A framework for the next generation of risk science

Abstract

Objectives: In 2011, the U.S. Environmental Protection Agency initiated the NexGen project to develop a new paradigm for the next generation of risk science.

Methods: The NexGen framework was built on three cornerstones: the availability of new data on toxicity pathways made possible by fundamental advances in basic biology and toxicological science, the incorporation of a population health perspective that recognizes that most adverse health outcomes involve multiple determinants, and a renewed focus on new risk assessment methodologies designed to better inform risk management decision making.

Results: The NexGen framework has three phases. Phase I (objectives) focuses on problem formulation and scoping, taking into account the risk context and the range of available risk management decision-making options. Phase II (risk assessment) seeks to identify critical toxicity pathway perturbations using new toxicity testing tools and technologies, and to better characterize risks and uncertainties using advanced risk assessment methodologies. Phase III (risk management) involves the development of evidence-based population health risk management strategies of a regulatory, economic, advisory, community-based, or technological nature, using sound principles of risk management decision making.

Conclusions: Analysis of a series of case study prototypes indicated that many aspects of the NexGen framework are already beginning to be adopted in practice.

Figure 1

The NexGen framework for risk science. Phase I: objectives—problem formulation and ­scoping takes into consideration the risk context, decision-making options, and value of information. Phase II: risk assessment: health determinants and interactions—incorporates a population health approach that takes into account multi­ple health determinants that interact with the risk factor(s) of interest. Hazard identification, dose–response assessment, and exposure assessment make use of new scientific tools and technologies, based on high throughput screening assays and computational methods in biology and toxicology for hazard identification and dose–response assessment; in vitro to in vivo extrapolation methods for calibration of in vitro and human dosimetry; molecular and genetic epidemiology to identify toxic­ity pathway perturbations in population-based studies; and high-performance mass spectrometry to generate human exposure data, to assess risk. Characterization of risk and uncertainty applies new risk assessment methodologies to develop human exposure guidelines. Phase III: risk management—risk-based decision making considers fundamental risk management principles, economic analysis, socio­political consideration and risk perception to select one or more risk management interventions of a regulatory, economic, advisory, community-based, or technological nature for risk management. [The center section on hazard identification, dose–response assessment, and exposure assessment is adapted from Figure 2 of Krewski et al. (2011).]