CAP study: Cluster randomised triAl of prostate specific antigen (PSA) testing for Prostate cancer (ODR1617_022)

The University of Bristol requires access to NHS England data for the purpose of the following research project: CAP study: Cluster randomised triAl of prostate specific antigen (PSA) testing for Prostate cancer (ODR1617_022)

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

• To provide an unbiased estimate of the effect of a single screen for prostate cancer on prostate cancer-specific and all-cause mortality in the population.

• To contribute to the international effort to investigate the impact of prostate cancer screening.

• To estimate the cost implications of prostate cancer screening and use the data collected to develop and refine a probabilistic model of the cost-effectiveness of prostate cancer screening in the UK.

Few international issues in health care are as controversial as prostate cancer screening. Prostate cancer has a major impact on public health in the UK. There were 8,500 deaths from prostate cancer in England and Wales in 1998, making it the second leading cause of cancer mortality in men. The aetiology of prostate cancer remains unclear and opportunities for primary prevention are limited. Developments in diagnostic tests for prostate cancer, in particular the introduction of Prostate-Specific Antigen (PSA) testing, has led to increased interest in the possibility of secondary prevention through population screening.

Screening to identify prostate cancer while it is localised to the gland has provoked much public and scientific attention and there is intense debate about its role in improving men's health. Current UK health policy does not advocate population screening, but the policy remains under active review by the UK National Screening Committee. Major concerns remain about the lack of evidence about the effectiveness of treatments (the rationale for the ProtecT treatment trial) and the potential for diagnosis and over-treatment of tumours that might never become clinically significant. In the UK the introduction of routine prostate cancer screening is being delayed until adequate evidence becomes available to inform policy.

The following NHS England Data will be accessed:

- NDRS Cancer Registrations - Necessary to support the study in achieving these goals dissemination. The National Cancer Registry data was disseminated and linked to the CAP trial cohort generated by the University Of Bristol. NDRS Cancer Registry Data for this study has previously been shared with the University of Bristol when the data was controlled and managed by Public Health England (PHE).

The level of the Data will be:

- Identifiable

The Data will be minimised as follows:

- Men aged between 50 to 69 years who were invited between 2001-2008 to undergo PSA testing for prostate cancer (Intervention arm of the study)

- Men aged between 50 and 69 years who underwent standard, unscreened NHS management between 2001-2008 (Control arm of the study)

The Population Health Sciences Unit at Bristol Medical School (part of the University of Bristol) is the research sponsor and 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) (i) processing is necessary for reasons of public interest in the area of public health and is completed under the supervision of a medical professional (the PI is registered with the General Medical Council). The processing also falls under 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 the Department of Health and Cancer Research UK. The funding is specifically for the study described.

The CAP study is funded by The Department of Health and Cancer Research UK, these organisations play no role in determining the purpose and means of processing, and have no access to data disseminated under this Agreement.

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

Annual reports will be produced for Cancer Research UK. Papers will be prepared for publication in general, epidemiological and urological peer-reviewed journals. The findings will also be presented at national and international conferences and fed directly to other appropriate bodies such as the NHS National Screening Committee.

The median 15-year follow-up were reached in 2021 and it is anticipated that the publication will report these results early 2024, the University has successfully applied to CRUK for additional funding for longer term follow-up. CAP plan to publish median 15-year results in The Journal of the American Medical Association (JAMA), as was the case with the median 10-year results, https://jamanetwork.com/journals/jama/fullarticle/2673968

A statistical analysis plan detailing the median 15-year analyses was uploaded onto the University of Bristol research information repository prior to analysis being carried out (https://research-information.bris.ac.uk/en/publications/cluster-randomised-trial-of-psa-testing-for-prostate-cancer-cap-s) and also https://osf.io/7y3g6. Statistics involved in these papers usually refer to measures such as rate ratios and 95% confidence intervals rather than actual numbers of cases. CAP will apply statistical disclosure control for example NHS England non-disclosure rules for small numbers of cases and will not include any counts of less than 7 in a Table.

The papers will be available on the University of Bristol PURE pages https://research-information.bris.ac.uk/ - these publications are available to download with open access allowing anyone to access publications. The University of Bristol also publish with open access rights when submitting to journals, ensuring they maintain CRUKs publication ethos of ensuring research funded by them is available to all. Publications are also uploaded to 'researchfish' allowing the research community to clearly see what has been published.

The data requested and disseminated under previous iterations of this agreement (under PHE) has been used to evaluate the effectiveness and cost-effectiveness of population screening for prostate cancer by establishing a cluster randomised trial allocating general practices to either intensive case-finding (the ProtecT trial) or unscreened standard practice.

Data for this study has previously been shared when the data was controlled and managed by Public Health England (PHE). As such there are some yielded benefits to be observed from the access to the data for the study prior to NHS England becoming data controller. These yielded benefits are noted below:

The primary analyses including stage and grade data were undertaken at average 10-year follow-up (i.e. 2018) and published in JAMA (DOI:101001/jama.2018.0154) .

These results published: (1) have informed UK and international guidelines on PSA-based screening; and (2) were used to update GP and Patient Information sheets produced by Public Health England (January 2020), aimed at enabling men to make a fully informed decision about whether or not to undergo screening.

The results also influenced international screening guidelines for example: In the USA, the results of CAP had a major influence on the recommendations of the United States Preventative Services Task Force (USPSTF), a public health body, published in May 2018.

This is a request from the University of Bristol to receive a more up-to-date drop of identifiable National Disease Registration Service (NDRS) Cancer Registry Data in support of the Cluster Randomised Trial of PSA Testing for Prostate Cancer (CAP) study and the ProtecT trial. The ProtecT trial is the intervention arm of the CAP study.

Few international issues in health care are as controversial as prostate cancer screening. Prostate cancer has a major impact on public health in the UK. There were 8,500 deaths from prostate cancer in England and Wales in 1998, making it the second leading cause of cancer mortality in men. The aetiology of prostate cancer remains unclear and opportunities for primary prevention are limited. Developments in diagnostic tests for prostate cancer, in particular the introduction of Prostate-Specific Antigen (PSA) testing, has led to increased interest in the possibility of secondary prevention through population screening.

Screening to identify prostate cancer while it is localised to the gland has provoked much public and scientific attention and there is intense debate about its role in improving men's health. Current UK health policy does not advocate population screening, but the policy remains under active review by the UK National Screening Committee. Major concerns remain about the lack of evidence about the effectiveness of treatments (the rationale for the ProtecT treatment trial) and the potential for diagnosis and over-treatment of tumours that might never become clinically significant. In the UK the introduction of routine prostate cancer screening is being delayed until adequate evidence becomes available to inform policy.

The CAP Study is a long-running study randomised cluster-controlled trial in which GP practises in 8 centres in England and Wales have been randomly allocated to either population-based PSA testing akin to screening (the ProtecT study) or standard (unscreened) practice. In the ProtecT practices, men aged 50 to 69 years were invited between 2001-2008 to undergo PSA testing. In the control arm practices men ages 50 to 69 years undergo standard NHS management. All men are being followed up for vital status, incident and fatal prostate cancer via NHS digital.

Pseudonymised NDRS Cancer Registry Data for this study has previously been shared with the University of Bristol when the data was controlled and managed by Public Health England (PHE).

The data requested and disseminated under previous iterations of this agreement (under PHE) has been used to evaluate the effectiveness and cost-effectiveness of population screening for prostate cancer by establishing a cluster randomised trial allocating general practices to either intensive case-finding (the ProtecT trial) or unscreened standard practice.

The CAP study will be delivered by the team at The Population Health Sciences Unit at Bristol Medical School. Part of the University of Bristol who are the sole data controllers and data processors. The Population Health Sciences Unit is a leading centre for research in population health sciences. Their multi-disciplinary approach contributes to significant healthcare improvements and policy changes around the world. The CAP study is funded by The Department of Health and Cancer Research UK, these organisations play no role in determining the purpose and means of processing, and have no access to data disseminated under this Agreement.

The CAP study has 3 primary health improvement goals for men diagnosed with prostate cancer.

• To provide an unbiased estimate of the effect of a single screen for prostate cancer on prostate cancer-specific and all-cause mortality in the population.

• To contribute to the international effort to investigate the impact of prostate cancer screening.

• To estimate the cost implications of prostate cancer screening and use the data collected to develop and refine a probabilistic model of the cost-effectiveness of prostate cancer screening in the UK.

To support the study in achieving these goals dissemination of data from the National Cancer Registry Dataset is requested as a one-off request and will be linked to the CAP trial cohort generated by the University Of Bristol.

To address the GDPR Principle of Data Minimisation, this request is limited to all GP practices and patients who fall under the scope of this trial. GP Practices randomised to the intervention arm (ProtecT trial) will be approached and informed consent will be sought from the senior partner for inclusion of the practice.

The legal basis for personal data to be obtained and processed is the UK General Data Protection Regulation (GDPR) Article 6 (1) (e) processing is necessary for the performance of a task carried out in the public interest with a basis in law. This study has been determined to be in the public interest as this research has the potential to provide an evidence base for public policy decision-making, the basis in law is the University’s Royal Charter.

The legal basis for processing health data is Article 9 (2) (i) processing is necessary for reasons of public interest in the area of public health and is completed under the supervision of a medical professional (the PI is registered with the General Medical Council). The processing also falls under Article 9 (2)(j) , processing is necessary for reasons of public interest in the area of research with a basis in law. The research has the potential to provide an evidence base for public policy decision-making, the basis in law is the University’s Royal Charter.

Annual reports will be produced for Cancer Research UK. Papers will be prepared for publication in general, epidemiological and urological peer-reviewed journals. The findings will also be presented at national and international conferences and fed directly to other appropriate bodies such as the NHS National Screening Committee.

The median 15-year follow-up were reached in 2021 and it is anticipated that the publication will report these results in 2023, the University would nevertheless wish to apply for additional funding for longer term follow-up. CAP plan to publish median 15-year results in The Journal of the American Medical Association (JAMA), as was the case with the median 10-year results, https://jamanetwork.com/journals/jama/fullarticle/2673968

A statistical analysis plan detailing the median 15-year analyses was uploaded onto the University of Bristol research information repository prior to analysis being carried out (https://research-information.bris.ac.uk/en/publications/cluster-randomised-trial-of-psa-testing-for-prostate-cancer-cap-s) and also https://osf.io/7y3g6. Statistics involved in these papers usually refer to measures such as rate ratios and 95% confidence intervals rather than actual numbers of cases. CAP will apply statistical disclosure control for example NHS Digital non-disclosure rules for small numbers of cases and will not include any counts of less than 7 in a Table.

The papers will be available on the University of Bristol PURE pages https://research-information.bris.ac.uk/ - these publications are available to download with open access allowing anyone to access publications. The University of Bristol also publish with open access rights when submitting to journals, ensuring they maintain CRUKs publication ethos of ensuring research funded by them is available to all. Publications are also uploaded to 'researchfish' allowing the research community to clearly see what has been published.

Data for this study has previously been share when the data were controlled and managed by Public Health England (PHE). As such there are some yielded benefits to be observed from the access to the data for the study prior to NHS Digital becoming data controller. These yielded benefits are noted below:

The primary analyses including stage and grade data were undertaken at average 10-year follow-up (i.e. 2018) and published in JAMA (DOI:101001/jama.2018.0154) .

These results published: (1) have informed UK and international guidelines on PSA-based screening; and (2) were used to update GP and Patient Information sheets produced by Public Health England (January 2020), aimed at enabling men to make a fully informed decision about whether or not to undergo screening.

The results also influenced international screening guidelines for example: In the USA, the results of CAP had a major influence on the recommendations of the United States Preventative Services Task Force (USPSTF), a public health body, published in May 2018.