Routine Data Extraction for CAP (Cluster randomised trial of PSA testing for Prostate cancer) Section 251

The University of Bristol requires access to mortality, cancer registration, demographics and Hospital Episode Statistics (HES) data for the purpose of a Cluster randomised trial of Prostate Specific Antigen (PSA) testing for Prostate cancer (CAP). CAP is a pragmatic, cluster Randomised Clinical Trial (RCT) that compares an invitation to attend for population-based PSA-testing for prostate cancer (intervention group) with standard NHS care (control group).

There is currently no national screening programme for prostate cancer in the UK but men over 50 can ask their GP for a PSA test. This trial aims to assess the effectiveness of PSA testing in reducing prostate cancer mortality, and its cost-effectiveness (i.e. comparing the health-related costs in the two groups in combination with the effectiveness of PSA testing, in order to assist policy makers in their decisions about how to achieve the best use of resources).

The University of Bristol has been running this trial since 2001.

The median 10-year follow-up was completed and published in The Journal of the American Medical Association (JAMA) in 2018 doi:10.1001/jama.2018.0154. With the median 15-year follow-up was completed and published in The Journal of the American Medical Association (JAMA) in 2024 https://doi.org/10.1001/jama.2024.4011. The long lead-time for prostate cancer mortality, confirmed by the CAP publications necessitates follow-up beyond 15 years to comprehensively evaluate the full impact of screening and Cancer Research UK (CRUK) funded CAP to allow the completion of further follow-up to 20-years.

GP practices in 8 centres in England and Wales were randomly allocated to either population-based PSA testing, akin to screening (the ProtecT study), or standard (unscreened) practice.

In the intervention (ProtecT) practices, between 2001 and 2009, men aged 50-69 years were invited to undergo PSA testing. The individuals who accepted this invitation were asked to sign a consent form permitting follow-up of their health status. Of the men who took the PSA test, those with PSA levels of 3.0 ng/ml or greater were offered standardised 10-core transrectal ultrasound guided biopsy.

For any individuals registered with intervention practices who did not respond to the invitation for a PSA test, support under section 251 NHS Act 2006 permits access to their data for the purpose of follow-up without informed consent.

In the comparison arm practices, men aged 50-69 years undergo standard NHS management (provision of an informed choice to any man over the age of 50 who requests a PSA test). The University of Bristol obtained support under section 60 of the HSCA 2001 (later replaced by support under section 251 NHS Act 2006) to flag these individuals without informed consent.

All men regardless of whether they participated in the ProtecT study are followed up for mortality and cancer registrations contributing to the comparison between the intervention and comparison groups.

From 2005 onwards, the NHS England (formerly NHS Digital) reported deaths and cancer registrations relating to men in either arm of this study.

When the trial is notified that an individual in either arm has developed prostate cancer, a case review is undertaken. Case reviews involve paper notes and electronic records held by the hospital and not data supplied by NHS England under this Agreement. However, the follow-up data from NHS England is important as it can be the trigger to undertake a case review.

Because this study has a subset of data subjects who gave consent and a subset who did not, the University of Bristol has two connected Data Sharing Agreements with NHS England relating to this study.

• The Agreement under the reference DARS-NIC-119910-K6W9Q covers the individuals whose data are accessed with informed consent.

• The Agreement under the reference DARS-319171-G7H8K covers the individuals whose data are accessed without consent with support under section 251 NHS Act 2006.

The legal basis for personal data to be obtained and processed for is under the UK GDPR Article 6 (1) (e) processing is necessary for the performance of a task carried out in the public interest. The legal basis for health information data is Article 9 (2) (i) processing is necessary for reasons of public interest in the area of public health and Article 9 (2) (j) processing is necessary for reasons of public interest in the area of research. Public interest is defined here as: provide an evidence base for public policy decision-making; provide an evidence base for decisions which are likely to significantly benefit the UK economy, society or quality of life of people in the UK; and to replicate, validate or challenge existing research. Results from the average 20-year follow-up will directly inform UK policy on prostate cancer screening through the UK National Screening Committee (NSC) and have a wide influence internationally. They will also be used in the further development of an economic model estimating the cost-effectiveness of prostate cancer screening in the UK and add to the evidence-base for individualised shared decision making, providing validation for pre- and post-diagnostic risk-stratification tools.

The data generated will provide both clinical and policy relevant data on one of the most controversial issues in health care nationally and internationally: the potential benefits, harms and costs to the UK population of screening for prostate cancer.

It is unlikely that such a trial would be possible anywhere else in the world because information systems are not as comprehensive across primary and secondary care and across the whole population. The extensive, complete and long-term follow-up of these men is only possible because of the publicly funded national healthcare system the UK NHS and because of NHS England hospital and mortality information systems. These information systems provide comprehensive data on cancer diagnoses, deaths and costs to the NHS enabling very long term and cost-effective follow-up of the outcomes from screening.

The CAP Study aims to accurately estimate, for a UK population: a) the effect of a single PSA-testing round on prostate cancer specific and all-cause mortality, compared to standard (unscreened) practice in the CAP trial; b) age specific lead-time and over-diagnosis rates (utilising observed trial data); c) the projected lifetime effectiveness and cost effectiveness of a range of UK-focused screening options, incorporating parameter estimates computed from these data to create a UK-specific decision analytic model; d) the validity of pre- and post-diagnostic risk-stratification models.

Receipt of demographics, mortality and cancer registration data allowed the CAP Study to continue to follow-up men in the cohort across the UK to accurately estimate the effect of a single PSA-testing round on 20-year prostate cancer specific and all-cause mortality, compared to standard (unscreened) practice; as well as the age-specific lead-time and over-diagnosis rates (utilising observed trial data); the projected lifetime effectiveness and cost-effectiveness of UK focused screening strategies; and the validity of pre- and post-diagnostic risk-stratification tools.

Prostate cancer mortality and prostate cancer stage, grade and progression are critical outcomes for this trial, and it is essential for informing NHS screening policy that these data are of the highest quality. The CAP study would not be able to reliably determine the cause of death in deceased men, because without identifiable data the trained researchers would be unable to extract information from the medical records to compose the detailed case vignettes which are then used to validate the cause of death. Neither could the study access the electronic hospital records of individuals to extract stage and grade data.

Where cost implications of any national screening programme are considerable, and where survival is relatively good whatever form of management is adopted, it is essential to incorporate analysis of cost-effectiveness. To obtain timely and comprehensive UK-wide coverage, without bias or loss of power, the University of Bristol sought record linkage to hospital records (HES) and Diagnostic Imaging Dataset (DIDs) for over 400,000 men (the combined number of participants in the intervention arm (189,386) and the comparison arm (219,439).

The University of Bristol developed a process for NHS England to extract pseudonymised HES and DIDs data for the cohort, which was already flagged for follow-up on NHS England’s system, and the data was sent to Secure Anonymised Information Linkage (SAIL) Databank, University of Swansea, which acts as a trusted third party for linkage and using their secure remote access system so that no patient-level resource use data are transferred to the University of Bristol from NHS England.

The datasets and data items requested have been restricted to only those directly relevant to the aims and purpose of this research. The HES data includes routine information for administrative purposes when people access healthcare (such as the type of operation and the amount of time spent in hospital). Using these routine data allowed the CAP study to include all individuals in the trial in the budget impact analysis estimating the costs to the NHS, providing clinical and policy relevant data. The budget impact analysis of data via the SAIL Gateway informs evidence-based decisions about prostate cancer screening and treatment (published 2023 https://doi.org/10.1186/s12913-023-09503-7). A model-based economic evaluation addressing the issues of extrapolating results beyond median 10-year measurements incorporating utility estimates was published in 2022 (https://doi.org/10.1007/s40273-022-01191-1) and these data will enable the further development of this model calibrating to trial data of longer duration which may reduce uncertainty about the cost-effectiveness of screening strategies, forming the continued economic analysis for CAP.

The team have completed several validation studies that have made a methodological impact in the field and will publish the validation of pre- and post-diagnosis risk-stratification tools and developments of the model based economic evaluation following completion of this work.

The University of Bristol is the study sponsor and the sole Data Controller. The lead investigator and another principal investigator are based in Bristol. Two other principal investigators for CAP are based at the University of Oxford, one of whom was previously based at the University of Cambridge. They both have an advisory role for CAP. Historically the University of Oxford and the University of Cambridge were sub-contracted in the CRUK grant held by the University of Bristol. The University of Oxford and the University of Cambridge previously employed some of the CAP researchers but they were line-managed and supervised by the Trial Coordinator based at the University of Bristol. All researchers are now employed by the University of Bristol with honorary contracts for hospital trusts. Whilst historically researchers were employed in other centres to extract data from hospital notes, they did not process NHS England data.

Staff and investigators at Bristol have responsibility for all day to day running of the study, including but not limited to data processing and storage, analysis, and leading publications.

The Trial Steering Committee and Data Monitoring Committee have an advisory role, they do not have any control over how NHS England data is used or access to these data (except in the form of trial results produced for or presented at these meetings). They provide advice, guidance, and support to the trial.

The University of Swansea is a Data Processor holding the linked HES data accessible to investigators at the University of Bristol in the form of a pseudonymised dataset housed at the Secure Anonymised Information Linkage (SAIL) Databank. This means that it is totally separate to the identifiable data held at the University of Bristol and can never be linked to it.

The research is funded by Cancer Research UK (CRUK). CRUK does not access the data.

The main outcomes of the trial are the effectiveness of Prostate Specific Antigen (PSA) testing in reducing prostate cancer mortality, and its cost-effectiveness (i.e. comparing the health-related costs in the two groups in combination with the effectiveness of PSA testing, in order to assist policy makers in their decisions about how to achieve the best use of resources). The expected measurable benefits to health arise from the ability of these data to allow an unbiased comparison between men screened for prostate cancer and those not screened. The data generated will provide both clinical and policy relevant data on one of the most controversial issues in health care nationally and internationally: the potential benefits, harms and costs to the UK population of screening for prostate cancer. The median 15-year follow-up was published in 2024 (https://doi.org/10.1001/jama.2024.4011) and given the long lead-time for prostate cancer the University applied for additional funding for longer term follow-up. The median 20-year follow-up will be reached in March 2026, and CAP plan to publish median 20-year results in The Journal of the American Medical Association (JAMA), as was the case with the median 10 and 15-year results, https://jamanetwork.com/journals/jama/fullarticle/2673968 & https://doi.org/10.1001/jama.2024.4011

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/clusterrandomised-trial-of-psa-testing-for-prostate-cancer-cap-s) and https://osf.io/7y3g6. We are working on the median 20-year statistical analysis plan which it is anticipated will be uploaded in early 2025. 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. Outputs will also be fed directly to funders, Cancer Research UK and Department of Health. Other appropriate bodies such as the NHS National Screening Committee, NICE, or the Cochrane Centre will also be informed. Alongside the median 20-year results it is also anticipated that The University of Bristol will continue to develop and publish methodological work, these publications will be disseminated to inform the research community on the benefits and challenges of using NHS England data sources. The extension to the existing DSA will allow median 15-year data to be retained and processed enabling additional analyses and publications to be worked on, as well as allowing future releases of demographic, cancer and mortality data to enable the median 20-year trial outcomes to be completed. 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.

Research from the University of Bristol led to the Department of Health decision in 1997 that screening for prostate cancer would not be introduced in the UK until there was evidence that benefits outweighed harms. University of Bristol led, and collaborative research subsequently provided evidence to support informed decision-making in the NHS. A formal review by DH in 2010 endorsed the policy and confirmed that any change would be based on evidence from the teams randomised trials. The results published in 2018 have again informed this decision, and this research has ensured UK men have avoided known harms of prostate cancer screening in the context of uncertain benefits and saved the UK economy.

The CAP Trial, which spanned almost 600 GP practices in the UK and included more than 400,000 men aged 50-69, is the largest trial ever to investigate prostate cancer screening.

The trial compared 189,386 men who were invited to have a one-off PSA test with 219,439 men who were not invited for screening. After an average of 10 years follow up, there were 8,054 (4.3%) prostate cancers in the screened group and 7,853 (3.6%) cases in the control group. Crucially, both groups had the same percentage of men dying from prostate cancer (0.29%).

After following up for 15 years, there was a small difference in the number of men who died from prostate cancer between the two groups – nearly 7 men out of every 1,000 in the group invited for screening had died from prostate cancer, compared to nearly 8 men out of every 1,000 in the group who hadn’t been invited for screening.

The results of the trial show that an estimated 1 in 6 cancers found by the single PSA screening were overdiagnosed.

CAP results have informed national and international guidelines for the use of PSA testing as a screening tool for prostate cancer detection. In the UK, the CAP trial results have provided the Public Health England (PHE) National Screening Committee (NSC) with high-quality, UK-based evidence to inform a review of the balance of benefits against harms of PSA based prostate cancer screening. In the USA, results were included in the recommendations of the US Preventive Services Task Force (https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/prostatecancerscreening).

Alongside the RCT the CAP Study have been able to carry out important methodological work which has helped inform the use of routine data sources in pragmatic randomised trials. The dataset already held by SAIL was used to develop the STATA do files and confirm the feasibility of extracting unbiased health-related costs for comparison across the two groups in the budget impact analyses. Results of these analyses have now been published in the BMC Health Services ‘Impact of PSA testing on secondary care costs in England and Wales: estimates from the Cluster randomised triAl of PSA testing for prostate cancer (CAP)’ doi: 10.1186/s12913-023-09503-7 In the first year post-randomisation, secondary-care costs averaged across all men (irrespective of a prostate cancer diagnosis) in the intervention arm (n = 189279) were £44.80 (95% confidence interval: £18.30-£71.30) higher than for men in the control arm (n = 219357). Extrapolated to a population level, the introduction of a single PSA screening invitation could lead to additional secondary care costs of £314 million. Leading us to conclude that introducing a single PSA screening test for men aged 50–69 across England and Wales could lead to very high initial secondary-care costs.

We have also published in PharmacoEconomics (2022) the ‘Cost‑Effectiveness Analysis of Prostate Cancer Screening in the UK: A Decision Model Analysis Based on the CAP Trial’ doi.org/10.1007/s40273-022-01191-1 Which concluded that of the prostate-specific antigen-based strategies compared, only a once-off screening at age 50 years was potentially cost effective at current UK willingness-to-pay thresholds. An additional follow-up of CAP to 15 years may reduce uncertainty about the cost effectiveness of the screening strategies.

No further data will flow under this version of the agreement.

The University of Bristol requires access to mortality, cancer registration, demographics and Hospital Episode Statistics (HES) data for the purpose of a Cluster randomised trial of Prostate Specific Antigen (PSA) testing for Prostate cancer (CAP). CAP is a pragmatic, cluster Randomised Clinical Trial (RCT) that compares an invitation to attend for population-based PSA-testing for prostate cancer (intervention group) with standard NHS care (control group).

There is currently no national screening programme for prostate cancer in the UK but men over 50 can ask their GP for a PSA test. This trial aims to assess the effectiveness of PSA testing in reducing prostate cancer mortality, and its cost-effectiveness (i.e. comparing the health-related costs in the two groups in combination with the effectiveness of PSA testing, in order to assist policy makers in their decisions about how to achieve the best use of resources).

The University of Bristol has been running this trial since 2001.

The median 10-year follow-up was completed and published in The Journal of the American Medical Association (JAMA) in 2018 doi:10.1001/jama.2018.0154. The long lead-time for prostate cancer mortality, confirmed by the CAP publication, necessitates follow-up beyond 10 years to comprehensively evaluate the full impact of screening and Cancer Research UK (CRUK) funded CAP to allow the completion of 15-year analysis.

GP practices in 8 centres in England and Wales were randomly allocated to either population-based PSA testing, akin to screening (the ProtecT study), or standard (unscreened) practice.

In the intervention (ProtecT) practices, between 2001 and 2009, men aged 50-69 years were invited to undergo PSA testing. The individuals who accepted this invitation were asked to sign a consent form permitting follow-up of their health status. Of the men who took the PSA test, those with PSA levels of 3.0 ng/ml or greater were offered standardised 10-core transrectal ultrasound guided biopsy.

For any individuals registered with intervention practices who did not respond to the invitation for a PSA test, support under section 251 NHS Act 2006 permits access to their data for the purpose of follow-up without informed consent.

In the comparison arm practices, men aged 50-69 years undergo standard NHS management (provision of an informed choice to any man over the age of 50 who requests a PSA test). The University of Bristol obtained support under section 60 of the HSCA 2001 (later replaced by support under section 251 NHS Act 2006) to flag these individuals without informed consent.

All men regardless of whether they participated in the ProtecT study are followed up for mortality and cancer registrations contributing to the comparison between the intervention and comparison groups.

From 2005 onwards, the NHS England (formerly NHS Digital) reported deaths and cancer registrations relating to men in either arm of this study.

When the trial is notified that an individual in either arm has developed prostate cancer, a case review is undertaken. Case reviews involve paper notes and electronic records held by the hospital and not data supplied by NHS England under this Agreement. However, the follow-up data from NHS England is important as it can be the trigger to undertake a case review.

Because this study has a subset of data subjects who gave consent and a subset who did not, the University of Bristol has two connected Data Sharing Agreements with NHS England relating to this study.

• The Agreement under the reference DARS-NIC-119910-K6W9Q covers the individuals whose data are accessed with informed consent.

• The Agreement under the reference DARS-319171-G7H8K covers the individuals whose data are accessed without consent with support under section 251 NHS Act 2006.

The legal basis for personal data to be obtained and processed for is under the UK GDPR Article 6 (1) (e) processing is necessary for the performance of a task carried out in the public interest. The legal basis for health information data is Article 9 (2) (i) processing is necessary for reasons of public interest in the area of public health and Article 9 (2) (j) processing is necessary for reasons of public interest in the area of research. Public interest is defined here as: provide an evidence base for public policy decision-making; provide an evidence base for decisions which are likely to significantly benefit the UK economy, society or quality of life of people in the UK; and to replicate, validate or challenge existing research. Results from the average 15-year follow-up will directly inform UK policy on prostate cancer screening through the UK National Screening Committee (NSC) and have a wide influence internationally. They will also be used in the development of an economic model estimating the cost-effectiveness of prostate cancer screening in the UK, and in the budget impact analysis to be calculated from an NHS perspective.

The data generated will provide both clinical and policy relevant data on one of the most controversial issues in health care nationally and internationally: the potential benefits, harms and costs to the UK population of screening for prostate cancer.

It is unlikely that such a trial would be possible anywhere else in the world because information systems are not as comprehensive across primary and secondary care and across the whole population. The extensive, complete and long-term follow-up of these men is only possible because of the publicly funded national healthcare system the UK NHS and because of NHS England hospital and mortality information systems. These information systems provide comprehensive data on cancer diagnoses, deaths and costs to the NHS enabling very long term and cost-effective follow-up of the outcomes from screening.

The CAP Study aims to accurately estimate, for a UK population: a) the effect of a single PSA-testing round on prostate cancer specific and all-cause mortality, compared to standard (unscreened) practice in the CAP trial; b) age specific lead-time and over-diagnosis rates (utilising observed trial data); c) the projected lifetime effectiveness and cost effectiveness of a range of UK-focused screening options, incorporating parameter estimates computed from these data to create a UK-specific decision analytic model.

Receipt of demographics, mortality and cancer registration data allowed the CAP Study to continue to follow-up men in the cohort across the UK to accurately estimate the effect of a single PSA-testing round on 15-year prostate cancer specific and all-cause mortality, compared to standard (unscreened) practice; as well as the age-specific lead-time and over-diagnosis rates (utilising observed trial data); and the projected lifetime effectiveness and cost-effectiveness of UK focused screening strategies.

Prostate cancer mortality and prostate cancer stage, grade and progression are critical outcomes for this trial, and it is essential for informing NHS screening policy that these data are of the highest quality. The CAP study would not be able to reliably determine the cause of death in deceased men, because without identifiable data the trained researchers would be unable to extract information from the medical records to compose the detailed case vignettes which are then used to validate the cause of death. Neither could the study access the electronic hospital records of individuals to extract stage and grade data.

Where cost implications of any national screening programme are considerable, and where survival is relatively good whatever form of management is adopted, it is essential to incorporate analysis of cost-effectiveness. To obtain timely and comprehensive UK-wide coverage, without bias or loss of power, the University of Bristol sought record linkage to hospital records (HES) and Diagnostic Imaging Dataset (DIDs) for over 400,000 men (the combined number of participants in the intervention arm (189,386) and the comparison arm (219,439).

The University of Bristol developed a process for NHS England to extract pseudonymised HES and DIDs data for the cohort, which was already flagged for follow-up on NHS England’s system, and the data was sent to Secure Anonymised Information Linkage (SAIL) Databank, University of Swansea, which acts as a trusted third party for linkage and using their secure remote access system so that no patient-level resource use data are transferred to the University of Bristol from NHS England.

The datasets and data items requested have been restricted to only those directly relevant to the aims and purpose of this research. The HES data includes routine information for administrative purposes when people access healthcare (such as the type of operation and the amount of time spent in hospital). Using these routine data will allow the CAP study to include all individuals in the trial in the ongoing budget impact analysis to estimate the costs to the NHS, providing clinical and policy relevant data. The budget impact analysis of data via the SAIL Gateway will inform evidence-based decisions about prostate cancer screening and treatment. A model-based economic evaluation that will address the issues of extrapolating results beyond median 10-year measurements and incorporating disutility estimates is currently in progress and this will form the economic analysis for CAP.

The team have completed several validation studies that have made a methodological impact in the field and will publish the budget impact analysis and model based economic evaluation following completion of this work.

The University of Bristol is the study sponsor and the sole Data Controller. The lead investigator and another principal investigator are based in Bristol. Two other principal investigators for CAP are based at the University of Oxford, one of whom was previously based at the University of Cambridge. They both have an advisory role for CAP. Historically the University of Oxford and the University of Cambridge were sub-contracted in the CRUK grant held by the University of Bristol. The University of Oxford and the University of Cambridge previously employed some of the CAP researchers but they were line-managed and supervised by the Trial Coordinator based at the University of Bristol. All researchers are now employed by the University of Bristol with honorary contracts for hospital trusts. Whilst historically researchers were employed in other centres to extract data from hospital notes, they did not process NHS England data.

Staff and investigators at Bristol have responsibility for all day to day running of the study, including but not limited to data processing and storage, analysis, and leading publications.

The Trial Steering Committee and Data Monitoring Committee have an advisory role, they do not have any control over how NHS England data is used or access to these data (except in the form of trial results produced for or presented at these meetings). They provide advice, guidance, and support to the trial.

The University of Swansea is a Data Processor holding the linked HES data accessible to investigators at the University of Bristol in the form of a pseudonymised dataset housed at the Secure Anonymised Information Linkage (SAIL) Databank. This means that it is totally separate to the identifiable data held at the University of Bristol and can never be linked to it.

The research is funded by Cancer Research UK (CRUK). CRUK does not access the data.

The main outcomes of the trial are the effectiveness of Prostate Specific Antigen (PSA) testing in reducing prostate cancer mortality, and its cost-effectiveness (i.e. comparing the health-related costs in the two groups in combination with the effectiveness of PSA testing, in order to assist policy makers in their decisions about how to achieve the best use of resources).

The expected measurable benefits to health arise from the ability of these data to allow an unbiased comparison between men screened for prostate cancer and those not screened. The data generated will provide both clinical and policy relevant data on one of the most controversial issues in health care nationally and internationally: the potential benefits, harms and costs to the UK population of screening for prostate cancer.

The median 15-year follow-up was reached in 2021 and it is anticipated that the publication will report these results early 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/clusterrandomised-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.

Outputs will also be fed directly to funders, Cancer Research UK and Department of Health. Other appropriate bodies such as the NHS National Screening Committee, NICE, or the Cochrane Centre will also be informed.

Alongside the median 15-year results it is also anticipated that The University of Bristol will continue to develop and publish methodological work, these publications will be disseminated to inform the research community on the benefits and challenges of using NHS England data sources. The extension to the existing DSA will allow these data to be retained and processed enabling additional analyses and publications to be worked on.

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.

Research from the University of Bristol led to the Department of Health decision in 1997 that screening for prostate cancer would not be introduced in the UK until there was evidence that benefits outweighed harms. University of Bristol led, and collaborative research subsequently provided evidence to support informed decision-making in the NHS. A formal review by DH in 2010 endorsed the policy and confirmed that any change would be based on evidence from the teams randomised trials. The results published in 2018 have again informed this decision, and this research has ensured UK men have avoided known harms of prostate cancer screening in the context of uncertain benefits and saved the UK economy.

The CAP Trial, which spanned almost 600 GP practices in the UK and included more than 400,000 men aged 50-69, is the largest trial ever to investigate prostate cancer screening.

The trial compared 189,386 men who were invited to have a one-off PSA test with 219,439 men who were not invited for screening. After an average of 10 years follow up, there were 8,054 (4.3%) prostate cancers in the screened group and 7,853 (3.6%) cases in the control group. Crucially, both groups had the same percentage of men dying from prostate cancer (0.29%).

These results have informed national and international guidelines for the use of PSA testing as a screening tool for prostate cancer detection. In the UK, the CAP trial results have provided the Public Health England (PHE) National Screening Committee (NSC) with high-quality, UK-based evidence to inform a review of the balance of benefits against harms of PSA based prostate cancer screening. In the USA, the results were included in the recommendations of the US Preventive Services Task Force (https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/prostatecancerscreening).

Alongside the RCT the CAP Study have been able to carry out important methodological work which has helped inform the use of routine data sources in pragmatic randomised trials. The dataset already held by SAIL was used to develop the STATA do files and confirm the feasibility of extracting unbiased health-related costs for comparison across the two groups in the budget impact analyses. Results of these analyses have now been published in the BMC Health Services ‘Impact of PSA testing on secondary care costs in England and Wales: estimates from the Cluster randomised triAl of PSA testing for prostate cancer (CAP)’ doi: 10.1186/s12913-023-09503-7 In the first year post-randomisation, secondary-care costs averaged across all men (irrespective of a prostate cancer diagnosis) in the intervention arm (n = 189279) were £44.80 (95% confidence interval: £18.30-£71.30) higher than for men in the control arm (n = 219357). Extrapolated to a population level, the introduction of a single PSA screening invitation could lead to additional secondary care costs of £314 million. Leading us to conclude that introducing a single PSA screening test for men aged 50–69 across England and Wales could lead to very high initial secondary-care costs.

We have also published in PharmacoEconomics (2022) the ‘Cost‑Effectiveness Analysis of Prostate Cancer Screening in the UK: A Decision Model Analysis Based on the CAP Trial’ doi.org/10.1007/s40273-022-01191-1 Which concluded that of the prostate-specific antigen-based strategies compared, only a once-off screening at age 50 years was potentially cost effective at current UK willingness-to-pay thresholds. An additional follow-up of CAP to 15 years may reduce uncertainty about the cost effectiveness of the screening strategies.

The University of Bristol requires access to mortality, cancer registration, demographics and Hospital Episode Statistics (HES) data for the purpose of a Cluster randomised trial of Prostate Specific Antigen (PSA) testing for Prostate cancer (CAP), CAP is a pragmatic, cluster Randomised Clinical Trial (RCT) that compares an invitation to attend for population-based PSA-testing for prostate cancer (intervention group) with standard NHS care (control group).

There is currently no national screening programme for prostate cancer in the UK but men over 50 can ask their GP for a PSA test. This trial aims to assess the effectiveness of PSA testing in reducing prostate cancer mortality, and its cost-effectiveness (i.e. comparing the health-related costs in the two groups in combination with the effectiveness of PSA testing, in order to assist policy makers in their decisions about how to achieve the best use of resources).

The University of Bristol has been running this trial since 2001.

The median 10-year follow-up was completed and published in The Journal of the American Medical Association (JAMA) in 2018 doi:10.1001/jama.2018.0154. The long lead-time for prostate cancer mortality, confirmed by the CAP publication, necessitates follow-up beyond 10 years to comprehensively evaluate the full impact of screening and Cancer Research UK (CRUK) funded CAP to allow the completion of 15-year analysis.

GP practices in 8 centres in England and Wales were randomly allocated to either population-based PSA testing, akin to screening (the ProtecT study), or standard (unscreened) practice.

In the intervention (ProtecT) practices, between 2001 and 2009, men aged 50-69 years were invited to undergo PSA testing. The individuals who accepted this invitation were asked to sign a consent form permitting follow-up of their health status. Of the men who took the PSA test, those with PSA levels of 3.0 ng/ml or greater were offered standardised 10-core transrectal ultrasound guided biopsy.

For any individuals registered with intervention practices who did not respond to the invitation for a PSA test, support under section 251 NHS Act 2006 permits access to their data for the purpose of follow-up without informed consent.

In the comparison arm practices, men aged 50-69 years undergo standard NHS management (provision of an informed choice to any man over the age of 50 who requests a PSA test). The University of Bristol obtained support under section 60 of the HSCA 2001 (later replaced by support under section 251 NHS Act 2006) to flag these individuals without informed consent.

All men regardless of whether they participated in the ProtecT study are followed up for mortality and cancer registrations contributing to the comparison between the intervention and comparison groups.

From 2005 onwards, the HSCIC (latterly NHS Digital) reported deaths and cancer registrations relating to men in either arm of this study.

When the trial is notified that an individual in either arm has developed prostate cancer, a case review is undertaken. Case reviews involve paper notes and electronic records held by the hospital and not data supplied by NHS Digital under this Agreement. However, the follow-up data from NHS Digital is important as it can be the trigger to undertake a case review.

Because this study has a subset of data subjects who gave consent and a subset who did not, the University of Bristol has two connected Data Sharing Agreements with NHS Digital relating to this study.

• The Agreement under the reference DARS-NIC-119910-K6W9Q covers the individuals whose data are accessed with informed consent.

• The Agreement under the reference DARS-319171-G7H8K covers the individuals whose data are accessed without consent with support under section 251 NHS Act 2006.

The legal basis for personal data to be obtained and processed for is Article 6 (1) (e) processing is necessary for the performance of a task carried out in the public interest. The legal basis for health information data is Article 9 (2) (i) processing is necessary for reasons of public interest in the area of public health and Article 9 (2) (j) processing is necessary for reasons of public interest in the area of research. Public interest is defined here as: provide an evidence base for public policy decision-making; provide an evidence base for decisions which are likely to significantly benefit the UK economy, society or quality of life of people in the UK; and to replicate, validate or challenge existing research. Results from the average 15-year follow-up will directly inform UK policy on prostate cancer screening through the Public Health England (PHE) National Screening Committee (NSC) and have a wide influence internationally. They will also be used in the development of an economic model estimating the cost-effectiveness of prostate cancer screening in the UK, and in the budget impact analysis to be calculated from an NHS perspective.

The data generated will provide both clinical and policy relevant data on one of the most controversial issues in health care nationally and internationally: the potential benefits, harms and costs to the UK population of screening for prostate cancer.

It is unlikely that such a trial would be possible anywhere else in the world because information systems are not as comprehensive across primary and secondary care and across the whole population. The extensive, complete and long-term follow-up of these men is only possible because of the publicly funded national healthcare system the UK NHS and because of NHS Digital hospital and mortality information systems. These information systems provide comprehensive data on cancer diagnoses, deaths and costs to the NHS enabling very long term and cost-effective follow-up of the outcomes from screening.

The CAP Study aims to accurately estimate, for a UK population: a) the effect of a single PSA-testing round on prostate cancer specific and all-cause mortality, compared to standard (unscreened) practice in the CAP trial; b) age specific lead-time and over-diagnosis rates (utilising observed trial data); c) the projected lifetime effectiveness and cost effectiveness of a range of UK-focused screening options, incorporating parameter estimates computed from these data to create a UK-specific decision analytic model.

Continuing receipt of demographics, mortality and cancer registration data will allow the CAP Study to continue to follow-up men in the cohort across the UK to accurately estimate the effect of a single PSA-testing round on 15-year prostate cancer specific and all-cause mortality, compared to standard (unscreened) practice; as well as the age-specific lead-time and over-diagnosis rates (utilising observed trial data); and the projected lifetime effectiveness and cost-effectiveness of UK focused screening strategies.

Prostate cancer mortality and prostate cancer stage, grade and progression are critical outcomes for this trial, and it is essential for informing NHS screening policy that these data are of the highest quality. The CAP study would not be able to reliably determine the cause of death in deceased men, because without identifiable data the trained researchers would be unable to extract information from the medical records to compose the detailed case vignettes which are then used to validate the cause of death. Neither could the study access the electronic hospital records of individuals to extract stage and grade data.

Where cost implications of any national screening programme are considerable, and where survival is relatively good whatever form of management is adopted, it is essential to incorporate analysis of cost-effectiveness. To obtain timely and comprehensive UK-wide coverage, without bias or loss of power, the University of Bristol sought record linkage to hospital records (HES) and Diagnostic Imaging Dataset (DIDs) for over 400,000 men (the combined number of participants in the intervention arm (189,386) and the comparison arm (219,439).

The University of Bristol developed a process for NHS Digital to extract pseudonymised HES and DIDs data for the cohort, which was already flagged for follow-up on NHS Digital’s system, and the data was sent to Secure Anonymised Information Linkage (SAIL) Databank, University of Swansea, which acts as a trusted third party for linkage and using their secure remote access system so that no patient-level resource use data are transferred to the University of Bristol from NHS Digital.

The datasets and data items requested have been restricted to only those directly relevant to the aims and purpose of this research. The HES data includes routine information for administrative purposes when people access healthcare (such as the type of operation and the amount of time spent in hospital). Using these routine data will allow the CAP study to include all individuals in the trial in the ongoing budget impact analysis to estimate the costs to the NHS, providing clinical and policy relevant data. The budget impact analysis of data via the SAIL Gateway will inform evidence-based decisions about prostate cancer screening and treatment. A model-based economic evaluation that will address the issues of extrapolating results beyond median 10-year measurements and incorporating disutility estimates is currently in progress and this will form the economic analysis for CAP.

The team have completed several validation studies that have made a methodological impact in the field and will publish the budget impact analysis and model based economic evaluation following completion of this work.

The University of Bristol is the study sponsor and the sole Data Controller. The lead investigator and another principal investigator are based in Bristol. Two other principal investigators for CAP are based at the University of Oxford, one of whom was previously based at the University of Cambridge. They both have an advisory role for CAP. Historically the University of Oxford and the University of Cambridge were sub-contracted in the CRUK grant held by the University of Bristol. The University of Oxford and the University of Cambridge previously employed some of the CAP researchers but they were line-managed and supervised by the Trial Coordinator based at the University of Bristol. All researchers are now employed by the University of Bristol with honorary contracts for hospital trusts. Whilst historically researchers were employed in other centres to extract data from hospital notes, they did not process NHS Digital data.

Staff and investigators at Bristol have responsibility for all day to day running of the study, including but not limited to data processing and storage, analysis, and leading publications.

The Trial Steering Committee and Data Monitoring Committee have an advisory role, they do not have any control over how NHS Digital data is used or access to these data (except in the form of trial results produced for or presented at these meetings). They provide advice, guidance, and support to the trial.

The University of Swansea is a Data Processor holding the linked HES data accessible to investigators at the University of Bristol in the form of a pseudonymised dataset housed at the Secure Anonymised Information Linkage (SAIL) Databank. This means that it is totally separate to the identifiable data held at the University of Bristol and can never be linked to it.

The research is funded by Cancer Research UK (CRUK). CRUK does not access the data.

The main outcomes of the trial are the effectiveness of Prostate Specific Antigen (PSA) testing in reducing prostate cancer mortality, and its cost-effectiveness (i.e. comparing the health-related costs in the two groups in combination with the effectiveness of PSA testing, in order to assist policy makers in their decisions about how to achieve the best use of resources).

The expected measurable benefits to health arise from the ability of these data to allow an unbiased comparison between men screened for prostate cancer and those not screened. The data generated will provide both clinical and policy relevant data on one of the most controversial issues in health care nationally and internationally: the potential benefits, harms and costs to the UK population of screening for prostate cancer.

The median 15-year follow-up will be reached in 2021 and it is anticipated that the publication will report these results as soon as possible following this, 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 10-year analyses was uploaded onto the University of Bristol research information repository prior to analysis being carried out (http://hdl.handle.net/1983/6d41509f-ab93-4f96-9869-c320acbc4ae1)

A further statistical analysis plan will be uploaded detailing the median 15-year analyses that will be included in the publications. 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.

Outputs will also be fed directly to funders, Cancer Research UK and Department of Health. Other appropriate bodies such as the NHS National Screening Committee, NICE, or the Cochrane Centre will also be informed.

Alongside the median 15-year results it is also anticipated that The University of Bristol will continue to develop and publish methodological work, these publications will be disseminated to inform the research community on the benefits and challenges of using NHS digital data sources.

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.

Research from the University of Bristol led to the Department of Health decision in 1997 that screening for prostate cancer would not be introduced in the UK until there was evidence that benefits outweighed harms. University of Bristol led, and collaborative research subsequently provided evidence to support informed decision-making in the NHS. A formal review by DH in 2010 endorsed the policy and confirmed that any change would be based on evidence from the teams randomised trials. The results published in 2018 have again informed this decision, and this research has ensured UK men have avoided known harms of prostate cancer screening in the context of uncertain benefits and saved the UK economy.

The CAP Trial, which spanned almost 600 GP practices in the UK and included more than 400,000 men aged 50-69, is the largest trial ever to investigate prostate cancer screening.

The trial compared 189,386 men who were invited to have a one-off PSA test with 219,439 men who were not invited for screening.

After an average of 10 years follow up, there were 8,054 (4.3%) prostate cancers in the screened group and 7,853 (3.6%) cases in the control group. Crucially, both groups had the same percentage of men dying from prostate cancer (0.29%).

These results have informed national and international guidelines for the use of PSA testing as a screening tool for prostate cancer detection. In the UK, the CAP trial results have provided the Public Health England (PHE) National Screening Committee (NSC) with high-quality, UK-based evidence to inform a review of the balance of benefits against harms of PSA based prostate cancer screening. In the USA, the results were included in the recommendations of the US Preventive Services Task Force (https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/prostate-cancerscreening).

Alongside the RCT the CAP Study have been able to carry out important methodological work which has helped inform the use of routine data sources in pragmatic randomised trials. The dataset already held by SAIL has been used to develop the STATA do files and confirmed the feasibility of extracting unbiased health-related costs for comparison across the two groups in the budget impact analyses.

The University of Bristol requires access to mortality, cancer registration, demographics and Hospital Episode Statistics (HES) data for the purpose of a Cluster randomised trial of Prostate Specific Antigen (PSA) testing for Prostate cancer (CAP), CAP is a pragmatic, cluster Randomised Clinical Trial (RCT) that compares an invitation to attend for population-based PSA-testing for prostate cancer (intervention group) with standard NHS care (control group).

There is currently no national screening programme for prostate cancer in the UK but men over 50 can ask their GP for a PSA test. This trial aims to assess the effectiveness of PSA testing in reducing prostate cancer mortality, and its cost-effectiveness (i.e. comparing the health-related costs in the two groups in combination with the effectiveness of PSA testing, in order to assist policy makers in their decisions about how to achieve the best use of resources).

The University of Bristol has been running this trial since 2001.

The median 10-year follow-up was completed and published in The Journal of the American Medical Association (JAMA) in 2018 doi:10.1001/jama.2018.0154. The long lead-time for prostate cancer mortality, confirmed by the CAP publication, necessitates follow-up beyond 10 years to comprehensively evaluate the full impact of screening and Cancer Research UK (CRUK) funded CAP to allow the completion of 15-year analysis.

GP practices in 8 centres in England and Wales were randomly allocated to either population-based PSA testing, akin to screening (the ProtecT study), or standard (unscreened) practice.

In the intervention (ProtecT) practices, between 2001 and 2009, men aged 50-69 years were invited to undergo PSA testing. The individuals who accepted this invitation were asked to sign a consent form permitting follow-up of their health status. Of the men who took the PSA test, those with PSA levels of 3.0 ng/ml or greater were offered standardised 10-core transrectal ultrasound guided biopsy.

For any individuals registered with intervention practices who did not respond to the invitation for a PSA test, support under section 251 NHS Act 2006 permits access to their data for the purpose of follow-up without informed consent.

In the comparison arm practices, men aged 50-69 years undergo standard NHS management (provision of an informed choice to any man over the age of 50 who requests a PSA test). The University of Bristol obtained support under section 60 of the HSCA 2001 (later replaced by support under section 251 NHS Act 2006) to flag these individuals without informed consent.

All men regardless of whether they participated in the ProtecT study are followed up for mortality and cancer registrations contributing to the comparison between the intervention and comparison groups.

From 2005 onwards, the HSCIC (latterly NHS Digital) reported deaths and cancer registrations relating to men in either arm of this study.

When the trial is notified that an individual in either arm has developed prostate cancer, a case review is undertaken. Case reviews involve paper notes and electronic records held by the hospital and not data supplied by NHS Digital under this Agreement. However, the follow-up data from NHS Digital is important as it can be the trigger to undertake a case review.

Because this study has a subset of data subjects who gave consent and a subset who did not, the University of Bristol has two connected Data Sharing Agreements with NHS Digital relating to this study.

• The Agreement under the reference DARS-NIC-119910-K6W9Q covers the individuals whose data are accessed with informed consent.

• The Agreement under the reference DARS-319171-G7H8K covers the individuals whose data are accessed without consent with support under section 251 NHS Act 2006.

The legal basis for personal data to be obtained and processed for is Article 6 (1) (e) processing is necessary for the performance of a task carried out in the public interest. The legal basis for health information data is Article 9 (2) (i) processing is necessary for reasons of public interest in the area of public health and Article 9 (2) (j) processing is necessary for reasons of public interest in the area of research. Public interest is defined here as: provide an evidence base for public policy decision-making; provide an evidence base for decisions which are likely to significantly benefit the UK economy, society or quality of life of people in the UK; and to replicate, validate or challenge existing research. Results from the average 15-year follow-up will directly inform UK policy on prostate cancer screening through the Public Health England (PHE) National Screening Committee (NSC) and have a wide influence internationally. They will also be used in the development of an economic model estimating the cost-effectiveness of prostate cancer screening in the UK, and in the budget impact analysis to be calculated from an NHS perspective.

The data generated will provide both clinical and policy relevant data on one of the most controversial issues in health care nationally and internationally: the potential benefits, harms and costs to the UK population of screening for prostate cancer.

It is unlikely that such a trial would be possible anywhere else in the world because information systems are not as comprehensive across primary and secondary care and across the whole population. The extensive, complete and long-term follow-up of these men is only possible because of the publicly funded national healthcare system the UK NHS and because of NHS Digital hospital and mortality information systems. These information systems provide comprehensive data on cancer diagnoses, deaths and costs to the NHS enabling very long term and cost-effective follow-up of the outcomes from screening.

The CAP Study aims to accurately estimate, for a UK population: a) the effect of a single PSA-testing round on prostate cancer specific and all-cause mortality, compared to standard (unscreened) practice in the CAP trial; b) age specific lead-time and over-diagnosis rates (utilising observed trial data); c) the projected lifetime effectiveness and cost effectiveness of a range of UK-focused screening options, incorporating parameter estimates computed from these data to create a UK-specific decision analytic model.

Continuing receipt of demographics, mortality and cancer registration data will allow the CAP Study to continue to follow-up men in the cohort across the UK to accurately estimate the effect of a single PSA-testing round on 15-year prostate cancer specific and all-cause mortality, compared to standard (unscreened) practice; as well as the age-specific lead-time and over-diagnosis rates (utilising observed trial data); and the projected lifetime effectiveness and cost-effectiveness of UK focused screening strategies.

Prostate cancer mortality and prostate cancer stage, grade and progression are critical outcomes for this trial, and it is essential for informing NHS screening policy that these data are of the highest quality. The CAP study would not be able to reliably determine the cause of death in deceased men, because without identifiable data the trained researchers would be unable to extract information from the medical records to compose the detailed case vignettes which are then used to validate the cause of death. Neither could the study access the electronic hospital records of individuals to extract stage and grade data.

Where cost implications of any national screening programme are considerable, and where survival is relatively good whatever form of management is adopted, it is essential to incorporate analysis of cost-effectiveness. To obtain timely and comprehensive UK-wide coverage, without bias or loss of power, the University of Bristol sought record linkage to hospital records (HES) and Diagnostic Imaging Dataset (DIDs) for over 400,000 men (the combined number of participants in the intervention arm (189,386) and the comparison arm (219,439).

The University of Bristol developed a process for NHS Digital to extract pseudonymised HES and DIDs data for the cohort, which was already flagged for follow-up on NHS Digital’s system, and the data was sent to Secure Anonymised Information Linkage (SAIL) Databank, University of Swansea, which acts as a trusted third party for linkage and using their secure remote access system so that no patient-level resource use data are transferred to the University of Bristol from NHS Digital.

The datasets and data items requested have been restricted to only those directly relevant to the aims and purpose of this research. The HES data includes routine information for administrative purposes when people access healthcare (such as the type of operation and the amount of time spent in hospital). Using these routine data will allow the CAP study to include all individuals in the trial in the ongoing budget impact analysis to estimate the costs to the NHS, providing clinical and policy relevant data. The budget impact analysis of data via the SAIL Gateway will inform evidence-based decisions about prostate cancer screening and treatment. A model-based economic evaluation that will address the issues of extrapolating results beyond median 10-year measurements and incorporating disutility estimates is currently in progress and this will form the economic analysis for CAP.

The team have completed several validation studies that have made a methodological impact in the field and will publish the budget impact analysis and model based economic evaluation following completion of this work.

The University of Bristol is the study sponsor and the sole Data Controller. The lead investigator and another principal investigator are based in Bristol. Two other principal investigators for CAP are based at the University of Oxford, one of whom was previously based at the University of Cambridge. They both have an advisory role for CAP. Historically the University of Oxford and the University of Cambridge were sub-contracted in the CRUK grant held by the University of Bristol. The University of Oxford and the University of Cambridge previously employed some of the CAP researchers but they were line-managed and supervised by the Trial Coordinator based at the University of Bristol. All researchers are now employed by the University of Bristol with honorary contracts for hospital trusts. Whilst historically researchers were employed in other centres to extract data from hospital notes, they did not process NHS Digital data.

Staff and investigators at Bristol have responsibility for all day to day running of the study, including but not limited to data processing and storage, analysis, and leading publications.

The Trial Steering Committee and Data Monitoring Committee have an advisory role, they do not have any control over how NHS Digital data is used or access to these data (except in the form of trial results produced for or presented at these meetings). They provide advice, guidance, and support to the trial.

The University of Swansea is a Data Processor holding the linked HES data accessible to investigators at the University of Bristol in the form of a pseudonymised dataset housed at the Secure Anonymised Information Linkage (SAIL) Databank. This means that it is totally separate to the identifiable data held at the University of Bristol and can never be linked to it.

The research is funded by Cancer Research UK (CRUK). CRUK does not access the data.

The main outcomes of the trial are the effectiveness of Prostate Specific Antigen (PSA) testing in reducing prostate cancer mortality, and its cost-effectiveness (i.e. comparing the health-related costs in the two groups in combination with the effectiveness of PSA testing, in order to assist policy makers in their decisions about how to achieve the best use of resources).

The expected measurable benefits to health arise from the ability of these data to allow an unbiased comparison between men screened for prostate cancer and those not screened. The data generated will provide both clinical and policy relevant data on one of the most controversial issues in health care nationally and internationally: the potential benefits, harms and costs to the UK population of screening for prostate cancer.

The median 15-year follow-up will be reached in 2021 and it is anticipated that the publication will report these results as soon as possible following this, 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 10-year analyses was uploaded onto the University of Bristol research information repository prior to analysis being carried out (http://hdl.handle.net/1983/6d41509f-ab93-4f96-9869-c320acbc4ae1)

A further statistical analysis plan will be uploaded detailing the median 15-year analyses that will be included in the publications. 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.

Outputs will also be fed directly to funders, Cancer Research UK and Department of Health. Other appropriate bodies such as the NHS National Screening Committee, NICE, or the Cochrane Centre will also be informed.

Alongside the median 15-year results it is also anticipated that The University of Bristol will continue to develop and publish methodological work, these publications will be disseminated to inform the research community on the benefits and challenges of using NHS digital data sources.

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.

Research from the University of Bristol led to the Department of Health decision in 1997 that screening for prostate cancer would not be introduced in the UK until there was evidence that benefits outweighed harms. University of Bristol led, and collaborative research subsequently provided evidence to support informed decision-making in the NHS. A formal review by DH in 2010 endorsed the policy and confirmed that any change would be based on evidence from the teams randomised trials. The results published in 2018 have again informed this decision, and this research has ensured UK men have avoided known harms of prostate cancer screening in the context of uncertain benefits and saved the UK economy.

The CAP Trial, which spanned almost 600 GP practices in the UK and included more than 400,000 men aged 50-69, is the largest trial ever to investigate prostate cancer screening.

The trial compared 189,386 men who were invited to have a one-off PSA test with 219,439 men who were not invited for screening.

After an average of 10 years follow up, there were 8,054 (4.3%) prostate cancers in the screened group and 7,853 (3.6%) cases in the control group. Crucially, both groups had the same percentage of men dying from prostate cancer (0.29%).

These results have informed national and international guidelines for the use of PSA testing as a screening tool for prostate cancer detection. In the UK, the CAP trial results have provided the Public Health England (PHE) National Screening Committee (NSC) with high-quality, UK-based evidence to inform a review of the balance of benefits against harms of PSA based prostate cancer screening. In the USA, the results were included in the recommendations of the US Preventive Services Task Force (https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/prostate-cancerscreening).

Alongside the RCT the CAP Study have been able to carry out important methodological work which has helped inform the use of routine data sources in pragmatic randomised trials. The dataset already held by SAIL has been used to develop the STATA do files and confirmed the feasibility of extracting unbiased health-related costs for comparison across the two groups in the budget impact analyses.

This Data Sharing Agreement permits the retention of the data provided under previous iterations of this Agreement for an interim period. This is a pragmatic approach to provide an active Agreement whilst enabling The University of Bristol to complete the necessary actions to enable a subsequent application to extend the Agreement meeting all applicable data sharing standards as published in NHS Digital’s website (see: https://digital.nhs.uk/services/data-access-request-service-dars/dars-guidance).

The following provides background information on the purpose of the original study:

Cluster randomised trial of testing for Prostate cancer (CAP) is a pragmatic, cluster Randomised Clinical Trial (RCT) that compares an invitation to attend for population-based Prostate Specific Antigen (PSA)-testing for prostate cancer (intervention arm) with standard NHS care (control arm) amongst men aged 50 to 69 years registered with GP practices in eight centres in England and Wales. Recruitment to the DH/CRUK-funded CAP trial was completed in 2009 and it is currently in the follow-up phase. Over 415,000 men are being followed-up for incident and fatal prostate cancer via NHS Digital.

Where cost implications of any national screening programme are considerable, and where survival is relatively good whatever form of management is adopted, it is essential to incorporate analysis of cost-effectiveness. To obtain timely and comprehensive UK-wide coverage to estimate the cost effectiveness of prostate cancer screening in the UK CAP are applying for permission to perform record linkage for all 415,000 men in the CAP trial with NHS Digital for the provision of resource use information.

This Agreement permits the secure retention of the data only and no other processing.

No new outputs will be produced under this Data Sharing Agreement.

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 analyses that will be included in the publications has been uploaded onto the University of Bristol research information repository (http://hdl.handle.net/1983/6d41509f-ab93-4f96-9869-c320acbc4ae1)

An updated statistical analysis plan will be uploaded to reflect the median 15-year analysis. 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 follow ONS non-disclosure rules for small numbers of cases and will not include any counts of less than 5 in a Table. The median 15 years follow-up will be reached in 2021, the applicant would nevertheless wish to apply for additional funding for longer term follow–up.

Follow-up for the median 15 years is reached in 2021. As stated above the median 10-year results were published in 2018, listed below with other recent publications directly related to the study:

Martin, Donovan, Turne, et al (2018) Effect of low intensity PSA-based screening Intervention on Prostate Cancer Mortality: The CAP randomized clinical trial. JAMA 319(9):883-895. [DOI: 10.1001/jama.2018.0154].

Donovan, Young, Walsh, et al (2018) A prospective cohort and extended comprehensive-cohort design provided insights about the generalizability of a pragmatic trial. Journal of Clinical Epidemiology.96:35-46.

Merriel, Turner, Walsh, et al (2017) Cross-sectional study evaluating data quality of the National Cancer Registration and Analysis Service (NCRAS) prostate cancer registry data using the Cluster randomised triAl of PSA testing for Prostate cancer (CAP) BMJ Open 7 (11) e015994

Young, Harrison, Turner, et al (2017) Prostate Specific Antigen (PSA) testing of men in UK general practice. BMJ Open. 7 (10) e017729

Harrison, Tilling, Turner, et al (2016) Investigating the prostate specific antigen, body mass index and age relationship: is an age–BMI-adjusted PSA model clinically useful? Cancer Causes & Control 27:12, 1465-1474; doi:10.1007/s10552-016-0827-1

Walsh, Turner, Lane, et al (2016) Characteristics of men responding to an invitation to undergo testing for prostate cancer as part of a randomised trial. Trials 17, 497; doi:10.1186/s13063-016-1624-6

Hamdy, Donovan, Lane et al (2016) 10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer. NEJM; doi:10.1056/NEJMoa1606220

Donovan, Hamdy, Lane, et al (2016) Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer. NEJM; doi:10.1056/NEJMoa1606221

Turner, Metcalfe, Donovan et al (2016) Contemporary accuracy of death certificates for coding prostate cancer as a cause of death: Is reliance on death certification good enough? A comparison with blinded review by an independent cause of death evaluation committee. Br J Cancer; 115:90-4 doi: 10.1038/bjc.2016.162

Thorn, Turner, Hounsome, et al (2016) Validating the use of hospital episode statistics data and comparison of costing methodologies for economic evaluation: An end-of-life case study from the cluster randomised triAl of PSA testing for prostate cancer (CAP). BMJ Open 6:4, e011063 doi:10.1136/bmjopen-2016-011063

Thorn, Turner, Hounsome, et al (2015) Validation of the Hospital Episode Statistics Outpatient Dataset in England. PharmacoEconomics. doi:10.1007/s40273-015-0326-3

Williams NJ, Hill EM, Ng SY, Martin RM, Metcalfe C, Donovan JL, Evans S, Hughes LJ, Davies CF, Hamdy FC, Neal DE, Turner EL, for the CAP Cause of Death Committee. Standardisation of information submitted to an endpoint committee for cause of death assignment in a cancer screening trial – lessons learnt from CAP (Cluster randomised triAl of PSA testing for Prostate cancer). BMC Medical Research Methodology (2015) 15:6 (doi:10.1186/1471-2288-15-6)

Turner EL, Metcalfe C, Donovan JL, Noble S, Sterne JAC, Lane A, Avery K, Down L, Walsh E, Davis M, Ben-Shlomo Y, Oliver S, Evans S, Brindle P, Williams N, Hughes LJ, Hill E, Davies C, Ng SY, Neal DE, Hamdy FC, Martin RM. Design and preliminary recruitment results of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP). British Journal of Cancer (2014) 110; 2829-36 (doi: 10.1038/bjc.2014.242)

Lane JA, Donovan JL, Davis M, Walsh E, Dedman D, Down L, Turner EL, Mason MD, Metcalfe C, Peters TJ, Martin RM, Neal DE, Hamdy FC, for the ProtecT study group. Active monitoring, radical prostatectomy, or radiotherapy for localised prostate cancer: study design and diagnostic and baseline results of the ProtecT randomised phase 3 trial. Lancet Oncology (2014) 15: 1109-18 (http://dx.doi.org/10.1016/ S1470-2045(14)70361-4)

Hill EM, Turner EL, Martin RM & Donovan JL. "Let's get the best quality research we can": public awareness and acceptance of consent to use existing data in health research: a systematic review and qualitative study. BMC Medical Research Methodology (2013) 13:72 (doi: 10.1186/1471-2288-13-72)

Williams NJ, Hughes LJ, Turner EL, Donovan JL, Hamdy FC, Neal DE, Martin RM, Metcalfe C. Prostate-specific antigen testing rates remain low in UK general practice: A cross-sectional study in six English cities. British Journal of Urology International (2011) 108:9; 1402-08 (doi:10.1111/j.1464-410X.2011.10163.x)

Lane JA, Hamdy FC, Martin RM, Turner EL, Neal DE, Donovan JL. Latest results from the UK trials evaluating prostate cancer screening and treatment: The CAP and ProtecT studies. European Journal of Cancer (2010) 46; 3095-3101 (doi:10.1016/j.ejca.2010.09.016)

Outputs will also be fed directly to funders, Cancer Research UK and Department of Health. Other appropriate bodies such as NICE or the Cochrane Centre will also be informed.

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. We also publish with open access rights when submitting to journals, ensuring we 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.

Median 10-year results were published in 2018 and have already had an impact on screening policy in UK and worldwide.

Mortality and Cancer data were supplied to the University of Bristol by ONS and subsequently the Health and Social Care Information Centre (which has since become NHS Digital) for the purpose of a research project referred to as ’The CAP study'. Diagnostic Imaging Data and HES Admitted Patient Care, Critical Care, Outpatient and Accident Emergency data has been supplied by NHS Digital.

This Data Sharing Agreement permits the retention and processing of the data for an interim period. This is a practical step to enable the study to comply with the necessary legal and ethical requirements. If, for any reason, it is not possible for the study to meet the necessary requirements, this Agreement will be terminated and destruction of the data will be required.

The following provides background information on the purpose of the original study:

Cluster randomised trial of testing for Prostate cancer (CAP) is a pragmatic, cluster Randomised Clinical Trial (RCT) that compares an invitation to attend for population-based Prostate Specific Antigen (PSA)-testing for prostate cancer (intervention arm) with standard NHS care (control arm) amongst men aged 50 to 69 years registered with GP practices in eight centres in England and Wales. Recruitment to the DH/CRUK-funded CAP trial was completed in 2009 and it is currently in the follow-up phase. Over 415,000 men are being followed-up for incident and fatal prostate cancer via NHS Digital.

Where cost implications of any national screening programme are considerable, and where survival is relatively good whatever form of management is adopted, it is essential to incorporate analysis of cost-effectiveness. To obtain timely and comprehensive UK-wide coverage to estimate the cost effectiveness of prostate cancer screening in the UK CAP are applying for permission to perform record linkage for all 415,000 men in the CAP trial with NHS Digital for the provision of resource use information.

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 analyses that will be included in the publications has been uploaded onto the University of Bristol research information repository (http://hdl.handle.net/1983/6d41509f-ab93-4f96-9869-c320acbc4ae1)

An updated statistical analysis plan will be uploaded to reflect the median 15-year analysis. 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 follow ONS non-disclosure rules for small numbers of cases and will not include any counts of less than 5 in a Table. The median 15 years follow-up will be reached in 2021, the applicant would nevertheless wish to apply for additional funding for longer term follow–up.

Follow-up for the median 15 years is reached in 2021. As stated above the median 10-year results were published in 2018, listed below with other recent publications directly related to the study:

Martin, Donovan, Turne, et al (2018) Effect of low intensity PSA-based screening Intervention on Prostate Cancer Mortality: The CAP randomized clinical trial. JAMA 319(9):883-895. [DOI: 10.1001/jama.2018.0154].

Donovan, Young, Walsh, et al (2018) A prospective cohort and extended comprehensive-cohort design provided insights about the generalizability of a pragmatic trial. Journal of Clinical Epidemiology.96:35-46.

Merriel, Turner, Walsh, et al (2017) Cross-sectional study evaluating data quality of the National Cancer Registration and Analysis Service (NCRAS) prostate cancer registry data using the Cluster randomised triAl of PSA testing for Prostate cancer (CAP) BMJ Open 7 (11) e015994

Young, Harrison, Turner, et al (2017) Prostate Specific Antigen (PSA) testing of men in UK general practice. BMJ Open. 7 (10) e017729

Harrison, Tilling, Turner, et al (2016) Investigating the prostate specific antigen, body mass index and age relationship: is an age–BMI-adjusted PSA model clinically useful? Cancer Causes & Control 27:12, 1465-1474; doi:10.1007/s10552-016-0827-1

Walsh, Turner, Lane, et al (2016) Characteristics of men responding to an invitation to undergo testing for prostate cancer as part of a randomised trial. Trials 17, 497; doi:10.1186/s13063-016-1624-6

Hamdy, Donovan, Lane et al (2016) 10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer. NEJM; doi:10.1056/NEJMoa1606220

Donovan, Hamdy, Lane, et al (2016) Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer. NEJM; doi:10.1056/NEJMoa1606221

Turner, Metcalfe, Donovan et al (2016) Contemporary accuracy of death certificates for coding prostate cancer as a cause of death: Is reliance on death certification good enough? A comparison with blinded review by an independent cause of death evaluation committee. Br J Cancer; 115:90-4 doi: 10.1038/bjc.2016.162

Thorn, Turner, Hounsome, et al (2016) Validating the use of hospital episode statistics data and comparison of costing methodologies for economic evaluation: An end-of-life case study from the cluster randomised triAl of PSA testing for prostate cancer (CAP). BMJ Open 6:4, e011063 doi:10.1136/bmjopen-2016-011063

Thorn, Turner, Hounsome, et al (2015) Validation of the Hospital Episode Statistics Outpatient Dataset in England. PharmacoEconomics. doi:10.1007/s40273-015-0326-3

Williams NJ, Hill EM, Ng SY, Martin RM, Metcalfe C, Donovan JL, Evans S, Hughes LJ, Davies CF, Hamdy FC, Neal DE, Turner EL, for the CAP Cause of Death Committee. Standardisation of information submitted to an endpoint committee for cause of death assignment in a cancer screening trial – lessons learnt from CAP (Cluster randomised triAl of PSA testing for Prostate cancer). BMC Medical Research Methodology (2015) 15:6 (doi:10.1186/1471-2288-15-6)

Turner EL, Metcalfe C, Donovan JL, Noble S, Sterne JAC, Lane A, Avery K, Down L, Walsh E, Davis M, Ben-Shlomo Y, Oliver S, Evans S, Brindle P, Williams N, Hughes LJ, Hill E, Davies C, Ng SY, Neal DE, Hamdy FC, Martin RM. Design and preliminary recruitment results of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP). British Journal of Cancer (2014) 110; 2829-36 (doi: 10.1038/bjc.2014.242)

Lane JA, Donovan JL, Davis M, Walsh E, Dedman D, Down L, Turner EL, Mason MD, Metcalfe C, Peters TJ, Martin RM, Neal DE, Hamdy FC, for the ProtecT study group. Active monitoring, radical prostatectomy, or radiotherapy for localised prostate cancer: study design and diagnostic and baseline results of the ProtecT randomised phase 3 trial. Lancet Oncology (2014) 15: 1109-18 (http://dx.doi.org/10.1016/ S1470-2045(14)70361-4)

Hill EM, Turner EL, Martin RM & Donovan JL. "Let's get the best quality research we can": public awareness and acceptance of consent to use existing data in health research: a systematic review and qualitative study. BMC Medical Research Methodology (2013) 13:72 (doi: 10.1186/1471-2288-13-72)

Williams NJ, Hughes LJ, Turner EL, Donovan JL, Hamdy FC, Neal DE, Martin RM, Metcalfe C. Prostate-specific antigen testing rates remain low in UK general practice: A cross-sectional study in six English cities. British Journal of Urology International (2011) 108:9; 1402-08 (doi:10.1111/j.1464-410X.2011.10163.x)

Lane JA, Hamdy FC, Martin RM, Turner EL, Neal DE, Donovan JL. Latest results from the UK trials evaluating prostate cancer screening and treatment: The CAP and ProtecT studies. European Journal of Cancer (2010) 46; 3095-3101 (doi:10.1016/j.ejca.2010.09.016)

Outputs will also be fed directly to funders, Cancer Research UK and Department of Health. Other appropriate bodies such as NICE or the Cochrane Centre will also be informed.

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. We also publish with open access rights when submitting to journals, ensuring we 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.

Median 10-year results were published in 2018 and have already had an impact on screening policy in UK and worldwide.

Mortality and Cancer data were supplied to the University of Bristol by ONS and subsequently the Health and Social Care Information Centre (which has since become NHS Digital) for the purpose of a research project referred to as ’The CAP study'. Diagnostic Imaging Data and HES Admitted Patient Care, Critical Care, Outpatient and Accident Emergency data has been supplied by NHS Digital.

This Data Sharing Agreement permits the retention and processing of the data for an interim period. This is a practical step to enable the study to comply with the necessary legal and ethical requirements. If, for any reason, it is not possible for the study to meet the necessary requirements, this Agreement will be terminated and destruction of the data will be required.

The following provides background information on the purpose of the original study:

Cluster randomised trial of testing for Prostate cancer (CAP) is a pragmatic, cluster Randomised Clinical Trial (RCT) that compares an invitation to attend for population-based Prostate Specific Antigen (PSA)-testing for prostate cancer (intervention arm) with standard NHS care (control arm) amongst men aged 50 to 69 years registered with GP practices in eight centres in England and Wales. Recruitment to the DH/CRUK-funded CAP trial was completed in 2009 and it is currently in the follow-up phase. Over 415,000 men are being followed-up for incident and fatal prostate cancer via NHS Digital.

Where cost implications of any national screening programme are considerable, and where survival is relatively good whatever form of management is adopted, it is essential to incorporate analysis of cost-effectiveness. To obtain timely and comprehensive UK-wide coverage to estimate the cost effectiveness of prostate cancer screening in the UK CAP are applying for permission to perform record linkage for all 415,000 men in the CAP trial with NHS Digital for the provision of resource use information.

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 analyses that will be included in the publications has been uploaded onto the University of Bristol research information repository (http://hdl.handle.net/1983/6d41509f-ab93-4f96-9869-c320acbc4ae1)

An updated statistical analysis plan will be uploaded to reflect the median 15-year analysis. 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 follow ONS non-disclosure rules for small numbers of cases and will not include any counts of less than 5 in a Table. The median 15 years follow-up will be reached in 2021, the applicant would nevertheless wish to apply for additional funding for longer term follow–up.

Follow-up for the median 15 years is reached in 2021. As stated above the median 10-year results were published in 2018, listed below with other recent publications directly related to the study:

Martin, Donovan, Turne, et al (2018) Effect of low intensity PSA-based screening Intervention on Prostate Cancer Mortality: The CAP randomized clinical trial. JAMA 319(9):883-895. [DOI: 10.1001/jama.2018.0154].

Donovan, Young, Walsh, et al (2018) A prospective cohort and extended comprehensive-cohort design provided insights about the generalizability of a pragmatic trial. Journal of Clinical Epidemiology.96:35-46.

Merriel, Turner, Walsh, et al (2017) Cross-sectional study evaluating data quality of the National Cancer Registration and Analysis Service (NCRAS) prostate cancer registry data using the Cluster randomised triAl of PSA testing for Prostate cancer (CAP) BMJ Open 7 (11) e015994

Young, Harrison, Turner, et al (2017) Prostate Specific Antigen (PSA) testing of men in UK general practice. BMJ Open. 7 (10) e017729

Harrison, Tilling, Turner, et al (2016) Investigating the prostate specific antigen, body mass index and age relationship: is an age–BMI-adjusted PSA model clinically useful? Cancer Causes & Control 27:12, 1465-1474; doi:10.1007/s10552-016-0827-1

Walsh, Turner, Lane, et al (2016) Characteristics of men responding to an invitation to undergo testing for prostate cancer as part of a randomised trial. Trials 17, 497; doi:10.1186/s13063-016-1624-6

Hamdy, Donovan, Lane et al (2016) 10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer. NEJM; doi:10.1056/NEJMoa1606220

Donovan, Hamdy, Lane, et al (2016) Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer. NEJM; doi:10.1056/NEJMoa1606221

Turner, Metcalfe, Donovan et al (2016) Contemporary accuracy of death certificates for coding prostate cancer as a cause of death: Is reliance on death certification good enough? A comparison with blinded review by an independent cause of death evaluation committee. Br J Cancer; 115:90-4 doi: 10.1038/bjc.2016.162

Thorn, Turner, Hounsome, et al (2016) Validating the use of hospital episode statistics data and comparison of costing methodologies for economic evaluation: An end-of-life case study from the cluster randomised triAl of PSA testing for prostate cancer (CAP). BMJ Open 6:4, e011063 doi:10.1136/bmjopen-2016-011063

Thorn, Turner, Hounsome, et al (2015) Validation of the Hospital Episode Statistics Outpatient Dataset in England. PharmacoEconomics. doi:10.1007/s40273-015-0326-3

Williams NJ, Hill EM, Ng SY, Martin RM, Metcalfe C, Donovan JL, Evans S, Hughes LJ, Davies CF, Hamdy FC, Neal DE, Turner EL, for the CAP Cause of Death Committee. Standardisation of information submitted to an endpoint committee for cause of death assignment in a cancer screening trial – lessons learnt from CAP (Cluster randomised triAl of PSA testing for Prostate cancer). BMC Medical Research Methodology (2015) 15:6 (doi:10.1186/1471-2288-15-6)

Turner EL, Metcalfe C, Donovan JL, Noble S, Sterne JAC, Lane A, Avery K, Down L, Walsh E, Davis M, Ben-Shlomo Y, Oliver S, Evans S, Brindle P, Williams N, Hughes LJ, Hill E, Davies C, Ng SY, Neal DE, Hamdy FC, Martin RM. Design and preliminary recruitment results of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP). British Journal of Cancer (2014) 110; 2829-36 (doi: 10.1038/bjc.2014.242)

Lane JA, Donovan JL, Davis M, Walsh E, Dedman D, Down L, Turner EL, Mason MD, Metcalfe C, Peters TJ, Martin RM, Neal DE, Hamdy FC, for the ProtecT study group. Active monitoring, radical prostatectomy, or radiotherapy for localised prostate cancer: study design and diagnostic and baseline results of the ProtecT randomised phase 3 trial. Lancet Oncology (2014) 15: 1109-18 (http://dx.doi.org/10.1016/ S1470-2045(14)70361-4)

Hill EM, Turner EL, Martin RM & Donovan JL. "Let's get the best quality research we can": public awareness and acceptance of consent to use existing data in health research: a systematic review and qualitative study. BMC Medical Research Methodology (2013) 13:72 (doi: 10.1186/1471-2288-13-72)

Williams NJ, Hughes LJ, Turner EL, Donovan JL, Hamdy FC, Neal DE, Martin RM, Metcalfe C. Prostate-specific antigen testing rates remain low in UK general practice: A cross-sectional study in six English cities. British Journal of Urology International (2011) 108:9; 1402-08 (doi:10.1111/j.1464-410X.2011.10163.x)

Lane JA, Hamdy FC, Martin RM, Turner EL, Neal DE, Donovan JL. Latest results from the UK trials evaluating prostate cancer screening and treatment: The CAP and ProtecT studies. European Journal of Cancer (2010) 46; 3095-3101 (doi:10.1016/j.ejca.2010.09.016)

Outputs will also be fed directly to funders, Cancer Research UK and Department of Health. Other appropriate bodies such as NICE or the Cochrane Centre will also be informed.

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. We also publish with open access rights when submitting to journals, ensuring we 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.

Median 10 year results published and impact on screening policy in UK and worldwide.