Comments on recent discussions providing differing causation methodologies

Abstract

Recently, we and others have proposed the methods of mapping the widely accepted logic underlying evidence-based medicine (EBM) in the field of toxicology. The goal of evidence-based toxicology (EBT) is to provide a consistent, objective, and rule-based methodology for evaluating human and animal toxicology data to determine whether a chemical creates a human health risk; that is, whether the chemical is known to cause a specific toxic or adverse health effect in humans. Early adopters of EBT include scientists and regulatory groups such as the U.S. Food and Drug Administration and the National Academy of Sciences critique of the U.S. Environmental Protection Agency (USEPA). EBT is being evaluated by the USEPA itself at a recent workshop with some evident initial confusion. A report by some presenters miscites the order and contents of originating EBT publications, incorrectly suggests that the systematic reviews are somehow equivalent to EBT rather than just one fundamental step in the process, and would have EBT focus on nonhuman animal studies to the virtual exclusion of human effects. Remarkably, the word ‘‘cause’’ or ‘‘causation’’ does not appear in the article, even though Hartung, a basic toxicologist initiator of EBT, considers causation of human health effects as one of the four pillars of the ‘‘temple’’ of EBT. Recently, two publications discussed alternative, but contradictory, approaches for analyzing animal and human data when trying to reach cause and effect conclusions. Here, we discuss some shortcomings of these two contrasting proposals viewed from a perspective of a comprehensive framework for causation, that is, EBT.