Master of Science / Department of Statistics / Christopher I. Vahl / Chemicals and drugs applied to animals used in meat production often have the potential to cause adverse effects on human consumers. To ensure safety, a withdrawal period, i.e. the minimum time allowed between application of the drug and entry of the animal into the food supply, must be determined for each drug used on food-producing animals. The withdrawal period is based on an upper tolerance limit at a given time point. It is not uncommon that the concentration of the drug in some tissue samples to be measured at a level below the limit of quantitation (LOQ). Because the measurement of the tissue concentration cannot be confidently determined with enough precision, these types of observations are often treated as if they were left censored where the censoring value is equal to the limit of quantitation. Several methods are commonly used in practice to deal with this situation. The simplest methods are either to exclude observations below the limit of quantitation or to replace those values with zero, LOQ or ½ LOQ. Previous studies have shown that these methods result in biased in estimation of the population mean and population variance. Alternatively, one could incorporate censoring into the likelihood and compute the maximum likelihood estimate (MLE) for the population mean and variance assuming a normal or lognormal distribution. These estimates are also biased but it has been shown that they are asymptotically unbiased. However, it is not clear yet how these various methods affect estimation of the upper tolerance limit, especially when the sample size is small, e.g. less than 35. In this report, we will examine the effects of substituting the LOQ or ½ LOQ for censored values as well as using the MLEs of the mean and variance in the construction of an upper tolerance limit for a normal population through simulation. Additionally, we propose a modified substitution method where observations below the LOQ are replaced by functions of the order statistics of non-censored observations under an assumption of symmetry. Its performance relative to the above methods will also be evaluated in the simulation study. In the end, the results from this study will be applied to an environmental study.
| Identifer | oai:union.ndltd.org:KSU/oai:krex.k-state.edu:2097/18198 |
| Date | January 1900 |
| Creators | Yan, Donglin |
| Publisher | Kansas State University |
| Source Sets | K-State Research Exchange |
| Language | en_US |
| Detected Language | English |
| Type | Report |
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