Multi-indication Evidence Synthesis in Oncology Health Technology Assessment: Meta-analysis Methods and Their Application to a Case Study of Bevacizumab.

Background: Multi-indication cancer drugs receive licensing extensions to include additional indications, as trial evidence on treatment effectiveness accumulates. We investigate how sharing information across indications can strengthen the inferences supporting health technology assessment (HTA).

Methods: We applied meta-analytic methods to randomized trial data on bevacizumab, to share information across oncology indications on the treatment effect on overall survival (OS) or progression-free survival (PFS) and on the surrogate relationship between effects on PFS and OS.

Challenges and opportunities for identifying people with Familial hypercholesterolaemia in the UK: Evidence from the National FH PASS database.

Background: Familial Hypercholesterolaemia (FH) is a monogenic disorder that causes high levels of low-density lipoprotein (LDL) cholesterol. Cascade testing, where relatives of known individuals with FH ('index') are genetically tested, is effective and cost-effective, but implementation in the UK varies.

Objective: This study aims to provide evidence on current UK FH cascade yields and to identify common obstacles cascade services face and individual- and service-level predictors of success.

Percutaneous Revascularization for Ischemic Left Ventricular Dysfunction: Cost-Effectiveness Analysis of the REVIVED-BCIS2 Trial.

Background: Percutaneous coronary intervention (PCI) is frequently undertaken in patients with ischemic left ventricular systolic dysfunction. The REVIVED (Revascularization for Ischemic Ventricular Dysfunction)-BCIS2 (British Cardiovascular Society-2) trial concluded that PCI did not reduce the incidence of all-cause death or heart failure hospitalization; however, patients assigned to PCI reported better initial health-related quality of life than those assigned to optimal medical therapy (OMT) alone. The aim of this study was to assess the cost-effectiveness of PCI+OMT compared with OMT alone.

A randomised controlled trial of compression therapies for the treatment of venous leg ulcers (VenUS 6): study protocol for a pragmatic, multicentre, parallel-group, three-arm randomised controlled trial.

Background: Venous leg ulcer(s) are common, recurring, open wounds on the lower leg, resulting from diseased or damaged leg veins impairing blood flow. Wound healing is the primary treatment aim for venous leg ulceration, alongside the management of pain, wound exudate and infection. Full (high) compression therapy delivering 40 mmHg of pressure at the ankle is the recommended first-line treatment for venous leg ulcers.

How does cholesterol burden change the case for investing in familial hypercholesterolaemia? A cost-effectiveness analysis.

Background And Aims: This study aimed to ascertain how the long-term benefits and costs of diagnosis and treatment of familial hypercholesterolaemia (FH) vary by prognostic factors and 'cholesterol burden', which is the effect of long-term exposure to low-density lipoprotein cholesterol (LDL-C) on cardiovascular disease (CVD) risk.

Methods: A new cost-effectiveness model was developed from the perspective of the UK National Health Service (NHS), informed by routine data from individuals with FH. The primary outcome was net health gain (i.

Percutaneous Revascularization for Ischemic Left Ventricular Dysfunction.

Background: Whether revascularization by percutaneous coronary intervention (PCI) can improve event-free survival and left ventricular function in patients with severe ischemic left ventricular systolic dysfunction, as compared with optimal medical therapy (i.e., individually adjusted pharmacologic and device therapy for heart failure) alone, is unknown.

Digital interventions in mental health: evidence syntheses and economic modelling.

Background: Economic evaluations provide evidence on whether or not digital interventions offer value for money, based on their costs and outcomes relative to the costs and outcomes of alternatives.

Objectives: (1) Evaluate and summarise published economic studies about digital interventions across different technologies, therapies, comparators and mental health conditions; (2) synthesise clinical evidence about digital interventions for an exemplar mental health condition; (3) construct an economic model for the same exemplar mental health condition using the previously synthesised clinical evidence; and (4) consult with stakeholders about how they understand and assess the value of digital interventions.

Methods: We completed four work packages: (1) a systematic review and quality assessment of economic studies about digital interventions; (2) a systematic review and network meta-analysis of randomised controlled trials on digital interventions for generalised anxiety disorder; (3) an economic model and value-of-information analysis on digital interventions for generalised anxiety disorder; and (4) a series of knowledge exchange face-to-face and digital seminars with stakeholders.

Digital Interventions for Generalized Anxiety Disorder (GAD): Systematic Review and Network Meta-Analysis.

Generalized anxiety disorder is the most common mental health condition based on weekly prevalence. Digital interventions have been used as alternatives or as supplements to conventional therapies to improve access, patient choice, and clinical outcomes. Little is known about their comparative effectiveness for generalized anxiety disorder.

Effects of Bladder Cancer on UK Healthcare Costs and Patient Health-Related Quality of Life: Evidence From the BOXIT Trial.

Background: Limited evidence exists regarding the cost and health-related quality of life (HRQoL) effects of non-muscle-invasive bladder cancer (NMIBC) recurrence and progression to muscle-invasive bladder cancer (MIBC). We examined these effects using evidence from a recent randomized control trial.

Material And Methods: The costs and HRQoL associated with bladder cancer were assessed using data from the BOXIT trial (bladder COX-2 inhibition trial; n = 472).

The Value of Further Research: The Added Value of Individual-Participant Level Data.

Judgements based on average cost-effectiveness estimates may disguise significant heterogeneity in net health outcomes. Decisions about coverage of new interventions are often more efficient when they consider between-patient heterogeneity, which is usually operationalized as different selections for different subgroups. While most model-based cost-effectiveness studies are populated with aggregated-level sub-group estimates, individual-level data are recognized as the best source of evidence to produce unbiased and efficient estimates to explore this heterogeneity.

Patients with surgical wounds healing by secondary intention: A prospective, cohort study.

Background: Surgical wounds healing by secondary intention can be difficult and costly to manage and are profoundly under researched. This prospective inception, cohort study aimed to derive a better understanding of surgical wounds healing by secondary intention and to facilitate the design of future research investigating effective treatments.

Objectives: To investigate the clinical characteristics of patients with surgical wounds healing by secondary intention and the surgeries that preceded their wounds; to clearly delineate the clinical outcomes of these patients, specifically focusing on time to wound healing and its determinants; to explore the types of treatments for surgical wounds healing by secondary intention; and to assess the impact surgical wounds healing by secondary intention have on patients' quality of life.

Brodalumab for the Treatment of Moderate-to-Severe Plaque Psoriasis: An Evidence Review Group Evaluation of a NICE Single Technology Appraisal.

As part of the National Institute for Health and Care Excellence single technology appraisal process, brodalumab was assessed to determine the clinical and cost effectiveness of its use in the treatment of moderate-to-severe plaque psoriasis. The Centre for Reviews and Dissemination and the Centre for Health Economics Technology Assessment Group at the University of York were commissioned to act as the independent Evidence Review Group. This article provides a summary of the Evidence Review Group's review of the company's submission, the Evidence Review Group report and the National Institute for Health and Care Excellence Appraisal Committee's subsequent guidance issued in March 2018.

High-throughput non-invasive prenatal testing for fetal rhesus D status in RhD-negative women not known to be sensitised to the RhD antigen: a systematic review and economic evaluation.

Background: High-throughput non-invasive prenatal testing (NIPT) for fetal rhesus (D antigen) (RhD) status could avoid unnecessary treatment with routine anti-D immunoglobulin for RhD-negative women carrying a RhD-negative fetus, although this may lead to an increased risk of RhD sensitisations.

Objectives: To systematically review the evidence on the diagnostic accuracy, clinical effectiveness and implementation of high-throughput NIPT and to develop a cost-effectiveness model.

Methods: We searched MEDLINE and other databases, from inception to February 2016, for studies of high-throughput NIPT free-cell fetal deoxyribonucleic acid (DNA) tests of maternal plasma to determine fetal RhD status in RhD-negative pregnant women who were not known to be sensitised to the RhD antigen.

High-throughput, non-invasive prenatal testing for fetal Rhesus D genotype to guide antenatal prophylaxis with anti-D immunoglobulin: a cost-effectiveness analysis.

Objective: To evaluate the cost-effectiveness of high-throughput, non-invasive prenatal testing (HT-NIPT) for fetal Rhesus D (RhD) genotype to guide antenatal prophylaxis with anti-D immunoglobulin compared with routine antenatal anti-D immunoglobulin prophylaxis (RAADP).

Design: Cost-effectiveness decision-analytic modelling.

Setting: Primary care.

Cost-effectiveness of adjunct non-pharmacological interventions for osteoarthritis of the knee.

Background: There is limited information on the costs and benefits of alternative adjunct non-pharmacological treatments for knee osteoarthritis and little guidance on which should be prioritised for commissioning within the NHS. This study estimates the costs and benefits of acupuncture, braces, heat treatment, insoles, interferential therapy, laser/light therapy, manual therapy, neuromuscular electrical stimulation, pulsed electrical stimulation, pulsed electromagnetic fields, static magnets and transcutaneous electrical nerve Stimulation (TENS), based on all relevant data, to facilitate a more complete assessment of value.

Methods: Data from 88 randomised controlled trials including 7,507 patients were obtained from a systematic review.

Methods for network meta-analysis of continuous outcomes using individual patient data: a case study in acupuncture for chronic pain.

Background: Network meta-analysis methods, which are an extension of the standard pair-wise synthesis framework, allow for the simultaneous comparison of multiple interventions and consideration of the entire body of evidence in a single statistical model. There are well-established advantages to using individual patient data to perform network meta-analysis and methods for network meta-analysis of individual patient data have already been developed for dichotomous and time-to-event data. This paper describes appropriate methods for the network meta-analysis of individual patient data on continuous outcomes.

VenUS IV (Venous leg Ulcer Study IV) - compression hosiery compared with compression bandaging in the treatment of venous leg ulcers: a randomised controlled trial, mixed-treatment comparison and decision-analytic model.

Background: Compression is an effective and recommended treatment for venous leg ulcers. Although the four-layer bandage (4LB) is regarded as the gold standard compression system, it is recognised that the amount of compression delivered might be compromised by poor application technique. Also the bulky nature of the bandages might reduce ankle or leg mobility and make the wearing of shoes difficult.

Point prevalence of complex wounds in a defined United Kingdom population.

Complex wounds (superficial-, partial-, or full-thickness skin loss wounds healing by secondary intention) are common; however, there is a lack of high-quality, contemporary epidemiological data. This paper presents point prevalence estimates for complex wounds overall as well as for individual types. A multiservice, cross-sectional survey was undertaken across a United Kingdom city (Leeds, population 751,485) during 2 weeks in spring of 2011.

Network meta-analysis of (individual patient) time to event data alongside (aggregate) count data.

Background: Network meta-analysis methods extend the standard pair-wise framework to allow simultaneous comparison of multiple interventions in a single statistical model. Despite published work on network meta-analysis mainly focussing on the synthesis of aggregate data, methods have been developed that allow the use of individual patient-level data specifically when outcomes are dichotomous or continuous. This paper focuses on the synthesis of individual patient-level and summary time to event data, motivated by a real data example looking at the effectiveness of high compression treatments on the healing of venous leg ulcers.

Cost-effectiveness of interventions for increasing the possession of functioning smoke alarms in households with pre-school children: a modelling study.

Background: The UK has one of the highest rates for deaths from fire and flames in children aged 0-14 years compared to other high income countries. Evidence shows that smoke alarms can reduce the risk of fire-related injury but little exists on their cost-effectiveness. We aimed to compare the cost effectiveness of different interventions for the uptake of 'functioning' smoke alarms and consequently for the prevention of fire-related injuries in children in the UK.

Deriving input parameters for cost-effectiveness modeling: taxonomy of data types and approaches to their statistical synthesis.

Background: The evidence base informing economic evaluation models is rarely derived from a single source. Researchers are typically expected to identify and combine available data to inform the estimation of model parameters for a particular decision problem. The absence of clear guidelines on what data can be used and how to effectively synthesize this evidence base under different scenarios inevitably leads to different approaches being used by different modelers.

Mixed treatment comparisons using aggregate and individual participant level data.

Mixed treatment comparisons (MTC) extend the traditional pair-wise meta-analytic framework to synthesize information on more than two interventions. Although most MTCs use aggregate data (AD), a proportion of the evidence base might be available at the individual level (IPD). We develop a series of novel Bayesian statistical MTC models to allow for the simultaneous synthesis of IPD and AD, potentially incorporating study and individual level covariates.