KRAS mutation testing of tumours in adults with metastatic colorectal cancer: a systematic review and cost-effectiveness analysis

__Abstract__ Background: Bowel cancer is the third most common cancer in the UK. Most bowel cancers are initially treated with surgery, but around 17% spread to the liver. When this happens, sometimes the liver tumour can be treated surgically, or chemotherapy may be used to shrink the tumour to make surgery possible. Kirsten rat sarcoma viral oncogene (KRAS) mutations make some tumours less responsive to treatment with biological therapies such as cetuximab. There are a variety of tests available to detect these mutations. These vary in the specific mutations that they detect, the amount of mutation they detect, the amount of tumour cells needed, the time to give a result, the error rate and cost. Objectives: To compare the performance and cost-effectiveness of KRAS mutation tests in differentiating adults with metastatic colorectal cancer whose metastases are confined to the liver and are unresectable and who may benefit from first-line treatment with cetuximab in combination with standard chemotherapy from those who should receive standard chemotherapy alone

Cost Effectiveness of Modified Fractionation Radiotherapy versus Conventional Radiotherapy for Unresected Non–Small-Cell Lung Cancer Patients

IntroductionModified fractionation radiotherapy (RT), delivering multiple fractions per day or shortening the overall treatment time, improves overall survival for non -small-cell lung cancer (NSCLC) patients compared with conventional fractionation RT (CRT). However, its cost effectiveness is unknown. Therefore, we aimed to examine and compare the cost effectiveness of different modified RT schemes and CRT in the curative treatment of unresected NSCLC patients.MethodsA probabilistic Markov model was developed based on individual patient data from the meta-analysis of radiotherapy in lung cancer (N = 2000). Dutch health care costs, quality-adjusted life years (QALYs), and net monetary benefits (NMBs) were compared between two accelerated schemes (very accelerated RT [VART] and moderately accelerated RT [MART]), two hyperfractionated schemes (using an identical (HRTI) or higher (HRTH) total treatment dose than CRT) and CRT.ResultsAll modified fractionations were more effective and costlier than CRT (1.12 QALYs, €24,360). VART and MART were most effective (1.30 and 1.32 QALYs) and cost €25,746 and €26,208, respectively. HRTI and HRTH yielded less QALYs than the accelerated schemes (1.27 and 1.14 QALYs), and cost €26,199 and €29,683, respectively. MART had the highest NMB (€79,322; 95% confidence interval [CI], €35,478-€133,648) and was the most cost-effective treatment followed by VART (€78,347; 95% CI, €64,635-€92,526). CRT had an NMB of €65,125 (95% CI, €54,663-€75,537). MART had the highest probability of being cost effective (43%), followed by VART (31%), HRTI (24%), HRTH (2%), and CRT (0%).ConclusionImplementing accelerated RT is almost certainly more efficient than current practice CRT and should be recommended as standard RT for the curative treatment of unresected NSCLC patients not receiving concurrent chemo-radiotherapy

Immunocap® ISAC and microtest for multiplex allergen testing in people with difficult to manage allergic disease: A systematic review and cost analysis

__Background__ Allergy is a form of immune-mediated exaggerated sensitivity (hypersensitivity) to a substance that is either inhaled, swallowed, injected or comes into contact with the skin. Foreign substances that provoke allergies are called allergens. It has been claimed that multiplex allergen testing may help in diagnosing the cause of symptoms in patients with an unclear cause of allergy or who are allergic to more than one substance. __Objectives__ To evaluate multiplex allergen testing [devices that can measure the presence of multiple immunoglobulin E (IgE) antibodies in a patient’s blood at the same time], by assessing (1) clinical effectiveness (allergy symptoms, incidence of acute exacerbations, mortality, adverse events of testing and treatment, health-care presentations or admissions, health-related quality of life); (2) effects on treatment (diet, immunotherapy medications, other potential testing); (3) any additional diagnostic information provided by multiplex allergen testing; and (4) cost-effectiveness (cost of different assessment strategies). __Methods__ Fifteen databases were searched from 2005 to April 2015, including MEDLINE (via OvidSp), MEDLINE In-Process Citations, MEDLINE Daily Update, PubMed (National Library of Medicine), EMBASE, Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment (HTA) database, Science Citation Index (SCI), Conference Proceedings Citation Index-Science (CPCI-S), BIOSIS Previews, Latin American and Caribbean Health Sciences Literature (LILACS), National Institute for Health Research (NIHR) HTA programme, and the US Food and Drug Administration (FDA); supplementary searches of conference proceedings and trials registries were performed. Review methods followed published guidance from the Cochrane Collaboration and the Centre for Reviews and Dissemination, University of York, UK. The methodological quality of included studies was assessed using appropriate published tools or a review-specific tool designed by the project team. Studies were summarised in a narrative synthesis. Owing to a lack of data on the clinical effectiveness of multiplex allergen testing, no long-term cost-effectiveness model was developed. A conceptual model structure was developed and cost analyses were performed to examine the short-term costs of various possible diagnostic pathways. __Results__ Fifteen studies were included in the review. The very limited available data indicated that the addition of multiplex allergen testing [ImmunoCAP® Immuno Solid-phase Allergen Chip (ISAC), Thermo Fisher Scientific/Phadi

Development and Validation of the TRansparent Uncertainty ASsessmenT (TRUST) Tool for Assessing Uncertainties in Health Economic Decision Models.

Background An increasing number of technologies are obtaining marketing authorisation based on sparse evidence, which causes growing uncertainty and risk within health technology reimbursement decision making. To ensure that uncertainty is considered and addressed within health technology assessment (HTA) recommendations, uncertainties need to be identifed, included in health economic models, and reported. Objective Our objective was to develop the TRansparent Uncertainty ASsessmenT (TRUST) tool for systematically identifying, assessing, and reporting uncertainties in decision models, with the aim of making uncertainties and their impact on cost efectiveness more explicit and transparent. Methods TRUST was developed by drawing on the uncertainty and risk assessment literature. To develop and validate this tool, we conducted HTA stakeholder discussion meetings and interviews and applied it in six real-world HTA case studies in the Netherlands and the UK. Results The TRUST tool enables the identifcation and categorisation of uncertainty according to its source (transparency issues, methodology issues, and issues with evidence: imprecision, bias and indirectness, and unavailability) in each model aspect. The source of uncertainty determines the appropriate analysis. The impact of uncertainties on cost efectiveness is also assessed. Stakeholders found using the tool to be feasible and of value for transparent uncertainty assessment. TRUST can be used during model development and/or model review. Conclusion The TRUST tool enables systematic identifcation, assessment, and reporting of uncertainties in health economic models and may contribute to more informed and transparent decision making in the face of uncertainty

Research Costs Investigated: A Study Into the Budgets of Dutch Publicly Funded Drug-Related Research

Background: The costs of performing research are an important input in value of information (VOI) analyses but are difficult to assess. Objective: The aim of this study was to investigate the costs of research, serving two purposes: (1) estimating research costs for use in VOI analyses; and (2) developing a costing tool to support reviewers of grant proposals in assessing whether the proposed budget is realistic. Methods: For granted study proposals from the Netherlands Organization for Health Research and Development (ZonMw), type of study, potential cost drivers, proposed budget, and general characteristics were extracted. Regression analysis was conducted in an attempt to generate a ‘predicted budget’ for certain combinations of cost drivers, for implementation in the costing tool. Results: Of 133 drug-related research grant proposals, 74 were included for complete data extraction. Because an association between cost drivers and budgets was not confirmed, we could not generate a predicted budget based on regression analysis, but only historic reference budgets given certain study characteristics. The costing tool was designed accordingly, i.e. with given selection criteria the tool returns the range of budgets in comparable studies. This range can be used in VOI analysis to estimate whether the expected net benefit of sampling will be positive to decide upon the net value of future research. Conclusion: The absence of association between study characteristics and budgets may indicate inconsistencies in the budgeting or granting process. Nonetheless, the tool generates useful information on historical budgets, and the option to formally relate VOI to budgets. To our knowledge, this is the first attempt at creating such a tool, which can be complemented with new studies being granted, enlarging the underlying database and keeping estimates up to date

High-sensitivity troponin assays for the early rule-out or diagnosis of acute myocardial infarction in people eith acute chest pain: a systematic review and cost-effectiveness analysis

Background: Early diagnosis of acute myocardial infarction (AMI) can ensure quick and effective treatment but only 20% of adults with emergency admissions fo

The impact of late treatment-toxicity on generic health-related quality of life in head and neck cancer patients after radiotherapy

SummaryTo examine the impact of late treatment-related xerostomia and dysphagia on health-related quality of life (HRQOL) in head and neck cancer (HNC) patients after radiotherapy. A multi-center cross-sectional survey was performed. Patients with a follow-up of at least 6months after curative radiotherapy, without evidence of recurrent disease were eligible for inclusion. The Euroqol-5D questionnaire (EQ-5D) was filled out and toxicity was scored and converted to the RTOG scale. The EQ-5D measures generic HRQOL in terms of utility and visual analogue scale (VAS) scores. Missing data on the EQ-5D were imputed using multiple imputation. HRQOL was compared between subgroups of patients with and without toxicity. Subsequently, the impact of xerostomia and dysphagia on HRQOL was analyzed using multivariate regression analyses. Both analyses were performed separately for utility scores and VAS scores. The study population was composed of 396 HNC patients. The average utility and VAS scores were 0.85 (scale 0–1) and 75 (scale 0–100). Subgroups of patients with xerostomia and/or dysphagia showed statistically significantly lower utility and VAS scores (P=0.000–0.022). The multivariate regression model showed that xerostomia and dysphagia were negative predictors of both utility and VAS scores. Other factors which influenced HRQOL in at least one of the two regression models were: sex, tumor location and the addition of surgery to radiotherapy. Xerostomia and dysphagia diminish generic HRQOL. Moreover dysphagia affects patients’ HRQOL stronger than xerostomia

Response to Letter to the Editor Regarding "Abiraterone Acetate for the Treatment of Chemotherapy-Naive Metastatic Castration-Resistant Prostate Cancer: An Evidence Review Group Perspectiveaof a NICE Single Technology Appraisal"

This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programm

EMA and NICE appraisal processes for cancer drugs : current status and uncertainties

The Evidence Review Group members that contributed to this editorial are funded by the UK NIHR HTA Programme. The views and opinions expressed are those of the authors and do not necessarily reflect those of the UK Department of Health and the NIHR.Peer reviewedPublisher PD