A new method for model-based health economic evaluation utilising and extending moment-generating functions

This is the author accepted manuscript. The final version is available from SAGE Publications via the DOI in this record.The dataset associated with this article is located in ORE at: https://doi.org/10.24378/exe.643Background Health economic evaluations frequently include projections for lifetime costs and health effects using modelling frameworks such as Markov modelling or discrete event simulation (DES). Markov models typically cannot represent events whose risk is determined by the length of time spent in state (sojourn time) without the use of tunnel states. DES is very flexible, but introduces Monte Carlo variation which can significantly limit the complexity of model analyses. Methods We present a new methodological framework for health economic modelling which is based on, and extends, the concept of moment-generating functions (MGFs) for time-to-event random variables. When future costs and health effects are discounted, MGFs can be used to very efficiently calculate the total discounted life years spent in a series of health states. Competing risks are incorporated into the method. This method can also be used to calculate discounted costs and health effects when these payoffs are constant per unit time, one-off or exponential with regard to time. MGFs are extended to additionally support costs and health effects which are polynomial with regard to time (as in a commonly used model of population norms for EQ-5D utility). Worked example A worked example is used to demonstrate application of the new method in practice, and to compare it to Markov modelling and DES. Results are compared in terms of convergence and accuracy, and computation times are compared. R code and an Excel workbook are provided. Conclusions The MGF method can be applied to health economic evaluations in the place of Markov modelling or DES and has certain advantages over both

Methods for modelling the cost-effectiveness of interventions for prostate cancer: a systematic review - Protocol

This is a protocol for a systematic review of methods for modelling the cost-effectiveness of interventions for prostate cancer. It will aim to identify and bring together all health economic modelling studies in prostate cancer, to inform the subsequent development of a whole disease model for prostate cancer. This protocol is being deposited prospectively. The following review activities have been completed at the time of depositing: Bibliographic database search strategies designed (MEDLINE, Embase, NHSEED, HTA) Bibliographic database searches conducted and results combined into an EndNote library prepared for screening Random sample of 100 citations selected for pilot screening No further review activities have been initiated or completed at time of depositing

Low-dose computed tomography for lung cancer screening in high risk populations: a systematic review and economic evaluation

This is the final version. Available from NIHR Journals Library via the DOI in this record.The dataset associated with this article is located in ORE at: https://doi.org/10.24378/exe.564Background Diagnosis of lung cancer frequently occurs in its later stages. Low-dose computed tomography (LDCT) could detect lung cancer early. Objectives To estimate the effectiveness and cost-effectiveness of LDCT lung cancer screening in high risk populations. Methods Clinical effectiveness A systematic review of randomised controlled trials (RCTs) comparing LDCT screening programmes with usual care (no screening) or other imaging screening programme (such as chest X-ray (CXR)) was conducted. Bibliographic sources included MEDLINE, Embase, Web of Science and the Cochrane Library. Meta-analyses, including network meta-analyses, were performed. Cost-effectiveness An independent economic model employing discrete event simulation and using a natural history model calibrated to results from a large RCT was developed. There were twelve different population eligibility criteria and four intervention frequencies (single screen, triple screen, annual screening and biennial screening) and a no screening control arm. Results Clinical effectiveness Twelve RCTs were included, four of which currently contribute evidence on mortality. Meta-analysis of these demonstrated that LDCT with up to 9.80 years of follow-up was associated with a non-statistically significant decrease in lung cancer mortality (pooled RR 0.94, 95% CI 0.74 to 1.19). The findings also showed that LDCT screening demonstrated a non-statistically significant increasein all-cause mortality. Given the considerable heterogeneity detected between studies for both outcomes, the results should be treated with caution. Network meta-analysis including six RCTs was performed to assess the relative effectiveness of LDCT, CXR and usual care. The results showed that LDCT was ranked as the best screening strategy in terms of lung cancer mortality reduction. CXR had a 99.7% probability of being the worst intervention with usual care intermediate. Cost-effectiveness Screening programmes are predicted to be more effective than no screening, reduce lung cancer mortality and result in more lung cancer diagnoses. Screening programmes also increase costs. Screening for lung cancer is unlikely to be cost-effective at a threshold of £20,000/QALY, but may be cost-effective at a threshold of £30,000/QALY. The incremental cost-effectiveness ratio for a single screen in smokers aged 60–75 years with at least a 3% risk of lung cancer is £28,169 per QALY. Sensitivity and scenario analyses were conducted. Screening was only cost-effective at a threshold of £20,000/QALY in a minority of analyses. Limitations Clinical effectiveness The largest of the included RCTs compared LDCT with CXR screening rather than no screening. Cost-effectiveness A representative cost to the NHS of lung cancer has not been recently estimated according to key variables such as stage at diagnosis. Certain costs associated with running a screening programme have not been included. Conclusions LDCT screening may be clinically effective in reducing lung cancer mortality but there is considerable uncertainty. There is evidence that a single round of screening could be considered cost-effective at conventional thresholds, but there is significant uncertainty about the effect on costs and the magnitude of benefits. Future work Effectiveness and cost-effectiveness estimates should be updated with the anticipated results from several ongoing RCTs (particularly NELSON).This report was commissioned by the NIHR Health Technology Assessment Programme as project number 14/151/0

The Manchester International Consensus Group recommendations for the management of gynecological cancers in Lynch syndrome.

PURPOSE: There are no internationally agreed upon clinical guidelines as to which women with gynecological cancer would benefit from Lynch syndrome screening or how best to manage the risk of gynecological cancer in women with Lynch syndrome. The Manchester International Consensus Group was convened in April 2017 to address this unmet need. The aim of the Group was to develop clear and comprehensive clinical guidance regarding the management of the gynecological sequelae of Lynch syndrome based on existing evidence and expert opinion from medical professionals and patients. METHODS: Stakeholders from Europe and North America worked together over a two-day workshop to achieve consensus on best practice. RESULTS: Guidance was developed in four key areas: (1) whether women with gynecological cancer should be screened for Lynch syndrome and (2) how this should be done, (3) whether there was a role for gynecological surveillance in women at risk of Lynch syndrome, and (4) what preventive measures should be recommended for women with Lynch syndrome to reduce their risk of gynecological cancer. CONCLUSION: This document provides comprehensive clinical guidance that can be referenced by both patients and clinicians so that women with Lynch syndrome can expect and receive appropriate standards of care

Immunosuppressive therapy for kidney transplantation in adults: Economic model (dataset)

This is an economic model, developed in Microsoft Excel, for evaluating the cost-effectiveness (cost-utility) of different immunosuppressive regimens for adult kidney transplant recipients. This is the Assessment Group economic evaluation for the National Institute for Health and Care Excellence (NICE) Technology Appraisal guidance in development: Kidney transplantation (adults) - immunosuppressive therapy (review of TA 85) [ID456]. It produces the deterministic base case analysis for the model, and the probabilistic sensitivity analysis (PSA) as reported to NICE and in the monograph [Jones-Hughes T, Snowsill T, Haasova M, et al. Immunosuppressive therapy for kidney transplantation in adults: a systematic review and economic evaluation. Health Technology Assessment 2016;20(62)]. It includes the specific PSA dataset upon which the results were based, but can be used to generate a new PSA dataset

Variation in Model-Based Economic Evaluations of Low Dose Computed Tomography (LDCT) Screening for Lung Cancer: a Methodological Review

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordObjectives: There is significant heterogeneity in the results of published model-based economic evaluations of low dose computed tomography (LDCT) screening for lung cancer. We sought to understand and demonstrate how these models differ. Methods: An expansion and update of a previous systematic review (n=19). Databases (including Medline and Embase) were searched. Studies were included if strategies involving (single or multiple) LDCT screening were compared to no screening or other imaging modalities, in a population at risk of lung cancer. More detailed data extraction of studies from the previous review was conducted. Studies were critically appraised using the Consensus Health Economic Criteria list. Results: Sixteen new studies met the inclusion criteria, giving a total of 35 studies. There are geographic and temporal differences, and differences in screening intervals and eligible populations. Studies varied in the types of models used, e.g. decision tree, Markov, microsimulation models. Most conducted a cost-effectiveness analyses (using life years gained) or cost-utility analysis. The potential for overdiagnosis was considered in many models, unlike with other potential consequences of screening. Some studies report considering lead-time bias, but fewer mention length bias. Generally, the more recent studies, involving more complex modelling, tended to meet more of the critical appraisal criteria, with notable exceptions. Conclusions: There are many differences across the economic evaluations contributing to variation in estimates of the cost-effectiveness of LDCT screening for lung cancer. A number of methodological factors and evidence needs have been highlighted that will require consideration in future economic evaluations to achieve better agreement.National Institute for Health Research (NIHR