Observational Study: Image Collection of Infant/Toddler Stools for Danone Software Development
Conditions: Healthy
Sponsor: Danone Asia Pacific Holdings Pte, Ltd.

Study Number: OBVIO-DAN-002 
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STUDY PROTOCOL 
 
 
Study Number 
OBVIO-DAN-002 
Title 
Observational Study: Image Collection of 
Infant/Toddler Stools for Danone Software 
Development 
Sponsor 
Danone 
Country 
United States 
Date 
12OCT2018 
Version Number 
2 
 
 
 
 
 
 
 
 

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Table of Contents 
1 
Investigator Signature Page............................................................................................. 4 
2 
Team Signature Page ...................................................................................................... 4 
3 
Abbreviations ................................................................................................................. 7 
4 
Synopsis ......................................................................................................................... 8 
5 
Introduction ................................................................................................................. 13 
6 
Objectives of the Trial ................................................................................................... 14 
6.1 
Primary Objectives ......................................................................................................... 14 
6.2 
Exploratory Objectives ................................................................................................... 14 
7 
Trial Design ................................................................................................................... 15 
7.1 
Study Calendar .............................................................................................................. 15 
7.2 
Type of Trial ................................................................................................................... 15 
7.3 
Endpoints ...................................................................................................................... 15 
7.4 
Participants and Location ............................................................................................... 16 
7.4.1 
Participants .................................................................................................................. 16 
7.4.2 
Location ....................................................................................................................... 16 
7.5 
Study Duration............................................................................................................... 16 
8 
Study Population .......................................................................................................... 17 
8.1 
Subject Inclusion Criteria ................................................................................................ 17 
8.2 
Subject Exclusion Criteria ............................................................................................... 18 
8.3 
Subject Withdrawal Criteria ........................................................................................... 18 
9 
Assessment of Safety .................................................................................................... 20 
10 Execution of the Trial .................................................................................................... 21 
10.1 
Screening and Enrollment .............................................................................................. 21 
10.2 
Data Collection .............................................................................................................. 22 
10.3 
End of Study .................................................................................................................. 23 
10.4 
Application Description .................................................................................................. 24 
10.5 
Monitoring .................................................................................................................... 24 
10.6 
Computerized Data Entry - Security and Privacy of User Data .......................................... 25 
10.7 
Computerized Edit Checks .............................................................................................. 25 
10.8 
Audit Trail ...................................................................................................................... 25 
11 Statistics ....................................................................................................................... 25 
11.1 
Sample Size Calculations ................................................................................................ 25 
12 Legal and Ethical Prerequisites ...................................................................................... 27 
12.1 
Legal Requirements ....................................................................................................... 27 
12.2 
Ethical Aspects ............................................................................................................... 27 
12.2.1 Protection of the Subject's Confidentiality ................................................................ 27 
12.2.2 Informed Consent ...................................................................................................... 27 
12.2.3 Ethics Committee Approval ....................................................................................... 28 
12.2.4 Declaration of Helsinki ............................................................................................... 28 

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13 Quality Control and Quality Assurance .......................................................................... 29 
13.1 
Monitoring .................................................................................................................... 29 
13.2 
Quality Control .............................................................................................................. 29 
13.2.1 Quality Control of Essential Documents .................................................................... 29 
13.3 
Responsibilities of the PI ................................................................................................ 29 
14 Study End Procedures ................................................................................................... 31 
14.1 
Premature Termination of Study .................................................................................... 31 
14.2 
Termination of Study ..................................................................................................... 31 
15 References .................................................................................................................... 32 
16 Appendices ................................................................................................................... 33 
APPENDIX I: 
Brussels Infant and Toddler Stool Scale (BITSS) ............................................. 33 
APPENDIX II: 
Prescreening eQuestionnaire ....................................................................... 34 
APPENDIX III: 
Screening eQuestionnaire ......................................................................... 38 
APPENDIX IV: 
Compliance eQuestionnaire ...................................................................... 40 
APPENDIX V: 
Parental Satisfaction with ClaimIt Platform .................................................. 41 
APPENDIX VI: 
Good/Bad Stool Image Examples .............................................................. 44 
 
 
 

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1 Investigator Signature Page 
 
PRINCIPAL INVESTIGATOR (PI) AND CO-INVESTIGATOR (CO-PI) 
 
Parth Shah, MD 
Sr. Director, Medicine and Economics 
ObvioHealth 
 
 ___________________  
  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 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. 
2 Team Signature Page 
 

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CLINICAL PROJECT MANAGER 
 
Jill Wong 
Digital Program Manager 
Digital Team, Early Life Nutrition 
Danone Nutricia 
 
 
 ____________________  
 Date 
 
 ____________________  
 Signature 
 
PRINCIPAL SCIENTIST 
 
Thomas Ludwig, M.D. 
Principal Scientist  
Pediatric Gastroenterology  
Danone Nutricia 
 
 
 ____________________  
 Date 
 
 ____________________  
 Signature 
 
BIOSTATISTICIAN (CRO) 
 
Jerrod Nelms, PhD, MPH 
SVP, Global Head of Biostatistics 
ObvioHealth  
 
 
 ___________________  
 Date 
 
 ___________________  
 Signature 
OBVIOHEALTH PROGRAM LEADER 

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Cherlynn Basignani BSN, RN, CCRC 
Senior Director, Clinical Operations 
ObvioHealth 
 
 ___________________  
 Date 
 
 ___________________  
 Signature 
 
 
 
 
 

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3 Abbreviations 
BITSS 
Brussels Infant and Toddler Stool Scale 
CDM 
Clinical Data Manager 
CPM 
Clinical Project Manager 
CRO 
Contract Research Organization 
DHC 
Data Handling Conventions 
eCRF 
Electronic Case Report Form 
eIC 
Electronic Informed Consent 
GCP 
Good Clinical Practice 
HCP 
Healthcare Providers 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
IP 
Investigational Product 
PI 
Principal Investigator 
SOP 
Standard Operating Procedure 
TMF 
Trial Master File 
 
 

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4 Synopsis                
Study Title 
Observational Study: Image Collection of Infant/Toddler Stools for 
Danone Software Development 
Study Objectives  
Primary  
 To create a database of stool images scored by mothers that are 
suitable for Danone software development purposes 
 To create a database containing at least 200 pictures of diapers 
containing fecal (stool) material per each stool consistency score 
(type 1 to 7) of the BITSS (Brussels Infant and Toddler Stool Scale) 
and 200 images of empty (no stool) disposable diapers 
 
Exploratory  
 To compare the stool consistency scores from mothers on-study 
to re-scores of mothers (not enrolled on-study) based only on 
the uploaded images  
 To assess mothers' perceptions of the usability of the stool 
scoring process and the usability of the ClaimIt app  
Study Design 
An observational study of stool images among infants/toddlers, ages 
0-24 months 
Study Observation 
Duration 
30 days per child  
NOTE: If participants upload a low number of quality images due to 
infant/toddler constipation and infrequency of stooling, the mother 
may be asked if she would like to continue in the study for an 
additional >30 days or more. If she chooses to continue, she may do 
so as long as images continue to be provided at a reasonable 
frequency and/or until stool strata are satisfied (at the PI
discretion). 
Country of 
Implementation 
United States of America 
Study Population  
 
Approximately 100 healthy infants/toddlers (until 200 images per 
stool score reached), age 0-24 months (at time of enrollment) 

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Inclusion Criteria 
 
 Healthy infants/toddlers (0-24 months of age at time of 
enrollment)  
 Informed consent from mother 
 
 In-home access to reliable internet connections; a mobile 
device suitable for electronic communication; and a device 
suitable for capturing and transmitting high-quality electronic 
images as per the PI
discretion  
 Infant/toddler consumes standard, age-appropriate food 
(breast milk; formula; commercial/homemade baby, table or 
finger food)  
 Based on the number of stools already acquired per relevant 
strata at time of enrollment, infant/toddler may or may not 
be required to regularly produce stools scored as a Score 1, 2, 
6 or 7 (per Appendix II) 
Exclusion Criteria 
Mothers of Infants/Toddlers: 
 The use of cloth diapers (mothers must commit to using 
disposable diapers for the duration of the study) 
 Known to have a significant condition (including during 
pregnancy) that might interfere with the study compliance, as 
per PI
clinical judgment 
 Deemed likely to be non-compliant with the study protocol, 
as per PI
clinical judgment 
 
Endpoints 
 
Primary: 
 Creation of a database containing at least 1600 pictures of 
individual diapers: 
o 200 images of diapers with stool per each score 
(BITSS types 1 to 7)  
o 200 images of empty (no stool) disposable diapers 
 
Exploratory:  
 A comparison of the stool consistency scores from the 
mothers on-study to re-scores from mothers (not enrolled on-
study) based only on the uploaded images  
 An assessment of mothers' perceptions of the usability of the 
stool scoring process  
 An assessment of mothers' perceptions of the usability of the 
ClaimIt app 

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Study 
Implementation 
Prescreening: 
Administer 
the 
inclusion/exclusion 
criteria 
eQuestionnaire 
to mother which includes 
estimated stool frequency and consistency (e.g., liquid, soft/mushy, 
solid, firm, hard). After 
 information is 
shown to satisfy predetermined prescreen criteria (including 
distribution by groups), the mother will be provided access to the 
ClaimIt app along with the following information: 
 How to complete the electronic informed consent (eIC), 
screening and enrollment process 
 Overview of trial tasks and relevant notifications 
 ClaimIt navigation: How to interact with the ClaimIt app 
during the observation period 
 
 Additional study details & instructions on how to take high-
quality, standardized pictures with proper lighting 
 All relevant contact information that may be required during 
the study 
          
 
Screening: The mother will complete a detailed eQuestionnaire for 
confirmation of inclusion and exclusion criteria. The mother will also 
stool via ClaimIt, each with a corresponding score based on her 
judgment made in comparison with the BITSS scoring tool. Images 
must be uploaded within 10 days of receiving ClaimIt app access. 
 
An adaptive recruitment approach will be leveraged to ensure that 
200 pictures of each stool type are collected over the duration of 
the study.  
The mother and infant/toddler will be enrolled into the study if the 
test images are successfully uploaded, and they meet all the 
inclusion criteria and none of the exclusion criteria for the study, 
based on the 
 judgment and appropriate fit into predetermined 
bowel function strata. 
Observation Period: The mother will be asked to interact with the 
ClaimIt app daily for 30 days (or longer) as follows: 
 Two empty (no stool) disposable diaper images are to be 
uploaded: one at Baseline and one at End of Study 
o Images should be taken of the type of disposable 
diaper used most frequently for the infant/toddler 

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o Additional empty (no stool) disposable diaper images 
may only be submitted if the brand/type of diaper 
changes; if the diaper size changes, no additional 
pictures need to be uploaded 
 Stool images will be taken with a smartphone (or alternative 
suitable for capturing and transmitting high-quality 
electronic images) and uploaded daily:  
o Mothers will be given instructions on how to take 
high-quality, standardized pictures with proper 
lighting 
o Every bowel movement is to be imaged, potentially 
providing several images per day 
o Mothers who have not submitted at least one image 
in the previous 24-hour period will be sent 
notifications to encourage compliance  
o Only 1 representative image per bowel movement is 
to be transmitted 
 Along with each stool image uploaded, the mother will rate 
the stool characteristic type on the BITSS (type 1 to 7); scores 
will be based only on consistency and not color 
 
End of Observation Period:  
 The mother will be asked to complete an eQuestionnaire to 
assess and comment on the usability of the ClaimIt app and 
the scoring process (Appendix V) 
 Two mothers who were not enrolled in the study will be 
provided a collection of study stool images and asked to re-
score each image according to the BITSS 
Statistical 
Considerations 
 
A sample size of 100 subjects is estimated with the following 
considerations: 
 Progression of potential subjects will be gated at the 
prescreening and screening steps to facilitate enrollment of 
an appropriately diversified set of infants/toddlers based on 
bowel patterns to reach 200 images per each stool 
consistency score (type 1 to 7) of the BITSS  
 The Sponsor and ObvioHealth will review the distribution of 
the scores and image quality and will determine when the 
prescreening requirements can be modified 
 A comparison will be made between the stool consistency 
scores from the mothers on-study to re-scores from mothers 
(not enrolled on-study) based only on the uploaded images 

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 Based on Sponsor review of the data, the following may be 
performed: 
o A post hoc analysis  
o Descriptive summary statistics for categorical and 
quantitative data  
 The expectation is that not all the mothers will be compliant 
with study tasks for all 30 days 
 A dropout rate of 15% is anticipated (if dropout rate exceeds 
15%, replacements will be made for all additional 
withdrawals) 
 
 
 

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5 Introduction  
 
Accurately classifying stool consistency for infants and toddlers who are not yet toilet trained 
remains challenging. A recent study showed that among parents of infants and toddlers, only 
fair agreement existed between the parental report of stool consistency and the Bristol Stool 
Form Scale (BSS),1 a gold standard in the classification of stool consistency in adults and older 
children who are toilet trained.2 While there are alternative assessment methods which are 
used in clinical practice, such as the modified BSS and the Amsterdam Infant Stool Scale, a 
universally-accepted tool does not exist.3 The Brussels Infant and Toddler Stool Scale (BITSS) 
was recently initiated based on the BSS to provide a classification tool to describe stool 
consistency for infants and toddlers.4  
This observational study is designed to collect a series of images that span the range of stool 
consistencies associated with the stools of infants and toddlers to create a significant and 
varied photographic image database.  For essentially healthy infants/toddlers (0-24 months) 
stool consistencies range from liquid (frequently associated with diarrhea) to hard formed 
(frequently associated with constipation) stools. This database will be used to assist in the 
further development of Danone software to facilitate evaluation of stool type remotely and 
permit evaluation beyond the interpretation of parents. The study is designed to collect at 
least 1600 images: at least 200 images per stool score (type 1 to 7) of the BITSS (at least 1400 
total) plus 200 images of empty (no stool) diapers, generating further data to assist in the 
assessment and classification of infant/toddler stools and gastrointestinal function. 
 
 

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6 Objectives of the Trial 
6.1 Primary Objectives  
 To create a database of stool images scored by mothers that are suitable for 
Danone software development purposes 
 To create a database containing at least 200 pictures of disposable diapers 
containing fecal (stool) material per each stool consistency score (type 1 to 7) of 
the BITSS (Brussels Infant and Toddler Stool Scale), and 200 images of empty (no 
stool) disposable diapers  
6.2 
Exploratory Objectives 
 To compare the stool consistency scores from mothers on-study to the re-scores 
of mothers (not enrolled on-study) based only on the uploaded images 
 To assess mothers' perceptions of the usability of the stool scoring process and 
the usability of the ClaimIt app  
 
 

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7 Trial Design 
7.1 Study Calendar 
Pre-
screening 
Baseline 
Daily 
Weekly 
End of 
Study 
Prescreening 
Eligibility Review 
X 
 
 
 
 
Prescreening 
Image Upload 
X 
 
 
 
 
eIC  
X 
 
 
 
 
Screening 
eQuestionnaire  
 
X 
 
 
 
Upload of Stool 
Image(s) 
 
 
X 
 
 
Sponsor and CRO 
Review of Images 
and Distribution 
of Scores 
 
 
 
X 
 
End of Study 
eQuestionnaire 
 
 
 
 
X 
 
7.2 Type of Trial 
An observational study of 100 essentially healthy infants/toddlers, 0-24 months of age. 
7.3 Endpoints 
Primary Endpoint:  
Creation of a database containing at least 1600 images: 
 At least 200 images of disposable diapers containing stool per each score (type 1 
to 7) of the BITSS  
 At least 200 images of empty (no stool) disposable diapers  

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Exploratory Endpoints: 
 A comparison of the stool consistency scores from the mothers on-study to re-
scores from mothers (not enrolled on-study) based only on the uploaded images  
 An assessment of 
the usability of the stool scoring process  
 An assessment of 
the usability of the ClaimIt app  
7.4 Participants and Location 
7.4.1 Participants 
Study participants will include the mother and their infant/toddler. The 
prescreening recruitment process will be administered through an online 
eQuestionnaire to the mother evaluating the typical stool and consistency (e.g., 
liquid, soft/mushy, solid, hard).   
7.4.2 Location 
The trial will be conducted remotely in the United States. Communication 
between mothers and study personnel will be conducted via the internet 
(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 five (5) months in total. 
The expected study duration is 30 days per mother and infant/toddler. If a participant 
uploads a low number of quality images due to infant/toddler constipation and 
infrequency of stooling, a member of the study team may contact the mother to ask if 
she wants to continue with study for an additional 30 days or more. If she chooses to 
continue, they may do so as long as images continue to be provided at a reasonable 
frequency and/or until stool strata are satisfied (at the 
discretion). 
 
 

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8 Study Population 
 
It is expected that the infant and their mother will sustain these eligibility criteria for the 
duration of their enrollment. 
8.1 Subject Inclusion Criteria 
Subjects must meet the following: 
 Healthy infants/toddlers (0-24 months of age at time of enrollment)  
 Informed consent from mother 
 
 In-home access to reliable internet connections; a smartphone (or alternative 
suitable for capturing and transmitting high-quality electronic images) as per the 
PI
discretion  
 The infant/toddler consumes age-appropriate, standard food (breastmilk; 
formula; commercial/homemade baby, table or finger food) 
 Based on the number of stool images already acquired per relevant strata at time 
of enrollment, the infant/toddler may or may not be required to regularly produce 
stools scored as a Score 1, 2, 6 or 7 (per Appendix II) 

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8.2 Subject Exclusion Criteria 
Mothers of Infants/Toddlers: 
 The use of cloth diapers (mothers must commit to using disposable diapers for the 
duration of the study) 
 Known to have a significant condition (including during pregnancy) that might 
interfere with the study compliance, as per PI's clinical judgment 
 Deemed likely to be non-compliant with the study protocol, as per PI's clinical 
judgment 
8.3 Subject Withdrawal Criteria 
Mothers and their infants/toddlers may be withdrawn from the study at any time and 
for any reasons including but not limited to the following: 
1) At their request or the request of their legally authorized representative. 
2) If, in the PI's opinion, continuation in the study would be detrimental to the 
-being. 
3) Poor compliance: if the mother and infant/toddler consistently do not adhere to 
the study procedures (per the 
discretion). 
4) Protocol deviation(s) which in the opinion of Sponsor warrant discontinuation 
from the study; e.g., violation of inclusion and/or exclusion criteria. 
Study Note: If the infant/toddler experiences an illness (other than 
diarrhea/constipation) lasting longer than 7 days, has surgery or is 
admitted to the hospital for more than 24 hours, they should be 
withdrawn from the study immediately. 
Due to the 15% dropout rate built into the estimated total sample size, subjects whose 
study participation is terminated prematurely for any of the above-listed criteria will 
not be replaced.  If the dropout rate exceeds 15%, replacements will be made for all 
additional withdrawals. The PI will make every effort to contact subjects lost to follow-
up during the study.  Attempts to contact the subject will be documented in the 
, dates and times of attempted telephone contact). 

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The number and percentage of subjects who withdraw early and their reasons for 
withdrawal will be presented in a table and a CONSORT flow diagram equivalent. 
The following information will be documented in the 
 
record 
 
I. 
Date of withdrawal 
II. 
Reasons for withdrawal 
Even if consent is withdrawn, all data and all images that were acquired before consent 
was withdrawn will be maintained.  
 
 

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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 not collected or reported for this study.  
 
 
 

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10 Execution of the Trial 
10.1 Screening and Enrollment 
Prescreening: 
The prescreening recruitment step will recruit healthy infants/toddlers (0-24 months 
of age at enrollment) residing in the United States through an online eQuestionnaire 
administered to the mother. Questions will include an estimation of the frequency of 
stools of varied consistency (e.g., liquid, soft/mushy, solid, firm, hard). After satisfying 
predetermined prescreen criteria (including distribution by groups), the mother will be 
provided access to the ClaimIt app along with the following information: 
 Overview of trial tasks and relevant notifications 
 Instruction on how to complete the electronic informed consent (eIC), screening 
and enrollment process 
 Instruction on how to interact with the ClaimIt app during the observation period 
 Additional study details & instructions  
The mother will be sent an electronic consent (eIC) for review and will have the 
opportunity to ask questions and receive answers either through online 
communication or in-person telephone conversation.  Mothers who choose to 
participate will voluntarily sign an eIC as instructed by the ClaimIt app. 
Screening and Enrollment 
After the eIC is voluntarily signed, a detailed eQuestionnaire for confirmation of 
inclusion and exclusion criteria will be administered to the mother. She will also be 
with a corresponding score, within 10 days of receiving ClaimIt app access. The mother 
and infant/toddler will be enrolled into the study if the mother successfully uploads 
the test images and scores and meets all the inclusion and none of the exclusion criteria 
for the study based on PI
judgment. Depending on the distribution of stool images 
already acquired per score, the mothers and infant/toddlers may be further qualified 
based on the likelihood of filling gaps in the image collection. 

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This adaptive recruitment approach will be leveraged to ensure that 200 pictures of 
each type are collected over the duration of the study. The enrollment of potential 
subjects will be gated at either (or both) the prescreening and screening steps based 
on the 
  
The sponsor (Danone) and the CRO (ObvioHealth) will review images and the 
BITSS scores to assess the overall distribution of images per each score and will 
determine when the prescreening requirements can be modified. Total study 
enrollment may be expanded or modified until target values are attained.  
10.2 Data Collection 
The mother will be asked to interact with the ClaimIt app daily for 30 days (or more) as 
follows:  
 Stool images will be taken with a smartphone (or alternative suitable for 
capturing and transmitting high-quality, electronic images) and uploaded daily 
 Every bowel movement will be photographed, potentially providing several 
images per day 
o Only 1 representative image per bowel movement should be transmitted 
 If the mother has not uploaded an image in 24 hours, a notification and the 
Compliance eQuestionnaire requiring a response will be sent to her (Appendix IV) 
 The following steps should be taken to ensure the image quality: 
o The picture should be taken in a well-lit room and with sufficient lighting on 
the diaper itself; pictures should not be taken in rooms requiring flash 
o The diaper should be placed on a table or area apart from any other objects; 
primarily only the soiled portion of the diaper should be in the picture 
o The diaper must be fully opened, and the contents must be clearly visible in 
the photograph 

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o The camera should be zoomed-in as appropriate and focused on the stool 
itself 
 The image will include all the stool while excluding as much of the 
dry diaper as is reasonable  
o The pictures should be taken within 10 minutes after the child has soiled 
the diaper 
 Images in which the stool form is not recognizable (e.g., stools that 
have been distorted or significantly smushed) should not be 
uploaded 
 Along with each stool image uploaded, mothers will rate the stool consistency 
type compared to examples provided by the BITSS (Score 1 to 7) 
o Scoring will be based only on consistency, not color 
o Sample images of each score will be provided 
 A total of two empty (no stool) disposable diapers, spread open, are to be 
submitted: one at Baseline and one at the End of Study 
o Images should be taken of the type of diaper used most frequently for the 
infant/toddler  
o Additional empty (no stool) disposable diaper images may only be 
submitted if the brand/type of diaper is changed; if only the diaper size 
changes, no additional pictures need to be uploaded 
10.3 End of Study 
At the end of the study, the mother will be asked to complete an eQuestionnaire to 
assess and comment on the usability of the ClaimIt app and the scoring process 
(Appendix V). 

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Also, the Sponsor will identify two mothers who were not enrolled in the study. They 
will be provided a collection of uploaded study images and asked to re-score each 
image according to the BITSS.  
10.4 Application Description 
The ClaimIt app is a mobile application available to study participants during their 
period of enrollment so they can perform certain study-related tasks and receive and 
transmit communications from and to the CRO staff. 
10.5 Monitoring  
The study will be monitored on an ongoing basis beginning with enrollment of the first 
mother and infant/toddler and continuing through the study exit of the last enrolled 
pair. Regular monitoring will be done 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 by the mother: 
 Dedicated study personnel will maintain contact with the mother to answer 
questions about the study or the ClaimIt app, as necessary   
 In some circumstances, the PI or study team personnel may call the mother to 
determine the compliance with study protocol  
 Study team (Sponsor and CRO members) will review the BITSS scores provided by 
the mothers to assess the distribution of strata and daily compliance which 
includes: 
o Adherence to study protocol; including sustained quality of images 
o Proper uploading of the images in a timely manner 
 If the mother has not uploaded an image in the previous >24 hours, a notification 
and the Compliance eQuestionnaire will be sent (Appendix IV) 
Since there are no physical sites involved in this protocol, monitoring will be 
implemented throughout the study via remote data reviews. The monitor will check 

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eCRF data for completeness and consistency. 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. 
Electronic CRFs (eCRFs) will be completed by the mother for their infant/toddler. Data 
from the completed eCRF will then be reviewed by the designated study team member 
and 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 
mother. 
10.6 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.     
10.7 Computerized Edit Checks 
The database will incorporate the needed programmed edit checks to help ensure 
quality data.  Messages to the mother may be generated automatically to alert her to 
any entry error.  
10.8 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. 
11 Statistics                 
11.1 Sample Size Calculations 
A sample size of 100 subjects is estimated to be sufficient to collect images of at least 
200 pictures of diapers containing fecal (stool) material per score (type 1 to 7) of the 
BITSS plus 200 images of empty (no stool) disposable diapers. 

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12 Legal and Ethical Prerequisites 
12.1 Legal Requirements 
The study will initiate after approval from the IntegReview IRB which follows the 
guidance of USA regulatory bodies and general Good Clinical Practice 
(GCP)/International Conference on Harmonisation (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 complete the HIPAA 
release of information form during the eIC process. 
12.2.2 Informed Consent 
Electronic Informed Consent (eIC) signed by the subject indicating their consent 
to her 
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 eIC will inform the mother about all aspects of 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 eIC.  Any 
amendments to these documents must be approved by the IRB/EC. 
The mother must sign the eIC prior to the initiation of any study-related 
activities beyond prescreening.   
The decision to participate in the study is entirely voluntary.  The PI and/or 
his/her designee must emphasize to the mother that the consent to participate 
can be withdrawn at any time without penalty or loss of benefits to which the 
mother and infant/toddler are otherwise entitled. 

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12.2.3 Ethics Committee Approval 
The study protocol will be submitted by the PI (or designee) for examination by 
the US Institutional Review Board (IRB)/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 is made and approved by the IRB/EC, 
subjects must 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 laid down in 
the Declaration of Helsinki and its subsequent amendments. 
  
 
 

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13 Quality Control and Quality Assurance 
13.1 Monitoring 
Since there are no physical sites involved in this protocol, monitoring will be 
implemented throughout the study via remote data reviews. The monitor will check 
eCRF data for completeness and consistency. 
The main protocol deviations for consideration on this trial are:  
 
Informed consent process not adequately performed  
 
Violation of inclusion and/or exclusion criteria 
 
Non-compliance with study-related daily requirements  
 
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 study team to maintain subject confidentiality. 
13.2 Quality Control  
13.2.1 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 compliance to the protocol, GCP/ICH standards, and other 
applicable local regulations.  
13.3 Responsibilities of the PI 
The PI is responsible for the following: 
 
Selection of participants/subjects in accordance with the inclusion and exclusion 
criteria (in this study the mother and infant/toddler) 

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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 the eIC to remain in the trial 
 
During the trial, provide subjects with any newly available information that may 
be relevant to them 
 
Cooperation in the case of an audit and/or a regulatory inspection, providing 
direct access to data and/or documents 
 
 
 
 
 

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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.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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15 References 
 
1. Koppen IJ, Velasco-Benitez CA, Benninga MA, et al. Using the Bristol Stool Scale and parental 
report of stool consistency as part of the Rome III Criteria for functional constipation in infants 
and toddlers. J Pediatr 2016;177:44 8.e1. 
2. Heaton KW, Radvan J, Cripps H, et al. Defecation frequency and timing, and stool form in the 
general population: a prospective study. Gut 1992;33:818 24 
3. Lane, M.M., Czyzewski, D.I., Chumpitazi, B.P., and Shulman, R.J. Reliability and validity of a 
modified Bristol Stool Form Scale for children. J Pediatr. 2011; 159: 437 441.  
4. Vandenplas Y, Szajewska H, Benninga M, et al. Development of the Brussels Infant and 
Toddler Stool 
 
 
 

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16 Appendices  
 
 
APPENDIX I: Brussels Infant and Toddler Stool Scale (BITSS) 
Refer to the following BITSS (Score 1 to Score 7) images in order to rate each stool image 
prior to uploading through the ClaimIt app: 
 
 
 

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APPENDIX II: Prescreening eQuestionnaire 
Date: ________________ 
Mother  
Name: (First and Last) __________________   
Relationship to Infant: ____Mother  
Date of Birth: _________________ (excluded if not 
) 
Phone: (best # to call) _____________________  
Best time of day to call: ____Morning ____Afternoon ____Evening ____Other (open ended) 
Email: ______________________________ 
Confirm Email: ______________________________ 
Infant/Toddler 
Name (First and Last) ____________________   Gender: ___Boy or ___ Girl 
Date of Birth: _________________ (excluded if not in age group 0-24 months at time of 
enrollment) 
The following is a questionnaire to help us better understand you and your child; this will help us 
determine if this study is right for you.  Please pick the best answer choice. 
 
1. Do you or your child have a significant limitation (including medical or physical concerns, 
travel, etc.), which may interfere with daily study participation for 30 days in a row? 
a. Yes (exclusion) 
b. No 
c. 
 (exclusion) 
 

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2. Do you live in a household where you have an easy, reliable access, 24-hours per day to the 
internet, and do you also have one or more of the following electronic devices: tablet or 
smartphone?  
a. Yes 
b. No (exclusion) 
 
3. Is the smartphone or tablet being used to capture and upload images for this study more 
than 4 years old?  
a. Yes (exclusion) 
b. No  
 
4. Are you now using, or are you willing to use, disposable diapers for your child? 
a. Yes  
b. No (exclusion) 
 

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5. Using the images below, please select: (formatted as two questions in ClaimIt) 
a. 
Y
most frequent stool consistency  
b. 
second most frequent stool consistency  
 
 
 
 
 
 
 
 

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6. Does your child experience the following (liquid or hard stools) at least once a week? 
 
a. Yes, both 
b. Yes, liquid stools 
c. Yes, hard stools 
d. No 
 
IF YOU HAVE ANY QUESTIONS OR PROBLEMS COMPLETING AND/OR SUBMITTING THIS 
QUESTIONNAIRE, PLEASE CALL US AT: 1-XXX-XXX-XXXX 
 
 

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APPENDIX III: Screening eQuestionnaire 
Date: ________________ 
Mother (Info below was also collected at prescreening, verify accuracy) 
Name (First and Last):  __________________  
Relationship to Infant: ____Mother  
Date of Birth: _________________ (excluded if not 
) 
Phone: (best # to call) _____________________  
Best time of day to call: ____Morning ____Afternoon ____Evening ____Other (open ended) 
Address: (# and street) ________________________________________________________  
(City, State, Zip Code)________________________________________________________ 
Email: ______________________________ 
Infant/Toddler (Info below was also collected at prescreening, verify accuracy) 
Name (First and Last) ____________________   Gender: ___Boy or ___ Girl 
Date of Birth: _________________ (excluded if not in age group 0-24 months at time of 
enrollment) 
The following is a questionnaire to help us better understand you and your child; this will help us 
determine if this study is right for you.  Please pick the best answer choice. 
 
1. Does your child consume standard food (breastmilk; formula; commercial/homemade baby, 
table or finger food) appropriate for their age? 
a. Yes  
b. No (exclusion) 
 
2. Do you or your child have a significant limitation (including medical or physical concerns, 
travel, etc.), which may interfere with daily study participation for 30 days in a row? 
a. Yes (exclusion) 
b. No 
c. 
 (exclusion) 

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3. Do you live in a household where you have reliable, easy access to the internet and electronic 
devices such as a smartphone or tablet?  
a. Yes 
b. No (exclusion) 
 
4. Is the smartphone/tablet being used capable of capturing and sending high quality electronic 
images?  
a. Yes  
b. No (exclusion) 
 
5. What device will be used for capturing and transmitting high quality electronic images? 
______________________________________ (open ended question) 
 
IF YOU HAVE ANY QUESTIONS OR PROBLEMS COMPLETING AND/OR SUBMITTING THIS 
QUESTIONNAIRE, PLEASE CALL US AT: 1-XXX-XXX-XXXX 
 
 

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APPENDIX IV: Compliance eQuestionnaire 
To be sent to participant when no image has been uploaded for >24 hours. 
 
1. Did your child produce a stool in the last 24 hours? 
a. Yes  
b. No 
 
(If yes) Please remember that images should be taken and uploaded no longer than 10 
minutes after your child has soiled the diaper, unless the stool was significantly 
smushed. 
 
(If no) Why did your child not have stool in the last 24 hours? 
_______Probably constipated _______
know _______Other (Open ended) 
 
 
 
 
 
 
 

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APPENDIX V: Parental Satisfaction with ClaimIt Platform 
The following questions are regarding the use of the ClaimIt application during your 
participation in this clinical trial: 
 
1. 
 
(Very Difficult) 1   2   3   4   5 (Very Easy) 
 
2. Did the ClaimIt application malfunction? 
a. Yes (will be asked a follow-up question) 
b. No 
 
If Yes, please describe what happened: 
________________________________________________________________________
____________________________________________________________________ 
 
3. Have you participated in any other clinical study? 
a. Yes (will be asked a follow-up question) 
b. No 
 
(If yes) What did you prefer about study participation using the ClaimIt application? 
Why? 
________________________________________________________________________
____________________________________________________________________ 
 
(If yes) What did you prefer about participation in the previous study? Why?   
________________________________________________________________________
____________________________________________________________________ 
 

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4. Do you have any comments about using the application (favorable or unfavorable) that 
you would like the PIs to know?  
_____________________ (Open ended question) 
 
5. Did you find it difficult to score the stool pictures? 
a. Yes 
b. No 
(If yes) Why? 
a. Because the app was not easy to use to see the example pictures  
b. Because it was not easy for me to score the stool, even with the example 
pictures provided 
c. Because sometimes the stool seemed in between two examples  
d. Because I did not have the time to make a decision 
e. Other __________________________________ (Open ended question) 
 
6. 
 you feel it would be 
helpful to have an automatized tool to score the stool pictures for you? 
a. Yes 
b. No 
 
7. Would you say your child  stool pattern is, or was, a concern to you?  
a. Yes, frequently 
b. Yes, when my baby was younger 
c. No, never 
 
8. Was it easy to take the pictures of the diaper? 
a. Yes 
b. No 
(if no) Why? __________________________________ 

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APPENDIX VI: Good/Bad Stool Image Examples 
Good 
Bad