Search results for "endpoint"
showing 10 items of 437 documents
Rare Cancers Europe (RCE) methodological recommendations for clinical studies in rare cancers: A European consensus position paper
2015
While they account for one-fifth of new cancer cases, rare cancers are difficult to study. A higher than average degree of uncertainty should be accommodated for clinical as well as for population-based decision making. Rules of rational decision making in conditions of uncertainty should be rigorously followed and would need widely informative clinical trials. In principle, any piece of new evidence would need to be exploited in rare cancers. Methodologies to explicitly weigh and combine all the available evidence should be refined, and the Bayesian logic can be instrumental to this end. Likewise, Bayesian-design trials may help optimize the low number of patients liable to be enrolled in …
Exercise training improves peak oxygen consumption and hemodynamics in patients with pulmonary hypertension – A prospective, randomized, controlled t…
2016
Aims: This prospective randomized controlled study investigates the effects of exercise training on peak VO 2 /kg, hemodynamics and further clinically relevant parameters in pulmonary hypertension (PH) patients. Methods: Eighty-seven patients with pulmonary arterial hypertension and inoperable chronic thromboembolic PH (54% female, 56±15years, 84% WHO functional class III/IV, 53% combination therapy) on stable disease-targeted medication were randomly assigned to a control and training group. Medication remained unchanged during the study period. Non-invasive assessments and right heart catheterization at rest and during exercise were performed at baseline and after 15 weeks. Primary endpoi…
Real-World Management of Myelofibrosis with Ruxolitinib: Initial Analysis of an Italian Observational Study (ROMEI)
2018
Abstract Introduction ROMEI (CINC424AIT04 Ruxolitinib Observational study in Myelofibrosis treated patiEnts in Italy) is a prospective observational study that aims to bridge the knowledge gap between the clinical experience of registration trials and routine patient management by following roughly 200 myelofibrosis (MF) patients (pts) treated with ruxolitinib in everyday clinical practice. Enrollment began in April 2017 and ended in May 2018. Methods The primary endpoint is to evaluate changes in symptoms and quality of life during treatment with ruxolitinib through the Myeloproliferative Neoplasm 10 (MPN-10) disease-specific questionnaire and EuroQoL-5D-5L (EQ-5D-5L) general health questi…
Predictors of scaffold failure and impact of optimized scaffold implantation technique on outcome: Results from the German-Austrian ABSORB RegIstRy.
2021
Aims We aimed to investigate predictors of scaffold failure and the potential impact of an optimized scaffold implantation technique by means of a learning curve on long-term clinical outcome after bioresorbable scaffold (BRS) implantation and to evaluate predictors of scaffold failure. Methods and results A total of 3326 patients were included in this prospective, observational, multi-center study (ClinicalTrials.gov NCT02066623) of consecutive patients undergoing BRS implantation between November 2013 and January 2016. The 3144 patients completed follow-up after 24 months, 3265 patients were eligible for time-to-event-analysis. Clinical endpoints were major adverse cardiac events-a compos…
HALT-C in the final analysis: A molehill out of a mountain
2009
Prolonged therapy of advanced chronic hepatitis C with low-dose peginterferon. Di Bisceglie AM, Shiffman ML, Everson GT, Lindsay KL, Everhart JE, Wright EC, Lee WM, Lok AS, Bonkovsky HL, Morgan TR, Ghany MG, Morishima C, Snow KK, Dienstag JL, HALT-C Trial Investigators. Background In patients with chronic hepatitis C who do not have a response to antiviral treatment, the disease may progress to cirrhosis, liver failure, hepatocellular carcinoma, and death. Whether long-term antiviral therapy can prevent progressive liver disease in such patients remains uncertain. Methods We conducted a randomized, controlled trial of peginterferon alfa-2a at a dosage of 90μg per week for 3.5 years, as comp…
The Evolving Scenario in the Assessment of Radiological Response for Hepatocellular Carcinoma in the Era of Immunotherapy: Strengths and Weaknesses o…
2022
Hepatocellular carcinoma (HCC) is a challenging malignancy characterised by clinical and biological heterogeneity, independent of the stage. Despite the application of surveillance programs, a substantial proportion of patients are diagnosed at advanced stages when curative treatments are no longer available. The landscape of systemic therapies has been rapidly growing over the last decade, and the advent of immune-checkpoint inhibitors (ICIs) has changed the paradigm of systemic treatments. The coexistence of the tumour with underlying cirrhosis exposes patients with HCC to competing events related to tumour progression and/or hepatic decompensation. Therefore, it is relevant to adopt prop…
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…
A weighted combined effect measure for the analysis of a composite time-to-first-event endpoint with components of different clinical relevance
2018
Composite endpoints combine several events within a single variable, which increases the number of expected events and is thereby meant to increase the power. However, the interpretation of results can be difficult as the observed effect for the composite does not necessarily reflect the effects for the components, which may be of different magnitude or even point in adverse directions. Moreover, in clinical applications, the event types are often of different clinical relevance, which also complicates the interpretation of the composite effect. The common effect measure for composite endpoints is the all-cause hazard ratio, which gives equal weight to all events irrespective of their type …
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…
Sample size in cluster-randomized trials with time to event as the primary endpoint
2011
In cluster-randomized trials, groups of individuals (clusters) are randomized to the treatments or interventions to be compared. In many of those trials, the primary objective is to compare the time for an event to occur between randomized groups, and the shared frailty model well fits clustered time-to-event data. Members of the same cluster tend to be more similar than members of different clusters, causing correlations. As correlations affect the power of a trial to detect intervention effects, the clustered design has to be considered in planning the sample size. In this publication, we derive a sample size formula for clustered time-to-event data with constant marginal baseline hazards…