Evaluation using Surrogates

Recovery evaluation using surrogates or spikes implies the assumption that the extraction of spike is equivalent of the native analyte. In practice, it is often difficult to demonstrate that equivalence, and the only solution left is to accept the above assumption (extraction of spike is equivalent to that of native compound). A special form of this method is the standard addition method, where spiking at different levels is performed. Depending on the number of levels (i.e., two, three, or more) and/or the concentration jump chosen for the spiking experiment, a different recovery evaluation can be obtained. 

The fate of four petroleum mixtures has been evaluated using three approaches—evaluating the fate of (1) indicator chemicals, (2) the mixture of the whole with a surrogate, and (3) the hydrocarbon mixture as a whole. The four mixtures were crude oil, JP-5, mineral spirits, and diesel. The choice of approach requires the consideration of availability and quality of data on the mixture, the mobility and toxicity of the mixture, and the availability of site data (Custance et al. 1992). 

In the evaluation of pharmaceutical products, commonly used surrogate efficacy endpoints include ... 

For GC/MS analyses, some laboratories use surrogate standard recovery limits from outdated versions of EPA Methods 8260 and 8270. These recovery limits, shown in Example 4.18, are fairly close to the statistically derived control limits at most laboratories and can be safely used in the evaluation of data quality. The surrogate... 

An external archive of actual evaluations is maintained and used to create the surrogate models. The archive only maintains the unique candidate solutions evaluated using actual evaluations over generations. 

RBF model if at least one solution exists in the archive that is within a distance threshold. This distance threshold plays an important role in the early stages of evolution where more candidate solutions are evaluated using actual computations even during the surrogate phase. Furthermore, a candidate solution is only evaluated using the surrogate model if the MSE of the surrogate on the validation set is below an user defined threshold. 

EPA critically evaluated the quality and quantity of the blood and brain ChE data and determined that the female brain ChE inhibition was the most appropriate data for developing RPFs. The brain ChE data typically have tighter confidence limits compared to RBC ChE data and therefore eonfer less uncertainty on cumulative risk e.stimates. Brain ChE inhibition also represents a direct measure of the common mechanism of toxicity as opposed to using surrogate measures. The toxic potencies and PoDs for brain cholinesterase inhibition for these OPs are generally similar to the RBC data for the oral, inhalation, and dermal exposures (EPA, 2002c). For some OPs, female rats are more sensitive than male rats. 

Protein Biomarker Assays. NextGen Sciences has developed a mass spectrometry method for protein biomarker assays that does not depend on antibodies but instead uses surrogate proteins to facihtate development of assays. The mass spectrometer measures the amount of surrogate peptides and apphes statistical evaluation to assess each biomarker. This first stage requires that a protein be confirmed then only these selected proteins are used for the second stage of validation of these protein biomarkers. The mass spectrometry data are used along with carbon-13 or... 

From Ihopoulou, E.F., Heracleous, E., Dehmitis, A., Lappas, A.A., 2014. Producing high quality biofuels Pt-based hydroisomerization catalysts evaluated using BtL-naphtha surrogates. Applied Catalysis B 145, 177—186. 

Before sample preparation, surrogate compounds must be added to the matrix. These are used to evaluate the efficiency of recovery of sample for any analytical method. Surrogate standards are often brominated, fluorinated, or isotopically labeled compounds that are not expected to be present in environmental media. If the surrogates are detected by GC/MS within the specified range, it is... 

Continuing calibration for a Series Method is performed using calibration check compounds. Surrogate compounds are added to the matrix before sample preparation to evaluate recovery levels. To check GC retention times, internal standards are added to a sample after its preparation for analysis. 

Belliot, G., Lavaux, A., Souihel, D., Agnello, D., and Pothier, P. (2008). Use of murine norovirus as a surrogate to evaluate resistance of human norovirus to disinfectants. 

Phase II investigates the compound s efficacy and safety in controlled clinical trials for a specific therapeutic indication. To eliminate as many competing factors as possible, Phase II trials are narrowly controlled. They are characterized as small—several hundred subjects with the indicated disease or symptoms—and are closely monitored. The control may be either a placebo study arm or an active control arm. The endpoint measured may be the clinical outcome of interest or a surrogate. Phase II trials may last for several months or even several years. Early pilot trials to evaluate safety and efficacy are called Phase Ila. Later trials, called Phase lib, are important tests of the compound s efficacy. These trials may constitute the pivotal trials used to establish the drug s safety and efficacy. At least one pivotal trial (most frequently a large, randomized Phase III study) is done. Only about one third of compounds entered into Phase II will begin Phase III studies [61],... 

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