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 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).

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.

Validating the use of Hospital Episode Statistics data and comparison of costing methodologies for economic evaluation: an end-of-life case study from the Cluster randomised triAl of PSA testing for Prostate cancer (CAP).

OBJECTIVES: To evaluate the accuracy of routine data for costing inpatient resource use in a large clinical trial and to investigate costing methodologies. DESIGN: Final-year inpatient cost profiles were derived using (1) data extracted from medical records mapped to the National Health Service (NHS) reference costs via service codes and (2) Hospital Episode Statistics (HES) data using NHS reference costs. Trust finance departments were consulted to obtain costs for comparison purposes. SETTING: 7 UK secondary care centres. POPULATION: A subsample of 292 men identified as having died at least a year after being diagnosed with prostate cancer in Cluster randomised triAl of PSA testing for Prostate cancer (CAP), a long-running trial to evaluate the effectiveness and cost-effectiveness of prostate-specific antigen (PSA) testing. RESULTS: Both inpatient cost profiles showed a rise in costs in the months leading up to death, and were broadly similar. The difference in mean inpatient costs was £899, with HES data yielding ∼8% lower costs than medical record data (differences compatible with chance, p=0.3). Events were missing from both data sets. 11 men (3.8%) had events identified in HES that were all missing from medical record review, while 7 men (2.4%) had events identified in medical record review that were all missing from HES. The response from finance departments to requests for cost data was poor: only 3 of 7 departments returned adequate data sets within 6 months. CONCLUSIONS: Using HES routine data coupled with NHS reference costs resulted in mean annual inpatient costs that were very similar to those derived via medical record review; therefore, routinely available data can be used as the primary method of costing resource use in large clinical trials. Neither HES nor medical record review represent gold standards of data collection. Requesting cost data from finance departments is impractical for large clinical trials. TRIAL REGISTRATION NUMBER: ISRCTN92187251; Pre-results.

Validation of the Hospital Episode Statistics Outpatient Dataset in England.

OBJECTIVES: The Hospital Episode Statistics (HES) dataset is a source of administrative 'big data' with potential for costing purposes in economic evaluations alongside clinical trials. This study assesses the validity of coverage in the HES outpatient dataset. METHODS: Men who died of, or with, prostate cancer were selected from a prostate-cancer screening trial (CAP, Cluster randomised triAl of PSA testing for Prostate cancer). Details of visits that took place after 1/4/2003 to hospital outpatient departments for conditions related to prostate cancer were extracted from medical records (MR); these appointments were sought in the HES outpatient dataset based on date. The matching procedure was repeated for periods before and after 1/4/2008, when the HES outpatient dataset was accredited as a national statistic. RESULTS: 4922 outpatient appointments were extracted from MR for 370 men. 4088 appointments recorded in MR were identified in the HES outpatient dataset (83.1%; 95% confidence interval [CI] 82.0-84.1). For appointments occurring prior to 1/4/2008, 2195/2755 (79.7%; 95% CI 78.2-81.2) matches were observed, while 1893/2167 (87.4%; 95% CI 86.0-88.9) appointments occurring after 1/4/2008 were identified (p for difference <0.001). 215/370 men (58.1%) had at least one appointment in the MR review that was unmatched in HES, 155 men (41.9%) had all their appointments identified, and 20 men (5.4%) had no appointments identified in HES. CONCLUSIONS: The HES outpatient dataset appears reasonably valid for research, particularly following accreditation. The dataset may be a suitable alternative to collecting MR data from hospital notes within a trial, although caution should be exercised with data collected prior to accreditation.