UPSTREAM Phase II – Further Follow Up Study (Urodynamics for Prostate Surgery Trial; Randomised Evaluation of Assessment Methods).

The Bristol Medical School (BMS) based at the University of Bristol (UoB) requires Hospital Episode Statistics (HES), Admitted Patient Care and Outpatient data in addition to Civil registration death data from NHS England as part of a National Institute for Health Research (NIHR) Health Technology Assessment (HTA) funded research project, entitled: “Urodynamics for Prostate Surgery Trial; Randomised Evaluation of Assessment Methods (UPSTREAM) for diagnosis and management of bladder outlet obstruction in men” (NIHR HTA ref: 12/140/01), which consists of two phases as summarised below. This data request is linked with the second phase of the project, i.e. the five year follow up, “UPSTREAM – Phase II”.

UPSTREAM OVERVIEW

Lower urinary tract symptoms (LUTS) are a common feature of ageing. They can be categorised as problems with voiding (passing urine) or storing urine. In men with voiding LUTS, benign prostate enlargement (BPE) with ageing causes benign prostatic obstruction (BPO). For such patients, prostate surgery, such as transurethral resection of the prostate (TURP), may improve LUTS. However, voiding LUTS can also be caused by bladder dysfunction: e.g. poor expulsion strength of the bladder muscle, called ‘detrusor underactivity’ (DU). In such men, it is hard to justify prostate surgery if BPO is not present, especially in view of potential adverse effects.

The UPSTREAM participants were originally recruited between 2014 and 2016 to join what is now referred to as UPSTREAM-Phase I, which was the main randomised controlled trial. Participants provided written informed consent to join the trial using the consent, and study information, materials provided.

The UPSTREAM trial (“UPSTREAM - Phase I”) evaluated the assessment of LUTS in men who were seeking further treatment for their bothersome LUTS, which may have included surgical intervention. Between October 2014 and December 2016, 820 men were recruited and randomised to a care pathway which included or omitted invasive urodynamic (UDS) testing (Urodynamics arm [intervention] and Routine Care arm [control]). Following assessments, men decided their therapy in discussion with their healthcare professional, which could have been conservative (advice, medication) or interventional (procedures to relieve BPO). The primary outcome was the patient-reported International Prostate Symptom Score (IPSS) at 18-months post-randomisation, and a key secondary outcome was rates of bladder outlet surgery. “UPSTREAM – Phase I” ended September 2018.

During the trial (“UPSTREAM - Phase I”), it was established that there is considerable variability in the diagnostic pathway, including duration, across 26 secondary care sites across England, as well as in patient factors. The trial identified that several patients had not fully completed their therapy for LUTS at the time of the primary outcome assessment (18-months post-randomisation) or had completed it less than six-months beforehand. Clinically this is an insufficient time frame to offer full insight into impacts of surgical interventions. Thus, additional funding was obtained to conduct a second phase of the UPSTREAM project (“UPSTREAM - Phase II”) to undertake the follow up of existing UPSTREAM participants at five years post-randomisation, aiming to identify: 1) definitive surgery rates in the two arms; 2) symptom outcomes of treatment, allowing enough time for full recovery from surgery; and 3) the long-term impacts of LUTS and its therapy, including evaluation of the resource use and health economic implications.

Thus, this long-term further follow up will help understanding of the sustained response, placebo impact and the behaviour of storage LUTS over time. It is hoped that it will help the project to state for sure whether or not UDS delivered non-inferior symptom outcomes with lower surgery rates. Furthermore, there is very little information documented about men’s attitudes to the long-term experience on LUTS and its treatments, and the European Association of Urology (EAU) has identified this as a priority research need.

UPSTREAM-Phase II has two main components: (1) a longer-term follow-up participant questionnaire completed ~5-years post original randomisation (Patient Reported Outcome Measures (PROMS) study component); and (2) NHS England data extraction study component. The Protocol for UPSTREAM – Phase II (version 1, 21 October 2019, Sections 6.1 and 6.2) outlines the identification and recruitment aspects for these two different study components.

The start date for “UPSTREAM - Phase II” was 01 July 2021, and the study duration is expected to be 36 months, due to 30 June 2022 (subject to change). Around 5-years after men were randomised to “UPSTREAM Phase I”, the research team sent a “Further Follow Up Patient Pack, inviting them to take part in this further follow up study, “UPSTREAM – Phase II pack contained an Invitation letter, Participant Information Sheet, questionnaire booklet & prepaid (freepost) envelope (plus online/ telephone request form).

Consent and 5-Year Post-Randomisation Questionnaire Follow Up

Participants returned a completed questionnaire about their urinary symptoms, their effect on their everyday life, and their general state of health.

DATA CONTROLLERS

North Bristol NHS Trust (NBT) and The University of Bristol (UoB) are joint Data Controllers of this project. NBT have a research contract for funding for this research project with the Secretary of State (SoS) for Health and NBT will only have oversight of the processes in their role of Sponsor and Data Controller. NBT will only see data in aggregated form (i.e. not at an individual level record).

The SoS have oversight of the funding but do not undertake any decision making on the purposes for which the data being processed under this Data Sharing Agreement (DSA) as such NHS England are satisfied that they are not a data controller.

The University of Bristol (UoB) will also process the data. While the NIHR are the funder, they do not determine the purpose or the way the data will be processed. Data processing activities will take place by specified personnel who are employees of the UoB.

CO-INVESTIGATORS

The co-investigators listed in the protocol are members of the project management group who provide general project oversight and advise the study coordination team (based at The University of Bristol (UoB)) as required. Co-investigators will not have a role as either Data Controller or Data Processor and will only see data in aggregated form. Substantive colleagues at UoB are the only individuals who will access the record level data being disseminated.

The co-investigators are not determining the means by which the data are being processed nor are they acting any a data controllership capacity in any way for this research. They are advisory only all decisions are made by NBT and UoB.

JUSTIFICATION FOR THE DATASETS REQUESTED:

The six key objectives of “UPSTREAM – Phase II” are:

A) What are the symptomatic outcomes for Lower Urinary Tract Symptoms (LUTS), measured by the International Prostate Symptom Score (IPSS)?

B) What are the surgery rates in the two diagnostic pathways (the relative proportion of men having surgery)?

C) Was additional diagnostic testing (e.g. Urodynamic studies (UDS) undertaken after the completion of UPSTREAM - Phase I? (where possible)

D) What are the differential effects on other outcomes, such as symptom: severity and bother; sexual function; quality of life (QoL); and general health?

E) What is the cost effectiveness from an NHS secondary care perspective using the Quality Adjusted Life Year (QALY) as the economic outcome?

F) What is the differential use of NHS resources?

To achieve these objectives no clinical assessments are proposed, rather data collection is via (1) a participant completed questionnaire around 5-years post randomisation and (2) a one-off bespoke data dissemination via NHS England.

Between October 2014 and December 2016 (“UPSTREAM - Phase I”), participating sites identified, assessed and enrolled 820 men (aged ≥18 years) into the study. All participants provided written informed consent to take part in Phase I of the study.

“UPSTREAM – Phase II”. “UPSTREAM - Phase II” was in part funded due to the efficient study design, that includes utilising linkage with routine healthcare data and centrally administered questionnaires. Using research nurses at 26 hospitals to collect such follow up data would add considerable cost and time. Participants have been provided with information about the nature of the research and how their personal and sensitive data are processed, which is also made available via the study website http://www.bristol.ac.uk/population-health-sciences/projects/upstream/taking-part/upstream--phase-ii-active/

(1) 5-Year Questionnaire.

Participants will be invited to complete a questionnaire (booklet) around five years post-randomisation (objectives A, D and E). Participants will be able to complete the questionnaire booklet via post, online or telephone. As per ethical and regulatory approvals, return of the completed questionnaire is sufficient evidence of implicit consent for the questionnaire element of the 5-year follow up. (416 responses to the 5-year questionnaire were received back to the UPSTREAM II study).

In the UPSTREAM PHASE II part of the study, no new ‘written consent forms’ were completed for Phase II. All applicable participants were suitably contacted and provided with information. Furthermore, brief details about the follow-up study were included in our Participant Newsletter (September 2019) and all study information materials are also displayed on our study website (https://www.bristol.ac.uk/population-health-sciences/projects/upstream/).

(2) the data provided by NHS England will be used to assess surgery rates, whether additional diagnostic testing was undertaken after the completion of “UPSTREAM - Phase I” (where possible), and resource use (objectives B, C and F), the UPSTREAM study will utilise individual level data obtained from NHS England which will include individual level data about participants’ relevant: inpatient stays; outpatient attendances and cause of death (where applicable). UPSTREAM Phase II envisage the data dissemination to include the last participant’s five year post-randomisation time point.

For this element of the project (i.e. the bespoke data dissemination of HES and HES-ONS linked data, via NHS England), men who were enrolled (randomised) to the UPSTREAM randomised controlled trial (“UPSTREAM - Phase I”) will be included. The following patients will, however, be excluded: (1) patients who are not already enrolled to UPSTREAM trial (“UPSTREAM - Phase I”); and (2) Phase I participants who, at the time of their 18-month timepoint, withdrew permission for the study to continue to access sections of their medical notes and NHS records, ONS and NHS Central registers information.

To ensure data minimisation, only data items necessary for this analysis are requested; UPSTREAM Phase II will not, for example, request data for patients that did not originally enrol in the UPSTREAM project. For each participant to be included, data will be required from when they joined the UPSTREAM trial (“UPSTREAM - Phase I”) through to the date of their 5-year follow up time point (5-years post-randomisation). In line with the objectives noted above, the types of data required are: Hospital Episode Statistics (HES Admitted Patient Care (APC), Outpatients (OP) and Civil Registration Deaths. UPSTREAM Phase II have not requested sensitive or identifiable fields.

The University of Bristol will send a cohort to NHS England for linkage to the specified datasets; this will include UPSTREAM Study Identification (I.D) number, patient identifying NHS number, forename, surname, date of birth, gender and current postcode as held on study records, plus date of initial randomisation and 5-year follow up. In return, UPSTREAM Phase II anticipate that data provided by NHS England under this DSA will be pseudonymised (i.e. identified by the UPSTREAM Study ID number).

LEGAL BASIS:

The lawful basis for processing personal data for UPSTREAM are Articles 6.1(e) “where processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller” and 9.2(j) “where the processing of personal data is necessary for archiving purposes, scientific or historical research purposes or statistical purposes in the public interest”.

The justification for processing the data by University of Bristol and North Bristol NHS Trust is Article 6(1)(e) of the GDPR: (processing is necessary for the performance of a task in the public interest or in the exercise of official authority vested in the controller).

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

These can be justified on the grounds that UPSTREAM is a NIHR HTA funded, peer-reviewed randomised controlled trial and additional longer term follow up, that is Sponsored by North Bristol NHS Trust (a NHS organisation) and delivered by the University of Bristol (UOB; a UK Higher Education Institute). Both organisations have a public interest to undertake such processing of personal and sensitive data to advance the evidence base in the clinical care and cost effectiveness of the treatment of men with LUTS in the NHS. No element of this work is taking place outside the UK.

Data provided by NHS England that are held for analysis will not be transferred outside the UoB to any third countries or organisation. As a Data Controller, UPSTREAM Phase II (UoB) and North Bristol NHS Trust have the legal responsibility to safeguard the information provided and to ensure it is processed lawfully.

COMMON LAW DUTY OF CONFIDENTIALITY:

Throughout the project the study keep participants informed by sending them appropriate newsletters and updating the study website, where appropriate. Members of the Patient and Public Involvement (PPI) group assist with the development of the newsletters, which aim to keep the participant informed of progress, including any changes to the study, and remind them where they can find out further information, including the contact details of the Study Office.

NHS England – data extraction study component, a member of the research team will review relevant data of all 820 UPSTREAM participants; these data will be extracted from the existing UPSTREAM databases, and manual checking of the UPSTREAM (Phase I) consent forms and withdrawal/change of permissions forms, if required.

Specifically, the team will check that the participants did not withdraw permission for the study to continue to access sections of their medical notes and NHS records, ONS and NHS Central registers information, at the time of their 18-month timepoint; data extraction via NHS England will only be requested for men meeting this criteria.

As noted above, all men who originally enrolled in the UPSTREAM trial (Phase I) provided written informed consent, which included the essential statement “I agree that information relevant to the UPSTREAM study may be collected from my hospital and NHS records, including Office of National Statistics (ONS), NHS central registers and the Health and Social Care Information Centre, and that this data may be used to follow my ongoing health after the study”.

Based on the original written consent provided by men, information from central NHS records (including NHS England linked data) will be requested for all (eligible) participants who enrolled in the UPSTREAM study (Phase I), irrespective of longer term (5-year) questionnaire completion.

There will be no data linkage undertaken with NHS England data provided under this DSA that is not already noted in the DSA.

Data will only be accessed and processed by substantive employees of the University of Bristol and North Bristol NHS Trust will not be accessed or processed by any other third parties not mentioned in this DSA.

References to ‘UPSTREAM’ within this section refer only to the processing activity related to the “data extraction via NHS England” element of “UPSTREAM – Phase II”; information about “UPSTREAM – Phase I” and the questionnaire component of “UPSTREAM – Phase II” are not detailed, unless relevant.

“UPSTREAM-Phase II” - NHS England data extraction component.

(1) Between October 2014 and December 2016, patients were invited to take part in the UPSTREAM randomised controlled trial, referred within this section as “UPSTREAM – Phase I”.

(2) Written informed consent to take part was obtained for 820 eligible patients, which included agreement that information relevant to the UPSTREAM study may be collected from the patient’s hospital and NHS records, including Office of National Statistics (ONS), NHS central registers and the Health & Social Care Information Centre, and that this data may be used to follow their ongoing health after the study. When a patient joined the study, they were allocated a unique Participant Study I.D. number to main pseudonymisation. Participants will continue to utilise this I.D number throughout all stages of the project.

(3) As part of the 5-year follow up (“UPSTREAM – Phase II”), a member of The University of Bristol (UoB) research team will review relevant data of all existing UPSTREAM participants; these data will be extracted from the existing UPSTREAM databases, and manual checking of the UPSTREAM (Phase I) consent forms and withdrawal/change of permissions forms, if required. Specifically, the team will check that the participants did not withdraw permission for the study to continue to access sections of their medical notes and NHS records, ONS and NHS Central registers information, at the time of their 18-month timepoint; data extraction via NHS England will only be requested for participants meeting these criteria.

To access the desired information, (UoB) will securely send NHS England a cohort file for linkage to specified HES and HES-ONS datasets. The cohort file will include: UPSTREAM Study Identification (I.D) number, patient identifying NHS number, forename, surname, date of birth, gender and postcode (current postcode as per study records), plus date of initial randomisation and 5-year follow up.

(4) NHS England will use the patient identifiers to achieve linkage to the specified datasets for the periods of time specified per participant. NHS England will prepare a file(s) containing the UPSTREAM I.D number (but removing other direct identifiers, e.g. NHS number, name etc.). NHS England will then securely transfer the file(s) to the UPSTREAM project team at UoB

(5) The UPSTREAM team at UoB will store the data in a secure environment with appropriate security firewalls and controls in place and with secure access via approved personal. UoB substantive colleagues are the only individuals who will access the record level data being disseminated.

(6) Data from NHS England will be linked via the unique study (participant) I.D number to other pseudonymised data collected as part of the trial (including case report forms and questionnaires) to enable full analysis as per the study objectives. Data analysis will be performed by specific members of the UPSTREAM team, who are employed by the UoB. Analysis will take place on designated encrypted computer(s) working with data stored on the EVM. In line with the UoB DSPT, data processing will only be conducted by substantive employees of the data processor(s) and or data controller(s) who have been appropriately trained in data protection and confidentiality.

Raw, individual level data from NHS England will only be processed at UoB and will not flow out of UoB. It will be used to derive event rates (e.g. hospital admission rates and rates of death) in an analysis file. As noted in previous sections, data from NHS England will be used to address key objectives for this further follow up (“UPSTREAM - Phase II”). These will be added to the main analysis files for the trial. A Statistical Analysis Plan (SAP) and Heath Economics Analysis Plan (HEAP) have been developed and will be signed off by the Trial Management Group, and wider Independent Trial Steering Committee, prior to analysis. UoB plan to publish aggregated data, which is appropriate for the public domain, however no patient will be identifiable from such publications, as noted in our participant information materials.

The data from the original UPSTREAM (Phase I) study are kept safely on the University of Bristol secure file system. The NHS England data, collected as part of Phase II, will be stored securely using the University’s Encapsulated Virtual Machine (EVM). Analysis will take place on designated encrypted computer(s) working with data stored on the EVM. As an additional precaution, the identifiers used in Phase I will not match the identifiers used in Phase II. The trial statistician and health economist will have access to the “linking” IDs for analysis purposes only. They will stored in a secure place, separately to the Phase I and Phase II datasets.

As stated in the study protocol, pseudonymised research data will be stored and kept for future analysis.

The UPSTREAM research team will not be sharing the NHS England data with anyone not listed as a data controller or processor. No other 'teams' at UoB will be able to put in a request for individual-level NHS England data. No individual-level NHS England data will be shared with other 'teams' at UoB. No other areas of UoB will access record level data supplied under this DSA.

This project (“UPSTREAM – Phase II”) has been allocated a Bristol Medical School Data Security and Protection Authorisation Number (DSPAN; reference A1034). This DSPAN permits us to proceed with the research study under the umbrella Bristol Medical School DSP application [UNIVERSITY OF BRISTOL - Bristol Medical School (EE133799-BRMS)]. The UPSTREAM team have taken the following steps/actions to meet the BMS (UoB) DSPT:

a) Detailed information of the researchers accessing, processing and handling data have been provided to the UoB BMS DPS Administrator and has met the UoB DSPT eligibility criteria. Researchers have been kept to a minimum to support data management. If staff members/access requirements change, the team will update UoB as required.

b) Named researchers accessing, processing and handling data have completed the UoB “GDPR Information Security Training”.

All named researchers who will be processing and handling the data are substantive employees at the University of Bristol.

c) Identifiable data will not appear in study outputs, nor will it be supplied to third parties.

All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide.

The UPSTREAM project is formed of two phases. The original trial (“UPSTREAM - Phase I”) started 01 April 2014 and ended 30 September 2018. The start date for the second phase of UPSTREAM (“UPSTREAM - Phase II, Further Follow Up”) was 01 July 2019, and the study duration is expected to be 36 months, to May 2022. (subject to change)

Outputs from “Phase I” have already been disseminated and a full list of journal articles (and more) is available via the study website: http://www.bristol.ac.uk/population-health-sciences/projects/upstream/outputs-and-latest-updates/journal-articles/

This includes the protocol and statistical analysis plan, the baseline characteristics and initial diagnostic testing outcomes for the trial, as well as results of the main outcomes. Furthermore, qualitative evidence regarding the attitudes to, and experience of, UDS testing from men at each end of the clinical pathway, and men’s perspective on treatment decision-making for LUTS are also published. The study team expect to publish additional findings following completion of the further follow up, UPSTREAM-Phase II.

Planned reporting for “Phase II” is expected from Summer 2024 onwards (subject to change). Dissemination for the further follow up study will be like that of the trial (“UPSTREAM - Phase I”), and a comprehensive plan will be developed by the Project Management Group. For example, once results are available, the main forms of dissemination will be through the academic press, NIHR HTA monograph report, guidelines and workshops for clinical staff, and by lay summaries on websites and other more accessible forms for patients.

All participants have been provided with a lay summary of the main findings of the study (e.g. via newsletters and the study website). Dissemination to clinicians will be through papers in major urology journals and conferences (e.g. the European Association of Urology), workshops and presentations to national meetings e.g. the British Association of Urological Surgeons (BAUS) which is the specialist body with the responsibility for guiding clinical practice, policy matters, research priorities, governance and training in matters related to male lower urinary tract symptoms. BAUS is well placed to implement the findings by informing NHS policy (NICE) and dissemination of evidence-based clinical practice to its members. The Patient Panel working with the project will assist in the best methods to disseminate the results to patients, including interacting with the relevant charities in this area.

The UPSTREAM trial is part of the portfolio of the new Royal College of Surgeons of England Surgical Centre in Bristol so will be used as a platform for clinical trial training for new surgeon investigators, as well as the opportunity to conduct methodological research in surgical trials which would be disseminated by the surgical centre through workshops and publications. UPSTREAM study data will not be used for sales and marketing purposes.

As noted in participant information materials and the study protocol, no one will be able to identify participants from any publications that result from the study. Data will only be published in anonymised, aggregate form.

Lower urinary tract symptoms (LUTS) are a common feature of ageing. They can be categorised as problems with voiding (passing urine) or storing urine. In men with voiding LUTS, benign prostate enlargement (BPE) with ageing causes benign prostatic obstruction (BPO). For such patients, prostate surgery, such as transurethral resection of the prostate (TURP), may improve LUTS. However, voiding LUTS can also be caused by bladder dysfunction: e.g. poor expulsion strength of the bladder muscle, called ‘detrusor underactivity’ (DU). In such men, it is hard to justify prostate surgery if BPO is not present, especially in view of potential adverse effects.

The clinical pathway in findings of the main trial (“UPSTREAM - Phase I”) showed no difference between the two arms in the key secondary outcome of surgery rates. However, the clinical pathway proved to take longer than expected, such that some patients listed for surgery did not receive it by the end of their participation in the trial, or underwent surgery close to the 18-month follow up. This was an unexpected problem, representing failure of sites to comply achieve with NHS referral-to-treatment targets. This deficiency, which worsened during the trial, is potentially a fundamental issue, as the trial is predicated on differential surgery rates between the two arms (we hypothesised that the Urodynamics intervention arm would be non-inferior for symptoms, but at a lower surgery rate). Thus, the study team need scrupulous surgery data captured over a sufficient timescale to be able to report whether surgery rates were indeed lower.

LUTS are complex and it is recognised that: they are potentially a long-term problem; prone to manifest a placebo response, including with surgery; and they respond differentially to treatment (most importantly that storage LUTS, such as urgency and nocturia, are less likely to respond to surgery relieving BOO than voiding LUTS are). Following completion of the main trial (UPSTREAM - Phase I), the men with persisting voiding symptoms managed conservatively may subsequently have received surgery in the ensuing years (with a surgical recommendation based on "in case symptoms improve"/ "nothing else to offer") in the ensuing years. Thus, further follow up (“UPSTREAM - Phase II”), that includes the use of data extracted from NHS England, is needed to address the issue of uncertainty whether surgery rates were fully captured. This, which would be a definite step to maximising impact, avoiding the "doing the operation anyway, regardless of assessment" mentality sometimes encountered in clinical practice.

Thus, this long-term further follow up may help understanding of the sustained response, placebo impact and the behaviour of storage LUTS over time. This further follow up may help us to state for sure whether or not UDS delivered non-inferior symptom outcomes with lower surgery rates. Furthermore, there is very little information documented about men’s long-term experience on LUTS and its treatments, and the European Association of Urology (EAU) has identified this as a priority research need.

UPSTREAM is potentially very important. It will be the first large scale randomised study with long-term data for men who underwent comprehensive diagnostic assessment for LUTS. Hence, for participants it is hoped to provide proper insight into the merits of the diagnostic tests and the implications of test results for therapy outcomes. For society it may enable the best use of resources to focus on testing as relevant to therapy. For clinicians, it may counteract the "do the operation anyway, regardless of assessment" mentality sometimes encountered in clinical practice; it is expected that they may now be able to recommend intervention with evidence-based justification.

The one-off bespoke data extraction of routine data obtained via NHS England may allow the study team to answer some of the key objectives of the longer term follow up (i.e. “UPSTREAM – Phase II”). Using research nurses (and/or other suitable staff) at 26 hospitals to collect such follow up data would add considerable cost and time.

The health economics analysis will use specified HES and Civil Registration death datasets to understand the probability that diagnostic tests for LUTS is cost-effective compared to usual care. More specifically, it is expected that the intervention arm has the potential to lead to lower amounts of hospital care and thus hospital resource use including costly prostate surgery, as well as the expectation that the intervention arm could lead to improved quality of life post-care.

Good quality evidence which suggests this is the case would lead to more efficient use of resources across hospitals in England. A measure of the difference in hospital resource use, resulting from data requested from NHS England, has the potential to lead to changes in clinical practice where resources are allocated more efficiently within hospitals. In turn the improved allocation of resources could lead to a reduction in surgery waiting times for patients who have benign prostatic obstruction, where prostate surgery may be the most appropriate treatment for their LUTS.

UPSTREAM PHASE I, the randomised trial part of the study, identified that the urodynamic arm is non-inferior (primary outcome), but the rate of surgery was not lower (key secondary outcome). Additional analyses identified specific contributions of separate components of the diagnostic pathway, along with qualitative information, and thresholds for testing. This information was derived without using NHS England data.

----

Data from NHS England has been received and used for analyses which will be reported in various trial outputs from UPSTREAM Phase II. The first is the funder final report (drafted, with the journal editorial team for review) and then the main trial results paper (in draft). These outputs will utilise the linked data obtained from NHS England to assess surgery rates, whether additional diagnostic testing was undertaken after the end of Phase I and resource use. Additional health economics publications (in draft) will focus on this final point of resource use.

A dissemination event is also being planned for late 2024, targeting clinical colleagues involved in urodynamics testing to provide testing based on the findings of the UPSTREAM study.