A Pilot Study Evaluating Sleep, Stress, and Infant Nutrition Using a Chatbot With Parents of Preterm and Full-term Infants
Conditions: Preterm Birth, Healthy
Sponsor: Danone Asia Pacific Holdings Pte, Ltd.

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 1 of 39 
 
 
STUDY PROTOCOL 
 
 
Study Number 
OBVIO-DAN-003 
Title 
A pilot study evaluating sleep, stress, and infant 
nutrition using a chatbot with parents of preterm 
and full-term infants 
Sponsor 
Danone 
Country 
Singapore 
Date 
31AUG2018 
Version Number 
3 
 
 
 

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 2 of 39 
 
Table of Contents 
1 
Investigator Signature Page ............................................................................................ 4 
2 
Sponsor Team Signature Page ......................................................................................... 5 
3 
Abbreviations ................................................................................................................. 7 
4 
Synopsis…. ..................................................................................................................... 8 
5 
Introduction ................................................................................................................. 13 
6 
Objectives of the Trial ................................................................................................... 15 
6.1 
Primary Objective .......................................................................................................... 15 
6.2 
Secondary Objective ...................................................................................................... 15 
6.3 
Exploratory Objective .................................................................................................... 15 
7 
Trial Design .................................................................................................................. 16 
7.1 
Study Calendar .............................................................................................................. 16 
7.2 
Type of Trial ................................................................................................................... 16 
7.3 
Endpoints ...................................................................................................................... 16 
7.3.1 
Primary Endpoint ........................................................................................................ 16 
7.3.2 
Secondary Endpoint .................................................................................................... 16 
7.3.3 
Exploratory Endpoint .................................................................................................. 17 
7.4 
Participants and Location ............................................................................................... 17 
7.4.1 
Participants ................................................................................................................. 17 
7.4.2 
Centers ........................................................................................................................ 17 
7.5 
Study Duration............................................................................................................... 17 
8 
Study Population .......................................................................................................... 18 
8.1 
Subject Inclusion Criteria ................................................................................................ 18 
8.2 
Subject Exclusion Criteria ............................................................................................... 18 
8.3 
Subject Withdrawal Criteria ........................................................................................... 19 
9 
Assessment of Safety .................................................................................................... 21 
10 Execution of the Trial .................................................................................................... 22 
10.1 
Screening and Enrollment .............................................................................................. 22 
10.2 
Study Period .................................................................................................................. 23 
10.3 
Data Collection .............................................................................................................. 23 
10.4 
Compliance .................................................................................................................... 24 
10.5 
End of Study .................................................................................................................. 24 
10.6 
Application Description .................................................................................................. 24 
10.7 
Monitoring .................................................................................................................... 25 
10.8 
Computerized Data Entry - Security and Privacy of User Data .......................................... 26 
10.9 
Computerized Edit Checks .............................................................................................. 26 
10.10 
Audit Trail .................................................................................................................. 26 
11 Statistics…. ................................................................................................................... 27 
11.1 
Sample size calculations ................................................................................................. 27 

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 3 of 39 
 
11.2 
Datasets to be analyzed ................................................................................................. 27 
11.2.1 Intent-to-treat (ITT) analysis dataset ........................................................................ 27 
11.2.2 Per Protocol (PP) analysis dataset ............................................................................. 27 
11.3 
Statistical Analysis ......................................................................................................... 27 
12 Legal and Ethical Prerequisites ...................................................................................... 29 
12.1 
Legal Requirements ....................................................................................................... 29 
12.2 
Ethical Aspects ............................................................................................................... 29 
12.2.1 Protection of the Subject's Confidentiality ............................................................... 29 
12.2.2 Informed Consent...................................................................................................... 29 
12.2.3 Ethics Committee Approval ....................................................................................... 30 
12.2.4 Declaration of Helsinki .............................................................................................. 30 
13 Quality Control and Quality Assurance .......................................................................... 31 
13.1 
Monitoring .................................................................................................................... 31 
13.2 
Quality Control of Essential Documents .......................................................................... 31 
13.3 
Responsibilities of the PI ................................................................................................ 32 
14 Study End Procedures ................................................................................................... 33 
14.1 
Premature Termination of Study .................................................................................... 33 
14.2 
Termination of Study ..................................................................................................... 33 
15 References ................................................................................................................... 34 
16 Appendices ................................................................................................................... 35 
APPENDIX I: 
Chatbot Study Screening eQuestionnaire ..................................................... 35 
APPENDIX II: 
Usability of Chatbot and ClaimIt eQuestionnaire .......................................... 38 
 
 
 

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 4 of 39 
 
1 Investigator Signature Page 
 
PRINCIPAL INVESTIGATOR (PI)  
 
Principal Investigator: 
Dr. Chua Mei Chien 
 
 
 
 
 _________________________ 
Date 
 _________________________ 
Signature 
 
 
I have read this protocol and agree that it contains all necessary details for carrying out this study. 
I will conduct the study as outlined herein and will complete the study within the time designated.  
I will provide copies of the protocol and all pertinent information to all individuals responsible to 
me who assist in the conduct of this study. I will discuss this material with them to ensure they 
are fully informed regarding the conduct of the study. 
I will only use the informed consent language approved by the sponsor or its representative and 
will fulfill all responsibilities for submitting pertinent information to the Independent Ethics 
Committee (IEC) and/or Institutional Review Board (IRB) responsible for this study. 
I agree that the sponsor or its representatives shall have access to any source documents from 
which case report form information may have been generated. 
 
 

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 5 of 39 
 
2 Sponsor Team Signature Page 
 
CLINICAL PROGRAM LEADER 
 
Agathe Foussat 
Senior Digital Program Leader 
Research and Innovation -  
Early Life Nutrition 
Danone Nutricia 
 
 ______________________ 
Date 
 ______________________ 
Signature 
PROJECT SCIENTIFIC DIRECTOR 
 
Ruurd Van Elburg 
Preterm Science and Program Director  
Research and Innovation 
Early Life Nutrition  
Danone Nutricia 
 
 ______________________ 
Date 
 ______________________ 
Signature 
 
BIOSTATISTICIAN (CRO) 
 
Jerrod Nelms, PhD, MPH 
Director, Biostatistics 
ObvioHealth 
 
 ____________________  
Date 
 ____________________ 
Signature 
12/11/2018
12 Nov 2018

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 6 of 39 
 
OBVIOHEALTH PROGRAM LEADER 
 
Camisha Harge 
Senior Director, Clinical Operations 
ObvioHealth 
 
 ______________________ 
Date 
 ______________________ 
Signature 
 
 
 
 
 
 

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 7 of 39 
 
3 Abbreviations 
 
CDM 
Clinical Data Manager 
CPM 
Clinical Project Manager 
CRO 
Contract Research Organization 
eCRF 
Electronic Case Report Form 
GCP 
Good Clinical Practice 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
ICU 
Intensive Care Unit 
 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
PI 
Principal Investigator 
SOP 
Standard Operating Procedure 
TMF 
Trial Master File 
 
 
 
 

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 8 of 39 
 
4 Synopsis 
 
Study Title 
A pilot study evaluating sleep, stress and infant nutrition using a 
chatbot with parents of preterm and full-term infants 
 
Study Objectives  
Primary Objective: 
To generate real-life, in-home data from parents with infants 
(preterm and full-term) on sleep, stress, and infant nutrition via the 
study chatbot  
Secondary Objective: 
To investigate differences in data obtained from parents of preterm 
infants versus data obtained from parents of full-term infants on 
sleep, stress, and infant nutrition 
Exploratory Objective: 
To evaluate the usability of ClaimIt, the study chatbot, and chatbot 
tools in general, among this population 
Study Design 
An observational study of parents with infants (preterm and full-
term) 
Study Observation 
Duration 
28 days per family 
Country of 
Implementation 
Singapore 
Study Population  
 
• 20 parents with healthy preterm infants (born at <37 weeks of 
gestation), age 0-6 months and discharged from the hospital at 
time of enrollment 
• 20 parents with healthy full-term infants (born at ≥37 weeks of 
gestation), age 0-6 months and discharged from the hospital at 
time of enrollment 

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 9 of 39 
 
Inclusion Criteria 
 
Subjects (parent and infant) must meet the following criteria: 
• Healthy infants (preterm and full-term) must be 0-6 months of 
age at time of enrollment 
• Infants must be at home (discharged from the hospital) at time 
of enrollment 
• Informed consent from parent whose age is ≥21 years  
• Parent must be proficient in the English language 
• Parent must be able to comply with the required study tasks, as 
per PI’s judgment 
• In-home access to reliable internet connections; a mobile device 
suitable for electronic communication 
Exclusion Criteria 
Infant must not meet any of the following criteria: 
• Known to have current or previous illnesses/conditions which 
could interfere with the study outcome (per PI’s clinical 
judgment)  
• Must not be currently participating in any other clinical study  
Parent must not meet any of the following criteria: 
• Must not be known to have a significant medical condition that 
might interfere with the study (per PI’s clinical judgment) that 
meets one of the following criteria: 
o Presence of current mental illness or history of mental 
illness 
o Any acute or chronic illness that makes the parent 
unsuitable for the study based on the PI's judgment 
• Must not be a single parent 
• Inability of the parent to comply with the study protocol or PI’s 
uncertainty about the willingness or ability of the parent to 
comply with the protocol requirements 
 
Endpoints 
 
Primary:  
Obtaining records of sleep, stress, and infant nutrition from parents 
of infants (preterm and full-term) through interaction with the study 
chatbot   

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 10 of 39 
 
Secondary: 
Comparison of the data obtained from parents of preterm infants 
and parents of full-term infants on sleep, stress, and infant nutrition  
Exploratory: 
An evaluation of the usability of ClaimIt, the study chatbot and 
chatbot tools in general, among this population   
Study 
Implementation 
Prescreening 
• 
Participants (parents and infants [preterm or full-term]) will 
be recruited by study team personnel in the Department of 
Neonatology at KK Women's and Children's Hospital  
• 
Upon successfully fitting the basic eligibility criteria, the 
parent will be provided:  
o Informed Consent Form (ICF) for review 
 The parent will have the opportunity to ask 
questions and receive answers from study team 
personnel 
o Access to the ClaimIt app along with the following 
information: 
 Overview of trial tasks and relevant notifications 
 ClaimIt navigation instructions: How to interact 
with the ClaimIt app during the study period 
 
 Additional study details & instructions   
 All relevant contact information that may be 
required during the study 
 
 

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 11 of 39 
 
Screening and Enrollment  
• 
Upon signing the ICF, the parent will be asked to respond to 
a detailed eQuestionnaire (Appendix I) to assess eligibility 
• 
If all the inclusion and none of the exclusion criteria are 
satisfied, the PI will enroll the subjects into the study 
• 
Upon enrollment, the parent will be provided full access to 
the study chatbot along with the following information: 
o How to connect to the study chatbot  
o Overview of trial requirements & parameters 
o The Chatbot navigation: How to interact with the study 
chatbot during the 28-day period 
o Overview of notifications related to trial activities  
o Additional study details & instructions  
Data Collection Period 
• 
The parent will be asked to regularly interact with the study 
chatbot on three (3) topics, three (3) days a week (suggested 
schedule: M, W, F) for 28 days 
• 
Through regular interaction with the study chatbot, records 
of parents’ sleep, stress, and infant nutrition will be obtained  
End of Study  
• 
At the end of the 28-day data collection period, the parent 
will be asked to complete an eQuestionnaire about the 
usability of the study chatbot and ClaimIt (Appendix II) 
Statistical 
Considerations 
 
A sample size of 40 parents and their infants is estimated with the 
following considerations: 
• Descriptive summary statistics for the categorical and 
quantitative data will be reported 

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 12 of 39 
 
 
 
 
• Expected dropout rate of ≤10 subjects (if the dropout threshold 
of 10 is reached, up to 10 additional subjects may be replaced at 
the sponsor's discretion) 
• A subject will be considered to have dropped out if they are 
determined to be non-compliant 
Ethical 
Considerations 
This study should be performed in accordance with the ethical 
principles based in the Declaration of Helsinki and its subsequent 
amendments, and in accordance with the International Council for 
Harmonisation (ICH) Good Clinical Practice (GCP) guideline (ICH 
E6(R1), 1996) and applicable regulatory requirements. 

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 13 of 39 
 
5 Introduction  
An estimated 15 million infants, slightly more than 1 in 10, are born preterm each year 
worldwide.1 Approximately 60% of those are born in South Asia and sub-Saharan Africa.1 As 
the leading cause of death in children under the age of 5 years, about one million preterm 
infants die each year worldwide due to preterm birth complications, with a significantly 
greater mortality rate in low-income countries compared to high-income countries.1 
Consequently, given the significance of meticulous care required for the preterm infants, 
healthcare providers and parents play a central role in assuring proper care of these 
vulnerable children. 
Parental involvement in caring for infants can lead to anxiety, worry, and psychological 
distress. In a follow-up clinic evaluation of parents and their premature infants, many 
reported parental concerns about medical and developmental outcomes were unsupported 
by their child’s diagnosis.2 In a study done with parents of late-preterm infants (≥34 to <37 
weeks gestation), mothers reported significantly more stress than fathers on the Parent 
Stress Index (PSI-3), a tool designed for the early identification of parental and familial 
characteristics that fail to foster normal development and function in children.3 An 
assessment of maternal psychological distress in singleton versus multiple-birth preterm 
infants found that mothers of multiples had greater posttraumatic stress symptoms, anxiety 
at discharge and depressive symptoms at six months as compared to mothers of singletons.4  
Among mothers of school-aged children who were born late preterm and admitted to an 
intensive care unit (ICU), there was a significant 18-fold increase in total stress compared to 
stress among mothers of full-term children.5 In a parallel study group involving mothers of 
school-aged children who were born late preterm, but not admitted to the ICU, there was a 
24-fold increase in total stress when compared to the mothers of full-term children.5 Overall, 
multiple studies have demonstrated that parental stress, anxiety, and psychological distress 
are not only short-term problems when caring for a preterm infant, but may also have long-
lasting effects. 

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 14 of 39 
 
In this study, data will be collected comparing infant nutrition, stress, and sleep in parents 
of both preterm infants and full-term infants (after they have been discharged from the 
hospital), using a chatbot application. A chatbot is defined as, “an instant messaging account 
that is able to provide services using instant messaging frameworks with the aim of providing 
conversational services to users in an efficient manner.” In short, a chatbot can respond to 
a user as though they are communicating with another person via instant messenger, except 
there is a computer on the other end.6 The chatbot application in this study is designed to 
provide an interactive tool for the parents to provide input on infant nutrition and parent 
stress and sleep.  
 
 

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 15 of 39 
 
6 Objectives of the Trial 
6.1 Primary Objective 
To generate real-life, in-home data from parents with infants (preterm and full-term) 
on sleep, stress, and infant nutrition via the study chatbot. 
6.2 
Secondary Objective 
To investigate differences in data obtained from parents of preterm infants versus 
data obtained from parents of full-term infants on sleep, stress, and infant nutrition. 
6.3 
Exploratory Objective 
To evaluate the usability of ClaimIt, the study chatbot, and chatbot tools in general, 
among this population. 
 
 

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 16 of 39 
 
7 Trial Design 
7.1 Study Calendar 
Schedule of Activities 
Prescreening 
Screening and 
Enrollment 
Data 
Collection 
End of Study 
Basic study information 
provided to parents 
X 
- 
- 
- 
Inclusion/exclusion 
criteria met 
X 
X 
- 
- 
Review of Informed 
Consent Form (ICF) and 
consent provided by 
parent 
- 
X 
- 
- 
Chatbot app and 
instructions provided 
- 
X 
- 
- 
28-day data collection via 
study chatbot  
- 
- 
X 
- 
Chatbot/ClaimIt usability 
eQuestionnaire 
- 
- 
- 
X 
 
7.2 Type of Trial 
This is an observational study of 40 parent and infant pairs (20 parents of preterm 
infants, 20 parents of full-term infants) residing in Singapore. 
7.3 Endpoints 
7.3.1 Primary Endpoint 
Obtaining records of sleep, stress, and infant nutrition from parents of infants 
(preterm and full-term) through interaction with the study chatbot   
7.3.2 Secondary Endpoint 
Comparison of the data obtained from parents of preterm infants and parents 
of full-term infants on sleep, stress, and infant nutrition obtained via the study 
chatbot   

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 17 of 39 
 
7.3.3 Exploratory Endpoint 
An evaluation of the usability of ClaimIt, the study chatbot and chatbot tools 
in general, among this population. 
7.4 Participants and Location 
7.4.1 Participants 
Parents of healthy infants (preterm and full-term) residing in Singapore will be 
recruited through the prescreening process. Subjects will be identified by the 
site study staff and a brief explanation of the study will be provided to the 
parent.  
7.4.2 Centers 
Participants will be recruited through the Department of Neonatology at KK 
Women's and Children's Hospital. After the screening visit, infants and parents 
will not be required to visit a physical trial site (unless reconsent is required). 
Communication between parents and study personnel will be conducted via 
the ClaimIt platform and/or over the telephone or email messaging, as 
appropriate. 
7.5 Study Duration 
It is expected that the enrollment period will be four (4) months in total. 
For each subject pair, the total study duration beginning with the initiation of 
recruitment and screening (approximately 3 weeks); 28 days of data collection; 
administration of a feedback eQuestionnaire; and follow-up monitoring, is expected to 
be approximately 7-8 weeks total. 
 
 

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 18 of 39 
 
8 Study Population 
Subjects (parent and infant) must meet the following: 
8.1 Subject Inclusion Criteria 
• 
Healthy infants (preterm [born at <37 weeks of gestation] and full-term [born at 
≥37 weeks of gestation]), 0-6 months of age at time of enrollment 
• 
Infants must be at home (discharged from the hospital) at time of enrollment 
• 
Informed consent from the parent (whose age is ≥21 years) 
• 
Parent must be proficient in the English language 
• 
Parent must be able to comply with the required study tasks, as per PI’s judgment 
• 
In-home access to reliable internet connections and a tablet and/or mobile device 
suitable for electronic communication 
8.2 Subject Exclusion Criteria 
To be considered for enrollment, the subjects must not meet any of the exclusion 
criteria listed below: 
Infants: 
• Known to have current or previous illnesses/conditions which could interfere with 
the study outcome, as per PI’s clinical judgment  
• Must not be currently participating in any other clinical study  
Parent of infants: 
• Must not be known to have a significant medical condition that might interfere 
with the study (per PI’s clinical judgment) that meets one of the following criteria: 
o Presence of current mental illness or history of mental illness 
o Any acute or chronic illness that makes the parent (subject) unsuitable for the 
study based on the PI's judgment 
• Must not be a single parent 
• Inability of the parent to comply with the study protocol or PI’s uncertainty about 
the willingness or ability of the subject to comply with the protocol requirements 

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 19 of 39 
 
8.3 Subject Withdrawal Criteria 
Subjects may be withdrawn from the study at any time for any reason, including but 
not limited to: 
1) At their request or the request of the legally authorized representative. 
2) If, in the PI's opinion, continuation in the study would be detrimental to the parent 
or infant’s well-being. 
3) Non-compliance (failure to complete five [5] or more consecutive sessions), at the 
discretion of the PI (a situation where the parent consistently does not adhere to 
the study procedures). 
4) Protocol deviation(s) which, in the opinion of Sponsor, warrant discontinuation from 
study (e.g., violation of inclusion and/or exclusion criteria). 
A dropout of ≤10 families is built into the estimated total sample size. If the dropout 
threshold of 10 is reached, up to 10 additional participants may be replaced at the 
sponsor’s discretion. The PI must make every effort to contact parents that are lost to 
follow-up. Attempts to contact the parent must be documented in the family’s record 
(e.g., dates and times of attempted telephone/email contact). 
The primary analysis will be an ITT (Intent-to-Treat) analysis; all enrolled families who 
engage with the study chatbot for at least one complete interaction (on all three topics) 
will be included in the final comparative analysis. The number and percentage of 
subjects who withdraw early and their reasons for withdrawal will be presented in a 
table and the equivalent of a CONSORT flow diagram.  
The following information will be documented in the mother and infant/toddler’s 
record in the event of a subject’s withdrawal from the study: 
I. 
Date of withdrawal 
II. 
Reasons for withdrawal 

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 20 of 39 
 
Even if consent is withdrawn, all data that were acquired before consent was 
withdrawn will be maintained. 
 
 

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 21 of 39 
 
9 Assessment of Safety 
As this is an observational study and the study procedures present no more than minimal 
risk, adverse events are not expected and therefore will not be collected or reported for this 
study.  
 
 
 

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 22 of 39 
 
10 Execution of the Trial 
10.1 Screening and Enrollment 
Prescreening: 
1. Prescreening will be conducted through the Department of Neonatology at KK 
Women's and Children's Hospital with parents of healthy infants (preterm and full-
term) residing in Singapore. Study personnel will assess alignment with the 
inclusion and exclusion criteria of the study and capability and willingness of the 
parent to comply with all aspects of the study design.  
2. If the prescreening suggests that the infant and parent are appropriate for study 
inclusion, the parent will have an opportunity to review and ask questions about 
the ICF. 
3. The decision to participate in the study is entirely voluntary by the parent. The PI 
and/or his/her designee(s) must emphasize to the parent that the consent to 
participate can be withdrawn at any time, without penalty or loss of benefits to 
which the subject is otherwise entitled. 
4. The informed consent process will be managed on-site at the KK Hospital, 
supported as necessary by study personnel. If the parent agrees to participate, 
they will voluntarily sign the ICF prior to the conduct of any study related 
procedures. 
Note:  During the study, any amendments to the ICF and/or protocol (outside of 
defined parameters) must be approved by the IRB prior to use/distribution. Based 
on the assessment of the IRB, the subjects may be required to review and re-sign 
the revised ICF to remain in the study. 

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 23 of 39 
 
Screening and Enrollment: 
1. After the ICF is voluntarily signed, the parent will respond to a detailed 
eQuestionnaire (Appendix I). Their responses will be reviewed by the PI (or their 
designee) to further confirm that they and their infant appropriately meet all the 
inclusion and none of the exclusion criteria for the study before being formally 
enrolled.   
2. If all the criteria are met, then the parent and infant will be enrolled in the study.  
Those who do not meet the screening criteria will be informed that they are not 
eligible for the study and dismissed.  
3. Upon enrollment, the parent will be provided access to the study chatbot for 
regular interaction. Approximately 40 parent and infant pairs will be enrolled. 
10.2 Study Period 
The parent will be asked to interact with the study chatbot three times a week (e.g., 
Monday, Wednesday and Friday [suggested schedule]) over a maximum 28-day period. 
During each of those interactions, they will be asked to interact on all three topics: 
sleep, stress, and infant nutrition.  Reminder notifications will be sent via ClaimIt for 
any parent that does not interact with the chatbot per protocol. 
The maximum number of interactions per subject pair is 12 (in total). 
10.3 Data Collection 
Chatbot transcripts will be created based on each interaction between the parent and 
study chatbot.  
eCRFs will be completed by the parent for their infant based on data from: 
• the Screening eQuestionnaire 
• the end-of-study Usability eQuestionnaire   

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 24 of 39 
 
10.4 Compliance 
Compliance with the study expectations will be monitored through the study chatbot’s 
regular use and reported as follows: 
• Compliant: Defined as having completed a total of 7 or more interactions with the 
study chatbot in the 4-week study period 
Note: If only seven (7) sessions are completed with the study chatbot, the five (5) 
missing interactions must not be consecutive 
• Non-compliant: Defined as the failure to complete five (5) or more consecutive 
sessions in the 4-week study period 
Subjects may be withdrawn from the study in the event of non-compliance. 
10.5 End of Study 
At the end of the study, the parent will be asked to complete an eQuestionnaire to 
assess and comment on the usability of ClaimIt, the study chatbot and chatbot tools in 
general (Appendix II). Access to the study chatbot will be discontinued, and the study 
team may contact the parent if there are any outstanding study related queries.   
10.6 Application Description 
The study chatbot is an interactive, conversational application where the parent can 
initiate a conversation with the chatbot, and it will respond appropriately.  In certain 
instances, the study chatbot may also initiate a conversation with parent. The 
application converses with the user through the messaging platform. Transcripts of the 
chatbot conversations will be accessed and reviewed by the study team. 
Completion of the Screening and Usability eQuestionnaires will occur via the ClaimIt 
app for each of the parents. The ClaimIt app is a mobile application available to subjects 
during their period of enrollment so they can perform specific study-related tasks and 
receive and transmit communications from and to the CRO staff. 

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 25 of 39 
 
10.7 Monitoring  
The study will be monitored on an ongoing basis starting from the enrollment of the 
first parent and infant and continuing through the study exit of the last enrolled pair. 
Regular monitoring will be conducted by the designated ObvioHealth personnel during 
the study. The monitoring activities will be detailed in a monitoring plan. The following 
measures are in place to ensure consistent and regular engagement with the parent: 
• Dedicated study personnel will be available for contact with the infant’s parent 
to answer questions about the study, the study chatbot or the ClaimIt app, as 
necessary 
o KKH staff will manage all questions during the recruitment and 
enrollment process. After enrollment, subjects will have the ability to 
contact the KKH Study Coordinator/Study Nurse via the common e-
mail provided for questions related to the study. Participants are 
encouraged to seek advice from their physician for their baby’s health 
related issues. 
o ObvioHealth staff will be responsible for any ClaimIt, app-related 
questions and any other questions routed to them via the ClaimIt app. 
ObvioHealth staff will notify and/or redirect questions to KKH staff, as 
needed. 
• Regular interactions with the study chatbot will determine compliance 
• In some circumstances, the PI or study team personnel may initiate contact with 
the parent to determine compliance with chatbot use and study protocol 
• Study team (Sponsor and CRO members) will review daily compliance with the 
study chatbot  
As the parent and infant are not required to visit a physical site during the study period 
(unless reconsent is required), monitoring will be conducted throughout the study via 

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 26 of 39 
 
remote data reviews. The monitor will check the chatbot transcripts and eCRF data for 
completeness, consistency and any concerning text. If any errors are identified, they 
may be corrected consistent with the Data Handling Conventions (DHC) or may be 
addressed through direct contact with the parent. Concerning text will be 
communicated to the PI who will take appropriate action. 
Protocol deviations will be reported in the monitoring report and a corrective action 
plan implemented, as necessary. The monitor will communicate any detected protocol 
deviations to the PI. These deviations will be recorded in a Protocol Deviation Log. 
10.8 Computerized Data Entry - Security and Privacy of User Data 
All data is hosted on Microsoft Azure service. All ObvioHealth employees and their 
affiliates are bound by strict confidentiality agreements.  Transport Layer Security (TLS) 
is used to secure all data in transit.         
10.9 Computerized Edit Checks 
The database will incorporate the needed programmed edit checks to help ensure 
quality data.  Messages to the parent may be generated automatically to alert him/her 
to any entry error or protocol non-compliance.  
10.10 Audit Trail 
All entries and alterations made in the database will be captured by an audit trail in 
which the individuals accessing the database and providing entries and/or making 
alterations are identified via their user IDs and passwords. 
 
 

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 27 of 39 
 
11 Statistics  
11.1 Sample size calculations 
A sample size of 40 subjects is estimated under the following considerations: 
• 
Descriptive summary statistics for the categorical and quantitative data will be 
reported 
• 
Expected dropout rate of ≤10 subjects (if the dropout threshold of 10 is reached, 
up to 10 additional participants may be replaced at the sponsor’s discretion) 
• 
A subject will be considered to have dropped out if they are determined to be 
non-compliant; however, qualifying chatbot interactions will be included in ITT 
11.2 Datasets to be analyzed 
11.2.1 Intent-to-treat (ITT) analysis dataset  
All parents participating in at least one-day chatbot interactions (on all three 
topics) will be included in the collected data and safety analyses, in accordance 
with the Intent-to-treat (ITT) principle. 
11.2.2 Per Protocol (PP) analysis dataset 
All subjects who have no protocol violations (protocol deviations are permitted 
and reportable) and remained in the study for the full data collection period 
will be included. 
Protocol violations and deviations and study completion data will be evaluated 
through statistical analysis. 
11.3 Statistical Analysis 
Free text qualitative data will be generated from transcripts recorded through daily 
interactions with the study chatbot. The resulting datasets will be analyzed and 
appropriately categorized to sleep, stress, and infant nutrition as primary endpoints 
using the RDQA package in R version 3.4.3. All patterns will be categorized and 
tabulated as appropriate.  

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 28 of 39 
 
 
Descriptive statistical analysis will be performed on data generated from the study’s 
two surveys (Screening, and Usability). Data points from the Screening questionnaire 
will be categorized with like questions in each questionnaire being compared to each 
other as a simple test for within subject consistency. All other variables will be 
presented as univariate and bivariate distributions as appropriate.  
Likert scale data from the Usability Questionnaire will be analyzed using univariate 
descriptive statistics (mean, median, standard deviation) and bi/multivariate 
categorizations as appropriate. As the number of responses will likely be low, open-
ended questions will be reviewed manually for patterns and described in either 
paragraph or tabular form.   
 
 

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 29 of 39 
 
12 Legal and Ethical Prerequisites 
12.1 Legal Requirements 
The study will be conducted after approval from SingHealth Centralised Institutional 
Review Board (CIRB), which follows the guidance of Singapore regulatory bodies and 
general GCP/ICH regulations. 
12.2 Ethical Aspects 
12.2.1 Protection of the Subject's Confidentiality 
Confidentiality of all study participants will be maintained; codes for subject 
identification will be utilized. Subjects will review and consent to the SingHealth 
Data Protection Policy during the informed consent process. 
12.2.2 Informed Consent 
A signed ICF by the parent indicating consent to his/her and his/her infant’s 
participation in the study is required. This will be completed prior to conducting 
any study-related activities and will be done in accordance with all applicable 
regulatory requirements. 
The ICF will inform the parent about all aspects of the parent and infant’s study 
participation. Dedicated study personnel will be available to the parent to 
answer questions about the study or the informed consent. The IRB/EC will 
approve the ICF. Any amendments to these documents must be approved by 
the IRB/EC. 
The parent must sign the ICF prior to the initiation of any study-related 
activities beyond prescreening. Parents must be ≥21 years of age.  
The decision to participate in the study is entirely voluntary. The PI and/or 
his/her designee must emphasize to the parent that the consent to participate 
can be withdrawn at any time without penalty or loss of benefits to which the 
subject is otherwise entitled. 

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 30 of 39 
 
12.2.3 Ethics Committee Approval 
The study protocol will be submitted by the PI for examination by the 
SingHealth Centralised Institutional Review Board (CIRB)/EC.  Commencement 
of the clinical trial is not permitted without written approval of the IRB/EC. 
The IRB/EC must be notified of all subsequent additions or changes in the study 
protocol.  If a protocol amendment and revisions to the consent form are made 
and approved by IRB/EC, subjects may be required to re-sign the ICF after 
review to remain in the trial. 
12.2.4 Declaration of Helsinki 
This trial will be conducted according to the principles and rules detailed in the 
Declaration of Helsinki and its subsequent amendments. 
 
 

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 31 of 39 
 
13 Quality Control and Quality Assurance 
13.1 Monitoring 
As the parent and infant are not required to visit a physical site during the study period 
(unless reconsent is required), monitoring will be conducted throughout the study via 
remote data reviews. The monitor will check the chatbot transcripts and eCRF data for 
completeness, consistency and any concerning text. If any errors are identified, they 
may be corrected consistent with the Data Handling Conventions (DHC) or may be 
addressed through direct contact with the parent. Concerning text will be 
communicated to the PI who will take appropriate action.  
The main protocol deviations that will be targeted are:  
• 
Informed consent process not adequately performed  
• 
Violation of inclusion and/or exclusion criteria 
• 
Non-compliance with study-related daily requirements (interactions with the 
study chatbot) 
• 
Any other GCP non-compliance 
Protocol deviations will be tracked and logged in the Protocol Deviation Log. 
At the end of the trial, the monitor and/or Clinical Data Manager (CDM) will ensure 
that all documentation and the Trial Master File (TMF) are complete. In all cases, it is 
the responsibility of the CPM, CDM and other study team members to maintain subject 
confidentiality. 
13.2 Quality Control of Essential Documents 
ObvioHealth will implement and maintain quality assurance, and quality control 
systems with Standard Operating Procedures (SOPs) to ensure that this clinical trial is 
conducted, and data are generated, documented (recorded) and reported in 

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 32 of 39 
 
compliance with the protocol, GCP/ICH standards, and other applicable local 
regulations.  
13.3 Responsibilities of the PI 
The PI is responsible for the following: 
• 
Obtaining the written and dated approval of the applicable IRB/EC and other 
regulatory agency, if any, prior to the conduct of the study 
• 
Address any concerning text with the parent, as communicated via the monitor 
• 
Selection of participants/subjects in accordance with the inclusion and exclusion 
criteria after obtaining written informed consent of the parent 
• 
Maintain confidentiality and safety of subjects in accordance with the 
Declaration of Helsinki 
• 
Adherence to the study protocol and the spirit of GCP 
• 
If modification becomes necessary, the rationale will be provided in a protocol 
amendment signed by the PI and Sponsor for submission to the IRB/EC 
o After the protocol amendment approval, subjects may be required to re-
sign an amended ICF to remain in the trial 
• 
During the trial, provide subjects with any newly available information regarding 
the study or its components that may be relevant to them 
• 
Cooperation in the case of an audit and/or a regulatory inspection, providing 
direct access to source data and/or documents 
 
 
 

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 33 of 39 
 
14 Study End Procedures 
14.1 Premature Termination of Study 
Should it prove necessary to discontinue the study permanently prior to completion, 
the Sponsor will notify ObvioHealth, the subjects, and the IRB/EC of the rationale.  All 
relevant study documents and data will then be sent to the Sponsor. 
14.2 Termination of Study 
After the completion or termination of the study, all relevant study documents and 
data will then be sent to the Sponsor.  The PI will inform the IRB/EC of the end of the 
study, and a certificate of study closure will be issued.  
 
 
 
 
 
 
 
 
 

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 34 of 39 
 
15 References 
1. World Health Organization. (2017). Preterm birth. 2017 November [Accessed February 2, 
2018]; Fact Sheet.  Available from: http://www.who.int/mediacentre/factsheets/fs363/en/. 
2. Fletcher, L., et al. (2017). Parental Perception of Risk Associated With Their Premature Infant. 
Adv Neonatal Care, 2017. 17(4): p. 306-312. 
3. Mughal, M.K., et al. (2017). Parenting stress and development of late preterm infants at 4 
months corrected age. Res Nurs Health, 2017. 40(5): p. 414-423. 
4. Gondwe, K.W., et al. (2017). Maternal Psychological Distress and Mother-Infant Relationship: 
Multiple-Birth Versus Singleton Preterm Infants. Neonatal Netw, 2017. 36(2): p. 77-88. 
5. Polic, B., et al. (2016). Late preterm birth is a strong predictor of maternal stress later in life: 
Retrospective cohort study in school-aged children. J Paediatr Child Health, 2016. 52(6): p. 
608-13. 
6. Rahman, A. M., Al Mamun, A., & Islam, A. (2017). Programming challenges of chatbot: Current 
and future prospective. Humanitarian Technology Conference (R10-HTC), 2017 IEEE Region 
10: p. 75-78. 
 
 
 
 

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 35 of 39 
 
16 Appendices  
 
 
APPENDIX I: Chatbot Study Screening eQuestionnaire 
Date: ________________ 
Parent  
Relationship to Infant: ___Father ____Mother  
Date of Birth: _________________ (excluded if not in ≥21 years of age)  
 
Infant  
Gender: ___Boy ___ Girl 
Date of Birth: _________________ (excluded if not in age group 0-6 months at time of 
enrollment) 
The following is a questionnaire to help us better understand you and your baby; this will allow 
us to determine if this study is right for you.  Please pick the best answer. 
1. Was your baby from a singleton pregnancy? 
a. Yes 
b. No (exclusion) 
 
2. Was your baby born after 37 weeks of gestation?  (i.e., how many weeks pregnant were you 
at delivery?) 
a. Yes  
b. No  
c. Don’t Know/Not sure (exclusion) 
 
3. How many weeks pregnant were you at delivery? 
_________________ (Open-ended question) 
 

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 36 of 39 
 
4. What type of food does your baby typically eat? (check all that apply) 
____ Breastmilk _____ Formula    _____ Solid-food   _____ Other [Open-ended question] 
(if breastmilk) 
a. At what approximate age (in weeks) do you plan to stop feeding your baby breastmilk? 
[Open-ended question] 
b. Do you know when you are planning on introducing solid food? 
i. Yes 
ii. No 
(if yes) When do you plan on introducing solid food? [Open-ended question] 
 
5. Is your baby currently in the hospital? 
a. Yes (exclusion) 
b. No  
 
6. Are you a single parent? 
a. Yes (exclusion) 
b. No 
 
7. Are you proficient in the English language? 
a. Yes 
b. No (exclusion) 
 
8. Do you or your baby have a significant limitation (including medical or physical concerns, etc.), 
which may interfere with daily study participation for 30 days in a row? 
a. Yes (exclusion) 
b. No 
c. Don’t Know/Not Sure 

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 37 of 39 
 
9. Do you live in a household where you have reliable, easy access to the internet and 
electronic devices such as a computer, laptop, smartphone or tablet?  
a. Yes 
b. No (exclusion) 
 
10. Has your baby been diagnosed with a current or previous illness or medical condition 
(other than prematurity)? 
a. Yes  
b. No 
(if yes) What illness or medical condition? (open-ended response; PI to follow up) 
 
11. Have you been diagnosed with any of the following (please check all that apply; check “not 
applicable” if you have not been diagnosed with any of those listed below): 
☐ Current or history of mental illness 
☐ Recent or new illness/medical condition 
☐ Ongoing illness/medical condition 
☐ Not applicable (if not applicable checked, participant is eligible to proceed)  
If any responses (except not applicable) are checked: 
What specifically have you been diagnosed with? (Open-ended response; PI to follow up)  
 
 
 
 
 
 

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 38 of 39 
 
APPENDIX II: Usability of Chatbot and ClaimIt eQuestionnaire 
The following is a questionnaire is for you to provide feedback on your interactions with the 
chatbot. Please pick the best answer. 
1. Please rate the study chatbot’s overall ease of use on a scale of 1 to 5: 
(Very Difficult) 1   2   3   4   5 (Very Easy) 
2. Please rate the ClaimIt application's overall ease of use on a scale of 1 to 5: 
(Very Difficult) 1   2   3   4   5 (Very Easy) 
3. How satisfied were you with your interactions with the study chatbot? 
(Very Dissatisfied) 1   2   3   4   5 (Very Satisfied) 
4. How satisfied were you with your interactions with ClaimIt? 
(Very Dissatisfied) 1   2   3   4   5 (Very Satisfied) 
5. Did the study chatbot malfunction? 
a. Yes (will be asked a follow-up question) 
b. No 
(If Yes) How did the study chatbot malfunction? [Open-ended question] 
6. Did ClaimIt malfunction? 
a. Yes (will be asked a follow-up question) 
b. No 
(If Yes) How did ClaimIt malfunction? [Open-ended question] 
7. How likely are you to consider using a chatbot application as an interactive tool to provide 
input on similar topics? 
(Not at all Likely) 1   2   3   4   5 (Very Likely)  
8. How would you rate the length of interactions you had with the study chatbot?   
(Too Long) 1   2   3   4   5 (Easily Manageable)  
9. What did you like the least about the study chatbot? ____________ [Open-ended question] 
10. What did you like the most about the study chatbot? _____________ [Open-ended question]  
11. Do you have any other comments about the study chatbot that you would like the 
investigators to know?   __________________________________ [Open-ended question] 

 
Study Number: OBVIO-DAN-003 
Protocol 
V3 31AUG2018 
 
CONFIDENTIAL 
Page 39 of 39 
 
12. What did you like the least about the ClaimIt app? ____________ [Open-ended question] 
13. What did you like the most about the ClaimIt app? _____________ [Open-ended question]  
14. Do you have any other comments about the ClaimIt app that you would like the investigators 
to know?   __________________________________ [Open-ended question] 
15. How worried were you about sharing your data with the study chatbot? 
(Not at all worried) 1   2   3   4   5 (Very worried) 
16. How likely would you be to use a chatbot tool like this in real life to get access to information 
and reassurance if you could? 
(Not at all likely) 1   2   3   4   5 (Very likely) 
Why or why not? [Open-ended question]