The cost-effectiveness of nivolumab monotherapy for the treatment of advanced melanoma patients in England

Background: Nivolumab was the first programmed death receptor 1 (PD-1) immune checkpoint inhibitor to demonstrate long-term survival benefit in a clinical trial setting for advanced melanoma patients. Objective: To evaluate the cost effectiveness of nivolumab monotherapy for the treatment of advanced melanoma patients in England. Methods: A Markov state-transition model was developed to estimate the lifetime costs and benefits of nivolumab versus ipilimumab and dacarbazine for BRAF mutation-negative patients and versus ipilimumab, dabrafenib, and vemurafenib for BRAF mutation-positive patients. Covariate-adjusted parametric curves for time to progression, pre-progression survival, and post-progression survival were fitted based on patient-level data from two trials and long-term ipilimumab survival data. Indirect treatment comparisons between nivolumab, ipilimumab, and dacarbazine were informed by these covariate-adjusted parametric curves, controlling for differences in patient characteristics. Kaplan–Meier data from the literature were digitised and used to fit progression-free and overall survival curves for dabrafenib and vemurafenib. Patient utilities and resource use data were based on trial data or the literature. Patients are assumed to receive nivolumab until there is no further clinical benefit, assumed to be the first of progressive disease, unacceptable toxicity, or 2 years of treatment. Results: Nivolumab is the most cost-effective treatment option in BRAF mutation-negative and mutation-positive patients, with incremental cost-effectiveness ratios of £24,483 and £17,362 per quality-adjusted life year, respectively. The model results are most sensitive to assumptions regarding treatment duration for nivolumab and the parameters of the fitted parametric survival curves. Conclusions: Nivolumab is a cost-effective treatment for advanced melanoma patients in England

A Pilot Study of Value of Information Analysis to Support Research Recommendations for the National Institute for Health and Clinical Excellence

Background - This project developed as a result of the activities of the Research Teams at the Centre for Health Economics, University of York, and ScHARR at the University of Sheffield in the methods and application of decision analysis and value of information analysis as a means of informing the research recommendations made by NICE, as part of its Guidance to the NHS in England and Wales, and informing the deliberations of the NICE Research and Development Committee. Objectives - The specific objectives of the pilot study were to: • Demonstrate the benefits of using appropriate decision analytic methods and value of information analysis to inform research recommendations. • Establish the feasibility and resource implications of applying these methods in a timely way, to inform NICE. • Identify critical issues and methodological challenges to the use of value of information methods for research recommendations (with particular regard to the new reference case as a suitable basis for this type of analysis).

Challenges and opportunities for conducting a vaccine trial during the COVID-19 pandemic in the United Kingdom

The COVID-19 pandemic has resulted in unprecedented challenges for healthcare systems worldwide. It has also stimulated research in a wide range of areas including rapid diagnostics, novel therapeutics, use of technology to track patients and vaccine development. Here, we describe our experience of rapidly setting up and delivering a novel COVID-19 vaccine trial, using clinical and research staff and facilities in three National Health Service Trusts in Cambridgeshire, United Kingdom. We encountered and overcame a number of challenges including differences in organisational structures, research facilities available, staff experience and skills, information technology and communications infrastructure, and research training and assessment procedures. We overcame these by setting up a project team that included key members from all three organisations that met at least daily by teleconference. This group together worked to identify the best practices and procedures and to harmonise and cascade these to the wider trial team. This enabled us to set up the trial within 25 days and to recruit and vaccinate the participants within a further 23 days. The lessons learned from our experiences could be used to inform the conduct of clinical trials during a future infectious disease pandemic or public health emergency

Global urban environmental change drives adaptation in white clover

Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale

Good Practice Guidelines for Decision-Analytic Modelling in Health Technology Assessment: A Review and Consolidation of Quality Assessment

The use of decision-analytic modelling for the purpose of health technology assessment (HTA) has increased dramatically in recent years. Several guidelines for best practice have emerged in the literature; however, there is no agreed standard for what constitutes a `good model' or how models should be formally assessed. The objective of this paper is to identify, review and consolidate existing guidelines on the use of decision-analytic modelling for the purpose of HTA and to develop a consistent framework against which the quality of models may be assessed. The review and resultant framework are summarised under the three key themes of Structure, Data and Consistency. `Structural' aspects relate to the scope and mathematical structure of the model including the strategies under evaluation. Issues covered under the general heading of `Data' include data identification methods and how uncertainty should be addressed. `Consistency' relates to the overall quality of the model. The review of existing guidelines showed that although authors may provide a consistent message regarding some aspects of modelling, such as the need for transparency, they are contradictory in other areas. Particular areas of disagreement are how data should be incorporated into models and how uncertainty should be assessed. For the purpose of evaluation, the resultant framework is applied to a decision-analytic model developed as part of an appraisal for the National Institute for Health and Clinical Excellence (NICE) in the UK. As a further assessment, the review based on the framework is compared with an assessment provided by an independent experienced modeller not using the framework. It is hoped that the framework developed here may form part of the appraisals process for assessment bodies such as NICE and decision models submitted to peer review journals. However, given the speed with which decision-modelling methodology advances, there is a need for its continual update.Cost-effectiveness, Modelling

Options for managing low grade cervical abnormalities detected at screening : cost effectiveness study

Objective To estimate the cost effectiveness of alternative methods of managing low grade cervical cytological abnormalities detected at routine screening. Design Cost analysis within multicentre individually randomised controlled trial. Setting Grampian, Tayside, and Nottingham. Participants 4201 women with low grade abnormalities. Interventions Cytological surveillance or referral to colposcopy for biopsy and recall if necessary or referral to colposcopy with immediate treatment based on colposcopic appearance. Main outcome measures Data on resource use collected from participants throughout the duration of the trial (36 months), enabling the estimation of both the direct (health care) and indirect (time and travel) costs of management. Quality of life assessed at recruitment and at 12, 18, 24, and 30 months, using the EQ-5D instrument. Economic outcomes expressed as costs per case of cervical intraepithelial neoplasia (grade II or worse) detected, by trial arm, as confirmed at exit, and cost utility ratios (cost per quality adjusted life year (QALY) gained) for the three pairwise comparisons of trial arms. Results The mean three year discounted costs of surveillance, immediate treatment, and biopsy and recall were £150.20 (€177, $249), £240.30 (€283,$415), and £241.10 (€284, $4000), respectively, viewed from the health service perspective. From the social perspective, mean discounted costs were £204.40 (€241,$339), £339.90 (€440, $563), and £327.50 (€386,$543), respectively. Estimated at the means, the incremental cost effectiveness ratios indicated that immediate treatment was dominated by the other two management methods, although it did offer the lowest cost per case of cervical intraepithelial neoplasia detected and treated. The pronounced skews in the distributions indicated that probabilistic uncertainty analysis would offer more meaningful estimates of cost effectiveness. The observed differences in the cost effectiveness ratios between trial arms were not significant. Conclusion Judged within the time frame of the TOMBOLA evaluation, there is no compelling economic reason to favour any one follow-up method over either of the others