Assessment endpoint, definition

The US Environmental Protection Agency (USEPA 1998) describes problem formulation as an iterative process with 4 main components integration of available information, definition of assessment endpoints, definition of conceptual model, and development of an analysis plan. These 4 components apply also to probabilistic assessments. In addition, it is useful to emphasize the importance of a 5th component dehnition of the assessment scenarios. The relationships between all 5 components are depicted in Figure 2.1. Note that the bidirectional arrows represent the interdependency of the different components and imply that they may need to be revised iteratively as the formulation of the problem is rehned. 

Laboratory data are most often associated with safety analyses, but they may play a part in efficacy analyses as well, especially if the laboratory data are part of the clinical endpoint definition. From a CDISC perspective, laboratory data are a finding, as they are a planned assessment. 

If the assessment is to be probabilistic, the risk assessor and risk manager should consider together how this influences the definition of the assessment endpoint. Suter (1998) suggests 5 questions for the risk assessor to ask the risk manager to help define the assessment endpoint ... 

Essential prereqnisites for a probabilistic risk assessment are a well thought-out problem formulation and a clear definition of the assessment endpoints. The probabilistic approach according to its very natnre aims at making predictions on quantities or the occurrence of certain events. Snch qnantities and events must be specified precisely such that, at least in principle, there is no doubt on what the quantity is or whether the event happened (Morgan and Henrion 1990). 

Formulating the assessment problem well is an essential foundation for risk assessment. The workshop considered how the use of probabilistic models and uncertainty analysis affects problem formulation and its main components the integration of available information, definition of the assessment endpoint, specification of the conceptual model, and planning of the analysis phase. 

Endpoint entity An organism, population, species, community, or ecosystem that has been chosen for protection. The endpoint entity is 1 component of the definition of an assessment endpoint. 

The result of the Phase II trial is information needed to determine the effective dose and the dosing regimen of frequency and duration. Specihc chnical endpoints or markers are used to assess interaction of drug and disease. There are two types of markers definitive and surrogate. For example, in the case of cancer or hypertension, the definitive markers are mortality and stroke, respectively, and the surrogate markers may be tumor size, or cancer-associated proteins p53, TGF-a in the case of cancer, and blood pressure or cholesterol level in hypertension. Statistical analysis is carried out to evaluate the... 

It is in this context, that in 2009, the DART committee formed a Steering Team to work on a project titled Consensus List of Developmental Toxicants. The Steering Team published a report of their deliberations and defined developmental toxicant in terms of its concentration in vitro (27). Daston et al. (27) based the definitions of positive and negative developmental toxicants according to their exposure conditions. That is, compounds on the list could have an exposure concentration that is unequivocally positive and a concentration that is unequivocally negative. In addition, only permanent effects that alter fetal organization, particularly structural malformations, were considered developmental toxicity. For example, fetal weight decreases (which are commonly used endpoints in risk assessment) are not considered developmental toxicity for the purposes of this list. 

In this chapter we will follow the structure suggested by the OECD recommendations. We will review the development of measures of goodness of fit, robustness, assessment of predictability for continuous models and models for classified endpoints, and the definition of domains of applicability. The aim is not to provide a comprehensive summary of all papers in this field, but to provide key references that have influenced the author s continuing journey to becoming a better QSAR scientist. 

Patients with osteoarthritis or rheumatoid arthritis are randomized to one of three treatments, celecoxib, ibuprofen, or naproxen, and the primary endpoint is the occurrence of a cardiovascular endpoint a nonfatal myocardial infarction, a nonfatal stroke, or any cardiovascular death. Non-inferiority will be assessed for three different pairwise comparisons celecoxib versus ibuprofen, celecoxib versus naproxen, and ibuprofen versus naproxen. The definition of non-inferiority differs somewhat from the fixed margin approach describe earlier in that there are separate criteria for the confidence interval and the point estimate. The hazard ratio for each comparison will be calculated, and non-inferiority will be concluded if the upper end of the... 

A uniform experimental assessment scheme cannot reflect the varying ambient (field) situations and transformation processes. A (defined) test system needs clear evaluation criteria, but the various test procedures do not agree on a definite endpoint. Accordingly, it has to be recognized that biodegradability is not a uniform principal property of chemical contaminants and that biodegradability is not a well-defined parameter. 

In order to define these aspects, providing a risk decision basis to assess the permissive logics matrix, this paper presents a hazard evaluation approach which applies HAZOP and LOPA methodologies to the coke drums operation. The application of this approach to a Petrobras DCU coke drums cycle raised the discussion about specific aspects of these methodologies, such as the nodes definition the HAZOP scenarios consequence endpoints which are the interest of LOPA the HAZOP cause-by-cause documentation approach and the criteria used to select a HAZOP scenario for the LOPA analysis. The disadvantages of perfonning HAZOP and LOPA analyses in two separated facditated session were also discussed. 

---