Tiered Analysis

The rise of easy-to-use numerical models has led to a similar rise in complaints that some users treat them as black boxes or as if the model were one of those magic balls where the answer to any question mysteriously appears in a tiny window. In truth, the phenomenon of mindlessly accepting answers from any fool, be it a slide rule or a physical model, has always been with us however, numerical models have evolved to the point that we can generate many more incorrect answers than ever before. A solution to the black box problem exists in the form of an old solution technique—the tiered analysis, sometimes called the phased approach. 

In its basic form, tiered analysis consists of at least three steps  

At each step, ask, Is this result reasonable Does it agree with other steps Be able to explain the differences among the results. 

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Measured as part of a CAH panel by Minutti et al. [58], using the transition 287—>97, see above ("17-Hydroxyprogesterone ). They stress the added specificity of CAH detection in second-tier analysis for CAH when androstenedione is measured as well as 17-hydroxyprogesterone. This is also measured commercially by Quest Diagnostics and included in the Guo et al. hormonal profile [24, 25] (see Hormonal Steroid Profiles below). 

Typically, exposure and risk assessments conducted during regulatory evaluations are performed in a tiered or phased approach. A tiered approach refers to a process in which the exposure or risk assessment progresses systematically from relatively simple to more complex. An important feature of a tiered analysis is that the exposure or risk assessment and the accompanying uncertainty analysis may be refined in successive iterations. 

The biosensor and response system used a tiered approach. Samples of airborne biological material were taken continuously by the Joint Biological Point Detection System (JBPDS) equipment, which was not commercially available. Operation of these systems was monitored continuously at a separate control facility. Initial detection by the JBPDS equipment was followed by a second-tier assay analysis that, if positive, would result in physical collection of sampled material for additional analysis off-site. The confirmed second-tier analysis would result in notification of JBPDS leadership and shipment of a sample to the Utah Department of Health for further laboratory analysis. Because the confirmatory test would take 12-24 hours to complete, the primary function of the higher-tiered detection was to define treatment and decontamination responses (LP-3 options). Change in building or HVAC operation on the fifth and sixth floors would not be initiated until the Utah Department of Health analysis confirmed detection of a biological threat agent. 

Some labs utilize second-tier testing to limit false positives while avoiding false negatives. Second-tier analysis is based on more conservative cutoffs, in order for more newborn screens to initially flag as abnormal. Abnormal newborn screens in tier one will undergo more specialized studies immediately from the same newborn screening card. Only those samples that have abnormal second-tier studies will be reported as abnormal. This limits the number of infants... 

It is possible to take atty of the accident causation factors and break them down further in order to closer examine the influence that particular factor is having on the work system. This second tier analysis further increases knowledge about the work system through developing a better understanding of the individual processes that make up the system. It is in this area of investigation and analysis where we come closest to discovering tme accident causation. 

Olh cr I cacLiori s arc con trolled kin ctically, and the most stable product is not the major one observed. In these cases, you must look at the reactant side of the reaction coordinate to discover factors determ in in g th e ou tcorn e. Kloptn an an d Salem developed an analysis of reactivity in terms of two factois an electrostatic in leraclion approxim ated by atom ic ch arges an d a Kron tier orbital interaction, Fleming s book provides an excellent introduction to Ih ese ideas. 

Tiers N L, W D Carlson and M Karplus 1987 Analysis of Side-Chain Orientations in Homologous Proteins. Journal of Molecular Biology 196 175-198. 

Labor Expenses. In the majority of situations, projects will cause a company s labor requirements to change. This change could be a positive effect that increases available productive time, or there could be a decrease in employees production time depending upon the practice. When computing labor expenses, the Tier 1 costs could be significant. Labor expense calculations can be simplistic or comprehensive. The most direct and basic approach is to multiply the wage rate by the hours of labor. More comprehensive calculations include the associated costs of payroll taxes, administration, and benefits. Many companies routinely track these costs and establish an internal burdened labor rate to use in financial analysis. 

Tan, K. C. D., Goh, N. K., Chia, L. S., Treagust, D. F. (2002). Development and application of a two-tier multiple choice diagnostic instrument to assess high school students understanding of inorganic chemistry qualitative analysis. Journal of Research in Science Teaching, 39(4), 283-301. 

FIGURE 5.3 The Albumin in Acute Stroke (ALIAS) Phase II Trial. Data represent mean SEM. p-Value according to multiple regression analysis. Dead patients have been censored, (a) Mean change in NIH Stroke Scale score over time since treatment in rt-PA and non-rt-PA cohorts receiving the three lowest doses (Tiers I, 0.34 mg/kg II, 0.68 mg/kg III, 1.03 mg/kg) and three highest doses of albumin (Tiers IV, 1.37 mg/kg V, 1.71 mg/kg VI, 2.03 mg/kg). 

Tier II analysis Quantitative structure-activity relationships... 

Tier III analysis Toxicokinetic/toxicodynamics. The role of ADME in designing safer chemicals... 

Factors that may be considered in selecting a tier include the physical characteristics of the facility and surrounding terrain, the anticipated waste compositions and feed rates, and the level of resources available for conducting the analysis. The main distinction between the tiers is the focal... 

EPA-Diesel RIA, Regulatory Impact Analysis—Control of Air Pollution from New Motor Vehicles Tier 2 Motor Vehicle Emissions Standards and Gasoline Sulfur Control Requirements United States Environmental Protection Agency, Air and Radiation EPA420-R, 99-023. 1999. December. 

More recently, the National Institute of Environmental Health Sciences and the National Institute for Occupational Safety and Health convened a workshop in which experts in the field of developmental immunotoxicology developed a tiered approach for assaying the developmental immunotoxicity of chemicals.18 The recommended assays were separated into three groups (1) an initial set of screening assays, (2) assays for validation of a correlation between the assay end point and functional outcomes in humans, and (3) assays for research development.18 The initial screening assays included analysis of the primary antibody response to a T-dependent antigen, the delayed type... 

Whatever the specific need or application, the use of a tier testing scheme can significantly reduce, and in some cases eliminate, the use of animals. An example of a decision-making tree and its applications in ocular testing is provided in Figure 17.3. First, all available data about a test material (or related compounds), including chemical characteristics, historical data, other known toxicity, and the like, are collected. Analysis of these data could provide a strong indication of irritation potential, in which case the material would be labeled a presumed positive and... 

Tier 3 review An intensitve scientific and labeling review of submissions for products associated with high risk or for products with technical features requiring detailed analysis to determine safety and effectiveness. Frequently advisory panel review and recommendations would be sought as a component of this type or review. 

In higher tier assessments, the question is not so much whether uncertainty analysis is required, but rather whether it should be quantitative and what methods should be used for it. The previous Pellston workshop made the following recommendations as a general guide (Warren-Hicks and Moore 1998) ... 

When the data for a situation of specihc interest are inadequate, a common approach is to make some use of more generic information, including possibly information less representative of the situation of specific interest. For example, if the information for a specihc pesticide is inadequate, then some features of an analysis may be based on information from a set of other pesticides, considered to be comparable. This can be appropriate particularly for an early-tier assessment, in which case the criteria may be designed to be protective, so far as we can judge. 

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