KRAS mutation as a prognostic factor and predictive factor in advanced/metastatic non-small cell lung cancer: A systematic literature review and meta-analysis.

KRAS (Kirsten Rat Sarcoma) is the most common oncogenic mutation detected in patients with non-small cell lung cancer (NSCLC). However, the role of KRAS as either a prognostic factor or predictive factor (modifier of treatment effects) in NSCLC is not well established at this time. This systematic literature review (SLR) and meta-analysis synthesized the available evidence regarding the role of KRAS mutation as a predictive factor and/or prognostic factor of survival and response outcomes in patients with advanced/metastatic (stage IIIB-IV) NSCLC.

A cost-effectiveness analysis of first-line induction and maintenance treatment sequences in patients with advanced nonsquamous non-small-cell lung cancer in France.

Background: Comparative effectiveness and cost-effectiveness data for induction-maintenance (I-M) sequences for the treatment of patients with nonsquamous non-small-cell lung cancer (nsqNSCLC) are limited because of a lack of direct evidence. This analysis aimed to compare the cost-effectiveness of I-M pemetrexed with those of other I-M regimens used for the treatment of patients with advanced nsqNSCLC in the French health-care setting.

Materials And Methods: A previously developed global partitioned survival model was adapted to the France-only setting by restricting treatment sequences to include 12 I-M regimens most relevant to France, and incorporating French costs and resource-use data.

Bayesian Model Assessment in Joint Modeling of Longitudinal and Survival Data with Applications to Cancer Clinical Trials.

Joint models for longitudinal and survival data are routinely used in clinical trials or other studies to assess a treatment effect while accounting for longitudinal measures such as patient-reported outcomes (PROs). In the Bayesian framework, the deviance information criterion (DIC) and the logarithm of the pseudo marginal likelihood (LPML) are two well-known Bayesian criteria for comparing joint models. However, these criteria do not provide separate assessments of each component of the joint model.

JMFit: A SAS Macro for Joint Models of Longitudinal and Survival Data.

Joint models for longitudinal and survival data now have a long history of being used in clinical trials or other studies in which the goal is to assess a treatment effect while accounting for a longitudinal biomarker such as patient-reported outcomes or immune responses. Although software has been developed for fitting the joint model, no software packages are currently available for simultaneously fitting the joint model and assessing the fit of the longitudinal component and the survival component of the model separately as well as the contribution of the longitudinal data to the fit of the survival model. To fulfill this need, we develop a SAS macro, called JMFit.

First-Line Pemetrexed Plus Cisplatin Followed by Gefitinib Maintenance Therapy Versus Gefitinib Monotherapy in East Asian Never-Smoker Patients With Locally Advanced or Metastatic Nonsquamous Non-Small-cell Lung Cancer: Quality of Life Results From a Randomized Phase III Trial.

Background: The efficacy results from an open-label, randomized, multicenter study found no significant difference in progression-free survival between pemetrexed plus cisplatin followed by maintenance gefitinib (PC/G) and gefitinib monotherapy (G) in patients with advanced nonsquamous non-small-cell lung cancer (NSCLC) and unknown epidermal growth factor receptor (EGFR) mutation status (hazard ratio favored PC/G). The present report describes the quality of life (QoL) results from that trial.

Patients And Methods: Chemotherapy-naive, East Asian, light ex-smokers or never-smokers with advanced nonsquamous NSCLC and unknown EGFR mutation status (n = 236) were randomly assigned (1:1) to PC/G or G.

Cost-effectiveness of first-line induction and maintenance treatment sequences in non-squamous non-small cell lung cancer (NSCLC) in the U.S.

Objectives: Due to the lack of direct head-to-head trials, there are limited data regarding the comparative effectiveness of induction-maintenance sequences. The objective of this study was to develop a cost-effectiveness model to compare induction-maintenance sequences in the US for the treatment of advanced non-squamous NSCLC.

Materials And Methods: Decision analytic modelling was used to synthesize the treatment effect and baseline risk estimates for nine induction and maintenance treatment sequences, reflecting treatments used in the US.

Can bundled payment improve quality and efficiency of care for patients with hip fractures?

The current Medicare reimbursement for hip fractures lacks accountability and promotes cost cutting. A bundled payment system-analogous to the Medicare Acute Care Episodes Demonstration for Orthopedic and Cardiovascular Surgery-may help curtail costs, foster communication among health care providers, and improve their accountability for patient outcomes. In hip fracture care, bundled payment may spur development of multidisciplinary best practice guidelines, quality assessment, and reporting, and result in benchmarking and best practices sharing.

Assessing model fit in joint models of longitudinal and survival data with applications to cancer clinical trials.

Joint models for longitudinal and survival data now have a long history of being used in clinical trials or other studies in which the goal is to assess a treatment effect while accounting for longitudinal assessments such as patient-reported outcomes or tumor response. Compared to using survival data alone, the joint modeling of survival and longitudinal data allows for estimation of direct and indirect treatment effects, thereby resulting in improved efficacy assessment. Although global fit indices such as AIC or BIC can be used to rank joint models, these measures do not provide separate assessments of each component of the joint model.

Joint modeling of survival and longitudinal non-survival data: current methods and issues. Report of the DIA Bayesian joint modeling working group.

Explicitly modeling underlying relationships between a survival endpoint and processes that generate longitudinal measured or reported outcomes potentially could improve the efficiency of clinical trials and provide greater insight into the various dimensions of the clinical effect of interventions included in the trials. Various strategies have been proposed for using longitudinal findings to elucidate intervention effects on clinical outcomes such as survival. The application of specifically Bayesian approaches for constructing models that address longitudinal and survival outcomes explicitly has been recently addressed in the literature.

Direct medical costs for complications among children and adults with diabetes in the US commercial payer setting.

Background: Complications associated with diabetes are a major contributor to the burden of the disease. To better inform decision modelling, there is a need for cost estimates of specific diabetes-related complications, stratified by diabetes type and patient age group.

Objective: To obtain direct medical costs of managing and treating diabetes-related complications over a 2-year period, for adults and children with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM), using data from a large commercially insured US subscriber database.

Joint modeling of longitudinal outcomes and survival using latent growth modeling approach in a mesothelioma trial.

Joint modeling of longitudinal and survival data can provide more efficient and less biased estimates of treatment effects through accounting for the associations between these two data types. Sponsors of oncology clinical trials routinely and increasingly include patient-reported outcome (PRO) instruments to evaluate the effect of treatment on symptoms, functioning, and quality of life. Known publications of these trials typically do not include jointly modeled analyses and results.

Joint modeling of multiple longitudinal patient-reported outcomes and survival.

Researchers often include patient-reported outcomes (PROs) in Phase III clinical trials to demonstrate the value of treatment from the patient's perspective. These data are collected as longitudinal repeated measures and are often censored by occurrence of a clinical event that defines a survival time. Hierarchical Bayesian models having latent individual-level trajectories provide a flexible approach to modeling such multiple outcome types simultaneously.

Multicenter phase II trial of enzastaurin in patients with relapsed or refractory advanced cutaneous T-cell lymphoma.

This multicenter, single-arm, open-label non-randomized phase II trial (NCT00744991) was conducted in patients with recurrent/refractory mycosis fungoides (MF), stage IB-IVB, or Sézary syndrome (SS). A Simon two-stage design required 25 patients enrolled in stage 1 with ≥7 confirmed objective responses for expansion into stage 2. Patients were treated with oral enzastaurin (250 mg twice daily) until disease progression or intolerable toxicity.

The economic burden of metastatic breast cancer: a systematic review of literature from developed countries.

Objective: Breast cancer, the most common malignant cancer among women in Western countries, has poor prognosis following metastasis. New therapies potentially extend survival, but their value is questioned when benefits are incremental and expensive. The objective of our study was to understand the economic impact of metastatic breast cancer (MBC) and its treatment, and to evaluate the designs of these studies.

Economic burden of follicular non-Hodgkin's lymphoma.

Follicular non-Hodgkin's lymphoma (FNHL), a slow-growing cancer of the immune system, constitutes about 15-30% of all incident non-Hodgkin's lymphoma in developed countries. Its incidence is rising worldwide. Patients can live many years, but FNHL is considered incurable.

Validity of 24-h recall ratings of pain severity: biasing effects of "Peak" and "End" pain.

Despite the frequent use of pain recall ratings in clinical research, there remains doubt about the ability of individuals to accurately recall their pain. In particular, previous research indicates the possibility that the most pain experienced during a recall period and the most recent pain experienced (known as peak and end effects, respectively) might bias recall ratings. The current study used data from a published clinical trial to determine the relative validity of a 24-h recall rating of average post-operative pain and the nature and extent of any biasing influence of peak and end effects on nine separate 24-h recall ratings.

Safety and efficacy of the cyclooxygenase-2 inhibitors parecoxib and valdecoxib after noncardiac surgery.

Background: Valdecoxib and its intravenous prodrug parecoxib are reported to increase thromboembolic risk after coronary artery bypass grafting. The authors conducted a randomized trial to examine their safety and analgesic efficacy in patients recovering from major noncardiac surgical procedures.

Methods: The trial was randomized and double-blind, with 10 days of treatment and 30 days of follow-up.

Medical visits among adults with symptoms commonly associated with an overactive bladder.

Objectives: To examine nationally representative data and thus obtain estimates of the use of healthcare providers associated with the overactive bladder (OAB) symptoms, a condition characterized by frequency, urgency and nocturia, with or with no urge incontinence, as although it is ranked among the 10 most common chronic medical conditions in the USA, the level of OAB-associated medical treatment remains largely unknown.

Methods: To estimate the number of annual OAB-associated medical visits among patients aged > or =18 years, three national databases in the USA (year 2000) were examined: the National Ambulatory Medical Care Survey, the National Hospital Ambulatory Medical Care Survey, and the National Hospital Discharge Survey. Population estimates were constructed using design-based statistical analyses to account for the complex survey designs of data.