Search results for "controlled"

Field-practice study of sorafenib therapy for hepatocellular carcinoma: a prospective multicenter study in Italy

2011

A multicenter randomized controlled trial established sorafenib as a standard of care for patients with advanced hepatocellular carcinoma (HCC). Because the study was prematurely interrupted due to survival benefits in the sorafenib arm, we conducted an observational study to adequately assess risks and benefits of this regimen in field practice. Starting in 2008, all clinically compensated patients with advanced HCC and those with an intermediate HCC who were unfit or failed to respond to ablative therapies were consecutively evaluated in six liver centers in Italy, for tolerability as well as radiologic and survival response to 800-mg/d sorafenib therapy. Treatment was down-dosed or inter…

Outcomes of hepatocellular carcinoma patients treated with sorafenib: a meta-analysis of Phase III trials

2019

Aim: To benchmark overall survival (OS) and time to radiological progression (TTP) of patients enrolled in randomized controlled trials (RCTs) assessing sorafenib in advanced hepatocellular carcinoma using individual participant survival data, and to meta-analyze prognostic factors for OS and TTP. Methods: RCTs were identified through literature search until December 2018. Individual participant survival was reconstructed with an algorithm from published Kaplan–Meier curves. Results: Ten RCTs were included. Median OS was 10.0 months (95% CI: 9.6–10.5), and median TTP was 4.1 months (95% CI: 3.8–4.3). Multivariable analyses showed HCV positivity, absence of macrovascular invasion and extra-…

Systemic therapy for intermediate and advanced hepatocellular carcinoma: Sorafenib and beyond.

2018

The hepatocellular carcinoma (HCC) treatment landscape changed a decade ago, with sorafenib demonstrating survival benefit in the first-line setting and becoming the first systemic therapy to be approved for HCC. More recently, regorafenib and nivolumab have received approval in the second-line setting after sorafenib, with further positive phase 3 studies emerging in the first line (lenvatinib non-inferior to sorafenib) and second line versus placebo (cabozantinib and ramucirumab). A key recommendation in the management of patients receiving sorafenib is to promote close communication between the patient and the physician so that adverse events (AEs) are detected early and severe AEs can b…

Immediate effects of the respiratory stimulation on ventilation parameters in ischemic stroke survivors: A randomized interventional study (CONSORT).

2019

Background: Post-stroke brain damage, which affects the central control of respiration, leads to various respiratory disorders. They can be caused by the weakening of the respiratory muscles and chest movements, which can indirectly contribute to an impairment of the ventilation function. The aim of the study is an objective assessment of the effect of a single-session intervention of respiratory stimulation through Proprioceptive Neuromuscular Facilitation (PNF) on chosen respiratory parameters and the following comparison of these changes with a group in which positioning was used (intra- and intergroup comparison). Methods: This was a randomized interventional study evaluating the respir…

Effect of a common exercise programme with an individualised progression criterion based on the measurement of neuromuscular capacity versus current …

2021

IntroductionHigh-load resistance training has shown positive effects in pain and function in lower limb tendinopathies. However, some authors suggest that current exercise programmes produce an increase in tolerance to load and exercise in general but without fixing some existing issues in tendinopathy. This may indicate the need to include training aspects not currently taken into account in the current programmes. The main objective of this study will be to compare the effect of a common exercise protocol for the three predominant lower limb tendinopathies (Achilles, patellar and gluteal), based on an individualised control of the dose and training of specific aspects of the neuromuscular…

Statin therapy in patients with aortic stenosis after the ASTRONOMER trial: is there still any space?

2011

Power of the Wilcoxon–Mann–Whitney test for non‐inferiority in the presence of death‐censored observations

2017

In clinical trials with patients in a critical state, death may preclude measurement of a quantitative endpoint of interest, and even early measurements, for example for intention-to-treat analysis, may not be available. For example, a non-negligible proportion of patients with acute pulmonary embolism will die before 30 day measurements on the efficacy of thrombolysis can be obtained. As excluding such patients may introduce bias, alternative analyses, and corresponding means for sample size calculation are needed. We specifically consider power analysis in a randomized clinical trial setting in which the goal is to demonstrate noninferiority of a new treatment as compared to a reference t…

On the analysis of a random walk-jump chain with tree-based transitions and its applications to faulty dichotomous search

2018

Random Walks (RWs) have been extensively studied for more than a century [1]. These walks have traditionally been on a line, and the generalizations for two and three dimensions, have been by extending the random steps to the corresponding neighboring positions in one or many of the dimensions. Among the most popular RWs on a line are the various models for birth and death processes, renewal processes and the gambler’s ruin problem. All of these RWs operate “on a discretized line”, and the walk is achieved by performing small steps to the current-state’s neighbor states. Indeed, it is this neighbor-step motion that renders their analyses tractable. When some of the transitions are to non-ne…

Assessing covariate imbalance in meta-analysis studies.

2010

The main goal of meta-analysis is to combine data across studies or data sets to obtain summary estimates. In this paper, the novelty is to propose a statistical tool to assess a possible covariate imbalance in baseline variables to investigate similarity of trials. We conducted the detection of the covariate imbalance, first, through some graphical comparison of the empirical cumulative distribution functions or ECDFs, which are built by putting together arms or trials according to some risk factor, and second, through some non-parametric tests such as the Kolmogorov–Smirnov and the Anderson–Darling tests. To overcome the huge presence of ties, we conducted the statistical tests on perturbe…

Test and power considerations for multiple endpoint analyses using sequentially rejective graphical procedures

2009

A variety of powerful test procedures are available for the analysis of clinical trials addressing multiple objectives, such as comparing several treatments with a control, assessing the benefit of a new drug for more than one endpoint, etc. However, some of these procedures have reached a level of complexity that makes it difficult to communicate the underlying test strategies to clinical teams. Graphical approaches have been proposed instead that facilitate the derivation and communication of Bonferroni-based closed test procedures. In this paper we give a coherent description of the methodology and illustrate it with a real clinical trial example. We further discuss suitable power measur…