Cancer Loyalty Card Study: a Retrospective Observational Case-Control Study
Conditions: Ovarian Neoplasms
Sponsor: Imperial College London

 
 
1 
 
 
 
CLOCS 
 
 
 
 
Cancer Loyalty Card Study 
 
 
 
 
Version 3 06/05/2020 
 
 
 
 
MAIN SPONSOR: Imperial College London 
FUNDERS: Cancer Research UK 
STUDY COORDINATION CENTRE: Ovarian Cancer Action Research Centre 
   
 
 
 
    Imperial College London 
   
 
 
 
    4th Floor, Institute of Reproductive and Developmental Biology (IRDB) 
IRAS Project ID: 262776 
 
 
 
Protocol authorised by: 
 
Name & Role 
Date 
Signature 
James Flanagan, 
Principal Investigator 
08/08/2019 
 
Hannah Brewer, 
Research Associate 
08/08/2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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Study Management Group 
 
Chief Investigator: James Flanagan 
 
Co-investigators: Hannah Brewer, Yasemin Hirst, Sudha Sundar, Marc Chadeau-Hyam 
 
Statistician: Marc Chadeau-Hyam 
 
Study Management: James Flanagan 
 
 
Study Coordination Centre  
 
For general queries, supply of study documentation, and collection of data, please contact: 
 
Study Coordinator: James Flanagan 
Address: Division of Cancer, Department of Surgery and Cancer 
Imperial College London 
4th Floor, IRDB, Hammersmith Campus 
Du Cane Rd, London, W12 0NN 
 
 
 
 
 
Registration:  
Tel: 0207 5942127 
 
 
 
 
                E-mail: clocs@imperial.ac.uk 
Fax:          
 
 
          
 
 
Web address: clocsproject.org.uk  
 
A list of research sites where recruitment will take place in the clinic can be found in 
Appendix 3. 
 
Clinical Queries 
 
Clinical queries should be directed to James Flanagan who will direct the query to the 
appropriate person. 
 
Sponsor 
 
Imperial College London is the main research Sponsor for this study. For further information 
regarding the sponsorship conditions, please contact the Head of Regulatory Compliance at: 
 
 
 
Joint Research Compliance Office 
Imperial College London and Imperial College Healthcare NHS Trust 
Room 215, Level 2, Medical School Building 
Norfolk Place 
London, W2 1PG 
Tel: 0207 594 1862 
 
Funder 
 
Cancer Research UK Early Diagnosis Project Grant (C38463/A26726)  
 
This protocol describes the Cancer Loyalty Card study (CLOCS) and provides information about 
procedures for entering participants. Every care was taken in its drafting, but corrections or 
amendments may be necessary. These will be circulated to investigators in the study. Problems 
relating to this study should be referred, in the first instance, to the Chief Investigator.  

 
 
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This study will adhere to the principles outlined in the UK Policy Frame Work for Health and Social 
Care Research. It will be conducted in compliance with the protocol, the Data Protection Act and other 
regulatory requirements as appropriate.  
 
Table of Contents 
1. 
INTRODUCTION 
5 
1.1 
BACKGROUND 
5 
2.   
STUDY OBJECTIVES 
6 
3.   
STUDY DESIGN 
6 
3.1 
STUDY OUTCOME MEASURES 
8 
4. 
PARTICIPANT ENTRY 
8 
4.1 
PRE-REGISTRATION EVALUATIONS 
8 
4.2 
INCLUSION CRITERIA 
8 
4.3 
EXCLUSION CRITERIA 
8 
4.4 
WITHDRAWAL CRITERIA 
8 
5. 
PARTICIPANT RECRUITMENT AND CONSENT 
8 
5.1 
RECRUITMENT OF WOMEN WITHOUT OVARIAN CANCER (CONTROLS) 
8 
5.2 
RECRUITMENT OF WOMEN WITH OVARIAN CANCER (CASES) 
9 
5.3. 
RECRUITMENT CONTINGENCY PLAN (COVID-19 RESTRICTIONS) 
10 
6.  
OVARIAN CANCER RISK FACTOR AND SYMPTOM DATA COLLECTION
 
10 
7. 
LOYALTY CARD DATA COLLECTION 
11 
8. 
ASSESSMENT AND FOLLOW-UP 
12 
9. 
STATISTICS AND DATA ANALYSIS 
13 
9.1 
DATA MANAGEMENT AND FLOW 
13 
9.2 
DATA ANALYSIS 
14 
10.  
REGULATORY ISSUES 
15 
10.1 
ETHICS APPROVAL 
15 
10.2 
CONSENT 
15 
10.3 
CONFIDENTIALITY 
15 
10.4 
INDEMNITY 
16 
10.5 
SPONSOR 
16 
10.6 
FUNDING 
16 
11. 
STUDY MANAGEMENT 
16 
12. 
PUBLICATION POLICY 
16 
13. 
REFERENCES 
17 
APPENDIX 1. 
SUMMARY OF CLOCS RECRUITMENT PROCESS 
19 
APPENDIX 2. 
SUMMARY OF CLOCS DATA FLOW 
20 

 
 
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APPENDIX 3. OVERVIEW OF RESEARCH SITES 
21 
 
 

 
 
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GLOSSARY OF ABBREVIATIONS 
CLOCS 
Cancer Loyalty Card Study 
HSR1 
High Street Retailer 1 
HSR2  
High Street Retailer 2 
 
KEYWORDS 
Ovarian Cancer 
Epidemiology 
Observational Study 
Risk Assessment 
 
STUDY SUMMARY 
TITLE Cancer Loyalty Card Study (CLOCS) 
DESIGN Observational, retrospective case-control study 
AIMS The CLOCS aims to investigate whether or not women have distinctive self-
management behaviours prior to seeing their doctor with symptoms that are 
associated with ovarian cancer. 
OUTCOME MEASURES The primary outcome of the CLOCS will be to define the time by which the 
cases and controls are statistically significantly different in their purchase 
behaviours leading up to diagnosis on a population level. 
The secondary outcome of the CLOCS will be defining a purchase threshold 
as an “alert” about cancer symptoms in individuals and determining the 
predictive utility of purchasing behaviours in the early detection of ovarian 
cancer. Exploratory analyses will include longitudinal analyses, frequency of 
purchases and an unbiased analysis of other purchase categories. 
POPULATION At least 1000 women in the UK (500 ovarian cancer cases and 500 controls)  
ELIGIBILITY Women, at least 18 years old, who own at least one participating high street 
retailer loyalty card are eligible to join the CLOCS. Among these women, 
those who have been diagnosed with ovarian cancer can join the CLOCS 
as cases, and those who have no prior ovarian cancer diagnosis are eligible 
to join as controls. 
DURATION 3 years 
 
 
1. 
INTRODUCTION  
 
1.1 
BACKGROUND 
The ten‐year survival rate for epithelial ovarian cancer (EOC) is only 35% in the UK 
and is dramatically different for stage 1 disease (90%) compared with stage 3‐4 (5‐
15%). Survival in the UK lags behind Europe; this is attributed partly to a delay in 
diagnosis [1]. Earlier detection of low‐volume disease or earlier stage ovarian cancer 
will save lives [2]. 
 
EOC is a heterogeneous disease with different histological subtypes that show 
strikingly different molecular [3] and mutational profiles [4,5]. With the Ovarian 

 
 
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Cancer Association Consortium (OCAC), we have identified 34 common genetic 
polymorphisms contributing to polygenic risk [6–9]. Epidemiological risk factors 
provide a predictive model with a modest discriminatory power (AUC=0.65), 
improved slightly with polygenic risk (AUC=0.66) [10], and this model has been 
proposed to improve EOC detection with risk stratified screening [11]. 
 
EOC usually presents with vague and non‐alarming symptoms. As a result, most 
women are diagnosed late when the cancer has already spread and the prognosis is 
poor. The most common symptoms associated with EOC are increased abdominal 
size, pelvic pain, abdominal pain and bloating, feeling full quickly and difficulty eating 
[12,13]. The major reasons for not presenting to the GP with symptoms such as 
these are “not wanting to waste the GP’s time” [14] and normalisation of these 
symptoms [15]. The persistence of a symptom, social influence and awareness 
encourage help‐seeking behaviours in primary care [16]. However, few believe that 
their symptom(s) might be a sign of cancer [17]. Consequently, people might choose 
to self‐manage their symptoms by using over‐the-counter medication, and to seek 
advice from other sources, (pharmacists, family, internet), rather than a primary care 
physician. 
 
1.2 
RATIONALE FOR CURRENT STUDY 
Approximately 7,400 new cases of ovarian cancer are diagnosed each year in the UK, 
and with over 4,000 women dying from the disease each year it is a particularly lethal 
form of cancer. The symptoms are not well known, are vague and non-specific and 
most women are diagnosed at a late stage when the cancer has already spread around 
the peritoneum with poor prognosis. Novel methods are needed to improve earlier 
detection and thereby improve survival from this disease. We hypothesise that a 
change in purchasing behaviour, primarily an increase in self-medication to treat these 
vague cancer symptoms, may provide a novel avenue for earlier diagnosis for cancer. 
 
In this study we propose to use loyalty card data from two participating high street 
retailers (Boots and Tesco) to investigate purchase behaviour as an opportunity for 
cancer symptom surveillance. We aim to conduct a case-control study of women with 
ovarian cancer (cases) matched with women who do not have ovarian cancer 
(controls) and define the time by which the cases are statistically significantly different 
in their purchase behaviours leading up to date of diagnosis, compared with the control 
purchase behaviours. 
 
 
2.   
STUDY OBJECTIVES 
 
2.1 
The primary aim of the CLOCS will be to define the time by which participants with 
ovarian cancer are statistically significantly different in their purchase behaviours 
leading up to date of diagnosis, compared with purchase behaviours of participants 
without ovarian cancer. 
 
2.2  
The secondary aim of the CLOCS will be to define a purchase threshold as an “alert” 
about cancer symptoms in individuals and determining the predictive utility of 
purchasing behaviours in the early detection of ovarian cancer. 
 
3.   
STUDY DESIGN 
 
Purpose and Design 

 
 
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The Cancer Loyalty Card Study (CLOCS) is addressing whether or not data already 
collected by high street retailers can detect significant changes in purchase behaviours of 
ovarian cancer patients prior to their diagnosis. We aim to conduct a case-control study of 
ovarian cancer patients matched with women who do not have ovarian cancer. We will 
recruit at least 500 recently diagnosed ovarian cancer patients and at least 500 healthy 
women as controls and collate up to 6 years of prior purchase data. 
 
Recruitment 
Women living with ovarian cancer and who own at least one of the participating high street 
retailer’s loyalty cards will be recruited in a clinic by a member of their healthcare team 
where the study is open (recruitment sites listed in Part C).  
 
Women, 18 years or older, living in the UK who have a loyalty card at the participating high 
street retailers will be recruited through the study website (www.clocsproject.org.uk) where 
data collection will be safeguarded using an encrypted web form that includes study consent 
and the self-report questionnaire.  There will be a press release and social media about the 
study inviting loyalty card holders to visit the CLOCS website for more information and join 
the study. Any woman considering joining the study can contact the research team using the 
contact details on the information sheet.  
 
Consent 
Ovarian cancer patients will be given the information sheet and consent form in the clinic by 
a member of their healthcare team. They can take as much time as they need to read 
through the information sheet. If they choose to participate, they can complete the consent 
form whenever is convenient for them and return it to the CLOCS team in the freepost 
envelope provided to them in the clinic.  
 
Alternative recruitment strategy during Covid-19 lockdown to minimise contact with patients 
The research sites will be asked to identify the patients who may be eligible for the study 
using their records and contact them by phone to facilitate recruitment to CLOCS. During 
this process, the research nurse will read out the information sheet and ask participants if 
they wish to take part. If patients are interested in taking part, then they will complete the 
consent forms and the questionnaire on their behalf. They will take a copy of the completed 
questionnaire and the consent form and post the original to the CLOCS team using CLOCS 
freepost envelope and post the copy including the information sheet and privacy policy to the 
patients. Patients similar to the previous protocol can withdraw their consent at any stage of 
the study.  
 
Women without ovarian cancer will be presented with the information sheet and consent 
form on the study website and can consent to participate online.   
 
Methods 
Consenting participants will complete a brief questionnaire about ovarian cancer risk factors, 
which will also be returned to the CLOCS team through the mail or on the website (healthy 
volunteers only). Participants with ovarian cancer will also have a clinical form for a member 
of their clinical team to complete in the clinic. This will be sent to the CLOCS team along with 
their consent and risk factor questionnaire in the freepost envelope. In order to adhere with 
participating high street retailers’ policies, healthy volunteers will need to provide a photo ID 
and utility bill for ID verification. This is not required for participants with ovarian cancer 
because they will be recruited by a member of their care team in the clinic. 
 
Two ovarian cancer patients have reviewed all questionnaires and CLOCS documents and 
expressed their approval. Women without ovarian cancer from the general UK population 
have also reviewed the risk factor questionnaire and expressed their approval saying the 
questionnaire is 'easy to understand' and 'straightforward'. 

 
 
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If participants consent to be re-contacted by the CLOCS team for future studies or for loyalty 
card detail clarification, they will provide either a contact email or phone number. There is no 
further action needed from participants once they complete their consent form and 
questionnaire (and clarify loyalty card details if necessary). 
 
3.1 
STUDY OUTCOME MEASURES 
We aim to detect significant changes in purchase behaviours of ovarian cancer 
patients prior to diagnosis, and potentially improve the sensitivity of detection of 
cancer “alert symptoms” by stratifying the analysis on risk profiles, cancer stage or 
histology. 
 
4. 
PARTICIPANT ENTRY  
 
4.1 
PRE-REGISTRATION EVALUATIONS  
No tests need to be done before patient entry to the study.   
 
4.2 
INCLUSION CRITERIA 
Women, at least 18 years old, recently diagnosed and living with ovarian cancer (all 
ovarian and peritoneal cancer diagnoses will be eligible),preferably recruited just 
after diagnosis and during treatment period but are still eligible if diagnosed up to 2 
years prior, at the latest, who hold at least one participating high street retailer loyalty 
card are eligible to join the CLOCS as cases. 
 
Women, at least 18 years old, who have not been diagnosed with ovarian cancer and 
hold at least one participating high street retailer loyalty card are eligible to join the 
CLOCS as controls. 
 
4.3 
EXCLUSION CRITERIA 
Women under the age of 18 years and, since this is a study about ovarian cancer, 
men will not be eligible to join this study.  
 
4.4 
WITHDRAWAL CRITERIA 
If at any point, a CLOCS participant wishes to withdraw her participation, she can 
email the CLOCS research team at clocs@imperial.ac.uk expressing her desire to 
withdraw consent. 
 
The CLOCS team will then delete that participant’s information from the CLOCS 
database. 
 
5. 
PARTICIPANT RECRUITMENT AND CONSENT  
 
The CLOCS will recruit loyalty card holders through advertisement of the study and through 
clinics around the UK where the CLOCS is open. Advertisement of the CLOCS will start with 
a press release introducing the study to the general population, inviting loyalty card holders 
to visit the CLOCS website for more information and possibly participate.  
 
5.1 
RECRUITMENT OF WOMEN WITHOUT OVARIAN CANCER (CONTROLS) 
Women without ovarian cancer will be recruited through the study website 
(www.clocsproject.org.uk) where data collection will be safeguarded using an 
encrypted web form that includes study consent and the self-report questionnaire. No 
clinical questionnaire is needed for control participants.  
 

 
 
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The online participation will take up to 15 minutes and data will be transferred 
immediately to the secure CLOCS server. The website approach was adopted as 
one of the outcomes of the proof-of-concept study. It aims to provide a transparent 
environment where potential participants can make informed decisions about 
participation in CLOCS, and the data risks are minimised using encryption. We have 
carefully designed the website to inform the general public about how we will process 
their data in CLOCS, how they can withdraw from the study if they wish to do so and 
use it as a platform to provide feedback as we progress in the larger CLOCS project.  
The research team will use several methods to recruit control participants to the 
study which will include a press release carried out by the project funders and the 
Imperial College London public engagement team, dissemination of study flyers and 
leaflets, and social media marketing techniques on Twitter and Facebook using paid 
advertisement and unpaid methods. The application of the social media recruitment 
methods will allow researchers to reach a larger cohort in the UK. The application of 
both paper-based and online recruitment methods will be carried out throughout 
CLOCS and will be recorded.  
 
5.1.1 ID Verification  
In order to adhere with participating high street retailers’ policies on data 
portability,  healthy volunteers are required to provide a photo ID in the form 
of a photo of their passport or drivers licence and a utility bill (e.g. council tax 
or electricity/gas bill) for ID verification. This is an added step to confirm that 
participants did not complete the survey on behalf of someone else and to 
ensure that our research is complaint with the GDPR. Based on this, This 
information will be stored and deleted as described in section 9.1.6a.  
 
Control participants will be presented with a separate encrypted link for 
uploading their ID verification details once they consent to the study and 
complete the survey. If participants do not provide this data, we cannot retain 
their data or request their information from the retailers. To allow sufficient 
time to gather the necessary documents and doing it on their own time, we 
will be sending two reminders to the participants who agreed to the study and 
have given consent for ID verification. The first reminder will be sent 24 hours 
after the risk factor questionnaire submission, and a final reminder will be sent 
one week after the first reminder if the participant still has not completed the 
ID verification step. The copy of the verification page and the reminders are 
included in the appendices.  
 
 
 
 
 
5.2 
RECRUITMENT OF WOMEN WITH OVARIAN CANCER (CASES) 
Women living with ovarian cancer and at least one loyalty card will be eligible to 
participate in this study. Ovarian cancer patients will first be approached by a 
member of their direct care team.  
 
The member of the direct care team will discuss the study with the patients and give 
them the patient information sheet. They will be made aware that participation is 
voluntary and even if they do not want to participate it will not affect their care and 
treatment. They will also be made aware that they can withdraw at any time without 
affecting their usual care and treatment. Patients will be made aware they can take 
as much time as they need to decide on participation including discussing their 
participation with relatives and personal doctors. If they have any further questions 
that the member of the direct care team cannot answer, they will be encouraged to 

 
 
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contact the CLOCS team using the contact details included in the patient information 
sheet. The CLOCS team will be available to explain the study further and answer all 
questions. If they are willing to participate, they will then be given the consent form to 
sign and complete whenever is convenient for them and return to the study team 
using the freepost envelope. 
 
5.3. 
RECRUITMENT CONTINGENCY PLAN (COVID-19 RESTRICTIONS) 
 
 
5.3.1 During the COVID-19 pandemic, participating recruitment centres are 
consulting with patients over the phone and not seeing them in person. 
Where feasible, research nurses or clinicians will recruit patients using the 
following process: 
 
1. Read through the information sheet and complete the consent form and 
questionnaires with patient on the phone. 
2. Make a copy of the information sheet and completed forms and post them 
to the patient who chose to take part in CLOCS. This would include a 
cover letter provided by the CLOCS team. 
3. Post the original completed forms to the CLOCS team using the CLOCS 
Freepost name (Freepost CLOCS PROJECT). 
 
5.3.2 Recruitment for controls will remain on the CLOCS website. 
 
5.4 
Any queries from potential participants about joining and participating in the CLOCS 
will be answered by the research team via the CLOCS email address: 
clocs@imperial.ac.uk. 
 
5.5 
Upon choosing to participate, women will complete a consent form to participate in 
the CLOCS and return it to the study team either via mail or the CLOCS website 
(controls only), giving permission to the CLOCS team to request access to and 
analyse loyalty card information from the participating high street retailers. 
 
5.6 
The consent form requests permission from the participants for the CLOCS research 
team to re-contact participants regarding their loyalty card details for verification or 
future related studies. If a participant consents to be contacted again by the CLOCS 
team, she will provide either a contact email address or phone number. 
 
5.7 
A member of the of ovarian cancer patient’s clinical team can approach a patient who 
meets the study eligibility criteria, explain the study to the patient and let the patient 
know that participation is voluntary, and if the patient does not want to take part, it will 
not affect patient care. 
 
5.8 
Any participant can withdraw from the study at any time after consent without 
providing any reason. 
 
6.  
OVARIAN CANCER RISK FACTOR AND SYMPTOM DATA 
COLLECTION 
 
6.1 
Upon choosing to participate in the CLOCS, participants will also complete a 
questionnaire requesting information about well-established ovarian cancer risk 
factors and symptoms.  
 
6.1.1 The well-established risk factors include ethnicity, marital status, body mass 
index, age at menarche, menopausal status, age at menopause, parity, 

 
 
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breastfeeding, hysterectomy, tubal ligation, cancer history, endometriosis, 
aspirin use, oral contraceptive use, hormone replacement therapy (HRT), 
family history of ovarian and breast cancers, vaping, and cigarette smoking 
 
6.1.2 The questionnaire asks participants about the symptoms experienced (if any) 
and number of visits to the general practitioner in the year leading up to 
cancer referral or diagnosis. 
 
6.1.3  The questionnaire asks participants about which food and pharmacy stores 
they shop at regularly, at which stores they own a loyalty card, frequency of 
use of those loyalty cards, where they heard about the study (for controls 
only), and the number of people in their household (for adjustment in 
analysis). 
 
6.1.4  In order to understand the impact of COVID-19 on purchase history and 
ovarian cancer diagnosis delays, the questionnaire includes a question about 
whether participants have had Covid19 (diagnosed and recovered/diagnosed 
and still ill/suspected but not formally diagnosed/did not have covid) 
 
6.1.5  For participants diagnosed with ovarian cancer (considered cases), this will 
occur in the clinic or at home if they choose to complete it at home. 
 
6.1.6 For participants who do not have ovarian cancer (considered controls), this 
questionnaire will be completed online. 
 
6.2 
For participants with ovarian cancer, there will be a separate questionnaire to be 
completed by their recruiting clinician or member of their healthcare team regarding 
information about ovarian cancer diagnosis date, type, grade, stage, and surgical 
outcome, if any. If a patient chooses to complete the questionnaire at home, a 
member of the clinical care team will send their completed clinical questionnaire with 
them.  
 
6.3 
The clinical care teams will not keep a copy of the CLOCS participant consent form. 
 
6.4 
The member of the clinical care team who recruits the patient in the clinic is 
responsible for reporting the number of patients recruited to CLOCS on their Local 
Portfolio Management System (LPMS), and a member of the CLOCS research team 
will confirm these reports on the Central Portfolio Management System (CPMS). 
 
 
6.5 
Once all relevant risk factor and symptom questionnaires are completed, they will be 
returned to the CLOCS research team either via mail or through the CLOCS website 
(controls only). 
 
6.6 
All questionnaire data will be entered into an encrypted database housed on the 
secure server at Imperial College London, linked only by the pseudonymised study 
barcode. 
 
7. 
LOYALTY CARD DATA COLLECTION 
 
7.1 
The CLOCS team has discussed the study with the two participating high street 
retailers and data sharing agreements will be signed with them before any data is 
transferred between the study and the high street retailers. 
 

 
 
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7.2  
Women who choose to voluntarily participate in the CLOCS will provide signed, 
informed consent for their loyalty card data from participating high street retailers to 
be shared with the CLOCS research team. 
 
7.3 
When the consent form is returned to the CLOCS research team, the CLOCS team 
will transfer the encrypted  list of CLOCS participants and their loyalty card numbers 
to a secure Imperial College London file exchange that will be accessible to the high 
street retailer using a password. The completed paper consent form will be stored in 
a locked cabinet in a locked room in a building that requires a security badge to 
access.    
 
7.4 
The high street retailer will verify the participant information with their loyalty card 
data and will transfer the encrypted past purchase data back to the CLOCS research 
team using the secure Imperial College London file exchange.  
 
7.5 
If the participant’s loyalty card details provided by the participant in the consent form 
does not match the high street retailer’s records for that participant’s name and the 
participant consented to be re-contacted, then the CLOCS research team will attempt 
to contact the participant to verify the card details.  
 
7.5.1 CLOCS participants will only be re-contacted using their preferred method of 
contact they indicated in the consent form. 
 
7.5.2 The CLOCS team aim to only re-contact participants as needed and will be 
mindful of participants’ time and space. 
 
7.6 
If the participant’s loyalty card details provided by the participant in the consent form 
do not match the high street retailer’s records for that participant’s name and the 
participant did not consent to be re-contacted, then the CLOCS research team will 
not be able to access the participant’s loyalty card data and will exclude them from 
the study. 
 
7.7 
The date of recruitment as written on the questionnaire and consent forms will be the 
final date of purchase data requested by the CLOCS team. At most, up to 6 years of 
participants’ past purchasing data prior to the date of recruitment will be shared with 
the CLOCS team, depending on the high street retailer’s records and when the 
participant obtained the loyalty card. This includes data about the items purchased 
(e.g. paracetamol), when (i.e. date of purchase) and where they were purchased (i.e. 
store postcode). This will not include information on NHS prescriptions or any 
personally identifiable information, e.g. full name, postcode, ethnicity.  
 
7.8 
The CLOCS team will save the past purchase data to a secure and encrypted server 
based at Imperial College London. 
 
8. 
ASSESSMENT AND FOLLOW-UP  
 
CLOCS participants will only be re-contacted after joining to either confirm loyalty card 
details and ID verification or to contact participants about future studies related to the 
CLOCS, subject to their consent to be re-contacted.  
 
The CLOCS is funded from 1 February 2019 to 1 February 2022, but risk factor and 
symptom data collected in this phase will be available for analysis for up to ten years after 
completion of the study. Past purchase history data will only be kept for five years or until the 

 
 
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results are published, whichever happens first. Then the purchase data will be completely 
anonymised and any link to identifiable data deleted.  
 
 
9. 
STATISTICS AND DATA ANALYSIS 
 
9.1 
Data management and flow 
9.1.1    All data will be stored and processed in the College’s ISO27001 certified 
secure environment – the “Secure Enclave”. This is a fully managed 
infrastructure and secure environment providing high availability, resilience 
and business continuity through multiple servers, back-ups and disaster 
recovery measures. 
 
A robust data security model has been designed to protect sensitive personal 
and medical data from the potential risk of unauthorised access or 
distribution. All information input, viewed or extracted is be protected so that 
only users with the correct authority and access can create, view, amend or 
delete information. Access to the system will be governed by authentication 
and authorisation privileges that will check: 
• 
Access is by an authorised person and the user is who they say they 
are. This is controlled by a username and complex password; 
• 
The user accessing the system is authorised to do what they are 
attempting to do. That includes searching, updating, deleting and 
uploading information at the appropriate authorised level for the 
database(s) or table(s). 
 
In summary, the security architecture provides the optimal level of protection 
available through implementing best practice network, hardware, software 
and data security measures. 
 
9.1.2 All analysis data will be pseudonymised. 
 
9.1.3 Past purchase data will be kept until the results are published or five years 
from the date of participation in CLOCS, whichever comes first. Then all past 
purchase data will be anonymised and any link to identifiable data will be 
deleted.   
 
9.1.4  Ten years after the study is complete, all paper-based documents and 
electronically held identifiable data, including consent and contact details, will 
be destroyed or deleted in accordance with Imperial College London’s data 
deletion and retention processes.  
 
9.1.5 The CLOCS research team is committed to protecting the confidentiality of 
data. Systems have been established for the secure data flow and storage of 
data to protect confidentiality. All identifiable information, including contact 
details will remain secure at the research site. A master file, allowing re-
identification and linkage will be managed by James Flanagan, the CLOCS 
chief investigator. The access to de-identified data within Imperial College will 
be limited to approved researchers. 
 
9.1.6 Once completed consent forms, risk factor and symptom questionnaires, and 
clinical questionnaires (for cases) are returned to the CLOCS research team, 
all information will be entered onto the secure server. The encrypted   list of 
consenting CLOCS participant names and loyalty card numbers for each 

 
 
14 
 
 
participating high street retailer will be transferred to participating high street 
retailer 1 (HSR1) and participating high street retailer 2 (HSR2) using a 
secure file exchange provided by Imperial College London. The file transfer 
will require a password to access what has been transferred. The flow of data 
is shown in Appendix 2. 
 
HSR1 and HSR2 will never know the cancer status of participants nor their 
loyalty card status or details at the other HSR. 
 
9.1.6a In accordance with the participating high street retailers’ policies, 
healthy volunteers will need to provide a photo ID and utility bill for ID 
verification. These will be stored in the Secure Enclave, checked, and 
confirmed to match the details on the consent form. Once confirmed 
and the high street retailers have returned the purchase history, the 
photo ID and utility bill be deleted.   
9.1.6b After two reminders, if we do not receive relevant information to 
confirm the identity of the participants, we will remove their consent 
and questionnaire data from our database and permanently delete 
their responses as they would be considered ‘not validated’ and we 
cannot request their data from HSR1 and HSR2.  
 
9.1.7 HSR1 and HSR2 will verify participant loyalty card information, and will 
transfer encrypted participant past purchase data, linked only via the 
pseudonymised barcode id, back to the CLOCS research team, in line with 
the data sharing contracts. 
 
9.1.8 The CLOCS research team will then save the encrypted participant purchase 
history data to the CLOCS secure server to be used for analysis.  
 
9.2 
Data analysis 
9.2.1 The statistical software R will be used for all data analyses. 
 
9.2.2 We will define the time prior to diagnosis by which the cases become 
statistically significantly different in their purchase behaviours to the controls.  
 
9.2.3 We will explore this using a multivariable, conditional logistic regression 
model with ovarian cancer as the outcome and “purchase proportion” at 
different times prior to diagnosis as the exposure, adjusting for stage and 
histology and other potentially confounding variables collected from the risk 
factor questionnaire. 
 
9.2.4 We will compare the proportions of purchases in cases to controls, stratified 
by risk quintiles defined by the epidemiological risk model (estimated n=86 
per quintile) or by histology (with expected proportions of high grade serous 
cases n=335; mucinous cases n=70; endometriod n=35; clear cell n=35, and 
low grade serous n=25).  
 
9.2.5 We will estimate the predictive values (ROC AUC, PPV, NPV, specificity and 
sensitivity) of this “early diagnosis” test for each stratum. 
 
9.2.6 We will conduct exploratory analyses investigating other methods leveraging 
the auto correlation in the longitudinal data. Specifically, we will investigate 
the frequency of purchases and purchase trajectories, to identify purchase 
patterns (e.g. increasing purchases before diagnosis, purchase peaks, etc.), 
that are indicative/predictive of the individual disease onset.  

 
 
15 
 
 
 
9.2.7 Using longitudinal approaches, we will investigate if these patterns help in 
predicting the time‐to‐onset.  
 
9.2.8 This type of approach could be generalised using other purchase categories 
for further hypothesis generation. 
 
 
10.  REGULATORY ISSUES 
 
10.1 
ETHICS APPROVAL 
The Chief Investigator has obtained approval from the North West - Greater 
Manchester South Research Ethics Committee (19/NW/0427). The study must also 
receive confirmation of capacity and capability from each participating NHS Trust 
before accepting participants into the study. The study will be conducted in accordance 
with the recommendations for physicians involved in research on human subjects 
adopted by the 18th World Medical Assembly, Helsinki 1964 and later revisions. 
 
 
10.2 
CONSENT  
Consent to enter the study must be sought from each participant only after a full 
explanation has been given, an information leaflet offered and time allowed for 
consideration. Signed participant consent should be obtained. The right of the 
participant to refuse to participate without giving reasons must be respected.  After the 
participant has entered the study the clinician remains free to give alternative treatment 
to that specified in the protocol at any stage if he/she feels it is in the participant’s best 
interest, but the reasons for doing so should be recorded.  In these cases the 
participants remain within the study for the purposes of follow-up and data analysis.  
All participants are free to withdraw at any time from the protocol treatment without 
giving reasons and without prejudicing further treatment. 
 
10.3 
CONFIDENTIALITY 
The Chief Investigator will preserve the confidentiality of participants taking part in the 
study and is registered under the Data Protection Act. 
 
Any CLOCS documents in paper form will be kept in a locked cupboard in a locked 
office within a locked department in the Imperial College main study site, and only the 
chief investigator will have access.  
 
All data are kept in the Secure Enclaves, an isolated environment within Imperial 
College network. It is split into two main sections, one for holding identifiable data, and 
the other for de-identified research data. It was created to give Imperial College 
assurance that groups holding personal health data were compliant with all their 
processing requirements. All access into the enclaves is controlled and audited by the 
Security Manager and Quality Assurance Officer. The environment is Data Security 
and Protection Toolkit compliant and ISO27001 certified.   
 
Data Handling and Security 
The CLOCS research team is committed to protecting the confidentiality of data. 
Systems have been established for the secure data flow and storage of data to protect 
confidentiality. All identifiable information, including contact details will remain secure 
at the research site. A masterfile, allowing re-identification and linkage will be managed 
by James Flanagan, the CLOCS chief investigator. The access to de-identified data 
within Imperial College will be limited to approved researchers. 
 

 
 
16 
 
 
Secure Operating Environments 
All data will be stored and processed in the College’s ISO27001 certified secure 
environment – the “Secure Enclave”. This is a fully managed infrastructure and secure 
environment providing high availability, resilience and business continuity through 
multiple servers, back-ups and disaster recovery measures. 
 
A robust data security model has been designed to protect sensitive personal and 
medical data from the potential risk of unauthorised access or distribution. All 
information input, viewed or extracted is protected so that only users with the correct 
authority and access can create, view, amend or delete information. Access to the 
system will be governed by authentication and authorisation privileges that will check: 
• 
Access is by an authorised person and the user is who they say they are.  This 
is controlled by a username and complex password; 
• 
The user accessing the system is authorised to do what they are attempting to 
do. That includes searching, updating, deleting and uploading information at the 
appropriate authorised level for the database(s) or table(s). 
In summary, the security architecture provides the optimal level of protection available 
through implementing best practice network, hardware, software and data security 
measures. 
 
Participant identity will be linked to the analysis datasets only through a unique barcode 
assigned when completing the recruitment questionnaire, meaning the data will be 
pseudonymised. The only identifiable information will be on the consent form along 
with the participant barcode. Retailer data and questionnaire data will only be linked 
via the pseudonymised participant barcode. The only person with access to the link 
between participant identity and the barcode is the chief investigator and this 
information will be kept in a locked cupboard (paper form) and on the secure encrypted 
server (electronic form). All researchers on the study team understand all data is 
confidential. 
 
10.4 
INDEMNITY 
Imperial College London holds negligent harm and non-negligent harm insurance 
policies which apply to this study. 
 
10.5 
SPONSOR 
Imperial College London will act as the main Sponsor for this study.  Delegated 
responsibilities will be assigned to the NHS trusts taking part in this study.   
 
10.6 
FUNDING 
Cancer Research UK are funding this study under the Cancer Research UK Early 
Diagnosis Project Grant (C38463/A26726). 
  
The study may be subject to inspection and audit by Imperial College London under 
their remit as sponsor and other regulatory bodies to ensure adherence to GCP and 
the UK Policy Frame Work for Health and Social Care Research. 
 
 
11. 
STUDY MANAGEMENT 
 
The day-to-day management of the study will be co-ordinated through the CLOCS research 
team.   
 
12. 
PUBLICATION POLICY 
 

 
 
17 
 
 
At the end of the study, we aim to publish results of findings in peer-reviewed journals and 
present them at conferences. Extra care will be taken to ensure no participants are identifiable 
in any of the dissemination. The final study report will be produced summarising the 
information we have learned and will be hosted on the study website. 
 
 
13. 
REFERENCES 
1.  
Coleman M, Forman D, Bryant H, Butler J, Rachet B, Maringe C, et al. Cancer 
survival in Australia, Canada, Denmark, Norway, Sweden, and the UK, 1995–2007 
(the International Cancer Benchmarking Partnership): an analysis of population-based 
cancer registry data. Lancet 2011;377:127–38.  
2.  
Gilbert L, Basso O, Sampalis J, Karp I, Martins C, Feng J, et al. Assessment of 
symptomatic women for early diagnosis of ovarian cancer: results from the 
prospective DOvE pilot project. Lancet Oncol. 2012;13:285–91.  
3.  
Bell D, Berchuck A, Birrer M, Chien J, Cramer DW, Dao F, et al. Integrated genomic 
analyses of ovarian carcinoma. Nature 2011;474:609–15.  
4.  
Patch AM, Christie EL, Etemadmoghadam D, Garsed DW, George J, Fereday S, et 
al. Whole-genome characterization of chemoresistant ovarian cancer. Nature 
2015;521:489–94.  
5.  
Rojas V, Hirshfield KM, Ganesan S, Rodriguez-Rodriguez L. Molecular 
characterization of epithelial ovarian cancer: Implications for diagnosis and treatment. 
Int. J. Mol. Sci.2016;17.  
6.  
Bojesen SE, Pooley KA, Johnatty SE, Beesley J, Michailidou K, Tyrer JP, et al. 
Multiple independent variants at the TERT locus are associated with telomere length 
and risks of breast and ovarian cancer. Nat. Genet. 2013;45:371–84.  
7.  
Bolton KL, Tyrer J, Song H, Ramus SJ, Notaridou M, Jones C, et al. Common 
variants at 19p13 are associated with susceptibility to ovarian cancer. Nat. Genet. 
2010;42:880–4.  
8.  
Pharoah PDP, Tsai YY, Ramus SJ, Phelan CM, Goode EL, Lawrenson K, et al. 
GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian 
cancer. Nat. Genet. 2013;45:362–70.  
9.  
Phelan CM, Kuchenbaecker KB, Tyrer JP, Kar SP, Lawrenson K, Winham SJ, et al. 
Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian 
cancer. Nat. Genet. 2017;49:680–91.  
10.  
Clyde M, Palmieri Weber R, Iversen E, Poole M, Doherty J, Goodman M, et al. Risk 
Prediction for Epithelial Ovarian Cancer in 11 United States-Based Case-Control 
Studies: Incorporation of Epidemiologic Risk Factors and 17 Confirmed Genetic Loci. 
Am. J. Epidemiol. 2016;184:555–69.  
11.  
Meisel SF, Side L, Fraser L, Gessler S, Wardle J, Lanceley A. Population-based, risk-
stratified genetic testing for ovarian cancer risk: A focus group study. Public Health 
Genomics 2013;16:184–91.  
12.  
Ebell MH, Culp MB, Radke TJ. A Systematic Review of Symptoms for the Diagnosis 
of Ovarian Cancer. Am. J. Prev. Med. 2016;50:384–94.  
13.  
Goff B. Symptoms associated with ovarian cancer. Clin. Obstet. Gynecol. 
2012;55:36–42.  
14.  
ICBP. The international cancer benchmarking partnership evidence for policy and 
practice October 2016. 2016.  
15.  
Low EL, Whitaker KL, Simon AE, Sekhon M, Waller J. Women’s interpretation of and 
responses to potential gynaecological cancer symptoms: A qualitative interview study. 
BMJ Open 2015;5.  
16.  
Whitaker KL, Macleod U, Winstanley K, Scott SE, Wardle J. Help seeking for cancer 
‘alarm’ symptoms: a qualitative interview study of primary care patients in the UK. Br. 
J. Gen. Pract. 2015;65:e96–105.  
17.  
Whitaker KL, Winstanley K, Macleod U, Scott SE, Wardle J. Low cancer suspicion 

 
 
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following experience of a cancer “warning sign.” Eur. J. Cancer 2015;51:2473–9.  
 
 

 
 
19 
 
 
Appendix 1. 
Summary of CLOCS recruitment process 
 
 
 
Cases 
CLOCS clinician identifies patient with 
ovarian cancer and checks for eligibility 
criteria 
 
Controls 
Visit CLOCS website after interest from invitation 
from press release or advertisement on social 
media 
 
Does not join 
CLOCS 
Yes 
Does potential participant meet eligibility criteria? 
✓
Female, at least 18 years old 
✓
Owns at least one of the loyalty cards from 
CLOCS participating high street retailers  
Cases 
Healthcare team member presents patient 
with information sheet 
Controls 
 Presented with information about CLOCS on the 
CLOCS website or through the mail 
No 
Does potential participant wish to volunteer as a 
case or a control? 
No 
Yes 
Cases 
•
Complete Consent Form 
•
Complete Risk Factor Questionnaire 
•
Complete Clinical Questionnaire 
•
Returns forms to CLOCS team 
Controls 
•
Complete Consent Form on CLOCS website or paper if 
sent through mail 
•
Complete Risk Factor Questionnaire 
•
Complete ID verification on secure CLOCS link  
•
Submits forms to CLOCS team  
CLOCS team notifies high street retailers of participant consent and 
requests participant purchase history 
High street retailer shares encrypted data through secure file 
exchange, linked via participant pseudonymised barcode ID 
CLOCS team manages data and consent forms with any identifiable 
data locked in a cupboard and stored on a secure server 
Access to data for analysis limited to CLOCS research team 

 
 
20 
 
 
Appendix 2. 
Summary of CLOCS data flow 
 
 
4. Once verified, 
HSR2 encrypted 
loyalty card data 
file is dropped 
using unique 
barcode ID 
3. HSR2 verify 
participant loyalty 
card information 
5. HSR1 loyalty 
card encrypted 
data picked-up 
and saved  
1a. Consent forms received, and 
scanned copy saved and locked away 
1b. Risk factor and clinical data (cases 
only) entered and saved 
1c. ID verification complete (controls 
only) 
CLOCS 
recruiting 
centre 
(cases) 
 
CLOCS 
website 
(controls) 
2. HSR1 scanned consent 
form encrypted file drop, 
requesting loyalty card 
data 
Imperial 
College London 
Secure File 
Exchange 
High street 
retailer 2 
(HSR2) loyalty 
card past 
purchase data
2. HSR2 scanned consent 
form encrypted file drop, 
requesting loyalty card 
data 
4. Once verified, 
HSR1 encrypted 
loyalty card data file 
is dropped using 
unique barcode ID 
3. HSR1 verify 
participant loyalty 
card information 
5. HSR2 loyalty 
card encrypted 
data picked-up 
and saved 
CLOCS 
SECURE 
SERVER 
External 
Imperial 
College London 
Secure File 
Exchange  
High street 
retailer 1 
(HSR1) loyalty 
card past 
purchase data
External 
External 

 
 
21 
 
 
Appendix 3. Overview of research sites 
 
Research Site 
Investigator Name 
Imperial College London, Department of 
Surgery and Cancer (Main Study Centre) 
James Flanagan 
Imperial College Healthcare Trust, St. Marys 
Hospital 
Jon Krell 
Brighton and Sussex University Hospitals 
University Trust 
Rebecca Herbertson 
NHS Greater Glasgow and Clyde, Gartnavel 
Royal Hospital 
Ros Glasspool 
Sandwell and West Birmingham Hospitals NHS 
Trust, City Hospital 
Sudha Sundar 
University College London Hospitals NHS 
Foundation Trust 
Michelle Lockley 
County Durham And Darlington NHS 
Foundation Trust, Darlington Memorial Hospital 
Partha Sengupta 
Walsall Healthcare NHS 
Trust, Manor Hospital 
Lisa Richardson 
Surrey and Sussex Healthcare NHS Trust, East 
Surrey Hospital 
Samantha Weller 
Airedale NHS Foundation Trust, Airedale 
General Hospital 
Dan Lee 
 Swansea Bay University Health Board 
Rachel Jones 
Gateshead Health NHS 
Foundation Trust, Queen Elizabeth Hospital 
Raj Naik 
Leeds Teaching Hospitals NHS Trust, St. James 
University Hospital 
David Jackson 
NHS Lothian, Waverly Gate 
Charlie Gourley 
East Lancashire Hospitals 
NHS Trust, Royal Blackburn Hospital 
Doina Badea 
University Hospitals Bristol 
NHS Foundation Trust 
Axel Walther 
Royal Surrey County Hospital 
NHS Foundation Trust 
Agnieszka Michael 
The Royal Marsden NHS Foundation Trust 
Susana Banerjee 
Velindre NHS Trust 
Emma Hudson 
Cardiff & Vale University LHB, University 
Hospital of Wales 
Aarti Sharma 
South Tees Hospitals NHS Foundation Trust, 
James Cook University Hospital, Middlesbrough 
Talal Mansy 
West Hertfordshire Hospitals NHS Trust, West 
Hertfordshire Cancer Centre 
S Radhika Vikram 
Manchester University NHS Foundation Trust 
Richard Edmondson