Is There a Need to Enhance Transparency of Decision-Making Process? Robert Russell, M.D. Tufts University Boston, MA

Transcription

1 Is There a Need to Enhance Transparency of Decision-Making Process? Robert Russell, M.D. Tufts University Boston, MA

2 Problems with Lack of Transparency (Garza & Pelletier) 1) Perceived inconsistency 2) Perceived lack of objectivity 3) Complexity in presentation 4) Lack of clarity (e.g. why exclusions made) 5) Difficulty in implementation 6) Decreases chances of replicability 7) Hides research gaps

3 Initial Problem Panel process biased- particularly when dealing with large numbers of nutrients. e.g. micronutrients panel = 14 for 14 nutrients Strong personalities can rule

4 Problem 2 Differences in seriousness of end points chosen and in terms of public health significance. Not clear- why? e.g. UL for niacin based on flushing vs. liver toxicity and teratogenicity for vitamin A e.g. UL for zinc based on reduced enzyme activity (ESOD) vs. bulging fontanels for excess vitamin A in infants

5 Problem 2 (cont.) e.g. EAR for vitamin E based on red cell hemolysis upon exposure to H 2 O 2 vs. EAR for vitamin B12 based on anemia (maintenance of hematologic status)

6 Choice of End Points Lack of complete, up front documentation as to criteria used for literature searches (e.g. inclusion/exclusion) and criteria used for evaluating and weighing the evidence

7 Examples: B6, B, Zn, B-CaroteneB Same data base Same framework Different conclusions (why?- not clear)

8 Vitamin B6- UL North America 1) Based on Bernstein and Lobitz (neurologic exam) 2) UL- 200mg/day (NOAEL) 2 = 100mg/day as pyridoxine. UF based on small amount of data on doses under 200mg Britain 1) Based on Phillips, et al study of ataxia in dogs 2) UL- 3000mg/day (LOAEL) 300 = 10mg/day. UF based on use of LOAEL, interspecies variation, and interindividual variation European Union 1) Based on Dalton et Dalton study (neurological symptoms) 2) UL- 100mg/day (LOAEL) 4 = 25mg/day. UF based on deficiencies of data base

9 Zinc- UL North America 1) Based on Yadrick,, et al study ESODismutase at 60mg (total intake) 2) UL- 60mg (LOAEL) 1.5 (UF) = 40mg/day; UF due to interindividual variation and use of a LOAEL Britain 1) Based on Yadrick,, et al study (ESOD) 2) UL- 50mg (LOAEL) 2 = 25mg/day. UF due to use of LOAEL European Union 1) Based on Davies, et al and Milne, et al studies (balance) 2) UL- 50mg (NOAEL) 2 = 25mg/day. UF due to small number of subjects and short duration

10 Beta Carotene UL North America None established No dose response Data conflicting Britain Based on ATBC (ferret) LOAEL = 20 mg/day, UF = 3, UL = 7 mg/day EU None established No dose response Formulation differences

11 FAO/WHO Vitamin A RNI vs. IOM RDA (19-50 years, female) FAO/WHO 500ug IOM 700ug Narratives- Not Very Useful

12 USE OF SYSTEMATIC EVIDENCE BASED REVIEWS MINIMIZES BIAS AND EMPHASIZES TRANSPARENCY VIA: 1) DOCUMENTATION OF SCIENTIFIC EVALUATION 2) DOCUMENTATION AND RANKING OF SCIENTIFIC UNCERTAINTIES AROUND THE ESTIMATION 3) RANKING OF HEALTH IMPLICATIONS OF INTAKES ABOVE OR BELOW THE REFERENCE INTAKE 4) PROVISION OF CLEAR RATIONALE FOR DECISION REACHED NARRATIVES- NOT VERY USEFUL

13 Sources of Uncertainty Interindividual Variation Animal to Human Extrapolations Short Term vs. Chronic Exposures Use of a LOAEL instead of a NOAEL Small numbers Severity UF = Uncertainty Factor Highly Subjective

14 Uncertainty Factors Minimize bias by following predefined rules (not by jiggering- aiming for a convenient UL or an UL above recommended intake)

15 Beginning Solutions Change panel process Use Evidence Based Review for key decisions (e.g. endpoint selection) with thorough documentation tables Use rating scales for certainty, public health importance, etc. Follow predefined rules (UF) to minimize bias