 
medications, the right time go to the right patient. The camera logs every dose using facial recognition 
and provides real-time consumption logs. Investigators have access to video observation logs, patient 
dose time, adherence trends, and study-level adherence through the platform’s dashboard. Study 
participant can set up the device in minutes using their smartphone. Data is stored securely in the cloud 
and accessible in real-time. The technology has been awarded a provisional patent.  
Medications may be filled by a pharmacist or clinical trial site.  The device is not locked, which allows 
patients to retrieve or refill medications manually if needed, but notifies the researcher whenever the 
closing mechanism on the back of the unit is opened. A cap is selected that indicates the pill size and 
type, which is then placed on the pill bottle. The 40-dram (5 oz.) bin for each medication is inserted into 
the HiDO unit; up to 7 different medications can be housed at one time in separate bins. The HiDO unit 
senses the medication(s) and dispenses the medication(s) at the specified time and dosage level. 
Patients are alerted by the desktop HiDO unit and via smartphone when it is time to take their 
medication. Facial recognition software detects the patient through front-facing video cameras and 
identifies that it is, indeed, the person who is supposed to take the medication. The camera records and 
confirms that the patient consumes the medication, recording the exact time and medication(s) taken. 
The patient, caregivers, health care team (and clinic trial investigators) can track medication adherence 
in real time using a dashboard. The HiDO device enables remote monitoring and can also collect patient-
reported outcomes, adverse events, disease symptoms, treatment satisfaction, and other data. 

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HiDO is the first device of its kind to integrate medication reminders, patient reported outcomes, drug 
dispensing, and remote/recorded observed therapy is a single platform (see Figure 2). The device 
collects real-time data for medication adherence, dose administration time, 14-day adherence trend 
analysis and video recording of medication consumption. These capabilities help satisfy the new FDA 
remote-monitoring guidance issued August 2020. Both pharmaceutical and clinical trial organizations 
have expressed interest in leveraging the HiDO device across the HIV and other drug development 
pipelines. While clinical trialists do use body fluid sampling to assess adherence, the advent of COVID-19 
has dramatically reduced in-person clinical trial visits. Sponsors are aggressively pursuing ways to meet 
FDA requirements with fewer in-person visits.  
 
Figure 2. Comparison of HiDO with available medication adherence platforms. 
 
 
 
Demonstrating the feasibility of the technology proposed in this application is a critical step in device 
development. The data collected during this study will allow HiDO to refine and finalize the platform. It 
will also demonstrate preliminary impact, which will be important for determining whether the 
technology should be further developed and will likely be one of the factors that attracts financial 

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investors. Additional funding of a successful medication adherence device will allow expansion and 
commercialization of this platform, which can lower the costs of and disruptions to clinical trials, 
improve medication adherence in vulnerable patient populations, and ultimately change the trajectory 
of HIV/AIDS morbidity and mortality on a population level. 
 
 
2.3 
RISK/BENEFIT ASSESSMENT   
 
2.3.1 KNOWN POTENTIAL RISKS  
 
A potential risk to participants is breach of confidentiality, which exists both as an immediate and long-
term risk. There is also an immediate risk that the platform hardware or software may malfunction in 
some way, which may affect data capture, data transmission, or medication dispensing. These errors 
may affect the reliability of the device in providing timely dosage reminders, accurate remote 
monitoring, and accurate dispensing of medication.  
 
 
2.3.2 KNOWN POTENTIAL BENEFITS  
 
Participants may directly benefit from better and more consistent medication adherence resulting from 
use of the HiDO platform, which would increase the chance of achieving and maintaining viral 
suppression. Participants, as well as the population at large, may experience indirect long-term benefit 
from the development of automated medication adherence platforms that improve treatment 
outcomes and lower the cost of new drug development (as described previously in Section 2.2, 
Rationale).  
 
 
 
2.3.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS  
 
The risk of breach of confidentiality risk is mitigated through use of stringent data security procedures. 
Data collected through the HiDO device is stored on Amazon Web Services (AWS), a HIPAA-compliant 
cloud computing platform.  Other electronic data not stored on the AWS cloud platform are stored 
locally on encrypted and password-protected computers accessible only to the research staff. Any paper 
records generated are stored in locked cabinets accessible only to the researcher staff. Data accessed 
from clinical records are de-identified prior to being recorded into the research database. 
 
Regarding the risk of device malfunction, these risks are unavoidable to some degree, given that the 
purpose of the study is to assess device functioning. To mitigate the risk to participants posed by 
platform malfunctions, participants are advised of these risks and reminded to adhere to their 
prescribed ART treatment protocol in the event that the device malfunctions, both during the consent 
process and with written instructions included in HiDO device packaging (see Appendix A: HiDO Product 
Brochure). Additionally, participants are able to manually access medications loaded into the device, 
should the device fail to dispense them automatically.   
 
 

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3 
OBJECTIVES AND ENDPOINTS 
 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
Primary 
 
 
Determine the effect of 
automated medication 
adherence platform (HiDO) 
on medication compliance.  
 
 
Mean adherence rate to ART in all 
patients across 90 days (quantified 
as (n. of doses provided — n. of 
doses taken) / n. of doses provided x 
100) 
 
 
Adherence data are 
automatically and continuously 
recorded by HiDO device, and 
directly confirmable through 
manual audit of video 
recordings.  
 
Secondary 
 
 
 
Determine usability of 
automated medication 
adherence platform 
(HiDO), as indicated by user 
ease of adoption (Time on 
Task, error rates), 
standardized user 
experience metric (SUS), 
and user endorsement (Net 
Promoter Score).  
 
Measured at Week 2: 
• 
Time on Task for initial 
registration 
• 
Time on Task for “first click” 
testing 
• 
Time on Task for facial 
recognition setup 
• 
Time on Task for medication 
administration 
• 
Number and type of critical and 
non-critical errors 
• 
Error-free rate 
 
Measured after 90 days use of 
platform: 
• 
Score on System Usability Scale 
(SUS) 
• 
Net Promoter Score  
 
Time on Task and error rates 
may be compared to published 
benchmarks for similar 
platforms. 
 
According to usability.gov 
published by the U.S. 
Department of Health & 
Human Services, the SUS is 
regarded as a reliable tool to 
assess usability and has 
become the industry 
standard.24 Results from the 
SUS have been published in 
over 1,300 publications. 24 It can 
be used on small sample sizes 
with reliable results and can 
effectively discriminate 
between usable and unusable 
systems.  
 
The Net Promoter Score is 
based on the response to the 
question, “How likely is it that 
you would recommend our 
device to a friend or 
colleague?” on a 
5-point Likert scale.  
 
 
4 
STUDY DESIGN  
 
4.1 
OVERALL DESIGN 

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Study description: This is an unblinded, Phase 1 study of the HiDO automated medication adherence 
platform in patients ages 18 and older with HIV/AIDS who are currently taking ART. For this single-site 
device study, clinical collaborators will recruit 24 participants into a single study group.  After a 
screening period of up to 14 days, participants will receive the 90-day intervention that consists of using 
of an automated medication adherence platform. Medication adherence will be assessed through 
observed therapy using front-facing cameras on the device.  
 
Study device: HiDO is an automated Artificial Intelligence driven direct observation medication 
adherence platform. The platform is a 510K exempt Class I medical device that integrates medication 
dispensing, dose administration time, pill count and a front facing video camera to validate the right 
medications, at right time to the right patient. The camera logs every dose using facial recognition and 
provides real time consumption logs. The device dispenses up to 7 different types of medications 
simultaneously. Investigators have access to video observation logs, patient dose time, adherence 
trends, and study level adherence through a cloud-based electronic dashboard. Data is stored securely 
in the cloud and accessible real-time.  
 
Study Procedures: As part of screening procedures, participants complete a 10-minute medication 
adherence self-assessment via phone. The researcher will schedule a visit to the participant’s home, 
expected to last approximately 45 minutes, to conduct consent process and set up the device. After 
conducting consent procedures and collecting participant demographic information, the researcher will 
deliver the HiDO device to each participant’s home and assist each participant with platform setup, 
which includes loading ART medications into the dispenser (up to 7 different types), calibrating facial-
recognition, and setting up the participant’s smartphone to interact with the device. Following platform 
setup, participants use the HiDO platform for 90 days, which will provide notifications for, dispense, and 
monitor each participant’s ART dosing. At the end of the 90-day intervention period, participants 
complete a semi-structured interview, administered via phone and lasting approximately 30 minutes, to 
assess device usability and complete post-intervention medication adherence self-assessment. Excluding 
screening, total study duration is 104 days +/- 7 days.  
 
Data are collected for medication adherence and usability from the following sources: 
 
1. Medication adherence: 
a. Automated dosage logs generated by HiDO device 
b. Manual audit of automated dosage logs 
c. Pre- and post-study medication adherence self-assessment questionnaire  
 
2. Usability: 
a. Automated user logs generated by HiDO device 
b. Post-study semi-structured interview 
c. System Usability Scale 
d. Net Promoter Score 
 
Hypotheses: 
 
Hypothesis 1:  Use of the HiDO automated medication adherence platform will result in ≥95% 
medication adherence over 90 days. 
 

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Hypothesis 2:  Usability scores for the HiDO platform (as measured by Time on Task for initial 
registration, “first click” testing, facial recognition setup, and medication 
administration, number and type of critical and non-critical errors, and error-free 
rate) will be equal to or better than published benchmark rates for similar 
platforms.  
 
Hypothesis 3: The System Usability Scale (SUS) value for the HiDO platform will be equal to or 
better than published benchmark rates for similar platforms (>68).  
 
Hypothesis 4: Greater than 80% of participants will indicate that they are Likely or Strongly 
Likely to recommend the HiDO device to a friend or colleague.  
 
Selection bias: Every effort will be made to draw a sample that represents the patient population in 
terms of race, ethnicity, and gender.   
 
 
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
 
Our main goal is to demonstrate ≥95% adherence to ART in all patients across 90 days. Admittedly, this 
is a very high bar. However, we are confident that we will achieve it, even for patients who have 
problematic use. Our informal user testing to date has shown remarkable adherence rates with the 
HiDO device, and these have improved as we have moved into the current version (Version 3).  
 
For participants who completely withdraw from the study before 90 days, adherence percentage will 
only be calculated for the time that they participated. While we will likely glean important information 
from those who do drop out early, these dropouts will not affect our primary endpoint calculation. We 
may also fail to recruit a pool of participants that reflects the diversity of the national HIV patient 
population. We expect, however, to be close, and will be able to recruit a sample sufficient to 
intelligently plan for larger scale future testing in diverse populations. If successful, we will have 
demonstrated that our automated medication adherence platform is highly usable, preliminarily enables 
strict adherence to ART, and is ready for larger scale testing in Phase II. 
 
4.3 
JUSTIFICATION FOR DOSE 
 
Not applicable.  
 
 
4.4 
END OF STUDY DEFINITION 
 
A participant is considered to have completed the study if he or she has completed all phases of the 
study including the last visit or the last scheduled procedure shown in the Schedule of Activities (SoA), 
Section 1.3. 
 
5 
STUDY POPULATION 

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5.1 
INCLUSION CRITERIA 
 
To be eligible to participate in this study, an individual must meet all the following criteria: 
 
1. Provision of signed and dated informed consent form 
2. Stated willingness to comply with all study procedures and availability for the duration of the 
study  
3. Male or female, ages 18 and older 
4. Prescribed at least one existing ART 
5. Self-reported as taking less than 100% of ART does in past 30 days 
6. Access to a personal smartphone and Wi-Fi connection 
 
5.2 
EXCLUSION CRITERIA 
 
An individual who meets any of the following criteria will be excluded from participation in this study: 
 
1. Changes to ART regimen within the previous 2 months 
2. Anticipated changes to ART regiment during the study period 
3. Illicit drug use within the past 6 months, excluding marijuana 
4. Diagnosis of dementia of any type 
5. Participation in a clinical study within the previous 3 months 
 
Participants will be recruited without bias to gender/gender identity, race, ethnicity, religion, or sexual 
orientation from existing patient populations using anti-retroviral therapy. 
 
Children have been excluded from the current study; while they stand to benefit from such a device and 
may be included in future study phases, the proposed sample size is not large enough to account for the 
possible influence of parents upon children’s medication adherence. As both illicit drug use and 
dementia may also interfere with medication adherence in unanticipated ways, the current trial phase 
will exclude individuals self-reporting recent illicit drug use and/or a diagnosis of dementia; future trial 
phases may expand selection criteria to include these individuals. To maintain consistency in study 
conditions, individuals with recent or imminent changes to their ART regimen are also excluded. 
 
5.3 
LIFESTYLE CONSIDERATIONS 
 
Not applicable.  
 
5.4 
SCREEN FAILURES 
 
Screen failures are defined as participants who consent to participate in the clinical trial but are not 
subsequently assigned to the study intervention or entered in the study. A minimal set of screen failure 
information is required to ensure transparent reporting of screen failure participants, to meet the 
Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to respond to 
queries from regulatory authorities. Minimal information includes demography, screen failure details, 

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eligibility criteria, and any serious adverse event (SAE). Data from screen failures are retained as for 
other participant data (see Section 10.1.9.2). 
 
Individuals who do not meet the criteria for participation in this trial (screen failure) because of access 
to a personal smartphone and Wi-Fi connection may be rescreened. Rescreened participants will be 
assigned the same participant number as for the initial screening. 
 
5.5 
STRATEGIES FOR RECRUITMENT AND RETENTION 
  
 
The target sample will approximate the distribution of HIV/AIDS patients by race and ethnicity, and will 
equally enroll men and women, as seen in Figure 3.  
 
Figure 3. Target sample by gender, race, and ethnicity. 
 
 
 
Participants will be recruited from the outpatient population of HIV/AIDS patients in the San Francisco 
Bay region of California; the study will not enroll participants outside of the United States. Potential 
participants will be recruited using a 1-page flyer that will be posted in one or more medical practices in 
the Bay Area that specialize in the prevention and treatment of HIV/AIDS; providers and staff of these 
practices are not otherwise affiliated with the study. 
 
It is expected that approximately 75% of screened patients will be determined eligible for study 
enrollment, so approximately 32 individuals will be screened to reach the target sample size (n=24), 
which we expect to occur at a rate of approximately 2 participants per week.  
 
To aid retention efforts, medication adherence for each participant is monitored through the HiDO 
platform. The HiDO unit is first and foremost a medication adherence device. The device will transmit 
real time data about adherence and trial participation. To maintain study integrity, we cannot intervene 
to promote adherence beyond the reminders and prompts provided by the medication adherence 
system. That said, having the device in the home is a powerful, indirect participant retention tool. 
 
To compensate participants for their time, participants will receive $100 gift card, which is disbursed 
upon return of the HiDO device. Participants who do not complete study receive $5 for each full week 

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from device setup to date of notification by either party of study withdrawal, delivered by Visa gift card 
at device pickup. 
 
6 
STUDY INTERVENTION 
 
6.1 
STUDY INTERVENTION(S) ADMINISTRATION 
 
6.1.1 STUDY INTERVENTION DESCRIPTION 
 
HiDO (Health Information Data Outcomes) core product is an encrypted highly secure, Web-based 
system on AWS used to collect, track, and report patient medication consumption for the purpose of 
improving the data integrity of clinical research, patient care, and public health. The platform is a 510K 
exempt Class I medical device that integrates medication dispensing, dose administration time, pill 
count and a front facing video camera to validate the right medications, at right time to the right 
patient. The camera logs every dose using facial recognition and provides real time consumption logs. 
The device dispenses up to 7 different types of medications simultaneously from 40-dram bins.  
 
See Appendix A (HiDO Product Brochure) for hardware specifications.  
 
Core (AMCS) features and functions include: 1 
• 
Patient-compliance (Real-time): Dynamic clinical dashboards, mobile consent, adherence screen, 
push notifications, large font and buttons (single, multi, date, number, free-text, visual pain, 
VAS, etc.), multiple language capability, robust survey parameters 
o Flexible patient dashboards – Clinical Studies and Public Health populations are 
customized by individual principal investigators and public health departments: 
Validated compliance methodology and video observation therapy. 
o Conditional patient surveys – Surveys are dynamically built for an individual patient 
based on two levels of conditional parameters: Conditional survey assignments and 
questioning (branching logic within a survey takes the patient to new questions within 
the survey or to new surveys). 
• 
Patient embedded surveys:  
o Easy-to-use patient surveys – Form-based patient surveys quickly capture adverse 
events and treatment side effects, easy-to-use user interface, and reporting. 
o Multiple episodes of care – Clinical dashboards that show multiple consumptions, 
viewed, and recorded for clinician analysis; this allows for more accurate assessment of 
a patient’s longitudinal progress of care and better understand variability in aggregate 
data analysis. 
o Dynamic clinical protocols – On completion of a clinician survey, additional questions 
may be asked based on the protocols set up for that clinical area and a combination of 
clinician and patient survey responses; these protocols can be used to educate patients 
and track compliance with standard processes of care defined by the study protocols; 
 
 
1 Please note that the current study does not employ or test the mobile consent, patient survey, or patient 
education features. 

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such care processes could include evidence-based protocols, quality measures, red flag 
considerations, or study-based protocols. 
• 
Patient education: tailored to patient responses, drug information and disease guidance, web 
links to patient education (e.g., Healthwise, CDC) 
• 
Reporting: HiDO includes five types of reporting: 
o Clinician summary report – displays summary of individual patient-reported data, 
longitudinal adherence timeline, highlighted color coded (Green/Yellow/Red) 
o Patient-viewable mobile dashboards – tailored to patient adherence records, trend 
analysis of consumption, pills missed/taken, and links to websites 
o Standard aggregate data reports – aggregate survey responses, aggregate outcomes, 
individual summary scores (parameter-driven, save templates) 
o Standard operational reports – pending surveys, survey compliance, patient contact, 
etc. (parameter-driven, save templates) 
o Custom reporting via separate database – HL-7 outbound interface to client local 
database for client reporting 
• 
Workflow: Auto-queuing of surveys (based on logic), push notifications to mobile, role-based 
worklists, contact log 
• 
Site setup configuration: patient group, appointment types, queuing logic, site preferences, 
users, clinicians 
• 
Data transfer: System interfaces (Scheduling system, patient portal, EMR, data warehouse); 
Data extracts (tab-delimited, SAS) 
• 
Security: functionality security by role, standard or advanced data security by clinical area; 
HIPAA audit logs; HTTPS / 128-bit SSL; VPN; FTP over SSL; password security; server protection 
via multiple firewalls, intrusion detection system. 
o Patient Profile describes key components of a patient in an easy-to-use structure in four 
categories delineated by tab structures including: General, Insurance, Personal, and 
Clinical information for that patient; the goal is to minimize the information stored on 
this profile to be only the patient information needed to assign surveys (e.g., 
demographic, disease or condition, insurance type), assist the clinician in the clinician 
survey process, and provide a database suitable to support research and clinical studies; 
ideally, the information that is contained on the clinicians electronic medical record 
(EMR) is downloaded from that system and not re-entered  
 
Video/Audio recording of the medication consumption is about 10 seconds in duration.  The recording 
does not start until the patient unlocks the device with facial recognition and verifies the appropriate 
medication dispensing.  The research team is HIPPA certified, and recordings are encrypted via AWS 
secured HIPPA storage. 
6.1.2 DOSING AND ADMINISTRATION 
 
The Principal Investigator will deliver the device to the participant’s home and will assist each 
participant with initial device setup that includes filling the device with ART (the device holds and can 
dispense up to 7 different medications), installing the device app on the participant’s smartphone, and 
configuring the device and app. The participant receives a smartphone alert when it is time to take a 
medication. The participant then pushes the button on the device and receives the correct medicine at 
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device video records the interaction to verify that the medication was consumed. If the patient does not 
$respond, additional reminders are sent via SMS and read as: "It’s time to take your morning 
medication" (for late doses scheduled for 12pm Pacific Time or earlier) of “It’s time to take your evening 
medication” (for late doses scheduled after 12pm Pacific Time).  
 
6.2 
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY 
 
6.2.1 ACQUISITION AND ACCOUNTABILITY 
 
At the beginning of the study, the HiDO medication adherence platform will be delivered in person to 
the home of record of each participant. At the end of the 90-day intervention period, the device will be 
picked up from the participant’s home by the PI.  
  
6.2.2 FORMULATION, APPEARANCE, PACKAGING, AND LABELING 
 
See Appendix A (HiDO Product Brochure) 
 
 
6.2.3 PRODUCT STORAGE AND STABILITY 
 
The HiDO device should be kept away from damp or wet areas and out of reach of pets and children.    
 
 
6.2.4 PREPARATION 
 
Not applicable.  
 
6.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
 
Not applicable.  
 
 
6.4 
STUDY INTERVENTION COMPLIANCE 
 
Study compliance will be assessed through manual audits of HiDO dosage logs, which verify interaction 
with participant through video recording, and completion of post-intervention interview and 
questionnaire.  
 
6.5 
CONCOMITANT THERAPY 
 
Not applicable. 
 
6.5.1 RESCUE MEDICINE 
 
Not applicable. 
 

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7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
 
7.1 
DISCONTINUATION OF STUDY INTERVENTION 
 
Discontinuation from HiDO platform use does not mean discontinuation from the study, and remaining 
study procedures should be completed as indicated by the study protocol.  Although not expected to 
occur, if a clinically significant finding is identified after enrollment, the investigator or qualified 
designee will determine if any change in participant management is needed. Any new clinically relevant 
finding will be reported as an adverse event (AE). 
 
 
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
 
Participants are free to withdraw from participation in the study at any time upon request. 
An investigator may discontinue or withdraw a participant from the study for the following reasons: 
 
• 
Significant study intervention non-compliance  
• 
If any clinical adverse event (AE), laboratory abnormality, or other medical condition or situation 
occurs such that continued participation in the study would not be in the best interest of the 
participant 
• 
Disease progression which requires discontinuation of the study intervention 
• 
If the participant meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation 
• 
Incarceration 
The reason for participant discontinuation or withdrawal from the study will be recorded on the relevant 
Case Report Form (CRF). Participants who sign the informed consent form, and receive the study 
intervention, and subsequently withdraw, or are withdrawn or discontinued from the study, will be 
replaced as needed to ensure a sample size of at least 15 participants. 
 
7.3 
LOST TO FOLLOW-UP 
 
A participant will be considered lost to follow-up if he or she does not complete the post-intervention 
interview and questionnaire and is unable to be contacted by the study site staff. 
 
The following actions must be taken if an enrolled participant does not complete the post-intervention 
interview and questionnaire: 
• 
The site will attempt to contact the participant to determine the cause of the missed interview, 
and ascertain if the participant wishes to and/or should continue in the study. 
• 
Before a participant is deemed lost to follow-up, the investigator or designee will make every 
effort to regain contact with the participant (where possible, 3 telephone calls and, if necessary, 
a certified letter to the participant’s last known mailing address or local equivalent methods). 
These contact attempts will be documented in the participant’s study file.  

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• 
Should the participant continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up. 
 
8 
STUDY ASSESSMENTS AND PROCEDURES 
 
8.1 
EFFICACY ASSESSMENTS  
 
Study data will be gathered through the following procedures: 
 
• 
Interaction with HiDO platform. Dosage logs, video recording of participant during dosing 
• 
Questionnaires and interviews.  Self-reported medication adherence, usability metrics, open-
ended consumer feedback. 
 
 
8.2 
SAFETY AND OTHER ASSESSMENTS 
 
Automated medication logs from the HiDO device, and manual audits thereof, will be used to assess 
safety – for instance, in the unlikely event that the HiDO device contributes to substantially lower 
medication adherence as compared to baseline. Logs will be audited monthly beginning in Week 4 of the 
earliest participant enrollment.  
 
   
8.3 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
 
 
8.3.1 DEFINITION OF ADVERSE EVENTS (AE) 
 
Adverse event means any untoward medical occurrence associated with the use of an intervention in 
humans, whether or not considered intervention-related (21 CFR 312.32 (a)). 
 
 
8.3.2 DEFINITION OF SERIOUS ADVERSE EVENTS (SAE)  
 
An adverse event (AE) or suspected adverse reaction is considered "serious" if, in the view of either the 
investigator or sponsor, it results in any of the following outcomes: death, a life-threatening adverse 
event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant 
incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital 
anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or 
require hospitalization may be considered serious when, based upon appropriate medical judgment, 
they may jeopardize the participant and may require medical or surgical intervention to prevent one of 
the outcomes listed in this definition. Examples of such medical events include allergic bronchospasm 
requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions that do 
not result in inpatient hospitalization, or the development of drug dependency or drug abuse. 
 
8.3.3 CLASSIFICATION OF AN ADVERSE EVENT 

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8.3.3.1 SEVERITY OF EVENT 
 
The CTCAE V. 4.03 will be used in this study. Each adverse event must be assigned a Grade, which refers 
to the severity of the adverse event. The CTCAE v4.03 displays Grades 1 through 5 with unique clinical 
descriptions of severity for each adverse event on this general guideline: 
 
Grade 1 – Mild AE 
Grade 2 – Moderate AE 
Grade 3 – Severe AE 
Grade 4 – Life-threatening or disabling AE 
Grade 5 – Death related to AE 
 
 
8.3.3.2 RELATIONSHIP TO STUDY INTERVENTION 
 
All adverse events (AEs) must have their relationship to study intervention assessed by the clinician who 
examines and evaluates the participant based on temporal relationship and his/her clinical judgment. 
The degree of certainty about causality will be graded using the categories below. In a clinical trial, the 
study product must always be suspect.  
 
• 
Related – The AE is known to occur with the study intervention, there is a reasonable possibility 
that the study intervention caused the AE, or there is a temporal relationship between the study 
intervention and event. Reasonable possibility means that there is evidence to suggest a causal 
relationship between the study intervention and the AE. 
• 
Not Related – There is not a reasonable possibility that the administration of the study 
intervention caused the event, there is no temporal relationship between the study intervention 
and event onset, or an alternate etiology has been established. 
 
OR 
 
• 
Definitely Related – There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out. The clinical event, including an abnormal laboratory test 
result, occurs in a plausible time relationship to study intervention administration and cannot be 
explained by concurrent disease or other drugs or chemicals. The response to withdrawal of the 
study intervention (dechallenge) should be clinically plausible. The event must be 
pharmacologically or phenomenologically definitive, with use of a satisfactory rechallenge 
procedure if necessary. 
• 
Probably Related – There is evidence to suggest a causal relationship, and the influence of other 
factors is unlikely. The clinical event, including an abnormal laboratory test result, occurs within 
a reasonable time after administration of the study intervention, is unlikely to be attributed to 
concurrent disease or other drugs or chemicals, and follows a clinically reasonable response on 
withdrawal (dechallenge). Rechallenge information is not required to fulfill this definition. 
• 
Potentially Related – There is some evidence to suggest a causal relationship (e.g., the event 
occurred within a reasonable time after administration of the trial medication). However, other 
factors may have contributed to the event (e.g., the participant’s clinical condition, other 

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concomitant events). Although an AE may rate only as “possibly related” soon after discovery, it 
can be flagged as requiring more information and later be upgraded to “probably related” or 
“definitely related”, as appropriate. 
• 
Unlikely to be related – A clinical event, including an abnormal laboratory test result, whose 
temporal relationship to study intervention administration makes a causal relationship 
improbable (e.g., the event did not occur within a reasonable time after administration of the 
study intervention) and in which other drugs or chemicals or underlying disease provides 
plausible explanations (e.g., the participant’s clinical condition, other concomitant treatments). 
• 
Not Related – The AE is completely independent of study intervention administration, and/or 
evidence exists that the event is definitely related to another etiology. There must be an 
alternative, definitive etiology documented by the clinician. 
 
8.3.3.3 EXPECTEDNESS  
 
The Investigator will be responsible for determining whether an adverse event (AE) is expected or 
unexpected.  An AE will be considered unexpected if the nature, severity, or frequency of the event is 
not consistent with the risk information previously described for the study intervention. 
 
8.3.4 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
 
The occurrence of an adverse event (AE) or serious adverse event (SAE) may come to the attention of 
study personnel during study visits and interviews of a study participant presenting for medical care, or 
upon review by a study monitor. 
 
All AEs including local and systemic reactions not meeting the criteria for SAEs will be captured on the 
appropriate case report form (CRF). Information to be collected includes event description, time of 
onset, clinician’s assessment of severity, relationship to study product (assessed only by those with the 
training and authority to make a diagnosis), and time of resolution/stabilization of the event. All AEs 
occurring while on study must be documented appropriately regardless of relationship. All AEs will be 
followed to adequate resolution. 
 
Any medical condition that is present at the time that the participant is screened will be considered as 
baseline and not reported as an AE. However, if the study participant’s condition deteriorates at any 
time during the study, it will be recorded as an AE.  
 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the event 
at each level of severity to be performed. AEs characterized as intermittent require documentation of 
onset and duration of each episode. 
 
The Principal Investigator will record all reportable events with start dates occurring any time after 
informed consent is obtained until 7 (for non-serious AEs) or 30 days (for SAEs) after the last day of 
study participation.  At each study visit, the investigator will inquire about the occurrence of AE/SAEs 
since the last visit.  Events will be followed for outcome information until resolution or stabilization. 
 
 
8.3.5 ADVERSE EVENT REPORTING  

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Serious adverse events will be collected throughout the study period. All serious adverse events must be 
reported to HiDO Technologies within 24 hours of discovery or notification of the event. Initial serious 
adverse event information and all amendments or additions must be recorded on a Serious Adverse 
Event Report Form and submitted to HiDO Technologies. The Principal Investigator will notify the IRB of 
serious adverse events within seven days or as otherwise specified by local policies.  
 
Disease-related events (DREs) can be expected to occur among the study population, which may include 
HIV/AIDS patients. These events are recorded by research staff, but are not reported as for AEs.  
 
 
 
8.3.6 SERIOUS ADVERSE EVENT REPORTING  
 
The study investigator shall complete an Unanticipated Adverse Device Effect Form and submit to the 
reviewing Institutional Review Board (IRB) as soon as possible, but in no event later than 10 working 
days after the investigator first learns of the effect.  The study sponsor is responsible for conducting an 
evaluation of an unanticipated adverse device effect and shall report the results of such evaluation to 
the reviewing IRB and participating investigators within 10 working days after the sponsor first receives 
notice of the effect. Thereafter, the sponsor shall submit such additional reports concerning the effect 
as FDA requests. 
 
 
8.3.7 REPORTING EVENTS TO PARTICIPANTS  
 
Not applicable. 
 
8.3.8 EVENTS OF SPECIAL INTEREST  
 
Not applicable.  
 
8.3.9 REPORTING OF PREGNANCY  
 
Not applicable.  
 
 
8.4 
UNANTICIPATED PROBLEMS 
 
8.4.1 DEFINITION OF UNANTICIPATED PROBLEMS (UP) 
 
The Office for Human Research Protections (OHRP) considers unanticipated problems involving risks to 
participants or others to include, in general, any incident, experience, or outcome that meets all of the 
following criteria: 
 
• 
Unexpected in terms of nature, severity, or frequency given (a) the research procedures that are 
described in the protocol-related documents, such as the Institutional Review Board (IRB)-

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approved research protocol and informed consent document; and (b) the characteristics of the 
participant population being studied; 
• 
Related or possibly related to participation in the research (“possibly related” means there is a 
reasonable possibility that the incident, experience, or outcome may have been caused by the 
procedures involved in the research); and 
• 
Suggests that the research places participants or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or recognized. 
 
This definition could include an unanticipated adverse device effect, any serious adverse effect on 
health or safety or any life-threatening problem or death caused by, or associated with, a device, if that 
effect, problem, or death was not previously identified in nature, severity, or degree of incidence in the 
investigational plan or application (including a supplementary plan or application), or any other 
unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of 
participants (21 CFR 812.3(s)). 
 
 
8.4.2  UNANTICIPATED PROBLEM REPORTING  
 
The investigator will report unanticipated problems (UPs) to the reviewing Institutional Review Board 
(IRB) and to the Data Coordinating Center (DCC)/lead principal investigator (PI). The UP report will 
include the following information: 
 
• 
Protocol identifying information: protocol title and number, PI’s name, and the IRB project 
number; 
• 
A detailed description of the event, incident, experience, or outcome;  
• 
An explanation of the basis for determining that the event, incident, experience, or outcome 
represents an UP;  
• 
A description of any changes to the protocol or other corrective actions that have been taken or 
are proposed in response to the UP. 
 
To satisfy the requirement for prompt reporting, UPs will be reported using the following timeline:   
 
• 
UPs that are serious adverse events (SAEs) will be reported to the IRB within seven days of the 
investigator becoming aware of the event.  
• 
Any other UP will be reported to the IRB within 30 days of the investigator becoming aware of 
the problem.  
 
An investigator shall submit to the reviewing Institutional Review Board (IRB) a report of any 
unanticipated adverse device effect occurring during an investigation as soon as possible, but in no 
event later than 10 working days after the investigator first learns of the effect.  
 
8.4.3 REPORTING UNANTICIPATED PROBLEMS TO PARTICIPANTS  
 
Participants will be verbally notified about UPs as required to disclosure known risks and maintain 
informed consent.  
 
 

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9 
STATISTICAL CONSIDERATIONS  
 
9.1 
STATISTICAL HYPOTHESES 
 
Primary Efficacy Endpoint (1): Determine the effect of automated medication adherence platform 
(HiDO) on medication compliance. 
 
H0:  Use of the HiDO automated medication adherence platform will result in <94% medication 
adherence over 90 days. 
Ha:  Use of the HiDO automated medication adherence platform will result in ≥95% medication 
adherence over 90 days. 
 
Primary endpoint (1) will be analyzed once study intervention for all participants is completed. 
 
Secondary Efficacy Endpoint (2): Determine usability of automated medication adherence platform 
(HiDO), as indicated by user ease of adoption (Time on Task, error rates). 
 
H0:  Usability scores for the HiDO platform (as measured by Time on Task for initial registration, “first 
click” testing, facial recognition setup, and medication administration, number and type of critical 
and non-critical errors, and error-free rate) will be lower than published benchmark rates for similar 
platforms. 
Ha:  Usability scores for the HiDO platform (as measured by Time on Task for initial registration, “first 
click” testing, facial recognition setup, and medication administration, number and type of critical 
and non-critical errors, and error-free rate) will be equal to or better than published benchmark 
rates for similar platforms. 
 
Secondary endpoint (2) will be analyzed once all participants have completed 14 days of study 
intervention. 
 
Secondary Efficacy Endpoint (3): Determine usability of automated medication adherence platform 
(HiDO), as indicated by standardized user experience metric (SUS). 
 
H0:  The System Usability Scale (SUS) value for the HiDo platform will be lower than published 
benchmark rates for similar platforms (≤68).  
Ha:  The System Usability Scale (SUS) value for the HiDo platform will be better than published 
benchmark rates for similar platforms (>68).  
 
Secondary endpoint (3) will be analyzed once all participants have completed the post-intervention 
interview. 
 
Secondary Efficacy Endpoint (4): Determine usability of automated medication adherence platform 
(HiDO), as indicated by user endorsement (Net Promoter Score). 
 
H0:  80% or fewer participants will indicate that they are Likely or Strongly Likely to recommend the 
HiDo device to a friend or colleague.  

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Ha:  Greater than 80% of participants will indicate that they are Likely or Strongly Likely to 
recommend the HiDo device to a friend or colleague.  
 
Secondary endpoint (4) will be analyzed once all participants have completed the post-intervention 
interview. 
 
 
9.2 
SAMPLE SIZE DETERMINATION 
 
TARGET SAMPLE SIZE: 24  
 
The current study is a pilot study, the intent of which is to gather preliminary data on device usage to 
determine whether further study with a larger sample is both possible and merited based on early 
findings of the device’s efficacy and usability.  For this study, the expected effect of the device upon 
medication adherence is expected to be moderate to large, based on an expected 95% adherence rate 
post-study in relation to reported adherence rates in clinical trials of 54% to 68%, which is used to 
estimate baseline adherence.9 Based on the expectation of moderate treatment effect, a sample size of 
between 10-15 is indicated as sufficient. 26,27 A target sample size of 24 should be sufficient to ensure at 
least 15 participants will complete the study at an estimated 60% completion rate of recruited 
participants.   
 
 
9.3 
POPULATIONS FOR ANALYSES 
 
• 
Modified Intention-to-Treat Analysis Dataset: participants who are enrolled for at least 7 days of 
the 90-day intervention period  
• 
Per-Protocol Analysis Dataset: participants who complete the 90-day intervention period and 
post-study interview and questionnaire. 
 
 
9.4 
STATISTICAL ANALYSES 
 
9.4.1 GENERAL APPROACH 
 
Categorical and continuous data will be presented as percentages, means with standard deviations, 
median, range.  
 
9.4.2 ANALYSIS OF THE PRIMARY EFFICACY ENDPOINT(S) 
 
Given the small sample size and specification of secondary endpoints, descriptive statistics are sufficient 
to either accept or reject the null hypothesis.   
 
 
9.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
 

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Given the small sample size and specification of all secondary endpoints, descriptive statistics are 
sufficient to either accept or reject the null hypotheses.   
 
 
9.4.4 SAFETY ANALYSES 
 
Not applicable.  
 
9.4.5 BASELINE DESCRIPTIVE STATISTICS 
 
For each part of the study, descriptive statistics (N, mean, SD, median, minimum, and maximum) will be 
generated for continuous demographic variables and pre-intervention medication adherence variables.  
 
Demographic variables of screen failure participants and reasons for screen failures will 
be summarized overall for participants who are screened, but not enrolled in the study. Individual 
demographic characteristics, date of informed consent, and reason for screen failure will be listed. 
 
9.4.6 PLANNED INTERIM ANALYSES  
 
Not applicable.  
 
9.4.7 SUB-GROUP ANALYSES 
 
The sample size is not sufficient to conduct formal sub-group analyses, and the study was not designed 
for this purpose.  
 
9.4.8 TABULATION OF INDIVIDUAL PARTICIPANT DATA 
 
Individual participant data will be tabulated by measure and time point. 
 
9.4.9 EXPLORATORY ANALYSES 
 
Qualitative data produced by answers to open-ended interview questions will be reviewed to determine 
any relevant aspects of the participant’s experience with the device that were not captured by the 
System Usability Scale or the Net Promoter Scale.  
 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
 
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
 
 
10.1.1 INFORMED CONSENT PROCESS 
 
 
10.1.1.1 CONSENT/ASSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED TO 
PARTICIPANTS 

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Consent forms describing in detail the study intervention, study procedures, and risks are given to the 
participant and written documentation of informed consent is required prior to starting 
intervention/administering study intervention.  The following consent materials are submitted with this 
protocol: 
• 
Recruitment flyer 
• 
Device flyer 
• 
Consent form 
• 
Informed consent SOP2 
 
 
10.1.1.2 CONSENT PROCEDURES AND DOCUMENTATION 
 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the 
study and continues throughout the individual’s study participation. Consent forms will be Institutional 
Review Board (IRB)-approved and the participant will be asked to read and review the document. The 
investigator will explain the research study to the participant and answer any questions that may arise. 
A verbal explanation will be provided in terms suited to the participant’s comprehension of the 
purposes, procedures, and potential risks of the study and of their rights as research participants.  
Participants will have the opportunity to carefully review the written consent form and ask questions 
prior to signing. The participants should have the opportunity to discuss the study with their family or 
surrogates or think about it prior to agreeing to participate. The participant will sign the informed 
consent document prior to any procedures being done specifically for the study. Participants will be 
informed that participation is voluntary and that they may withdraw from the study at any time, without 
prejudice. A copy of the informed consent document will be given to the participants for their records. 
The informed consent process will be conducted and documented in the source document (including the 
date), and the form signed, before the participant undergoes any study-specific interventions. The rights 
and welfare of the participants will be protected by emphasizing to them that the quality of their 
medical care will not be adversely affected if they decline to participate in this study. 
 
10.1.2 STUDY DISCONTINUATION AND CLOSURE 
 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable 
cause.  Written notification, documenting the reason for study suspension or termination, will be 
provided by the suspending or terminating party to study participants, investigators, funding agencies, 
and regulatory authorities.  If the study is prematurely terminated or suspended, the Principal 
Investigator (PI) will promptly inform study participants, the Institutional Review Board (IRB), and 
sponsor and will provide the reason(s) for the termination or suspension.  Study participants will be 
contacted, as applicable, and be informed of changes to study visit schedule. 
  
Circumstances that may warrant termination or suspension include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to participants 
 
 
2 This document describes the steps of the consent process; it is not provided to participants.  

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• 
Demonstration of efficacy that would warrant stopping    
• 
Insufficient compliance to protocol requirements 
• 
Data that are not sufficiently complete and/or evaluable 
• 
Determination that the primary endpoint has been met 
• 
Determination of futility 
 
Study may resume once concerns about safety, protocol compliance, and data quality are addressed, 
and satisfy the sponsor, IRB and/or Food and Drug Administration (FDA). 
 
 
10.1.3 CONFIDENTIALITY AND PRIVACY  
 
Participant confidentiality and privacy is strictly held in trust by the participating investigators, their 
staff, and the sponsor(s) and their interventions. This confidentiality is extended to cover testing of 
biological samples and genetic tests in addition to the clinical information relating to participants. 
Therefore, the study protocol, documentation, data, and all other information generated will be held in 
strict confidence. No information concerning the study or the data will be released to any unauthorized 
third party without prior written approval of the sponsor.  
 
All research activities will be conducted in as private a setting as possible. 
 
The study monitor, other authorized representatives of the sponsor, representatives of the Institutional 
Review Board (IRB), regulatory agencies or pharmaceutical company supplying study product may 
inspect all documents and records required to be maintained by the investigator. The study site will 
permit access to such records. 
 
The study participant’s contact information will be securely stored at the research site for internal use 
during the study. At the end of the study, all records will continue to be kept in a secure location for as 
long a period as dictated by the reviewing IRB, Institutional policies, or sponsor requirements. 
 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will 
be transmitted to and stored at HiDO Technologies. This will not include the participant’s contact or 
identifying information. Rather, individual participants and their research data will be identified by a 
unique study identification number. The study data entry and study management systems used by 
clinical sites and by HiDO Technologies research staff will be secured and password protected. At the 
end of the study, all study databases will be de-identified and archived at HiDO Technologies. 
 
 
10.1.4 FUTURE USE OF STORED SPECIMENS AND DATA  
 
Not applicable.   
 
10.1.5 KEY ROLES AND STUDY GOVERNANCE 
 
Charles Gellman, MSHI, MBA (Principal Investigator). Mr. Gellman’s has a strong background in 
statistics, clinical informatics, and data analysis in which he has accelerated the understanding of health 
data to improve health outcomes. His thesis research focused on performance metrics of hospital 

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mortality, readmissions and health care associated infections across the country using the Centers for 
Medicare & Medicaid Services (CMS) aggregated hospital database. He will oversee all aspects of the 
trial including device manufacturing, deployment, recapture, data acquisition, analysis, and reporting. 
 
 
10.1.6 SAFETY OVERSIGHT 
 
Not applicable.  
 
10.1.7 CLINICAL MONITORING 
 
Not applicable.  
 
 
10.1.8 QUALITY ASSURANCE AND QUALITY CONTROL 
 
The clinical site will perform internal quality management of study conduct, data collection, 
documentation, and completion.  An individualized quality management plan will be developed to 
describe a site’s quality management. 
 
Quality control (QC) procedures will be implemented beginning with the data entry system and data QC 
checks that will be run on the database will be generated. Any missing data or data anomalies will be 
flagged for clarification/resolution. 
 
The investigational site will provide direct access to all trial related sites, source data/documents, and 
reports for the purpose of monitoring and auditing by the sponsor, and inspection by local and 
regulatory authorities. 
 
 
10.1.9 DATA HANDLING AND RECORD KEEPING  
 
10.1.9.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
 
Data collection is the responsibility of the investigator.  The investigator is responsible for ensuring the 
accuracy, completeness, legibility, and timeliness of the data reported. 
 
Hardcopies of the study visit worksheets will be provided for use as source document worksheets for 
recording data for each participant enrolled in the study.  Data recorded in the electronic case report 
form (eCRF) derived from source documents should be consistent with the data recorded on the source 
documents.  
 
Study data (including adverse events (AEs), concomitant medications, and expected adverse reactions 
data) are stored on AWS, a 21 CFR Part 11-compliant cloud computing platform.  The data system 
includes password protection; internal quality checks are conducted manually to identify data that 
appear inconsistent, incomplete, or inaccurate. Study data will be entered directly from the source 
documents. 
 

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10.1.9.2 STUDY RECORDS RETENTION  
 
Study documents may be retained indefinitely, and for a minimum of 3 years after the last approval of a 
marketing application in an International Conference on Harminosation (ICH) region and until there are 
no pending or contemplated marketing applications in an ICH region, or until at least 3 years from the 
date of the Federal Financial Report (FFR) submission. These documents should be retained for a longer 
period, however, if required by local regulations.  
 
 
10.1.10 
PROTOCOL DEVIATIONS  
 
A protocol deviation is any noncompliance with the clinical trial protocol, International Conference on 
Harmonisation Good Clinical Practice (ICH GCP), or Manual of Procedures (MOP) requirements. The 
noncompliance may be either on the part of the participant, the investigator, or the study site staff. As a 
result of deviations, corrective actions are to be developed by the site and implemented promptly.  
 
These practices are consistent with ICH GCP:  
• 
4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3  
• 
5.1 Quality Assurance and Quality Control, section 5.1.1  
• 
5.20 Noncompliance, sections 5.20.1, and 5.20.2.  
 
It is the responsibility of the investigator to use continuous vigilance to identify and report deviations 
within five working days of identification of the protocol deviation or scheduled protocol-required 
activity.  All deviations must be addressed in study source documents and reported to the reviewing 
Institutional Review Board (IRB) per their policies. The investigator is responsible for knowing and 
adhering to the reviewing IRB requirements.  
 
10.1.11 
PUBLICATION AND DATA SHARING POLICY 
 
Data from this study will not be shared. Findings of this study may be published.  
 
 
10.1.12 
CONFLICT OF INTEREST POLICY 
 
The independence of this study from any actual or perceived influence is critical.  Therefore, any actual 
conflict of interest of persons who have a role in the design, conduct, analysis, publication, or any aspect 
of this trial will be disclosed and managed in a way that is appropriate to the individual’s participation in 
the design and conduct of this trial.   
 
10.2 ADDITIONAL CONSIDERATIONS 
 
Not applicable. 
 
 

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10.3 ABBREVIATIONS 
 
AE 
Adverse Event 
ANCOVA 
Analysis of Covariance 
CFR 
Code of Federal Regulations 
CLIA 
Clinical Laboratory Improvement Amendments 
CMP 
Clinical Monitoring Plan 
COC 
Certificate of Confidentiality 
CONSORT 
Consolidated Standards of Reporting Trials 
CRF 
Case Report Form 
DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
DSMB 
Data Safety Monitoring Board 
DRE 
Disease-Related Event 
EC 
Ethics Committee 
eCRF 
Electronic Case Report Forms 
HER 
Electronic Health Records 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Amendments Act of 2007 
FFR 
Federal Financial Report 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practices 
HIPAA 
Health Insurance Portability and Accountability Act  
IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonisation  
ICMJE 
International Committee of Medical Journal Editors 
IDE 
Investigational Device Exemption 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
ISO 
International Organization for Standardization 
ITT 
Intention-To-Treat 
MedDRA 
Medical Dictionary for Regulatory Activities 
MOP 
Manual of Procedures 
MSDS 
Material Safety Data Sheet 
NCT 
National Clinical Trial 
NIH  
National Institutes of Health 
NIH IC 
NIH Institute or Center 
OHRP 
Office for Human Research Protections 
PI 
Principal Investigator 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SMC 
Safety Monitoring Committee 
SOA 
Schedule of Activities 
SOP 
Standard Operating Procedure 
UP 
Unanticipated Problem 
US 
United States 

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10.4 PROTOCOL AMENDMENT HISTORY 
The table below is intended to capture changes of IRB-approved versions of the protocol, including a 
description of the change and rationale. A Summary of Changes table for the current amendment is 
located in the Protocol Title Page.  
 
Version 
Date 
Description of Change  
Brief Rationale 
2.1 
7/1/21 
See separated sheet “2021-07-01 
Responses to review” 
Address pre-review comments 
2.2 
7/20/21 
Fixed a typo per reviewer’s request; 
clarified data retention policy 
Address reviewer conditions 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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11 REFERENCES  
 
1.  World Health Organization. HIV/AIDS: Key Facts. 2019; https://www.who.int/en/news-room/factsheets/ 
detail/hiv-aids. Accessed 03/18/2020. 
 
2.  Kassutto S, Maghsoudi K, Johnston MN, et al. Longitudinal analysis of clinical markers following antiretroviral 
therapy initiated during acute or early HIV type 1 infection. Clin Infect Dis. 2006;42(7):1024-1031. 10.1086/500410 
 
3.  Park LS, Tate JP, Sigel K, et al. Association of Viral Suppression With Lower AIDS-Defining and Non-AIDS-Defining 
Cancer Incidence in HIV-Infected Veterans: A Prospective Cohort Study. Ann Intern Med. 2018;169(2):87-96. 
10.7326/M16-2094 
 
4.  Smith CJ, Sabin CA, Youle MS, et al. Factors influencing increases in CD4 cell counts of HIV-positive persons 
receiving long-term highly active antiretroviral therapy. J Infect Dis. 2004; 190(10):1860-1868.10.1086/425075 
 
5.  Bavinton BR, Pinto AN, Phanuphak N, et al. Viral suppression and HIV transmission in serodiscordant male 
couples: an international, prospective, observational, cohort study. Lancet HIV. 2018;5(8):e438-e447. 
10.1016/S2352-3018(18)30132-2 
 
6.  Cohen MS, Chen YQ, McCauley M, et al. Antiretroviral Therapy for the Prevention of HIV-1 Transmission. N Engl 
J Med. 2016;375(9):830-839. 10.1056/NEJMoa1600693 
 
7.  Rodger AJ, Cambiano V, Bruun T, et al. Sexual Activity Without Condoms and Risk of HIV Transmission in 
Serodifferent Couples When the HIV-Positive Partner Is Using Suppressive Antiretroviral Therapy. JAMA. 
2016;316(2):171-181. 10.1001/jama.2016.5148 
 
8.  Vrijens B, Urquhart J. Methods for measuring, enhancing, and accounting for medication adherence in clinical 
trials. Clin Pharmacol Ther. 2014;95(6):617-626. 10.1038/clpt.2014.59 
 
9.  Czobor P, Skolnick P. The secrets of a successful clinical trial: compliance, compliance, and compliance. Mol 
Interv. 2011;11(2):107-110. 10.1124/mi.11.2.8 
 
10.  Gossec L, Tubach F, Dougados M, Ravaud P. Reporting of adherence to medication in recent randomized 
controlled trials of 6 chronic diseases: a systematic literature review. Am J Med Sci. 2007;334(4):248-254. 
10.1097/MAJ.0b013e318068dde8 
 
11.  Ickovics JR, Cameron A, Zackin R, et al. Consequences and determinants of adherence to antiretroviral 
medication: results from Adult AIDS Clinical Trials Group protocol 370. Antivir Ther 
2002;7(3):185-193. 
 
12.  Byrd KK, Hou JG, Hazen R, et al. Antiretroviral Adherence Level Necessary for HIV Viral Suppression Using Real-
World Data. J Acquir Immune Defic Syndr. 2019;82(3):245-251. 10.1097/QAI.0000000000002142 
 
13.  Alsumidaie M. Non-adherence: a direct influence on clinical trial duration and cost. Applied Clinical Trials 
online, Apr 2017(www appliedclinicaltrialsonline com/non-adherence-direct-influenceclinical-trialduration-and-
cost, Accessed May 2018). 2018. 
 
14.  Shiovitz TM, Bain EE, McCann DJ, et al. Mitigating the Effects of Nonadherence in Clinical Trials. J Clin 
Pharmacol. 2016;56(9):1151-1164. 10.1002/jcph.689 
 
15.  Kanters S, Park JJ, Chan K, et al. Interventions to improve adherence to antiretroviral therapy: a systematic 
review and network meta-analysis. Lancet HIV. 2017;4(1):e31-e40. 10.1016/S2352-3018(16)30206-5 

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16.  Macalino GE, Hogan JW, Mitty JA, et al. A randomized clinical trial of community-based directly observed 
therapy as an adherence intervention for HAART among substance users. AIDS. 2007;21(11):1473-1477. 
10.1097/QAD.0b013e32811ebf68 
 
17.  Taiwo BO, Idoko JA, Welty LJ, et al. Assessing the viorologic and adherence benefits of patient-selected HIV 
treatment partners in a resource-limited setting. J Acquir Immune Defic Syndr.2010;54(1):85-92. 
10.1097/01.qai.0000371678.25873.1c 
 
18.  Hart JE, Jeon CY, Ivers LC, et al. Effect of directly observed therapy for highly active antiretroviral therapy on 
virologic, immunologic, and adherence outcomes: a meta-analysis and systematic review. J Acquir Immune Defic 
Syndr. 2010;54(2):167-179. 10.1097/QAI.0b013e3181d9a330 
 
19.  Liechty CA, Bangsberg DR. Doubts about DOT: antiretroviral therapy for resource-poor countries. AIDS. 
2003;17(9):1383-1387. 10.1097/00002030-200306130-00013 
 
20.  Lucas GM, Flexner CW, Moore RD. Directly administered antiretroviral therapy in the treatment of HIV 
infection: benefit or burden? AIDS Patient Care STDS. 2002;16(11):527-535. 10.1089/108729102761041083 
 
21.  Ford N, Nachega JB, Engel ME, Mills EJ. Directly observed antiretroviral therapy: a systematic review and meta-
analysis of randomised clinical trials. Lancet. 2009;374(9707):2064-2071. 10.1016/S0140-6736(09)61671-8 
 
22.  GraphPad. QuickCalcs. http://www.graphpad.com/quickcalcs/index.cfm. Accessed April 1, 2020. 
 
23.  Simoni JM, Kurth AE, Pearson CR, Pantalone DW, Merrill JO, Frick PA. Self-report measures of antiretroviral 
therapy adherence: A review with recommendations for HIV research and clinical management. AIDS Behav. 
2006;10(3):227-245. 10.1007/s10461-006-9078-6 
 
24.  U.S. Department of Health & Human Services. System Usability Scale (SUS). 2020; 
https://www.usability.gov/how-to-and-tools/methods/system-usability-scale.html. Accessed March 2, 2020. 
 
25.  Rosner B. Fundamentals of Biostatistics. Nelson Education; 2015. 
 
26. Julious, Steven A. "Sample size of 12 per group rule of thumb for a pilot study." Pharmaceutical Statistics: The 
Journal of Applied Statistics in the Pharmaceutical Industry 4.4 (2005): 287-291. 
 
27. Whitehead AL, Julious SA, Cooper CL, Campbell MJ. Estimating the sample size for a pilot randomised trial to 
minimise the overall trial sample size for the external pilot and main trial for a continuous outcome variable. Stat 
Methods Med Res. 2016;25(3):1057-1073. doi:10.1177/0962280215588241  
 

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12 APPENDIX A: HIDO PRODUCT BROCHURE 
<attach product brochure here> 
 
 

 
Consent Form V 2.3, 7/20/2021 
 
Page 1 of 4 
 
EXPERIMENTAL SUBJECT’S BILL OF RIGHTS 
The rights below are set out by the California legislature as the rights of every 
person asked to be in a research study. 
As an Experimental subject, you have the following rights: 
1. 
To be told what the study is trying to find out. 
2. 
To be told what will happen to you and whether any of the procedures, 
drugs, or devices is different from what would be used in standard practice. 
3. 
To be told about the frequent and/or important risks, side effects, or 
discomforts of the things that will happen for research purposes. 
4. 
To be told if you can expect any benefit from participating and, if so, what 
the benefit might be. 
5. 
To be told the other choices you have and how they compare to being in 
the study. 
6. 
To be allowed to ask any questions concerning the study, both before 
agreeing to be involved and any time during the course of the study. 
7. 
To be told what sort of medical treatment is available if complications arise.   
8. 
To refuse to participate at all or to change your mind about participation 
after the study is started. The decision will not affect your right to receive 
the care you would receive if you were not in the study. 
9. 
To receive a copy of the signed and dated consent form. 
10. 
To be free of pressure when considering whether you want to agree to be 
in the study. 
 
If you have other questions, ask the researcher or the research assistant. In addition, 
you may contact Ethical & Independent Review Services (E&I) Institutional Review 
Board, which is concerned with protection of volunteers in this research project. You 
may reach the E&I office by calling (800) 472-3241 from 9:00 AM to 4:30 PM (Pacific 
Time) Monday to Friday or by writing them at subject@eandireview.com. 
 
I have been given a copy of this form to keep and to refer to as needed.  
 
 
Signature _______________________________ 
Date ___________________ 
 
 

 
Consent Form V 2.3, 7/20/2021 
 
Page 2 of 4 
 
CONSENT FORM 
for a Research Study titled:  
“Automated Medication Platform with Video Observation and Facial Recognition to Improve Adherence to 
Antiretroviral Therapy in Patients with HIV/AIDS” 
 
You are being asked to participate in a research study:  This study looks at whether a new “smart” medication 
dispenser will help HIV/AIDS patients have fewer late or missed doses of their antiretroviral therapy (ART) 
medications. You will use the smart medication dispenser for 90 days, and then complete a 30-minute interview 
about your experience with the smart medication dispenser.  
 
What will be involved if you participate? Before you start your participation in this study, you will provide some 
information about your background and recent medical history to determine if you are eligible to enroll in this 
study. If you are enrolled, a Wi-Fi enabled automated medication dispenser will be delivered to your home 
address. This device dispenses up to seven different medications at the time that you are scheduled to take them. 
The device also confirms your doses using facial recognition, video records you taking your medication, sends 
reminders and alerts to your smartphone, and sends information about your dosage to the researcher; if you do 
not want to be video recorded, you cannot take part in this study. The researcher will visit your home to deliver 
the device, help you set it up, and link it to your smartphone. This visit is expected to last about 45 minutes.   
 
After you use the device for 90 days, you will complete an interview that asks about your experience with the 
device. This interview may take place either remotely (by phone or through a videoconference platform such as 
Zoom), or in your home when the medication dispenser is picked up. The interview will take about 30 minutes. 
 
At the end of the study, the medication dispenser will be picked up from your house by the researcher.  
 
Are there any risks, discomforts, or costs?  There is a risk that your private information may be seen by someone 
other than the researcher. To protect you against this risk, the researchers will remove your name and contact 
information from the other information that you provide and store it separately. All of your information will be 
stored either in a locked file cabinet that only the researchers can access, on a computer that is encrypted and 
protected by a password known only to the researchers, or in secure cloud-based storage. Information that is 
transmitted over the internet is encrypted (scrambled) so that it cannot be viewed by others.  
 
There is a risk that the device may malfunction, which may include not dispensing the correct dose at the correct 
time or not reminding you when to take your dose. This is an unavoidable risk because the purpose of this study is 
to evaluate the device. Since the device can malfunction, it is your responsibility to take your prescribed 
medications as directed by your doctor. If your device fails to automatically dispense your medications, you will be 
able to open the device to access your medications manually.  This medication dispenser has a childproof lid, but 
as with any other medication container, you should keep this device out of the reach of children and pets.  
 
If you are injured by participating in this study please seek medical care. Report any research-related injury or if 
you think you may have been harmed by participating in this study to the study Principal Investigator Charles 
Gellman at charles@hidohealth.com or <add phone number>.  
 
Are there any benefits to yourself or others? By using the device, you may have fewer late or missed ART doses, 
which may decrease your viral load. In the future, other people may benefit from the availability of a “smart” 
medication dispenser.  
 
Are there any costs or payment if you decide to participate? At the end of the study, you will receive a $100 VISA 
gift card to compensate you for your participation when the researcher picks up the medication dispenser from 
your home. If you are unable to complete the study, you will receive partial compensation of $5 per week, which 
you will receive as a Visa gift card when the researcher picks up the medication dispenser from your home. 

 
Consent Form V 2.3, 7/20/2021 
 
Page 3 of 4 
 
Because the medication dispenser transmits data using Wifi, internet access, mobile text and minutes, and data 
usage costs may apply. 
 
You will not be compensated for any products, services, or intellectual property developed as a result of 
this study. 
 
Your participation is voluntary. This study does not involve any medical treatment. You may refuse to participate 
without any penalty or loss of benefits to which you are otherwise entitled. If you agree to participate, you can 
change your mind about participating, and can leave the study at any time without any penalty or loss of benefits 
to which you are otherwise entitled.  
 
Your confidentiality and privacy will be protected. Your identity will be kept as confidential as possible, meaning 
that it will not be shared with anyone other than this study’s research team. To further protect your 
confidentiality, the information you provide – which includes your medication logs and video recordings recorded 
by the medication dispenser, your interview responses, and any other information you provide to us – will be 
stored on an encrypted and password-protected computer or cloud-based storage that is only accessible by the 
research team.  The data collected in this research study may also be used for future product development and/or 
applications to the FDA or other regulatory agencies. The study data may be kept indefinitely.  
Except for video recordings, your information will be de-identified, meaning that any information that could be 
used to identify you (such as your name or address) will be removed from the rest of your information and 
replaced with an identification number.  Your de-identified data may be used in future research without asking for 
your consent.  
The device will take video recordings of your face. These recordings are used only to test a security feature of the 
device that confirms the medication dispensed by the device is taken by you and not another person. These video 
recordings will not be de-identified, will not be used for future research, and will not be shared with other 
researchers.  
There are some people that will have access to the research data such as the study sponsor HiDO Technologies, 
the Institutional Review Board (IRB) that reviewed this study, the Food and Drug Administration (FDA), and other 
regulatory agencies for monitoring and auditing purposes.  
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law. This 
Web site will not include information that can identify you. At most, the Web site will include a summary of the 
results. You can search this Web site at any time. 
Procedures for Termination of Study Participation. You can be removed from the study at any time and for any 
reason without your consent. Some of the reasons you can be removed are listed below. 
• 
You do not follow the instructions, rules, and restrictions given by the study staff. 
• 
You do not continue to meet the requirements for the study. 
• 
The study staff decides it is in your best interest. 
• 
The Sponsor stops the study or asks that you be removed from the study. 
 
If you have questions about this study, to offer input or if you are injured or harmed by participating in this 
study, please contact Charles Gellman at charles@hidohealth.com or <800-phone number TBD>.  
 
An Institutional Review Board (IRB) is an independent committee established to help protect the rights of research 
subjects. If you have any questions about your rights as a research subject, and/or concerns or complaints 
regarding this research study, contact Ethical & Independent Review Services IRB, at 1-800-472-3241 or by email at 
subject@eandireview.com. Reference E&I study number 21110.  
 

 
Consent Form V 2.3, 7/20/2021 
 
Page 4 of 4 
 
HAVING READ THE INFORMATION PROVIDED, YOU MUST DECIDE WHETHER OR NOT YOU WISH TO PARTICIPATE 
IN THIS RESEARCH STUDY. YOUR SIGNATURE INDICATES YOUR WILLINGNESS TO PARTICIPATE. 
 
I have read this consent form. I have been given enough time to consider participation, ask questions, and my 
questions have been answered. I am giving voluntary and informed consent to participate in this study. I agree to 
be video recorded. I will be given a signed copy of this consent form and the Experimental Subject’s Bill of Rights. 
 
 
 
_______________________________________________                                                        _____________ 
Signature of participant   
 
 
 
 
 
 
Date 
 
 
_______________________________________________                                           
Printed name of participant  
 
 
I have reviewed this study consent form with this person and answered all questions. In my opinion this person is 
giving voluntary and informed consent.  
 
 
_______________________________________________                                                        _____________ 
Signature of investigator obtaining consent  
 
 
 
 
Date 
 
 
_______________________________________________                                           
Printed name investigator obtaining consent