Composite endpoints variables

From these lines of evidence, it is apparent that the most likely reason for variability between interventional and medical management trials appears to be related to the frequency of early revascularization (100% in the former vs, <20% in the latter) and the utilization of periprocedural biomarker elevation criterion for Ml. Thus, treatment benefit associated with GPIIb/llla inhibitor is observed very early and is primarily driven by reduction in postprocedural biomarker elevation, the least robust but the most prevalent component of the composite endpoint with little benefit on death or Q-wave Ml. 

Experience profound compositional shifts in use May experience phases changes in use Site in the disease s location Operate at variable drug activity Highly nonstationary state kinetics Application technique and amount are highly individualized Applications short-acting Local tissue levels tied to efficacy Used on diseased, damaged skin No easy bioequivalency endpoint Systemic absorption absolutely undesirable, but some unavoidable... 

Another way of avoiding adjustment is to combine the multiple measurements into a single composite variable. Examples would be disease-lfee survival in oncology, where the variable is the time to either disease recurrence or death, whichever occurs first, or a composite of death, non-fatal stroke, MI and heart failure, a binary outcome in a cardiovascular setting. This approach does not require adjustment of the significance level we are back to having a single primary endpoint. 

The link between exposure to air pollutants and adverse health effects is well established, but the causal biological mechanisms are not clear and this is especially the case for particulate matter health effects. Airborne particulate matter is extremely variable in chemical composition, size and morphology all parameters of possible health relevance. This and the different health endpoints affected by exposure to ambient PM make the situation very complex. It may well be that more than one particle characteristic is needed to effectively describe the harmful outcomes of exposure. Possible parameters under discussion are particle number concentration, which is dominated by particles below 100 nm in size the so-called ultrafines [33], particle surface area concentration, which is dominated by particles around 200-800 nm in diameter [34, 35], black carbon or black smoke [36], or the reactivity of particles with respect to redox reactions, or their potential to form radical oxidative species (ROS) [37]. These and some other alternative particulate indicators are currently discussed [38] and investigated in several large European and US studies such as ESCAPE and Transphorm2. 

Stacking the isothermal Gibbs triangles on top of each other results in a phase prism (see Fig. 1.3(a)), which represents the temperature-dependent phase behaviour of ternary water-oil-non-ionic surfactant systems. As discussed above, non-ionic surfactants mainly dissolve in the aqueous phase at low temperatures (2). Increasing the temperature one observes that this surfactant-rich water phase splits into two phases (a) and (c) at the temperature T of the lower critical endpoint cepp, i.e. the three-phase body appears. Subsequently, the lower water-rich phase (a) moves towards the water corner, while the surfactant-rich middle phase (c) moves towards the oil corner of the phase prism. At the temperature Tu of the upper critical endpoint cepa a surfactant-rich oil phase is formed by the combination of the two phases (c) and (b) and the three-phase body disappears. Each point in such a phase prism is unambiguously defined by the temperature T and two composition variables. It has proved useful [6] to choose the mass fraction of the oil in the... 

Tiered ToxicologicaUSafety Approach Botanical substances may be used at variable levels in personal care products. This together with the type of product to which the extract is being added will define the level of exposure to the consumer. The safety assessment approach can be flexible based on the level of botanical or natural substances in the product. The approach to these extracts is based on tiers. The first tier would be based on very conservative assumptions using worst-case scenarios and the last tier would require an in-depth knowledge of the exact composition if the botanical extract to be used and specific toxicological data to address all relevant endpoints. The three tiers addresses Type I dermal and systemic endpoints. Explanation as to how these tiers were set is provided in detail in the corresponding book chapter. 

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