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.

Thulium laser transurethral vaporesection versus transurethral resection of the prostate for benign prostatic obstruction: the UNBLOCS RCT.

BACKGROUND: Transurethral resection of the prostate (TURP) is the standard operation for benign prostatic obstruction (BPO). Thulium laser transurethral vaporesection of the prostate (ThuVARP) vaporises and resects the prostate using a technique similar to TURP. The small amount of existing literature suggests that there may be potential advantages of ThuVARP over TURP. OBJECTIVE: To determine whether or not the outcomes from ThuVARP are equivalent to the outcomes from TURP in men with BPO treated in the NHS. DESIGN: A multicentre, pragmatic, randomised controlled parallel-group trial, with an embedded qualitative study and economic evaluation. SETTING: Seven UK centres - four university teaching hospitals and three district general hospitals. PARTICIPANTS: Men aged ≥ 18 years who were suitable to undergo TURP, presenting with bothersome lower urinary tract symptoms (LUTS) or urinary retention secondary to BPO. INTERVENTIONS: Patients were randomised 1 : 1 to receive TURP or ThuVARP and remained blinded. MAIN OUTCOME MEASURES: Two co-primary outcomes - patient-reported International Prostate Symptom Score (IPSS) and clinical measure of maximum urine flow rate (Qmax) at 12 months post surgery. RESULTS: In total, 410 men were randomised, 205 to each arm. The two procedures were equivalent in terms of IPSS [adjusted mean difference 0.28 points higher for ThuVARP (favouring TURP), 95% confidence interval (CI) -0.92 to 1.49 points]. The two procedures were not equivalent in terms of Qmax (adjusted mean difference 3.12 ml/second in favour of TURP, 95% CI 0.45 to 5.79 ml/second), with TURP deemed superior. Surgical outcomes, such as complications and blood transfusion rates, and hospital stay were similar for both procedures. Patient-reported urinary and sexual symptoms were also similar between the arms. Qualitative interviews indicated similar patient experiences with both procedures. However, 25% of participants in the ThuVARP arm did not undergo their randomised allocation, compared with 2% of participants in the TURP arm. Prostate cancer was also detected less frequently from routine histology after ThuVARP (65% lower odds of detection) in an exploratory analysis. The adjusted mean differences between the arms were similar for secondary care NHS costs (£9 higher for ThuVARP, 95% CI -£359 to £376) and quality-adjusted life-years (0.01 favouring TURP, 95% CI -0.04 to 0.01). LIMITATIONS: Complications were recorded in prespecified categories; those not prespecified were excluded owing to variable reporting. Preoperative Qmax and IPSS data could not be collected for participants with indwelling catheters, making adjustment for baseline status difficult. CONCLUSIONS: TURP was superior to ThuVARP in terms of Qmax, although both operations resulted in a Qmax considered clinically successful. ThuVARP also potentially resulted in lower detection rates of prostate cancer as a result of the smaller volume of tissue available for histology. Length of hospital stay after ThuVARP, anticipated to be a key benefit, was equal to that after TURP in this trial. Overall, both ThuVARP and TURP were effective procedures for BPO, with minor benefits in favour of TURP. Therefore, the results suggest that it may be appropriate that new treatment alternatives continue to be compared with TURP. FUTURE WORK: Longer-term follow-up to assess reoperation rates over time, and research into the comparative effectiveness of ThuVARP and TURP in large prostates. TRIAL REGISTRATION: Current Controlled Trials ISRCTN00788389. 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. 24, No. 41. See the NIHR Journals Library website for further project information.

An enlarged prostate can make it difficult, or even impossible, for a man to pass urine by blocking the urine flow from the bladder. This can cause significant problems, and 25,000 men in the UK each year are treated with an operation to relieve their symptoms. The standard operation [transurethral resection of the prostate (TURP)], which uses electricity to shave off the enlarged prostate, is successful, but it can have some complications. There is some evidence to suggest that laser surgery can lead to less blood loss and a shorter stay in hospital, but laser operations can be difficult for surgeons to carry out. This trial has looked at a procedure using a new type of laser called thulium, which uses a very similar surgical technique to TURP and has shown promising results so far. A total of 410 men needing a prostate operation received either TURP or a laser operation. Participants were unaware of which operation they received until the end of the study to ensure a fair comparison. Seven hospitals across the UK were involved over 4 years. The trial mainly assessed the benefits of the operations using a urinary symptom questionnaire completed by participants, and by measuring the speed of passing urine after surgery. Overall, both procedures achieved positive results, and participants expressed high levels of satisfaction with the outcomes. Participants who had either operation reported a similar improvement in urinary symptoms in their questionnaires. However, although both operations did a good job of improving the speed of passing urine, TURP was better. Participants experienced few complications, and the complications that did occur were similar after both operations, including levels of bleeding and time spent in hospital. The cost of the two operations to the NHS was also similar. Overall, we concluded that both operations are suitable for patients with prostate enlargement, with TURP showing some minor additional benefits.

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.

Understanding usual care for patients with multimorbidity: baseline data from a cluster-randomised trial of the 3D intervention in primary care.

OBJECTIVES: Recent evidence has highlighted the high prevalence and impact of multimorbidity, but the evidence base for improving management is limited. We have tested a new complex intervention for multimorbidity (the 3D model). The paper describes the baseline characteristics of practices and patients in order to establish the external validity of trial participants. It also explores current 'usual primary care' for multimorbidity, against which the 3D intervention was tested. DESIGN: Analysis of baseline data from patients in a cluster-randomised controlled trial and additional data from practice staff. SETTING: Primary care in the UK. PARTICIPANTS: Patients with multimorbidity (n=5253) and 154 practice staff. PRIMARY AND SECONDARY OUTCOME MEASURES: Using surveys and routinely available data, we compared the characteristics of participating and non-participating practices and participating and non-participating eligible patients.Baseline questionnaire data from patient participants was used to examine participant illness burden, treatment burden and perceptions of receiving patient-centred care. We obtained data about usual care preintervention from practice staff using questionnaires and a structured pro forma. RESULTS: Participating practices were slightly larger, in less deprived areas, and with slightly higher scores for patient satisfaction compared with non-participating practices. Patients with dementia or learning difficulties were likely to be excluded by their general practitioners, but comparison of participants with non-participants identified only minor differences in characteristics, suggesting that the sample was otherwise representative. Patients reported substantial illness burden, and an important minority reported high treatment burden. Although patients reported relatively high levels of satisfaction with care, many reported not having received potentially important components of care. CONCLUSION: This trial achieved good levels of external validity. Although patients were generally satisfied with primary care services, there was significant room for improvement in important aspects of care for multimorbidity that are targeted by the 3D intervention. TRIAL REGISTRATION NUMBER: ISRCTN06180958; Post-results.

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.

A randomised controlled trial to determine the clinical and cost effectiveness of thulium laser transurethral vaporesection of the prostate (ThuVARP) versus transurethral resection of the prostate (TURP) in the National Health Service (NHS) - the UNBLOCS trial: a study protocol for a randomised controlled trial.

BACKGROUND: Transurethral resection of the prostate (TURP) has been the standard operation for benign prostatic obstruction (BPO) for 40 years, with approximately 25,000 procedures performed annually, and has remained largely unchanged. It is generally a successful operation, but has well-documented risks for the patient. Thulium laser transurethral vaporesection of the prostate (ThuVARP) vaporises and resects the prostate using a surgical technique similar to TURP. The small amount of study data currently available suggests that ThuVARP may have certain advantages over TURP, including reduced blood loss and shorter hospital stay, earlier return to normal activities, and shorter duration of catheterisation. DESIGN: A multicentre, pragmatic, randomised, controlled, parallel-group trial of ThuVARP versus standard TURP in men with BPO. Four hundred and ten men suitable for prostate surgery were randomised to receive either ThuVARP or TURP at four university teaching hospitals, and three district general hospitals. The key aim of the trial is to determine whether ThuVARP is equivalent to TURP judged on both the patient-reported International Prostate Symptom Score (IPSS) and the maximum urine flow rate (Qmax) at 12 months post-surgery. DISCUSSION: The general population has an increased life expectancy. As men get older their prostates enlarge, potentially causing BPO, which often requires surgery. Therefore, as the population ages, more prostate operations are needed to relieve obstruction. There is hence sustained interest in the condition and increasing need to find safer techniques than TURP. Various laser techniques have become available but none are widely used in the NHS because of lengthy training required for surgeons or inferior performance on clinical outcomes. Promising initial evidence from one RCT shows that ThuVARP has equivalent clinical effectiveness when compared to TURP, as well as other potential advantages. As ThuVARP uses a technique similar to that used in TURP, the learning curve is short, potentially making it also very quickly generalisable. This randomised study is designed to provide the high-quality evidence, in an NHS setting, with a range of patient-reported, clinical and cost-effectiveness outcomes, which will underpin and inform future NICE guidance. TRIAL REGISTRATION: ISRCTN registry, ISRCTN00788389 . Registered on 20 September 2013.

Can oral corticosteroids reduce the severity or duration of an acute cough, and the associated National Health Service and societal costs, in adults presenting to primary care? Study protocol for a randomised controlled trial.

BACKGROUND: Acute lower respiratory tract infection (LRTI) is one of the most common conditions managed internationally and is costly to health services and patients. Despite good evidence that antibiotics are not effective for improving the symptoms of uncomplicated LRTI, they are widely prescribed, contributing to antimicrobial resistance. Many of the symptoms observed in LRTI are mediated by inflammatory processes also observed in exacerbations of asthma, for which there is strong evidence of corticosteroid effectiveness. The primary aim of the OSAC (Oral Steroids for Acute Cough) Trial is to determine whether oral prednisolone (40 mg daily for 5 days) can reduce the duration of moderately bad (or worse) cough and the severity of all its associated symptoms on days 2 to 4 post-randomisation (day 1 is trial entry) by at least 20% in adults ≥18 years with acute LRTI presenting to primary care. METHODS/DESIGN: OSAC is a two-arm, multi-centre, placebo-controlled, randomised superiority trial. The target sample size is 436 patients, which allows for a 20% dropout rate. Patients will be recruited from primary care sites (General Practitioner surgeries) across England and followed up until symptom resolution. The two primary clinical outcomes are the duration of moderately bad (or worse) cough, and the severity of all its associated symptoms on days 2 to 4 post-randomisation. Secondary outcomes include: antibiotic consumption; symptom burden; adverse events; participant satisfaction with treatment and intention to consult for future similar illnesses. A parallel economic evaluation will investigate the cost-effectiveness of the intervention. DISCUSSION: Results from the OSAC trial will increase knowledge regarding the clinical and cost-effectiveness of corticosteroids for LRTI, and will establish the potential of a new treatment option that could substantially improve patient health. We have chosen a relatively high 'efficacy dose' as this will enable us to decide on the potential for further research into lower dose oral and/or inhaled corticosteroids. This trial will also contribute to a growing body of research investigating the natural course of this very common illness, as well as the effects of steroids on the undesirable inflammatory symptoms associated with infection. TRIAL REGISTRATION: Current Controlled Trials ISRCTN57309858 (31 January 2013).

Developing core outcomes sets: methods for identifying and including patient-reported outcomes (PROs).

BACKGROUND: Synthesis of patient-reported outcome (PRO) data is hindered by the range of available PRO measures (PROMs) composed of multiple scales and single items with differing terminology and content. The use of core outcome sets, an agreed minimum set of outcomes to be measured and reported in all trials of a specific condition, may improve this issue but methods to select core PRO domains from the many available PROMs are lacking. This study examines existing PROMs and describes methods to identify health domains to inform the development of a core outcome set, illustrated with an example. METHODS: Systematic literature searches identified validated PROMs from studies evaluating radical treatment for oesophageal cancer. PROM scale/single item names were recorded verbatim and the frequency of similar names/scales documented. PROM contents (scale components/single items) were examined for conceptual meaning by an expert clinician and methodologist and categorised into health domains. A patient advocate independently checked this categorisation. RESULTS: Searches identified 21 generic and disease-specific PROMs containing 116 scales and 32 single items with 94 different verbatim names. Identical names for scales were repeatedly used (for example, 'physical function' in six different measures) and others were similar (overlapping face validity) although component items were not always comparable. Based on methodological, clinical and patient expertise, 606 individual items were categorised into 32 health domains. CONCLUSION: This study outlines a methodology for identifying candidate PRO domains from existing PROMs to inform a core outcome set to use in clinical trials.

A scored form of the Bristol Female Lower Urinary Tract Symptoms questionnaire: data from a randomized controlled trial of surgery for women with stress incontinence.

OBJECTIVE: Lower urinary tract symptoms are common among older women. The Bristol Female Lower Urinary Tract Symptoms (BFLUTS) questionnaire was designed to assess a wide range of symptoms, including incontinence, and impact on sexual function and quality of life. This paper describes development and validation of a scored form BFLUTS questionnaire. STUDY DESIGN: Baseline and 6-month follow-up data from a randomized trial compared tension-free vaginal tape with colposuspension for 344 women with urodynamically proven stress incontinence. Problematic and responsive items were identified and subjected to factor analysis to develop a scoring system. RESULTS: Three domains were identified to assess symptoms: incontinence (5 items); voiding (3 items); and filling (4 items); with additional subscales for sexual function (2 items) and quality of life (5 items). All scales have simple additive scores. CONCLUSION: A scored form of the BFLUTS questionnaire is now available and should be useful in research and clinical practice in urology and gynecology.