Prioritization of biomarkers in the French human biomonitoring programme

Transcription

1 Prioritization of biomarkers in the French human biomonitoring programme Nadine Fréry, Clémence Fillol, Stéphanie Vandentorren French Institute for Public Health Surveillance (InVS)

2 Context A French national biomonitoring programme: to estimate the exposure of the French population to chemicals in food and environment to better understand the determinants of chemical exposures Two new studies in this programme A cross-sectional survey in the French continental population aged 6-74 years (Biomonitoring Health Nutrition Survey) From the ELFE cohort (Longitudinal Study from Childhood) in children

3 Aims of Human biomonitoring PNSE2 Aims of Nutrition PNNS Aims of chronic diseases Elfe cohort (Children from birth) children born in 2011 ~ 2000 for HBM cross-sectional Biomonitoring Health Nutrition Survey (6-74 yrs) 4000 adults children representative of the French population ~ 50 analyses for 100 environmental chemicals (subsamples) Which biomarkers to select?

4 Selection of chemicals: preparatory work Elaboration of the strategy of HBM programme ( ) Working groups including: Ministry of Health Ministry of Ecology Ministry of Work Scientific committee Representatives of civil society (NGOs, Industry) Obtention of a list of chemicals classified in 51 groups based on: feasibility criteria (foreign and French experiences: ENNS study) toxicity (IARC, endocrine disruptors ) relevance (regulation in air, water or food, law, priorities)

5 Prioritization of BM: General Principle Provisory list of BM Preliminary No prioritization Delphi group Too numerous Final list of BM Prioritization Final meeting group Limited number Application of judgement criteria on relevance to study these BM

6 Prioritization of biomarkers : Methods Delphi method to obtain a consensus list of prioritized groups of biomarkers according to: agreed selection criteria and a formalized approach A meeting to finalize the list of biomarkers (BM) Two groups of experts consulted: speaking French (11 experts (toxicologists, epidemiologists including a Belgium and a Canadian experts, 1 member from NGO and 1 from industry) Experts in human biomonitoring from Europe and Canada Two steps for the prioritization

7 Prioritization of biomarkers : First step on criteria A short questionnaire Experts invited to weigh 8 criteria with a score from 0 to 10 Experts could justify the score given and add comments Based on the median score from all experts (W1-8), the initial scores of each expert could be commented and changed

8 8 CRITERIA Score Hazard identification Toxicity of substances and severity of effects, known or potential: carcinogenicity, reproductive toxicity (possible impact on several generations...), mutagenicity and other (neurotoxicity, immunotoxicity,...) Exposure characteristics Contamination sources (anthropogenic and natural), dispersive or not (exposure of consumers and the public versus workers only), multimedia exposure, human exposure known, susceptible population exposure Social perception Level of public concern (exposure and potential effects) Biomarker characteristics reflect current, cumulated past exposure, or biologically effective dose, sensibility, specificity, intra and inter individual variability 0 to 10

9 CRITERIA Feasibility of results interpretation Existence of information for results interpretation: distribution in reference populations, known relationship between level and risk (dose-response relationship...), PBPK model known, health risk assessment available Logistic and analytic feasibility invasiveness of the sampling, volume required, conditions for collection (transport...), analytical (validated assay method): sufficiency information (LOD...), cost analysis Feasibility of the prevention European legislation, national regulations, toxicity reference value (TRV), support a public health policy, reductions techno-economic and social of exposure feasible ) Score 0 to 10 Contribution in terms of new knowledge (particularly in France) Gaps or no knowledge at national, international level, French specificities (exposure, behavior, susceptibility...), Harmonization and national, European and international comparisons

10 Delphi Results: weight of each criterion (French-speaking experts) A B C D E F G H I J K Hazards 8, Exposure Social perception BM characteristics Interpretation Analytic feasability Prevention 8, , New knowledges ((Foreign experts) L M N O P Q R S T U V Med. Hazards Exposure Social perception BM characteristics Interpretation Analytic feasability Prevention New knowledges Med. W1-8

11 Prioritization of biomarkers : Second step on chemicals For the 51 groups of chemicals, each criterion was scored Experts invited to select one of 4 possible answers (corresponding to a score from 0.2 to 0.8) for each group of chemicals and for each criterion (Cij): totally yes: score 0.8 rather yes: 0.6 rather no: 0.4 totally no: 0.2 Total ratings to obtain a prioritized list, calculated for all the chemical groups: [ median weight Wi X mean score of Cij ] given to each of the 8 criteria at the first step (ex: 8 ) Rate for the biomarker j: given by all experts for a chemical j and for a particular criterion i (ex: 0.85 ) BMj = (W1 x C1i) + (W2 x C2i) + +

12 Example: urinary arsenic (ias+mma+dma), answer from an expert X Criteria Answer score Hazard identification: "Is Arsenic toxic?" Totally yes 0.8 Importance of exposure: "Is the exposed population to arsenic rather large?" rather yes 0.6 Social Perception: "Is Arsenic a matter of public concern? " rather yes 0.6 Characteristics of the biomarker: " Is the measure of urinary ias and its metabolites a good indicator of exposure to As?" Feasibility of results interpretation: " Is there enough information (eg dose-response) to interpret the As levels?" Logistic and analytic feasibility: "Does any validated analytic method exist?" Feasibility of prevention: "Is it possible to reduce As exposures?" Contribution expected in terms of new knowledge: "Will As levels provide new knowledge? Could French As levels be compared with other countries? rather yes 0.6 rather yes 0.6 rather yes 0.6 rather no 0.4 rather yes 0.6

13 Biomarker groups Example: urinary arsenic and bisphenol A 3 experts: A, B, C Hazard, toxicity (X 10 (W1)) Criteria Exposure Importance (x 8 (W2)) Social perception (x 5 (W3)) Total Experts A B C Total A B C Total A B C Total Total score iarsenic and metabolites (MMA+DMA) 0.8 Cij Bisphenol A

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15 Prioritization of biomarkers : Last step A final meeting To further exchange and fine tune the ranking Obtention of a prioritized list of biomarkers

16 Conclusion A formalized approach for prioritization of biomarkers - long and beware of the same understanding of criteria definition - but useful to explain the final selection of biomarkers in the HBM programme Results already obtained from French-speaking experts Next step with foreign experts Final results presented to the different stakeholders

17 Thank you for your attention