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Opportunities and challenges in conducting systematic reviews to support the development of nutrient reference values: vitamin A as an example

¹ From the Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA (RR and AHL); the Office of Dietary Supplements, National Institutes of Health, Bethesda, MD (RR); the Tufts Medical Center Evidence-based Practice Center, Tufts Medical Center, Boston, MA (MC, EMB, SI, AHL, GR, TAT, and JL); McMaster University, Hamilton, Canada (SA); the Harvard School of Public Health and Brigham and Women's Hospital, Boston, MA (ELG); the Yale University School of Public Health, New Haven, CT (STM); Pennsylvania State University, University Park, PA (ACR); and the Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (KPW).

² The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by the Agency for Healthcare Research and Quality, the National Institutes of Health, or the US Department of Health and Human Services.

³ This project was conducted under contract no. 290-020-0022 from the Agency for Healthcare Research and Quality with funding from the Office of Dietary Supplements, the National Institutes of Health, US Department of Health and Human Services.

⁴ Reprints not available. Address correspondence to J Lau, Tufts Medical Center Evidence-based Practice Center, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Box 63, 800 Washington Street, Boston, MA 02111. E-mail: jlau1{at}tuftsmedicalcenter.org.

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.