Modelling the impact of referral guideline changes for mild dyskaryosis on colposcopy services in England

Objectives: This model examines the effects of changing referral strategies within the established structure of NHS cervical screening driven colposcopy practice. It considers the effects of the new strategy on colposcopy workload, patient waiting times, and associated costs and health benefits. Methods: By postal survey, the current operational strategies of colposcopy services were established by questionnaire with respect to referral practices and management protocols. After first-cut piloting, and utilising published and original research, a Markovian model was constructed, and the impact of the new strategy was determined on colposcopy workload and patient waiting times for three hypothetical clinic types. Expected costs and benefits of the new policy were assessed through the adaptation of a previous ScHARR cervical screening model. Results: Clinic workload is expected to increase by between 21% and 35% within three years of the policy change, depending on clinic efficiency in other areas; the majority of this impact would be seen within the first year. It is predicted that particularly inefficient clinics would struggle to meet the existing waiting time requirements for women referred with low-grade disease, owing to the increased level of workload seen throughout the patient pathway as a result of the implementation of the new policy. The impact of the new policy can, however, be mitigated through improving the efficiency of existing clinics, by altering policies relating to surveillance of low grade disease, post-treatment follow-up, treatment policy (whether or not treatment is performed at the initial colposcopy visit), and through adherence to national guidelines. A cost-effectiveness analysis using the ScHARR liquid-based cytology model suggests that the policy change is likely to be have a cost per quality-adjusted lifeyear gained of between £1,400 and £5,500 per quality-adjusted life-year gained (excluding the costs of follow-up), which would be deemed acceptable to organisations such as the National Institute for Health and Clinical Excellence

Climatological predictions of the auroral zone locations driven by moderate and severe space weather events

Auroral zones are regions where, in an average sense, aurorae due to solar activity are most likely spotted. Their shape and, similarly, the geographical locations most vulnerable to extreme space weather events (which we term ‘danger zones’) are modulated by Earth’s time-dependent internal magnetic field whose structure changes on yearly to decadal timescales. Strategies for mitigating ground-based space weather impacts over the next few decades can benefit from accurate forecasts of this evolution. Existing auroral zone forecasts use simplified assumptions of geomagnetic field variations. By harnessing the capability of modern geomagnetic field forecasts based on the dynamics of Earth’s core we estimate the evolution of the auroral zones and of the danger zones over the next 50 years. Our results predict that space-weather related risk will not change significantly in Europe, Australia and New Zealand. Mid-to-high latitude cities such as Edinburgh, Copenhagen and Dunedin will remain in high-risk regions. However, northward change of the auroral and danger zones over North America will likely cause urban centres such as Edmonton and Labrador City to be exposed by 2070 to the potential impact of severe solar activity

Cost-effectiveness of 4 mg dibotermin alfa/absorbable collagen sponge versus iliac crest bone graft for lumbar degenerative disc disease in the United Kingdom

Aims: To develop a model to evaluate the cost-effectiveness of 4 mg dibotermin alfa/absorbable collagen sponge (ACS) versus iliac crest bone graft (ICBG) in patients with lumbar degenerative disc disease in the United Kingdom. Materials & methods: A Markov decision-analytic model was constructed to calculate costs and quality-adjusted life-years over a 4-year time horizon in each treatment group, from a United Kingdom National Health Service perspective. An individual patient data meta-analysis was undertaken to synthesize data from four randomized controlled trials and two single-arm studies concerning health-related quality of life and procedural resource use. Current cost data from the United Kingdom were then applied to determine the overall mean cost per patient in each group. One-way and probabilistic sensitivity analyses were undertaken to explore the impact of parameter uncertainty. Results: The model predicted 4-year discounted cost savings of £192 per patient treated with dibotermin alfa/ACS, compared with ICBG, and a gain of 0.0114 QALYs per patient over the same time period. Sensitivity analyses indicated that the results were most sensitive to variability in the differences in health-related quality of life and secondary surgery rate, with dibotermin alfa/ACS having a 60% probability of being cost-effective at a willingness-to-pay threshold of £20,000 per QALY gained. Limitations: There is uncertainty in the difference in cost and QALYs between the two groups. However, comprehensive sensitivity analyses were undertaken to explore this and present the results in a transparent manner. Conclusions: Our results provide an economic case for the use of 4 mg dibotermin alfa/ACS versus iliac crest bone graft, with additional health benefits predicted at reduced overall cost

Replicating Health Economic Models: Firm Foundations or a House of Cards?

Health economic evaluation is a framework for the comparative analysis of the incremental health gains and costs associated with competing decision alternatives. The process of developing health economic models is usually complex, financially expensive and time-consuming. For these reasons, model development is sometimes based on previous model-based analyses; this endeavour is usually referred to as model replication. Such model replication activity may involve the comprehensive reproduction of an existing model or 'borrowing' all or part of a previously developed model structure. Generally speaking, the replication of an existing model may require substantially less effort than developing a new de novo model by bypassing, or undertaking in only a perfunctory manner, certain aspects of model development such as the development of a complete conceptual model and/or comprehensive literature searching for model parameters. A further motivation for model replication may be to draw on the credibility or prestige of previous analyses that have been published and/or used to inform decision making. The acceptability and appropriateness of replicating models depends on the decision-making context: there exists a trade-off between the 'savings' afforded by model replication and the potential 'costs' associated with reduced model credibility due to the omission of certain stages of model development. This paper provides an overview of the different levels of, and motivations for, replicating health economic models, and discusses the advantages, disadvantages and caveats associated with this type of modelling activity. Irrespective of whether replicated models should be considered appropriate or not, complete replicability is generally accepted as a desirable property of health economic models, as reflected in critical appraisal checklists and good practice guidelines. To this end, the feasibility of comprehensive model replication is explored empirically across a small number of recent case studies. Recommendations are put forward for improving reporting standards to enhance comprehensive model replicability

The clinical and cost-effectiveness of oxaliplatin and capecitabine for the adjuvant treatment of colon cancer : systematic review and economic evaluation

Objectives: To assess the clinical and cost-effectiveness of oxaliplatin in combination with 5-fluorouracil/leucovorin (5-FU/LV), and capecitabine monotherapy (within their licensed indications), as adjuvant therapies in the treatment of patients with Stage III (Dukes’ C) colon cancer after complete surgical resection of the primary tumour, as compared with adjuvant chemotherapy with an established fluorouracil-containing regimen. Data sources: Ten electronic bibliographic databases were searched from inception to January 2005. Searches were supplemented by hand searching relevant articles, sponsor and other submissions of evidence to the National Institute of Health and Clinical Excellence and conference proceedings. Review methods: A systematic review and meta-analysis (where appropriate) of clinical efficacy evidence and a cost-effectiveness review and economic modelling were carried out. Marginal costs, life years gained and cost-effectiveness acceptability curves were estimated. Probabilistic sensitivity analysis was used to generate information on the likelihood that each of the interventions was optimal. Results: Three randomised active-controlled trials, of varying methodological quality, were included in the review. The MOSAIC trial and NSABP C-07 study considered the addition of oxaliplatin to adjuvant treatment (albeit administered in different 5-FU/LV regimens) and the X-ACT study compared oral capecitabine with bolus 5-FU/LV alone. A review of the available evidence indicated that in patients with Stage III colon cancer, oxaliplatin in combination with an infusional de Gramont schedule of 5-FU/LV (FOLFOX4) was more effective in preventing and delaying disease recurrence than infusional 5-FU/LV alone (de Gramont regimen). Serious adverse events and treatment discontinuations due to toxicity were more evident with oxaliplatin-based regimens (FOLFOX4 and FLOX regimen) than infusional or bolus 5-FU/LV alone (de Gramont and Roswell Park regimen). Oral capecitabine was at least equivalent in disease-free survival to the bolus Mayo Clinic 5-FU/LV regimen for patients with resected Stage III colon cancer. Although, the safety and tolerability profile of capecitabine was superior to that of the Mayo Clinic 5-FU/LV regimen, it has not been evaluated in comparison with other less toxic 5-FU/LV regimens currently in common use in the UK. Based on the assumptions and survival analysis methods used, the cost-effectiveness analysis using economic modelling estimated that capecitabine was a dominating strategy and resulted in a cost-saving of approximately £3320 per patient in comparison with the Mayo Clinic 5-FU/LV regimen, while also providing an additional 0.98 quality-adjusted life-years (QALYs) over a 50-year model time horizon. Oxaliplatin in combination with 5-FU/LV (FOLFOX4 regimen) is estimated to cost an additional £2970 per QALY gained when compared with the de Gramont 5-FU/LV regimen and demonstrated superior survival outcomes with marginal costs. The uncertainty analysis suggests that both interventions have a high probability of being cost-effective at a threshold of both £20,000 and £30,000. An indirect comparison of the FOLFOX4 and Mayo Clinic 5-FU/LV regimens suggests that the use of FOLFOX4 in place of the Mayo Clinic 5-FU/LV regimen would cost an additional £5777 per QALY gained. An incremental cost-effectiveness ratio (ICER) is estimated to be approximately £13,000 per QALY gained from treatment with FOLFOX4 compared with capecitabine. However, if the Mayo Clinic and the de Gramont 5-FU/LV regimens are assumed to be equivalent in terms of effectiveness, the ICER of FOLFOX4 in comparison with capecitabine may be greater than £30,000 per QALY. Conclusions: The evidence suggests that both capecitabine and FOLFOX4 are clinically effective and cost-effective in comparison with 5-FU/LV regimens (Mayo Clinic and de Gramont schedules). Further research is suggested into the effectiveness, tolerability, patient acceptability and costs of different oxaliplatin/fluoropyrimidine schedules in the adjuvant setting; the effects of treatment duration on efficacy; adverse events; resource data collection strategies and reporting of summary statistics; subgroups benefiting most from adjuvant chemotherapy; and methods for estimating mean survival

A pilot study of value of information analysis to support research recommendations for NICE

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. Bayesian decision analysis and value of information analysis (DA-VOI) provides a methodological framework which explicitly considers the uncertainty surrounding the decision of a health care system to adopt a health technology. Specifically, using existing evidence, these methods focus on the likelihood of making a wrong decision if the technology is adopted. The value of additional research is based on the extent to which further information will reduce this decision uncertainty. This framework values the additional information, which may be generated by further research, in a way which is consistent with the objectives and the resource constraints of heath care provision (the cost-effectiveness threshold). This allows a comparison of the potential benefits of further research with the costs of further investigation, a comparison and prioritisation of alternative research recommendations, both within and between Technology Assessments, as well as an assessment of the value of investing resources in research or other activities, such as the provision of health service. In this sense it provides a unified and coherent framework for prioritisation of research and the use of heath care technologies. 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). The project consists of a series of case studies based on recent technology assessment reports completed by the York and Sheffield group for NICE. These included: • Screening for age related macular degeneration (AMD) • Glycoprotein IIb/IIIa antagonists for acute coronary syndrome (GPAs) • Clopidogrel and dipyridamole in the secondary prevention of occlusive vascular events (CLO) • Neurominidase inhibitors for the treatment of influenza (NIs) • Liquid based cytology screening for cervical cancer (LBC) • Beta interferon and glatiramer acetate in the management of MS (MS) The purpose was to establish the feasibility and requirements of value of information analysis once submissions and Technology Assessment Reports (TARs) are conducted within the reference case specified in the recent methods guidance. Therefore case studies were selected on the basis that the existing TAR comes as close to the new reference case analysis as possible (continues..

The use of irinotecan, oxaliplatin and raltitrexed for the treatment of advanced colorectal cancer : systematic review and economic evaluation (review of NICE guidance no. 33)

Objectives: To evaluate three technologies for the management of advanced colorectal cancer: (1) first-line irinotecan combination [with 5-fluorouracil (5-FU)] or second-line monotherapy; (2) first- or second-line oxaliplatin combination (again, with 5-FU); and (3) raltitrexed, where 5-FU is inappropriate. To examine the role of irinotecan and oxaliplatin in reducing the extent of incurable disease before curative surgery (downstaging)