Search results for "Endpoint Determination"
showing 6 items of 36 documents
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…
The use of three-dimensional oral mucosa cell cultures to assess the toxicity of soldered and welded wires
2007
The aim of the present study was to determine whether there is a difference in toxicity and loss of viability of three-dimensional (3D) reconstructed human oral epithelium (RHOE) cell cultures induced by point-welded (PW), laser-welded (LW), and silver-soldered (SiS) orthodontic wires. Three types of soldered stainless steel (SS) wires: PW, LW, and SiS were prepared ( n = 3) and subjected to multiple end-point analysis (MEA). Six pieces were cut from each wire. Each piece was placed on the triplicate cell cultures (RHOE model based on TR 146 cells). After 24 hours of topical exposure, the cell cultures were cut and stained with haematoxylin/eosin. Toxicity was assessed by evaluating the mor…
Guidelines for time-to-event end point definitions in sarcomas and gastrointestinal stromal tumors (GIST) trials: results of the DATECAN initiative (…
2015
ABSTRACT The DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials) aims to provide recommendations for definitions of time-to-event end points in cancer randomized controlled trials. We relied on a consensus method based on a multidisciplinary panel of experts to develop these guidelines for trials on sarcomas and gastrointestinal stromal tumors. Background The use of potential surrogate end points for overall survival, such as disease-free survival (DFS) or time-to-treatment failure (TTF) is increasingly common in randomized controlled trials (RCTs) in cancer. However, the definition of time-to-event (TTE) end points is rarely precise and lacks unif…
Is time to joint replacement a valid outcome measure in clinical trials of drugs for osteoarthritis?
2003
The rate of radiographic joint space narrowing is commonly used today as a structural outcome measure in clinical trials evaluating potential disease-modifying drugs in patients with hip osteoarthritis, but this results in a continuous variable. Among the methods proposed to circumvent this problem, it has been suggested that the incidence of total hip arthoplasty (THA) provides a hard outcome measure. It is a dichotomized variable, easy to measure and sensitive to change, with acceptable intrinsic validity. However, because this measure is limited by the variability of factors underlying the decision to perform surgery and the length of waiting lists, it has been suggested that time to ful…