Bootstrap methods for simultaneous benchmark analysis with quantal response data.

A primary objective in quantitative risk assessment is the characterization of risk which is defined to be the likelihood of an adverse effect caused by an environmental toxin or chemcial agent. In modern risk-benchmark analysis, attention centers on the "benchmark dose" at which a fixed benchmark level of risk is achieved, with a lower confidence limits on this dose being of primary interest. In practice, a range of benchmark risks may be under study, so that the individual lower confidence limits on benchmark dose must be corrected for simultaneity in order to maintain a specified overall level of confidence.

On use of the multistage dose-response model for assessing laboratory animal carcinogenicity.

We explore how well a statistical multistage model describes dose-response patterns in laboratory animal carcinogenicity experiments from a large database of quantal response data. The data are collected from the US EPA's publicly available IRIS data warehouse and examined statistically to determine how often higher-order values in the multistage predictor yield significant improvements in explanatory power over lower-order values. Our results suggest that the addition of a second-order parameter to the model only improves the fit about 20% of the time, while adding even higher-order terms apparently does not contribute to the fit at all, at least with the study designs we captured in the IRIS database.

Is risk of axillary lymph node metastasis associated with proximity of breast cancer to the skin?

Introduction: Risk of axillary lymph node metastasis, the most important predictor of disease-free and overall survival in breast cancer patients, is estimated primarily from histologic features of the primary cancer including tumor size, histologic type and grade, and hormone receptor expression. Based upon a clinical impression, and research showing that palpable cancers are more likely to be node positive, we hypothesized that primary breast cancers more proximal to the skin of the breast are more likely to be positive for axillary lymph node metastasis.

Methods: This is a retrospective medical record review of 209 women with stage T1 or T2 ( View Article and Find Full Text PDF

Multiplicity-adjusted inferences in risk assessment: benchmark analysis with quantal response data.

A primary objective in quantitative risk or safety assessment is characterization of the severity and likelihood of an adverse effect caused by a chemical toxin or pharmaceutical agent. In many cases data are not available at low doses or low exposures to the agent, and inferences at those doses must be based on the high-dose data. A modern method for making low-dose inferences is known as benchmark analysis, where attention centers on the dose at which a fixed benchmark level of risk is achieved.

Can hyperbaric oxygen therapy reduce breast cancer treatment-related lymphedema? A pilot study.

Objective: Arm lymphedema after surgery or radiation for breast cancer is common, causing pain and limitation of activities. Previous reports of hyperbaric oxygen (HBO) therapy for breast edema led us to consider the use of HBO therapy for arm lymphedema.

Methods: Ten healthy postmenopausal women (age 58 +/- 5.

Confidence bands for low-dose risk estimation with quantal response data.

We study the use of simultaneous confidence bands for low-dose risk estimation with quantal response data, and derive methods for estimating simultaneous upper confidence limits on predicted extra risk under a multistage model. By inverting the upper bands on extra risk, we obtain simultaneous lower bounds on the benchmark dose (BMD). Monte Carlo evaluations explore characteristics of the simultaneous limits under this setting, and a suite of actual data sets are used to compare existing methods for placing lower limits on the BMD.