7

Breakout Discussions: Applications, Facilitating Quality, and Cost-Effectiveness

OVERVIEW

The breakout discussions in session 4, moderated by Lindsay Allen, were designed by the planning committee to encourage all workshop participants to provide input into ways to harmonize methods for setting nutrient reference values. Each breakout session addressed one of three questions (i.e., two groups per question): (1) What are the advantages of global harmonization of methodologies for developing nutrient intake recommendations, from your standpoint? (2) What additional resources and expertise would facilitate adoption of a harmonized approach in your region/country? (3) What are the likely barriers and challenges to achieving global harmonization from your standpoint? Afterward, representatives from each discussion reported back to the workshop participants on strategic points made by individual discussants. Their reports are summarized here. As is true of this report in its entirety, the opinions and ideas summarized here are those of individual workshop participants and should not be construed as consensus. Also included in this chapter are summaries of Catherine Leclercq’s introduction to the breakout discussions, Allen’s synthesis of the breakouts, and the open discussion that took place afterward.

SETTING THE STAGE¹

Leclercq set the stage and provided guidance for the breakout discussions by emphasizing that addressing the three questions was not to be an academic exercise, that is, the goal was not to list advantages or barriers in a theoretical way, but rather to identify actual advantages and barriers. She urged participants not to be “good wishers,” that is, not to simply respond to others by saying, for example, “oh, what a nice initiative,” but to be outspoken and honest and to think about what has really been important in their own work or in the work of colleagues or other institutions. She cautioned that if actual barriers are not identified, those same barriers will still exist 10 years from now, and she urged identification of actual advantages so institutions can move in those directions.

By way of illustration, she told the story of her own “relationship” with nutrient intake recommendations, beginning when she was a Ph.D. student conducting a survey on the intake of sodium. At the end of her work on the survey, she wanted to see how well intakes in the population aligned with recommendations. At the time, she said, that was an easy comparison to make, as there was only one recommended value, the World Health Organization (WHO) population goal.

But later in her career, while serving on a committee in Italy to derive nutrient intake recommendations, she was challenged by how few resources were available. This is still true today, she remarked, as is the case with many countries. But back then they did not have the European Food Safety Authority (EFSA), only documents from the European Commission. Yet, those documents proved “so useful,” she said, because they provided the committee with a regional nutrient intake recommendation that they could then adapt for their own country. She agreed with a comment from the previous day regarding the value of regional nutrient intake recommendations, especially for countries with few resources.

Later, Leclercq was involved with a nationwide survey in Italy, one that she described as quite comprehensive and with quite good quality data on food consumption for a large number of nutrients and vitamins. Those data have been published since then and used widely. However, they were unable to assess dietary adequacy (except for macronutrients). According to Leclercq, doing so would have required a dedicated Ph.D. student to study the assumptions and approach needed to estimate usual intake and other variables for each nutrient. The significance of this, she interpreted, is that even in Italy where many resources are available, they were unable to assess dietary adequacy for nutrients and minerals.

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¹ This section summarizes information and opinions expressed by Catherine Leclercq, Ph.D., nutrition officer, Nutrition and Food Systems Division, Nutrition Division, Food and Agriculture Organization (FAO) of the United Nations, Rome, Italy.

Most recently in her professional life, Leclercq joined the United Nations’ Food and Agriculture Organization (FAO) and was recruited to develop the FAO/WHO Global Individual Food consumption data Tool (GIFT).² She described the tool as being useful not only for developing nutrient intake recommendations, but also for using nutrient intake recommendations to assess adequacy. However, she admitted that the latter application has been a “bit slow” and has been done thus far only for vitamin A. Vitamin A was, she said, “the easy one.” For the next nutrient, they will need to consider political issues, for example, whether to use old WHO values or more recent values that come from a specific institution. She explained that the tool allows users to input any nutrient recommendation, either FAO’s or a user’s own.

Leclercq emphasized that the focus of this workshop was global harmonization, that is, harmonization that serves not just EFSA, the United States, Canada, and other large countries that have many scientists and skills, but harmonization that serves the world. She pointed out that, in fact, most people live in Asia. Additionally, she encouraged workshop participants to keep in mind women and children, including pregnant women; people who are doing hard work; and people who grow old. Consider how harmonization work will cover their needs, she urged. Will it influence these people when they are eating at home? Will it influence their consumption out of the home, such as when children are at school? She predicted that the influence would be more controlled where food is being distributed (e.g., at school) or when supplements are provided.

Additionally, she encouraged stakeholders to keep in mind the intermediate end user, such as people who are developing standards for school meals. She mentioned a survey on school meal standards in 33 low-income countries that found only three countries using their own standards even though many of these countries had their own nutrient intake recommendations. The other 30 were relying on the U.S. school meal standards. She mentioned people who are involved with dietary assessments as another intermediate end user to keep in mind when thinking about harmonization.

Finally, she cautioned against developing a harmonized process that requires the same level of skills and resources currently relied on in the United States, Canada, and the European Union. She encouraged stakeholders to keep in mind countries not represented at this meeting, for example, countries in Latin America.

In closing, she encouraged stakeholders to be concrete, but also to be inspired; to think globally; and to consider end users not present at the workshop.

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² Both Rosalind Gibson and Umi Fahmida discussed GIFT in their presentations, which are summarized in Chapter 6.

QUESTION 1: ADVANTAGES OF GLOBAL HARMONIZATION OF METHODOLOGIES

As reported by Amanda MacFarlane and Anura Kurpad, participants in the two breakout groups assigned to the first question described three strategic advantages of global harmonization:

• Many individuals identified a better use of limited resources as one of the primary advantages. Discussants described a streamlined approach that would make better use of limited resources to set nutrient reference values, one that might allow resources to be directed to nutrients that have been ignored in the past because of lack of resources, lack of evidence, or inattention to important subgroups (e.g., pregnant women, children, elderly).
• A second, related advantage identified by many discussants would be increased country-level application of nutrient reference values derived by harmonized methodologies, such as the development of food-based guidelines. Kurpad described use of the same resources (i.e., those made available through harmonization) as “cutting to the chase.” As an example, there was some discussion in one of the groups around iodine intake levels and how countries could save time by using the U.S.-defined upper limit for iodine and applying it to local situations.
• Yet another, related advantage identified by several discussants would be increased scientific capacity, including expertise for particular nutrients. Kurpad described the greater pool of scientists that would be made available, one extending across regions, as a “global village,” with everyone being available to everyone.

Other advantages identified by individual discussants, again, as reported by MacFarlane and Kurpad, included

• Increased transparency around setting nutrient reference values;
• Increased trust and confidence among both governments and consumers in the science that emerges from having a transparent harmonized approach and in the recommendations stemming from that science;
• Empowerment of countries and regions to set their own nutrient reference values and to implement these values to meet their needs;
• Facilitation of the global trade of staples and processed foods (e.g., through the use of similar nutrient requirements for staples and unprocessed foods or through the use of standardized labels and claims for processed foods);

• Easier identification of gaps in knowledge once a common scientific paradigm is in place, with several individuals pointing to gaps in knowledge around folate requirements as an example; and
• Opportunities for a transparent, open access systematic review repository.

Additionally, Kurpad relayed that several individuals in his group had discussed the value of a harmonized single number in addition to a harmonized process, perhaps across regions. “We’re not saying that you should have one,” he said, “but we’re not saying that you shouldn’t have one.” In his opinion, a single number would help to standardize criteria for trade and food.³

QUESTION 2: ADDITIONAL RESOURCES AND EXPERTISE TO FACILITATE ADOPTION OF A HARMONIZED APPROACH

As reported by Umi Fahmida and Joseph Lau:

• Several individuals in both breakout sessions identified an evidence repository as the number one additional resource needed to facilitate adoption of a harmonized approach. They envisioned a repository containing a wide range of information, not just systematic reviews, but also food composition tables, food consumption data, bioavailability data, and other related data. Additionally, some discussants envisioned that, for the sake of transparency, this information repository would also include detailed documentation of processes. Others imagined a database occupying a single spot online where anyone can access it.
• Many individuals also envisioned a technical brief, or guide, with the brief containing detailed methods not only for developing nutrient recommendations, but also for adjusting recommendations to allow for differences in genetics, physiology, infection, aging, and bioavailability. Additionally, several participants also envisioned a statistical software package to support the technical brief, as well as an online or face-to-face collaborative training on use of the manual.
• Some individuals identified regional networks as an additional needed resource, with each network representing the different countries’ nutritional societies.

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³ See Chapter 6 for a summary of some earlier discussion on this same issue: the difference between harmonizing processes, which was the focus of this workshop, versus harmonizing numbers.

• In addition to training users of the technical brief, some individuals suggested training on how to use the nutrient recommendations themselves. There was some concern expressed that, currently, many countries do not use nutrient intake recommendations appropriately. As with the training for the imagined technical brief, it was suggested that such a training course be made available either online, so it is easily accessible, or through collaboration.
• Finally, some discussants identified the need for a feedback mechanism to ensure that actual food intakes align with derived nutrient recommendations.

QUESTION 3: LIKELY BARRIERS AND CHALLENGES TO ACHIEVING GLOBAL HARMONIZATION

Discussants identified a multitude of barriers and challenges to achieving global harmonization, as reported by James Ntambi and Laura Martino:

• Reluctance to accept global harmonization, not only among end users, but also politically.
• Confusing terminology, with different terms being used to define the same concept and different concepts being associated with the same term, such that even very basic aspects of the discussion create obstacles. Some individuals discussed how even the term recommendation has multiple interpretations.
• Lack of resources, not just funding, but also scientific interest, including lack of new scientists who want to work in this area.
• Lack of data in some countries or populations, for example, the HIV/AIDS population.
• The scattering of data, including data not in the public domain
• Heterogeneity in the quality of data.
• Lack of openness, or sharing, of data, technology, and results because of legal or political constraints.
• Inherent uncertainties and lack of transparency around recommended intake values and the implicit and explicit assumptions underlying those values, which makes it difficult for a country to adopt other countries’ numbers or to develop its own values. Martino commented that sometimes the population to which a value or method applies is not clear. For example, she asked, what is meant by “healthy adults”?⁴

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⁴ See the summary of Caryl Nowson’s presentation on aging in Chapter 6 for some earlier discussion on this same issue.

• Difficult decisions about inclusion versus exclusion of evidence when setting recommendations and differences among countries and regions in how these decisions are made.
• Different endpoints among countries and regions.
• Differences in the updating of recommendations.
• The difficulty of bringing existing methodologies from different regions or countries together.
• Lack of scientific platforms in some countries, including access to information on harmonization (e.g., at meetings like this).

SYNTHESIS OF BREAKOUT DISCUSSION⁵

Lindsay Allen was asked to synthesize the breakout discussion and highlight what she interpreted as main points. This section summarizes her synthesis.

A main advantage of global harmonization is that it could generate more resources into setting nutrient intake recommendations, she began. She described three additional advantages: (1) empowerment of countries, nutrition societies, and others; (2) improved translation of information, because there would be information available on how to use the data; and (3) increased transparency around where the numbers (i.e., nutrition reference values) come from.

Critical additional resources needed to facilitate adoption of a harmonized approach include not only sources of funding, Allen continued, but also a data, or information, repository. She described the data repository as one that could contain a wide range of information, including available systematic reviews and other scientific evidence, food composition tables (which she noted are mostly online already, but could be converged), and bioavailability data. As had the discussants, she envisioned that such a repository would engender larger bodies of scientific expertise around particular nutrients.

Additionally, Allen highlighted the need for a technical brief, or methods manual, coupled with software and some form of training (e.g., online, face to face, via scientific collaboration or country nutrition societies). The manual should detail the harmonized process methodology and should include clear terminology, separate assessment methods for each nutrient, information on how to set bioavailability values, guidance on when to include or exclude data, guidance on how to set endpoints, and instructions for how to interpret the software.

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⁵ This section summarizes information and opinions presented by Lindsay Allen, Ph.D., center director, Agricultural Research Service Western Human Nutrition Research Center, U.S. Department of Agriculture, Davis, California.

Regarding challenges to harmonization, Allen emphasized the need to convince stakeholders everywhere that a harmonized approach is needed, first, by explaining why it is needed and, second, by providing examples. Other main challenges, in Allen’s opinion, are variable terminology, lack of scientific platforms and resources, and questions about how readily people will actually share information nationally, regionally, or internationally.

DISCUSSION

The discussion following Allen’s synthesis revolved around three main issues: the potential effect of harmonization on future research, the potential for data to be misused, and how harmonization of methods can help when data are missing.

How Will Harmonization Affect Research?

Allen wondered what harmonization would mean for nutrition research. Specifically, she asked, by having a harmonized process in place that empowers people to set their own guidelines, “Are we actually wiping out the need to do research on this?” Would it slow research in countries without resources and inhibit development of original data? Or, on the other hand, would it create interest? Hasan Hutchinson opined that an available methodology for all would stimulate research by making it easier to identify gaps and problems with implementation in particular regions. Allen responded that, while Hutchinson’s prediction may be very true in countries with more resources, her concern was with countries with few resources.

The Potential for Misuse of Data

In response to the many calls for a database located in a single place and accessible to everyone, Anura Kurpad cautioned, “We live in a world of social media . . . data can be misused as well.” One of his concerns was the many things that can be done in a systematic review that are not necessarily transparent, such as removing a single study, which, he said, can “ever so slightly change things around so that you get what you want.” But an even bigger worry for him is that people without knowledge of the biology of what they are looking at will apply these freely available databases and methodologies and develop recommendations. He expressed uncertainty regarding how this potential for misuse could be regulated. Additionally, he cautioned that creation of a harmonized methodology must also consider the consequences, particularly in terms of medicalization.

Martino agreed that misuse is a risk, as it is with any scientific paper (i.e., people can extract data and misuse them), but she emphasized the

importance of sharing information. No individual scientist, institution, or country can do this alone. “We have to be aware of the risks and address them,” she said, “but not stop this process.”

In fact, there are a couple of ways to address these risks with respect to systematic reviews, George Wells explained. First, at the beginning of a systematic review, protocols for the review are often published and openly available, similar to the way ClinicalTrials.gov publishes information on clinical trials.⁶ Second, systematic reviews can be transparent and reproducible if information is provided in the review for a third party to reproduce the review, ensure that the original review actually followed the protocol and did not cherry-pick evidence, and verify the results of the original review.

Harmonization When Data Are Missing

In response to the many comments that had been made during the breakout discussion about lack of data, Patrick Stover pointed out that this workshop was about harmonization. He asked, “Shouldn’t we be talking about, ‘How do you harmonize approaches when there are no data?’ What do you do? Isn’t that the big question?”

Leclercq emphasized making clear that the proposed technical brief should address not only how to use primary data but also how to extrapolate from existing data and adapt those data to other countries or age groups. Especially for small countries, this section of the brief may be the most useful part, in her opinion. Ruth Charrondiere agreed that an added challenge is the large amount of missing evidence not just for some geographic areas, but also for some age groups, like infants and children.

Allen imagined that use of data would be a critical component of the manual, given that most countries do not even have access to numbers they can use as average requirements or upper levels.

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⁶ Guidance on accessing U.S. registered clinical trial protocols is available at https://ClinicalTrials.gov/ct2/help/for-researcher (accessed May 18, 2018).

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