Biomedical subjects

Matthew W Wheeler

Publications and source records attributed to Matthew W Wheeler.

3 recordsLinked to original sources

PubMed2006

Comparing median lethal concentration values using confidence interval overlap or ratio tests.

Experimenters in toxicology often compare the concentration-response relationship between two distinct populations using the median lethal concentration (LC50). This comparison is sometimes done by calculating the 95% confidence interval for the LC50 for each population, concluding that no significant difference exists if the two confidence intervals overlap. A more appropriate test compares the ratio of the LC50s to 1 or the log(LC50 ratio) to 0. In this ratio test, we conclude that no difference exists in LC50s if the confidence interval for the ratio of the LC50s contains 1 or the confidence interval for the log(LC50 ratio) contains 0. A Monte Carlo simulation study was conducted to compare the confidence interval overlap test to the ratio test. The confidence interval overlap test performs substantially below the nominal alpha = 0.05 level, closer to p = 0.005; therefore, it has considerably less power for detecting true differences compared to the ratio test. The ratio-based method exhibited better type I error rates and superior power properties in comparison to the confidence interval overlap test. Thus, a ratio-based statistical procedure is preferred to using simple overlap of two independently derived confidence intervals.

Animals↗

PubMed2005

Model uncertainty and risk estimation for experimental studies of quantal responses.

Experimental animal studies often serve as the basis for predicting risk of adverse responses in humans exposed to occupational hazards. A statistical model is applied to exposure-response data and this fitted model may be used to obtain estimates of the exposure associated with a specified level of adverse response. Unfortunately, a number of different statistical models are candidates for fitting the data and may result in wide ranging estimates of risk. Bayesian model averaging (BMA) offers a strategy for addressing uncertainty in the selection of statistical models when generating risk estimates. This strategy is illustrated with two examples: applying the multistage model to cancer responses and a second example where different quantal models are fit to kidney lesion data. BMA provides excess risk estimates or benchmark dose estimates that reflects model uncertainty.

Animals↗

PubMed2003

A simulation study of methods for constructing confidence intervals for bioaccumulation factors.

Toxicokinetics describe the time course of xenobiotics in an exposed organism. The steady state concentration of the xenobiotic is a characteristic of frequent concern, often summarized in terms of bioaccumulation factors (BAFs). Two experimental protocols are commonly used when estimating BAFs: a continuous exposure experiment and a start-stop exposure experiment. Nonlinear regression is then used for estimating components of the BAF. A variety of methods are available for constructing confidence intervals (CI) for the BAF, including the delta method and Fieller's method. The properties of these CI methods are explored through a simulation study. In particular, the coverage properties of the two CI methods along with their interval widths are examined for a variety of time-course patterns, error distributions, experimental protocols, and sampling designs. Fieller's method is observed to exceed nominal coverage probabilities for all conditions considered (the coverage probability being the probability that a confidence interval contains a parameter it estimates over repeated experiments). The delta method exhibited observed coverage probabilities lower than nominally specified for a number of conditions. For sampling designs in which more of the sampling times are prior to steady state or the stop exposure time, the delta method is observed to provide nominal coverage probabilities with interval widths much narrower than observed with the Fieller's method. Thus, the delta method is preferable when the above sampling time condition is met; however, in all other cases, Fieller's method should be used.

Animals↗