Multiplicity-Adjusted Confidence Limits in Risk Assessment with Quantal Response Data

Abstract

ABSTRACTIn risk assessment, it is often desired to make inferences on the risk at certain low doses or on the dose(s) at which a specific benchmark risk (BMR) is attained. At times, dose levels or BMRs are of interest, and some form of multiplicity adjustment is necessary to ensure a valid simultaneous inference. Bonferroni correction is often employed in practice for such purposes. Though relative simple to implement, the Bonferroni strategy can suffer from extreme conservatism (Nitcheva et al., 2005; Al-Saidy et al., 2003). Recently, Kerns (2017) proposed the use of simultaneous hyperbolic and three-segment bands to perform multiple inferences in risk assessment under Abbott-adjusted log-logistic model with the dose level constrained to a given interval. In this paper, we present and compare methods for deriving multiplicity-adjusted upper limits on extra risk and lower bounds on the benchmark dose under Abbott-adjusted log-logistic model. Monte Carlo simulations evaluate the characteristics of the simultaneous limits. An example is given to illustrate the use of the methods.