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Abstract Objectives To understand how best to further reduce the inappropriate use of pre‐surgical androgen deprivation therapy (ADT), we investigated the determinants (influences) of ADT prescribing in urologists in two European countries using an established behavioural science approach. Additionally, we sought to understand how resource limitations caused by COVID‐19 influenced this practice. Identification of key determinants, of undistributed and disrupted practice, will aid development of future strategies to reduce inappropriate ADT prescribing in current and future resource‐limited settings. Participants and Methods We conducted semi‐structured qualitative interviews with urologists practicing in Italy and the UK from February to July 2022. Interviews focussed on undisrupted (usual) practice and disrupted practice (changes made during COVID‐19 restrictions). Codes were generated inductively and were mapped to the 14 domains of the Theoretical Domains Framework. Relevant domains of influence were identified, and the similarities and differences between the UK and Italy were distinguished. Results We identified 10 domains that were influential to ADT prescribing in the UK and eight in Italy. The role of guidance and evidence, the cancer care setting, the patients and the urologist's beliefs and experiences were identified as areas that were influential to ADT prescribing before surgery. Twenty‐one similarities and 22 differences between the UK and Italy, for usual and COVID‐19 practice, were identified across these 10 domains. Conclusion Similarities and differences influencing ADT prescribing prior to surgery should be considered in behavioural strategy development and tailoring to reduce inappropriate ADT use. We gained an understanding of usual, undistributed care and resource‐limited or disrupted care due to COVID‐19 in two European countries. This gives an indication of how influences on ADT prescribing may change in future resource‐limited circumstances and where efforts can be focused now and in future.

Abstract Background /Aims De-implementation, including the removal or reduction of unnecessary or inappropriate prescribing, is crucial to ensure patients receive appropriate evidence-based health care. The utilization of de-implementation efforts is contingent on the quality of strategy reporting. To further understand effective ways to de-implement medical practices, specification of behavioural targets and components of de-implementation strategies are required. This paper aims to critically analyse how well the behavioural targets and strategy components, in studies that focused on de-implementing unnecessary or inappropriate prescribing in secondary healthcare settings, were reported. Methods A supplementary analysis of studies included in a recently published review of de-implementation studies was conducted. Article text was coded verbatim to two established specification frameworks. Behavioural components were coded deductively to the five elements of the Action, Actor, Context, Target, Time (AACTT) framework. Strategy components were mapped to the nine elements of the Proctor’s ‘measuring implementation strategies’ framework. Results The behavioural components of low-value prescribing, as coded to the AACTT framework, were generally specified well. However, the Actor and Time components were often vague or not well reported. Specification of strategy components, as coded to the Proctor framework, were less well reported. Proctor’s Actor, Action target: specifying targets, Dose and Justification elements were not well reported or varied in the amount of detail offered. We also offer suggestions of additional specifications to make, such as the ‘interactions’ participants have with a strategy. Conclusion Specification of behavioural targets and components of de-implementation strategies for prescribing practices can be accommodated by the AACTT and Proctor frameworks when used in conjunction. These essential details are required to understand, replicate and successfully de-implement unnecessary or inappropriate prescribing. In general, standardisation in the reporting quality of these components is required to replicate any de-implementation efforts. Trial registration Not registered.

Background and objective: The treatment landscape of metastatic prostate cancer (mPCa) has evolved significantly over the past two decades. Despite this, the optimal therapy for patients with mPCa has not been determined. This systematic review identifies available predictive models that assess mPCa patients’ response to treatment. Methods: We critically reviewed MEDLINE and CENTRAL in December 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Only quantitative studies in English were included with no time restrictions. The quality of the included studies was assessed using the PROBAST tool. Data were extracted following the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews criteria. Key findings and limitations: The search identified 616 citations, of which 15 studies were included in our review. Nine of the included studies were validated internally or externally. Only one study had a low risk of bias and a low risk concerning applicability. Many studies failed to detail model performance adequately, resulting in a high risk of bias. Where reported, the models indicated good or excellent performance. Conclusions and clinical implications: Most of the identified predictive models require additional evaluation and validation in properly designed studies before these can be implemented in clinical practice to assist with treatment decision-making for men with mPCa. Patient summary: In this review, we evaluate studies that predict which treatments will work best for which metastatic prostate cancer patients. We found that existing studies need further improvement before these can be used by health care professionals.

Combination therapies in metastatic hormone-sensitive prostate cancer (mHSPC), which include the addition of an androgen receptor signaling inhibitor and/or docetaxel to androgen deprivation therapy, have been a game changer in the management of this disease stage. However, these therapies come with their fair share of toxicities and side effects. The goal of this observational study is to report drug-related adverse events (AEs), which are correlated with systemic combination therapies for mHSPC. Determining the optimal treatment option requires large cohorts to estimate the tolerability and AEs of these combination therapies in “real-life” patients with mHSPC, as provided in this study. We use a network of databases that includes population-based registries, electronic health records, and insurance claims, containing the overall target population and subgroups of patients defined by unique certain characteristics, demographics, and comorbidities, to compute the incidence of common AEs associated with systemic therapies in the setting of mHSPC. These data sources are standardised using the Observational Medical Outcomes Partnership Common Data Model. We perform the descriptive statistics as well as calculate the AE incidence rate separately for each treatment group, stratified by age groups and index year. The time until the first event is estimated using the Kaplan-Meier method within each age group. In the case of episodic events, the anticipated mean cumulative counts of events are calculated. Our study will allow clinicians to tailor optimal therapies for mHSPC patients, and they will serve as a basis for comparative method studies.

Background and objective: The ability of health care professionals to communicate with patients compassionately and effectively is crucial for shared decision-making, but little research has investigated patient-clinician communication. As part of PIONEER—an international Big Data Consortium led by the European Association of Urology to answer key questions for men with prostate cancer (PCa), funded through the IMI2 Joint Undertaking under grant agreement 777492— we investigated communication between men diagnosed with PCa and the health care professional(s) treating them across Europe. Methods: We used the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Communication 26, which was shared via the PIONEER and patient organisations on March 11, 2022. We sought men who spoke French, Italian, Spanish, German, Dutch, or English who were diagnosed with PCa and were undergoing or had already received treatment for their PCa. Results and limitations: A total of 372 men reported that they communicated with their clinician during either the diagnostic or the treatment period. Overall, the majority of participants reported positive experiences. However, important opportunities to enhance communication were identified, particularly with regard to correcting misunderstandings, understanding the patient’s preferred approach to information presentation, addressing challenging questions, supporting the patient’s comprehension of information, attending to the patient’s emotional needs, and assessing what information had already been given to patients about their disease and treatment, and how much of it was understood. Conclusions and clinical implications: These results help us to identify gaps and barriers to shared treatment decision making. This knowledge will help devise measures to improve patient-health care professional communication in the PCa setting. Patient summary: As part of the PIONEER initiative, we investigated the communication between men diagnosed with prostate cancer and their health care professionals across Europe. A total of 372 men from six different countries participated in the study. Most participants reported positive experiences, but areas where communication could be improved were identified. These included addressing misunderstandings, tailoring the presentation of information to the patient’s preferences, handling difficult questions, supporting emotional needs, and assessing the patient’s understanding of their diagnosis and treatment.

Background: Currently, the landscape of surgical training is undergoing rapid evolution, marked by the initial implementation of standardized surgical training programs, which are further facilitated by the emergence of new technologies. However, this proliferation is uneven across various countries and hospitals. Objective: To offer a comprehensive overview of the existing surgical training programs throughout Europe, with a specific focus on the accessibility of simulation resources and standardized surgical programs. Design, setting, and participants: A dedicated survey was designed and spread in May 2022 via the European Association of Urology (EAU) mail list, to Young Urologist Office (YUO), Junior membership, European Urology Residents Education Program participants between 2014 and 2022, and other urologists under 40 yr, and via the EAU Newsletter. Intervention: A 64-item, online-based survey in accordance with the Checklist for Reporting Results of Internet E-Surveys (CHERRIES) using the platform of Survey Monkey (Portland, OR, USA) was realized. Outcome measurements and statistical analysis: The study involved an assessment of the demographic characteristics. Additionally, it explored the type of center, availability of various surgical approaches, presence of training infrastructure, participation in courses, organization of training, and participants' satisfaction with the training program. The level of satisfaction was evaluated using a Likert-5 scale. The subsequent sections delved into surgical training within the realms of open, laparoscopic, robotic, and endoscopic surgery, each explored separately. Finally, the investigation encompassed the presence of a structured training course and the availability of a duly validated final evaluation process. Results and limitations: There were 375 responders with a completion rate of 82%. Among them, 75% were identified as male, 50.6% were young urologists, 31.7% were senior residents, and 17.6% were junior residents. A significant majority of participants (69.6%) were affiliated with academic centers. Regarding the presence of dry lab training facilities, only 50.3% of respondents indicated its availability. Among these centers, 46.7% were primarily focused on laparoscopy training. The availability of virtual and wet lab training centers was even more limited, with rates of 31.5% and 16.2%, respectively. Direct patient involvement was reported in 80.5% of cases for open surgery, 58.8% for laparoscopy, 25.0% for robotics, and 78.6% for endourology. It is worth noting that in

Abstract Objective To report on the cost‐effectiveness of adjustable anchored single‐incision mini‐slings (mini‐slings) compared with tension‐free standard mid‐urethral slings (standard slings) in the surgical management of female stress urinary incontinence (SUI). Patients and Methods Data on resource use and quality were collected from women aged ≥18 years with predominant SUI undergoing mid‐urethral sling procedures in 21 UK hospitals. Resource use and quality of life (QoL) data were prospectively collected alongside the Single‐Incision Mini‐Slings versus standard synthetic mid‐urethral slings Randomised Control Trial (SIMS RCT), for surgical treatment of SUI in women. A health service provider's (National Health Service [NHS]) perspective with 3‐year follow‐up was adopted to estimate the costs of the intervention and all subsequent resource use. A generic instrument, EuroQol EQ‐5D‐3L, was used to estimate the QoL. Results are reported as incremental costs, quality adjusted life years (QALYs) and incremental cost per QALY. Results Base case analysis results show that although mini‐slings cost less, there was no significant difference in costs: mini‐slings versus standard slings: £‐6 [95% CI −228–208] or in QALYs: 0.005 [95% CI −0.068–0.073] over the 3‐year follow‐up. There is substantial uncertainty, with a 56% and 44% probability that mini‐slings and standard slings are the most cost‐effective treatment, respectively, at a £20 000 willingness‐to‐pay threshold value for a QALY. Conclusions At 3 years, there is no significant difference between mini‐slings and standard slings in costs and QALYs. There is still some uncertainty over the long‐term complications and failure rates of the devices used in the treatment of SUI; therefore, it is important to establish the long‐term clinical and cost‐effectiveness of these procedures.

Cancer survivorship was recently identified as a prostate cancer (PCa) research priority by PIONEER, a European network of excellence for big data in PCa. Despite being a research priority, cancer survivorship lacks a clear and agreed definition, and there is a distinct paucity of patient-reported outcome (PRO) data available on the subject. Data collection on cancer survivorship depends on the availability and implementation of (validated) routinely collected patient-reported outcome measures (PROMs). There have been recent advances in the availability of such PROMs. For instance, the European Organisation for Research and Treatment of Cancer Quality of Life Group (EORTC QLG) is developing survivorship questionnaires. This provides an excellent first step in improving the data available on cancer survivorship. However, we propose that an agreed, standardised definition of (prostate) cancer survivorship must first be established. Only then can real-world data on survivorship be collected to strengthen our knowledge base. With more men than ever surviving PCa, this type of research is imperative to ensure that the quality of life of these men is considered as much as their quantity of life. Patient summary: As there are more prostate cancer survivors than ever before, research into cancer survivorship is crucial. We highlight the importance of such research and provide recommendations on how to carry it out. The first step should be establishing agreement on a standardised definition of survivorship. From this, patient-reported outcome measures can then be used to collect important survivorship data.

Abstract Background/aims Considerable efforts have been made to improve guideline adherence in healthcare through de-implementation, such as decreasing the prescription of inappropriate medicines. However, we have limited knowledge about the effectiveness, barriers, facilitators and consequences of de-implementation strategies targeting inappropriate medication prescribing in secondary care settings. This review was conducted to understand these factors to contribute to better replication and optimisation of future de-implementation efforts to reduce low-value care. Methods A systematic review of randomised control trials was conducted. Papers were identified through CINAHL, EMBASE, MEDLINE and Cochrane register of controlled trials to February 2021. Eligible studies were randomised control trials evaluating behavioural strategies to de-implement inappropriate prescribing in secondary healthcare. Risk of bias was assessed using the Cochrane Risk of Bias tool. Intervention characteristics, effectiveness, barriers, facilitators and consequences were identified in the study text and tabulated. Results Eleven studies were included, of which seven were reported as effectively de-implementing low-value prescribing. Included studies were judged to be mainly at low to moderate risk for selection biases and generally high risk for performance and reporting biases. The majority of these strategies were clinical decision support at the ‘point of care’. Clinical decision support tools were the most common and effective. They were found to be a low-cost and simple strategy. However, barriers such as clinician’s reluctance to accept recommendations, or the clinical setting were potential barriers to their success. Educational strategies were the second most reported intervention type however the utility of educational strategies for de-implementation remains varied. Multiple barriers and facilitators relating to the environmental context, resources and knowledge were identified across studies as potentially influencing de-implementation. Various consequences were identified; however, few measured the impact of de-implementation on usual appropriate practice. Conclusion This review offers insight into the intervention strategies, potential barriers, facilitators and consequences that may affect the de-implementation of low-value prescribing in secondary care. Identification of these key features helps understand how and why these strategies are effective and the wider (desirable or undesirable) impact of de-implementation. These findings can contribute to the successful replication or optimisation of strategies used to de-implement low-value prescribing practices in future. Trial registration The review protocol was registered at PROSPERO (ID: CRD42021243944).

Background: The Gambia has the 12th highest maternal mortality rate in the world, with 80% of deaths resulting from avoidable causes. Unawareness of pregnancy danger signs (DS) has been shown to be a barrier to seeking obstetric care, while app-based education intervention has shown promise. Objective: We aim to assess patient awareness of DS, identify barriers to awareness, and evaluate potential for implementing smartphone-based technologies for education. Methods: A cross-sectional semi-structured survey was administered to Gambian women (n = 100) across five hospitals/health centers. Data and informed consent were collected via an online survey portal. Analysis included bivariate analysis and descriptive statistics with p < 0.05 significance level. Recall of 0–2 DS per category was classified as “low” knowledge, 3–5 as “moderate” knowledge, and 6+ as “sufficient” knowledge. Cross-category recall was quantified for overall awareness level (0–6 = “low”, 7–12 = “moderate”, 13+ = “sufficient”. N = 28 total DS). Findings: Although 75% of participants (n = 100) self-perceived “sufficient” knowledge of DS, the average recall was only two (SD = 2, n = 11) pregnancy DS, one labor and delivery DS (SD = 1, n = 8), and one postpartum DS (SD = 1, n = 9). Twenty-one women were unable to recall any danger signs. “Low” awareness was identified in 77% of women, while 23%, and 0% of women showed “moderate” and “sufficient” overall awareness, respectively. Education level was significantly correlated with overall danger sign recall (ρ(98) = .243, p = .015) and awareness level (ρ(98) = .265, p = .008). Monthly income was significantly correlated with awareness level (ρ(97) = .311, p = .002). Smartphone ownership was reported by 76% of women, and 97% expressed interest in using app-based video (94%) or provider (93%) teaching. Conclusions: Women had low knowledge of obstetric danger signs, and true awareness of danger signs was remarkably lower than self-perceived knowledge. However, patients exhibited proper healthcare-seeking behavior when danger signs arose. Findings suggest that video- or messaging-based education from local healthcare providers may be effective DS educational interventions.

Objectives To elicit and value patient preferences for the processes and outcomes of surgical management of stress urinary incontinence in women.Design A discrete choice experiment survey to elicit preferences for type of anaesthesia, postoperative recovery time, treatment success, adverse events, impact on daily activities and cost. An experimental design generated 40 choice tasks, and each respondent completed 1 block of 10 and 2 validity tests. Analysis was by multinomial logistical regression.Setting N=21 UK hospitals.Participants N=325 adult women who were a subsample of those randomised to the single-incision mini-slings clinical trial.Outcomes Patient preferences; valuation obtained using willingness to pay.Results N=227 of 325 (70%) returned a questionnaire, and 94% of those completed all choice tasks. Respondents preferred general anaesthesia, shorter recovery times, improved stress urinary incontinence symptoms and avoidance of adverse events. Women were willing to pay (mean (95% CI)) £76 (£33 to £119) per day of reduction in recovery time following surgery. They valued increases in Patient Global Impression of Improvement, ranging from £8173 (£5459 to £10 887) for ‘improved’ to £11 706 (£8267 to £15 144) for ‘very much improved’ symptoms, compared with no symptom improvement. This was offset by negative values attached to the avoidance of complications ranging between £−8022 (£−10 661 to £−5383) and £−10 632 (£−14 077 to £−7187) compared to no complications. Women valued treatments that reduced the need to avoid daily activities, with willingness to pay ranging from £−967 (£−2199 to £266) for rarely avoiding activities to £−5338 (£−7258 to £−3417) for frequently avoiding daily activities compared with no avoidance.Conclusion This discrete choice experiment demonstrates that patients place considerable value on improvement in stress urinary incontinence symptoms and avoidance of treatment complications. Trade-offs between symptom improvement and adverse event risk should be considered within shared decision-making. The willingness to pay values from this study can be used in future cost–benefit analyses.Trial registration number ISRCTN: 93264234; Post-results.

Abstract Background Various washout policies are widely used in adults living with long-term catheters (LTC). There is currently insufficient evidence on the benefits and potential harms of prophylactic LTC washout policies in the prevention of blockages and other LTC-related adverse events, such as urinary tract infections. CATHETER II tests the hypothesis that weekly prophylactic LTC washouts (normal saline or citric acid) in addition to standard LTC care reduce the incidence of catheter blockage requiring intervention compared to standard LTC care only in adults living with LTC. Methods CATHETER II is a pragmatic three-arm open multi-centre superiority randomised controlled trial with an internal pilot, economic analysis, and embedded qualitative study. Eligible participants are adults aged ≥ 18 years, who have had a LTC in use for ≥ 28 days, have no plans to discontinue the use of the catheter, are able to undertake the catheter washouts, and complete trial documentation or have a carer able to help them. Participants are identified from general practitioner practices, secondary/tertiary care, community healthcare, care homes, and via public advertising strategies. Participants are randomised 1:1:1 to receive a weekly saline (0.9%) washout in addition to standard LTC care, a weekly citric acid (3.23%) washout in addition to standard LTC care or standard LTC care only. Participants and/or carers will receive training to administer the washouts. Patient-reported outcomes are collected at baseline and for 24 months post-randomisation. The primary clinical outcome is catheter blockage requiring intervention up to 24 months post-randomisation expressed per 1000 catheter days. Secondary outcomes include symptomatic catheter-associated urinary tract infection requiring antibiotics, catheter change, adverse events, NHS/ healthcare use, and impact on quality of life. Discussion This study will guide treatment decision-making and clinical practice guidelines regarding the effectiveness of various prophylactic catheter washout policies in men and women living with LTC. This research has received ethical approval from Wales Research Ethics Committee 6 (19/WA/0015). Trial registration ISRCTN ISRCTN17116445 . Registered prospectively on 06 November 2019

Background: Stress urinary incontinence is the most common type of urinary incontinence in premenopausal women. Until recently, synthetic mid-urethral slings (mesh/tape) were the standard surgical treatment, if conservative management failed. Adjustable anchored single-incision mini-slings are newer, use less mesh and may reduce perioperative morbidity, but it is unclear how their success rates and safety compare with those of standard tension-free mid-urethral slings. Objective: The objective was to compare tension-free standard mid-urethral slings with adjustable anchored single-incision mini-slings among women with stress urinary incontinence requiring surgical intervention, in terms of patient-reported effectiveness, health-related quality of life, safety and cost-effectiveness. Design: This was a pragmatic non-inferiority randomised controlled trial. Allocation was by remote web-based randomisation (1 : 1 ratio). Setting: The trial was set in 21 UK hospitals. Participants: Participants were women aged ≥ 18 years with predominant stress urinary incontinence, undergoing a mid-urethral sling procedure. Interventions: Single-incision mini-slings, compared with standard mid-urethral slings. Main outcome measures: The primary outcome was patient-reported success rates on the Patient Global Impression of Improvement scale at 15 months post randomisation (≈ 1 year post surgery), with success defined as outcomes of ‘very much improved’ or ‘much improved’. The primary economic outcome was incremental cost per quality-adjusted life-year gained. Secondary outcomes were adverse events, impact on other urinary symptoms, quality of life and sexual function. Results: A total of 600 participants were randomised. At 15 months post randomisation, adjustable anchored single-incision mini-slings were non-inferior to tension-free standard mid-urethral slings at the 10% margin for the primary outcome [single-incision mini-sling 79% (212/268) vs. standard mid-urethral sling 76% (189/250), risk difference 4.6, 95% confidence interval –2.7 to 11.8; pnon-inferiority

Background: The burden of urological diseases is rising as the worldwide population ages. Although specialist urological provision is needed, a large proportion of these conditions will be managed in primary care. The importance of including urology in medical education currently remains unclear. Objective: To provide recommendations on undergraduate medical education for urology in Europe. Design, setting, and participants: A three-round Delphi process to reach consensus on standardising the undergraduate urology curriculum in Europe was endorsed by the European School of Urology. Outcome measurements and statistical analysis: The levels of agreement were set using a nine-point scale according to the GRADE grid: 1–3, disagree; 4–6, uncertain; and 7–9, agree. Consensus was defined as at least 70% of the participants scoring within the same 3-point grouping. Results and limitations: Overall, consensus was reached for 20 of 34 statements (70.5%) across the three Delphi rounds, with agreement for 75% (n = 15) and disagreement for 25% (n = 5). The following main points were agreed. Urological teaching should be introduced before year 5 of medical school, with at least 20 h of theoretical activities and at least 30 h of practical activities. Urology should be taught as a stand-alone subject rather than combined with another surgical specialty or a nephrology programme. The participants agreed that urology should be taught according to symptoms. A urology programme should include the anatomy and physiology of the urinary tract, and students should know how to clinically assess a urological patient. Conclusions: Our recommended urology pathway will allow European medical schools to provide a more comprehensive undergraduate urology curriculum. It will also help to improve and maintain standards of urology undergraduate teaching across Europe. Patient summary: Our survey showed that urology in universities should have, at minimum, time for theoretical and practical activities and should be taught as a stand-alone subject on the basis of symptoms. Students should give feedback to facilitate constant improvement and evolution of the teaching programme.

Background: Around 7500 people are diagnosed with non-muscle-invasive bladder cancer in the UK annually. Recurrence following transurethral resection of bladder tumour is common, and the intensive monitoring schedule required after initial treatment has associated costs for patients and the NHS. In photodynamic diagnosis, before transurethral resection of bladder tumour, a photosensitiser that is preferentially absorbed by tumour cells is instilled intravesically. Transurethral resection of bladder tumour is then conducted under blue light, causing the photosensitiser to fluoresce. Photodynamic diagnosis-guided transurethral resection of bladder tumour offers better diagnostic accuracy than standard white-light-guided transurethral resection of bladder tumour, potentially reducing the chance of subsequent recurrence. Objective: The objective was to assess the clinical effectiveness and cost-effectiveness of photodynamic diagnosis-guided transurethral resection of bladder tumour. Design: This was a multicentre, pragmatic, open-label, parallel-group, non-masked, superiority randomised controlled trial. Allocation was by remote web-based service, using a 1 : 1 ratio and a minimisation algorithm balanced by centre and sex. Setting: The setting was 22 NHS hospitals. Participants: Patients aged ≥ 16 years with a suspected first diagnosis of high-risk non-muscle-invasive bladder cancer, no contraindications to photodynamic diagnosis and written informed consent were eligible. Interventions: Photodynamic diagnosis-guided transurethral resection of bladder tumour and standard white-light cystoscopy transurethral resection of bladder tumour. Main outcome measures: The primary clinical outcome measure was the time to recurrence from the date of randomisation to the date of pathologically proven first recurrence (or intercurrent bladder cancer death). The primary health economic outcome was the incremental cost per quality-adjusted life-year gained at 3 years. Results: We enrolled 538 participants from 22 UK hospitals between 11 November 2014 and 6 February 2018. Of these, 269 were allocated to photodynamic diagnosis and 269 were allocated to white light. A total of 112 participants were excluded from the analysis because of ineligibility (n = 5), lack of non-muscle-invasive bladder cancer diagnosis following transurethral resection of bladder tumour (n = 89) or early cystectomy (n = 18). In total, 209 photodynamic diagnosis and 217 white-light participants were included in the clinical end-point analysis population. All randomised participants were included in the cost-effectiveness analysis. Over a median follow-up period of 21 months for the photodynamic diagnosis group and 22 months for the white-light group, there were 86 recurrences (3-year recurrence-free survival rate 57.8%, 95% confidence interval 50.7% to 64.2%) in the photodynamic diagnosis group and 84 recurrences (3-year recurrence-free survival rate 61.6%, 95% confidence interval 54.7% to 67.8%) in the white-light group (hazard ratio 0.94, 95% confidence interval 0.69 to 1.28; p = 0.70). Adverse event frequency was low and similar in both groups [12 (5.7%) in the photodynamic diagnosis group vs. 12 (5.5%) in the white-light group]. At 3 years, the total cost was £12,881 for photodynamic diagnosis-guided transurethral resection of bladder tumour and £12,005 for white light. There was no evidence of differences in the use of health services or total cost at 3 years. At 3 years, the quality-adjusted life-years gain was 2.094 in the photodynamic diagnosis transurethral resection of bladder tumour group and 2.087 in the white light group. The probability that photodynamic diagnosis-guided transurethral resection of bladder tumour was cost-effective was never > 30% over the range of society’s cost-effectiveness thresholds. Limitations: Fewer patients than anticipated were correctly diagnosed with intermediate- to high-risk non-muscle-invasive bladder cancer before transurethral resection of bladder tumour and the ratio of intermediate- to high-risk non-muscle-invasive bladder cancer was higher than expected, reducing the number of observed recurrences and the statistical power. Conclusions: Photodynamic diagnosis-guided transurethral resection of bladder tumour did not reduce recurrences, nor was it likely to be cost-effective compared with white light at 3 years. Photodynamic diagnosis-guided transurethral resection of bladder tumour is not supported in the management of primary intermediate- to high-risk non-muscle-invasive bladder cancer. Future work: Further work should include the modelling of appropriate surveillance schedules and exploring predictive and prognostic biomarkers. Trial registration: This trial is registered as ISRCTN84013636. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 40. See the NIHR Journals Library website for further project information.

The ability to use clinical and research data at scale is central to hopes for data-driven medicine. However, in using such data researchers often encounter hurdles–both technical, such as differing data security requirements, and social, such as the terms of informed consent, legal requirements and patient and public trust. Federated or distributed data networks have been proposed and adopted in response to these hurdles. However, to date there has been little consideration of how FDNs respond to both technical and social constraints on data use. In this Perspective we propose an approach to thinking about data in terms that make it easier to navigate the health data space and understand the value of differing approaches to data collection, storage and sharing. We set out a socio-technical model of data systems that we call the “Concentric Circles View” (CCV) of data-relationships. The aim is to enable a consistent understanding of the fit between the local relationships within which data are produced and the extended socio-technical systems that enable their use. The paper suggests this model can help understand and tackle challenges associated with the use of real-world data in the health setting. We use the model to understand not only how but why federated networks may be well placed to address emerging issues and adapt to the evolving needs of health research for patient benefit. We conclude that the CCV provides a useful model with broader application in mapping, understanding, and tackling the major challenges associated with using real world data in the health setting.

Background: Urinary stone disease affects 2–3% of the general population. Ureteric stones are associated with severe pain and can have a significant impact on a patient’s quality of life. Most ureteric stones are expected to pass spontaneously with supportive care; however, between one-fifth and one-third of patients require an active intervention. The two standard interventions are shockwave lithotripsy and ureteroscopic stone treatment. Both treatments are effective, but they differ in terms of invasiveness, anaesthetic requirement, treatment setting, number of procedures, complications, patient-reported outcomes and cost. There is uncertainty around which is the more clinically effective and cost-effective treatment. Objectives: To determine if shockwave lithotripsy is clinically effective and cost-effective compared with ureteroscopic stone treatment in adults with ureteric stones who are judged to require active intervention. Design: A pragmatic, multicentre, non-inferiority, randomised controlled trial of shockwave lithotripsy as a first-line treatment option compared with primary ureteroscopic stone treatment for ureteric stones. Setting: Urology departments in 25 NHS hospitals in the UK. Participants: Adults aged ≥ 16 years presenting with a single ureteric stone in any segment of the ureter, confirmed by computerised tomography, who were able to undergo either shockwave lithotripsy or ureteroscopic stone treatment and to complete trial procedures. Intervention: Eligible participants were randomised 1 : 1 to shockwave lithotripsy (up to two sessions) or ureteroscopic stone treatment. Main outcome measures: The primary clinical outcome measure was resolution of the stone episode (stone clearance), which was operationally defined as ‘no further intervention required to facilitate stone clearance’ up to 6 months from randomisation. This was determined from 8-week and 6-month case report forms and any additional hospital visit case report form that was completed by research staff. The primary economic outcome measure was the incremental cost per quality-adjusted life-year gained at 6 months from randomisation. We estimated costs from NHS resources and calculated quality-adjusted life-years from participant completion of the EuroQol-5 Dimensions, three-level version, at baseline, pre intervention, 1 week post intervention and 8 weeks and 6 months post randomisation. Results: In the shockwave lithotripsy arm, 67 out of 302 (22.2%) participants needed further treatment. In the ureteroscopic stone treatment arm, 31 out of 302 (10.3%) participants needed further treatment. The absolute risk difference was 11.4% (95% confidence interval 5.0% to 17.8%); the upper bound of the 95% confidence interval ruled out the prespecified margin of non-inferiority (which was 20%). The mean quality-adjusted life-year difference (shockwave lithotripsy vs. ureteroscopic stone treatment) was –0.021 (95% confidence interval 0.033 to –0.010) and the mean cost difference was –£809 (95% confidence interval –£1061 to –£551). The probability that shockwave lithotripsy is cost-effective is 79% at a threshold of society’s willingness to pay for a quality-adjusted life-year of £30,000. The CEAC is derived from the joint distribution of incremental costs and incremental effects. Most of the results fall in the south-west quadrant of the cost effectiveness plane as SWL always costs less but is less effective. Limitations: A limitation of the trial was low return and completion rates of patient questionnaires. The study was initially powered for 500 patients in each arm; however, the total number of patients recruited was only 307 and 306 patients in the ureteroscopic stone treatment and shockwave lithotripsy arms, respectively. Conclusions: Patients receiving shockwave lithotripsy needed more further interventions than those receiving primary ureteroscopic retrieval, although the overall costs for those receiving the shockwave treatment were lower. The absolute risk difference between the two clinical pathways (11.4%) was lower than expected and at a level that is acceptable to clinicians and patients. The shockwave lithotripsy pathway is more cost-effective in an NHS setting, but results in lower quality of life. Future work: (1) The generic health-related quality-of-life tools used in this study do not fully capture the impact of the various treatment pathways on patients. A condition-specific health-related quality-of-life tool should be developed. (2) Reporting of ureteric stone trials would benefit from agreement on a core outcome set that would ensure that future trials are easier to compare. Trial registration: This trial is registered as ISRCTN92289221. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 19. See the NIHR Journals Library website for further project information.

Background: Men who suffer recurrence of bulbar urethral stricture have to decide between endoscopic urethrotomy and open urethroplasty to manage their urinary symptoms. Evidence of relative clinical effectiveness and cost-effectiveness is lacking. Objectives: To assess benefit, harms and cost-effectiveness of open urethroplasty compared with endoscopic urethrotomy as treatment for recurrent urethral stricture in men. Design: Parallel-group, open-label, patient-randomised trial of allocated intervention with 6-monthly follow-ups over 24 months. Target sample size was 210 participants providing outcome data. Participants, clinicians and local research staff could not be blinded to allocation. Central trial staff were blinded when needed. Setting: UK NHS with recruitment from 38 hospital sites. Participants: A total of 222 men requiring operative treatment for recurrence of bulbar urethral stricture who had received at least one previous intervention for stricture. Interventions: A centralised randomisation system using random blocks allocated participants 1 : 1 to open urethroplasty (experimental group) or endoscopic urethrotomy (control group). Main outcome measures: The primary clinical outcome was control of urinary symptoms. Cost-effectiveness was assessed by cost per quality-adjusted life-year (QALY) gained over 24 months. The main secondary outcome was the need for reintervention for stricture recurrence. Results: The mean difference in the area under the curve of repeated measurement of voiding symptoms scored from 0 (no symptoms) to 24 (severe symptoms) between the two groups was –0.36 [95% confidence interval (CI) –1.78 to 1.02; p = 0.6]. Mean voiding symptom scores improved between baseline and 24 months after randomisation from 13.4 [standard deviation (SD) 4.5] to 6 (SD 5.5) for urethroplasty group and from 13.2 (SD 4.7) to 6.4 (SD 5.3) for urethrotomy. Reintervention was less frequent and occurred earlier in the urethroplasty group (hazard ratio 0.52, 95% CI 0.31 to 0.89; p = 0.02). There were two postoperative complications requiring reinterventions in the group that received urethroplasty and five, including one death from pulmonary embolism, in the group that received urethrotomy. Over 24 months, urethroplasty cost on average more than urethrotomy (cost difference £2148, 95% CI £689 to £3606) and resulted in a similar number of QALYs (QALY difference –0.01, 95% CI –0.17 to 0.14). Therefore, based on current evidence, urethrotomy is considered to be cost-effective. Limitations: We were able to include only 69 (63%) of the 109 men allocated to urethroplasty and 90 (80%) of the 113 men allocated to urethrotomy in the primary complete-case intention-to-treat analysis. Conclusions: The similar magnitude of symptom improvement seen for the two procedures over 24 months of follow-up shows that both provide effective symptom control. The lower likelihood of further intervention favours urethroplasty, but this had a higher cost over the 24 months of follow-up and was unlikely to be considered cost-effective. Future work: Formulate methods to incorporate short-term disutility data into cost-effectiveness analysis. Survey pathways of care for men with urethral stricture, including the use of enhanced recovery after urethroplasty. Establish a pragmatic follow-up schedule to allow national audit of outcomes following urethral surgery with linkage to NHS Hospital Episode Statistics. Trial registration: Current Controlled Trials ISRCTN98009168. Funding: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 61. See the NIHR Journals Library website for further project information.

Abstract Background Urinary stone disease is very common with an estimated prevalence among the general population of 2–3%. Ureteric stones are associated with severe pain as they pass through the urinary tract and have significant impact on patients’ quality of life due to the detrimental effect on their ability to work and need for hospitalisation. Most ureteric stones can be expected to pass spontaneously with supportive care. However, between one-fifth and one-third of cases require an intervention. The two standard active intervention options are extracorporeal shockwave lithotripsy (ESWL) and ureteroscopic stone retrieval. ESWL and ureteroscopy are effective in terms of stone clearance; however, they differ in terms of invasiveness, anaesthetic requirement, treatment setting, complications, patient-reported outcomes (e.g. pain after intervention, time off work) and cost. There is uncertainty around which is the most clinically effective in terms of stone clearance and the true cost to the NHS and to society (in terms of impact on patient-reported health and economic burden). The aim of this trial is to determine whether, in adults with ureteric stones, judged to require active intervention, ESWL is not inferior and is more cost-effective compared to ureteroscopic treatment as the initial management option. Methods The TISU study is a pragmatic multicentre non-inferiority randomised controlled trial of ESWL as the first treatment option compared with direct progression to ureteroscopic treatment for ureteric stones. Patients aged over 16 years with a ureteric stone confirmed by non-contrast computed tomography of the kidney, ureter and bladder (CTKUB) will be randomised to either ESWL or ureteroscopy. The primary clinical outcome is resolution of the stone episode (no further intervention required to facilitate stone clearance) up to six months from randomisation. The primary economic outcome is the incremental cost per quality-adjusted life years (QALYs) gained at six months from randomisation. Discussion Determining whether ESWL is not inferior clinically and is cost-effective compared to ureteroscopic treatment as the initial management in adults with ureteric stones who are judged to require active treatment is relevant not only to patients and clinicians but also to healthcare providers, both in the UK and globally. Trial registration ISRCTN registry, ISRCTN92289221. Registered on 21 February 2013.

Background: People carrying out clean intermittent self-catheterisation (CISC) to empty their bladder often suffer repeated urinary tract infections (UTIs). Continuous once-daily, low-dose antibiotic treatment (antibiotic prophylaxis) is commonly advised but knowledge of its effectiveness is lacking. Objective: To assess the benefit, harms and cost-effectiveness of antibiotic prophylaxis to prevent UTIs in people who perform CISC. Design: Parallel-group, open-label, patient-randomised 12-month trial of allocated intervention with 3-monthly follow-up. Outcome assessors were blind to allocation. Setting: UK NHS, with recruitment of patients from 51 sites. Participants: Four hundred and four adults performing CISC and predicted to continue for ≥ 12 months who had suffered at least two UTIs in the previous year or had been hospitalised for a UTI in the previous year. Interventions: A central randomisation system using random block allocation set by an independent statistician allocated participants to the experimental group [once-daily oral antibiotic prophylaxis using either 50 mg of nitrofurantoin, 100 mg of trimethoprim (Kent Pharmaceuticals, Ashford, UK) or 250 mg of cefalexin (Sandoz Ltd, Holzkirchen, Germany); n = 203] or the control group of no prophylaxis (n = 201), both for 12 months. Main outcome measures: The primary clinical outcome was relative frequency of symptomatic, antibiotic-treated UTI. Cost-effectiveness was assessed by cost per UTI avoided. The secondary measures were microbiologically proven UTI, antimicrobial resistance, health status and participants’ attitudes to antibiotic use. Results: The frequency of symptomatic antibiotic-treated UTI was reduced by 48% using prophylaxis [incidence rate ratio (IRR) 0.52, 95% confidence interval (CI) 0.44 to 0.61; n = 361]. Reduction in microbiologically proven UTI was similar (IRR 0.49, 95% CI 0.39 to 0.60; n = 361). Absolute reduction in UTI episodes over 12 months was from a median (interquartile range) of 2 (1–4) in the no-prophylaxis group (n = 180) to 1 (0–2) in the prophylaxis group (n = 181). The results were unchanged by adjustment for days at risk of UTI and the presence of factors giving higher risk of UTI. Development of antimicrobial resistance was seen more frequently in pathogens isolated from urine and Escherichia coli from perianal swabs in participants allocated to antibiotic prophylaxis. The use of prophylaxis incurred an extra cost of £99 to prevent one UTI (not including costs related to increased antimicrobial resistance). The emotional and practical burden of CISC and UTI influenced well-being, but health status measured over 12 months was similar between groups and did not deteriorate significantly during UTI. Participants were generally unconcerned about using antibiotics, including the possible development of antimicrobial resistance. Limitations: Lack of blinding may have led participants in each group to use different thresholds to trigger reporting and treatment-seeking for UTI. Conclusions: The results of this large randomised trial, conducted in accordance with best practice, demonstrate clear benefit for antibiotic prophylaxis in terms of reducing the frequency of UTI for people carrying out CISC. Antibiotic prophylaxis use appears safe for individuals over 12 months, but the emergence of resistant urinary pathogens may prejudice longer-term management of recurrent UTI and is a public health concern. Future work includes longer-term studies of antimicrobial resistance and studies of non-antibiotic preventative strategies. Trial registration: Current Controlled Trials ISRCTN67145101 and EudraCT 2013-002556-32. Funding: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment Vol. 22, No. 24. See the NIHR Journals Library website for further project information.

Background: Ureteric colic, the term used to describe the pain felt when a stone passes down the ureter from the kidney to the bladder, is a frequent reason for people to seek emergency health care. Treatment with the muscle-relaxant drugs tamsulosin hydrochloride (Petyme, TEVA UK Ltd) and nifedipine (Coracten®, UCB Pharma Ltd) as medical expulsive therapy (MET) is increasingly being used to improve the likelihood of spontaneous stone passage and lessen the need for interventional procedures. However, there remains considerable uncertainty around the effectiveness of these drugs for routine use. Objectives: To determine whether or not treatment with either tamsulosin 400 µg or nifedipine 30 mg for up to 4 weeks increases the rate of spontaneous stone passage for people with ureteric colic compared with placebo, and whether or not it is cost-effective for the UK NHS. Design: A pragmatic, randomised controlled trial comparing two active drugs, tamsulosin and nifedipine, against placebo. Participants, clinicians and trial staff were blinded to treatment allocation. A cost–utility analysis was performed using data gathered during trial participation. Setting: Urology departments in 24 UK NHS hospitals. Participants: Adults aged between 18 and 65 years admitted as an emergency with a single ureteric stone measuring ≤ 10 mm, localised by computerised tomography, who were able to take trial medications and complete trial procedures. Interventions: Eligible participants were randomised 1 : 1 : 1 to take tamsulosin 400 µg, nifedipine 30 mg or placebo once daily for up to 4 weeks to make the following comparisons: tamsulosin or nifedipine (MET) versus placebo and tamsulosin versus nifedipine. Main outcome measures: The primary effectiveness outcome was the proportion of participants who spontaneously passed their stone. This was defined as the lack of need for active intervention for ureteric stones at up to 4 weeks after randomisation. This was determined from 4- and 12-week case-report forms completed by research staff, and from the 4-week participant self-reported questionnaire. The primary economic outcome was the incremental cost per quality-adjusted life-year (QALY) gained over 12 weeks. We estimated costs from NHS sources and calculated QALYs from participant completion of the European Quality of Life-5 Dimensions health status questionnaire 3-level response (EQ-5D-3L™) at baseline, 4 weeks and 12 weeks. Results: Primary outcome analysis included 97% of the 1167 participants randomised (378/391 tamsulosin, 379/387 nifedipine and 379/399 placebo participants). The proportion of participants who spontaneously passed their stone did not differ between MET and placebo [odds ratio (OR) 1.04, 95% confidence interval (CI) 0.77 to 1.43; absolute difference 0.8%, 95% CI –4.1% to 5.7%] or between tamsulosin and nifedipine [OR 1.06, 95% CI 0.74 to 1.53; absolute difference 1%, 95% CI –4.6% to 6.6%]. There was no evidence of a difference in QALYs gained or in cost between the trial groups, which means that the use of MET would be very unlikely to be considered cost-effective. These findings were unchanged by extensive sensitivity analyses around predictors of stone passage, including sex, stone size and stone location. Conclusions: Tamsulosin and nifedipine did not increase the likelihood of stone passage over 4 weeks for people with ureteric colic, and use of these drugs is very unlikely to be cost-effective for the NHS. Further work is required to investigate the phenomenon of large, high-quality trials showing smaller effect size than meta-analysis of several small, lower-quality studies. Trial registration: Current Controlled Trials ISRCTN69423238. European Clinical Trials Database (EudraCT) number 2010–019469–26. Funding: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 63. See the NIHR Journals Library website for further project information.

Background: For people with localised prostate cancer, active treatments are effective but have significant side effects. Minimally invasive treatments that destroy (or ablate) either the entire gland or the part of the prostate with cancer may be as effective and cause less side effects at an acceptable cost. Such therapies include cryotherapy, high-intensity focused ultrasound (HIFU) and brachytherapy, among others. Objectives: This study aimed to determine the relative clinical effectiveness and cost-effectiveness of ablative therapies compared with radical prostatectomy (RP), external beam radiotherapy (EBRT) and active surveillance (AS) for primary treatment of localised prostate cancer, and compared with RP for salvage treatment of localised prostate cancer which has recurred after initial treatment with EBRT. Data sources: MEDLINE (1946 to March week 3, 2013), MEDLINE In-Process & Other Non-Indexed Citations (29 March 2013), EMBASE (1974 to week 13, 2013), Bioscience Information Service (BIOSIS) (1956 to 1 April 2013), Science Citation Index (1970 to 1 April 2013), Cochrane Central Register of Controlled Trials (CENTRAL) (issue 3, 2013), Cochrane Database of Systematic Reviews (CDSR) (issue 3, 2013), Database of Abstracts of Reviews of Effects (DARE) (inception to March 2013) and Health Technology Assessment (HTA) (inception to March 2013) databases were searched. Costs were obtained from NHS sources. Review methods: Evidence was drawn from randomised controlled trials (RCTs) and non-RCTs, and from case series for the ablative procedures only, in people with localised prostate cancer. For primary therapy, the ablative therapies were cryotherapy, HIFU, brachytherapy and other ablative therapies. The comparators were AS, RP and EBRT. For salvage therapy, the ablative therapies were cryotherapy and HIFU. The comparator was RP. Outcomes were cancer related, adverse effects (functional and procedural) and quality of life. Two reviewers extracted data and carried out quality assessment. Meta-analysis used a Bayesian indirect mixed-treatment comparison. Data were incorporated into an individual simulation Markov model to estimate cost-effectiveness. Results: The searches identified 121 studies for inclusion in the review of patients undergoing primary treatment and nine studies for the review of salvage treatment. Cryotherapy [3995 patients; 14 case series, 1 RCT and 4 non-randomised comparative studies (NRCSs)], HIFU (4000 patients; 20 case series, 1 NRCS) and brachytherapy (26,129 patients; 2 RCTs, 38 NRCSs) studies provided limited data for meta-analyses. All studies were considered at high risk of bias. There was no robust evidence that mortality (4-year survival 93% for cryotherapy, 99% for HIFU, 91% for EBRT) or other cancer-specific outcomes differed between treatments. For functional and quality-of-life outcomes, the paucity of data prevented any definitive conclusions from being made, although data on incontinence rates and erectile dysfunction for all ablative procedures were generally numerically lower than for non-ablative procedures. The safety profiles were comparable with existing treatments. Studies reporting the use of focal cryotherapy suggested that incontinence rates may be better than for whole-gland treatment. Data on AS, salvage treatment and other ablative therapies were too limited. The cost-effectiveness analysis confirmed the uncertainty from the clinical review and that there is no technology which appears superior, on the basis of current evidence, in terms of average cost-effectiveness. The probabilistic sensitivity analyses suggest that a number of ablative techniques are worthy of further research. Limitations: The main limitations were the quantity and quality of the data available on cancer-related outcomes and dysfunction. Conclusions: The findings indicate that there is insufficient evidence to form any clear recommendations on the use of ablative therapies in order to influence current clinical practice. Research efforts in the use of ablative therapies in the management of prostate cancer should now be concentrated on the performance of RCTs and the generation of standardised outcomes. Study registration: This study is registered as PROSPERO CRD42012002461. Funding: The National Institute for Health Research Health Technology Assessment programme.