Evaluation Of A Mobile Messaging Service (Text And / Or Graphic) In Improving Adherence With Ensured Supply Of Anti-Seizure Medications In People With Epilepsy In Kilifi And Nairobi, Kenya
Phase: NA
Conditions: Epilepsy, Treatment Adherence
Sponsor: KEMRI-Wellcome Trust Collaborative Research Program

KEMRI- Wellcome Trust Research Programme (KWTRP) 
Protocol number:240 
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KWTRP 
CLINICAL TRIAL PROTOCOL 
 
Evaluation of a Mobile Messaging Service (Text and / or Graphic) in Improving 
Adherence with Ensured Supply of Anti-seizure Medications in People with Epilepsy in 
Kilifi and Nairobi, Kenya 
1.0 GENERAL INFORMATION 
Protocol Number: 
CSC 240 
Trial Registration Number: 
TBD 
Investigational Product(s): 
Short messaging service (text or graphic) 
Funder [name and address: 
National Institute for Health Research 
Tel: 
020 8843 8000 
Email: 
ccf@nihr.ac.uk 
Sponsor [name and address]: 
University of Oxford 
Oxford OX1 2JD, United Kingdom 
Tel: 
01865 (2)82585 
Email: 
oxtrec@admin.ox.ac.uk 
Sponsor’s authorized representative 
[name and address]: 
Professor Charles Newton 
University of Oxford 
Tel: 
+44 (0)1865 618314 
Email: 
charles.newton@psych.ox.ac.uk 
Statistician [name and address]: 
Mr. Collins Kipkoech 
KEMRI-Wellcome Trust Research 
Programme 
Tel: 
+254 729295915 
Email: 
CKipkoech@kemri-wellcome.org 
 

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1.1 Confidentiality Statement 
The information contained herein is privileged or confidential and may not be disclosed unless 
such disclosure is required by applicable laws or regulations. In any event, persons to whom 
the information is disclosed must be informed that the information is privileged or confidential 
and may not be further disclosed by them. These restrictions on disclosure will apply equally 
to all future information supplied to you, which is indicated as privileged or confidential. This 
confidentiality statement also applies to data generated during the study. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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1.2 SPONSOR’S APPROVAL OF THE PROTOCOL  
 
Evaluation of a Mobile Messaging Service (Text and / or Graphic) in Improving 
Adherence with Ensured Supply of Anti-seizure Medications in People with Epilepsy in 
Kilifi and Nairobi, Kenya 
 
Protocol Number: 240 
 
 
The following personnel has reviewed and approved this protocol [SMS trial], version 
number 1.4, dated 22nd  October 2021. 
 
 
 
 
Signature:  
22/October/2021 
[Prof Charles Newton, Senior Clinical 
Researcher at KWTRP and Oxford 
University] 
Date 
 
 
 
 
 
 
 
 

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1.3 INVESTIGATOR’S APPROVAL OF THE PROTOCOL 
 
Evaluation of a Mobile Messaging Service (Text and / or Graphic) in Improving 
Adherence with Ensured Supply of Anti-seizure Medications in People with Epilepsy in 
Kilifi and Nairobi, Kenya 
Protocol Number: CSC 240 
 
The undersigned acknowledge possession of and have read the SMS trials protocol, version 
1.4 dated 22/10/2021. Having fully considered all the information available, the undersigned 
consider that it is ethically justifiable to give short messaging service (text or graphic) 
reminders to selected participants according to the agreed protocol. 
I understand that all information concerning the interventions supplied to me by [KEMRI-
Wellcome Trust Research Programme (KWTRP)] - and/or its agents in connection with this 
study and not previously published is confidential information. This includes the 
Investigators’ Brochure, Clinical Trial Protocol, Case Report Forms, and any other preclinical 
and clinical data provided by the KEMRI-Wellcome Trust Research Programme or University 
of Oxford. 
By my signature below, I hereby attest that I have read, understood, and agreed to abide by all 
the conditions, instructions and restrictions contained in SMS trial Protocol version 1.4 dated 
22/10/2021 and in accordance with the most recent Declaration of Helsinki and Good Clinical 
Practice and all applicable regulatory requirements. I acknowledge that the Sponsor of the 
study, University of Oxford, has the right to discontinue the study at any time. 
 
 
 
 
 
 
 
 
 
 
22 October 2021 
Principal Investigator Signature 
Date  
[Dr Symon Kariuki, postdoctoral scientist] 
 
 
 
22 October 2021 
Co-Investigator Signature 
Date 
[Dr Mercy Atieno, Investigator] 
 

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Contents 
 
1.0 GENERAL INFORMATION ........................................................................................................................... 1 
1.1 Confidentiality Statement ................................................................................................................................. 2 
1.2 SPONSOR’S APPROVAL OF THE PROTOCOL .......................................................................................... 3 
1.3 INVESTIGATOR’S APPROVAL OF THE PROTOCOL ............................................................................... 4 
1.4 PROTOCOL SYNOPSIS .................................................................................................................................. 7 
1.5 GLOSSARY OF TERMS AND ABBREVIATIONS ..................................................................................... 10 
2.0 LAY SUMMARY ........................................................................................................................................... 10 
3.0 LIST OF INVESTIGATORS .......................................................................................................................... 15 
4.0 ABSTRACT .................................................................................................................................................... 16 
5.0 INTRODUCTION .......................................................................................................................................... 18 
5.1 Background Information ................................................................................................................................. 18 
5.2 Name and description of the investigational product(s), ................................................................................. 22 
5.3 Justification ..................................................................................................................................................... 23 
6. TRIAL OBJECTIVES AND PURPOSE .......................................................................................................... 24 
6.1 Null hypothesis ............................................................................................................................................... 24 
6.2 Primary objective ............................................................................................................................................ 25 
6.3 Secondary objective(s) .................................................................................................................................... 25 
7.0 TRIAL DESIGN ............................................................................................................................................. 25 
7.1 Overall Study Design ...................................................................................................................................... 25 
7.2 Description of the study areas and population ................................................................................................ 26 
8.0 DESCRIPTION OF THE INTERVENTION ................................................................................................. 27 
8.1 Intervention ..................................................................................................................................................... 27 
8.2 Identity of the SMS ......................................................................................................................................... 27 
8.3 Frequency and timing of sending messages .................................................................................................... 27 
8.4 SMS dispensing procedures ............................................................................................................................ 27 
8.5 Intervention Compliance ................................................................................................................................. 28 
9.0 STUDY PLAN DESCRIPTION ..................................................................................................................... 28 
9.1 Pre-study focus group discussions .................................................................................................................. 28 
9.2 Roll out of the SMS trial ................................................................................................................................. 29 
9.2.1 Identification of Participants ................................................................................................................ 29 
9.2.2 Eligibility criteria ................................................................................................................................. 29 
9.2.3 Consenting/Assenting and screening for eligibility ............................................................................. 30 
9.2.4 Recruitment and enrolment  ................................................................................................................. 30 
9.2.5. Randomisation .................................................................................................................................... 30 
9.2.6. Procedures ........................................................................................................................................... 32 
9.3 
33 
Follow-up Visit(s) and End of Treatment Visit .................................................................................................... 33 
10.0 ASSESSMENT OF EFFICACY ................................................................................................................... 35 
10.1 Specification of the efficacy parameters. ...................................................................................................... 35 
10.1.1 Primary efficacy variable ................................................................................................................... 35 
10.1.2 
Secondary efficacy variable(s) .................................................................................................... 35 
11.0 EVALUATION OF COST EFFECTIVENESS OF THE INTERVENTION ............................................... 35 
12.0 STATISTICS ................................................................................................................................................ 36 
12.1 Determination of sample size ........................................................................................................................ 36 
12.2 Statistical and analytical plans ...................................................................................................................... 36 
12.2.1 Data management ............................................................................................................................... 36 
12.2.2 Planned statistical methods ................................................................................................................ 37 
13.0 STUDY MANAGEMENT............................................................................................................................ 38 
13.1 Protocol deviations and violation(s) .............................................................................................................. 38 
13.2 Discontinuation of the study ......................................................................................................................... 38 
13.3 Selection and Withdrawal of Study Participants ........................................................................................... 39 
13.3 Direct access to source data/documents ........................................................................................................ 39 
13.4 Quality control and quality assurance ........................................................................................................... 39 
13.5 Trial Registration and Monitoring ................................................................................................................ 39 
14.0 INTELLECTUAL PROPERTY .................................................................................................................... 39 

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15.0 TIME FRAME/DURATION OF THE TRIAL ............................................................................................. 40 
16.0 ETHICS ........................................................................................................................................................ 40 
16.1 Human Subjects ............................................................................................................................................ 41 
16.2 Informed Consent and/or Assent ................................................................................................................... 41 
16.3 Compensation ............................................................................................................................................... 41 
16.4 Patient Data Protection/Confidentiality................................................................................................. 41 
16.5 Data Sharing .................................................................................................................................................. 42 
16.6 Safety ............................................................................................................................................................ 42 
16.7 Stakeholder and community engagement...................................................................................................... 42 
17.0 ARCHIVING AND RECORD RETENTION .............................................................................................. 44 
18.0 FINANCING AND INSURANCE ............................................................................................................... 45 
18.1 Budget for each site ....................................................................................................................................... 45 
18.2 Justification of the Budget ............................................................................................................................ 45 
18.3 Insurance ....................................................................................................................................................... 45 
19.0 REPORTING, DISSEMINATION AND NOTIFICATION OF RESULTS ................................................ 46 
20.0 REFERENCES ............................................................................................................................................. 46 
21.0 APPENDICES .............................................................................................................................................. 47 
21.1 Roles of Investigators .................................................................................................................................... 47 
21.2 Informed Consent forms ................................................................................ Error! Bookmark not defined. 
21.3 Study questionnaires and scales ..................................................................... Error! Bookmark not defined. 
 
 
 
 
 
 
 

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1.4 PROTOCOL SYNOPSIS 
 
Full Title 
Evaluation of a Mobile Messaging Service (Text and / or Graphic) in Improving 
Adherence with Ensured Supply of Anti-seizure Medications in People with 
Epilepsy in Kilifi and Nairobi, Kenya 
Short Title 
SMS Trial 
Trial Phase Not Applicable 
Objectives 
Primary Objective: 
To examine the impact of sending text or graphic SMS reminders on anti-seizure 
medication (ASM) adherence people with epilepsy in Kilifi and Nairobi, Kenya 
Secondary Objectives: 
To describe the perceptions and perspectives of people with epilepsy (PWE) and 
their caregivers on the use of text and graphic SMS reminders to improve 
adherence to anti-seizure medications (ASMs) among PWE in Kilifi and Nairobi, 
Kenya 
To compare the effectiveness of text versus graphic messaging service in 
improving adherence in people with epilepsy in Kilifi and Nairobi, Kenya 
To identify the factors associated with improvement in adherence, improved 
quality of life (QoL) and reduction in stigma-associated suffering among PWE 
and family members. 
To document the common adverse drug reactions (ADRs) related to commonly 
prescribed ASMs and the plasma levels associated with these ADRs among PWE 
in Kilifi and Nairobi, Kenya 
To evaluate the cost-effectiveness of the interventions in each of the sites 
Trial Design Partially-blinded randomized controlled trial 
Sample Size 
1200 participants (900 participants in the intervention arm (300 receiving text 
SMS, 300 receiving graphic SMS, 300 receiving both text and graphic) and 300 in 
the control arm/receiving non-reminder messages) in each site 
Study 
Population 
We will include participants who fulfil the following criteria: 

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i. 
children or adults with a diagnosis of epilepsy ascertained by a 
clinician at the epilepsy clinic, taking anti-seizure medications at the 
time of the study, 
ii. 
persons living within an area defined as the Kilifi Health Demographic 
Surveillance System (KHDSS) or the Nairobi Urban Health 
Demographic Surveillance System (NUHDSS) at the time of the study, 
or attending the epilepsy clinics in Kilifi or the Kenya Association for 
the Welfare of persons with Epilepsy (KAWE) clinics in Nairobi 
iii. 
persons able to give written informed consent or assent (for children 
13-17 years old)  
iv. 
persons with access to a basic mobile phone in the household either 
through direct ownership, a caregiver or a member of the household 
nominated by the PWE 
Intervention
(s) 
This will be a behavioural intervention with no investigational medicinal product. 
The intervention will be a mobile messaging service that sends short messaging 
service (SMS) as texts or graphics to people with epilepsy to remind them to take 
their medication and to refill their prescription and educational messages to share 
important messages tackling stigma and tips to improve quality of life 
We will also engage peripheral health facilities where PWE participating in the 
study go for ASM refills, in collaboration with the respective county departments 
of health, to maintain adequate supply of anti-seizure medications through:  
i. 
ongoing capacity building studies in Kilifi such as the mental health 
Gap Action Programme-Intervention Guide (mhGAP-IG) training 
which is empowering primary healthcare providers at peripheral health 
facilities to identify and manage epilepsy and other mental health 
disorders 
ii. 
supporting healthcare providers at peripheral facilities through in-
person visits, if the COVID-19 situation, permits or by telephone or 
standard message reminders to restock their ASM supply 
The participants in the no-intervention group will receive “placebo” health   
messages not related to epilepsy such as use of bednets. 

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The SMS reminders will be sent at a frequency that will be agreed upon during 
pre-study engagements with potential participants, whether daily, weekly, or 
monthly. The participants will be able to respond to these texts to report on their 
health status and any adverse events.  
 
To evaluate whether SMS reminders improve adherence, we will use:  
i. 
Self-reporting adherence scales- the Morisky Medication Adherence 
Scale (MMAS-8) 
ii. 
Measurement of ASM plasma levels at 3, 6 and 12 months from 
baseline. 
Trial 
Duration 
Each individual participant’s participation will take 12 months. 
The trial itself will last up to three years to account for: 
i. 
different enrolment timepoints of participants 
ii. 
analyses, close out and dissemination of findings 
Safety 
Evaluation 
 
This trial doesn’t involve administration of medicinal products.  
No adverse events are expected in relation to administration of message 
reminders.  
However, we will document any ASM-related adverse events as part of routine 
pharmacovigilance in the care of PWE. 
Outcomes(s) 
Primary outcome: 
Adherence to anti-seizure medications as measured by self-reports and validated 
by optimal and detectable levels in blood. 
Secondary outcomes: 
i. 
Correct intake of drugs and refill rates- measured by checking record 
logs for participants attending the study clinics 
ii. 
Changes in seizure frequency as assessed by trained clinicians at the 
study clinics 
iii. 
Changes in stigma scores and quality of life scores assessed using 
standardized scales   
   
 

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1.5 GLOSSARY OF TERMS AND ABBREVIATIONS 
APHRC- Africa Population and Health Research Center 
ASMs- Anti-seizure medications 
DSMB- Data Safety and Monitoring Board 
KEMRI-CGMRC- Kenya Medical Research Institute- Center for Geographic Medical 
Research, Coast 
KHDSS- Kilifi Health Demographic Surveillance System 
KEBAS- Kilifi Beliefs and Attitudes Scale 
KAWE- Kenya Association for the Welfare of People with Epilepsy  
LMICs- Low- and middle-income countries 
LSM- Local safety monitor 
MMAS-8- Morisky Medication Adherence Scale-8 
MMS- Multimedia messaging service 
NUHDSS- Nairobi Urban Health and Demographic Surveillance System  
OxTREC- Oxford Tropical Research Ethics Committee 
PWE- People with epilepsy 
QoL- Quality of Life 
SERU- Scientific Ethics Review Unit 
SMS- Short messaging service 
USSD- Unstructured Supplementary Service Data  
WHOQOL-BREF- World Health Organization Quality of Life Scale 
 
 
2.0 LAY SUMMARY 
Formal Title: Evaluation of a Mobile Messaging Service (Text and / or Graphic) in 
Improving Adherence with Ensured Supply of Anti-seizure Medications for People with 
Epilepsy in Kilifi and Nairobi, Kenya 
Lay Title: Use of mobile messaging service reminders to improve how people with epilepsy 
take their medications and how they have access to supplies of medications in Kilifi and 
Nairobi, Kenya 
 

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What is the problem/background? 
Epilepsy is one of the most common conditions that affect the brain, and its impact is 
enormous, particularly in countries from sub-Saharan Africa (SSA). 
Many studies 
focus on the epilepsy treatment gap, which commonly defined as the number of people with 
epilepsy (PWE) who should be on treatment, often leaving out the people with epilepsy in the 
community who have never been formally diagnosed (diagnostic gap) and those who do not 
take their medication correctly (adherence gap). Good outcomes in people with epilepsy rely 
on an uninterrupted supply of medication and on them taking their medication correctly. In 
Kilifi County, more than 70% of people with epilepsy are either not on treatment (have never 
been diagnosed) or do not take their medication correctly due to a variety of reasons, an 
important one being forgetfulness. In addition, lack of a constant supply of medication and 
distance to health facilities also contributes to the number of people with epilepsy who 
receive inadequate care. In Nairobi County, the prevalence of epilepsy, especially in slum 
dwellings is largely unknown and subsequently data on the adherence gap is also unavailable 
Text and/or graphic messages sent to mobile phones of people with epilepsy, or their 
caregivers may be useful in reminding people with epilepsy to take their medications as 
required and reminding healthcare providers to restock antiseizure medications.  
 
What questions are we trying to answer? 
In this study, we plan to test the use of short message service (SMS) reminders sent to remind 
people with epilepsy to take their medication as prescribed and to engage the Kilifi and 
Nairobi County Departments of Health to ensure a continuous supply of medications used to 
manage epilepsy. A previous audit at the epilepsy clinic in Kilifi showed that about 90% of 
people with epilepsy, either through direct ownership or via a caregiver or a member of the 
household, have access to basic mobile phones that can receive unique text or graphic 
messages. After rolling out the SMS reminders, we will compare the different modes of 
messaging (graphic versus text) to find out which is more acceptable and successful in our 
local setting. 
 
Where is the study taking place, how many people does it involve and how are they 
selected? 

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This study will take place in Kilifi and Nairobi Counties, within two defined areas known as 
the Kilifi Health and Demographic Surveillance System (KHDSS) and the Nairobi Urban 
Health and Demographic Surveillance System (NUHDSS). In Nairobi, we will also conduct 
the study within clinics led by the Kenya Association for the Welfare of People with Epilepsy 
(KAWE). Before the roll out of the intervention, we will hold about 3 pre-study focus group 
discussion with about 10 PWE and one of their family members each about the preferred 
nature of SMS reminders and the timing and frequency. We plan to include 1,200 people with 
epilepsy (PWE) from each site. In Kilifi, PWE will be randomly selected from a large 
database of patients attending the Neuroscience epilepsy clinic, of whom majority were 
identified from previous large-scale community surveys within the KHDSS. In Nairobi, PWE 
will be randomly selected from those identified through a survey conducted by the African 
Population and Health Research Center (APHRC) within the NUHDSS and patients attending 
KAWE-led clinics. At each site, we will randomly divide the participants into four groups of 
300 people with epilepsy, to receive either text SMS, graphic SMS, both text and graphic or 
no intervention/non-reminder SMS (for comparison). Participants will be screened for 
eligibility by the attending epilepsy clinicians and referred to the field assistant for consenting 
and/or assenting and recruitment into the study.  
 
What does the study involve for those who are in it? 
We will send out reminders to some participants either as a text, a picture, or both a text and a 
picture to remind them to take their medication. In addition, we will also engage staff at 
peripheral health facilities where the PWE go for medication refills through ongoing capacity 
building of all healthcare providers in public health facilities in Kilifi County on management 
of epilepsy and direct engagement of the respective county Departments of Health to ensure 
sustained supply and availability of drugs for managing epilepsy. We will ask participants 
questions regarding how they take their medications, their quality of life and stigmatising 
experiences before and after they have received message reminders. These sessions will take 
about 3 hours, including breaks and time spent for clarification and obtaining samples. All 
study activities will take place at KWTRP in Kilifi and APHRC in Nairobi. Messages will be 
sent throughout the 12 months for each individual participant and assessment of adherence, 
quality of life and stigma will be done at the first visit and subsequent follow up visits at 3, 6 
and 12 months into the study. To confirm self-reported adherence, we will also collect blood 

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samples of not more than 5 ml from participants and compare the concentration of antiseizure 
medications before and after they have received message reminders. Blood samples will be 
collected at the clinics during the first visit and subsequent follow up visits. All the samples 
will be stored at KWTRP Main Laboratory and analyses will be conducted at the end of the 
study at the CREATES Laboratory (https://creates.strathmore.edu/) hosted by Strathmore 
University. Clinicians attending to PWE in the study will continue to advice all participants 
on the need for adhering to their medication for good outcomes as part of routine care. 
 
What are the benefits and risks/costs of the study for those involved?   
Benefits: 
If message reminders are found to be useful, they will help in improving adherence outcomes 
and quality of life among people with epilepsy while reducing misperceptions about epilepsy 
and stigma experienced by these people. 
 
Risks: 
Message reminders sent on mobile phones of people with epilepsy, or their caregivers may be 
accessed by other people, thereby, posing a risk of invasion of privacy. In addition, blood 
draws may be uncomfortable for participants resulting in pain, local swelling, itching, or 
redness, which gets better after a short while. The questionnaires administered before and 
after receiving message reminders together with blood draws may take up to 3 hours to 
administer, including breaks and time taken for clarifications. Therefore, participants will be 
compensated for out-of-pocket expenses (KES 350), provided with meals or a standard 
amount of KES 200, in line with the current COVID-19 regulations and reimbursed fare in 
Kilifi while in Nairobi, APHRC will reimburse participants a flat rate of KSH 1000 to include 
transport, lunch and out of pocket allowance.  
 
 
How will the study benefit society?  
The community may potentially benefit through improved adherence to medication and 
quality of life for people with epilepsy and their caregivers.  Results from this study may 
benefit the community by helping health administrators and policy makers in Kilifi and 
Nairobi and other similar settings optimize care for PWE e.g., improve drug supply for 
persons with seizures and associated illnesses. This intervention along with ensuring adequate 

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supply of medications may also be applicable for self-management of other chronic 
conditions in resource-limited settings. 
 
When does the study start and finish? 
The study will start as soon as ethics and scientific approvals are granted and will initially run 
for three years, with possibilities of continuing renewals for subsequent follow-ups. 

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3.0 LIST OF INVESTIGATORS AND COLLABORATORS 
Investigators 
 
Investigators 
Institution 
Role 
Dr Symon Kariuki 
KEMRI-CGMRC 
Principal investigator 
Dr Mercy Atieno 
KEMRI-CGMRC 
Investigator 
Mr. Gilbert Katana 
KEMRI-CGMRC  
Investigator 
Ms Maria Mumbo 
KEMRI-CGMRC 
Investigator 
Mr. Collins Kipkoech 
KEMRI-CGMRC 
Investigator 
Ms Mary Bitta 
KEMRI-CGMRC  
Investigator 
Dr Gershim Asiki 
APHRC 
Investigator 
Dr Damazo Kadengye 
APHRC 
Investigator 
Dr Fredrick Wekesah 
APHRC 
Investigator 
Mr Peter Otieno 
APHRC 
Investigator 
Prof Sloane Mahone 
University of Oxford 
Investigator 
Prof. Arjune Sen 
University of Oxford 
Investigator 
Prof Charles Newton 
KEMRI-CGMRC 
Co-principal 
investigator 
 
Collaborators 
Collaborators 
Institution 
Role 
Dr Haji Musuko and Dr Nadia 
Aliyan 
Kilifi County 
Collaborators 
Mr Peter Otieno 
Nairobi County 
Collaborators 

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4.0 ABSTRACT 
Improved outcomes for epilepsy treatment depend on a continuous supply and daily 
adherence to antiseizure medications (ASMs). In Kilifi County, the treatment gap which 
includes both the diagnostic and adherence gap, is greater than 70% and we have found 
interruption of supply of ASMs to peripheral clinics, distance from clinic and lack of 
availability of ASMs, to be barriers to adherence. In Nairobi County, factors such as 
environment hazards, lack of social amenities and correlates of poverty are preponderant in 
slums, but the prevalence of epilepsy has not been studied in such settings and consequently, 
the adherence gap remains unknown. Innovative mobile Health (mHealth) strategies including 
messages delivered by mobile phones have been used to ensure an adequate supply of drugs 
in health centres, and daily mobile messages have improved adherence to medication in 
Human Immunodeficiency Virus (HIV) programs, for example. Text messaging requires that 
the patient has access to a mobile phone and can understand the text message. Multimedia 
messaging, such as simple pictures, may improve understanding of the necessity to take 
medication, particularly in people who are illiterate, and we will explore this as an avenue to 
improve uptake.  
We plan to randomize 1200 people with epilepsy at each site, from a defined area in Kilifi 
and Nairobi County, Kenya. They will be divided into four groups of 300 each, to receive 
either text SMS, graphic SMS, both text and graphic or SMS on public health promotion not 
related to epilepsy e.g. use of bednets (for comparison). Our aim is to i) describe the 
perceptions and perspectives of people with epilepsy and their caregivers on the use of text 
and graphic SMS reminders to improve adherence to ASMs, ii) compare the effectiveness of 
text versus graphic messaging service in improving adherence in people with epilepsy and to 
engage the County Departments of Health through current ongoing training and capacity 
building studies to maintain supply of ASMs in peripheral clinics iii) identify the factors 
associated with improvement in adherence, improved QoL and reduction in stigma among 
PWE and family members and iv) conduct cost-effectiveness assessment for the roll out of 
the intervention. Besides medication-related messages, there will be other messages, from 
previous community-based feedback, selected to address stigmatization and improve quality 
of life. Blood-level monitoring and adherence questionnaires at baseline and during 
subsequent follow up visits will be used to assess as measures of medication adherence.  If 

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found useful, this intervention may be applicable for self-managing other chronic conditions 
in under-resourced settings. 
 
 

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5.0 INTRODUCTION 
5.1 Background Information 
Epilepsy is one of the most common neurological conditions worldwide with a higher 
prevalence in low- and middle-income countries (LMIC) and rural communities. In Africa, 
the burden of the disorder can be ascribed to central nervous system infections and adverse 
perinatal events (e.g., hypoxic ischaemic encephalopathy). Poor adherence to prescribed 
medication is considered to be the main cause of unsuccessful drug treatment for epilepsy, 
increased hospitalization, diminished quality of life (QoL), and a threefold increase in 
mortality risk (Tang et al., 2013). These factors widen the treatment gap which includes both 
the diagnostic gap (people with epilepsy who are undiagnosed) and the adherence gap (people 
with epilepsy who are not on treatment, or whose treatment is inadequate). Not dissimilar to 
the findings of other resource-poor areas, the epilepsy treatment gap in Kenya is about 60% 
and ranges from 60 to 90% throughout Africa (Mbuba et al., 2012; Meyer et al., 2010). 
Adherence to medication (80% rate of total pills taken, medication possession ratio, and days 
covered by prescriptions filled) (Faught, 2012) is influenced by: (i) patient-related factors, i.e. 
forgetfulness, stigmatization which is influenced by cultural, socioeconomic, educational and 
religious affiliation (Fernandes et al., 2007) and being seizure free for a period of time (Tang 
et al., 2013); (ii) medication-related factors, e.g. cost, side-effects, number of medications 
prescribed and dosing frequency; (iii) disease-related factors including seizure type, severity, 
associated risk factors, comorbidity of psychiatric conditions; onset and duration of illness 
(Sweileh et al., 2011). 
In predominantly rural Africa, poor adherence to anti-seizure medications (ASMs) is made 
worse by the expense of accessing treatment. The medication is the least costly component, 
compared to the long distances to health facilities (Berhanu et al., 2009), coupled with the 
financial implications of this; and the influence of cultural beliefs (Mbuba et al., 2012), which 
compound the challenges relating to adherence or compliance. 
A multisite study in Africa showed that the burden of epilepsy in many rural parts of Africa is 
greater than elsewhere across the globe (Ibinda et al., 2017b). Recent pilot studies in Kilifi of 
epilepsy (both with convulsive and non-convulsive seizures) revealed a hidden burden of non-
convulsive seizures (Kariuki et al., 2021), further widening the treatment gap for these people.  
 

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The pooled adherence treatment gap in Kilifi as measured by optimal drug levels has been 
reported as 79.1% (95% CI; 73.3 to 84.3%), with adherence based on blood levels being more 
reliable than self-reports using a locally validated and adapted Morisky Medication 
Adherence Scale (MMAS-8) (Ibinda et al., 2017b). An educational intervention in Kilifi, 
Kenya resulted in improved adherence in both arms (36% to 85% in cases and 38% to 74% in 
controls) probably due to sharing of learned information among participants or study staff 
offering psychosocial counselling to both groups (Ibinda et al., 2014). However, this 
intervention was costly to sustain and may not improve nonadherence due to forgetfulness 
associated with epilepsy-related intellectual disability (Mwangala et al., 2018).  
Poor compliance has been identified in scientific studies as affecting the concentrations of 
these medications in blood. These varying concentrations in blood can then affect how a 
person responds to treatment or whether they experience drug-related side effects including 
symptoms of psychosis (Chen et al., 2012), weak bones (Zhang et al., 2020) or enlarged gums 
(Silvado et al., 2018). Other people with epilepsy may also fail to take their medications 
correctly because of side effects caused by their medications which may discourage 
compliance. Therefore, we can plan to document drug-related toxicities as reported by 
patients and in relation to plasma ASM levels. 
People are increasingly migrating towards larger cities such as Nairobi, where the disease 
burden is yet to be determined or compared with the burden in rural areas. Factors such as 
environmental hazards, lack of social amenities and correlates of poverty are preponderant in 
slums (Kyobutungi et al., 2008), and can cause substantial disease burden (Kimani-Murage et 
al., 2015). Lead toxicity from industrial emissions and housing materials in informal 
settlements in Nairobi may also cause brain damage (Sanders et al., 2009) that can manifest as 
epilepsy. Data is urgently needed on the epilepsy treatment gap (both the diagnostic and 
adherence gap) in urban settings such as Nairobi and innovative interventions put in place to 
improve ASM compliance and adherence. 
The Kenya Association for the Welfare of people with Epilepsy (KAWE) is well-established 
(http://www.kawe-kenya.org/) and is affiliated to IBE. They have initiated many schemes for 
PWE including advocating for the registration of PWE with the National Council for People 
with Disabilities, and thus allowing PWE access to support for primary, secondary, and 
tertiary education, cash transfers for those with more than one form of disability, inter alia. 

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A study assessing community-level interventions from China (Wang et al., 2008) and the 
group-orientated Modular Service Package Epilepsy program (MOSES) study in Austria, 
Switzerland and Germany (May and Pfäfflin, 2002; Ried et al., 2001), illustrated how 
education helped to improve the understanding of epilepsy and the long-term implications if 
the disorder went untreated among people with epilepsy. These studies highlight that epilepsy 
education may only be effective as an intervention to improve adherence if it is continuous. 
Key information identified by the studies were: information about the symptoms and causes 
of epilepsy, advice about safety, advice about support within a social and cultural context that 
address stigma, and, for the service providers, further advice about the treatment. To be 
effective, interventions should build upon local existing practices, identify, and target the 
most receptive community members, bolster local skills and priorities, recognize constraints 
(time, financial, cognitive, and social) on sustained commitment and feature community 
engagement (Panter-Brick et al., 2006).  
Patient-related behaviours, such as irregular medication-taking or dose self-titration are major 
factors contributing to poor adherence. The consequences of self-management of ASMs may 
not appear instantly which may induce complacency (Faught, 2012). If a person with epilepsy 
(PWE) relies on family to help with ASM administration, and the support is misinformed, this 
can exacerbate the problem. A lack of understanding, made worse by forgetting, could be 
addressed through more personalized interventions to remind PWE to take their medication, 
or renew prescriptions. Mobile phone messaging is a potentially powerful tool for behaviour 
change because it is widely available, inexpensive, and instant (Cole-Lewis and Kershaw, 
2010). 
Mobile phone health (mHealth) messaging studies that have been conducted predominantly in 
high-income countries have focused mainly on smoking cessation (Free et al., 2011), self-
monitoring of diabetes (Vervloet et al., 2012), and asthma (Strandbygaard et al., 2010). Many 
of these have involved a small number of participants (<100) and for short periods of time 
(<6m). The focus of these studies has been on the logistics of sending and receiving text 
messages to raise awareness; for collecting health behaviour data (Kerr et al., 2012), or to 
assess the cost efficacy of preventive health care (Marshall et al., 2013), rather than collating 
high-quality evidence of behaviour change or reduction in health service utilisation (de Jongh 
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In LMICs, several studies have considered the effectiveness of text messaging (SMS) 
interventions to improve health workers’ practices (Kallander et al, 2013; Zurovac et al, 
2011), as a learning tool, and to improve adherence to medications and care, particularly 
antiretroviral drugs (de Tolly et al., 2012). To inform policy makers about the feasibility of 
facility-based SMS messaging interventions, coverage data on mobile phone ownership and 
SMS use among health workers and patients are needed. More studies are also needed to 
ascertain the usefulness and potential negative consequences of mobile phone messaging, 
both SMS and graphic / picture messaging (multimedia messaging service (MMS)), over 
extended periods of use for self-managing chronic conditions (de Tolly et al., 2012).   
It has been estimated that over two-thirds of the population in Africa is covered by a mobile 
network with a penetration rate of 93%, reaching just under a billion mobile phone 
subscribers across the continent https://data.gsmaintelligence.com/api-web/v2/research-file-
download?id=18809326&file=the-mobile-economy-sub-saharan-africa-2015-infographic-
1482139932154.pdf . In 2009, in collaboration with the Kenyan National Bureau of Statistics, 
the Financial Sector Deepening Kenya survey asked questions about mobile phone usage, 
ownership, and monthly expenditure on airtime, as well as detailed demographic questions 
concerning income, education level and housing type (32,748 individuals located at 646 
communities: http://www.fsdkenya.org). Based on three cluster surveys, 85% of the 
population reported using a mobile phone. In rural areas, mean phone ownership was 39% 
(90% range: 14%–43%) compared to urban regions where it was 58% (90% range: 65%–
80%). Ownership was determined by education level rather than gender in urban areas, 
whereas in the rural areas and among poor urban communities, 20% owned their own phone, 
while most households shared a mobile phone, and usage was higher among men. InfoDev’s 
findings from a survey of 6 districts in Kenya found no notable gender difference in mobile 
phone activities, but this did not translate into an absence of a gender disparity in mobile 
phone ownership (http://www.infodev.org/articles/mobile-usage-base-pyramid-kenya). Both 
phone owners and phone sharers reported similar monthly expenditure on mobile phones and, 
surprisingly, both groups spent approximately the same proportion of their income on airtime 
(13% and 10%, respectively) (Wesolowski et al., 2012). Another finding from both surveys 
was the deliberate sacrificing of food or bus fare to pay for airtime, in the belief that a call 
may lead to work. In addition, an audit of mobile phone ownership and usage assessment 
conducted at the epilepsy clinic in Kilifi in 2013 showed that, of the 222 PWE interviewed, 

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19% (44/222) owned a mobile phone, and 85% (189/222) could access mobile phones 
through close caregivers living with them. In Nairobi, the phone ownership rates are likely to 
be even much higher, considering this is an urban area and the capital city of the Country but 
PWE may be disadvantaged due to their medical condition leading to other psychosocial 
consequences such as lack of employment and poor marriage prospects. 
This rapid assimilation of mobile phone technology within Africa makes it culturally 
compelling  to help reduce the treatment gap of one of the most common neurological 
conditions worldwide (Panter-Brick et al., 2006). To our knowledge, no studies have used 
mobile phone messaging to improve adherence to ASMs and address stigma. The application 
of text messaging for behavioural change for mental and neurological disorders is at an early 
stage of research. Randomised controlled trials of such use of text (SMS) or picture (MMS) 
messaging, and / or with an auditory component are scarce, with few from semi-literate low- 
resource settings. There are few reported trials on antiretroviral treatment adherence from 
Kenya (van der Kop et al., 2018) and from India (De Costa et al., 2010). There is also a 
paucity of studies that assess community-based adherence interventions alongside improved 
supply of ASMs to health care centres in rural areas to bridge the adherence treatment gap. 
 
5.2 Name and description of the investigational product(s), 
An intervention that utilises a mobile messaging service could serve to remind patients with 
epilepsy (PWE) to take their medication. This has not been undertaken before and is now 
feasible because of greater mobile network coverage in rural areas in Kenya and increasing 
mobile phone ownership and usage in these areas. Use of SMS is more widespread in 
antiretroviral and antimalarial adherence studies in Africa and has shown great promise in 
improving adherence to medication and consequently, outcomes. This study will further test 
the evidence to support the use of graphics in impoverished semi-literate communities such as 
the study sites to convey health-related messages. These multi-media messages will be 
designed in a simple format that is compatible with both basic phones and smart phones. 
However, since the display characteristics of basic phones and smart phones may differ, we 
will document the type of phone used by the participant and this will be taken into 
consideration during the analyses and interpretation of findings. It is unclear whether either 
one of these interventions will improve adherence in a rural population or informal 
settlements with high rates of illiteracy.  

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A two-way SMS platform will be implemented such that PWE participating in the study will 
be able to receive messages from the study team and send messages to the study team via 
normal text or using an unstructured supplementary service data (USSD) prompt at no cost to 
the PWE. The SMS platform will also be able to send delivery reports to the study team if the 
message is delivered to the intended user and a read report once the message is opened by the 
intended user.  During planned follow up visits, we will also check for any issues regarding 
receiving messages, disruptions in the network service provider or electricity, change of 
phone number, change of handsets and whether caregivers relay messages to the PWE in the 
case that they are the ones receiving the SMS on behalf of the PWE. Those who do not relay 
messages will be encouraged to do so and changes in phone numbers will be updated. Since 
this is meant to be a pragmatic trial that can be rolled out in a sustainable fashion throughout 
resource-poor settings, challenges are to be expected and will be taken into consideration 
when interpreting the findings. 
 
5.3 Justification 
Epilepsy is one of the most common neurological conditions in Africa where it is associated 
with a great degree of stigma. Most people with epilepsy in this setting do not seek 
biomedical treatment and only a small proportion of those on treatment take their medication 
correctly. In fact, the precise magnitude of the epilepsy treatment gap (both the diagnostic and 
adherence gap) as measured from blood is unknown in urban settings such as Nairobi, where 
data is urgently needed. Poor adherence and denial of the disorder serve to widen the 
treatment gap and is associated with impaired quality of life (QoL) and premature mortality. 
These detrimental consequences can be prevented by improving daily adherence to 
therapeutic doses of anti-seizure medications (ASMs).  
An intervention that utilises a mobile messaging service could remind PWE to take their 
medication, leveraging on recent increase in mobile phone access over the past 20 years and 
proven benefit of mobile technology in improving drug adherence for other diseases. The 
service can also be used to monitor the supply of ASMs to peripheral health facilities. Current 
on-going studies in the Epilepsy Pathway Innovations in Africa (EPInA) studies in Kilifi and 
Nairobi are aimed at engaging the county department of health to ensure collaboration in 
improving care for people with epilepsy. As part of the EPInA studies, we plan to train 

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primary healthcare workers (PHWs) on diagnosis and management of epilepsy and other 
mental and neurological disorders using the World Health Organisation’s mental health Gap 
Action Programme-Intervention Guide (mhGAP-IG). These PHWs will be selected from 
public health facilities in both Kilifi, and Nairobi and these capacity building activities will 
offer a platform for lobbying for consistent supply of ASMs in the peripheral health facilities. 
SMS platforms have also been used to set up SMS-based stocktaking forms to monitor supply 
and reordering of antiretroviral medication to health clinics and this is yet to be explored for 
ASM supply. 
Both text (SMS) and picture messaging (MMS) demonstrate strong potential as tools for 
healthcare improvement for several reasons: these are accessible on almost every model of 
mobile phone even basic phones; the cost of transmission is relatively low; neither require 
great technological expertise, and the transmission of brief health-related messages are widely 
applicable to a variety of health behaviours and conditions. However, since reading text 
messages requires some level of literacy, we will compare texts versus graphic messages and 
the impact on ASM adherence. The messaging service also has the advantage of being 
asynchronous because it can be accessed at any time that is personally convenient. Use of 
SMS is more widespread in antiretroviral and antimalarial adherence studies in Africa. This 
study will further test the evidence to support the use of graphics in impoverished semi-
literate communities to convey health-related messages. Improved adherence may 
subsequently improve quality of life among people with epilepsy, reduce accidental injuries, 
psychiatric comorbidities, and premature mortality. Nevertheless, it is unclear whether either 
one of these interventions will improve adherence in a rural population with high rates of 
illiteracy. 
6. TRIAL OBJECTIVES AND PURPOSE 
6.1 Null hypothesis 
Utilising mobile messaging service to send reminders to people with epilepsy to take anti-
seizure medications is not associated with a difference in adherence to anti-seizure 
medications as measured by detectable and optimal drug levels in blood. 

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6.2 Primary objective 
To examine the effect of sending text or graphic SMS reminders among people with epilepsy 
in Kilifi and Nairobi, Kenya using a randomized controlled trial design on: 
i. 
ASM adherence 
ii. 
Quality of life 
iii. 
Epilepsy-related stigma scores     
6.3 Secondary objective(s) 
(i) Using qualitative methods, to describe the perceptions and perspectives of PWE and 
their caregivers on the use of text and graphic SMS reminders to improve adherence to 
ASMs among PWE in Kilifi and Nairobi, Kenya 
(ii) To compare the effectiveness of text versus graphic messaging service or both in 
improving adherence among people with epilepsy in Kilifi and Nairobi, Kenya 
(iii)To identify the factors associated with an improvement in adherence and improved 
QoL among PWE and reduction in stigma among PWE and their family members. 
(iv) To document the adverse drug reactions (ADRs) including neurologic and psychiatric 
ADRs related to frequently prescribed ASMs types and, where possible, plasma levels 
among PWE in Kilifi and Nairobi, Kenya 
(v) To conduct cost-effectiveness analysis of rolling out the interventions among PWE in 
Kilifi and Nairobi, Kenya 
 
7.0 TRIAL DESIGN 
7.1 Overall Study Design 
This study will follow a single-blinded randomized controlled trial design. Participants will be 
randomly selected from a database of over 3500 PWE. The selected participants will be 
invited to the clinic for screening against the eligibility criteria and enrolment into the study. 
The study sample will consist of 1,200 people with epilepsy in each site. Out of the 1200 
PWE, there will be 900 participants in the intervention arm (300 receiving text SMS, 300 
receiving graphic SMS, 300 receiving both text and graphic) and 300 in the control arm (non-
epilepsy related SMS) (Figure 1). The participants will be aware of the intervention status, but 
the researcher and clinical staff will not.  All participants will receive an SMS (cases to 

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encourage adherence and controls will receive non-epilepsy related messages) for 
comparability and to reduce the risk of disclosing the blind during follow up visits. 
Participants will be encouraged to not disclose the content of their messages during follow up 
visits. As a secondary outcome, ASM-related ADRs including neurological and psychiatric 
ADRs, will be documented for all participants on ASMs, and where possible, related to type 
(s) of ASM used. 
7.2 Description of the study areas and population  
This study is part of the EPInA studies planned in Kilifi and Nairobi. In Kilifi, the SMS trial 
will take place within the Kilifi Health and Demographic Surveillance System (KHDSS). The 
KHDSS was established in 2000, covers a defined geographical area of 900km2 located on 
the Kenyan coast and currently has a population of about 280,000 residents under active 
surveillance https://kemri-wellcome.org/programme/health-research-linked-to-a-
demographic-surveillance-system/. We will approach people with epilepsy currently taking 
ASMs from a database of over 3,500 patients attending the epilepsy clinic routinely. Written 
consent and/or assent (for children aged 13 to 17 years old) will be obtained from all 
participants and the study will be conducted with permission from a local ethics review 
committee. 
In Nairobi County, we are collaborating with APHRC, through their Nairobi Urban Health 
and Demographic Surveillance System (NUHDSS). The NUHDSS is in Nairobi city 
comprising two slum communities namely Korogocho and Viwandani, both with a total 
population of about 65,000 (Beguy et al., 2015). All houses are marked with unique 
identification numbers making it possible to obtain vital information on not only 
sociodemographic patterns but also pregnancy outcomes and movement in and out of 
NUHDSS. Children and adolescents comprise 35% of the total population. In 2012, the crude 
birth-rate was 28.9/1000 person-years, while mortality rate was 6.2/1,000 person-years. The 
NUHDSS offers an opportunity to conduct studies investigating the link between 
urbanisation, poverty, or lack of social amenities on health outcomes (Kimani-Murage et al., 
2015). Additionally, participants attending one KAWE-led clinic in Nairobi will also be 
invited to participate in the study. 

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8.0 DESCRIPTION OF THE INTERVENTION 
8.1 Intervention  
The intervention will be a short message service (SMS) reminder sent to the mobile phones of 
participants in the intervention group reminding them to take their anti-seizure medications. 
This will be a behavioural intervention with no investigational medicinal product. Each SMS 
(text or graphic or both) adherence message will be 120–140 characters long. To increase the 
probability that that the PWE or family member will read the messages and support family 
members with epilepsy, message will be randomly complemented with a quote (up to 60 
characters long) and unrelated to epilepsy treatment, but designed to be motivating, 
entertaining, or merely attention-getting. This motivational element was used with success in 
the health workers adherence to antimalarial guideline studies. The graphics will be hand 
drawn by a local illustrator and the accompanying text of no more than 15 characters will be 
scanned and sent as low-resolution jpeg files, suitable for the MMS format that is compatible 
with basic phones.  
8.2 Identity of the SMS 
We will use a validated software for the automated bulk SMS service and outsourced tool for 
the MMS transmission. The SMS company contracted will assist in the setting up and training 
of the software, plus on-going support. The SMS interface/platform will utilize an android 
application system for smartphones and Unstructured Supplementary Service Data (USSD) 
format for basic phones and will be accessible from a web browser and will be integrated into 
an encrypted central database. All requests and administrative actions made to the program 
and its responses will be logged chronologically and stored in the database.  
8.3 Frequency and timing of sending messages 
The messages will be transmitted at a frequency and time, determined during focus group 
discussions held before the roll-out of the intervention, that is convenient for both the PWE 
and their caregivers.  
8.4 SMS dispensing procedures 
Automated reminder messages will be sent out by the KEMRI-Wellcome Trust Research 
Programme data manager and from a password-protected computer within the Neuroscience 
Unit in Kilifi. These will be sent as mobile phone texts (SMS) or graphic picture messages 
(MMS).  

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8.5 Intervention Compliance 
It will be possible to view a delivery report of whether the messages were received or not due 
to network issues. After the screening visit, all participants will be contacted via phone call to 
check that their phones can receive the messages. Prior to the commencement of the SMS 
trial, ongoing EPInA studies will conduct engagements with the respective county 
departments of health on sustained availability of ASM at the health facilities within the study 
area where PWE are likely to visit for medication refill. Primarily PWE will visit the study 
clinics (epilepsy clinic in Kilifi, two APHRC clinics in Nairobi and one KAWE-led clinic in 
Nairobi). However, due to ongoing capacity building and task sharing studies in Kilifi (the 
mhGAP study), some PWE may visit any of the 128 public peripheral health facilities already 
contributing primary health care providers for training.  Since adherence may also be affected 
by availability of medications, we hope to be able to lobby for the set-up of an SMS platform 
to monitor supply and re-ordering of ASMs in Kilifi and Nairobi County in addition to 
ongoing engagements with the counties as part of capacity building and task sharing within 
the EPInA studies.  
9.0 STUDY PLAN DESCRIPTION 
9.1 Pre-study focus group discussions 
We will hold about 3 pre-study focus group discussions. During these FDGs, participants will 
propose the timing and frequency of the messages during pre-study focused group discussions 
(FGDs). Perceptions of PWE on use of mobile phone text messages to improve adherence 
will also be evaluated during the three pre-study FGDs before the roll out of the study. These 
will involve about 10 PWE and one of their family members in each group. The aim of these 
FGDs will be to inform the preferred timing and frequency of the messages to be sent out 
during the study. We will also review the nature of the messages and how best to relay 
sensitive information, especially for shared phones. Finally, we will establish the content of  
public health promotional messages (not related to epilepsy adherence) such as use of bednets  
and the types of messages controls would want to receive.  These discussions will be 
recorded. The audio records will be stored in cabinets under lock and key and destroyed upon 
transcription. Paper transcriptions will be stored under lock and key until all have been 
electronically replicated and validated.  

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9.2 Roll out of the SMS trial 
9.2.1 Identification of Participants 
Participants will be identified from the epilepsy clinic in Kilifi and three clinics in Nairobi 
(two APHRC clinics in Korogocho and Viwandani, respectively and one KAWE-led clinic). 
These PWE will have utilized the clinics more than once and live within either the KHDSS 
for participants in Kilifi or the NUHDSS for participants in Nairobi.  The epilepsy clinic in 
Kilifi has a database (built under an approved protocol: KEMRI/SERU/CGMR-C/125/3701) 
that has over 3,500 patients to date, who have accumulated from 30 patient visits a day, 10 of 
whom are usually new. They will be approached by the study clinician during their routine 
clinic visit. In Nairobi, participants will be identified from an on-going survey which is part of 
the EPInA studies. This survey is being conducted by APHRC to identify people with a likely 
diagnosis of epilepsy living in informal settlements in Korogocho and Viwandani. The 
diagnosis is confirmed by trained clinicians at two APHRC clinics conveniently located 
within the study areas. The identified PWE will be added to an epilepsy database from which 
participants for this study will be identified. Additional PWE will be identified from one 
KAWE-led clinic in Nairobi. 
In Kilifi, record logs usually taken during routine care will be reviewed from the database of 
those attending the epilepsy clinic and then those at Kilifi County Hospital. In Nairobi, 
records from participants identified during an on-going epilepsy survey in two slum dwellings 
conducted by APRHC and records from patients attending KAWE-led clinics will be 
screened for eligibility. 
9.2.2 Eligibility criteria 
9.2.2.1 Inclusion criteria 
(i) Children or adults with a diagnosis of epilepsy ascertained by a clinician at the 
epilepsy clinic 
(ii) Taking anti-seizure medications at the time of the study 
(iii) Living within an area defined as the Kilifi Health Demographic Surveillance System, 
or the Nairobi Urban Health and Demographic Surveillance System at the time of the 
study or attending the epilepsy clinic in Kilifi or a KAWE-led clinic in Nairobi 
(iv) Able to give written informed consent or assent in addition to parental consent (if aged 
between 13 and 17 years old) to participate in the study either by themselves or in the 
presence of an independent witness 

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(v) Access to a basic mobile phone in the household 
9.2.2.2 Exclusion criteria 
Participants who meet all the inclusion criteria above will not be eligible for inclusion in the 
study if they: 
i. 
have intellectual disability  
ii. 
do not have access to basic mobile phones 
iii. 
are currently enrolled in ongoing interventions aimed at improving their health 
care 
9.2.3 Consenting/Assenting and screening for eligibility 
Consenting and/or assenting (for children aged 13 to 17 years old) will be done by field 
workers during initial contact and participants booked for the first study visit. Investigators 
will emphasize that participation in the study is voluntary. All participants will have the study 
explained to them including potential risks and obligations before giving written informed 
consent and/or assent.  Once consented and/or assented, participants will be screened for 
eligibility based on the above-mentioned set of inclusion and exclusion criteria. Screening 
will be conducted by study fieldworkers in collaboration with the study clinicians. 
Participants who meet the inclusion criteria at the screening visit will be telephoned by a 
fieldworker a week prior to sending out the SMS to assess availability of mobile phone 
access. They will also be asked about any new medical complaints and concomitant 
medication since their screening visit. 
9.2.4 Recruitment and enrolment  
Only participants who are eligible for recruitment and willing to participate in the study 
through written informed consent/and or assent (for children aged 13 to 17 years old) will be 
recruited into the study. We plan to recruit a total of 1200 participants for the SMS trial from 
each site. All screened people with epilepsy will be informed of the inclusion criteria and 
their eligibility for enrolment. Eligible participants who give consent/and or assent will then 
be invited for the initial study visit for enrolment into the study and baseline assessments 
9.2.5. Randomisation 
Participants will be randomized to four groups, with randomisation assigned via a computer-
generated sequence by an independent statistician. The database manager will not know 
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will be used. A random sampling technique using computer-generated sequences will be used 
to ensure epilepsy factors such as focal features, age and gender are balanced between the 
intervention groups or arms.  The SMS randomisation platform will be linked to a central 
database that stores a pre-generated randomization sequence, which will be generated once at 
the beginning of the study. Each participant will be randomized once, failure to which the 
system will alert the data manager and decline the request. The data manager will use an 
automated system to send out the messages and they will be blinded to participant details. In 
addition, to prevent cross-contamination due to exchange of information among participants, 
we will emphasise the need to keep allocation  among confidential the participants and 
schedule follow up visits for participants in different arms on different days. However, cross-
contamination may still occur in the community, and this will be considered during 
interpretation of the findings. 
Figure 1. Recruitment strategy and randomization 
 
 
*All people with epilepsy in the databases will be screened for eligibility 
                                                 
                          
      
                
     
     
              
      
               
                    
      
                      
      
            
              
             
     
              
               
                         
       
        
            
            

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9.2.6. Procedures  
(i) Clinical evaluation, assessment of stigma scores and measures of quality of life 
 
During the baseline visit, information regarding epilepsy factors including seizure semiology, 
electroencephalography (EEG) and medical co-morbidities as well as sociodemographic 
characteristic will be assessed using tools that have been validated in this setting. 
Comprehensive clinical examination, and assessment of self-reported sigma and measures of 
quality of life and collection of blood samples will also be conducted at the baseline visit. 
Stigma scores will be assessed using standardized Kilifi Epilepsy Stigma Scale and while 
quality of life will be assessed using the World Health Organization Quality of Life Scale 
(WHOQOL-BREF).  These tools will be validated for the Nairobi site prior to administration. 
(ii) Measurement of adherence 
Information on adherence to ASMs will also be collected using a validated self-reporting tool, 
the Morisky Medication Adherence Scale (MMAS-8) and validated using blood samples. 
Blood will be drawn (not exceeding 5mls) to measure detectable and optimal plasma levels of 
ASMs at baseline and during three follow up timepoints; at three months, six months and at 
12 months (table 1). Optimal and detectable levels of ASMs in blood. All assays for ASMs 
will be done at the end of the study using a TDxFx analyser and automated VitaLab Selectra 
E Clinical Chemistry (Abbott Laboratories, Abbott Park, IL, USA) at Centre for Research in 
Therapeutic Sciences (CREATES), Strathmore University. 
(iii)Short message service (SMS) intervention 
An automated computer system will be used to generate standard text messages to remind 
patients to take their ASMs at the prescribed time and to refill their prescriptions. The system 
will have an algorithm to check time, send the text message and generate a delivery report. 
Participants will be able to send replies to the messages, either via text or USSD codes at no 
cost. A three-step verification SMS system will be designed to send a delivery report (which 
shows if the message has been delivered) and a read receipt (which shows if the message has 
been opened) back to the service provider and study team and each message will prompt for a 
USSD or text response at no cost to the participant asking if they have read the message. 
The participants in the no-intervention group will receive routine care, including clinic 
appointment for review of symptoms and medication review and refills and routine 
electroencephalography (EEG) recordings. For comparability, the control group will receive 

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public health promotion messages (not related to epilepsy) such as use of bednets. All other 
data will be collected in the case report forms during scheduled follow up visits at the clinic. 
(iv) Anti-seizure medication (ASM)-related adverse drug reactions (ADRs) 
Cognisant that this trial doesn’t involve administration of medicinal products, we would like 
to document and describe reported drug-related adverse events of ASM as part of routine 
care. These data have not been previously systematically documented in relation ASM use in 
the study population. ASM-related adverse drug reactions will be documented and graded 
according to Common Toxicity Criteria for Adverse Events (CTCAE), including date and 
time of onset, severity, and relationship to drug administration. Standardised assessment will 
be used to measure various emerging ADRs. These data will be used in a secondary analysis 
to investigate the association of toxicity with ASM concentrations. Any side effects of ASMs 
will be documented for all the participants and correlated with type of ASM used and where 
possible, the ASM levels in blood. This will include abnormalities during pregnancy such as 
congenital abnormalities/birth defects since certain ASMs such as sodium valproate are 
known to be teratogenic. This information will be collected into case review forms at baseline 
and during follow up visits. 
9.3 Follow-up Visit(s) and End of Treatment Visit 
Participants will be invited to the study clinics for follow up visits to examine adherence to 
anti-seizure medications and assess their quality of life and stigma scores three, six and 
twelve months from the first visit. The long follow up period per individual of 12 months is 
selected to ensure high exposure to the intervention to show proof of concept. All other 
routine clinical assessments will be done during this follow up visit including physical 
examination, EEG recordings and medication refill. Participants who fail to show up for 
scheduled follow up visits will be contacted by telephone up to three times and if 
unsuccessful, followed up at home to remind them to come for their scheduled visits. 
Participants who are not reached after 3 telephone calls and one home visit will be considered 
lost to follow up. 
 

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Table 1: Study Schedule 
 
 
Screenin
g visit 
1 
Pre-
enrolmen
t 
screening 
call 
Randomisatio
n visit 
2 at baseline 
Follo
w up 
visits 
1  
Follo
w up 
visits 
2  
End of 
interventio
n 
 
Study Month 
Use 
available 
data 
-1 week 
0 
3 
6 
12 
Assessment / 
Procedure 
 
 
 
 
 
 
Provide Patient 
Information Sheet and 
Informed Consent 
Form and/or Assent 
Form 
x 
 
 
 
 
 
Obtain written 
informed consent 
and/or assent 
x 
 
 
 
 
 
Call to check phone 
availability/accessibilit
y 
 
x 
 
 
 
 
Demography 
x 
 
 
 
 
 
Medical history 
x 
 
 
 
 
 
Physical examination 
x 
 
x 
x 
x 
x 
Vital statistics e.g., 
heart rate and blood 
pressure 
x 
 
x 
x 
x 
x 
12-lead EEG 
x 
 
 
 
 
x 
Blood for adherence 
levels  
x 
 
x 
x 
x 
x 
Morisky self-reported 
scale 
x 
 
x 
x 
x 
x 
Stigma scores scale 
x 
 
x 
x 
x 
x 
Quality of life scale 
 
 
x 
x 
x 
x 

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10.0 ASSESSMENT OF EFFICACY 
10.1 Specification of the efficacy parameters. 
10.1.1 Primary efficacy variable 
The primary outcome measures will be adherence to anti-seizure medications as measured by 
self-reports and validated by optimal and detectable levels in blood. 
10.1.2 Secondary efficacy variable(s) 
(i) Correct intake of drugs and refill rates- measured by checking record logs for 
participants attending the epilepsy clinics and identified in the surveys in NUHDSS 
(ii) Changes in seizure frequency as assessed by trained clinicians at the epilepsy clinics 
and identified in the surveys in NUHDSS 
(iii) Changes in stigma scores and quality of life scores assessed using standardized scales   
(iv) Unwanted drug-related adverse events as reported by participants and confirmed using 
standardized questionnaires. 
11.0 EVALUATION OF COST EFFECTIVENESS OF THE INTERVENTION 
The impact of measures to address the epilepsy treatment will be used to inform economic 
modelling that we will undertake to calculate the return on investment from investing in 
management. A decision analysis model will be constructed by collating data on the resources 
required for treatment strategies in epilepsy care.  
In addition, we shall draw on existing analyses of the costs of epilepsy, to estimate economic 
benefits from a health and societal perspective of averting epilepsy. The costs of treating 
epilepsy will be estimated by adapting existing resource use and cost estimates from Ethiopia 
so that they match the local Kenyan context using the WHO’s One Health Tool. Threshold 
analysis to identify the minimum level of effectiveness and/or costs needed to generate a 
positive return on investment. Drawing on data on the QoL benefits associated with 
preventing epilepsy a net monetary benefit approach to determining the economic case for 
action will also be conducted. 
Crucial to the sustainability of the project, although initially tailored to the local context in 
Kenya, the economic model will be made available in Excel format as a legacy of the 
proposal. Decision makers in SSA would then be able to look at the potential return on 
investment in their own contexts. They would be able to vary assumptions on 

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population reached, effectiveness, coverage, resource requirements and the short and longer-
term costs of both treated and untreated epilepsy. 
12.0 STATISTICS 
12.1 Determination of sample size 
The minimum sample size determination will be based on reducing the adherence treatment 
gap from the current estimates of 62% in Kilifi ((Ibinda et al., 2017a) aiming for a proportion 
of improvement of 40%-50%. Previous studies have shown non-adherence of >60% even 
among clinic attendants, especially when symptoms subside. Assuming a refusal/non-consent/ 
attrition rate of 10% and design effect of 1.5 (assuming possibility of modest clustering), if 
we recruit 300 patients at each arm, i.e., total of 1200 patients, we will have 95% power to 
detect a 50% improvement in adherence. Therefore 1,200 PWE will be randomized into 4 
arms as follows: text SMS (N=300), graphic SMS (N=300), both text and graphic SMS 
(N=300) and control/non-reminder SMS (N=300). An allocation ratio of 1:1:1:1 across the 4 
arms will be used. Since no prevalence estimates exist for the Nairobi site, we will utilise a 
similar sample size for each site. This sample size determination will account for these 
unprecedented withdrawals by recruiting a surplus of participants, assuming a proportion of 
20% loss to follow up. 
 
Table 2. Sample size adjusted for 10% attrition at varying improvements and powers 
 
Power 
Improvement  
80% 
90% 
95% 
40% 
588 
786 
971 
45% 
268 
358 
442 
50% 
154 
205 
253 
 
12.2 Statistical and analytical plans 
12.2.1 Data management 
Audio records from focus group discussions  and the hard copy files will be stored in cabinets 
under lock and key for the duration of the study and for use in future publications and training 
of master’s and PhD students. All data will be stored in KEMRI computers protected by 
passwords. The SMS company will set up and test an SMS/MMS gateway for the study and 

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provide on-going support. The data manager at Kilifi (CK) will be trained by the SMS 
company to utilize the software and ensure that the messages are sent out as planned. 
All analyses will be done on Stata Version 17 (College Station TX: StataCorp LP). We will 
use paired sign-rank tests to compare continuous scores of stigma and quality of life, and 
Man-Whitney U tests for cross-sectional comparisons during follow up. Analyses will be sub-
based on either outcomes (binary or continuous) or evaluation timepoints (cross-sectional or 
across all time points i.e. at baseline, 3, 6 and 12 months).  For evaluation timepoints across 
all time points, generalized estimating equations will be used to analyse adherence binary 
status in panel or long data format with appropriate link functions (i.e. specifying binomial 
family and log link). For cross-sectional evaluations at different timepoints (i.e., evaluation of 
either baseline, 3, 6 or 12 month- timepoint), we will calculate the relative risk (RR) using 
generalised linear models with appropriate link functions (i.e. specifying binomial family and 
log link). Relative risks will be used to efficacy by subtracting the RR ratio from 1. 
Adherence will be determined by comparing detectable ASM levels in blood against 
proportion of prescribed doses correctly taken. We will conduct interim analysis at the 
halfway mark to assess performance of the intervention. Multivariable logistic regression will 
be performed to investigate association between type and ASM blood levels and incidence of 
psychiatric comorbidity. 
12.2.2 Planned statistical methods 
All quantitative analyses will be done on Stata Version 17 (College Station TX: StataCorp 
LP). We will use paired sign-rank tests to compare continuous scores of stigmas and quality 
of life and Man-Whitney U tests for cross-sectional comparisons during follow up. Adherence 
(which is the primary efficacy variable) will be determined by comparing detectable ASM 
levels in blood against proportion of prescribed doses correctly taken, with a binary variable 
for adherence generated from established detectable and optimal levels of ASM in blood. 
Generalized estimating equations, with appropriate link functions (i.e. specifying binomial 
family and log link), will be used to analyse adherence binary status in panel data format, 
across the follow-up periods of baseline, 3 months, 6 months and 12 months. For cross-
sectional evaluations at each follow-up period e.g. at 3 months, will be done using generalised 
linear models with appropriate link function (i.e. specifying binomial family and log link). 
Both generalised estimating equations and generalised linear models will produce Absolute 
relative risks (RR) which  will be subtracted from one to compute efficacy (i.e. efficacy=1-

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RR). We will conduct interim analysis at the halfway mark to assess performance of the 
intervention. For secondary efficacy variables, specifically stigma scores and quality of life 
scores, we will first generate discrete variables of improvement by subtracting baseline scores 
from follow up scores and repeat efficacy analysis using the approaches described for primary 
efficacy variable i.e., adherence. All levels of efficacy analysis will be done including Full 
Analysis Set (FAS), Intention-to-treat population (ITT), and Per Protocol population (PP). 
Multivariable logistic regression will be performed to investigate association between type 
and ASM blood levels and incidence of adverse events.  
For qualitative studies, standard analysis approaches, will be used including transcribing 
verbatim, coming up with a preliminary thematic framework through reading a sample of the 
transcripts. The thematic framework will be used to create a coding structure in NVivo, the 
software that will be used for final analysis including inter-rater coding and data 
management/filing. 
13.0 STUDY MANAGEMENT 
13.1 Protocol deviations and violation(s) 
A protocol deviation will be any failure to adhere to the defined procedures or intervention 
plans outlined in the protocol version approved by Scientific Ethics Review Unit (SERU) and 
Oxford Tropical Research Ethics Committee (OxTREC). A protocol violation is any planned 
or inadvertent changes that may impact safety of study participants, affect integrity of the 
study data and/or affect study participants willingness to participate in the study previously 
approved by the SERU or OxTREC. Any unforeseen and unavoidable deviations from the 
protocol will be documented and filed in a protocol deviation folder, with explanation and 
reported to the relevant ethical and regulatory authorities during the annual reports to ethical 
review boards while violations will be reported immediately. 
13.2 Discontinuation of the study 
The study in its entirety may be discontinued prematurely by the Sponsor, or the Ethics 
Committee with oversight responsibilities at any time. All arms of the study may be 
discontinued by the sponsors in the event of the following but not limited to:  
i. 
occurrence of an unanticipated health or technological problem  
ii. 
evidence of serious and/or continuing noncompliance.  

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iii. 
safety or human rights concerns raised by the ethics committees in Kenya and 
Oxford. 
13.3 Withdrawal of Study Participants 
Participant may opt to withdraw from the study at any point. The study team may withdraw 
them from the study if it is established that they are not accessing SMS, have missed two of 
the follow up periods, have stopped taking anti-seizure medications following advice by the 
attending clinician or those who have emigrated or died. Participants may terminate their 
participation prematurely, or have their participation terminated by the Investigator 
 
13.3 Direct access to source data/documents 
The regulatory agency, and other authorised representatives of the sponsor will have direct 
access to source documents to permit trial related monitoring and audits. 
13.4 Quality control and quality assurance 
The quality assurance manager at the trial site will conduct internal audits to check that the 
trial is being conducted, data is being recorded, analysed, and accurately reported according 
to the protocol, trial SOPs, and in compliance with ICH GCP. The audits will also include 
laboratory activities for the collected blood samples according to an agreed audit schedule. 
The Clinical Trials and Research Governance Office in Oxford may carry out an audit to 
ensure compliance with the protocol, GCP and appropriate regulations. 
13.5 Trial Registration and Monitoring 
The trial will be registered on the clinical trial registry before participant enrolment into the 
study. The trial will be monitored as a behavioural intervention by the monitoring department 
of the Clinical Trials Facility (CTF) at KEMRI-Wellcome Trust Research Programme 
(KWTRP). Regular monitoring will be performed according to International Council for 
Harmonisation (ICH) Good Clinical Practice (GCP) and a Monitoring Plan. Monitors will 
check whether the clinical trial is conducted, and data are generated, documented, and 
reported in compliance with the protocol, GCP and the applicable regulatory requirements. 
14.0 INTELLECTUAL PROPERTY 
Any intellectual property rights that arise from the work will be safeguarded according to the 
current KEMRI guidelines and the Industrial Property Act of 2001, sections 32, 58 and 80 and 

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APHRC guidelines. The scientific and intellectual contributions of all persons involved in the 
research will be appropriately acknowledged in all publications and presentations arising from 
the work. 
15.0 TIME FRAME/DURATION OF THE TRIAL 
Activities 
2022 
2023 
2024 
Q3  
Q4  
Q1  
Q2  
Q3  Q4  
Q1  
Protocol development and internal 
review  
 
 
 
 
 
 
 
 
 
 
Engagement with the Kilifi and 
Nairobi County Department of 
Health and the SMS company 
 
 
 
 
 
 
 
 
 
 
 
Ethical board reviews (SERU, PPB, 
NaCOSTI, OxTREC) and trial 
registration 
 
 
 
 
 
 
 
 
 
 
 
 
Pre-study focus groups and 
community engagement 
 
 
 
 
 
 
 
 
 
 
 
Audit of phone ownership and ASM 
availability, enrolment, and 
randomisation 
 
 
 
 
 
 
 
 
 
 
 
Roll out the SMS trial: sample 
collection and assessment  
 
 
 
 
 
 
 
 
 
 
 
Data cleaning, entry, and analysis 
 
 
 
 
 
 
 
 
 
 
 
Report writing and close out 
 
 
 
 
 
 
 
 
 
 
 
 
16.0 ETHICS  
Ethical approval will be sought from the Oxford Tropical Research Ethics Committee 
(OxTREC), KEMRI Scientific & Ethics Review Unit (SERU), Pharmacy and Poisons Board 
and NACOSTI. 

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16.1 Human Subjects 
The SMS trial will be conducted in accordance with the latest version of the Declaration of 
Helsinki, ICH Good Clinical Practice and all local regulatory requirements. The safety of the 
participants will be monitored throughout the trial. All patients will have access to routine 
care at the study clinics in Kilifi and Nairobi. Since the ASM plasma levels will be 
determined at the end of the study, the investigators will not be aware of any non-adherence 
based on optimal or detectable levels, but all participants will be informed of the importance 
of adhering to their ASMs during clinic visits as part of routine care. 
16.2 Informed Consent and/or Assent 
The consent/assent form (for children aged 13 to 17 years old) will be explained to the 
participant and / or their carer by a fieldworker. The participant and / or their carer will be 
asked to sign the form or use an ink stamp to provide a thumb print. The consent forms will 
be in English and translated into Swahili and Giriama (for the Kilifi site). Adults will give 
individual consent, unless the participant is unable to, in which case a close 
caretaker/parent/guardian will be approached to give consent on behalf of the participant or as 
a witness. Parents will give consent on behalf of participating children, with those between 
13-17 years allowed to give assent in addition to parental consenting. 
16.3 Compensation 
It may take the participant at least 3 hours for clinical and neurological assessments at the 
epilepsy clinic, including the informed consent/assent process, undergoing clinical evaluation 
to determine seizure semiology, neurological and physical exam and to record EEGs; and 
answering questions related to stigma experiences and perceived quality of life. Participants 
invited to the clinics will be provided with meals (or KSH 200 if the COVID situation is 
restrictive) and reimbursed transport (based on individual place of residence) and out of 
pocket expenses (KSH 350) for the Kilifi site. Transport will be reimbursed based on travel 
and meals will be provided. In the Nairobi site, APHRC will reimburse participants with a flat 
rate of KSH 1000 to cover all expenses. 
16.4 Patient Data Protection/Confidentiality 
Participants will be assured about confidentiality of the personal details obtained from them 
since seizure disorders are associated with stigma in most rural areas of Kenya (Mbuba et al., 
2012b). We will deliberately explain to community members and PWE that epilepsy is not a 

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mental health disorder in all communications and that people with either conditions should 
not be stigmatised. Any clinical interviews will be carried out in private rooms. The messages 
will not have any personally identifiable information to ensure privacy of the participants. 
Caregivers/members of the household, especially those who receive messages on behalf of 
PWE will also be encouraged to handle the messages with confidentiality to prevent access of 
the messages by others outside the household which may lead to stigmatisation or breach of 
confidentiality. We are also running community awareness studies as part of the EPInA 
studies to reduce the enacted and perceived stigma around epilepsy. All current COVID-19 
mitigation protocols will be adhered to during clinic visits including wearing of masks, social 
distancing, sanitising and temperature checks in line with the Ministry of Health guidelines. 
Participants will be provided with contact details of investigators for any enquiries and 
clarifications.  
16.5 Data Sharing 
Individual-level anonymized data will be shared with the Sponsor. Summary-level statistical 
analyses will be shared with wider stakeholder engagement and the medical community. 
Information collected or generated during this study may be anonymised for use to support 
new research on epilepsy. Any future research using information from this study must first be 
approved by a local or national expert committee to make sure that the interests of 
participants and their communities are protected. Data will be managed by the data 
governance committee of KEMRI CGMRC. 
16.6 Safety 
The study team will employ epilepsy clinicians to provide medical care to participants during 
the study follow-up period for epilepsy-related complicated managed in epilepsy clinics in 
Kilifi and Nairobi. The study team will not become responsible for long-standing chronic 
conditions that were present before vaccination, or those that are unrelated to epilepsy and 
psychiatric comorbidity.  
16.7 Stakeholder and community engagement 
Community members will be informed and educated about the study through local radio 
announcements and chief’s meetings (observing COVID-19 containment measures). Public 
engagement in Kilifi will be conducted through KEMRI Community engagement Advice for 
STudies (CAST) of which Community Liaison Group (CLG) is a member.  

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The following groups/offices will be targeted for community engagement:  
(i) The Sub-County Health Management Team (SCHMT).  
(ii) The County health research office.  
(iii)The Chiefs and Assistant chiefs within the KHDSS and  
(iv) KEMRI Community representatives – to be informed about the study as they are 
community representatives. 
The aim of these engagements will be to establish buy-in on the use of mobile technology to 
improve adherence to ASMs. We will be keen to deduce pre-study community perceptions on 
epilepsy and adherence to treatment as well as type, frequency, and timing of the messages. 
During the study, the CLG and CAST groups will be useful avenues for targeted community 
engagement or sensitizations to ensure the planned engagements do not increase 
stigmatization against people with epilepsy who have poor response to treatment or unwanted 
side effects. 
17.0 COVID-19 MITIGATION 
All study staff will follow COVID-19 safety measures as described below: 
(i) 
Ensure attendance of all trainings on rational use of Personal Protective Equipment 
(PPE) and infection prevention and control as regards COVID-19 as scheduled by the study 
coordinator  
(ii) 
Sit only at designated marked areas at their workstation and ensure 2-meter physical 
distance between themselves and others  during field visits 
(iii) 
Invite a limited number of participants for interviews on allocated days as per an 
agreed schedule for studies sharing space workspaces.  
(iv) 
Ensure participants invited to the clinic are seated at a designated tent outside when 
waiting their turn to avoid overcrowding with patients at the waiting areas.   
(v) 
Disinfect all frequently touched surfaces after each participant assessment   
(vi) 
Disinfect hands frequently with available sanitisers  and carry extra sanitisers to offer 
to potential participants during field visits 
(vii) 
Adhere to Programme COVID-19 measures of temperature checkpoints at entry points 
(viii) Wear their mask correctly at all times 
(ix) 
Carry extra masks during field visits to offer to participants who inadvertently do have 
their own 

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(x) 
Do not exceed more than 5 people (including the driver) in Programme vehicles 
during field visits 
(xi) 
Set off early when planning to visit far-flung sites to ensure KWTRP and APHRC 
vehicles are back on campus by 3PM to allow for disinfection as per current KWTRP  and 
APHRC COVID-19 containment measures 
(xii) 
Plan reconnaissance visits for studies with activities outside KWTRP to identify 
suitable venues that will allow for adherence to KWTRP, APHRC, County and National 
COVID-19 guidelines 
Study participants will also be expected to always wear masks during study activities and 
those who show up without masks will be offered disposable masks. Participants visiting the 
clinics will be expected to adhere to institutional guidelines of handwashing, sanitizing, social 
distancing, and temperature checkpoints. 
 
The study coordinators and site investigators will be in-charge of ensuring these measures are 
adhered to and KWTRP and APHRC Health and Safety teams will conduct spot-checks to 
ensure compliance.  
18.0 ARCHIVING AND RECORD RETENTION 
The PI, co-investigators, and clinical research staff will have access to records. The 
investigators will maintain appropriate medical and research records for this study, in 
compliance with ICH E6 GCP, GDPR, regulatory and institutional requirements for the 
protection of confidentiality of participants. The investigators will permit authorized 
representatives in Oxford, and regulatory agencies to examine (and when required by 
applicable law, to copy) clinical records for the purposes of quality assurance reviews, audits, 
and evaluation of the study safety and progress. The master files including a copy of the final 
completed CRFs, as well as all source documentation will be maintained at KEMRI CGMRC 
retained by the PI and one copy will be maintained by the Sponsor, who will ensure that it is 
stored with other study documents, such as the signed informed consent/assent forms, 
protocol, the investigator’s brochure, and any protocol amendments, in a secure place 
following local regulations. The final study database will be securely kept with all archive 
tables for at least 25 years. Paper CRFs and study files at KEMRI CGMRC will be archived 
following local laws. 

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19.0 FINANCING AND INSURANCE 
19.1 Budget for each site 
  
USD $ 
Ksh 
a) Personnel, salaries, and benefits disbursements 
100,575.00 10,561,974.00 
b) Patient costs, travel, food, accommodation and/or supplies 
52,060.00 
13,338,000.00 
c) Equipment (SMS software and support) 
132,294 
297,000 
d) Supplies 
  
  
Laboratory consumables: blood draws and analyses at 
CREATES 
60,718.00 
22,494,600.00 
Clinical consumables: at epilepsy clinic 
24,278.00 
432,000.00 
e) Travel and accommodation 
  
  
Local (Nairobi) 
5,750 
782,000 
International to Oxford 
20,110 
3,950,000 
f) Transportation, vehicle repairs and field visits etc  
26,540 
4,700,000 
g) Operating expenses postage, printing etc.  
4,850 
1,500,000 
h) Contingency fees (15% of above) 
64,076.25 
8,708,400 
Total 
427,175.00 66,763,974.00 
 
19.2 Justification of the Budget 
Salaries are required for the project coordinator for the study, who will help with the study 
implementation, 3 clinicians to help with screening and clinical care for participants, and 4 
fieldworkers to help with recruitments, administration of questionnaires and household visits. 
The project will generate enough data for use in PhD studies, but there will be separate 
arrangements to fund this beyond the period of data collection. Some costs will go towards 
EEG consumables and MRI scans for routine investigations. We will contract a SMS software 
company to develop, set up and support the SMS messaging application system. Tablets and 
computers are needed for online data collection and capture. Meals and reimbursements for 
fares will be provided. Fuels for motorbikes and a car are needed for recruitment of 
participants, and for doing follow-ups in the community. Stationeries are needed for record 
keeping and for making reports. This work is funded by a NIHR grant. 
19.3 Insurance 
The University of Oxford will sponsor the study and provide insurance for the trial. The 
University of Oxford has a specialist insurance policy in place which would operate in the 
event of any participant suffering harm because of their involvement in the research. 

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20.0 REPORTING, DISSEMINATION AND NOTIFICATION OF RESULTS 
The findings of this study will made available through publications in scientific journals. We 
will feedback individual results with clinical relevance to participants in real-time. Summaries 
of the outcomes of the trial will be provided during community meetings in the areas from 
which participants are recruited This work will also be presented at local and international 
conferences as posters or platform presentations and at key policy meetings concerning 
epilepsy. In addition, we will upload videos on a YouTube channel and other online platforms 
to help dispel epilepsy-related stigma. Positive messaging on epilepsy will also be shared 
through barazas (community meetings), local newspaper articles and discussions on the radio 
and television based on information from oral histories. Caution will be taken to ensure 
participants are not remotely identifiable through face blurring and voice masking 
technologies. 
21.0 REFERENCES 
Berhanu, S., et al., 2009. Primary care treatment of epilepsy in rural Ethiopia: Causes of default from follow-up. 
Seizure. 18, 100-103. 
Chen, Z.J., et al., 2012. Simultaneous determination of valproic acid and 2-propyl-4-pentenoic acid for the 
prediction of clinical adverse effects in Chinese patients with epilepsy. Seizure. 21, 110-7. 
Cole-Lewis, H., Kershaw, T., 2010. Text messaging as a tool for behavior change in disease prevention and 
management. Epidemiol Rev. 32, 56-69. 
De Costa, A., et al., 2010. Design of a randomized trial to evaluate the influence of mobile phone reminders on 
adherence to first line antiretroviral treatment in South India--the HIVIND study protocol. BMC Med 
Res Methodol. 10, 25. 
de Jongh, T., et al., 2012. Mobile phone messaging for facilitating self-management of long-term illnesses. 
Cochrane Database Syst Rev. 12, Cd007459. 
de Tolly, K., et al., 2012. Investigation into the use of short message services to expand uptake of human 
immunodeficiency virus testing, and whether content and dosage have impact. Telemed J E Health. 18, 
18-23. 
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22.0 APPENDICES 
22.1 Roles of Investigators 
Symon Kariuki: the principal investigator for the study will be involved in the overall 
supervision of implementation of the study, will identify a contact to provide the pen and ink 
line drawings for the scanned graphics, and writing up of the findings for publication. 
Mercy Atieno: EPInA study project coordinator who will help with study implementation; 
statistical analyses; and writing up of the findings for publication. 
County Department of Health representative: to be the contacts / liaison persons for the MoH. 
Gilbert Katana and Maria Mumbo: will provide the clinical data for study participants. 
Collins Kipkoech: will select the participants, send out SMS and manage data. 
Mary Bitta: She has experience in public mental health and will share her experiences setting 
up and running the mhGAP trial.  

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Gershim Asiki- is a research scientist with interests in Public Health, Health systems, 
Maternal and Child Health, non-communicable diseases, and HIV 
Damazo Kadengye- is a Biostatistician and Research Epidemiologist with over 17 years of 
multidisciplinary experience in public health and educational sciences. He is mostly interested 
in research projects that espouse Implementation Science or Impact Evaluation theories, and 
making effective use of data and data systems to enhance evidence-informed policy-making 
processes that inform development investments. He will be involved in data analyses and 
modelling in the Nairobi site. 
Fredrick Wekesah- is a chronic disease epidemiologist and a postdoctoral research scientist at 
APHRC. His research interests span non-communicable diseases and adolescent mental 
health. He will be involved in project implementation in the Nairobi site. 
Peter Otieno- is a PhD candidate and a Research Officer at APHRC based in Nairobi, Kenya. 
His interests are in implementing studies on health system strengthening through the 
development of evidence-based decision models to inform public health policy. He will be 
involved in project implementation in the Nairobi site. 
Sloan Mahone – historian with extensive experience of working in Africa and other LMICs, 
specific expertise in acquiring oral histories, keen interest in studying neurological illness. 
She will be involved in the post-study questionnaire and the writing up of the findings for 
publication. 
Arjune Sen– head of Oxford Epilepsy Research Group, topic advisor to NICE epilepsy 
guidelines, ILAE Council member, and consultant epileptologist. He is leading the project 
from Oxford including coordination of activities of collaborating institutions. . 
Charles Newton: the co-principal investigator and concept originator will continue to 
facilitate the communications between KEMRI, University of Oxford; assist with study 
proposal writing, contribute to design of the text and graphic messaging content; and the 
writing up of the outcomes for publication.