An ad hoc committee under the auspices of the National Academies of Sciences, Engineering, and Medicine (the Academies) will undertake a study to assess options presented in the document Options for Consideration of Chronic Disease Endpoints for Dietary Reference Intakes (DRIs): Summary Report from a Joint U.S./Canadian-sponsored Expert Panel (hereafter Options Report) and determine guiding principles for the inclusion of chronic disease endpoints for food substances that will be used by future Academies' committees in establishing Dietary Reference Intakes (DRIs). The committee shall provide justification for the selection (and non-selection) of options that served as the basis for the guiding principles, including additions not considered in the Options Report. In carrying out its work, the committee shall:
1) Consider that the term "food substances" for the purposes of this study refers to nutrients that have been established as essential or conditionally essential, energy nutrients, and other naturally-occurring bioactive components in foods. Revisions to this definition need to be justified.
2) For the purposes of this study, interpret the terms "chronic disease" and "apparently healthy population" (also referred to as general population and healthy population in DRI reports) in a manner consistent with the use of those terms in the Options Report.
3) Organize the guiding principles in a manner consistent with the components of the risk assessment framework (hereafter organizing framework) currently used in developing DRIs. In particular, the guiding principles are to address the initial two organizing framework components that relate to the evidentiary and intake-response key questions addressed in the Options Report: a) indicator review and selection and b) intake-response assessment and specification of reference values.
4) Specify, on the basis of its review of the Options Report, guiding principles relevant to the development of chronic disease-based reference values for benefit (disease risk reduction) for the population and for risk (disease risk increase or tolerable upper intake level) for the population or any sub-population that may be susceptible to the food substance. While many principles may be similar for the development of benefit and risk reference values, it is anticipated that there are likely to be differences, often subtle in nature, which will require specification.
5) Ensure that the guiding principles that articulate (a) the evaluation of evidence to assess causal relationships and (b) development of intake-response relationships and values include, but are not limited to rationale and criteria for:
a) Evaluating the usefulness of different types of studies and data to establish causality and to derive intake-response relationships;
b) Selecting appropriate outcome measures for chronic diseases – for determinations of causality and for determinations of intake-response relationships;
c) Weighing the strength of evidence (degree of confidence) for establishing both causality and intake-response relationships;
d) Evaluating the accuracy and usefulness of intake evidence for assessing causality, intake-response relationships, and population status;
e) Selecting reference values when a food substance is related to more than one chronic disease, possibly with different intake-risk relationships, or for selecting reference values when a chronic disease is related to more than one food substance;
f) Addressing situations where the intake-response curve for benefit overlaps with the potential risk associated with higher intakes; and
g) Types of reference values based on chronic disease endpoints taking into account the wide array of DRI uses.
6) Recognize that recommendations for risk management and policy are outside the scope of this study.
7) Prepare a report written in clear language for use by future DRI committees and other stakeholders. The rationale for principles chosen, and those rejected, should be clear.