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Use of New or Existing Systematic Reviews to Support Future Dietary Reference Intakes

USE OF SYSTEMATIC REVIEWS IN SUPPORT OF NUTRITON RESEARCH

The use of systematic reviews in nutrition research and applications is advantageous because it enhances the ability to evaluate the rigor and overall strength of a body of evidence. Further, the process enhances transparency by documenting the decision-making process. Inclusion of an analytic framework provides clarity to the research questions and contributes to the supporting logic (Arnesen et al., 2020a; Lichtenstein et al., 2008).

SYSTEMATIC REVIEWS

A systematic review is a qualitative synthesis of evidence for evaluating a defined scientific issue. Systematic reviews are commonly used to inform policy decisions such as the establishment of Dietary Reference Intake (DRI) values. Once a review topic is identified, the core elements of a systematic review are: (1) a defined question (or a series of defined questions) structured according to the Population – Intervention (Exposure) – Comparator – Outcome (PI[E]CO) format; (2) inclusion/exclusion criteria for selecting studies; (3) a documented search strategy and analytic framework; and (4) systematic analysis of included studies and meta-analysis if there is sufficient quantitative evidence.

The standing committee was asked to consider for application to a DRI study, de novo, “qualified,” and updated systematic reviews. A de novo

or new systematic review combines the results of primary studies identified through a strategic search that meets the inclusion/exclusion criteria to answer a prespecified research question. For the DRI review on sodium and potassium (NASEM, 2019), a de novo systematic review was commissioned specifically. The Nordic Nutrition Recommendations (NNR2022) (Arnesen et al., 2020a) proposed to “qualify” existing de novo reviews done as replacements for specific de novo reviews. The intended audience was the nutrition community, rather than for DRI reviews. An update of an existing systematic review incorporates new evidence, analytical methodologies, or statistical analyses into the existing review. The DRI review of calcium and vitamin D updated an existing systematic review (IOM, 2011). Based on its assessment of this evidence the standing committee concludes that the scientific quality and criteria needed for DRI applications is the same for all applications of systematic reviews.

ARE NEW SYSTEMATIC REVIEWS ALWAYS NEEDED IN A DRI REVIEW OR CAN EXISTING SYSTEMATIC REVIEWS BE USED?

The committee determined that de novo (i.e., new) systematic reviews are not always required. When deciding the appropriateness of an existing systematic review to support a DRI study, there are important points to consider. The standing committee concluded that a high-quality systematic review that would meet the needs of a DRI committee should encompass several key characteristics to assure both quality and transparency as described below.

• The research questions and content are relevant to the PI(E)CO criteria for the DRI decisions of interest.
• The systematic review was conducted by qualified systematic review methodologists who are both knowledgeable about best practices for conducting systematic reviews and are independent of the user or sponsoring groups.¹
• The systematic review has been peer reviewed and is made publicly available.
• The systematic review was not sponsored by parties that have substantial conflicts of interest, including financial conflicts of interest.²

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¹ Qualified methodologists cannot be employees or paid associates of the sponsoring group and such individuals should not participate in the systematic review process.

² Conflicts of interest and any policies regarding conflicts of interest will be defined by the user or sponsoring group that is commissioning the systematic review.

The standing committee notes that non-peer-reviewed reports, theses, dissertations, official documents, informal communication, research-in-progress, or clinical trials produced by government agencies, academic institutions, or business do not meet the standard of evidence for a DRI review and thus would not be included in the process.

Identifying an Appropriate Systematic Review to Support a DRI Study

Based on the general criteria for systematic reviews as well as the eligibility criteria identified in NNR2022 (Arnesen et al., 2020b) that should be considered, the standing committee identified specific criteria that it considered necessary for determining when to conduct a de novo systematic review or utilize or update an existing one.

Criteria for Systematic Reviews

The standing committee recommends the following criteria be considered for systematic reviews:

1. Systematic reviews should document how they were conducted.
2. The PI(E)CO criteria in an existing systematic review needs to be closely aligned with the key DRI questions. Specific attention should be given to the methodologies used to assess nutrient or food substance intakes or status.
3. The decision about eligibility of studies for inclusion in the systematic review should be made and agreed to by more than one reviewer.
4. The publication range of dates used in an existing systematic review must be considered to ensure that the most relevant and up-to-date evidence has been captured.
5. Consideration should be given to heterogeneity across studies, including outcomes, interventions, intake response, and methodological heterogeneity.
6. The systematic review should include discussion of biases that affect the evidence base, including publication and time-lag bias, and the reporting of individual study results (reporting biases).
7. The systematic review includes an assessment of risk of bias, using an appropriate tool.
8. The systematic review includes a strength of evidence evaluation (e.g., GRADE).³

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³ GRADE = Grading of Recommendations, Assessment, Development, and Evaluations.

9. The scientific quality of the review should be assessed using a recognized standard quality assessment tool such as AMSTAR.⁴

Nordic Nutrition Recommendation’s Criteria for “Qualified” Systematic Reviews

NNR2022 created the term “qualified” systematic review to describe a high-quality review designed and conducted for purposes other than evaluating nutrient reference intakes as the preferred evidence source for evaluating causal relationships between nutrients or food groups and health outcomes (Arnesen, et al., 2020b).

The standing committee suggests the term “eligible” be used as an alternative term to “qualified” for systematic reviews for DRI considerations. For purposes of nutrition labeling in the United States, the term “qualified” is used to identify those nutrient/health relationships on food labels for which there is not significant scientific agreement.⁵ To avoid confusion between the scientific standard used for DRI decisions vs. the standard used for qualified labeling decisions, the committee suggests the term “eligible” be used in place “qualified” systematic reviews.

The NNR2022 identified six criteria needed in a “qualified” systematic review. These are:

1. A clearly stated set of objectives and research questions with predefined eligibility criteria for the studies;
2. An explicit methodology;
3. A systematic search that attempts to identify all studies that would meet the eligibility criteria;
4. An assessment of the validity of the findings of the included studies through an assessment of the risk of bias of the studies;
5. A systematic presentation and synthesis of the characteristics and findings of the included studies; and
6. A grading of the overall evidence.

Interpreting and applying these criteria to the decision about whether and how to use a systematic review should be made by the DRI review committee.

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⁴ AMSTAR = Assessment of Multiple Systematic Reviews. This tool would be used at the level of assessment by a DRI committee as part of its overall assessment of the systematic review (SR) quality.

⁵ See https://www.fda.gov/food/food-labeling-nutrition/qualified-health-claims for additional detail.

Need for Meta-Analyses in Systematic Reviews

A meta-analysis is a quantitative synthesis of results from separate studies. As part of a systematic review, it can be used to evaluate heterogeneity and estimate “consensus” dose-response relationships when there are multiple published scientific studies addressing the same question. Importantly, a meta-analysis based on a systematic review can only be conducted when adequate quantitative data, including effect size estimates, relative risk, and standard errors, are available.⁶ The advantage of a meta-analysis is that it can increase the power and precision of an identified health outcome, reduce over-interpretation of individual studies, and summarize the overall strength of the evidence. A limitation is that the quality of the results depends on the quality of the studies. An additional limitation is the introduction of bias, which must be reported in the published review (NASEM, 2017). A meta-analysis that uses the results of a systematic review should only be conducted when adequate high-quality data are available. Systematic reviews with or without a meta-analysis, due to inadequate or poor data, are useful because they provide an unbiased evaluation of the data. The appropriateness of a meta-analysis would be determined on the basis of available high-quality data.

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⁶ Available at: https://training.cochrane.org/handbook/current/chapter-10 (accessed June 29, 2023).

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