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Workshops sponsored by the Institute of Medicine (IOM) and the World Health Organization suggested that incorporating systematic (evidence) reviews into the process of updating nutrient reference values would provide a comprehensive and distilled evidence document to decision makers and enhance the transparency of the decision-making process the IOM used in recommending the Dietary Reference Intake values (DRIs) for US and Canadian populations. At the request of the US and Canadian government sponsors of the ongoing review of the 1997 vitamin D and calcium DRI values, the Tufts Evidence-based Practice Center performed a systematic review for the current DRI Committee to use early in its deliberations. We described the approach used to include systematic review into the IOM process for updating nutrient reference values and highlighted major challenges encountered along with the solutions used. The challenges stemmed from the need to review and synthesize a large number of primary studies covering a broad range of outcomes. We resolved these challenges by 1) working with a technical expert panel to prioritize and select outcomes of interest, 2) developing methods to use existing systematic reviews and documenting the limitations by doing so, 3) translating results from studies not designed to address issues of interest by using a transparent process, and 4) establishing tailored quality-assessment tools to assist in decision making. The experiences described in this article can serve as a basis for future improvements in systematic reviews of nutrients and to better integrate systematic review into development of future nutrient reference values.

Nutrient reference values have significant public health and policy implications. Given the importance of defining reliable nutrient reference values, there is a need for an explicit, objective, and transparent process to set these values. The Tufts Medical Center Evidence-based Practice Center assembled a group of nutrition experts from academic institutions and federal government agencies, led participants in discussions, conducted exercises in formulating questions and evidence review criteria that would be amenable to systematic reviews of the scientific literature, performed a literature search on the questions to identify potentially relevant publications, and identified challenges and limitations of applying this method to support the development of nutrient reference values using vitamin A as an example. The workgroup concluded that the systematic review approach could be productively used to inform the development of reference values. Challenges identified in this exercise include prioritizing and defining research questions when the volume of literature is large, relying on intermediate (surrogate) outcomes when few or no studies directly linking nutrient intake with clinical outcomes are available, and determining reliable nutrient biomarkers. Ultimately, an objective, unbiased systematic review of a defined question could be useful, not only in helping to set nutrient reference values, but also for increasing the transparency of the decision making process.