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Consortia: A Tool for Interdisciplinary Research in Cancer Genetic Epidemiology Daniela Seminara, Ph.D., MPH EGRP.

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Presentation on theme: "Consortia: A Tool for Interdisciplinary Research in Cancer Genetic Epidemiology Daniela Seminara, Ph.D., MPH EGRP."— Presentation transcript:

1 Consortia: A Tool for Interdisciplinary Research in Cancer Genetic Epidemiology Daniela Seminara, Ph.D., MPH EGRP

2 Desirable Characteristics of Interdisciplinary Consortia in Cancer Genetic Epidemiology Large studies with interdisciplinary teams working at solving complex scientific problems and responding to an obvious opportunity to advance scientific discovery and its applications Intensely collaborative Common Protocol and Methods Coordinated Parallel and Pooled Analyses Development of a resource for testing hypotheses from entire research community Exchange of concepts, approaches and intellectual discourse produces results beyond these possible with single-discipline approaches

3 Why Consortia in Cancer Genetic Epidemiology? A Consortium can support the study of: Interactions with environmental exposures Complex multigenic effects Gene discovery Etiologic heterogeneity for tumor subgroups Prognostic factors A Consortium can facilitate: Rapid replication of findings. Pooling of data to increase sample size. New large-scale efforts.

4 Where are Epidemiologic Consortia on the NIH Roadmap? Interdisciplinary Research Implementation Group Interdisciplinary Research (IR) Centers. Planning grants will be awarded to begin IR programs that will address significant and complex biomedical problems, particularly those that have been resistant to more traditional approaches. Planning activities will include approaches to overcoming traditional institutional barriers to IR, which are intended to lay the foundation and prepare investigators for submitting a subsequent application for support through an IR Consortium. (NIH website)

5 EGRP $ In Consortia (in Millions)

6 EGRP- Supported Epidemiology Consortia: Flexibility of Design Cohorts Consortium Breast and Colon CFRs (hybrid design) Familial Consortia Case-Control Consortia Gene discovery Gene characterization GxG and GxE Translational Clinical Genetics Screening/prevention /treatment

7 Design-Based Consortia Cohorts: multiple outcomes converging mechanisms Case-control: less common tumors specialized components Family-based: high and intermediate penetrance genes environmental modifiers

8 Existing or Developing Consortia by Cancer Site ( ) Prostate Lung Melanoma Breast Colon Chronic Lymphocytic Leukemia Multiple Myeloma Brain Lymphoma Bladder Esophagus Head and Neck Pancreas Ovarian Endometrial Others…

9 Characteristics of Consortia in Cancer Genetic Epidemiology Retrospective and/or prospective data Based on cancer site or research theme Initially formed by investigators or solicited by funded agency Support for infrastructure and/or for research project (s) Different levels of data and biospecimen sharing Centralized or de-centralized molecular technologies

10 How does the Epidemiology and Genetics Research Program (EGRP) Foster Consortia? Identify research priorities Assess needs Provide resources, coordination and communication among participating groups and with other consortia (website, portal, meetings) Facilitate and expedite research implementation and translational process Performance evaluation: in cooperation with investigators, develops milestones and best practices Involvement in planning and liaison with other agencies/institutions

11 Emerging Consortia: Criteria for Evaluation (EGRP-CWG) Emerging consortium: a group of three or more groups of investigators from different institutions planning to launch a joint initiative by combining resources from case-control, familial or cohort studies. Criteria: Scientific rationale and justification of need : what are the scientific questions that only the consortium can address Preliminary rationale that large numbers are needed to address questions outlined in #1 Outline of proposed internal leadership and organizational structure Outline of guidelines for sharing of data and specimen resources and publication policies Tabulation of similarities and differences in design, data variables, and specimen acquisition and storage (if applicable) across studies Proposed plan to address informed consent issues

12 Consortia Challenges and Possible Solutions (CWG) CHALLENGESPOSSIBLE SOLUTIONS Communication and coordination Informed consent and IRBs variable behaviors Website, portals, teleconferences and in- person meetings Prospective consortia, re-consent, IRBseducation Informatics and analytic support for collection, management and analysis of extremely large and complex datasets Central informatics units, standardization of informatics platform (caBIG), think tank for analytic challenges Rapid and continuous integration of cutting- edge genomic and other technologies Centralized technology platforms, public- private partnership Biorepositories: centralized versus local, large scale retrieval of tissue Work toward maximizing bioresources (transformed cell lines,WGA, pooling, tissue microdissection, multiplex microarrays) Integration of disciplinesInterdisciplinary training, integration of new knowledge and concepts as they arise, shift in academic culture triggered by multiple outcome funding approaches

13 CHALLENGESPOSSIBLE SOLUTIONS Intellectual property rightsCarefully crafted agreements, involving all partners Authorship and principal investigatorship (especially for young investigators) Change in structure of funding mechanisms, tenure criteria, publication credits. Access for the scientific community at large (Data sharing) Development of clear process and policies (I.E. CFRs), NIH may help with cost of sharing data Review ProcessAppropriate IRG, education of peer scientists Interdisciplinary science requires interdisciplinary peer-review Interdisciplinary research teams take time to assemble and require unique resources Appropriate criteria for evaluation and measure of productivity taking in account planning and time to establish Infrastructure. Evaluate core activities and tools developed …and More

14 The Breast and Colon Cancer Family Registry A Hypothesis-Driven Research Infrastructure Sponsored by the National Cancer Institute

15 BC-CFR Objectives To establish a comprehensive research resource infrastructure to assist with the implementation of collaborative, interdisciplinary research protocols in the genetic epidemiology of breast, ovarian, colon and related cancers To identify, characterize, and follow-up a cohort of individuals and their family members, spanning the spectrum of cancer risk To identify diverse genetically susceptible populations that could benefit from enrollment in preventive and therapeutic interventions To develop an adaptive and evolving informatics model to support ongoing and future research consortia

16 BC-CFRs Components Funding B-CFR Phase IB-CFR Phase IIB-CFR Phase III C-CFR Phase IC-CFR Phase II Informatics Center Fiscal Year (Phase I, Phase II, Proposed Phase III ) BC-CFR Funding Support

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19 BC-CFR Sites Colon CFR: Australia Consortium, University of Melbourne John Hopper Cancer Care Ontario Steve Gallinger Fred Hutchinson Cancer Research Center, Seattle John Potter Mayo Clinic Noralane Lindor Cancer Research Center of Hawaii Loic Le Marchand USC (LA) Consortium Robert Haile Affiliated Sites – Galicia, Spain; Newfoundland, Canada; Northern California Cancer Center Breast CFR: Australia Consortium, University of Melbourne John Hopper Fox Chase Cancer Center, Philadelphia Mary Daly Metropolitan New York Ruby T. Senie Northern California Cancer Center Esther M. John Cancer Care Ontario Irene Andrulis University of Utah, Huntsman Cancer Institute Saundra Buys

20 BC-CFR Organizational Structure NCI Program Officer Core Working Groups Research Working Groups Steering Committee Advisory Committee Informatics Center Six Awarded Sites (and Affiliates) Adapted John et al. Breast Cancer Res 2004

21 Design of the BC-CFR COLLABORATIVECOLLABORATIVE FAMILIES Population Based Clinic-based Participating Sites (U01s) Central Registry Data Base Central Registry Data Base Informatics Center (Contract) Biospecimen Repositories Molecular Genetics Laboratories Family History Risk Factors Qs Clinical/Pathology Biospecimen Tracking Follow-up Molecular Characterization Informatics Units Pilot Studies S T U D I E S

22 BC-CFR Core Activities Core Activities Follow-up of enrolled proband/families and new families Molecular characterization (mutational/genotyping) Biospecimen repositories Virtual tissue repository Informatics Support Administrative, travel and coordination Accrual of new probands/families Minorities/ethnic projects Ashkenazi* Additional Activities Pilot/ancillary projects Establishment of fresh frozen tissue repository

23 BC-CFR Core Study Designs (Genetic Epidemiology) Adapted from Study Designs to Identify and Characterize Disease Susceptibility Genes, AS Whittemore and LM Nelson, JNCI Monograph 26, 1999 GoalDesign Identify new disease genes Linkage StudiesParametric Linkage Non-parametric Linkage Association StudiesCase-unrelated Control Case-related Control Characterize known disease genes Estimating Allele Frequency Cross-sectional Studies Estimating Penetrance Case-unrelated Control

24 B-CFR Consented Participants Collected ( )

25 C-CFR Consented Participants Collected ( )

26 Strengths of BC-CFR Dual-ascertainment Families across spectrum of risk Large sample size Quality and comprehensive collection Establishment of immortalized cell lines Interdisplinary team of experts Development of collaborative projects Flexibility in study design Prospective follow-up and data collection Diverse sample Race/ethnicity International sites Isolated populations (Ashkenazi Jewish and Newfoundland)

27 Designs for Studying Association in the CFRs D. Thomas, Genetic Epidemiology Population-based case-control studies Family-based designs: Case-parent triads Discordant sibships Kin-cohort designs Case-control family designs High-risk family designs

28 BC-CFR Review Process Advisory Committee Review (scientific merit) Steering Committee Review (availability of data/biospecimen; conflict of interest) Access to BC-CFR infrastructure granted P.I seeks funding for research project Contact: Alysa Lesemann (Scientific Review Coordinator)

29 Applications for BC-CFR Collaborative Projects Total # 122 B-CFR Total # 98 C-CFR

30 Cumulative Publications from BC-CFR Peer-Approved Research Projects Total # 117 B-CFR Total # 41 C-CFR

31 We Still Have a Long Way to Go


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