Compliance is an important determinant of clinical trials and can be improved through effective participant engagement. This paper describes how Synegys' AI-powered platform uses AI to improve medication adherence by sending reminders only when necessary, using natural language processing, automatically generating responses, and personalizing messages based on a patient's preferences and past interactions. The solution can be delivered using text message services and/or mobile web app channels. Use mComply to: - Promote adherence through effective appointment, medication and diary entry reminders. Motivate and remind participants to adhere to study protocols. - Monitor how well participants are progressing through the automated submission and processing of participant diary information. - Alert Site Coordinators or a wider support network regarding protocol violations or health concerns. Synegys' mComply offers a significant impact on patient outcomes and is a powerful tool for improving medication adherence and overall study compliance to Study Sponsors, Contract Research Organizations, Research Sites, and Patient Recruitment Agencies

1. POWERED BY
mCOMPLY
Running Successful Clinical Trials - Compliance Delivered.

2. mComply - Adherence Delivered.
mComply - Adherence Delivered.
2 3
mComply
Compliance is an important determinant of clini-
cal trials and can be improved through effective
participant engagement using mComply.
Achieve high adherence rates by sending par-
ticipants timely messages including appoint-
ment, medication and diary entry reminders, and
motivation messages. Automate the submission
of diary entries through the mobile phone.
Why mComply?
The ubiquity of mobile devices, combined with
their personal nature and text messaging func-
tionality, make mobile phones an effective plat-
form for delivering health interventions.
mComply is a validated, CFR-compliant mobile
messaging system supported by over 1,200 mo-
bile network operators in 200 countries.
mComply is configured and customized to fit
ANY trial need.
Promote adherence through effective
appointment, medication and diary entry
reminders. Motivate and remind partici-
pants to adhere to study protocols.
Monitor how well participants are pro-
gressing through the automated submis-
sion and processing of participant diary
information.
Alert Site Coordinators or a wider sup-
port network regarding protocol viola-
tions or health concerns.
The case for mComply
Situation
Implication
Solution
Prevalence of Nonadherence
Significant Financial Impact
mComply
Mean adherence rates in clinical trials for ap-
pointment keeping, short-term medication-tak-
ing, and long-term medication-taking have been
estimated to be 39%, 62%, and 63% respectively
for prevention trials and 78%, 78%, and 59% for
treatment trials.1
Linear increases in nonadherence have an ex-
ponential effect on the volume of participants
you need to enrol in order to achieve the same
statistical outcome for a trial. Enrolling additional
participants will increase drug development costs
and the associated opportunity cost for time and
capital. Assuming a nonadherence rate of 30%
in a typical Phase 2 study, a 1% improvement
would deliver nearly $400,000 in cost sav-
ings.2,3,4,5,6,7,8
mComply helps your study achieve the level of
participant compliance and retention your trial
needs to stay on track for success. The solu-
tion focuses on text messaging interventions, a
ubiquitous approach to realize adherence rates in
excess of 97%.
mComply is also available in mobile app and web
app form with extended capabilities; however, at
the cost of service ubiquity.

3. mComply - Adherence Delivered.
mComply - Adherence Delivered.
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Nonadherence occurs as participants deviate from treatment protocol e.g. forgetting to take doses,
taking medications at incorrect times, taking an incorrect dose or missing study visits. Nonadherence
by participants can lead to underestimated harms, misinterpretation of results, type II error and low
statistical power - all leading to increased costs.
A study found that 40% of
participants become non-
adherent to investigational
medical product (IMP) after
150 days. Furthermore, IMP
nonadherence “not only
causes temporary bouts of
toxicity (double dosing) and
lack of efficacy (skipping
doses), but also introduces
data variability into the
equation.”13
A meta-analysis of trials of interventions to improve medication adherence showed increases in adher-
ence in the range of 4% - 11%.9
This was achieved through two types of interventions: behavioural and
educational.
Compliance
Medication adherence may be defined as “the extent to which a person’s behaviour (in terms of taking
medications, following diets, or executing lifestyle changes) coincides with medical or health advice.”12
Not to be confused with “compliance”, “adherence” acknowledges participants’ participation in the
treatment process. Compliance on the other hand, implies subservience on the part of the participant
with a focus on the PROVIDER’S goals.
Nonadherence in Research Settings
In clinical trials, medication
adherence averages 75% and
appointment-keeping ranges
from 39-78%.1,14
Behavioural Interventions included the
use of any tool or action that would
change a participant’s skill level or nor-
mal routine, including reminders, and
dosage-schedule changes.
Educational interventions were those
that taught the participant about the
medication and how to take it through
oral, written, or audiovisual communica-
tion.
Pathways to Adherence
Financial Impact
Drug development has two main cost components: the actual costs for drug development and the
opportunity cost for time and capital. Medication nonadherence forces study teams to enrol more
participants, resulting in higher operating costs and missed trial deadlines.
More Participants
Higher Operating and Opportunity Costs
Addressing Nonadherence - The Case for mComply
Using Synegys’ mComply, study teams can manage behaviours that
impact costs. Consider a scenario of running a Phase 2 study with
203 participants at 30% noncompliance. Each participant is to fol-
low a medication regimen every 3 days for 3.5 months with study
appointments every month. Reducing IMP nonadherence to 3% to
maintain equivalent statistical power results in nearly $12 million in
cost of capital savings. When only considering variable operating ex-
penditures, $1.5 million can be saved through lower enrolment and
retention costs, reduced compliant episodes, improved data collec-
tion and reduced “no-shows”.3,4,5,6,7,8
Linear increases in nonadherence has an expo-
nential impact on the number of participants
needed to yield the same statistical outcome.4
For example, a 20%-30% decrease in investiga-
tional medicinal product (IMP) adherence may
result in increasing the participant sample size
by 50% in order to maintain sufficient statistical
power.
Assuming a constant 30% IMP nonadherence rate for a typical Phase 2 trial, sponsors need to enrol
additional participants in order to maintain equivalent statistical power. The cost for for participant
enrollment and retention for a typical study is estimated at $13.3 million. By reducing nonadherence
by 1% (to 29%), sponsors need to enrol less participants to maintain equivalent statistical power,
resulting in nearly $400,000 in cost savings, and naturally, minimizing timeline slippage.2,3,4,5,6,7,8
Note: We’ve expanded on Alsumidaie’s15
original analysis by considering an IMP nonadherence rate of 30%, including
direct variable cost categories (participant retention, registered nurse/CRA, physician, clinical procedure and central
lab costs) and inflating the sample size by the square of people expected to not comply rather than using an imputed
linear sample size multiple.
Adherence Rate
with mComply
97.5%

4. mComply - Adherence Delivered.
mComply - Adherence Delivered.
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mComply
mComply helps participants follow a medication regimen and subsequently improves study compli-
ance. It supports any front-facing, communications interface including any one or combination of text
messaging (i.e. SMS), mobile app, email, interactive voice response, web app or live agents. Given that
text messaging offers instantaneous relay of information and boundless reach, this paper focuses on
the text messaging engagement channel.
Participant Engagement Channel
Application
Backend Interface
Participants submit or obtain information via different channels. Notifications
are best delivered via text messaging given its ubiquitous nature. mComply is
fully compliant with local text messaging regulations and messages are local-
ized with diacritic support.
The mComply platform is configured and modules are customized according to
functional requirements supporting ANY study protocol. Alongside the Appli-
cation is a secure database containing study data.
A secure web portal acts as the backend interface. Study Coordinators can se-
curely access all the data sent/received between the participants and the Ap-
plication. The web portal is used to enrol, withdraw and manage participants;
access pre-defined reports; export data; and manage study performance. Dif-
ferent access privileges can be assigned to different user groups.
How does mComply work?
Study Coordinators can easily enrol participants
via a secure web portal or participants can enrol
directly by sending a registration text. Conversely,
participants can opt out via mobile phone at
anytime or have a Study Coordinator do it on their
behalf.
Enrol
Available engagement tools include sending 1-way
or 2-way study appointment and medication re-
minders, collecting diary entries or feedback from
participants, helping participants visualize study
progress, rewarding participants for adhering to
study outcomes through gamification, and provid-
ing motivation messages among others.
Engage
Reminders and appointment schedules can be
managed online. Escalations are logged as they
arise and are flagged until they are addressed. An
audit trail is maintained as Study Team members
add, edit and delete data.
Manage
The Study Team can review, analyze and extract
all participant data via the web portal. Insights into
study performance can be provided across various
levels including participant, site and geography.
Analyze

5. AUSTRALIA
KENYA
mComply - Adherence Delivered. 9
Medication adherence is
critical to a clinical trial’s
success. Introducing
a simple and effective
communication tool like
text messaging can im-
prove study compliance.
“ Text Messaging - A Ubiquitous Solution
A feature of mobile health interventions is the potential for scal-
ability owing to affordability and ability to deliver personalized
services. Mobile phone interventions that focus on text messag-
ing have particular value, because they do not require a smart-
phone and are agnostic to the mobile operating system. Further-
more, most people across all income groups own a mobile phone.
With global mobile penetration reaching 103% in 201910
, a text
message–based intervention has the potential to have substan-
tial population effects.
UNITED STATES
Smartphone Penetration
By Age Group (%)11
Smartphones as Percentage of all Mobile10
5.2+ Billion
Unique Mobile
Subscribers10
65%
Smartphone
Connections10
HUNGARY

6. 1 2
3c 3d
mComply - Adherence Delivered.
mComply - Adherence Delivered.
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Operationalizing mComply in Clincal Trials
Participants need to sign a consent form before using mComply. During this process, par-
ticipants are informed about system benefits, participant’s role, opt-in / opt-out capabilities,
costs and privacy. Moreover, participants are provided with support materials to use the
system. Once consent is obtained, participants are registered via the mComply web portal or
via the participant’s mobile in real-time.
Study Team Obtains Consent and Registers Participants
3a
The participant submits a time-stamped diary entry with relevant details associated with
dose information. This can be through a single submission or through multiple interactive
messages, depending on what information is required.
In the example below, a participant informs mComply that three 150mg capsules were
taken on February 15 at 8:40pm and his last meal was at 5:30pm.
Participant Submits Diary Entry
Following a review of your study protocol and discussions with the study team, we configure and
customize mComply to satisfy your study’s needs. Unlike general reminder and adherence solu-
tions in the market, mComply can accommodate complex dosing regimens and support overall
study workflow.
If a diary entry was not received after a pre-
determined number of sent reminders or
timeframe, an escalation can be raised with
the Site and Study Coordinators via text mes-
sage or email. The Study Team can visit the
web portal to review the escalation details
and intervene according to agreed protocol.
mComply Sends Escalations based on Pre-defined Logic
Based on user access levels, Study Team
members can edit / delete doses and partici-
pants’ profiles (e.g. dose amount, dose times,
drug type, etc.). An audit trail of all changes
made by whom and at what time is main-
tained.
Study Team Manages Participants and Diary Entries
If a submission is not received when expected
by mComply, reminders are sent until the par-
ticipant submits a diary entry. Reminders are
specific to each participant and can be sched-
uled for ANY time interval and can include
exceptions.
mComply Sends Reminders based on Pre-defined Logic
3b
3e

7. mComply - Adherence Delivered.
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mComply Applications
97% mobile phone users read text
messages within 15 minutes. SMS /
text-based programs are the most simple,
straightforward, and effective for getting
information to people and allowing them
to interact quickly.
mComply offers a tailored approach based
on optimal timing, adaptation and content.
With customizable logic applications and
conditional triggers, mComply fully sup-
ports organizations to collect data and to
improve adherence.
Send messages with further assistance, informa-
tion, and feedback to users (or AI-driven chat
services) depending on answers. If a user indi-
cates that they’re symptomatic, for instance,
auto-responses can provide guidance on testing
centers, hospitals and general care.
Have participants come fully prepared on their
next site visit. Send messages informing par-
ticipants how to prepare for their next visit (e.g.
treatment, fasting, etc.) or what to bring with
them (e.g. remaining medication, diary, etc.).
Wellness Checks
Visit Preparation Reminders
Remind participants to take or apply medica-
tion and/or provide instructions on how to take
or apply treatment medication. Deliver tailored
content based on the type and cause of nonad-
herence and participant needs.
Schedule visits on our web portal and have re-
minders sent on when to attend, how to confirm
and/or how to reschedule. Send a text three days
prior to the appointment as a general reminder,
or 24 hours prior as a final reminder.
Make your participants feel supported and ap-
preciated. Send timely messages with the sole
purpose of educating and motivating the par-
ticipant. This helps them stay on track with their
personalized healthcare plans and recommenda-
tions.
Collect data using text message surveys / ques-
tionnaires. Qualify and recruit participants for
studies using interactive text chat. Various types
of response formatting are available, including
multiple choice and user-defined phrases.
Medication Reminders Appointment Reminders
Motivation & Info Messages Surveys & Questionnaires

8. mComply - Adherence Delivered.
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14 15
Project Description
mComply is configured and applica-
tion logic customized to support
study protocol requirements. Derived
from over 15 years of experience,
our patient engagement tools and
processes help health organizations
engage patients, improve outcomes
and lower costs.
DEFINE
MODEL
VERIFY
DEPLOY
“
DEFINE
MODEL
VERIFY
DEPLOY
√
√ Project Plan
√
√ Requirements
√
√ Design
√
√ IRB Documents
√
√ Solution Build
√
√ Design Review
√
√ Data Setup
√
√ System Testing
√
√ User Acceptance
Testing
√
√ Training
√
√ Go-Live
√
√ Support & Mainte-
nance
Every study is different. Implementing an “off-
the-shelf” technology solution will have mini-
mal impact on adherence, if at all. Leverage our
experience and technical know-how to develop
a solution that will deliver against your study
protocol.
mComply is supported by over 1,200 mobile
operators in 200 countries. 1-way and 2-way
messaging is supported along with diacritics.
mComply is validated against the specifications
set forth by your study protocol. The solution is
21 CFR part 11 compliant, HIPAA-ready, and is
compliant with GDPR, local text messaging regu-
lations and local privacy laws.
To successfully deliver a participant compli-
ance system, you also need to consider training
guides, IRB documentation for mComply, par-
ticipant consent forms, translations and the like.
We can help you realize a compliance system on
time and on budget.
Customization Service Coverage
Compliance Comprehensive Delivery
Why Synegys?
Confirm overall study ob-
jectives and develop a set
of functional requirements.
Formulate SMS content,
configure platform and
customize application logic.
Develop IRB documenta-
tion for submission.
Program, setup, test and
prepare mComply for vali-
dation.
Train the study team and
prepare supporting docu-
mentation. Host and main-
tain mComply until trial
completion.

9. mComply - Adherence Delivered.
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16 17
References
1. Robiner, William N. Enhancing adherence in clinical trials. Contemporary Clinical Trials.
2005;26:59–77.
2. Synegys Analysis. Source of information used in this analysis for aggregated clinical trials and
patient average data: www.clinicaltrials.gov via www.karmadata.com. Cost elements sourced by
Medidata Solutions.
3. Eastern Research Group, Inc. Examination of Clinical Trial Costs and Barriers for Drug Develop-
ment. July 25, 2014.
4. Wittes, Janet. Sample Size Calculations for Randomized Controlled Trials. Epidemiologic Reviews.
Vol 24, No. 1, 2002.
5. Damodaran, Weighted Average Cost of Capital for drugs (biotechnology). http:/
/people.stern.nyu.
edu/adamodar/New_Home_Page/data.html. Updated Jan 5, 2018.
6. CMR International. Pharmaceutical R&D Factbook 2011. Thomson Reuters, May 2011.
7. DiMasi, Briefing - Cost of Developing a New Drug. Nov 18, 2014. https:/
/csdd.tufts.edu/cs-
ddnews/2018/3/9/march-2016-tufts-csdd-rd-cost-study.
8. Biotechnology Innovation Organization. Clinical Development Success Rates 2006-2016. 2016.
9. Andrew M. Peterson, Liza Takiya, Rebecca Finley. Meta-Analysis of Trials of Interventions to Im-
prove Medication Adherence. Am J Health Syst Pharm. 2003;60(7).
10. GSMA 2021.
11. Pew Research Center 2020.
12. Meichenbaum D, Turk DC. Facilitating Treatment Adherence: A Practitioner’s Guidebook. New
York: Plenum; 1987.
13. Blaschke TF, Osterberg L, Vrijens B, Urquhart J. Adherence to Medications: Insights Arising from
Studies on the Unreliable Link Between Prescribed and Actual Drug Dosing Histories. Annu Rev
Pharmacol Toxicol. 2012.
14. Dimatteo et al. Variations in Patients’ Adherence to Medical Recommendations. Med Care.
2004;42:200-209.
15. Alsumidaie Moe, Non-Adherence: A Direct Influence on Clinical Trial Duration and Cost, Applied
Clinical Trials, Apr 2017.
William Eng
Managing Director
 +420 736 767 732
 william@synegys.com
Contacts
 Americas & Asia-Pacific: +1 403 708 3910
 Europe & Africa: +420 603 429 748
 info@synegys.com
Á www.synegys.com
Á www.mobilehealthworks.com
This publication has been written in general terms and we recommend that you obtain pro-
fessional advice before acting or refraining from action on any of the contents of this publica-
tion. Synegys s.r.o. accepts no liability for any loss occasioned to any person acting or refrain-
ing from action as a result of any material in this publication.
© 2018, 2021 Synegys s.r.o. All rights reserved.

10. Contact Information
Synegys s.r.o.
Washingtonova 1567/25
110 00 Prague 1
Czech Republic
info@synegys.com
www.synegys.com