Modelled cost-effectiveness analysis of the Support and Treatment After Replacement (STAR) care pathway for chronic pain after total knee replacement compared with usual care.

BACKGROUND: The aim of the study was to estimate the long-term cost-effectiveness of the Support and Treatment After Replacement (STAR) care pathway for chronic pain after total knee replacement compared with usual postoperative care. METHODS: Study design: A decision-analytic (cohort Markov) model was used for the simulation with time dependent annual transition probabilities and a time horizon of five years. SETTING: Patients treated by National Health Service (NHS) hospitals in England and Wales. STUDY POPULATION: Adults classified as having chronic pain three months after undergoing a total knee replacement. INTERVENTION: The STAR care pathway following a total knee replacement. COMPARATOR: Usual postoperative care following a total knee replacement. PERSPECTIVE: The study was undertaken from the perspective of the NHS. OUTCOME MEASURES: Quality-adjusted life years and healthcare costs. Discounting: A rate of 3.5% for both costs and health utility. RESULTS: Model results indicate that the STAR intervention would dominate current practice by providing a gain in quality-adjusted life years (QALYs) of 0.086 and a reduction of £375 (per person) in costs over the first five years. The incremental net monetary benefit of the STAR intervention was estimated at £2,086 (at a threshold of £20,000 per QALY). Probabilistic sensitivity analysis suggests the STAR intervention is likely to be cost-effective with a probability of 0.62. The results remain robust to changes in model assumptions on comparator utility and the timing of the start of the intervention. If hospital admission costs are assumed not to be reduced by the STAR intervention, it would no longer be cost saving, but it would likely be cost-effective based on probabilistic sensitivity analysis (0.59). CONCLUSION: Evidence from the economic model suggests that the STAR care pathway is likely to be cost-effective and potentially dominant from an NHS perspective. TRIAL REGISTRATION: The STAR trial is registered with ISRCTN, ISRCTN92545361.

Prostate-Specific Antigen Screening and 15-Year Prostate Cancer Mortality: A Secondary Analysis of the CAP Randomized Clinical Trial.

Importance: The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) reported no effect of prostate-specific antigen (PSA) screening on prostate cancer mortality at a median 10-year follow-up (primary outcome), but the long-term effects of PSA screening on prostate cancer mortality remain unclear. Objective: To evaluate the effect of a single invitation for PSA screening on prostate cancer-specific mortality at a median 15-year follow-up compared with no invitation for screening. Design, Setting, and Participants: This secondary analysis of the CAP randomized clinical trial included men aged 50 to 69 years identified at 573 primary care practices in England and Wales. Primary care practices were randomized between September 25, 2001, and August 24, 2007, and men were enrolled between January 8, 2002, and January 20, 2009. Follow-up was completed on March 31, 2021. Intervention: Men received a single invitation for a PSA screening test with subsequent diagnostic tests if the PSA level was 3.0 ng/mL or higher. The control group received standard practice (no invitation). Main Outcomes and Measures: The primary outcome was reported previously. Of 8 prespecified secondary outcomes, results of 4 were reported previously. The 4 remaining prespecified secondary outcomes at 15-year follow-up were prostate cancer-specific mortality, all-cause mortality, and prostate cancer stage and Gleason grade at diagnosis. Results: Of 415 357 eligible men (mean [SD] age, 59.0 [5.6] years), 98% were included in these analyses. Overall, 12 013 and 12 958 men with a prostate cancer diagnosis were in the intervention and control groups, respectively (15-year cumulative risk, 7.08% [95% CI, 6.95%-7.21%] and 6.94% [95% CI, 6.82%-7.06%], respectively). At a median 15-year follow-up, 1199 men in the intervention group (0.69% [95% CI, 0.65%-0.73%]) and 1451 men in the control group (0.78% [95% CI, 0.73%-0.82%]) died of prostate cancer (rate ratio [RR], 0.92 [95% CI, 0.85-0.99]; P = .03). Compared with the control, the PSA screening intervention increased detection of low-grade (Gleason score [GS] ≤6: 2.2% vs 1.6%; P < .001) and localized (T1/T2: 3.6% vs 3.1%; P < .001) disease but not intermediate (GS of 7), high-grade (GS ≥8), locally advanced (T3), or distally advanced (T4/N1/M1) tumors. There were 45 084 all-cause deaths in the intervention group (23.2% [95% CI, 23.0%-23.4%]) and 50 336 deaths in the control group (23.3% [95% CI, 23.1%-23.5%]) (RR, 0.97 [95% CI, 0.94-1.01]; P = .11). Eight of the prostate cancer deaths in the intervention group (0.7%) and 7 deaths in the control group (0.5%) were related to a diagnostic biopsy or prostate cancer treatment. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, a single invitation for PSA screening compared with standard practice without routine screening reduced prostate cancer deaths at a median follow-up of 15 years. However, the absolute reduction in deaths was small. Trial Registration: isrctn.org Identifier: ISRCTN92187251.

Development of a brief, generic, modular resource-use measure (ModRUM): piloting with patients.

BACKGROUND: Bespoke self-report resource-use measures (RUMs) are commonly developed or adapted for each new randomised controlled trial. Consequently, RUMs lack standardisation and validation is rarely conducted. A new generic RUM, ModRUM, has been developed using a rigorous process, including consultation with health economists and patients. ModRUM includes a concise core healthcare module, designed to be included in all trials, and depth-adding questions, which can replace or be added to core questions as needed. Modules covering other sectors are under development. The aim of this study was to test the acceptability, feasibility, and criterion and construct validity of the healthcare module of ModRUM. METHODS: Patients who had a recent appointment at their GP practice were invited to complete ModRUM (core module or core module with depth questions), a characteristics form and the EQ-5D-5L. Acceptability was assessed via response rates and questionnaire completion time. Feasibility was assessed by reviewing issues observed in participants' responses and question completion rates. Construct validity was tested via hypothesis testing and known-group analyses, using Wilcoxon rank-sum and Kruskal-Wallis tests, and a generalised linear model. Criterion validity was tested by comparing ModRUM results with primary care medical records. Sensitivity, specificity, and agreement using Lin's concordance correlation coefficient (pc) were estimated. RESULTS: One hundred patients participated from five GP practices in the South-West of England. Acceptability was higher for the core module (20% versus 10% response rate). Question completion rates were high across both versions (> 90%). Some support was observed for construct validity, with results suggesting that healthcare costs differ dependent on the number of long-term conditions (p < 0.05) and are negatively associated with health-related quality of life (p < 0.01). Sensitivity was high for all questions (> 0.83), while specificity varied (0.33-0.88). There was a good level of agreement for GP contacts and costs, and prescribed medication costs (pc > 0.6). CONCLUSION: This study provided preliminary evidence of the acceptability, feasibility, and criterion and construct validity of ModRUM. Further testing is required within trials and with groups that were less well represented in this study.

Impact of PSA testing on secondary care costs in England and Wales: estimates from the Cluster randomised triAl of PSA testing for Prostate cancer (CAP).

BACKGROUND: Screening men for prostate cancer using prostate-specific antigen (PSA) testing remains controversial. We aimed to estimate the likely budgetary impact on secondary care in England and Wales to inform screening decision makers. METHODS: The Cluster randomised triAl of PSA testing for Prostate cancer study (CAP) compared a single invitation to men aged 50-69 for a PSA test with usual care (no screening). Routinely collected hospital care data were obtained for all men in CAP, and NHS reference costs were mapped to each event via Healthcare Resource Group (HRG) codes. Secondary-care costs per man per year were calculated, and cost differences (and population-level estimates) between arms were derived annually for the first five years following randomisation. RESULTS: In the first year post-randomisation, secondary-care costs averaged across all men (irrespective of a prostate cancer diagnosis) in the intervention arm (n = 189279) were £44.80 (95% confidence interval: £18.30-£71.30) higher than for men in the control arm (n = 219357). Extrapolated to a population level, the introduction of a single PSA screening invitation could lead to additional secondary care costs of £314 million. CONCLUSIONS: Introducing a single PSA screening test for men aged 50-69 across England and Wales could lead to very high initial secondary-care costs.

The STAR care pathway for patients with chronic pain after total knee replacement: four-year follow-up of a randomised controlled trial.

BACKGROUND: The Support and Treatment After Replacement (STAR) care pathway is a clinically important and cost-effective intervention found to improve pain outcomes over one year for people with chronic pain three months after total knee replacement (TKR). We followed up STAR trial participants to evaluate the longer-term clinical- and cost-effectiveness of this care pathway. METHODS: Participants who remained enrolled on the trial at one year were contacted by post at a median of four years after randomisation and invited to complete a questionnaire comprising the same outcomes collected during the trial. We captured pain (co-primary outcome using the Brief Pain Inventory (BPI) pain severity and interference scales; scored 0-10, best to worst), function, neuropathic characteristics, emotional aspects of pain, health-related quality of life, and satisfaction. Electronic hospital informatics data on hospital resource use for the period of one to four years post-randomisation were collected from participating hospital sites. The economic evaluation took an National Health Service (NHS) secondary care perspective, with a four-year time horizon. RESULTS: Overall, 226/337 (67%) of participants returned completed follow-up questionnaires, yielding adjusted between-group differences in BPI means of -0.42 (95% confidence interval, CI (-1.07, 0.23); p = 0.20) for pain severity and - 0.64 (95% CI -1.41, 0.12); p = 0.10) for pain interference. Analysis using a multiple imputed data set (n = 337) showed an incremental net monetary benefit in favour of the STAR care pathway of £3,525 (95% CI -£990 to £8,039) at a £20,000/QALY willingness-to-pay threshold, leading to a probability that the intervention was cost-effective of 0.94. CONCLUSIONS: The magnitude of the longer-term benefits of the STAR care pathway are uncertain due to attrition of trial participants; however, there is a suggestion of some degree of sustained clinical benefit at four years. The care pathway remained cost-effective at four years. TRIAL REGISTRATION: ISRCTN: 92,545,361.

Thulium laser transurethral vaporesection of the prostate versus transurethral resection of the prostate for men with lower urinary tract symptoms or urinary retention (UNBLOCS): a randomised controlled trial.

BACKGROUND: Transurethral resection of the prostate (TURP) is the standard operation for benign prostatic obstruction. Thulium laser transurethral vaporesection of the prostate (ThuVARP) is a technique with suggested advantages over TURP, including reduced complications and hospital stay. We aimed to investigate TURP versus ThuVARP in men with lower urinary tract symptoms or urinary retention secondary to benign prostatic obstruction. METHODS: In this randomised, blinded, parallel-group, pragmatic equivalence trial, men in seven UK hospitals with bothersome lower urinary tract symptoms or urinary retention secondary to benign prostatic obstruction were randomly assigned (1:1) at the point of surgery to receive ThuVARP or TURP. Patients were masked until follow-up completion. Centres used their usual TURP procedure (monopolar or bipolar). All trial surgeons underwent training on the ThuVARP technique. Co-primary outcomes were maximum urinary flow rate (Qmax) and International Prostate Symptom Score (IPSS) at 12-months post-surgery. Equivalence was defined as a difference of 2·5 points or less for IPSS and 4 mL per s or less for Qmax. Analysis was done according to the intention-to-treat principle. The trial is registered with the ISRCTN Registry, ISRCTN00788389. FINDINGS: Between July 23, 2014, and Dec 30, 2016, 410 men were randomly assigned to ThuVARP or TURP, 205 per study group. TURP was superior for Qmax (mean 23·2 mL per s for TURP and 20·2 mL per s for ThuVARP; adjusted difference in means -3·12, 95% CI -5·79 to -0·45). Equivalence was shown for IPSS (mean 6·3 for TURP and 6·4 for ThuVARP; adjusted difference in means 0·28, -0·92 to 1·49). Mean hospital stay was 48 h in both study groups. 91 (45%) of 204 patients in the TURP group and 96 (47%) of 203 patients in the ThuVARP group had at least one complication. INTERPRETATION: TURP and ThuVARP were equivalent for urinary symptom improvement (IPSS) 12-months post-surgery, and TURP was superior for Qmax. Anticipated laser benefits for ThuVARP of reduced hospital stay and complications were not observed. FUNDING: UK National Institute for Health Research Health Technology Assessment Programme.

Content of Health Economics Analysis Plans (HEAPs) for Trial-Based Economic Evaluations: Expert Delphi Consensus Survey.

OBJECTIVES: Health economics analysis plans (HEAPs) currently lack consistency, with uncertainty surrounding appropriate content. We aimed to develop a list of essential items that should be included in HEAPs for economic evaluations conducted alongside randomized trials. METHODS: A list of potential items for inclusion was developed by examining existing HEAPs. An electronic Delphi survey was conducted among professional health economists. Respondents were asked to rate potential items from 1 (least important) to 9 (most important), suggest additional items, and comment on proposed items (round 1). A second survey (round 2) was emailed to participants, including the participant's own scores from round 1 along with summary results from the whole panel; participants were asked to rerate each item. Consensus criteria for inclusion in the final list were predefined as >70% of participants rating an item 7-9 and <15% rating it 1-3 after round 2. A final item selection meeting was held to scrutinize the results and adjudicate on items lacking consensus. RESULTS: 62 participants completed round 1 of the survey. The initial list included 72 potential items; all 72 were carried forward to round 2, and no new items were added. 48 round 1 respondents (77.4%) completed round 2 and reached consensus on 53 items. At the final meeting, the expert panel (n = 9) agreed that 58 items should be included in the essential list, moved 9 items to an optional list, and dropped 5 items. CONCLUSIONS: Via expert consensus opinion, this study identified 58 items that are considered essential in a HEAP.

Development of a brief, generic, modular resource-use measure (ModRUM): cognitive interviews with patients.

BACKGROUND: Self-report resource-use measures (RUMs) are often used to collect healthcare use data from participants in healthcare studies. However, RUMs are typically adapted from existing measures on a study-by-study basis, resulting in a lack of standardisation which limits comparability across studies. Psychometric testing of RUMs is rarely conducted. This paper reports on cognitive interviews with patients to test the content validity and acceptability of a new RUM (ModRUM). ModRUM is a brief, generic RUM with a core module on healthcare use and questions/modules to increase depth and breadth. METHODS: A purposeful sampling strategy with maximum variation was used to recruit patients from primary care to participate in "think-aloud" interviews with retrospective probing. Participants verbalised their thought processes as they completed ModRUM, which allowed errors (issues with completion) to be identified. The interviewer asked follow-up and probing questions to investigate errors, clarity and acceptability. Interviews were audio-recorded and transcribed verbatim. Research team members independently scored transcripts to identify errors in comprehension, recall, judgement and response. Members met to agree on final scores. Interview transcripts were analysed qualitatively using techniques of constant comparison, to identify common themes and ideas for improvement. Data collection and analysis were performed concurrently and in rounds. RESULTS: Twenty participants were interviewed between December 2019 and March 2020. Interviews were conducted in three rounds, with revisions made iteratively and in response to interview findings. Seven participants completed the core module and 13 completed the core module plus depth questions. Of 71 issues, 28 were in comprehension, 14 in retrieval, 10 in judgement, 18 in response and 1 uncategorised. Most issues (21 issues by 2 participants) were due to participants including family healthcare use. Other issues included using incorrect recall periods (5 issues) and overlooking questions leading to missing responses (9 issues). Common participant suggestions included highlighting important details and providing additional definition or examples for some terms. The length, content and layout were acceptable to most participants. CONCLUSIONS: A generic RUM is needed to increase study comparability. RUM development requires thorough testing to demonstrate and enhance validity. Cognitive interviewing has demonstrated the acceptability and content validity of ModRUM.

The ProtecT randomised trial cost-effectiveness analysis comparing active monitoring, surgery, or radiotherapy for prostate cancer.

BACKGROUND: There is limited evidence relating to the cost-effectiveness of treatments for localised prostate cancer. METHODS: The cost-effectiveness of active monitoring, surgery, and radiotherapy was evaluated within the Prostate Testing for Cancer and Treatment (ProtecT) randomised controlled trial from a UK NHS perspective at 10 years' median follow-up. Prostate cancer resource-use collected from hospital records and trial participants was valued using UK reference-costs. QALYs (quality-adjusted-life-years) were calculated from patient-reported EQ-5D-3L measurements. Adjusted mean costs, QALYs, and incremental cost-effectiveness ratios were calculated; cost-effectiveness acceptability curves and sensitivity analyses addressed uncertainty; subgroup analyses considered age and disease-risk. RESULTS: Adjusted mean QALYs were similar between groups: 6.89 (active monitoring), 7.09 (radiotherapy), and 6.91 (surgery). Active monitoring had lower adjusted mean costs (£5913) than radiotherapy (£7361) and surgery (£7519). Radiotherapy was the most likely (58% probability) cost-effective option at the UK NICE willingness-to-pay threshold (£20,000 per QALY). Subgroup analyses confirmed radiotherapy was cost-effective for older men and intermediate/high-risk disease groups; active monitoring was more likely to be the cost-effective option for younger men and low-risk groups. CONCLUSIONS: Longer follow-up and modelling are required to determine the most cost-effective treatment for localised prostate cancer over a man's lifetime. TRIAL REGISTRATION: Current Controlled Trials number, ISRCTN20141297: http://isrctn.org (14/10/2002); ClinicalTrials.gov number, NCT02044172: http://www.clinicaltrials.gov (23/01/2014).

What are the inpatient and day case costs following primary total hip replacement of patients treated for prosthetic joint infection: a matched cohort study using linked data from the National Joint Registry and Hospital Episode Statistics.

BACKGROUND: Prosthetic joint infection (PJI) following total hip replacement (THR) surgery is a serious complication that negatively impacts patients' lives and is financially burdensome for healthcare providers. As the number of THRs increases, so does this financial burden. This research estimates the economic burden with respect to inpatient and day case hospital admissions for patients receiving revision surgery for PJI following primary THR. METHODS: In this matched cohort study, the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man (NJR) was used to identify patients. Patients revised for PJI with a one- or two-stage revision following THR and patients not revised for PJI were matched on several characteristics using exact and radius matching. Hospital inpatient and day case healthcare records from the English Hospital Episode Statistics database were obtained for 5 years following the identified patient's primary THR. UK national unit costs were applied to hospital admissions and the 5-year total cost was estimated. A two-part model (Probit and generalised linear model) was employed to estimate the incremental difference in costs between those revised and not revised for PJI. RESULTS: Between 2006 and 2009, 1914 revisions for PJI were identified in the NJR. The matching resulted in 422 patients revised for PJI and 1923 matches not revised for PJI who were included in the analysis. The average cost of inpatient and day case admissions in the 5 years following primary THR was approximately £42,000 for patients revised for PJI and £8000 for patients not revised for PJI. The difference in costs over the 5 years was £33,452 (95% CI £30,828 to £36,077; p < 0.00). CONCLUSIONS: In the 5 years following primary THR, patients who develop PJI and have revision surgery cost approximately £33,000 (over 5-fold) more than patients not revised for PJI based on their hospital inpatient and day case admissions alone. The total burden of PJI is likely to be much higher when also considering outpatient, primary and community care costs. This highlights the need to find both ways to reduce the incidence of PJI following THR and cost-effective treatment strategies if PJI occurs.

The cost-effectiveness of transurethral resection of the prostate vs thulium laser transurethral vaporesection of the prostate in the UNBLOCS randomised controlled trial for benign prostatic obstruction.

OBJECTIVE: To determine the cost-effectiveness of the current 'gold standard' operation of transurethral resection of the prostate (TURP) compared to the new laser technique of thulium laser transurethral vaporesection of the prostate (ThuVARP) in men with benign prostatic obstruction (BPO) within the UK National Health Service (NHS). PATIENTS AND METHODS: The trial was conducted across seven UK centres (four university teaching hospitals and three district general hospitals). A total of 410 men aged ≥18 years presenting with either bothersome lower urinary tract symptoms (LUTS) or urinary retention secondary to BPO, and suitable for surgery, were randomised (whilst under anaesthetic) 1:1 to receive the TURP or ThuVARP procedure. Resource use in relation to the operation, initial inpatient stay, and subsequent use of NHS services was collected for 12 months from randomisation (equivalent to primary effectiveness outcome) using hospital records and patient questionnaires. Resources were valued using UK reference costs. Quality adjusted life years (QALYs) were calculated from the EuroQoL five Dimensions five Levels (EQ-5D-5L) questionnaire completed at baseline, 3- and 12-months. Total adjusted mean costs, QALYs and incremental Net Monetary Benefit statistics were calculated: cost-effectiveness acceptability curves and sensitivity analyses addressed uncertainty. RESULTS: The total adjusted mean secondary care cost over the 12 months in the TURP arm (£4244) was £9 (95% CI -£376, £359) lower than the ThuVARP arm (£4253). The ThuVARP operation took on average 21 min longer than TURP. The adjusted mean difference of QALYs (0.01 favouring TURP, 95% CI -0.01, 0.04) was similar between the arms. There is a 76% probability that TURP is the cost-effective option compared with ThuVARP at the £20 000 per QALY willingness to pay threshold used by National Institute for Health and Care Excellence (NICE). CONCLUSION: One of the anticipated benefits of the laser surgery, reduced length of hospital stay with an associated reduction in cost, did not materialise within the study. The longer duration of the ThuVARP procedure is important to consider, both from a patient perspective in terms of increased time under anaesthetic, and from a service delivery perspective. TURP remains a highly cost-effective treatment for men with BPO.

Core Items for a Standardized Resource Use Measure: Expert Delphi Consensus Survey.

BACKGROUND: Resource use measurement by patient recall is characterized by inconsistent methods and a lack of validation. A validated standardized resource use measure could increase data quality, improve comparability between studies, and reduce research burden. OBJECTIVES: To identify a minimum set of core resource use items that should be included in a standardized adult instrument for UK health economic evaluation from a provider perspective. METHODS: Health economists with experience of UK-based economic evaluations were recruited to participate in an electronic Delphi survey. Respondents were asked to rate 60 resource use items (e.g., medication names) on a scale of 1 to 9 according to the importance of the item in a generic context. Items considered less important according to predefined consensus criteria were dropped and a second survey was developed. In the second round, respondents received the median score and their own score from round 1 for each item alongside summarized comments and were asked to rerate items. A final project team meeting was held to determine the recommended core set. RESULTS: Forty-five participants completed round 1. Twenty-six items were considered less important and were dropped, 34 items were retained for the second round, and no new items were added. Forty-two respondents (93.3%) completed round 2, and greater consensus was observed. After the final meeting, 10 core items were selected, with further items identified as suitable for "bolt-on" questionnaire modules. CONCLUSIONS: The consensus on 10 items considered important in a generic context suggests that a standardized instrument for core resource use items is feasible.

Effect of a Low-Intensity PSA-Based Screening Intervention on Prostate Cancer Mortality: The CAP Randomized Clinical Trial.

Importance: Prostate cancer screening remains controversial because potential mortality or quality-of-life benefits may be outweighed by harms from overdetection and overtreatment. Objective: To evaluate the effect of a single prostate-specific antigen (PSA) screening intervention and standardized diagnostic pathway on prostate cancer-specific mortality. Design, Setting, and Participants: The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) included 419 582 men aged 50 to 69 years and was conducted at 573 primary care practices across the United Kingdom. Randomization and recruitment of the practices occurred between 2001 and 2009; patient follow-up ended on March 31, 2016. Intervention: An invitation to attend a PSA testing clinic and receive a single PSA test vs standard (unscreened) practice. Main Outcomes and Measures: Primary outcome: prostate cancer-specific mortality at a median follow-up of 10 years. Prespecified secondary outcomes: diagnostic cancer stage and Gleason grade (range, 2-10; higher scores indicate a poorer prognosis) of prostate cancers identified, all-cause mortality, and an instrumental variable analysis estimating the causal effect of attending the PSA screening clinic. Results: Among 415 357 randomized men (mean [SD] age, 59.0 [5.6] years), 189 386 in the intervention group and 219 439 in the control group were included in the analysis (n = 408 825; 98%). In the intervention group, 75 707 (40%) attended the PSA testing clinic and 67 313 (36%) underwent PSA testing. Of 64 436 with a valid PSA test result, 6857 (11%) had a PSA level between 3 ng/mL and 19.9 ng/mL, of whom 5850 (85%) had a prostate biopsy. After a median follow-up of 10 years, 549 (0.30 per 1000 person-years) died of prostate cancer in the intervention group vs 647 (0.31 per 1000 person-years) in the control group (rate difference, -0.013 per 1000 person-years [95% CI, -0.047 to 0.022]; rate ratio [RR], 0.96 [95% CI, 0.85 to 1.08]; P = .50). The number diagnosed with prostate cancer was higher in the intervention group (n = 8054; 4.3%) than in the control group (n = 7853; 3.6%) (RR, 1.19 [95% CI, 1.14 to 1.25]; P < .001). More prostate cancer tumors with a Gleason grade of 6 or lower were identified in the intervention group (n = 3263/189 386 [1.7%]) than in the control group (n = 2440/219 439 [1.1%]) (difference per 1000 men, 6.11 [95% CI, 5.38 to 6.84]; P < .001). In the analysis of all-cause mortality, there were 25 459 deaths in the intervention group vs 28 306 deaths in the control group (RR, 0.99 [95% CI, 0.94 to 1.03]; P = .49). In the instrumental variable analysis for prostate cancer mortality, the adherence-adjusted causal RR was 0.93 (95% CI, 0.67 to 1.29; P = .66). Conclusions and Relevance: Among practices randomized to a single PSA screening intervention vs standard practice without screening, there was no significant difference in prostate cancer mortality after a median follow-up of 10 years but the detection of low-risk prostate cancer cases increased. Although longer-term follow-up is under way, the findings do not support single PSA testing for population-based screening. Trial Registration: ISRCTN Identifier: ISRCTN92187251.

Lessons from a peer-led obesity prevention programme in English schools.

Obesity in young people is a major public health concern. Energy balance, the interrelationship between diet and physical activity, is known to be a key determinant. Evidence supports the development of school-based approaches to obesity prevention. ASSIST (A Stop Smoking in Schools Trial) is an effective school-based, peer-led smoking prevention programme for 12-13-year-old students, based on diffusion of innovations theory. The AHEAD (Activity and Healthy Eating in ADolescence) study tested the feasibility of adapting ASSIST to an obesity prevention intervention. The AHEAD intervention was tested and refined during a pilot study in one school, followed by an exploratory trial in six schools. Quantitative (self-report behavioural questionnaires and evaluation forms) and qualitative (structured observations, focus groups and interviews) research methods were used to examine the implementation and acceptability of the intervention. The potential effectiveness of the intervention in increasing healthy eating was measured using self-report behavioural questionnaires. Activity monitors (accelerometers) were used to measure physical activity. Results show it was feasible to implement the AHEAD intervention, which was well received. However, implementation was resource and labour intensive and relatively expensive. Furthermore, there was no evidence of promise that the intervention would increase physical activity or healthy eating in adolescents. Although diet and physical activity are both relevant for obesity prevention, the focus on two behaviours appeared too complex for informal diffusion through peer networks. This identifies a tension, particularly for adolescent peer-led health promotion, between the desire not to isolate or oversimplify health behaviours and the need to present clear, succinct health promotion messages.

Contemporary accuracy of death certificates for coding prostate cancer as a cause of death: Is reliance on death certification good enough? A comparison with blinded review by an independent cause of death evaluation committee.

BACKGROUND: Accurate cause of death assignment is crucial for prostate cancer epidemiology and trials reporting prostate cancer-specific mortality outcomes. METHODS: We compared death certificate information with independent cause of death evaluation by an expert committee within a prostate cancer trial (2002-2015). RESULTS: Of 1236 deaths assessed, expert committee evaluation attributed 523 (42%) to prostate cancer, agreeing with death certificate cause of death in 1134 cases (92%, 95% CI: 90%, 93%). The sensitivity of death certificates in identifying prostate cancer deaths as classified by the committee was 91% (95% CI: 89%, 94%); specificity was 92% (95% CI: 90%, 94%). Sensitivity and specificity were lower where death occurred within 1 year of diagnosis, and where there was another primary cancer diagnosis. CONCLUSIONS: UK death certificates accurately identify cause of death in men with prostate cancer, supporting their use in routine statistics. Possible differential misattribution by trial arm supports independent evaluation in randomised trials.

Local anaesthetic wound infiltration in addition to standard anaesthetic regimen in total hip and knee replacement: long-term cost-effectiveness analyses alongside the APEX randomised controlled trials.

BACKGROUND: The Arthroplasty Pain Experience (APEX) studies are two randomised controlled trials in primary total hip (THR) and total knee replacement (TKR) at a large UK orthopaedics centre. APEX investigated the effect of local anaesthetic wound infiltration (LAI), administered before wound closure, in addition to standard analgesia, on pain severity at 12 months. This article reports results of the within-trial economic evaluations. METHODS: Cost-effectiveness was assessed from the health and social care payer perspective in relation to quality adjusted life years (QALYs) and the primary clinical outcome, the WOMAC Pain score at 12-months follow-up. Resource use was collected from hospital records and patient-completed postal questionnaires, and valued using unit cost estimates from local NHS Trust finance department and national tariffs. Missing data were addressed using multiple imputation chained equations. Costs and outcomes were compared per trial arm and plotted in cost-effectiveness planes. If no arm was dominant (i.e., more effective and less expensive than the other), incremental cost-effectiveness ratios were estimated. The economic results were bootstrapped incremental net monetary benefit statistics (INMB) and cost-effectiveness acceptability curves. One-way deterministic sensitivity analyses explored any methodological uncertainty. RESULTS: In both the THR and TKR trials, LAI was the dominant treatment: cost-saving and more effective than standard care, in relation to QALYs and WOMAC Pain. Using the £20,000 per QALY threshold, in THR, the INMB was £1,125 (95 % BCI, £183 to £2,067) and the probability of being cost-effective was over 98 %. In TKR, the INMB was £264 (95 % BCI, -£710 to £1,238), but there was only 62 % probability of being cost-effective. When considering an NHS perspective only, LAI was no longer dominant in THR, but still highly cost-effective, with an INMB of £961 (95 % BCI, £50 to £1,873). CONCLUSIONS: Administering LAI is a cost-effective treatment option in THR and TKR surgeries. The evidence, because of larger QALY gain, is stronger for THR. In TKR, there is more uncertainty around the economic result, and smaller QALY gains. Results, however, point to LAI being cheaper than standard analgesia, which includes a femoral nerve block. TRIAL REGISTRATION: ISRCTN96095682 , 29/04/2010.

A randomised controlled trial comparing opt-in and opt-out home visits for tracing lost participants in a prospective birth cohort study.

BACKGROUND: Attrition is an important problem in cohort studies. Tracing cohort members who have moved or otherwise lost contact with the study is vital. There is some debate about the acceptability and relative effectiveness of opt-in versus opt-out methods of contacting cohort members to re-engage them in this context. We conducted a randomised controlled trial to compare the two approaches in terms of effectiveness (tracing to confirm address and consenting to continue in the study), cost-effectiveness and acceptability. METHODS: Participants in this trial were individuals (young people and mothers) recruited to the Avon Longitudinal Study of Parents and Children (ALSPAC), who had not engaged with the study in the previous 5 years and for whom mail had been returned from their last known address. The sampling frame was restricted to those for whom database searching led to a potential new address being found in the Bristol area. 300 participants were randomly selected and assigned using stratified randomisation to the opt-in or opt-out arm. A tailored letter was sent to the potential new address, either asking participants to opt in to a home visit, or giving them the option to opt out of a home visit. Fieldworkers from Ipsos MORI conducted home visits to confirm address details. RESULTS: The proportion who were traced was higher in the opt-out arm (77/150 = 51 %) than the opt-in arm (6/150 = 4 %), as was the proportion who consented to continue in ALSPAC (46/150 = 31 % v 4/150 = 3 %). The mean cost per participant was £8.14 in the opt-in arm and £71.93 in the opt-out arm. There was no evidence of a difference in acceptability between the opt-in and opt-out approaches. CONCLUSION: Since the opt-in approach yielded very low response rates, and there were no differences in terms of acceptability, we conclude that the opt-out approach is the most effective method of tracing disengaged study members. The gains made in contacting participants must be weighed against the increase in cost using this methodology.

Disclosing total waiting times for joint replacement: evidence from the English NHS using linked HES data.

For the last decade, stringent monitoring of waiting time performance targets provided English hospitals with incentives to reduce official waiting times for elective surgery. It is less clear whether the total amount of time patients waited in secondary care, from first referral to outpatient clinic until treatment, has also fallen. We used Hospital Episode Statistics inpatient data for patients undergoing total joint replacement during a period of active monitoring of targets (between 2006/7 and 2008/9) and linked it to outpatient data to reconstruct patients' pathway in the 3 years before surgery and provide alternative measurements of waiting times. Our findings suggest that although official waiting times decreased drastically in our study period, total waiting time in secondary care has not declined. Patients with shorter official waits spent a longer time in a 'work-up' period prior to inclusion in the official waiting list, and socio-economic inequities persisted in waiting times for joint replacement. We found no evidence that target policies achieved efficiency gains during our study period.

Identification and prioritisation of items for a draft participant-reported questionnaire to measure use of social care, informal care, aids and adaptations.

BACKGROUND: Resource-use measurement is integral for assessing cost-effectiveness within trial-based economic evaluations. Methods for gathering resource-use data from participants are not well developed, with questionnaires typically produced for each trial and rarely validated. The healthcare module of a generic, modular resource-use measure, designed for collecting self-report resource-utilisation data, has recently been developed in the UK. The objective of this research is to identify and prioritise items for new, bolt-on modules, covering informal care, social care and personal expenses incurred due to health and care needs. METHODS: Identification and prioritisation, conducted between April and December 2021, involved a rapid review of questionnaires included in the Database of Instruments for Resource Use Measurement and economic evaluations published from 2011 to 2021 to identify candidate items, an online survey of UK-based social care professionals to identify omitted social care items and focus groups with UK-based health economists and UK-based people who access social care services either for themselves or as carers to prioritise items. RESULTS: The review identified 203 items. Over half of the 24 survey respondents reported no missing items. Five academic health economists and four people who access social care services participated in focus groups. Feedback shaped the social and informal care modules and indicated that no specific personal expenses were essential to collect in all trials. Aids/adaptations were highlighted as costly personal expenses when relevant; therefore, the personal expenses module was narrowed to aids/adaptations only. CONCLUSION: Draft informal care, social care and aids/adaptations modules were developed, ready for further testing.

Cost-effectiveness of a primary healthcare intervention to treat male lower urinary tract symptoms: the TRIUMPH cluster randomised controlled trial.

OBJECTIVES: To estimate the cost-effectiveness of a primary care intervention for male lower urinary tract symptoms (LUTS) compared with usual care. DESIGN: Economic evaluation alongside a cluster randomised controlled trial from a UK National Health Service (NHS) perspective with a 12-month time horizon. SETTING: Thirty NHS general practice sites in England. PARTICIPANTS: 1077 men aged 18 or older identified in primary care with bothersome LUTS. INTERVENTIONS: A standardised and manualised intervention for the treatment of bothersome LUTS was compared with usual care. The intervention group (n=524) received a standardised information booklet with guidance on conservative treatment for LUTS, urinary symptom assessment and follow-up contacts for 12 weeks. The usual care group (n=553) followed local guidelines between general practice sites. MEASURES: Resource use was obtained from electronic health records, trial staff and participants, and valued using UK reference costs. Quality-adjusted life-years (QALYs) were calculated from the EQ-5D-5L questionnaire. Adjusted mean differences in costs and QALYs and incremental net monetary benefit were estimated. RESULTS: 866 of 1077 (80.4%) participants had complete data and were included in the base-case analysis. Over the 12-month follow-up period, intervention and usual care arms had similar mean adjusted costs and QALYs. Mean differences were lower in the intervention arm for adjusted costs -£29.99 (95% CI -£109.84 to £22.63) while higher in the intervention arm for adjusted QALYs 0.001 (95% CI -0.011 to 0.014). The incremental net monetary benefit statistic was £48.01 (95% CI -£225.83 to £321.85) at the National Institute for Health and Care Excellence UK threshold of £20 000 per QALY. The cost-effectiveness acceptability curve showed a 63% probability of the intervention arm being cost-effective at this threshold. CONCLUSIONS: Costs and QALYs were similar between the two arms at 12 months follow-up. This indicates that the intervention can be implemented in general practice at neutral cost. TRIAL REGISTRATION NUMBER: ISRCTN11669964.