Views, obstacles, and uncertainties around the inclusion of children and young people's time in economic evaluations: Findings from an international survey of health economists.

People's time is a limited resource and, in economic evaluations that adopt a societal perspective, it is important that it is valued and accounted for. Yet, in economic evaluations of interventions for children and young people (CYP), attempts to take into account the opportunity cost of their time are rare. To understand why this is the case, we need to first understand what views health economists hold in relation to CYP time, and what challenges they face in incorporating this in their evaluations. We planned and carried out an international survey of health economists. We used a combination of approaches to identify potential survey respondents (the survey's sampling frame), we developed a questionnaire that sought to capture respondents' views and practice through close- and open-ended questions, we piloted the questionnaire through a series of cognitive interviews, and we e-mailed unique links to the final version of the questionnaire to 1956 individuals in the sampling frame. We analysed data using quantitative (descriptive and inferential statistics) and qualitative (thematic analysis) methods. We received 274 complete responses. Most respondents (87%) believe CYP time should be considered for inclusion in economic evaluations conducted from a societal perspective. However, they identify a number of obstacles to doing so, most prominently uncertainties around appropriate practice (e.g., when CYP's time should or should not be included in calculations), methodological gaps (e.g., what value to attach to CYP's time), and practical difficulties in measuring displaced time in CYP. Reporting on their own practice, most respondents found it challenging to consider CYP time in their studies, and stressed the need for clear guidance on when, and further research on how, to appropriately account for CYP's time in economic evaluations. We offer our views on how to move the topic forwards and make suggestions further research.

Impact of updated trial data on the cost-effectiveness of percutaneous mitral repair.

When updated clinical trial data becomes available reassessing the cost-effectiveness of technologies may modify estimates and influence decision-making. We investigated the impact of updated trial outcomes on the cost-effectiveness of percutaneous mitral repair (PR) for secondary mitral regurgitation. We updated our previous three-state time-varying Markov model to assess the cost-effectiveness of PR + guideline directed medical treatment (GDMT) versus GDMT alone. Key clinical inputs (overall survival (OS) and heart failure hospitalisations (HFH)) were obtained using the 3-year trial findings from the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy) RCT. We calculated incremental cost-effectiveness ratios (ICER) and report how these differ between analyses based on early (2-year) and updated (3-year) evidence. Updated trial data showed an increase in mortality in the intervention arm between two and three years follow-up that was not seen in the control arm. Deterministic and multivariate cost-effectiveness modelling yielded incremental cost effectiveness ratios ICERs of €38,123 and €31,227 /QALY. Compared to our 2-year based estimate (€21,918 / QALY) these results imply an approximate 1.5-fold increase in ICER. The availability of updated survival analyses from the COAPT pivotal trial suggests previous estimates based on 2-year trial findings were over optimistic for the intervention.

REducing Colonoscopies in patients without significant bowEl DiseasE: the RECEDE Study - protocol for a prospective diagnostic accuracy study.

INTRODUCTION: Demand for colonoscopies and CT colonography (CTC) is exceeding capacity in National Health Service Trusts. In many patients colonoscopies and CTCs show no significant bowel disease (SBD). Faecal Immunochemical Testing (FIT) is being introduced to prioritise patients for colonoscopies but is insufficient to identify non-SBD patients meaning colonoscopy and CTC demand remains high. The REducing Colonoscopies in patients without significant bowEl DiseasE (RECEDE) study aims to test urine volatile organic compound (VOC) analysis alongside FIT to improve detection of SBD and to reduce the number of colonoscopies and CTCs. METHODS AND ANALYSIS: This is a multicentre, prospective diagnostic accuracy study evaluating whether stool FIT plus urine VOC compared with stool FIT alone improves detection of SBD in patients referred for colonoscopy or CTC due to persistent lower gastrointestinal symptoms. To ensure SBD is not missed, the dual test requires a high sensitivity, set at 97% with 95% CI width of 5%. Our assumption is that to achieve this sensitivity requires 200 participants with SBD. Further assuming 19% of all participants will have SBD and 55% of all participants will return both stool and urine samples we will recruit 1915 participants. The thresholds for FIT and VOC results diagnosing SBD have been pre-set. If either FIT or VOC exceeds the respective threshold, the participant will be classed as having suspected SBD. As an exploratory analysis we will be testing different thresholds. The reference comparator will be a complete colonoscopy or CTC. Secondary outcomes will look at optimising the FIT and VOC thresholds for SBD detection. An economic evaluation, using a denovo decision analytic model, will be carried out determine the costs, benefits and overall cost-effectiveness of FIT +VOC vs FIT followed by colonoscopy. ETHICS AND DISSEMINATION: Ethical approval was obtained by Liverpool Central Research Ethics Committee (20/NW/0346). TRIAL REGISTRATION NUMBER: RECEDE is registered on Clinicaltrials.gov NCT04516785 & ISRCTN14982373. This protocol was written and published before results of the trial were available.

Procedural and 12-month in-hospital costs of primary infra-popliteal bypass surgery, infrapopliteal best endovascular treatment, and major lower limb amputation for chronic limb threatening ischemia.

OBJECTIVE: Chronic limb-threatening ischemia (CLTI) is a growing global problem due to the widespread use of tobacco and increasing prevalence of diabetes. Although the financial consequences are considerable, few studies have compared the relative cost-effectiveness of different CLTI management strategies. The Bypass vs Angioplasty in Severe Ischaemia of the Leg (BASIL)-2 trial is randomizing patients with CLTI to primary infrapopliteal (IP) vein bypass surgery (BS) or best endovascular treatment (BET) and includes a comprehensive within-trial cost-utility analysis. The aim of this study is to compare over a 12-month time horizon, the costs of primary IP BS, IP best endovascular treatment (BET), and major limb major amputation (MLLA) to inform the BASIL-2 cost-utility analysis. METHODS: We compared procedural human resource (HR) costs and total in-hospital costs for the index admission, and over the following 12-months, in 60 consecutive patients undergoing primary IP BS (n = 20), IP BET (n = 20), or MLLA (10 transfemoral and 10 transtibial) for CLTI within the BASIL prospective cohort study. RESULTS: Procedural HR costs were greatest for BS (BS £2551; 95% confidence interval [CI], £1934-£2807 vs MLLA £1130; 95% CI, £1046-£1297 vs BET £329; 95% CI, £242-£390; P < .001, Kruskal-Wallis) due to longer procedure duration and greater staff requirement. With regard to the index admission, MLLA was the most expensive due to longer hospital stay (MLLA £13,320; 95% CI, £8986-£18,616 vs BS £8714; 95% CI, £6097-£11,973 vs BET £4813; 95% CI, £3529-£6097; P < .001, Kruskal-Wallis). The total cost of the index admission and in-hospital care over the following 12 months remained least for BET (MLLA £26,327; 95% CI, £17,653-£30,458 vs BS £20,401; 95% CI, £12,071-£23,926 vs BET £12,298; 95% CI, £6961-£15,439; P < .001, Kruskal-Wallis). CONCLUSIONS: Over a 12-month time horizon, MLLA and IP BS are more expensive than IP BET in terms of procedural HR costs and total in-hospital costs. These economic data, together with quality of life data from BASIL-2, will inform the calculation of incremental cost-effectiveness ratios for different CLTI management strategies within the BASIL-2 cost-utility analysis.

Economic costs at age five associated with very preterm birth: multinational European cohort study.

BACKGROUND: This study aims to estimate the economic costs of care provided to children born very preterm and extremely preterm across 11 European countries, and to understand what perinatal and socioeconomic factors contribute to higher costs. METHODS: Generalised linear modelling was used to explore the association between perinatal and sociodemographic characteristics and total economic costs (€, 2016 prices) during the fifth year of life. RESULTS: Lower gestational age was associated with increased mean societal costs of €2755 (p < 0.001), €752 (p < 0.01) and €657 (p < 0.01) for children born at < 26, 26-27 and 28-29 weeks, respectively, in comparison to the reference group born at 30-31 weeks. A sensitivity analyses that excluded variables (BPD, any neonatal morbidity and presence of congenital anomaly) plausibly lying on the causal pathway between gestational age at birth and economic outcomes elevated incremental societal costs by €1482, €763 and €144 at < 26, 26-27 and 28-29 weeks, respectively, in comparison to the baseline model. CONCLUSION: This study provides new evidence about the main cost drivers associated with preterm birth in European countries. Evidence identified by this study can act as inputs within cost-effectiveness models for preventive or treatment interventions for preterm birth. IMPACT: What is the key message of your article? This study provides new evidence about the magnitude and drivers of economic costs associated with preterm birth in European countries. What does it add to the existing literature? Lower gestational age is associated with increased mean societal costs during mid-childhood with indirect costs representing a key driver of increased costs. What is the impact? For policy makers, this study adds to sparse evidence about the main cost drivers associated with preterm birth in European countries beyond the first 2 years of life.

High Healthcare Use at Age 5 Years in a European Cohort of Children Born Very Preterm.

OBJECTIVES: To describe parent-reported healthcare service use at age 5 years in children born very preterm and investigate whether perinatal and social factors and the use of very preterm follow-up services are associated with high service use. STUDY DESIGN: We used data from an area-based cohort of births at <32 weeks of gestation from 11 European countries, collected from birth records and parental questionnaires at 5 years of age. Using the published literature, we defined high use of outpatient/inpatient care (≥4 sick visits to general practitioners, pediatricians, or nurses, ≥3 emergency room visits, or ≥1 overnight hospitalization) and specialist care (≥2 different specialists or ≥3 visits). We also categorized countries as having either a high or a low rate of children using very preterm follow-up services at age 5 years. RESULTS: Overall, 43% of children had high outpatient/inpatient care use and 48% had high specialist care use during the previous year. Perinatal factors were associated with high outpatient/inpatient and specialist care use, with a more significant association with specialist services. Associations with intermediate parental educational level and unemployment were stronger for outpatient/inpatient services. Living in a country with higher rates of very preterm follow-up service use was associated with lower use of outpatient/inpatient services. CONCLUSIONS: Children born very preterm had high healthcare service use at age 5 years, with different patterns for outpatient/inpatient and specialist care by perinatal and social factors. Longer follow-up of children born very preterm may improve care coordination and help avoid undesirable health service use.

Will the US$5 million onasemnogene abeparvosec treatment for spinal muscular atrophy represent 'value for money' for the NHS? A rapid inquiry into suggestions that it may be cost-effective.

OBJECTIVES: Nusinersen (Spinraza®, Biogen) and onasemnogene abeparvosec (Zolgensma®, Novartis) are novel gene-based therapies for the orphan disease Spinal Muscular Atrophy. Onasemnogene abeparvosec has been allocated an acquisition cost of up to US$5 million per patient. We undertook a rapid inquiry to evaluate if onasemnogene abeparvosec is likely to be cost-effective for the UK NHS. METHODS: We used publicly available cost-effectiveness data and recommended methodology to perform cost-utility evaluation of onasemnogene abeparvosec versus best supportive care and nusinersen. RESULTS: Our evaluations highlight wide variations in cost and benefit estimates of nusinersen and indicate that onasemnogene abeparvosec is unlikely to represent value for money according to current standards of reimbursement. Results are discussed in the context of reimbursement decisions for orphan diseases. CONCLUSION: Commonly implemented commercial confidentiality practices combined with uncertain data obscure scrutiny and justification of past and present reimbursement decisions for orphan drugs. Future cutting edge expensive therapies will be numerous, they will entail very substantial economic strains. We conclude that there is an urgent and increasing need for the development of improved procedures that can lead to equitable, consistent, and transparent decision-making.

Measuring, valuing and including forgone childhood education and leisure time costs in economic evaluation: Methods, challenges and the way forward.

Economic evaluations carried out to inform the allocation of finite public funds ought to take into account all relevant costs and benefits. When such evaluations adopt a societal perspective, it is important that they include 'time-related' costs arising from productivity and leisure time losses due to receipt of care, ill health or both. For programmes that relate to children, similar costs arise from forgone time, though there is a distinct lack of insights into how such costs should be identified, measured and valued. We set out to explore how forgone time-including absence from formal education and childhood leisure time-can be estimated and incorporated into economic evaluations. To do so, we look at theories and approaches to time valuation proposed in different disciplines and we discuss their suitability for use in health economics research. We find that, while there is a sizeable literature on time valuation methods in education, labour and transportation economics, much of this is not directly applicable to economic evaluation of health care interventions for children. We identify gaps in existing methods and practice, we outline challenges in moving forwards and we provide a list of considerations aiming to assist researchers in deciding whether, and how, to include foregone time-related costs in economic evaluation.

Are acceptance and mindfulness-based interventions 'value for money'? Evidence from a systematic literature review.

OBJECTIVES: Acceptance and mindfulness-based interventions (A/MBIs) are recommended for people with mental health conditions. Although there is a growing evidence base supporting the effectiveness of different A/MBIs for mental health conditions, the economic case for these interventions has not been fully explored. The aim of this systematic review was to identify and appraise all available economic evidence of A/MBIs for the management of mental health conditions. METHODS: Eight electronic bibliographic databases (MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Web of Science, NHS Economic Evaluation Database (EED), Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment (HTA) database, and EconLit) were searched for relevant economic evaluations published from each database's inception date until November 2017. Study selection, quality assessment, and data extraction were carried out according to published guidelines. RESULTS: Ten relevant economic evaluations presented in 11 papers were identified. Seven of the included studies were full economic evaluations (i.e., costs and effects assessed), and three studies were partial economic evaluations (i.e., only costs were considered in the analysis). The A/MBIs that had been subjected to economic evaluation were acceptance and commitment therapy (ACT), dialectical behaviour therapy (DBT), mindfulness-based cognitive therapy (MBCT), and mindfulness-based stress reduction (MBSR). In terms of clinical presentations, the evaluation of cost-effectiveness of A/MBIs has been more focused on depression and emotional unstable personality disorder with three and four economic evaluations, respectively. Three out of seven full economic evaluations observed that A/MBIs were cost-effective for the management of mental health conditions. Nevertheless, the heterogeneity of included populations, interventions, and economic evaluation study types limits the extent to which firm conclusions can currently be made. CONCLUSION: This first substantive review of economic evaluations of A/MBIs indicates that more research is needed before firm conclusions can be reached on the cost-effectiveness of A/MBIs for mental health conditions. PRACTITIONER POINTS: The findings of the review provide information that may be relevant to mental health service commissioners and decision-makers as all economic evidence available on acceptance and mindfulness-based interventions for mental health conditions is summarized. Evidence relating to the cost-effectiveness and cost-saving potential of acceptance and mindfulness-based interventions is focused mainly on depression and emotional unstable personality disorder to date. Heterogeneity in the specific forms of acceptance and mindfulness-based interventions may limit generalizability of the findings. The number of health economic evaluations relating to acceptance and mindfulness-based interventions remains relatively small. Further research in this area is required.

Is the Venner-PneuX Endotracheal Tube System a Cost-Effective Option for Post Cardiac Surgery Care?

BACKGROUND: Ventilator-associated pneumonia (VAP) is common and costly. In a recent randomized controlled trial, the Venner-PneuX (VPX) endotracheal tube system (Qualitech Healthcare Limited, Maidenhead, United Kingdom) was found to be superior to standard endotracheal tubes (SET) in preventing VAP. However, VPX is considerably more expensive. We evaluated the costs and benefits of VPX to determine whether replacing SET with VPX is a cost-effective option for intensive care units. METHODS: We developed a decision analytic model to compare intubation with VPX or SET for patients requiring mechanical ventilation after cardiac operations. The model was populated with existing evidence on costs, effectiveness, and quality of life. Cost-effectiveness and cost-utility analyses were conducted from a National Health Service hospital perspective. Uncertainty was assessed through deterministic and probabilistic sensitivity analyses. RESULTS: Compared with SET, VPX is associated with an expected cost saving of £738 per patient. VPX led to a small increase in quality-adjusted life years, indicating that the device is overall less costly and more effective than SET. The probability of VPX being cost-effective at £30,000 per quality-adjusted life year is 97%. VPX would cease to be cost-effective if (1) it led to a risk reduction smaller than 0.02 compared with SET, (2) the acquisition cost of VPX was as high as £890, or (3) the cost of treating a case of VAP was lower than £1,450. CONCLUSIONS: VPX resulted in improved outcomes and savings that far offset the cost of the device, suggesting that replacing SET with VPX is overall beneficial. Findings were robust to extreme values of key variables.

Cost of treating ventilator-associated pneumonia post cardiac surgery in the National Health Service: Results from a propensity-matched cohort study.

BACKGROUND: Ventilator-associated pneumonia is associated with significant morbidity, mortality and healthcare costs. Most of the cost data that are available relate to general intensive care patients in privately remunerated institutions. This study assessed the cost of managing ventilator-associated pneumonia in a cardiac intensive care unit in the National Health Service in the United Kingdom. METHODS: Propensity-matched study of prospectively collected data from the cardiac surgical database between April 2011 and December 2014 in all patients undergoing cardiac surgery (n = 3416). Patients who were diagnosed as developing ventilator-associated pneumonia, as per the surveillance definition for ventilator-associated pneumonia (n = 338), were propensity score matched with those who did not (n = 338). Costs of treating post-op cardiac surgery patients in intensive care and cost difference if ventilator-associated pneumonia occurred based on Healthcare Resource Group categories were assessed. Secondary outcomes included differences in morbidity, mortality and cardiac intensive care unit and in-hospital length of stay. RESULTS: There were no significant differences in the pre-operative characteristics or procedures between the groups. Ventilator-associated pneumonia developed in 10% of post-cardiac surgery patients. Post-operatively, the ventilator-associated pneumonia group required longer ventilation (p < 0.01), more respiratory support, longer cardiac intensive care unit (8 vs 3, p < 0.001) and in-hospital stay (16 vs 9) days. The overall cost for post-operative recovery after cardiac surgery for ventilator-associated pneumonia patients was £15,124 compared to £6295 for non-ventilator-associated pneumonia (p < 0.01). The additional cost of treating patients with ventilator-associated pneumonia was £8829. CONCLUSION: Ventilator-associated pneumonia was associated with significant morbidity to the patients, generating significant costs. This cost was nearer to the lower end for the cost for general intensive care unit patients in privately reimbursed systems.

Intrathecal Drug Delivery Systems for the Management of Chronic Noncancer Pain: A Systematic Review of Economic Evaluations.

BACKGROUND: Intrathecal drug delivery (ITDD) systems are one of a limited number of management options for chronic noncancer pain, cancer pain, and spasticity. Concerns over their effectiveness and high initial costs led National Health Service (NHS) England to decommission ITDD for patients with chronic noncancer pain. However, the extent to which this decision is in line with existing economic evidence is unclear. The aim of this systematic review was to identify and review the existing evidence on the cost effectiveness of ITDD for chronic noncancer pain. METHODS: Full and partial economic evaluations on ITDD were identified through systematic searches in MEDLINE, Embase, Web of Science, and the NHS for Reviews and Dissemination databases. Database searches were complemented by hand searching of reference lists of relevant studies and searches of grey literature. Study selection was carried out by 2 assessors, independently. Study quality assessment was performed to inform critical appraisal of health economics studies. Data were extracted using a data extraction form developed for the purposes of this study. RESULTS: Four thousand four hundred and sixty-four unique studies were identified, of which 7 met the inclusion criteria. With the exception of 1 study, the studies found ITDD to be either cost saving or cost effective compared to conventional medical management. ITDD became cost ineffective in 1 further study following price year adjustment to 2016. CONCLUSIONS: Study findings showed ITDD to be not cost effective only in extremely conservative scenarios. There is limited evidence on the effectiveness of ITDD in noncancer pain; however, the available economic evidence controverts arguments to refute the treatment on economic grounds.

Cost-Effectiveness of Treatments for the Management of Bone Metastases: A Systematic Literature Review.

BACKGROUND: Metastatic cancers occur when cancer cells break away from the primary tumour. One of the most common sites of metastasis is the bone, with several therapeutic options currently available for managing bone metastases. In a resource-constrained environment, policy makers and practitioners need to know which options are cost effective. OBJECTIVE: The aim of this systematic review was to review and appraise published economic evaluations on treatments for the management of bone metastases. METHODS: We searched eight bibliographic databases (MEDLINE, MEDLINE in Process, EMBASE, CSDR, DARE, HTA, EED and CPCI) for relevant economic evaluations published from each database's inception date until March 2017. Study selection, quality assessment and data extraction were carried out according to published guidelines. RESULTS: Twenty-four relevant economic analyses were identified. Seventeen of these studies focused on bone metastases resulting from a particular type of cancer, i.e. prostate (n = 8), breast (n = 7), lung (n = 1) or renal (n = 1), while seven report results for various primary tumours. Across types of cancer, evidence suggests that bisphosphonates result in lower morbidity and improved quality of life, for an additional cost, which is typically below conventional cost-effectiveness thresholds. While denosumab leads to health gains compared with zoledronic acid, it also results in substantial additional costs and is unlikely to represent value for money. The limited literature on the radiopharmaceutical strontium-89 (Sr89) and external beam radiotherapy (EBR) suggest that these treatments are cost effective compared with no treatment. CONCLUSIONS: The reviewed evidence suggests that bisphosphonate treatments are cost-effective options for bone metastases, while denosumab is unlikely to represent value for money. Evidence on EBR and Sr89 is limited and less conclusive.

A mixed-methods feasibility and external pilot study to inform a large pragmatic randomised controlled trial of the effects of surgical wound dressing strategies on surgical site infections (Bluebelle Phase B): study protocol for a randomised controlled trial.

BACKGROUND: Surgical site infections (SSIs) are common, occurring in up to 25% of > 4 million operations performed in England each year. Previous trials of the effect of wound dressings on the risk of developing a SSI are of poor quality and underpowered. METHODS/DESIGN: This study is a feasibility and pilot trial to examine the feasibility of a full trial that will compare simple dressings, no dressing and tissue-glue as a dressing. It is examining the overall acceptability of trial participation, identifying opportunities for refinement, testing the feasibility of and validating new outcome tools to assess SSI, wound management issues and patients' wound symptom experiences. It is also exploring methods for avoiding performance bias and blinding outcome assessors by testing the feasibility of collecting wound photographs taken in theatre immediately after wound closure and, at 4-8 weeks after surgery, taken by participants themselves or their carers. Finally, it is identifying the main cost drivers for an economic evaluation of dressing types. Integrated qualitative research is exploring acceptability and reasons for non-adherence to allocation. Adults undergoing primary elective or unplanned abdominal general surgery or Caesarean section are eligible. The main exclusion criteria are abdominal or other major surgery less than three months before the index operation or contraindication to dressing allocation. The trial is scheduled to recruit for nine months. The findings will be used to inform the design of a main trial. DISCUSSION: This pilot trial is the first pragmatic study to randomise participants to no dressing or tissue-glue as a dressing versus a simple dressing. Early evidence from the ongoing pilot shows that recruitment is proceeding well and that the interventions are acceptable to participants. Combined with the qualitative findings, the findings will inform whether a main, large trial is feasible and, if so, how it should be designed. TRIAL REGISTRATION: ISRCTN49328913 . Registered on 20 October 2015.

BAlloon versus Stenting in severe Ischaemia of the Leg-3 (BASIL-3): study protocol for a randomised controlled trial.

BACKGROUND: Severe limb ischaemia (SLI) is defined as the presence of rest pain and/or tissue loss secondary to lower extremity atherosclerotic peripheral arterial disease. The superficial femoral and popliteal arteries are the most commonly diseased vessels in such patients and are being increasingly treated using endovascular revascularisation techniques. However, it is currently unknown whether drug-eluting stents and drug-coated balloons confer additional clinical benefits over more established techniques using plain balloons and bare metal stents, or whether they represent a cost-effective use of NHS resources. METHODS: The BASIL-3 trial is a UK National Institute for Health Research, Health Technology Assessment Programme-funded, multicentre, randomised controlled trial (RCT) comparing the clinical and cost-effectiveness of plain balloon angioplasty with or without bail-out bare metal stenting, drug-coated balloon angioplasty with or without bail-out bare metal stenting, and primary stenting with drug-eluting stents for SLI secondary to femoro-popliteal disease. Patients with 'multilevel' disease may receive aorto-iliac and/or infrapopliteal treatments concurrently with their randomised femoro-popliteal intervention. The primary clinical outcome is amputation-free survival defined as the time to major (above the ankle) amputation of the index limb or death from any cause. The primary outcome for the economic analysis is cost per quality-adjusted life year. Secondary outcome measures include overall survival, major adverse limb events, major adverse cardiac events, relief of ischaemic pain, healing of tissue loss, and quality of life. The required sample size has been calculated at 861 participants (287 on each arm). These patients will be recruited over 3 years and followed-up for between 2 and 5 years. DISCUSSION: BASIL-3 is a pragmatic RCT designed to reflect current UK clinical practice. The results will inform decision-making regarding the appropriateness of funding the use of drug-coated balloons and drug-eluting stents, by the NHS, for the management of SLI due to femoro-popliteal disease. TRIAL REGISTRATION: ISRCTN Registry, identifier: ISRCTN14469736 . Registered on 22 October 2015.

Rationale and design of BISTRO: a randomized controlled trial to determine whether bioimpedance spectroscopy-guided fluid management maintains residual kidney function in incident haemodialysis patients.

BACKGROUND: Preserved residual kidney function (RKF) and normal fluid status are associated with better patient outcomes in incident haemodialysis patients. The objective of this trial is to determine whether using bioimpedance technology in prescribing the optimal post-dialysis weight can reduce the rate of decline of RKF and potentially improve patient outcomes. METHODS/DESIGN: 516 pateints commencing haemodialysis, aged >18 with RKF of > 3 ml/min/1.73 m2 or a urine volume >500 ml per day or per the shorter inter-dialytic period will be consented and enrolled into a pragmatic, open-label, randomized controlled trial. The intervention is incorporation of bioimpedance spectroscopy (BI) determination of normally hydrated weight to set a post-dialysis target weight that limits volume depletion, compared to current standard practice. Clinicians and participants will be blinded to BI measures in the control group and a standardized record capturing management of fluid status will be used in all participants. Primary outcome is preservation of residual kidney function assessed as time to anuria (≤100 ml/day or ≤200 ml urine volume in the short inter-dialytic period). A sample size of 516 was based upon a cumulative incidence of 30% anuria in the control group and 20% in the treatment group and 11% competing risks (death, transplantation) over 10 months, with up to 2 years follow-up. Secondary outcomes include rate of decline in small solute clearance, significant adverse events, hospitalization, loss of vascular access, cardiovascular events and interventions, dialysis efficacy and safety, dialysis-related symptoms and quality of life. Economic evaluation will be carried out to determine the cost-effectiveness of the intervention. Analyses will be adjusted for patient characteristics and dialysis unit practice patterns relevant to fluid management. DISCUSSION: This trial will establish the added value of undertaking BI measures to support clinical management of fluid status and establish the relationship between fluid status and preservation of residual kidney function in incident haemodialysis patients. TRIAL REGISTRATION: ISCCTN Number: 11342007 , completed 26/04/2016; NIHR Portfolio number: CPMS31766; Sponsor: Keele University.

Implementing the Keele stratified care model for patients with low back pain: an observational impact study.

BACKGROUND: The Keele stratified care model for management of low back pain comprises use of the prognostic STarT Back Screening Tool to allocate patients into one of three risk-defined categories leading to associated risk-specific treatment pathways, such that high-risk patients receive enhanced treatment and more sessions than medium- and low-risk patients. The Keele model is associated with economic benefits and is being widely implemented. The objective was to assess the use of the stratified model following its introduction in an acute hospital physiotherapy department setting in Gloucestershire, England. METHODS: Physiotherapists recorded data on 201 patients treated using the Keele model in two audits in 2013 and 2014. To assess whether implementation of the stratified model was associated with the anticipated range of treatment sessions, regression analysis of the audit data was used to determine whether high- or medium-risk patients received significantly more treatment sessions than low-risk patients. The analysis controlled for patient characteristics, year, physiotherapists' seniority and physiotherapist. To assess the physiotherapists' views on the usefulness of the stratified model, audit data on this were analysed using framework methods. To assess the potential economic consequences of introducing the stratified care model in Gloucestershire, published economic evaluation findings on back-related National Health Service (NHS) costs, quality-adjusted life years (QALYs) and societal productivity losses were applied to audit data on the proportion of patients by risk classification and estimates of local incidence. RESULTS: When the Keele model was implemented, patients received significantly more treatment sessions as the risk-rating increased, in line with the anticipated impact of targeted treatment pathways. Physiotherapists were largely positive about using the model. The potential annual impact of rolling out the model across Gloucestershire is a gain in approximately 30 QALYs, a reduction in productivity losses valued at £1.4 million and almost no change to NHS costs. CONCLUSIONS: The Keele model was implemented and risk-specific treatment pathways successfully used for patients presenting with low back pain. Applying published economic evidence to the Gloucestershire locality suggests that substantial health and productivity outcomes would be associated with rollout of the Keele model while being cost-neutral for the NHS.

Preventing vitamin D deficiency (VDD): a systematic review of economic evaluations.

Background: Vitamin D deficiency (VDD) is a public health concern worldwide. If untreated, it can lead to reduced quality of life and escalated costs brought about by ill-health. Preventive programmes to improve population vitamin D status exist but little is known about their cost-effectiveness. This information is vital so that decision-makers adopt efficient strategies and optimise use of public resources. Aims: Systematically review and critically appraise economic evaluations of population strategies to prevent VDD. Methods: The databases reviewed were MEDLINE, EMBASE, Econlit, NHS EED, CEA, and RepEc. All full economic evaluations of VDD prevention strategies were included. Interventions considered were food fortification, supplementation and public health campaigns. Data extracted included type of evaluation, population, setting, measure of benefit and main results. Results: Of the 2492 records screened, 14 studies were included. The majority of studies focused on supplementation within at-risk groups with the primary objective of either preventing fractures or falls in older adults. There was insufficient economic evidence to draw conclusions about the cost-effectiveness of population strategies. No study was identified that offered a direct comparison of the two main alternative population strategies: food fortification vs. supplementation. Conclusions: Whilst there is a growing body of evidence on the cost-effectiveness of micro nutrient programmes, there is a paucity of data on vitamin D fortification and how fortification programmes compare to population supplementation programmes. We highlight research gaps, and offer suggestions of what is required to undertake population-based cost-effectiveness analysis.

Cost-effectiveness of zoledronic acid and strontium-89 as bone protecting treatments in addition to chemotherapy in patients with metastatic castrate-refractory prostate cancer: results from the TRAPEZE trial (ISRCTN 12808747).

OBJECTIVE: To evaluate the cost-effectiveness of adding zoledronic acid or strontium-89 to standard docetaxel chemotherapy for patients with castrate-refractory prostate cancer (CRPC). PATIENTS AND METHODS: Data on resource use and quality of life for 707 patients collected prospectively in the TRAPEZE 2 × 2 factorial randomised trial (ISRCTN 12808747) were used to assess the cost-effectiveness of i) zoledronic acid versus no zoledronic acid (ZA vs. no ZA), and ii) strontium-89 versus no strontium-89 (Sr89 vs. no Sr89). Costs were estimated from the perspective of the National Health Service in the UK and included expenditures for trial treatments, concomitant medications, and use of related hospital and primary care services. Quality-adjusted life-years (QALYs) were calculated according to patients' responses to the generic EuroQol EQ-5D-3L instrument, which evaluates health status. Results are expressed as incremental cost-effectiveness ratios (ICERs) and cost-effectiveness acceptability curves. RESULTS: The per-patient cost for ZA was £12 667, £251 higher than the equivalent cost in the no ZA group. Patients in the ZA group had on average 0.03 QALYs more than their counterparts in no ZA group. The ICER for this comparison was £8 005. Sr89 was associated with a cost of £13 230, £1365 higher than no Sr89, and a gain of 0.08 QALYs compared to no Sr89. The ICER for Sr89 was £16 884. The probabilities of ZA and Sr89 being cost-effective were 0.64 and 0.60, respectively. CONCLUSIONS: The addition of bone-targeting treatments to standard chemotherapy led to a small improvement in QALYs for a modest increase in cost (or cost-savings). ZA and Sr89 resulted in ICERs below conventional willingness-to-pay per QALY thresholds, suggesting that their addition to chemotherapy may represent a cost-effective use of resources.