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

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

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

The effect of prophylactic cranial irradiation (PCI) for young stage III NSCLC patients: Subgroup analyses of the NVALT-11/DLCRG-02 study

Background: The NVALT-11/DLCRG-02 phase III study compared PCI to observation after chemo-radiotherapy (RT) for stage III NSCLC and showed a significant decrease in the cumulative incidence of symptomatic brain metastases (BM) in the PCI arm at two years (7% vs 27% [HR 0.23]). We here performed exploratory subgroup analyses. Methods: Two year cumulative incidence rates were calculated and competing risk regression, with death of any cause as competing risk, was used to examine the time to symptomatic BM in the following subgr

Epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutation testing in adults with locally advanced or metastatic non-small cell lung cancer: A systematic review and cost-effectiveness analysis

__Abstract__ Background: Non-small cell lung cancer (NSCLC) is the most common form of lung cancer. Some epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutations make tumours responsive to treatment with EGFR-TK inhibitors (EGFR-TKIs) but less responsive to treatment with standard chemotherapy. Patients with NSCLC are therefore tested for EGFR-TK tumour gene mutations to inform treatment decisions. There are a variety of tests available to detect these mutations. The different tests vary in the specific mutations that they attempt to detect, the amount of tumour cells needed for the test to work, the time that it takes to give a result, the error rate of the test, and the cost of the test. Objective: To compare the performance and cost-effectiveness of EGFR-TK mutation tests used to identify previously untreated adults with locally advanced or metastatic NSCLC, who may benefit from first-line treatment with TKIs. Data sources: Twelve databases to August 2012 [including MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations and Daily Update (OvidSP), 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 database (HTA), Science Citation Index (SCI), Latin American and Caribbean Health Sciences Literature (LILACS), BIOSIS Previews, NIHR Health Technology Assessment programme, PROSPERO (International Prospective Register of Systematic Reviews)], research registers and conference proceedings. A web-based survey gathered data on technical performance of EGFR-TK mutation tests. Methods: Randomised controlled trials were assessed for methodological quality using the Cochrane risk of bias tool. Diagnostic accuracy studies were assessed using QUADAS-2. There were insufficient data for m