Treatment pathways and clinical outcomes in BCG-unresponsive non-muscle-invasive bladder cancer

Tolley Ltd requires access to NHS England Data for the purpose of providing consultancy services to a client in the health sector.

The Data will be used to provide services to the following client:

• ImmunityBio

The Data will be used to provide the following services only:

• Care pathway analysis

• A health economics and outcomes research study

The project constitutes a single research study with the primary research question "What are the treatment pathways and clinical outcomes for patients diagnosed with non-muscle-invasive bladder cancer in England that are unrefractory to BCG?"

Via and in addition to services provided to the direct client of Tolley Ltd, the Data will be used to support NICE decision-making as recommended in the 2022 real-world evidence framework, as well as to inform clinical decision-making via the dissemination of study findings to UK clinicians, patient organisations and other stakeholders.

The following NHS England Data will be accessed:

National Disease Registration Service (NDRS) – Cancer Consolidated Dataset: necessary to identify the treatment pathways and clinical outcomes of adult patients diagnosed with non-muscle invasive bladder cancer (NMIBC) that have previously been treated with, and who are unresponsive to Bacillus Calmette-Guérin (BCG). This will be used to understand current treatment practices in England and to provide comparator evidence for new treatment options assessed by the National Institute for Health and Care Excellence (NICE).

Hospital Episodes Statistics (HES) outpatient (OP) data – if not included in the Cancer Consolidated Dataset – will be used to identify past treatment with BCG via OPCS-4 codes (feasibility testing has already been conducted by the NDRS team to confirm the existence of this information in the HES OP dataset) and relevant subsequent therapies.

HES Admitted Patient Care (APC) - if not included in the Cancer Consolidated Dataset – will be used to identify receipt of radical cystectomy or other inpatient treatments received by patients.

The level of the Data will be:

• Pseudonymised

The Data will be minimised as follows:

• Limited to a study cohort meeting the following criteria: Adult patients diagnosed with non-muscle-invasive bladder cancer (identified by ICD code ), that have been treated with Bacillus Calmette-Guérin (BCG) and were unresponsive to it. Access to all patient records with NMIBC will be required within the SDE for the purposes of deriving proxy identifiers of prior BCG treatment on the basis of OPCS-4 code records in HES outpatient data.

• Limited to the timeframe in which data from the Cancer Consolidated Dataset are available (from 2016 to the latest data year available at the time of approval).

• Limited to a one-off data readout without further updates during the period of the agreement being required.

ImmunityBio, as sponsor of the study, has commissioned Tolley Ltd. to undertake all activities involved in designing, analysing and reporting the research in order to minimise undue influence on the study and uphold the integrity of the analysis. ImmunityBio does not specify what data are required to deliver the work nor how the data shall be processed to achieve that purpose. Such decisions are to be taken by Tolley Ltd. alone.

ImmunityBio are seeking nationwide approval from NICE for their novel treatment, Anktiva, to treat patients with NMIBC in England and Wales. As an American Biotech, they have commissioned Consultancies across Europe (including Tolley and Solem GmbH) to best evaluate the relative clinical effectiveness and cost effectiveness of their product for potential use according to the methods and evidence needs required by the relevant HTA bodies and processes in each country.

ImmunityBio will not use the Data or outputs from its processing for purposes other than as a source of evidence for the NICE submission. ImmunityBio's agreement to fund the research stems from Tolley's recommendation that UK real-world evidence be presented to NICE according to their best-practice guidelines, rather than any ambition to use data for other purposes on ImmunityBio's part.

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

Article 6(1)(f) - processing is necessary for the purposes of the legitimate interests pursued by the controller or by a third party.

Tolley Ltd has determined the processing is necessary for its legitimate interests in being able to provide tools and services that will benefit healthcare organisations.

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 to be conducted by Tolley Ltd. as a HTA consultancy providing a submission to NICE is in the core public interest to ensure that new health technologies are both clinically effective and cost-effective for the NHS. Tolley Ltd.'s work aims to provide evidence-based recommendations that help the NHS make informed decisions about which treatments, devices, and other technologies to adopt, ultimately benefitting patients and the wider population.

The funding is provided by ImmunityBio. The funding is for consultancy being provided by Tolley Ltd. to support ImmunityBio's HTA submission to NICE and is not specifically limited to the project described. Funding is in place until May 2026.

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

Additional organisations involved in the project but not accessing the data include the patient advocacy group, Fight Bladder Cancer (www.fightbladdercancer.co.uk/); Eric Low Consulting Ltd., a consultancy specialising in strategic market access, patient engagement and life sciences and healthcare policy; and Solem GmBH, an international life sciences consultancy responsible for overseeing HTA activities in the UK and Europe on behalf of ImmunityBio.

Solem's overseeing of HTA activities in the UK involves coordinating submissions for regulatory approval of Anktiva and for HTA assessment by NICE. This involves managing communications with NICE and NHS England on behalf of ImmunityBio, contracting Tolley's services to develop a UK HTA submission portfolio and evidence generation activities such as this project, and coordinating between all parties to ensure submission timescales and requirements are adhered to.

The Interim Chief Executive of Fight Bladder Cancer, who is also a patient representative, has assisted in studies supporting this research project. The patient advocacy group strongly supports the inclusion of the patient voice and collection of data for the purposes of using real-world evidence to support the clinical and cost-effectiveness of innovative treatments for patient access on the NHS.

No data will flow to NHS England for the purposes of this Data Sharing Agreement (DSA).

NHS England will provide the relevant records from the NDRS datasets to Tolley Ltd. The Data will: be limited via the NHS England Secure Data Environment (SDE). 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 not be transferred to any other location.

The Data will be stored on servers at NHS England via the SDE.

All offsite back-up services for data stored on servers at NHS England Secure Data Environment will be managed by NHS England.

The Data will be accessed by authorised personnel via remote access. Tolley Ltd will ensure that remote devices comply with the data security obligations within this DSA and the Data Sharing Framework Contract, as outlined below.

 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 substantive employees of Tolley Ltd who have authorisation from the Principal Investigator.

No organisations or individuals except those named in this application will be permitted to access the data. Study funders (ImmunityBio) and other organisations not named as data processors or data controllers will not be permitted to access the data.

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

The aggregated information derived from the SDE will be analysed following output from the SDE alongside patient-level data from the single-arm Phase II/III QUILT-3.032 study (NCT03022825) for the purposes of an indirect treatment comparison (ITC) using a matching-adjusted indirect comparison or similar method.

As no study sites in the NCT03022825 study were located in the UK, there will be no overlap in patient populations. The aggregated Data will not be linked to other data sources corresponding to the NHS patients included in the Data cohort.

There will be no requirement and no attempt to reidentify individuals when using the Data.

Analysts from Tolley Ltd, will process and analyse the Data for the purposes described above.

NHS England’s Controlled Environment is a data storage and access platform that enables approved users to access de-identified data and analytical tools for approved projects. Users must identify themselves via a multi-factor authentication mechanism and are only able to access the datasets detailed within this agreement. Users can request that aggregated outputs are exported from the system following approval by trained NHSE staff. The access and use of the system is fully auditable, and all users must comply with the use of the data as specified in this agreement.

The expected outputs of the processing will be:

• A report of aggregate findings (with small numbers suppressed) to the study sponsor. This will include output in the form of aggregate tables describing baseline, patient characteristics, summary tables describing treatment pathways according to numbers and proportions of patients, and Kaplan-Meier curves and survival tables reporting available time-to-event endpoints including overall survival and (where available) disease progression and treatment discontinuation. Findings will be provided as a single analysis report, anticipated in Q3/Q4 2025.

• Submission of findings (using equivalent output and levels of aggregation to that described above) will be submitted for publication in a peer-reviewed journal with a target publication date in 2026. Depending on the relevance of findings to different stakeholder audiences, additional manuscripts and/or poster publications during a similar timeframe.

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:

• Health Technology Appraisal (HTA) submissions to NICE

• Peer-reviewed journals

• Direct bilateral engagement with UK clinicians

• Posters displayed at academic and/or clinical conferences

• Public promotion of the research through social media

• Reports aimed at UK clinicians, patients / patient organisations and academic audiences

The planned HTA submission to NICE for Nogapendekin alfa inbakicept with intravesical BCG for previously treated non-muscle-invasive bladder cancer unresponsive to BCG (NICE ID6582) is scheduled for January 2026.

Submission of an academic manuscript, describing aggregate treatment pathways and clinical outcomes among patients with BCG-unresponsive NMIBC in England, to a peer-reviewed journal is planned during 2026.

Output used as evidence to inform the forthcoming appraisal of Nogapendekin Alfa Inbakicept (NAI) with intravesical BCG will be of direct benefit to the public both as local taxpayers and as current or potential receivers of healthcare services subject to NICE’s decision-making.

As highlighted in NICE’s 2022 Real-world Evidence Framework, real-world data plays a key role in ensuring that reimbursement decisions influencing the allocation of NHS resources are appropriate and suitably informed, and reimbursement decisions (whether favourable to the commercial interests of funding organisations or otherwise) are made in consideration of evidence that reflects current care in England and Wales.

The publication of findings using the data outside the context of the NICE submission will also be of direct value to UK clinicians, who have highlighted the lack of available evidence around current treatment practices nationally.1,2 In academic publications, at clinical conferences and in direct communications with the research team, clinical experts have called for increased initiatives to provide published data to:

• better understand current practices, including the range of treatment options used at a national level

• provide a mechanism for assessing alignment of clinical practice to national and British Association of Urological Surgeons (BAUS) guidelines and recommendations promoting high standards of care

• facilitate planning of clinical trials in bladder cancer patient populations involving UK sites

• support patient-oriented care planning by demonstrating the influence of patient characteristics and treatment pathway on clinical outcomes

• encourage further dialogue between clinicians, patients and policymakers around unmet needs and optimal management of the care of patients with NMIBC

Findings informing NICE’s assessment of NAI, as well as any future technology appraisals drawing on published data, will ensure that proper consideration is given to the patient outcomes offered by current and new therapies. Should NICE’s decision-making result in a positive recommendation, this will benefit patients through the availability of new treatments on the NHS, addressing unmet needs and providing greater capacity for choice of appropriate treatment.

Published findings will also contribute directly to wider clinical ambitions to assess current treatment practices and improve patient care at a national level.

Current UK treatment pathways for BCG-unresponsive NMIBC are complex and often highly individualised according to patients’ individual clinical needs and preferences. Standard treatments include radical cystectomy, bladder sparing therapies such as hyperthermic mitomycin C and routine monitoring, but the availability and use of these services is understood to vary within England and Wales according to the services and expertise available at individual treatment centres.3,4

It is hoped that publishing evidence around current treatment practices and clinical outcomes will encourage and facilitate further discussion around optimal treatment pathways, empower patients and clinicians to make informed decisions and provide a robust picture of current practice against which to evaluate the clinical and cost effectiveness of new therapies considered for use by the NHS.

NICE’s committee meetings are held in a public online forum involving the participation of patient representatives and clinical experts, as well as seeking input from other stakeholders, and committee papers, slides and committee discussions of evidence are published on its website following the publication of guidance.

Tolley Ltd have also outlined plans to publish findings as a peer-reviewed journal manuscript independently of the use of output in the planned HTA submission to NICE. Tolley Ltd expect that evidence presented will be of high interest to clinicians involved in the care of bladder cancer patients, as well as to patients and patient charities.

The UK charity Fight Bladder Cancer has had close involvement in planning and providing input to the research. Fight Bladder Cancer, among other charities, has emphasised the need for real-world evidence for improving patient choice and outcomes in their published materials as well as through their involvement in the workstreams being conducted by Tolley Ltd.

Yielded Benefits is not a requirement for new applications.