fda webinar: precision medicine and minority health
TRANSCRIPT
Lost in Translation:Minority Health Latrice Landry, MMSc, PhD
April 23, 2019
Biomarkers, including Genomic Variants, are a Key Component to Precision Medicine
Patient Report
Molecular Findings
Stochastic Modeling
Causative Agent
Therapeutic Prospects
Disease Treatment/
Insufficient Evidence of Generalizability
European 15%
Non- European
CURRENT WORLD POPULATION
*Databases included are the database of genotypes and phenotypes (dbGaP) and the Genome Wide Association Study Catalogue (GWAS catalogue).
Landry, L, Ali, N., Williams, D., Rehm, H., Bonham, V. (2018). Lack of ancestral diversity in genomic databases – a barrier to clinical translation in precision medicine. Health Aff (Millwood), 37(5):780-785.
Chart1
European
Non-European
European Cohorts 71%
Non-European Cohorts 29%
2017 European vs. Non-European with Mixed and Race not listed
European
2067
Mixed
126
Ancestry Not Listed
2018 World Population
European Cohorts 54%
Mixed Cohorts 3%
Asian Cohorts 16%
URM Cohorts 6%
2017 European vs. Non-European with Mixed and Race not listed
European
2067
Mixed
126
Asian
618
URM
244
Ancestry Not Listed
2018 World Population
Predictive error for
POSSIBLE IMPACT ON BIOMARKERS
FDA/NIH Leadership Council Biomarker Program
Missed Biomarkers
Wallstreetfreepress.com
Clinical Utility
Challenge Question:
Is the clinical utility of a genetic test the same for all individuals?
The Medseq Case Study: Review of a Clinical Research Genome Report for
an African American participant
A Clinical Trial of Whole Genome Sequencing in Clinical Care.
Vassey, J. 2015. A one-page summary report of genome sequencing for the healthy adult. Public Health Genomics 8:123–129.
Johnson, J.A., Cavallari, H.H.(2015). “Warfarin Pharmacogenomics”. Trends in Cardiovascular Medicine. 25. 33-41.
Decreased dose
A Clinical Trial of Whole Genome Sequencing in Clinical Care.
Warfarin Pharmacogenomic Dosing
Decreased dose
A Clinical Trial of Whole Genome Sequencing in Clinical Care.
4 variants associated with warfarin dosing in AA not
included in dosing algorithm from Advisory Body
Our African American Participant
predominantly European populations were not generalizable.
Do you see the same bias in clinical practice?
Underrepresented Minorities have a Lower Detection Rate for both Cardiomyopathy compared to their White Counterparts and a higher rate of inconclusive results.
Landry, L., Rehm, H. (2018). The Association of Racial/Ethnic Categories With the Ability of Genetic Tests to Detect a Cause of Cardiomyopathy. JAMA Cardiology, 3(4):341-345.
Challenge Question:
Is the clinical utility of a genetic test the same for all individuals?
We have demonstrated there are differences in clinical utility of genetic
testing by population group.
Challenge Question:
True or False: There are no differences in access to genetic testing by population group.
Direct To Consumer Physician Mediated
Genetic Testing Models
Genetic Testing Models
Genetic Testing Models
Challenge Question:
True or False: There are no differences in access to genetic testing by population group.
Personal Utility
Challenge Question:
The personal utility of genetic testing for minorities compared with non- minorities is___?
A. The Same B. Different C. It Depends
Journal of Community Genetics
Traits and Ancestry related biomarkers
Utilization: Personal Utility
Challenge Question:
The Personal Utility of Genetic Testing for minorities compared with non- minorities is___?
A. The Same B. Different C. It Depends
Understanding the Gaps
Increasing Access to Precision Services
Building Infrastructure
Collaboration
Academia
Government
Industry
Many individuals in populations disproportionately burdened by disease are
looking for answers. To the extent that our research provides those
answers it is our duty to ensure clinical translation is equitable.
Acknowledgements
FDA NHGRI Partner’s Personalized Medicine CAMD at BWH Harvard Medical School Genomes 2 People Pgen Study Group Center for Global Cancer Prevention at Harvard School of Public Health Tim Rebbeck Nadya Ali Heidi Rehm Vence Bonham David Williams Robert Green Daiva Nielsen Alexis Carrere J.Scott Roberts
FDA Webinar: Precision Medicine and Minority Health
Slide Number 2
Slide Number 3
Slide Number 4
Slide Number 5
Slide Number 6
Slide Number 11
Slide Number 12
Slide Number 13
Challenge Question: Is the clinical utility of a genetic test the same for all individuals?
The Medseq Case Study: Review of a Clinical Research Genome Report for an African American participant
Pharmacogenomic Predictions
The evidence-based genomic test and clinical report designed from predominantly European populations were not generalizable.
Do you see the same bias in clinical practice?
Slide Number 25
Challenge Question: Is the clinical utility of a genetic test the same for all individuals?We have demonstrated there are differences in clinical utility of genetic testing by population group.
Slide Number 27
Challenge Question: True or False: There are no differences in access to genetic testing by population group.
Slide Number 29
Slide Number 30
Slide Number 31
Slide Number 32
Slide Number 33
Slide Number 34
Challenge Question: True or False: There are no differences in access to genetic testing by population group.
Slide Number 36
Challenge Question:The personal utility of genetic testing for minorities compared with non-minorities is___?A. The SameB. Different C. It Depends
Journal of Community Genetics
Challenge Question:The Personal Utility of Genetic Testing for minorities compared with non-minorities is___?A. The SameB. Different C. It Depends
Slide Number 45
Slide Number 46
Slide Number 47
Slide Number 48
Slide Number 49
April 23, 2019
Biomarkers, including Genomic Variants, are a Key Component to Precision Medicine
Patient Report
Molecular Findings
Stochastic Modeling
Causative Agent
Therapeutic Prospects
Disease Treatment/
Insufficient Evidence of Generalizability
European 15%
Non- European
CURRENT WORLD POPULATION
*Databases included are the database of genotypes and phenotypes (dbGaP) and the Genome Wide Association Study Catalogue (GWAS catalogue).
Landry, L, Ali, N., Williams, D., Rehm, H., Bonham, V. (2018). Lack of ancestral diversity in genomic databases – a barrier to clinical translation in precision medicine. Health Aff (Millwood), 37(5):780-785.
Chart1
European
Non-European
European Cohorts 71%
Non-European Cohorts 29%
2017 European vs. Non-European with Mixed and Race not listed
European
2067
Mixed
126
Ancestry Not Listed
2018 World Population
European Cohorts 54%
Mixed Cohorts 3%
Asian Cohorts 16%
URM Cohorts 6%
2017 European vs. Non-European with Mixed and Race not listed
European
2067
Mixed
126
Asian
618
URM
244
Ancestry Not Listed
2018 World Population
Predictive error for
POSSIBLE IMPACT ON BIOMARKERS
FDA/NIH Leadership Council Biomarker Program
Missed Biomarkers
Wallstreetfreepress.com
Clinical Utility
Challenge Question:
Is the clinical utility of a genetic test the same for all individuals?
The Medseq Case Study: Review of a Clinical Research Genome Report for
an African American participant
A Clinical Trial of Whole Genome Sequencing in Clinical Care.
Vassey, J. 2015. A one-page summary report of genome sequencing for the healthy adult. Public Health Genomics 8:123–129.
Johnson, J.A., Cavallari, H.H.(2015). “Warfarin Pharmacogenomics”. Trends in Cardiovascular Medicine. 25. 33-41.
Decreased dose
A Clinical Trial of Whole Genome Sequencing in Clinical Care.
Warfarin Pharmacogenomic Dosing
Decreased dose
A Clinical Trial of Whole Genome Sequencing in Clinical Care.
4 variants associated with warfarin dosing in AA not
included in dosing algorithm from Advisory Body
Our African American Participant
predominantly European populations were not generalizable.
Do you see the same bias in clinical practice?
Underrepresented Minorities have a Lower Detection Rate for both Cardiomyopathy compared to their White Counterparts and a higher rate of inconclusive results.
Landry, L., Rehm, H. (2018). The Association of Racial/Ethnic Categories With the Ability of Genetic Tests to Detect a Cause of Cardiomyopathy. JAMA Cardiology, 3(4):341-345.
Challenge Question:
Is the clinical utility of a genetic test the same for all individuals?
We have demonstrated there are differences in clinical utility of genetic
testing by population group.
Challenge Question:
True or False: There are no differences in access to genetic testing by population group.
Direct To Consumer Physician Mediated
Genetic Testing Models
Genetic Testing Models
Genetic Testing Models
Challenge Question:
True or False: There are no differences in access to genetic testing by population group.
Personal Utility
Challenge Question:
The personal utility of genetic testing for minorities compared with non- minorities is___?
A. The Same B. Different C. It Depends
Journal of Community Genetics
Traits and Ancestry related biomarkers
Utilization: Personal Utility
Challenge Question:
The Personal Utility of Genetic Testing for minorities compared with non- minorities is___?
A. The Same B. Different C. It Depends
Understanding the Gaps
Increasing Access to Precision Services
Building Infrastructure
Collaboration
Academia
Government
Industry
Many individuals in populations disproportionately burdened by disease are
looking for answers. To the extent that our research provides those
answers it is our duty to ensure clinical translation is equitable.
Acknowledgements
FDA NHGRI Partner’s Personalized Medicine CAMD at BWH Harvard Medical School Genomes 2 People Pgen Study Group Center for Global Cancer Prevention at Harvard School of Public Health Tim Rebbeck Nadya Ali Heidi Rehm Vence Bonham David Williams Robert Green Daiva Nielsen Alexis Carrere J.Scott Roberts
FDA Webinar: Precision Medicine and Minority Health
Slide Number 2
Slide Number 3
Slide Number 4
Slide Number 5
Slide Number 6
Slide Number 11
Slide Number 12
Slide Number 13
Challenge Question: Is the clinical utility of a genetic test the same for all individuals?
The Medseq Case Study: Review of a Clinical Research Genome Report for an African American participant
Pharmacogenomic Predictions
The evidence-based genomic test and clinical report designed from predominantly European populations were not generalizable.
Do you see the same bias in clinical practice?
Slide Number 25
Challenge Question: Is the clinical utility of a genetic test the same for all individuals?We have demonstrated there are differences in clinical utility of genetic testing by population group.
Slide Number 27
Challenge Question: True or False: There are no differences in access to genetic testing by population group.
Slide Number 29
Slide Number 30
Slide Number 31
Slide Number 32
Slide Number 33
Slide Number 34
Challenge Question: True or False: There are no differences in access to genetic testing by population group.
Slide Number 36
Challenge Question:The personal utility of genetic testing for minorities compared with non-minorities is___?A. The SameB. Different C. It Depends
Journal of Community Genetics
Challenge Question:The Personal Utility of Genetic Testing for minorities compared with non-minorities is___?A. The SameB. Different C. It Depends
Slide Number 45
Slide Number 46
Slide Number 47
Slide Number 48
Slide Number 49