CANDID - Cancer diagnosis decision rules

University of Southampton (UoS) requires access to NHS England data for the purpose of the following research project:

CANDID – Cancer Research diagnosis decision rules.

The following is a summary of the aims of the research project provided by UoS:

• To develop and validate Clinical Prediction Rules predicting cancer in patients presenting with symptoms in the lung and colon separately.

• To explore the incremental utility of incorporating additional measures (e.g. genetic, inflammatory, and lifestyle information including smoking and alcohol status) in the prediction models.

A multi-disciplinary panel of 28 experts from primary care, secondary care, and academic settings were invited to obtain consensus on diagnostic indicators for assessing the risk of lung or colorectal cancer in primary care consulters presenting with lung or abdominal symptoms. Over three rounds, participants rated each diagnostic indicator in terms of its importance, ranked them in order of importance, and rated each item as crucial or not crucial to assess during a GP consultation. This resulted in 25 items remaining for each type of cancer, which included established cancer symptoms but also included less frequently used indicators such as patients’ concerns about cancer. The importance of these predictors in assessing the risk of lung or colorectal cancer will be tested as part of this study.

Two cohorts of patients were recruited into the study within 4 weeks of the date they presented to their general practitioner with lung or colorectal symptoms.

Lung symptoms cohort:

• Inclusion criteria: Individuals aged >35 years presenting with focal chest symptoms lasting for 3 weeks (e.g., haemoptysis, dyspnoea, thoracic pain, cough); or systemic symptoms lasting for 3 weeks (e.g., loss of appetite, loss of weight, fatigue)

• Exclusion criteria: Known lung cancer, pregnancy, urgent admission to hospital (e.g., due to massive haemoptysis), other terminal illness, or inability to provide a good history (e.g., due to severe depression, psychosis, dementia, acute alcohol intoxication, learning impairment)

Colorectal symptoms cohort:

• Inclusion criteria: Individuals aged >35 years presenting with lower gastrointestinal symptoms, including rectal bleeding, bowel symptoms (e.g., change in bowel habit, tenesmus, urgency, incomplete emptying, nocturnal symptoms), systemic symptoms (e.g., weight loss, anorexia, fatigue), lower abdominal pain.

• Exclusion criteria: Known colorectal cancer, pregnancy, urgent admission to hospital (e.g., due to massive bleeding or acute abdomen), other terminal illness, inability to provide a good history (e.g., due to severe depression, psychosis, dementia, acute alcohol intoxication, learning impairment).

Individuals aged >35 years were chosen as colon and related cancers are very rarely diagnosed in the younger age group.

Participants provided their demographic information, details of their symptoms that were potential diagnostic indicators, and a blood sample and/or saliva sample for full blood count and further analysis of DNA and protein markers. At home they were asked to fill in lifestyle questionnaires on a secure website.

The following NHS England Data will be accessed:

• NDRS Cancer Registrations – necessary to achieve the aims of the project by creating prediction models to see which of the symptoms and examination findings are the most effective in predicting cancer.

The level of the Data will be:

• Identifiable – necessary to enable linkage of the participants’ symptoms to their cancer outcomes data.

The Data will be minimised as follows:

• Limited to a study cohort of 23,801 patients residing in England who consented to participate.

• Limited to data up to 5 years after each individual patient's date of consent (the date of recruitment to the study).

• Limited to conditions relevant to the study identified by specific ICD codes.

University of Southampton is the controller as the organisation responsible for ensuring that the Data will only be processed for the purpose described above.

The lawful basis for processing personal data under the UK GDPR is:

Article 6(1)(e) – processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller.

The lawful basis for processing special category data under the UK GDPR is:

Article 9(2)(j) – processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject.

This processing is in the public interest because it adheres to the UK Policy Framework for Health and Social Care Research, which protects and promotes the interests of patients, service users and the public, and aims to produce generalisable and publicly available information to inform future decisions over patients’ treatments or care. Improvements in the early diagnosis and treatment of cancer is one of the key aspects of NHS England’s 2024/25 priorities and operational planning guidance. This project aims to improve early diagnosis of cancer by identifying combinations of symptoms and full blood count that can be used to rule in/out cancer in patients presenting with lung or colorectal symptoms.

The study was funded by the National Institute for Health and Care Research (NIHR). The funding was specifically for the study described. The funder will have no ability to suppress or otherwise limit the publication of findings.

A Public and Patient Involvement and Engagement member has been involved from the beginning in advising the project, developing patient facing materials, and supporting the fundamental concepts of the use of its data in improvement patient management (both identifying individuals who do not need referral more efficiently, and with less anxiety, and those individuals who are likely to need urgent referral).

University of Bristol, University of Manchester, University of Oxford, University of London, University of Nottingham, University of Birmingham, and University of Keele were involved in the recruitment of participants. These organisations did not determine the purposes and means of the processing of the data.

The national data opt-out does not apply where explicit consent has been obtained from the patient for the specific purpose.

Where individuals have opted out of disease registration by the National Disease Registration Service (NDRS), their data has been permanently removed from the registry and therefore will not be disseminated under this Data Sharing Agreement (DSA). https://digital.nhs.uk/ndrs/patients/opting-out

UoS will transfer data to NHS England. The data will consist of identifying details (specifically NHS Number and date of birth), a unique person ID, and date of recruitment for each participant for the cohort to be linked with NHS England data.

NHS England will provide the relevant records from the Cancer Registration dataset to UoS. The Data will:

• contain no direct identifying data items but will contain a unique person ID which can be used to link the Data with other record level data already held by the recipient.

The Data will be stored on servers at UoS.

The Data will be accessed by authorised personnel via remote access.

The Controller(s) must confirm and provide evidence upon audit by NHS England that access via any remote device complies with the data security obligations within this DSA and the Data Sharing Framework Contract.

For remote access:

• Remote access will only be from secure locations situated within the territory of use (as further restricted elsewhere within the DSA if so done) stated within this DSA;

• Access controls granting users the minimum level of access required are in place;

• Remote access is only via secure connections (e.g., VPNs or secure protocols) to protect data;

• Multifactor authentication (MFA) is required for remote access;

• Device security, including up-to-date software and operating systems, antivirus software, and enabled firewalls are utilised for the remote access;

• All remote access is undertaken within the scope of the organisation’s DSPT (or other security arrangements as per this DSA) and complies with the organisation’s remote access policy.

The above applies in addition to any condition set out elsewhere within the DSA (e.g. who may carry out processing, and for what purpose).

The Data will not leave England/Wales at any time.

Access is restricted to individuals within the Southampton Clinical Trials Unit of UoS who have authorisation from the Chief Investigator. All such individuals are substantive employees of UoS.

All personnel accessing the Data have been appropriately trained in data protection and confidentiality.

The Data will not be linked with any other data.

The identifying details will be stored separately to the de-identified dataset used for analysis. All analyses will use the de-identified dataset. There will be no requirement and no attempt to reidentify individuals when using the de-identified dataset.

Researchers from the Southampton Clinical Trials Unit at UoS will process and analyse the Data for the purposes described above.

The expected outputs of the processing will be:

• A report of findings to the funder (NIHR)

• A minimum of two submissions to peer-reviewed journals

• A minimum of two presentations at international oncology conferences (such as American Society of Clinical Oncology or European Society For Medical Oncology)

• (If study analysis is sufficiently positive) production of a cancer prediction tool which will be made available to GPs under licence from UoS

The outputs will not contain NHS England Data and will only contain aggregated information with small numbers suppressed as appropriate in line with the relevant disclosure rules for the dataset(s) from which the information was derived.

The outputs will be communicated to relevant recipients through the following dissemination channels:

• Journals

• Poster and oral presentations at local, national, and international conferences

• Webpage for Southampton Clinical Trials Unit

• Social media

• Public engagement activities to enable access by the research participants

Production and dissemination of the outputs is expected to take place within 1 year of receipt of the Data.

The findings of this research study are expected to contribute to evidence-based decision-making for policy-makers, local decision-makers such as doctors, and patients to inform best practice to improve the care, treatment, and experience of health care users relevant to the subject matter of the study.

The use of the data could:

• help the system to better understand the health and care needs of populations.

• lead to the identification or improvement of treatments or interventions, or health and care system design to improve health and care outcomes or experience.

• inform planning health services and programmes, for example to improve equity of access, experience, and outcomes.

• support knowledge creation or exploratory research (and the innovations and developments that might result from that exploratory work).

If a cancer prediction model is produced in the analysis that has acceptable performance characteristics, such a model could be used by GPs to quickly risk-stratify patients presenting with lung or colorectal symptoms into those who can be confidently re-assured, and those who require investigations for potential cancer. For patients, this is hoped to speed up the cancer diagnosis process, improving the feasibility of curative rather than palliative treatment.

It is hoped that through publication of findings in appropriate media and production of a cancer risk prediction tool for use by GPs, the findings of this research will add to the body of evidence that is considered by the bodies, organisations and individual care practitioners charged with making policy decisions for or within the NHS or treatment decisions in relation to specific patients.

Results of the project will be summarised on the study’s webpage which is publicly accessible. If the results are sufficiently positive, then media outlets will be contacted and plans for public dissemination will be made.

Yielded Benefits is not a requirement for new applications.