Biomarker-Guided Antibiotic Duration for Hospitalized Patients With Suspected Sepsis: The ADAPT-Sepsis Randomized Clinical Trial.

Importance: For hospitalized critically ill adults with suspected sepsis, procalcitonin (PCT) and C-reactive protein (CRP) monitoring protocols can guide the duration of antibiotic therapy, but the evidence of the effect and safety of these protocols remains uncertain.

Objective: To determine whether decisions based on assessment of CRP or PCT safely results in a reduction in the duration of antibiotic therapy.

Design, Setting, And Participants: A multicenter, intervention-concealed randomized clinical trial, involving 2760 adults (≥18 years), in 41 UK National Health Service (NHS) intensive care units, requiring critical care within 24 hours of initiating intravenous antibiotics for suspected sepsis and likely to continue antibiotics for at least 72 hours.

Dynamic and Flexible Survival Models for Extrapolation of Relative Survival: A Case Study and Simulation Study.

Background: Extrapolation of survival data is a key task in health technology assessments (HTAs), which may be improved by incorporating general population mortality data via relative survival models. Dynamic survival models are a promising method for extrapolation that may be expanded to dynamic relative survival models (DRSMs), a novel development presented here. There are currently neither examples of dynamic models in HTA nor comparisons of DRSMs with other relative survival models when used for survival extrapolation.

Comparing current and emerging practice models for the extrapolation of survival data: a simulation study and case-study.

Background: Estimates of future survival can be a key evidence source when deciding if a medical treatment should be funded. Current practice is to use standard parametric models for generating extrapolations. Several emerging, more flexible, survival models are available which can provide improved within-sample fit.

The Extrapolation Performance of Survival Models for Data With a Cure Fraction: A Simulation Study.

Objectives: Curative treatments can result in complex hazard functions. The use of standard survival models may result in poor extrapolations. Several models for data which may have a cure fraction are available, but comparisons of their extrapolation performance are lacking.

Generalized Linear Models for Flexible Parametric Modeling of the Hazard Function.

Parametric modeling of survival data is important, and reimbursement decisions may depend on the selected distribution. Accurate predictions require sufficiently flexible models to describe adequately the temporal evolution of the hazard function. A rich class of models is available among the framework of generalized linear models (GLMs) and its extensions, but these models are rarely applied to survival data.

Modeling the Economic Impact of Interventions for Older Populations with Multimorbidity: A Method of Linking Multiple Single-Disease Models.

Individuals from older populations tend to have more than 1 health condition (multimorbidity). Current approaches to produce economic evidence for clinical guidelines using decision-analytic models typically use a single-disease approach, which may not appropriately reflect the competing risks within a population with multimorbidity. This study aims to demonstrate a proof-of-concept method of modeling multiple conditions in a single decision-analytic model to estimate the impact of multimorbidity on the cost-effectiveness of interventions.

The Cost-effectiveness of Sequences of Biological Disease-modifying Antirheumatic Drug Treatment in England for Patients with Rheumatoid Arthritis Who Can Tolerate Methotrexate.

Objective: To ascertain whether strategies of treatment with a biological disease-modifying antirheumatic drug (bDMARD) are cost-effective in an English setting. Results are presented for those patients with moderate to severe rheumatoid arthritis (RA) and those with severe RA.

Methods: An economic model to assess the cost-effectiveness of 7 bDMARD was developed.

Modelling the cost effectiveness of interventions for osteoporosis: issues to consider.

Expenditure on treating osteoporotic fractures and on preventative intervention is considerable and is likely to rise in forthcoming years due to the association between fracture risk and age. With funders such as the National Institute for Health and Care Excellence and the Pharmaceutical Benefits Advisory Committee explicitly considering cost-effectiveness analyses within the process of producing guidance, it is imperative that economic models are as robust as possible. This article details issues that need to be considered specifically related to health technology assessments of interventions for osteoporosis, and highlights limitations within the current evidence base.

Cost-effectiveness of presentation versus delayed troponin testing for acute myocardial infarction.

Objectives: To estimate the cost-effectiveness of delayed troponin testing for myocardial infarction compared with troponin testing at presentation.

Design: Decision analysis modelling of cost-effectiveness using secondary data sources.

Setting: Acute hospitals in the UK.

Granulocyte colony-stimulating factors for febrile neutropenia prophylaxis following chemotherapy: systematic review and meta-analysis.

Background: Febrile neutropenia (FN) occurs following myelosuppressive chemotherapy and is associated with morbidity, mortality, costs, and chemotherapy reductions and delays. Granulocyte colony-stimulating factors (G-CSFs) stimulate neutrophil production and may reduce FN incidence when given prophylactically following chemotherapy.

Methods: A systematic review and meta-analysis assessed the effectiveness of G-CSFs (pegfilgrastim, filgrastim or lenograstim) in reducing FN incidence in adults undergoing chemotherapy for solid tumours or lymphoma.

Consistency between direct and indirect trial evidence: is direct evidence always more reliable?

Objectives: To present a case study involving the reduction in incidence of febrile neutropenia (FN) after chemotherapy with granulocyte colony-stimulating factors (G-CSFs), illustrating difficulties that may arise when following the common preference for direct evidence over indirect evidence.

Methods: Evidence of the efficacy of treatments was identified from two previous systematic reviews. We used Bayesian evidence synthesis to estimate relative treatment effects based on direct evidence, indirect evidence, and both pooled together.

Cost-effectiveness of granulocyte colony-stimulating factor prophylaxis for febrile neutropenia in breast cancer in the United Kingdom.

Objective: We report a cost-effectiveness evaluation of granulocyte colony-stimulating factors (G-CSFs) for the prevention of febrile neutropenia (FN) after chemotherapy in the United Kingdom (UK).

Methods: A mathematical model was constructed simulating the experience of women with breast cancer undergoing chemotherapy. Three strategies were modeled: primary prophylaxis (G-CSFs administered in all cycles), secondary prophylaxis (G-CSFs administered in all cycles after an FN event), and no G-CSF prophylaxis.

The cost-effectiveness of group cognitive behavioral therapy compared with routine primary care for women with postnatal depression in the UK.

Objective: To assess the cost-effectiveness of group cognitive behavior therapy (gCBT) in comparison with routine primary care for women with postnatal depression in the UK.

Methods: Our analysis was based on a systematic literature review of the relative clinical effectiveness of gCBT compared with routine primary care and further reviews, supplemented with expert opinion of the likely cost of providing gCBT and the duration of comparative advantage for gCBT. Raw data were used to estimate a statistical relationship between changes in the Edinburgh Postnatal Depression Score (EPDS) values and changes in short-form six dimensions' (SF-6D) values.

The cost effectiveness of a randomized controlled trial to establish the relative efficacy of vitamin K1 compared with alendronate.

Purpose: The authors aimed to evaluate whether vitamin K(1) or alendronate (the recommended treatment in England and Wales for postmenopausal women with a previous fracture) appeared to be the more cost-effective treatment for fracture prevention. Furthermore, expected value of sample information (EVSI) analyses were undertaken to estimate whether a head-to-head trial of alendronate and vitamin K(1) would be considered cost effective.

Method: A published osteoporosis model structure, populated with data from literature reviews, was used to evaluate the costs and quality-adjusted life-years associated with each intervention being provided to women at high risk of fracture, given current information.

Carotid artery imaging for secondary stroke prevention: both imaging modality and rapid access to imaging are important.

Background And Purpose: Patients with transient ischemic attack require carotid imaging to diagnose carotid stenosis. The differing sensitivity/specificity and availability of carotid imaging methods have created uncertainty over which noninvasive method is best and whether intra-arterial angiography is still required. We evaluated the influence of carotid imaging methods on secondary stroke prevention.

The cost-effectiveness of bosentan in the United Kingdom for patients with pulmonary arterial hypertension of WHO functional class III.

Objectives: To assess whether bosentan or no active intervention, in addition to palliative care, is the more cost-effective first-line treatment option for patients with idiopathic pulmonary arterial hypertension (iPAH) or PAH associated with connective tissue disease (PAH-CTD) of WHO functional classification (FC) III in the United Kingdom.

Methods: A cost-utility model simulated the treatment of patients with PAH of FC III. Patients remained on the selected intervention until death or clinical deterioration to FC IV, which would trigger initiation of epoprostenol treatment.

The cost-effectiveness of an RCT to establish whether 5 or 10 years of bisphosphonate treatment is the better duration for women with a prior fracture.

Purpose: Five years of bisphosphonate treatment have proven efficacy in reducing fractures. Concerns exist that long-term bisphosphonate treatment may actually result in an increased number of fractures. This study evaluates, in the context of England and Wales, whether it is cost-effective to conduct a randomized controlled trial (RCT) and what sample size may be optimal to estimate the efficacy of bisphosphonates in fracture prevention beyond 5 years.