Recipient Organization
FRED HUTCHINSON CANCER CENTER
1100 FAIRVIEW AVE N
SEATTLE,WA 981090000
Performing Department
Cancer Prevention Program
Non Technical Summary
The central mission of the Seattle Dietary Biomarker Development Center (DBDC) is to advance the science of measuring complex dietary exposures by rigorous identification and validation of dietary biomarkers that improve upon measurement error prone self-reported diet. This is an important area of research because inconsistent evidence and measurement error in dietary self-report have prevented broad nutrition-focused population interventions and public health policy initiatives from moving forward in a consistent manner. Objective biomarkers of diet using blood and urine measured using metabolomics can help address this important issue. The Seattle Dietary Biomarker Development Center will use two phases of controlled feeding studies for metabolomics discovery of MyPlate foods, food groups and dietary patterns. Blood and urine samples collected during the feeding studies will be assayed using untargeted LC-MS metabolomics for biomarker discovery. In a third study phase, validation of the dietary biomarkers using targeted LC-MS metabolomics and comparison to both benchmark biomarkers and self-reported diet will be accomplished using data and archived biospecimens from three, diverse independent cohorts; the Cancer Prevention Study-3, the Hispanic Community Health Study/Study of Latinos and the Women's Health Initiative. Identification of biomarkers of diet has the potential to improve dietary assessment in the US population and to understand better the relationships between diet and health across the lifespan.
Animal Health Component
40%
Research Effort Categories
Basic
40%
Applied
40%
Developmental
20%
Goals / Objectives
The central mission of the Seattle Dietary Biomarker Development Center (DBDC) is to advance the science of measuring complex dietary exposures by rigorous identification and validation of dietary biomarkers that improve upon measurement error prone self-reported diet. The Seattle DBDC will conduct a three-phase Biomarkers Project (BP) as two controlled feeding studies (Phases 1 and 2) for discovery, followed by a validation study (Phase 3) in independent cohorts. BP Phase 1 is focused on discovery of biomarkers of USDA's MyPlate food groups/subgroup comparisons, their half-lives, and dynamic range. BP Phase 2 is focused on discovery of biomarkers of semi-habitual diet/dietary patterns, and comparison to both dietary self-report and benchmark biomarkers . Laboratory analyses for discovery (Phases 1 and 2) will be conducted with untargeted LC-MS metabolomics of aqueous and lipid molecules in feeding study collected biospecimens. Metabolites meeting discovery criteria will move forward for validation on a targeted LC-MS panel, informed by discovery metabolites from Phases 1 and 2. The validation (BP Phase 3) will utilize archived blood and urine specimens from three diverse cohorts: the American Cancer Society's Cancer Prevention Study-3, the Hispanic Community Health Study/Study of Latinos and the Women's Health Initiative. A Consortium will be comprised of the Seattle DBDC, other Biomarker Centers, a Data Coordinating Center, NIH and USDA-NIFA. The Consortium will guide, integrate and disseminate the research to maximize scientific impact with respect to improving dietary exposure measurement that will be applied to nutrition research and surveillance across the lifespan for health promotion and disease prevention.
Project Methods
The Seattle Dietary Biomarker Development Center (DBDC) will conduct a three-phase Biomarkers Project (BP). The methods, evaluation, milestones and deliverables are described below. The BP is preceded by a planning phasePlanning Phase Objective 1 - Harmonize and Collaborate with Consortium Steering Committee (Yr 1)Establish roles and responsibilities of Seattle DBDC Directors within the Consortium Steering Committee (SC).Develop plans to implement harmonized procedures and methods for: (a) performing metabolomics assays, QC and metabolite identification; (b) comparing biomarker performance with self-reported dietary assessment instruments and other gold standard, benchmark biomarkers; (c) data curation and harmonization; (e) Consortium policies for data sharing, data and safety monitoring, publications and presentations, and other Consortium-generated resources.Deliverables: Harmonized intervention designs and procedures; Consortium SC procedures; workflow for Seattle DBDC-DCC interactions.Planning Phase Objective 2 - BP preparations (Yr 1):Weekly Seattle DBDC Executive Committee (EC) and Core meetings, monthly Seattle DBDC meetings. Confirm roles, responsibilities, communication strategies and both internal and external timelines.Establish fiscal management and tracking systems.Finalize Data and Safety Monitoring Plans (DSMPs) and adverse event reporting procedures.Create cloud-based study database including QA/QC protocols to ensure accurate data collection and creation of common data elements (CDEs).Finalize BP Phase 1 feeding study preparations including clinical protocols, feeding study menus, consent forms, participant recruitment documents, data collection forms and participant questionnaires.Create manual of operations for BP Phase 1, including workflows.Complete training of personnel.Deliverables: Investigator and staff roles and responsibilities, subcontracts executed, protocols, consent forms, data collection forms and all other BP Phase 1 materials, manual of operations, database creation, staff training plan, fiscal systems in place.Planning Phase Objective 3 - Fulfill Regulatory Requirements (Yr 1):Obtain approval of BP protocols by the USDA-NIFA-appointed DSMB.Obtain single-site Fred Hutch IRB submission for BP Phase 1.Obtain Fred Hutch Clinical Research Support (CRS), Prevention Center Shared Resource (PCSR) and Nutrition Assessment Shared Resource (NASR) agreements for BP Phase 1.Obtain Fred Hutch cyber-security approval of cloud-based database.Deliverables: Consortium DSMB approval of Seattle DBDC protocols; Fred Hutch IRB, CRS, PCSR and NASR approvals and agreements.BP Phase 1 Objectives (Yr 1 -Yr 5)Screening, recruitment and retention of participants for Phase 1 feeding study.Collection, processing, tracking and storage of biospecimens.Data entry and QC checking of Phase 1 data, including data on unconsumed Phase 1 study foods.Send Phase 1 biospecimens to Metabolomics Core (MC) at end of Phase 1 for untargeted LC-MS assays; receive results.Perform QC checks on lab blinded duplicates, data cleaning, including merging of lab data with demographic and clinical data into cloud database. Metabolomics Core (MC), Data Analysis Core (DAC), DCC and other Centers work iteratively on biomarker discovery, identification of unknown metabolites and statistical analysis using the completed metabolomics assay data and Phase 1 feeding study data.Deliverables/Milestones for BP Phase 1: Meeting recruitment and retention goals with no more than 14% drop out rate, timely data entry and QC, successful collection and assay of biospecimens, initiate collaborative work on statistical analysis and biomarker identification.BP Phase 2 Objectives (Yr 2- Yr 4).Finalize Phase 2 feeding study materials: clinical protocols, feeding study menus, consent forms, participant recruitment documents, data collection forms (e.g. anthropometry, blood draw forms) and participant questionnaires.Initiate and obtain single-site Fred Hutch IRB submission for Phase 2 feeding study.Initiate and obtain Fred Hutch CRS, PCSR and NASR agreements for Phase 2.Manual of Operations modifications to include Phase 2 protocols.Screening, recruitment and retention of participants for Phase 2.Collection, processing, tracking and storage of biospecimens.Conduct self-reported dietary assessment.Data entry and QC checking of Phase 2 dataSend Phase 2 biospecimens to MC for untargeted LC-MS assaysPerform QC checks on lab blinded duplicates data cleaning, including merging of lab data with demographic and clinical data into cloud database. MC, DAC, DCC and other Centers work iteratively on biomarker discovery, identification of unknown metabolites and statistical analysis using the completed metabolomics assay data and Phase 2 feeding study data and confirmation of any metabolites emerging in both Phase 1 and Phase 2.Develop and test targeted LC-MS panel informed by Phase 1 and 2 results.Work collaboratively with DCC and Consortium on statistical methods for biomarker confirmation for metabolites identified in Phases 1 and 2.Deliverables/Milestones for BP Phase 2; Final protocols, consent forms, data collection forms and management plan, manual of operations, regulatory approvals for Phase 2, meeting recruitment and retention goals with no more than 16% drop out, completion of > 95% of 24hr dietary recalls and 100% of 4-day food records, timely data entry and QC, successful collection and assay of biospecimens, continuing collaborative work on biomarker identification and statistical analysis.BP Phase 3 Objectives (Yr 2 - Yr 4).Establish Phase 3 protocol and workflows.Obtain Fred Hutch IRB submission for Phase 3Modify database for new data elements from the validation cohorts.Set up and execute material transfer agreements (MTA) and data use agreements (DUA) with the three validation cohorts (CPS-3, HCHS/SOL, WHI) and with the DCC.Receive de-identified biospecimens from CPS-3, HCHS/SOL and WHI, log and track aliquots and send to MC.Receive de-identified archived study data (self-reported diet, participant characteristics) from CPS-3, HCHS/SOL and WHI. Conduct data cleaning, check for missing data, perform data harmonization as needed.Perform QC checks on lab blinded duplicates data cleaning, including merging of lab data with demographic, dietary and other data into cloud database.Send Phase 2 biospecimens for benchmark biomarkers to University of WA Core Lab.MC, DAC, DCC and other Centers work iteratively on biomarker validation, identification of unknown metabolites and statistical analysis using the completed metabolomics validation assay data, benchmark biomarkers and dietary self-report and Phase 3.Deliverables/Milestones for BP Phase 3: Successful transfer of biospecimens and data from independent cohorts, completion of laboratory assays and return of data, completion of data cleaning and harmonization, continuing collaborative work on biomarker validation, identification unknown metabolites and statistical analysis.BP completion (Year 5).?Complete remaining laboratory assays, including repeats due to QC issues or technical issues with equipment.Upload lab results to database, perform QC checks.Complete statistical analyses planned by the DAC and DCC.Upload datasets, data dictionary and all data documentation (including analysis code) to the DCC.Write and submit manuscriptsFinal report to USDA-NIFA .Final Deliverable/Milestones: Completion of data analysis, planned manuscripts, and data transfer to DCC. Finalize regulatory requirements.