ENDO1000 - A UK-wide Endometriosis Research Project
Conditions: Endometriosis
Sponsor: University of Edinburgh

 
 
 
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Sponsor 
The University of Edinburgh  
ACCORD 
Usher Building, The University of Edinburgh  
5-7 Little France Road  
Edinburgh BioQuarter – Gate 3  
Edinburgh  
EH16 4UX 
Funders 
Horizon Europe Framework Programme (HORIZON) and 
philanthropic donations 
Funding Reference Number 
101157146 
Chief Investigator 
Professor Andrew Horne 
Sponsor number 
AC25123 
Ethics Number 
TBC 
Project registration 
TBC 
Version Number and Date 
Version 1_14th August 2025 
 
 
 

 
 
 
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CONTENTS 
1 
INTRODUCTION .................................................................................................. 5 
BACKGROUND ...................................................................................................... 5 
Challenges in Diagnosis and Treatment ............................................................... 5 
RATIONALE FOR STUDY ...................................................................................... 6 
2 
STUDY OBJECTIVES ......................................................................................... 7 
2.1 
Primary Objective ..................................................................................... 7 
2.2 
Secondary Objectives ............................................................................... 7 
3 
STUDY DESIGN AND METHODS ....................................................................... 7 
4 
STUDY SETTING ................................................................................................ 8 
5 
STUDY POPULATION ......................................................................................... 9 
NUMBER OF PARTICIPANTS ................................................................................ 9 
INCLUSION CRITERIA ........................................................................................... 9 
EXCLUSION CRITERIA .......................................................................................... 9 
CO-ENROLMENT ................................................................................................... 9 
6 
PARTICIPANT SELECTION AND ENROLMENT .............................................. 10 
IDENTIFYING PARTICIPANTS ............................................................................ 10 
CONSENTING PARTICIPANTS ........................................................................... 10 
Withdrawal of Study Participants ........................................................................ 12 
LONG TERM FOLLOW UP ASSESSMENTS ....................................................... 12 
7 
STUDY ASSESSMENTS ................................................................................... 13 
8 
DATA COLLECTION/MANAGEMENT .............................................................. 16 
Source Data Documentation ................................................................................. 17 
PERSONAL DATA ................................................................................................ 17 
Data Information Flow ........................................................................................... 18 
Data Storage ......................................................................................................... 18 
Data Retention ...................................................................................................... 19 
Disposal of Data .................................................................................................... 19 
External Transfer of Data ...................................................................................... 19 
Data Controller ...................................................................................................... 19 
Data Breaches ...................................................................................................... 20 
Data Information Flow ........................................................................................ 20 
9 
BIOSAMPLE STORAGE AND ANALYSIS ........................................................ 21 
10 
STATISTICS AND DATA ANALYSIS ................................................................ 21 
SAMPLE SIZE ...................................................................................................... 21 
DATA ANALYSIS .................................................................................................. 22 
11 
OVERSIGHT ARRANGEMENTS ....................................................................... 23 
INSPECTION OF RECORDS ............................................................................... 23 
12 
GOOD CLINICAL PRACTICE ........................................................................... 23 
ETHICAL CONDUCT ............................................................................................ 23 
INVESTIGATOR RESPONSIBILITIES .................................................................. 23 
Informed Consent ............................................................................................... 23 

 
 
 
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Data Recording .................................................................................................. 24 
Investigator Documentation ................................................................................ 24 
GCP Training ..................................................................................................... 24 
Data Protection Training ..................................................................................... 24 
Information Security Training.............................................................................. 24 
Confidentiality .................................................................................................... 24 
Data Protection .................................................................................................. 25 
13 
STUDY CONDUCT RESPONSIBILITIES .......................................................... 25 
PROTOCOL AMENDMENTS ................................................................................ 25 
MANAGEMENT OF PROTOCOL NON-COMPLIANCE ........................................ 26 
Definitions .......................................................................................................... 26 
SERIOUS BREACH REQUIREMENTS ................................................................. 26 
END OF STUDY ................................................................................................... 27 
INSURANCE AND INDEMNITY ............................................................................ 27 
14 
REPORTING, PUBLICATIONS AND NOTIFICATION OF RESULTS ............... 27 
AUTHORSHIP POLICY ........................................................................................ 27 
Data Sharing ......................................................................................................... 28 
15 
REFERENCES .................................................................................................. 29 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
LIST OF ABBREVIATIONS 
 

 
 
 
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ACCORD Academic and Clinical Central Office for Research & Development - Joint office 
for The University of Edinburgh and Lothian Health Board 
BFI 
Brief Fatigue Inventory 
BMI 
Body Mass Index 
CI 
Chief Investigator 
CHI 
Community Health Index 
CRF 
Case Report Form 
EHP 
Endometriosis Health Profile 
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation 
ICH 
International Conference on Harmonisation 
ISF 
Investigator Site File 
MRI 
Magnetic Resonance Imaging 
NRS 
Numerical Rating Scale 
PI 
Principal Investigator 
PIS 
Participant Information Sheet 
PROM 
Patient Reported Outcome Measure 
QA 
Quality Assurance 
REC 
Research Ethics Committee 
SOP 
Standard Operating Procedure 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
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1 
INTRODUCTION 
 
BACKGROUND 
 
Endometriosis is characterised by the presence of endometrial-like tissue (‘lesions’) outside 
the uterus, commonly on the lining of the pelvic cavity. It is a chronic, inflammatory 
gynaecological condition that affects approximately 6-10% of women and those assigned 
female at birth (1, 2). It is associated with debilitating pelvic pain, gastrointestinal and 
urinary symptoms, fatigue and infertility (1, 3). Endometriosis can profoundly affect quality 
of life, limiting daily activities, social engagement, physical and sexual health, relationships, 
career and educational pursuits, mental well-being, and overall health. It is associated with 
a 45% reduction in work productivity with an annual cost for caring for women with 
endometriosis estimated at > £8.2 billion per year in the UK (4). 
 
Challenges in Diagnosis and Treatment 
People with endometriosis experience an average of 8 years of delay in the UK from the 
onset of their symptoms before receiving a diagnosis (5). There are no validated non-
invasive tests for endometriosis and the current gold standard for diagnosis is via a 
diagnostic laparoscopy (6, 7).  Currently, the waiting time for this procedure in the UK is 
variable across NHS Trusts and can be up to two years.  
Treatment options typically include: 
• Painkillers e.g. paracetamol, NSAIDs. 
• Surgery to remove endometriosis lesions, although this is ineffective in an estimated 
30 % of women and, even when its effective, symptoms return in up to 50% of 
women within 5 years of surgery (8). 
• Hormone therapies, which are not curative, can have significant side effects and are 
contraceptive (7). 
Some individuals explore lifestyle changes, such as dietary adjustments or exercise, but 
research on the effectiveness of these approaches remains limited (7). 

 
 
 
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RATIONALE FOR STUDY 
 
Endometriosis is a heterogeneous disease in terms of symptoms, trajectory, and indicated 
therapeutic course, which highlights the need to develop personalised and targeted 
approaches for effective longitudinal management which are acceptable and accessible to 
patients and their health care team. There is a clear unmet need for earlier diagnosis and 
more effective pain management for people who suffer from the condition (Horne, Saunders 
et al. 2017). 
 
Our goal is to accelerate discovery and advance data-driven research into endometriosis 
diagnosis and treatment by collecting large, multimodal, longitudinal data.  This study is for 
the collection of data which will be retrospectively analysed.  No feedback will be given to the 
individual participants on the results. 
 
To achieve our goal, we plan to deliver a longitudinal cohort study. We will invite 
approximately 3000 UK individuals with endometriosis to take part in the study. They will be 
asked to do the following over a 24-month period: 
 
(a) 
Record information about their pain, physical functioning, mental health/emotional 
functioning, diet/sleep, medical/surgical interventions and self-management 
strategies on a bespoke smartphone app specifically developed for the needs of this 
project  
(b) 
Wear smartwatches for up to four, six-week periods to collect raw actigraphy data 
(three-dimensional acceleration, wrist temperature, ambient light) from which we 
can objectively infer longitudinal physical activity, sleep, and circadian variability 
characteristics using algorithms we have developed in-house. The smartwatches will 
be posted to participants and include pre-paid envelopes for their return to the 
research team, following similar protocols we have already developed and 
successfully deployed at the University of Edinburgh in related longitudinal studies 
(e.g. the SHAW study, https://www.shaw.business-school.ed.ac.uk/). 
(c) 
Obtain serial self-collected samples of saliva, blood, faeces and urine on up to four 
occasions.  Sample collection kits will be sent to participants by our research team 

 
 
 
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by post, self-collected at home and posted by participants back to our research team 
for analysis in our laboratory. This approach in collecting samples remotely will allow 
us to collect information from a diverse population of patients with endometriosis 
UK-wide and builds on our experience with longitudinal data collection. 
 
Our proposed study has been informed by those with lived experience of endometriosis and 
by representatives from the UK patient organisation, Endometriosis UK.   
 
2 
STUDY OBJECTIVES 
 
2.1 
Primary Objective 
 
To generate a unique biomedical endometriosis resource with detailed clinical and lifestyle 
phenotyping. 
 
2.2 
Secondary Objectives 
 
To use the biomedical endometriosis resource to address fundamental questions in our 
understanding of endometriosis e.g. 
 
(i) To investigate the potential for patient stratification/prediction of treatment response 
from clinical/biological data profiles. 
(ii) To investigate the relationship between symptoms of pelvic pain and the gut-brain axis 
(including microbiome) using multi-omics data. 
(iii) To demonstrate longitudinal endometriosis symptom trajectories using app-based 
patient reported outcome measures (PROMs) and wearable technology (13). 
 
 
3 
STUDY DESIGN AND METHODS 
 
ENDO1000 is a UK-wide longitudinal cohort study.  Participants will be enrolled into the 
study, over a period of 36 months, via advertising on university and relevant websites, and 
by endometriosis support groups. We will also work with our established group to ensure 
that we can reach as diverse a population as possible. Participants will be asked to 
download our bespoke ENDO1000 app which will be available for both Android and iPhone 

 
 
 
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users, and, if needed, there will also be a web-based application.  The back-end server 
where everything will be controlled (from managing the PROMs to collecting data) will be 
hosted on a University of Edinburgh server and all data will be saved on a REDCap database 
on the same server.  They will then be given information about the trial and asked to sign an 
on-line consent form.  Following consent, they will be asked simple eligibility questions and 
will have access to the app.  The duration of study participation will be approximately 24 
months. During this time-period, the study participants will be asked to complete 
“trackers”, via the app, which will capture pain scores, menstrual cycle bleeding patterns, 
sleep patterns, bowel habits, analgesic use, hormone use, exercise patterns and dietary 
habits over time.  We will also record surgical interventions, self-management strategies 
e.g. acupuncture, etc.  If a participant has a significant change in their physical and mental 
health, they will also be asked to record this.   If a participant’s tracker completion is greater 
than 50%, they will be invited to take part in the biological sample collection component of 
the study and to wear a smartwatch on up to four occasions over the 24-month period.  At 
intervals, we will also ask participants to complete validated questionnaires which are 
detailed in Section 7 (this will correspond to when samples are collected, and the 
Smartwatch is worn).  
 
4 
STUDY SETTING 
 
The ENDO1000 study will be delivered entirely remotely via our bespoke mobile app. A 
web-based page will be available for those who prefer not to download or are unable to use 
the app (to mitigate against missing participants who might want to participate but do not 
own smartphones).  Participants will be asked to wear a smartwatch and obtain home self-
collected biological samples for laboratory analysis (genetics, inflammatory profiling, 
microbiomics, metabolomics). We have chosen this design to give us the ability to identify 
and relate changes in self-reported symptoms due to medical, surgical and self-
management, and to associate these changes with patterns in the gut microbiome and 
blood metabolome.  
 
 

 
 
 
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5 
STUDY POPULATION 
 
NUMBER OF PARTICIPANTS 
 
We aim to invite up to 3000 participants to take part in our study and obtain multimodal data 
(PROMs, biological samples and data from the wearables). We envisage that this will enable 
us to obtain our target of 1000 participants with complete data sets for analysis.  
 
INCLUSION CRITERIA 
• Aged 16 or over 
• Participants who confirm that they have received a clinical diagnosis of endometriosis 
(based on MRI, ultrasound or laparoscopy) within the last 10 years  
• Living within the UK  
Willing and able to consent to installing and using the mobile ENDO1000 app on their 
smartphone or use our web-based equivalent.  
 
EXCLUSION CRITERIA 
• Pregnant 
• Known severe coagulation disorder  
• Known active Hepatitis B/C and/or HIV (due to Royal Mail restrictions on 
biospecimen postage)  
CO-ENROLMENT 
 
Participants will be permitted to co-enroll in CTIMP and interventional non-CTIMP clinical 
trials. Participants will also be permitted to take part in non-interventional non-CTIMP 
research (e.g. questionnaire/tissue only studies).  
 
 
 
 

 
 
 
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6 
PARTICIPANT SELECTION AND ENROLMENT 
 
IDENTIFYING PARTICIPANTS 
 
We will advertise our study (images of posters and flyers)with the support of relevant UK 
endometriosis charities and support groups (through their websites and via their social media 
platforms), through mailshots.  Potential participants will self-refer to the study.  We will work 
with our endometriosis PPI group to ensure that we can reach difficult to reach populations. 
 
CONSENTING PARTICIPANTS 
Individuals who decide they wish to take part in our study will be able to install the bespoke 
ENDO1000 mobile app via a link on the ENDO1000 website (see screenshots below).   
1. For initial registration with the app, they will need to first agree to our ‘terms and 
conditions’ and ‘privacy policy’, by reading them and then confirming acceptance on 
the app.   
2. To register for the study, they will be required to submit minimal information – their 
name, email address and month and year of birth (this is stored on servers within 
the University of Edinburgh).   
3. If they wish to consider participating in the study, they will be invited to watch a 
short, animated video detailing the study and be given access to the study 
participant information sheet, both accessed via the app or via the ENDO1000 
website.    
4. If they agree to consent, they will then be directed to an online consent form that 
they will be asked to electronically sign.   
5. Once consent has been obtained, we will then ask three short eligibility questions to 
help us to direct them to relevant sections of the app and also their ongoing 
‘journey’ in the study. 
The app will have a “Frequently Asked Questions” section (FAQ). We will also include email 
contact details for the ENDO1000 research team should they have questions about the 
study/app that have not been answered within the mobile app itself.  We will ensure that it 
is clear that this email is only for questions related to the study and that clinical questions 
cannot be answered by the research team.    

 
 
 
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To incentivise participants to contribute their data, we will provide personalised reports on 
their activity and sleep patterns from the wearing of the smartwatches (if requested). We 
have delivered these personalised reports in similar projects where participants have 
contributed to our research, in terms of data from wearables, and it was very well received. 
Furthermore, we plan ENDO1000 webinars to disseminate findings to the study participants 
where we will address questions from participants after we have completed our data 
analysis. 
 
SCREENSHOTS OF ENDO1000 MOBILE APP 
 
 
 
 
 
 

 
 
 
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SCREENSHOTS OF REAL TIME DATA AVAILABLE FROM THE TRACKERS 
 
Withdrawal of Study Participants 
Participants will be free to withdraw from the study at any point by simply stopping using 
the app and without needing to provide any justification.  If they have provided data or 
biological samples, the data derived from these samples will be used, unless the participant 
expressly asks for them not to be used. We will make it clear that participants can make this 
request by contacting the research team directly on etmt@ed.ac.uk. 
 
LONG TERM FOLLOW UP ASSESSMENTS 
There is no planned longer term follow up for the study participants, but we will seek 
consent to contact participants for continuation of this study longer term should we obtain 
funding to extend it. We will also ask their permission to contact them to see if they would 
like to take part in other related studies, subject to further funding. 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
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7 
STUDY ASSESSMENTS 
 
Assessments completed over a 24-month period 
Self-referral by downloading the ENDO1000 App via the ENDO1000 website/app store. 
Electronic Consent – ‘terms and conditions’ of the app, ‘privacy notice’ (including data storage) and study 
consent. 
Eligibility, demographic data, contact details. 
Completion of WERF EPHect questionnaire (REF) – a questionnaire to collect medical history and 
endometriosis symptoms over their lifetime (completed once). 
Completion of app ‘trackers’ – record of pain scores, menstrual cycle bleeding patterns, sleep patterns, 
exercise patterns, bowel habits, dietary habits, analgesic use. 
If a participant’s tracker completion is greater than 50%, they will be sent a home self-collection kit for 
biological sample collection and a smartwatch. 
Self-collected sample collection kits will be sent to participant’s home address (saliva, blood, faeces and 
urine - up to four times during the 24-month time-period 
Completion of Study Questionnaires (detailed in section below)– a minimum of four times during the 24-
month time-period to correspond with sample collection. 
Wear Smartwatch – up to four times during the 24-month time-period 

 
 
 
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Flowchart of participation 
 
 
 
 
 
 
 

 
 
 
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Example of ENDO1000 app “Home” page 
 
 
 

 
 
 
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Biological sample collection 
Biosamples (saliva, blood, faeces and urine) will be collected at up to four timepoints over 
24 months.  The biosamples will be collected using the following approved home self-
collection kits (or similar available products): 
 
Biological 
sample 
Collection 
Kit 
Manufacturer 
Supplier 
reference 
Website link 
Saliva 
OMNIgene-
Oral  
DNA Genotek 
OM-501 
https://www.dnagenotek.com/row/support/collection-
instructions/omnigene-oral/OM-501 
 
Blood  
30ul Mitra 
micro 
sampling 
device 
Trajan 
Scientific 
Europe LTD 
30004 
https://1806452.fs1.hubspotusercontent-
na1.net/hubfs/1806452/VLBL-0125-R_Rev02_web.pdf 
 
Tasso+ 
600ul self-
collection 
Tasso Inc 
K1025-01-EDT 
https://www.tassoinc.com/eu/tassoplus-kit-ifu 
 
Faeces  
Omnigene-
Gut 
DNA Genotek  
OM-200 
https://www.dnagenotek.com/row/support/collection-
instructions/omnigene-gut/OM-200 
 
Urine 
Colli-Pee 
UCM 20ml 
DNA Genotek  
N00176_RUO 
https://dnagenotek.com/ROW/products/collection-
infectious-disease/colli-pee/colli-pee_first-void-urine-
collection#working 
 
 
Study questionnaires 
Questionnaires will include: 
WERF EPHect Patient Questionnaire: to collect epidemiological and genetic data in 
endometriosis research (9).  
Endometriosis Health Profile-30 (EHP-30): an endometriosis-specific questionnaire with 30 
questions and five scales (10) 
Brief Fatigue Inventory (BFI) (11) 
The Pittsburgh Sleep Quality Index (12) 
Food Frequency Questionnaire (FFQ) (REF) 
 
 
8 
DATA COLLECTION/MANAGEMENT 
 
All patient reported data will be recorded on our ENDO1000 mobile app which will use the 
Amazon Web Service (AWS) IS cloud, server hosting infrastructure. The app will be hosted 
on AWS where data will initially be captured but sent to UoE IGMM servers for long-term 

 
 
 
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storage.  This data will include questions to capture the baseline demographic and clinical 
characteristics of the participants.  
Participants will not be able to access any of their data from the smartwatches (there is no 
display). Anonymised data from the returned smartwatches will be downloaded to UoE 
servers via the Geneactiv Windows programme and will be matched to PROMs via the 
participant study IDs. The anonymised data will only be viewed by the research team.  There 
is no identifiable data contained within the dataset generated by the smartwatches, apart 
from raw three-dimensional acceleration, ambient light, and wrist temperature data.  When 
the data is uploaded to REDcap by our research team, the participants PIN will be allocated 
to the data. Datasets of raw measurements made from the anonymised human biological 
samples will only be accessible to members of the research team. 
 
Source Data Documentation 
In our study, source documents will include: 
Participant completed questionnaires 
Smartwatch data held in the GENEActiv PC Software App and uploaded to REDcap 
Laboratory results from analysis of biospecimens. 
 
PERSONAL DATA 
 
The following personal data will be collected as part of the study: name, email address, mobile 
telephone number, postcode, ethnicity and date of birth. An address will be required if 
participants consent to the collection of biological samples. 
All data will be collected, processed and stored in line with the General Data Protection 
Regulation (GDPR). 
Electronic personal data will be stored on UoE secure servers that require user 
authentication. Computers and database access will be password-protected.  . Name, email 
address, signature, and mobile number will be stored on AWS servers to enable app 
functionality (e.g., notifications, app logins, and questionnaire delivery). These data items 
will also pass through AWS servers during transit to UoE’s secure servers. AWS will be 
secured with two-factor authentication (2FA) and encrypted both at rest and in transit, 
with HTTPS-secured API communications. 
 

 
 
 
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Personal data will be stored for a minimum of 5 years following the end of the trial. The 
personal data will be held with separate access to the pseudo-anonymized data and will be 
linked via a participant study ID which will be the only identifier used to match the different 
modalities (PROMs, biological data samples, data from wearables). The data analysis team 
will only have access to the pseudo-anonymised data. 
Data Information Flow 
Participants will input their information directly into the app, which will be securely 
transferred via AWS servers to the REDCap database. Identifiable data (name, email, mobile, 
signature) is stored in AWS to support app functionality and is also stored within REDCap 
with restricted access. This identifiable data will not be accessible to the data analysis team. 
 
The electronic consent form and the participant ID log will be the only two places where 
identifiable data is collected and this will be stored within REDCap with restricted access.  
This will not be available to be viewed by the data analysis team.  The consent forms will 
contain the participants’ name. The ID log will have the name, address including postcode, 
details will all be stored only to contact the participant for sending of the biological sampling 
kits.  
 
The REDCap database will also contain email address (with consent) to allow for sending out 
the questionnaires electronically or via the mobile application (in the form of a notification). 
All other data collected will be anonymised. Identifiable data will not be released to the data 
analysis team or any third party.  
 
Data Storage 
 
As stated in section 8.1, personal data will be stored by the research team on a UoE secure 
server. This will be held separately to the information that can be accessed on the UoE server 
by the data analysis team. 
The trial data will be stored on our REDCap database hosted on the UoE secure server, 
requiring user authentication for access. The database will be validated, ensuring integrity 
and security of the data to be collected.  This will include mobile numbers (with consent) to 
send out notifications via the mobile application in the form of a notification should these 
require completion if non-engagement occurs. 

 
 
 
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Any exported data from the database will be stored in a DataShare point as a safe data 
server (which is regularly backed-up) from the University of Edinburgh to exchange 
information. Authorised (via dedicated personalised credentials) team members will be 
accessing to download the collected data and provide outputs of the analysis for internal 
circulation. This will be authorised by the PI who has the responsibility on who is given 
access to the data. 
Data Retention 
Personal data collected as part of this trial will be stored for a minimum of 5 years following 
the completion of the trial, for administration of the trial. This retention period will be 
longer for those who consent to be contacted about future research. This will be specific 
item on the consent form.  
Trial data will be archived at the end of the trial and stored for a minimum of 5 years on secure 
servers hosted by the UoE.  
Disposal of Data 
Data will be archived as per Sponsor’s SOPs.  When the minimum retention period has been 
reached, material will not be destroyed without authorisation from the Sponsor. Disposal of 
data will be as per Sponsor guidance. 
External Transfer of Data 
Selected anonymised data collected or generated by the study may also be shared with 
other researchers from other institutions once the study is finished. No participant can be 
identified by their data as this will be anonymised and the team is experienced in 
obfuscating e.g. PROMs and data from the wearable sensors to minimize any potential risk.  
Data transfer will be in accordance with General Data Protection Regulations, ICH GCP and 
SOPs of the Sponsoring organisation. 
Data Controller 
A data controller is the organisation that determines the purposes for which, and the 
manner in which, any personal data are processed. The UoE and NHS Lothian will be joint 
data controllers along with any other entities involved in delivering the study that may be a 
data controller in accordance with applicable laws (e.g. the site). 
 

 
 
 
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Data Breaches 
 
Any data breaches will be reported to the UoE Data Protection Officers (dpo@ed.ac.uk) who 
will onward report to the relevant authority according to the appropriate timelines if 
required. 
 
Data Information Flow 
 
Participant data for this study will be collected via our ENDO1000 purpose-built mobile 
application, which has been developed specifically for secure and user-friendly data capture 
in the context of clinical research. 
 
Each participant will be required to create a password-protected account to access the app. 
This ensures that only the individual participant can view or enter their own data. All login 
credentials are stored securely using hashed encryption, and multi-level safeguards are in 
place to prevent unauthorised access to personal or study data. 
 
All data entered into the app will be stored temporarily on a secure, region-locked Amazon 
Web Services (AWS) server located within the European Union (EU). This ensures full 
compliance with the General Data Protection Regulation (GDPR) in terms of data residency, 
security, and access controls. Data are encrypted both in transit and at rest, using industry-
standard cryptographic protocols. 
 
Data will then be transferred from the AWS environment to the study database hosted on 
the UoE’s REDCap platform. This transfer occurs over encrypted HTTPS channels using 
REDCap’s secure API functionality. Each transmission is authenticated using unique API 
tokens and logged to maintain a full audit trail. 
 
Once received, the data will be stored within REDCap on secure servers maintained by the 
UoE. Access to REDCap is strictly role-based, restricted to authorised study personnel, and 
governed by institutional policies on information governance and data security. 

 
 
 
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All aspects of data handling, transmission, and storage conform to GDPR and relevant local 
regulations.  
 
9 
BIOSAMPLE STORAGE AND ANALYSIS 
 
The biological samples will be processed, stored and analysed in Professor Andrew Horne’s 
laboratory (unless indicated otherwise) within the Centre for Reproductive Health, Institute 
of Regeneration and Repair, University of Edinburgh.  DNA will be extracted from salivary 
and faecal samples, and stored for genetic analysis.  The faecal DNA samples will be sent to 
Dr Siobhain O’Mahoney, University of Cork for microbiome analysis (covered by a material 
transfer agreement and data sharing agreement as required). Other analyses will include 
profiling of hormones and inflammatory markers (blood), the metabalome (blood/faeces), 
and proteomics (blood/urine). 
10 
STATISTICS AND DATA ANALYSIS 
 
SAMPLE SIZE  
 
It is challenging for us to provide a detailed power calculation for the study given that we 
will be collecting multidimensional data from heterogeneous sources. Therefore, the driving 
consideration is for us to have sufficient statistical power to explore hypotheses and 
develop robust statistical learning models. Given our extensive prior experience in 
endometriosis clinical practice and clinical trials, we are confident that recruitment 
ENDO1000 of up to 3000 women (to yield 1000 complete data sets) is ambitious yet 
feasible. This number of complete data sets will be sufficiently large to be hypothesis-
generating and enable exploratory statistical analysis, including data stratification to 
investigate specific subsets that might merit further exploration. It will be large enough to 
test specific, pre-determined hypotheses in endometriosis, e.g. the association between 
symptoms of pelvic pain and the gut-brain axis using multi-omics data. We envisage 
exploring data using standard statistical analysis techniques for visualisation (density plots, 
scatter plots), statistical association computations (e.g. correlation analysis), and feature 
selection/feature transformation/latent variable methods. Moreover, we will apply robust 
supervised machine learning algorithms and standard model validation schemes to assess 
the performance of the developed statistical learning models, providing robust estimates of 

 
 
 
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their likely generalisation in new unseen data. The requirement to collect a large sample 
size is to enable the exploration of different stratification strategies, e.g. exploring age-
based strata and other approaches that we may want to explore to study separate certain 
groups. 
 
DATA ANALYSIS 
 
Demographic information and self-reports on standardised questionnaires: The self-reports 
will be longitudinal on a regular basis (weekly). The raw data will be provided in *.csv 
format. WP18 will process these to derive characteristic patterns and summary data to 
characterize individual participants (e.g. in terms of self-reported symptom variability, 
symptom trajectory trends, and information for different strata based on age and 
endometriosis subtypes). Similarly, we will explore the presence of latent variables using a 
range of embedding algorithms (resulting in different derived datasets), as we have done in 
related studies processing self-reported outcome measures. 
 
Actigraphy data collected using smartwatches: We will request participants provide 
repeated entries (i.e. 3-4 times wearing these smartwatches, each time recording about 40 
days’ worth of data). From the actigraphy data, we will compute physical activity, sleep, and 
diurnal variability characteristics to infer participant-specific trajectories. The raw data from 
these devices will be in binary (*.bin) format, and we have 10+ years of experience working 
with this type of actigraphy data for further processing. We will process the raw actigraphy 
data to derive information about sleep, physical activity, and diurnal variability for every 
individual in the study. This will be used to characterise each day and will be used alongside 
the self-reports by participants to derive a multimodal dataset. 
 
We will process the biological samples to identify patterns in repetitive measurements, and 
these will complement the extracted information from the self-reports and the actigraphy 
data to derive a multimodal dataset comprising different types of information. 
 

 
 
 
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11 
OVERSIGHT ARRANGEMENTS 
 
INSPECTION OF RECORDS 
Investigators and institutions involved in the study will permit study related monitoring and 
audits on behalf of the Sponsor, ethics review, and regulatory inspection(s).  In the event of 
audit or monitoring, the Investigator agrees to allow the representatives of the Sponsor 
direct access to all study records and source documentation. In the event of regulatory 
inspection, the Investigator agrees to allow inspectors direct access to all study records and 
source documentation. 
 
12 
GOOD CLINICAL PRACTICE 
 
ETHICAL CONDUCT 
The study will be conducted in accordance with the principles of the International 
Conference on Harmonisation Tripartite Guideline for Good Clinical Practice (ICH GCP). 
Before the study can commence, all required approvals will be obtained and any conditions 
of approvals will be met. 
 
INVESTIGATOR RESPONSIBILITIES 
The Investigator is responsible for the overall conduct of the study and compliance with the 
protocol and any protocol amendments.  In accordance with the principles of ICH GCP, the 
following areas listed in this section are also the responsibility of the Investigator.  
Responsibilities may be delegated to an appropriate member of study site staff named on 
the list prior to undertaking applicable study-related procedures. 
 
Informed Consent 
The trial team is responsible for ensuring electronic informed consent is obtained before 
any protocol specific procedures are carried out. The decision of a participant to participate 
in research is voluntary and will be based on a clear understanding of what is involved. 
Participants must receive adequate information – appropriate Participant Information.  
It will be emphasised that the participant may withdraw their consent to participate at any 
time without loss of benefits to which they otherwise would be entitled. 

 
 
 
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The participant will be informed (if relevant) and agree to their data being inspected by 
representatives of the Sponsor, if applicable. 
Consent will be electronic and a copy of this will be available to them within the App. 
 
Data Recording 
The Principal Investigator will be responsible for the quality of the data recorded.  
 
Investigator Documentation 
The Principal Investigator will ensure that the required documentation is available. 
 
GCP Training 
All researchers involved in the study will be encouraged to undertake GCP training in order 
to understand the principles of GCP. GCP training status for all investigators will be indicated 
in their respective CVs.  
 
Data Protection Training 
All University of Edinburgh employed researchers and study staff will complete the Data 
Protection Training training module through Learn. 
 
Information Security Training 
All University of Edinburgh employed researchers, students and study staff will complete 
the Information Security Essentials modules through Learn and will have read the minimum 
and required reading setting out ground rules to be complied with. 
 
Confidentiality 
All, evaluation forms, reports, and other records will be identified in a manner designed to 
maintain participant confidentiality.  All records will be kept in a secure storage area with 
limited access.  Clinical information will not be released without the written permission of 
the participant.  The Investigator and study site staff involved with this study will not 
disclose or use for any purpose other than performance of the study, any data, record, or 

 
 
 
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other unpublished information, which is confidential or identifiable, and has been disclosed 
to those individuals for the purpose of the study.  Prior written agreement from the Sponsor 
or its designee will be obtained for the disclosure of any said confidential information to 
other parties. 
 
Data Protection 
All Investigators and study site staff involved with this study will comply with the 
requirements of the appropriate data protection legislation (including the UK General Data 
Protection Regulation legislation and Data Protection Act) with regard to the collection, 
storage, processing and disclosure of personal information. Any members of the team 
accessing and processing the data will be required to undergo training for sensitive data 
protection (e.g. the MRC Data confidentiality course) and will be expected to adhere to 
standard good practices to protect participant anonymity. 
Computers used to collate the data will have limited access measures via user names and 
passwords. Computers where the analysis will take place will be password protected and 
use the latest anti-virus and anti-malware protection; only anonymised/pseudo-anonymised 
data will be allowed to protect participant anonymity. 
Published results will not contain any personal data that could allow identification of 
individual participants. 
 
13 
STUDY CONDUCT RESPONSIBILITIES 
 
PROTOCOL AMENDMENTS 
Any changes in research activity, except those necessary to remove an apparent, immediate 
hazard to the participant in the case of an urgent safety measure, will be reviewed and 
approved by the Chief Investigator.   
Proposed amendments will be submitted to a Sponsor representative for review and 
authorisation before being submitted in writing to the appropriate EC (or any other local 
requirements) for approval prior to participants being enrolled into an amended protocol. 
 
 

 
 
 
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MANAGEMENT OF PROTOCOL NON-COMPLIANCE 
 
Prospective protocol deviations, i.e. protocol waivers, will not be approved by the Sponsor 
and therefore will not be implemented, except where necessary to eliminate an immediate 
hazard to study participants. If this necessitates a subsequent protocol amendment, this will 
be submitted to the EC, for review and approval if appropriate. 
 
Definitions 
Deviation - Any change, divergence, or departure from the study design, procedures defined 
in the protocol or GCP that does not significantly affect a subject’s rights, safety, or well-
being, or study outcomes. 
Violation - A deviation that may potentially significantly impact the completeness, accuracy, 
and/or reliability of the study data or that may significantly affect a subject’s rights, safety, 
or well-being. 
Protocol deviations will be recorded in a protocol deviation log and logs will be submitted to 
the Sponsor every 3 months. Each protocol violation will be reported to the Sponsor within 
3 days of becoming aware of the violation.  All protocol deviation logs and violation forms 
should be emailed to QA@accord.scot. 
Deviations and violations are non-compliance events discovered after the event has 
occurred.  Deviation logs will be maintained for each site in multi-centre studies.  
 
SERIOUS BREACH REQUIREMENTS 
A serious breach is a breach which is likely to affect to a significant degree: 
(a) the safety or physical or mental integrity of the participants of the research; or 
(b) the scientific value of the research. 
If a potential serious breach is identified by the Chief investigator, Principal Investigator or 
delegates, the Sponsor (qa@accord.scot) will be notified within 24 hours.  It will be the 
responsibility of the Sponsor to assess the impact of the breach on the scientific value of the 
research, to determine whether the incident constitutes a serious breach and report to EC 
as necessary.  
 

 
 
 
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END OF STUDY 
The end of study is defined as the last participant’s last data collection point.   
The Investigators or the Sponsor have the right at any time to terminate the study for 
clinical or administrative reasons.  
The end of the study will be reported to the EC and Sponsor within 90 days, or 15 days if the 
study is terminated prematurely. The Investigators will inform participants of the premature 
study closure and ensure that the appropriate follow up is arranged for all participants 
involved. End of study notification will be reported to the Sponsor via email to 
resgov@accord.scot. 
A summary report of the study will be provided to the EC within 1 year of the end of the 
study. 
 
INSURANCE AND INDEMNITY 
The Sponsor will be responsible for ensuring proper provision has been made for insurance 
or indemnity to cover their liability and the liability of the Chief Investigator and staff. 
The following arrangements are in place to fulfil the Sponsor responsibilities: 
The Protocol has been designed by the Chief Investigator and researchers employed by the 
University and collaborators.  The University has insurance in place (which includes no-fault 
compensation) for negligent harm caused by poor protocol design by the Chief Investigator 
and researchers employed by the University. 
Sites participating in the study will be liable for clinical negligence and other negligent harm 
to individuals taking part in the study and covered by the duty of care owed to them by the 
sites concerned.  The Sponsor requires individual sites participating in the study to arrange 
for their own insurance or indemnity in respect of these liabilities. 
Sites out with the United Kingdom will be responsible for arranging their own indemnity or 
insurance for their participation in the study, as well as for compliance with local law 
applicable to their participation in the study. 
 
14 
REPORTING, PUBLICATIONS AND NOTIFICATION OF RESULTS 
 
AUTHORSHIP POLICY 
Ownership of the data arising from this study resides with the study team.   

 
 
 
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Data Sharing 
At the end of the project or following publications we can make anonymised data available 
(subject to a data access request and appropriate contracts put in place) to other researchers 
to conform with good research practice allowing reproducibility of findings. 
 
 

 
 
 
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15 
REFERENCES 
 
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