What Are the Issues in Applying Systematic Evidence-Based Review Approaches to DRI Development?

Transcription

1 What Are the Issues in Applying Systematic Evidence-Based Review Approaches to DRI Development? Alice H. Lichtenstein, D.Sc. Gershoff Professor of Nutrition Science and Policy Tufts University

2 What is the meaning of systematic EBR relative to DRI development?

3 What is the meaning of systematic EBR relative to DRI development? Systematic EBR is an approach to comprehensively identify and tabulate available literature for use to supplement traditional approaches to DRI development.

4 What is the meaning of systematic EBR relative to DRI development? Systematic EBR is an approach to comprehensively identify and tabulate available literature for use to supplement traditional approaches to DRI development. Systematic EBR s are limited to specific questions formulated and refined by panel members and other designated individuals.

5 What is the meaning of systematic EBR relative to DRI development? Questions formulated and refined. Search strategy developed. Inclusion/exclusion criteria identified. Relevant literature retrieved and screened. Studies graded. Data summarized in tables. Report presented to DRI panel members.

6 Questions formulated and refined Example: Soy and Health Outcomes What is the scientific evidence of a doesresponse effect of different forms of soy and individual constituents of soy for cardiovascular risk factors; menopausal symptoms; endocrine function; cancer; osteoporosis; reproductive health; and kidney function?

7 For example What is the efficacy or association of omega-3 fatty acids in preventing incident CVD outcomes in people without known CVD (primary prevention) and with known CVD (secondary prevention)?

8 PICO Approach Population Intervention Comparator Outcome

9 PICO Approach Population Primary prevention, secondary prevention Intervention Comparator Outcome

10 PICO Approach Population Primary prevention, secondary prevention Intervention ALA; EPA/DHA Comparator Outcome

11 PICO Approach Population Primary prevention, secondary prevention Intervention ALA; EPA/DHA Comparator Diets, other oils (isocaloric) Outcome

12 PICO Approach Population Primary prevention, secondary prevention Intervention ALA; EPA/DHA Comparator Diets, other oils (isocaloric) Outcome All-cause mortality, MI, stroke, sudden death

13 Search strategy developed Example: multiple sources Identify cut point (e.g. June, 2007). Databases - MEDLINE, PreMEDLINE, Embase, Cochrane Library, Biological Abstracts, Commonwealth Agricultural Bureau of Health. Reference lists of reviews/primary articles. Domain experts.

14 Inclusion/exclusion criteria identified Example: Omega-3 fatty acids and CVD Published English language literature. Experimental or observational studies. Reported original outcome data & evaluated any potential source of omega-3 fatty acids. At least 5 human subjects. At least 1-year duration.

15 Relevant literature retrieved and screened Example: Omega-3 FA and primary prevention cohort studies Abstracts screened 7,464 Papers retrieved 768 Potentially relevant to CVD 118 outcomes Unique studies fulfilled inclusion 39 criteria

16 Studies graded methodological quality, applicability, overall effect. Methodological quality A - Least bias, results are valid. B - Susceptible to some bias, but not sufficient to invalidate the results. C - Significant bias that may invalidate the results.

17 Grade studies methodological quality, applicability, overall effect. Applicability I Sample is representative of the target population. It should be sufficiently large to cover both sexes, a wide age range, and other important features of the target population (e.g. diet). II - Sample is representative of a relevant subgroup of the target population, but not the entire population. III - Sample is representative of a narrow subgroup of subjects only, and is of limited applicability to other subgroups.

18 Grade studies methodological quality, applicability, overall effect. Overall effect + + Clinically meaningful benefit demonstrated. + A clinically meaningful beneficial trend exists but is not conclusive. 0 Clinically meaningful effect not demonstrated or is unlikely. - Harmful effect demonstrated or is likely.

19 Data meeting inclusion criteria summarized in tables Example: Omega-3 FA and secondary prevention randomized trials

20 Final step Report presented to DRI panel members.

21 How is the commonly practiced approach used for clinical medicine topics the same or different from needs related to DRI development?

22 How is the commonly practiced approach used for clinical medicine topics the same or different from needs related to DRI development? Data available to answer clinical medicine questions tend to be more straight forward than issues related to nutrient requirements. A group of subjects is given the active treatment or placebo (e.g. statins). Primary and secondary outcomes reported (e.g. all cause mortality, CHD mortality).

23 How is the commonly practiced approach used for clinical medicine topics the same or different from needs related to DRI development? Questions for DRI development more complex and numerous. Must arrive at answer in spite of high degree of uncertainty. High degree of variability among studies.

24 What issues have arisen, and what special considerations come into play relative to evaluating evidence for DRI development?

25 Special considerations when evaluating evidence for DRI development. Background diet (e.g. fish intake and omega-3 fatty acids) Nutrient status prior to intervention (e.g. Fe, Cr) Adequacy of nutrient stores (e.g. vitamin A) Body weight change (e.g. macronutrients)

26 Special considerations when evaluating evidence for DRI development. Bioequivalency of different forms of nutrients (phylloquinone and menaquinone; vitamin A and carotinoids) Bioavailability of different forms of nutrients (heme/nonheme iron; folate/folic acid) Altered bioavailability with co-ingestion of food (fat soluble vitamins and dietary fat; Fe/ Ca and phytic acid/oxalic acid containing foods).

27 Special considerations when evaluating evidence for DRI development. Altered bioavailability due to food processing (carotenoids and tomatoes; trytophan and lye treated corn). Altered bioavailability due to drug/nutrient interactions (isoniazid and vit. B6; coumadin and vit. K; folate and metformin). Altered bioavailability due to nutrient/nutrient interactions (vit. C and Fe/Cr; vit. D and Ca).

28 Special considerations when evaluating evidence for DRI development. Altered absorption efficiency due to habitual intake (calcium; iron). Altered absorption efficiency due to physiological state (age and Ca; pregnancy and Fe; achlorhydria and vit. B12). Non-food contribution of nutrient (gut microflora and vit. K, UV light and vit. D).

29 Special considerations when evaluating evidence for DRI development. Multiple effects of single nutrient (vitamin A). One nutrient masking effect deficiency symptom second nutrient (folate/vit. B12). Different nutrient bioavailability from food and synthetic form (folate/folic acid). Polymorphisms (vit. E and α-tocopherol binding protein; thiamin and transketolase [Wernicke- Korsakoff Syndrome])

30 Special considerations when evaluating evidence for DRI development. Validity of available data (carotenoid conversion factors; Se content food). Non-essential nutrients (cholesterol, omega-3 fatty acids, trans fatty acids). Energy containing versus non-energy containing nutrients (fat/carbohydrate/protein).

31 What impact would the systematic EBR process have on the consistency of DRI study panel approaches? Increase transparency. Provide structure to the approach for evaluating nutrients. Establish foundation to facilitate revision of DRI values. Identify research gaps.

32 What impact would the EBR approach not have on the DRI study panels? Automate review process and relegate decisions to computer modeling. Shift decision making process from IOM panel to EBR group. Diminish the need to expert opinion.

33 Questions/Comments