A retrospective observational study of patient characteristics, treatment patterns and healthcare resource utilisation for stage II melanoma in England

Adelphi Group Limited and Merck Sharp & Dohme (MSD) Medical Affairs UK require access to National Disease Registration Service (NDRS) National Cancer Registration and Analysis Service (NCRAS) data for the purposes of the following project:

A retrospective observational study of Patient Characteristics, treatment patterns and healthcare resource utilisation for Stage II Melanoma in England

The following is a summary of the aims of the research project:

• To gain a better understanding of the disease characteristics of patients diagnosed with stage II Melanoma.

• To gain a better understanding of the treatments patients with stage II Melanoma receive, and how effective these treatments are.

• To better understand the cost of the healthcare provided to stage II melanoma patients.

• Aid in categorising key sub-groups within the stage II melanoma patient population that could benefit from the use of new treatments to improve treatment outcomes.

In support of these aims the following NDRS data will be accessed by Adelphi Group Limited:

• NDRS Cancer Registrations- necessary to identify patients who have been diagnosed with stage II melanoma, as well as report demographics and disease characteristics

• NDRS Linked Diagnostics Imaging Dataset (DIDS)- necessary for providing details on imaging tests (such as x-ray or ultrasound) a patient received to confirm their diagnosis

• NDRS Linked Radiotherapy Dataset (RTDS)- necessary for our aim to gain a better understanding of treatments patients receive. RTDS will be used to identify any radiotherapy treatments received.

• NDRS Linked Cancer Waiting Times- necessary to assess the timing of treatment patterns (surgery, chemotherapy and radiotherapy), as well as identifying whether patients experienced disease progression (recurrence and metastases)

• NDRS Linked Hospital Episode Statistics (HES) Admitted Patient Care (APC)- necessary to access information on hospital stays, including surgeries and procedures, assess disease progression events and understand the cost of healthcare provided to patients

• NDRS Linked HES Accident & Emergency (A&E)- necessary to access information on A&E attendances and on treatments including surgeries or procedures occurring at this point-of-care, as well as understand the cost of healthcare provided to patients

• NDRS Linked HES Outpatients- necessary to access information on outpatient appointments and on treatments including surgeries or procedures occurring at this point-of-care, assess disease progression events and understand the cost of healthcare provided to patients

• NDRS Systemic Anti-Cancer Therapy (SACT) Dataset- necessary for the aim to gain a better understanding of treatments patients receive. SACT will be used to identify any chemotherapy treatments received

The level of the data will be pseudonymised.

The data will be minimised as follows:

• Limited to a study cohort identified by NHS England as meeting the following criteria: All adult patients (aged 18 or above) that have a diagnosis of stage II melanoma (as defined by specific diagnosis codes) between 01/01/2015 to 31/03/2018.

• The NDRS Cancer Registry will be limited between 01/01/2015 and 31/03/2018 plus any event data (as per selected variables) held in the cancer registry from date of diagnosis up to 31/07/2022 (or death if earlier)

• CWT, SACT and RTDS will be limited to the time from diagnosis to 31/07/2022 (or death if earlier)

• HES subsets and DIDS will be limited to 12 months prior to diagnosis to 31/07/2022 (or death if earlier)

MSD Medical Affairs UK has commissioned Adelphi Group Limited to undertake this work and has determined the purpose of processing. Adelphi Group Limited, in the form of their subsidiary Adelphi Real World, make decisions about the means of processing and is therefore considered a joint controller.

Merck Sharp & Dohme Limited do manufacture pembrolizumab (Keytruda) and it is approved for use in the UK for several indications, including advanced melanoma. While pembrolizumab has been approved for use in stage II melanoma patients, the indexing period and end of the study period has been limited to ensure treatment patterns and outcome data around pembrolizumab are not included. The study will not evaluate or capture the outcomes of any specific treatments (including MSD’s treatments). However, this study will provide analysis of a care pathway in which Merck Sharp & Dohme have a commercial interest as they produce a drug that is used in this area. The potential commercial benefit to Merck Sharp & Dohme Limited of better understanding this care pathway is proportionate to the potential public benefits of increased understanding of this area of care and appropriate use of drugs approved for patients with stage II melanoma. Results from the study will not be used in any submissions for reimbursement or licensing but will be used to inform wider medical plans on activities that should be prioritised, such as further data generation studies. The primary rationale for carrying out this study is that there is limited data on the patient pathway and outcomes for these patients. As such, Adelphi Group Limited will evaluate the real-world clinical characteristics, treatment patterns, patient outcomes and HCRU for patients with stage II melanoma to increase general understanding and increase awareness for multiple scientific and public groups including clinicians, researchers, the patient community, and the general public. The insights could lead to better clinical outcomes for a significant number of patients and ultimately improve survival outcomes.

There is the potential for direct commercial gain in the understanding of the care pathways for stage II melanoma patients for MSD Medical Affairs UK as they have a drug that is used in this area; however, the outcomes of specific treatments (including MSD’s treatments) will not be explored. Adelphi Group Limited have been commissioned to undertake the work, which may be considered to result in a direct commercial gain. Additionally, intangible commercial gain from this study may arise from publishing the outcomes of the study to provide information for the clinical community because Adelphi Group Limited and MSD Medical Affairs UK employees will be listed as the authors. For example, the research will evaluate the clinical characteristics, treatment patterns, healthcare resource utilisation and survival for all patients within the defined cohort. As such, all treatments patients receive will be assessed. Adelphi Group Limited will not be investigating the effectiveness of any specific treatments (including Merck Sharp & Dohme Limited treatments).

Adelphi Group Limited and MSD Medical Affairs UK both rely on Article 6 (1) (f) of the General Data Protection Regulation (GDPR) as the lawful basis of processing - "processing is necessary for the purposes of the legitimate interests pursued by the controller or by a third party”. It is in Adelphi Groups Limited legitimate interest to add value to data through the application of epidemiological methods and expertise. Adelphi Group Limited will provide MSD Medical Affairs UK with aggregated data, with small numbers suppressed and will help them to interpret these outputs for wider dissemination to the scientific and public community as outlined in the study outputs. MSD Medical Affairs UK has determined the processing is necessary for its legitimate interests in being able to inform and raise awareness of the care pathway for patients.

The lawful basis for processing special category data under the UK GDPR cited by Adelphi Group Limited and MSD Medical Affairs UK 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.

The funding is provided by MSD Medical Affairs UK. The funding is specifically for the project described.

The funder will have no ability to suppress or otherwise limit the publication of findings.

Adelphi Group Limited processes the data for the purposes described within this Agreement. No other subsidiary of Adelphi Group Limited will have access to the data disseminated under this Agreement.

Box.com Limited provides IT support and hosting services to Adelphi Group Limited and is therefore listed as a processor. They supply support to the system but do not access data.

With the exception of data that is aggregated with small numbers suppressed, MSD Medical Affairs UK does not process or have access to data released under this Agreement.

Adelphi Group Limited has been commissioned by MSD Medical Affairs UK to run the project, therefore, has received service/consultancy fees for the time spent on the project.

In line with the national data opt-out policy, opt-outs are not applied because the data is not Confidential Patient Information as defined in section 251(10) and section 251(11) of the National Health Service Act 2006.

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

No data will flow to NHS England for the purposes of this Agreement. Analysts from Adelphi Group Limited will analyse the data for the purposes described above.

NHS England will provide the relevant records from the NDRS Cancer Registrations, NDRS Linked Diagnostics Imaging Dataset (DIDS), NDRS Linked Radiotherapy Dataset (RTDS), NDRS Linked Cancer Waiting Times, NDRS Linked Hospital Episode Statistics (HES) Admitted Patient Care (APC), NDRS Linked HES Accident & Emergency (AE), NDRS Linked HES Outpatients and NDRS Systemic Anti-Cancer Therapy (SACT) Dataset. The data will contain no direct identifying data items. The data will be pseudonymised and individuals cannot be reidentified through linkage with other data in the possession of the recipient.

The data will be stored on the Cloud servers owned and managed by Box.Com Ltd.

The data will be accessed by authorised personnel via remote access. The data will remain on the server owned and managed by Box.Com Ltd at all times.

- 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 agreement) and complies with the organisation’s remote access policy.

The data will not be accessed outside of England/Wales at any time.

Access is restricted to employees of Adelphi Group Limited who have authorisation from the project lead. All personnel accessing the data have been appropriately trained in data protection and confidentiality.

MSD Medical Affairs UK and other subsidiaries that fall under Adelphi Group Limited are not permitted to access or view any data released under this Agreement that is not aggregated with small numbers suppressed.

The data will not be linked with any other data.

There will be no requirement or attempt to reidentify individuals when using the data.

The expected outputs of the processing will be:

• A report of findings to MSD Medical Affairs UK anticipated Q2 2024. The report will detail the study rationale, design, methods, aggregated results (in the form of graphs and tables, with small number suppressed) and conclusions. This is an internal document that Adelphi Group Limited develop for MSD Medical Affairs UK. The report is used as a basis for manuscript development for submission to peer reviewed journals, as well as abstracts/posters submitted to international conferences.

• Submissions to peer-reviewed journals (including but not limited to the Journal of Clinical Oncology, Frontiers in Oncology and Annals of Oncology). Submission is anticipated within one year of receiving the requested data.

• Presentations at appropriate conferences.

The outputs, including any data shared with MSD Medical Affairs UK, 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 datasets from which the information was derived.

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

• Journals

• Conferences

Outputs are expected to be produced within one year of receiving the data, however, data will be retained one year beyond this to respond to any queries resulting from the publication of results.

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 practices to improve the care, treatment and experience of health care users relevant to the subject matter of the study.

Early identification of melanoma is crucial for successful treatment outcomes. Although there have been several studies relating to the improvement of melanoma treatment and management, there is a crucial data gap in the UK looking at the patient pathway of stage II melanoma patients. A comprehensive investigation of the real-world patient pathway, treatment landscape and outcomes of stage II melanoma patients is therefore needed.

The findings of this work have the potential to contribute to the improvement of health and social care planning in England as the study aims to provide:

- A better understanding of the clinical characteristics of patients with stage II melanoma

- Treatment patterns and observed pathways for patients diagnosed with stage II melanoma

- An understanding of the burden of stage II melanoma on both patients and the NHS by assessing the real-world effectiveness outcomes (e.g. survival and progression rates), as well as healthcare resource use and costs incurred to the NHS

The dissemination strategy will provide evidence to support clinicians in the treatment of stage II melanoma, inform the ongoing standard of care improvement strategies in the use of new and emerging treatments, and appraise the implementation of future clinical trials in line with the overall aim to improve patient outcomes.

It is hoped that through the publication of findings in appropriate media, the results 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.

Yielded Benefits is not a requirement for new applications.