Choice and judgement in developing models for health technology assessment; a qualitative study

Introduction: The role of models in supporting health policy decisions is reliant on model credibility. Credibility is fundamentally determined by the choices and judgements that people make in the process of developing a model. However, the method of uncovering choices and making judgements in model development is largely unreported and is not addressed by modelling methods guidance. Methods: This qualitative study was part of a project examining errors in health technology assessment models. In-depth interviews with academic and commercial modellers were used to obtain descriptions of the model development process. Data were analysed using framework analysis and interpreted in the context of the methodological literature. Results: The activities involved in developing models were characterised according to the themes; understanding the decision problem, conceptual modelling, model implementation, model checking, and engaging with the decision maker. Finding and using evidence was frequently mentioned across these themes. There was marked variation between practitioners in the extent to which conceptual modelling was recognised as an activity distinct from model implementation. Discussion: Methodological approaches to addressing model credibility described in the wider modelling literature highlight the necessity to disentangle the conceptual modelling and implementation activities. Whilst interviewees talked of judgements and choice making throughout model development, discussion indicated that these were based upon skills and experience with no discussion of formal approaches. Methods are required that provide for a systematic approach to uncovering choices, to generating a shared view of consensus and divergence, and for making judgements and choices in model development

A cost-effectiveness analysis of condom distribution programmes for the prevention of sexually transmitted infections in England

Background Prevention of sexually transmitted infection (STI) incidence in England is a high priority, particularly among young people, men who have sex with men (MSM) and black ethnic minorities. An economic evaluation of condom distribution programmes (CDPs) to reduce STI transmission is presented. Methods An economic model using a Bernoulli process estimated the number of people acquiring an STI as a function of its prevalence, transmission rate, condom use, condom failure rate and number of sexual contacts. Models were developed for young people (13–24 years), black ethnic minorities, MSM and the general English population. Effectiveness evidence came from a recent systematic review. For young people, a CDP was modelled (relative risk for condom use=1.23), along with an exploratory analysis of the impact on unintended pregnancies. For other populations, threshold analyses were used to identify the combination of costs and effect size required to make a programme cost-effective. Results The base case predicted that CDP for all young people in England could avert 5123 STI cases per annum, with an incremental cost–effectiveness ratio of £17 411. In addition, it could avert 118 pregnancies and 82 abortions and save £333 000 in associated costs. Schemes for black ethnic minorities and MSM could also be cost-effective even with relatively high costs and small effect sizes. Conclusion CDPs for young people are likely to be cost-effective or cost-saving. CDPs for other high-risk populations may also be cost-effective if they can increase condom use, since high HIV prevalence in these groups imposes a considerable health and cost burden

Automatic generation of ISO 19650 compliant templates based on standard construction contracts using a microservices approach.

Abstract. This study aims to establish a framework for automatically generating evidence for ISO 19650 certification. The study starts with an investigation of the challenges organisations face in compliance with BIM standards ISO 19650, the key areas of interest identified in relation to this are an organisation’s ability to understand what their information requirements are. Once requirements have been identified, they are translated into format which is both machine and human readable. Extraction of text from existing project documentation is also investigated, proposing a microservice-based solution which formats and produces documents which meet the standards for information management requirements

An updated systematic review of studies mapping (or cross walking) measures of health related-quality of life to generic preference-based measures to generate utility values

Background Mapping is an increasingly common method used to predict instrument-specific preference-based health-state utility values (HSUVs) from data obtained from another health-related quality of life (HRQoL) measure. There have been several methodological developments in this area since a previous review up to 2007. Objective To provide an updated review of all mapping studies that map from HRQoL measures to target generic preference-based measures (EQ-5D measures, SF-6D, HUI measures, QWB, AQoL measures, 15D/16D/17D, CHU-9D) published from January 2007 to October 2018. Data sources A systematic review of English language articles using a variety of approaches: searching electronic and utilities databases, citation searching, targeted journal and website searches. Study selection Full papers of studies that mapped from one health measure to a target preference-based measure using formal statistical regression techniques. Data extraction Undertaken by four authors using predefined data fields including measures, data used, econometric models and assessment of predictive ability. Results There were 180 papers with 233 mapping functions in total. Mapping functions were generated to obtain EQ-5D-3L/EQ-5D-5L-EQ-5D-Y (n = 147), SF-6D (n = 45), AQoL-4D/AQoL-8D (n = 12), HUI2/HUI3 (n = 13), 15D (n = 8) CHU-9D (n = 4) and QWB-SA (n = 4) HSUVs. A large number of different regression methods were used with ordinary least squares (OLS) still being the most common approach (used ≥ 75% times within each preference-based measure). The majority of studies assessed the predictive ability of the mapping functions using mean absolute or root mean squared errors (n = 192, 82%), but this was lower when considering errors across different categories of severity (n = 92, 39%) and plots of predictions (n = 120, 52%). Conclusions The last 10 years has seen a substantial increase in the number of mapping studies and some evidence of advancement in methods with consideration of models beyond OLS and greater reporting of predictive ability of mapping functions

Denosumab, raloxifene, romosozumab and teriparatide to prevent osteoporotic fragility fractures: a systematic review and economic evaluation

Background Fragility fractures are fractures that result from mechanical forces that would not ordinarily result in fracture. Objectives The objectives were to evaluate the clinical effectiveness, safety and cost-effectiveness of non-bisphosphonates {denosumab [Prolia®; Amgen Inc., Thousand Oaks, CA, USA], raloxifene [Evista®; Daiichi Sankyo Company, Ltd, Tokyo, Japan], romosozumab [Evenity®; Union Chimique Belge (UCB) S.A. (Brussels, Belgium) and Amgen Inc.] and teriparatide [Forsteo®; Eli Lilly and Company, Indianapolis, IN, USA]}, compared with each other, bisphosphonates or no treatment, for the prevention of fragility fracture. Data sources For the clinical effectiveness review, nine electronic databases (including MEDLINE, EMBASE and the World Health Organization International Clinical Trials Registry Platform) were searched up to July 2018. Review methods A systematic review and network meta-analysis of fracture and femoral neck bone mineral density were conducted. A review of published economic analyses was undertaken and a model previously used to evaluate bisphosphonates was adapted. Discrete event simulation was used to estimate lifetime costs and quality-adjusted life-years for a simulated cohort of patients with heterogeneous characteristics. This was done for each non-bisphosphonate treatment, a strategy of no treatment, and the five bisphosphonate treatments previously evaluated. The model was populated with effectiveness evidence from the systematic review and network meta-analysis. All other parameters were estimated from published sources. An NHS and Personal Social Services perspective was taken, and costs and benefits were discounted at 3.5% per annum. Fracture risk was estimated from patient characteristics using the QFracture® (QFracture-2012 open source revision 38, Clinrisk Ltd, Leeds, UK) and FRAX® (web version 3.9, University of Sheffield, Sheffield, UK) tools. The relationship between fracture risk and incremental net monetary benefit was estimated using non-parametric regression. A probabilistic sensitivity analysis and scenario analyses were used to assess uncertainty. Results Fifty-two randomised controlled trials of non-bisphosphonates were included in the clinical effectiveness systematic review and an additional 51 randomised controlled trials of bisphosphonates were included in the network meta-analysis. All treatments had beneficial effects compared with placebo for vertebral, non-vertebral and hip fractures, with hazard ratios varying from 0.23 to 0.94, depending on treatment and fracture type. The effects on vertebral fractures and the percentage change in bone mineral density were statistically significant for all treatments. The rate of serious adverse events varied across trials (0–33%), with most between-group differences not being statistically significant for comparisons with placebo/no active treatment, non-bisphosphonates or bisphosphonates. The incremental cost-effectiveness ratios were > £20,000 per quality-adjusted life-year for all non-bisphosphonate interventions compared with no treatment across the range of QFracture and FRAX scores expected in the population eligible for fracture risk assessment. The incremental cost-effectiveness ratio for denosumab may fall below £30,000 per quality-adjusted life-year at very high levels of risk or for high-risk patients with specific characteristics. Raloxifene was dominated by no treatment (resulted in fewer quality-adjusted life-years) in most risk categories. Limitations The incremental cost-effectiveness ratios are uncertain for very high-risk patients. Conclusions Non-bisphosphonates are effective in preventing fragility fractures, but the incremental cost-effectiveness ratios are generally greater than the commonly applied threshold of £20,000–30,000 per quality-adjusted life-year. Study registration This study is registered as PROSPERO CRD42018107651. 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. 29. See the NIHR Journals Library website for further project information

Pembrolizumab for locally advanced or metastatic urothelial cancer where cisplatin is unsuitable: an evidence review group perspective of a NICE single technology appraisal

As part of its Single Technology Appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer (Merck Sharp & Dohme) of pembrolizumab (Keytruda®) to submit evidence of its clinical and cost effectiveness for the treatment of locally advanced or metastatic urothelial cancer where cisplatin is unsuitable. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a detailed review of the evidence for the clinical and cost effectiveness of the technology, based on the company’s submission (CS) to NICE. The clinical effectiveness evidence in the CS for pembrolizumab was based on one phase II, single-arm, open-label, non-randomised study (KEYNOTE-052), while the evidence for the comparator (carboplatin plus gemcitabine) was based on four studies, including one randomised controlled trial and three cohort studies. In the absence of head-to-head trials, the company conducted an indirect treatment comparison for both progression-free survival (PFS) and overall survival (OS), by firstly adjusting cross-study differences using a simulated treatment comparison approach and then synthesizing the evidence based on an assumption of constant hazard ratios using a standard meta-analysis model and time-varying hazard ratios using fractional polynomial models. The treatment effect of pembrolizumab was more favourable in the adjusted population compared with the observed effect in the KEYNOTE-052 study. The company submitted a de novo partitioned survival cohort simulation model, which partitions the OS time into PFS and post-progression survival. The probabilistic incremental cost-effectiveness ratio (ICER) for pembrolizumab compared with carboplatin plus gemcitabine was estimated to be £37,081 per quality-adjusted life-year (QALY) gained, based on the results within the company’s health economic model. Following a critique of the model, for their preferred base case the ERG corrected some minor model errors, chose a progression approach for estimating utilities, and revised the extrapolation of PFS and OS. The ERG’s probabilistic base case ICER was estimated to be £67,068 per QALY gained. The ERG also undertook a range of exploratory sensitivity analyses which suggested that the ICER was highly uncertain. In particular, the choices of extrapolation for the OS of pembrolizumab and the stopping rule for pembrolizumab had the largest impacts on the ICER. The NICE Appraisal Committee recommended pembrolizumab for use within the Cancer Drugs Fund as an option for treating locally advanced or metastatic urothelial carcinoma in adults who have had platinum-containing chemotherapy, provided that pembrolizumab was stopped at 2 years of uninterrupted treatment, or earlier if the disease progresses, and the conditions of the managed access agreement for pembrolizumab are followed

Treat-to-target strategies in rheumatoid arthritis: a systematic review and cost-effectiveness analysis

To systematically review clinical and health economic impacts of treat-to-target (TTT) strategies in patients with rheumatoid arthritis (RA) managed in specialist units, compared with routine care. Sixteen and seven electronic databases were searched for clinical RCTs and cost-effectiveness respectively. Study selection, data extraction and quality assessment (Cochrane Collaboration risk of bias criteria) were performed. Evidence was reported by (1) TTT vs. usual care; (2) comparison of different treatment protocols against each other; (3) comparison of different targets against each other. Narrative synthesis was undertaken and conclusions drawn on a trial by trial basis, due to study heterogeneity. Twenty-two RCTs were included. Sixteen were at high risk of bias, five unclear and one low risk. Three trials showed TTT to be more effective than usual care in terms of remissions, in some or all comparisons, whereas one other trial reported no significant difference. Two trials showed TTT to be more effective than usual care in terms of low disease activity (LDA), in some or all comparisons, whereas two trials reported little difference. Some evidence suggests that TTT strategies involving combination therapy can achieve more remissions than those involving monotherapy, but little impact of alternative treatment targets on remission or LDA. Overall, there is evidence that TTT increases remissions in early RA and mixed early and established RA populations, and increases LDA in established RA. Although results varied, typically TTT was estimated to be more cost-effective than usual care. No target appears more effective than others

Catheter event rates in medical compared to surgical peritoneal dialysis catheter insertion

Introduction: How patient, center, and insertion technique factors interact needs to be understood when designing peritoneal dialysis (PD) catheter insertion pathways. Methods: We undertook a prospective cohort study in 44 UK centers enrolling participants planned for first catheter insertion. Sequences of regressions were used to describe the associations linking patient and dialysis unit-level characteristics with catheter insertion technique and their impact on the occurrence of catheter-related events in the first year (catheter-related infection, hospitalization, and removal). Factors associated with catheter events were incorporated into a multistate model comparing the rates of catheter events between medical and surgical insertion alongside treatment modality transitions and mortality. Results: Of 784 first catheter insertions, 466 (59%) had a catheter event in the first year and 61.2% of transitions onto hemodialysis (HD) were immediately preceded by a catheter event. Catheter malfunction was less but infection was more common with surgical compared with medical insertions. Participants at centers with fewer late presenters and more new dialysis patients starting PD, had a lower probability of a catheter event. Adjusting for these factors, the hazard ratio for a catheter event following insertion (medical vs. surgical) was 0.70 (95% confidence interval [CI] 0.43 to 1.13), and once established on PD 0.77 (0.62 to 0.96). Conclusion: Offering both medical and surgical techniques is associated with lower catheter event rates and keeps people on PD for longer

Adalimumab for Treating Moderate-to-Severe Hidradenitis Suppurativa: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

As part of its single technology appraisal (STA) process, the UK National Institute for Health and Care Excellence (NICE) invited the manufacturer of adalimumab (AbbVie) to submit evidence on the clinical effectiveness and cost effectiveness of adalimumab for the treatment of moderate-to-severe hidradenitis suppurativa (HS). The appraisal assessed adalimumab as monotherapy in adult patients with an inadequate response to conventional systemic HS therapy. The School of Health and Related Research Technology Appraisal Group was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence for the clinical effectiveness and cost effectiveness of the technology based on the company’s submission to NICE. The evidence was mainly derived from three randomised controlled trials comparing adalimumab with placebo in adults with moderate-to-severe HS. The clinical-effectiveness review found that significantly more patients achieved a clinical response in the adalimumab groups than in the control groups but that the treatment effect varied between trials and there was uncertainty regarding its impact on a range of other relevant outcomes as well as long-term efficacy. The company’s submitted Markov model assessed the incremental cost effectiveness of adalimumab versus standard care for the treatment of HS from the perspective of the UK NHS and Personal Social Services (PSS) over a lifetime horizon. The original submitted model, including a patient access scheme (PAS), suggested that the incremental cost-effectiveness ratio (ICER) for adalimumab versus standard care was expected to be £16,162 per quality-adjusted life-year (QALY) gained. Following a critique of the model, the ERG’s preferred base case, which corrected programming errors and structural problems surrounding discontinuation rules and incorporated a lower unit cost for HS surgery, resulted in a probabilistic ICER of £29,725 per QALY gained. Based on additional analyses undertaken by the company and the ERG following the publication of the appraisal consultation document (ACD), the Appraisal Committee concluded that the maximum possible ICER for adalimumab compared with supportive care was between £28,500 and £33,200 per QALY gained but was likely to be lower. The Appraisal Committee recommended adalimumab (with the PAS) for the treatment of active moderate-to-severe HS in adults whose disease has not responded to conventional systemic therapy