Clinical Sequencing Evidence-Generating Research (CSER)

The CSER Consortium is rapidly advancing the knowledge necessary to develop best practices for the implementation of genomic sequence data into clinical care. CSER is uniquely positioned to answer questions about the clinical implementation of genomic sequencing to meet its growing use in the clinical care of patients with diverse needs.

Rationale

Reports of genomic sequencing being applied to the medical care of individual patients are becoming more frequent, but much more needs to be done before the use of sequence data becomes routine. Evidence regarding the most promising clinical applications and the specific diseases or individual susceptibilities most likely to be usefully addressed by a genomic sequencing approach still accumulating. Incorporation of comprehensive genomic sequence data into clinical care will require changes to institutional policies, standard procedures (including simplified analysis and interpretive tools), and improved to integrating sequence information into the clinical workflow. The ethical, legal, and psychosocial implications of returning genomic variation data, with all of the caveats regarding statistical uncertainties, incomplete knowledge, and unanticipated findings, remain incompletely understood. Furthermore, research is needed to assess and improve the current processes of recruitment, testing, and follow-up of patients from diverse racial and ethnic groups, as well as those from the range of as-yet understudied clinical healthcare settings where genomic medicine might be put into practice.

In 2010, NHGRI, with co-funding from NCI, subsequently crafted the Clinical Sequencing Exploratory Research (CSER) initiative to: 1) leverage the Institute's long-standing experience in genomic sequencing and analysis to ease the adoption of these methods into clinical care, 2) guide the development and dissemination of best practices for the integration of clinical sequencing into clinical care, and 3) research the ethical, legal, and psychosocial implications (ELSI) of bringing broad genomic data into clinical decision-making including, for example, evaluation of the risks and potential benefits associated with the return of incidental findings or information on variants of uncertain effect. The CSER consortium added three more clinical sites and one Coordinating Center, and incorporated the nine projects formerly comprising the ELSI Return of Results Consortium in mid-2013. Investigators from NHGRI's Intramural ClinSeq® project also participate.

Beginning in August, 2017, NHGRI, NCI and the National Institute on Minority Health and Health Disparities (NIMHD) jointly funded a renewal of the CSER program. Phase II CSER - renamed to Clinical Sequencing Evidence-Generating Research to reflect its new goals - includes 6 clinical sites, the ClinSeq® study, and one Coordinating Center who will work together to: 1) define, generate and analyze evidence regarding the clinical utility of genome sequencing; 2) research the critical interactions among patients, family members, health practitioners, and clinical laboratories that influence implementation of clinical genome sequencing; and 3) identify and address real-world barriers to integrating genomic, clinical, and healthcare utilization data within a healthcare system to build a shared evidence base for clinical decision-making.

Crucial and complementary to these efforts are a continuing focus on ELSI and a dedicated focus on engaging stakeholders such as professional societies, payers, regulatory agencies and patient groups. Phase II of CSER will develop a Stakeholder Engagement Plan to solicit and be responsive to input regarding clinical utility measures or other relevant evidence to be generated and refined in the second phase. In turn, this process is anticipated to enhance the applicability of CSER evidence for decision-making by stakeholders, such as the establishment or refinement of best practices or implementation or reimbursement policies, or contribution to other evidentiary frameworks. Opportunities will continue for external collaborators, such as NHGRI ClinSeq® investigators and investigators with complementary ELSI or other expertise, to participate in CSER as affiliate members.

CSER Website: https://cser-consortium.org/

Rationale

Reports of genomic sequencing being applied to the medical care of individual patients are becoming more frequent, but much more needs to be done before the use of sequence data becomes routine. Evidence regarding the most promising clinical applications and the specific diseases or individual susceptibilities most likely to be usefully addressed by a genomic sequencing approach still accumulating. Incorporation of comprehensive genomic sequence data into clinical care will require changes to institutional policies, standard procedures (including simplified analysis and interpretive tools), and improved to integrating sequence information into the clinical workflow. The ethical, legal, and psychosocial implications of returning genomic variation data, with all of the caveats regarding statistical uncertainties, incomplete knowledge, and unanticipated findings, remain incompletely understood. Furthermore, research is needed to assess and improve the current processes of recruitment, testing, and follow-up of patients from diverse racial and ethnic groups, as well as those from the range of as-yet understudied clinical healthcare settings where genomic medicine might be put into practice.
In 2010, NHGRI, with co-funding from NCI, subsequently crafted the Clinical Sequencing Exploratory Research (CSER) initiative to: 1) leverage the Institute's long-standing experience in genomic sequencing and analysis to ease the adoption of these methods into clinical care, 2) guide the development and dissemination of best practices for the integration of clinical sequencing into clinical care, and 3) research the ethical, legal, and psychosocial implications (ELSI) of bringing broad genomic data into clinical decision-making including, for example, evaluation of the risks and potential benefits associated with the return of incidental findings or information on variants of uncertain effect. The CSER consortium added three more clinical sites and one Coordinating Center, and incorporated the nine projects formerly comprising the ELSI Return of Results Consortium in mid-2013. Investigators from NHGRI's Intramural ClinSeq® project also participate.
Beginning in August, 2017, NHGRI, NCI and the National Institute on Minority Health and Health Disparities (NIMHD) jointly funded a renewal of the CSER program. Phase II CSER - renamed to Clinical Sequencing Evidence-Generating Research to reflect its new goals - includes 6 clinical sites, the ClinSeq® study, and one Coordinating Center who will work together to: 1) define, generate and analyze evidence regarding the clinical utility of genome sequencing; 2) research the critical interactions among patients, family members, health practitioners, and clinical laboratories that influence implementation of clinical genome sequencing; and 3) identify and address real-world barriers to integrating genomic, clinical, and healthcare utilization data within a healthcare system to build a shared evidence base for clinical decision-making.
Crucial and complementary to these efforts are a continuing focus on ELSI and a dedicated focus on engaging stakeholders such as professional societies, payers, regulatory agencies and patient groups. Phase II of CSER will develop a Stakeholder Engagement Plan to solicit and be responsive to input regarding clinical utility measures or other relevant evidence to be generated and refined in the second phase. In turn, this process is anticipated to enhance the applicability of CSER evidence for decision-making by stakeholders, such as the establishment or refinement of best practices or implementation or reimbursement policies, or contribution to other evidentiary frameworks. Opportunities will continue for external collaborators, such as NHGRI ClinSeq® investigators and investigators with complementary ELSI or other expertise, to participate in CSER as affiliate members.
CSER Website: https://cser-consortium.org/

Grantees

Clinical Sequencing Evidence-Generating Research (CSER2) Groups (2017-2021)

Institution	Lead PI(s)	Study Title	Clinical Focus
Baylor College of Medicine	Sharon Plon; Will Parsons, Amy McGuire	Evaluating utility and improving implementation of genomic sequencing for pediatric cancer patients in the diverse population and healthcare settings of Texas: The KidsCanSeq Study*	Pediatric cancer
Hudson-Alpha Institute for Biotechnology	Gregory Cooper, Gregory Barsh, Bruce Korf	Clinical sequencing across communities in the Deep South	Genetic disorders in newborns
Kaiser Foundation Research Institute	Katrina Goddard, Benjamin Wilfond	Exome sequencing in Diverse Populations in Colorado & Oregon	Cancer predisposition
Icahn School of Medicine at Mount Sinai	Eimear Kenny, Melissa Wasserstein, Carol Horowitz, Bruce Gelb	Incorporating genomics into the clinical care of diverse NYC children**	Pediatric undiagnosed disorders
University of California, San Francisco	Pui Kwok, Barbara Koenig, Mary Norton, Anne Slavotinek	Genomic sequencing to aid diagnosis in pediatric and prenatal practice: Examining clinical utility, ethical implications, payer coverage, and data integration in a diverse population.	Prenatal and pediatric undiagnosed developmental disorders
University of North Carolina, Chapel Hill	Jonathan Berg, Christine Rini, Bradford Powell	North Carolina Clinical Genomic Evaluation by Next-gen Exome Sequencing 2	Multiple adult and pediatric diseases
University of Washington	Gail Jarvik, Peter Tarczy-Hornoch, David Veenstra, Stephanie Fullerton, Deborah Nickerson	Evolving Our Partnership: The CSER2 Centralized Support Coordinating Center	Coordinating Center

* Co-funded by NCI

** Co-funded by NIMHD

Phase I Clinical Sequencing Exploratory Research Groups (2011-2017)

Institution	Lead PI(s)	Study Title	Clinical Focus
Baylor College of Medicine	Sharon Plon, Will Parsons and Amy McGuire	Evaluating utility and improving implementation of genomic sequencing for pediatric cancer patients in the diverse population and healthcare settings of Texas: The KidsCanSeq Study	Pediatric cancer
Brigham and Women's Hospital	Robert C. Green	Integration of Whole Genome Sequencing into Clinical Medicine	Primary care patients, cardiomyopathy patients
Children's Hospital of Philadelphia	Ian Krantz and Nancy Spinner	Applying Genomic Sequencing in Pediatrics	Pediatric patients with one of four conditions - intellectual disability, sudden cardiac arrest/death, hearing loss, and mitochondrial disorders
Dana-Farber Cancer Institute	Levi Garraway and Pasi Janne	The Use of Whole-Exome Sequencing to Guide the Care of Cancer Patients	Lung and colorectal cancer patients
Hudson-Alpha Institute for Biotechnology	Greg Cooper and Richard Myers	Genomic Diagnosis in Children with Developmental Delay	Children with intellectual disability and/or developmental delay
Kaiser Foundation Research Institute	Katrina Goddard and Benjamin Wilfond	Clinical Implementation of Carrier Testing Using Next Generation Sequencing (NGS)	Women and their partners seeking pre-conception carrier testing
University of Michigan, Ann Arbor	Arul Chinnaiyan	Exploring Precision Cancer Medicine for Sarcoma and Rare Cancers*	Patients with advanced sarcoma or other rare cancers
University of North Carolina, Chapel Hill	James Evans, Jonathan Berg and Gail Henderson	NC GENES	Patients from one of five clinical domains - cancer, cardiology, dysmorphology, neurodevelopmental and ophthalmology
University of Washington, Seattle	Gail Jarvik	Clinical sequencing in cancer: Clinical, ethical, and technological studies	Patients who have clinical indications for colorectal cancer/polyposis (CRCP) genetic testing
University of Washington, Seattle	Gail Jarvik	CSER Centralized Support Coordinating Center	The coordinating center is responsible for facilitating the scientific work of the CSER consortium and its working group by providing logistical and scientific expertise. It will also be a key partner in disseminating findings and approaches from the CSER program to the biomedical research community.

Ethical, Legal, and Social Implications-specific Projects (through 2017)

Formerly comprising the Return of Results Consortium

Institution	PI	Study Title	Grant Type
Cleveland Clinic	Richard Sharp	Presenting diagnostic results from large-scale clinical mutation testing	R01
Columbia University	Paul S. Appelbaum	Challenges of informed consent in return of data from genomic research	R21
Columbia University	Wendy K. Chung	Impact of return of incidental genetic test results to research participants in the genomic era	R01
Children's Hospital Boston	Ingrid A. Holm	Returning research results in children: Parental Preferences and Expert Oversight	R01
Children's Mercy Bioethics Center	Jeremy R. Garrett	The presumptive case against returning individual results in biobanking research	R21
Johns Hopkins University	Michelle Huckaby Lewis	Return of research results from samples obtained for newborn screening	R21
University of California, San Francisco	Gloria Peterson, Barbara Koenig, and Susan Wolf	Disclosing genomic incidental findings in a cancer biobank: An ELSI experiment*	R01
Seattle Children's Hospital	Holly K. Tabor	Innovative Approaches to Returning Results in Exome and Genome Sequencing Studies	R01
Vanderbilt University	Ellen Wright Clayton	Returning research results of pediatric genomic research to participants	R21

* Co-funded by NCI

Grantees

Clinical Sequencing Evidence-Generating Research (CSER2) Groups (2017-2021)

Institution	Lead PI(s)	Study Title	Clinical Focus
Baylor College of Medicine	Sharon Plon; Will Parsons, Amy McGuire	Evaluating utility and improving implementation of genomic sequencing for pediatric cancer patients in the diverse population and healthcare settings of Texas: The KidsCanSeq Study*	Pediatric cancer
Hudson-Alpha Institute for Biotechnology	Gregory Cooper, Gregory Barsh, Bruce Korf	Clinical sequencing across communities in the Deep South	Genetic disorders in newborns
Kaiser Foundation Research Institute	Katrina Goddard, Benjamin Wilfond	Exome sequencing in Diverse Populations in Colorado & Oregon	Cancer predisposition
Icahn School of Medicine at Mount Sinai	Eimear Kenny, Melissa Wasserstein, Carol Horowitz, Bruce Gelb	Incorporating genomics into the clinical care of diverse NYC children**	Pediatric undiagnosed disorders
University of California, San Francisco	Pui Kwok, Barbara Koenig, Mary Norton, Anne Slavotinek	Genomic sequencing to aid diagnosis in pediatric and prenatal practice: Examining clinical utility, ethical implications, payer coverage, and data integration in a diverse population.	Prenatal and pediatric undiagnosed developmental disorders
University of North Carolina, Chapel Hill	Jonathan Berg, Christine Rini, Bradford Powell	North Carolina Clinical Genomic Evaluation by Next-gen Exome Sequencing 2	Multiple adult and pediatric diseases
University of Washington	Gail Jarvik, Peter Tarczy-Hornoch, David Veenstra, Stephanie Fullerton, Deborah Nickerson	Evolving Our Partnership: The CSER2 Centralized Support Coordinating Center	Coordinating Center

* Co-funded by NCI

** Co-funded by NIMHD

Phase I Clinical Sequencing Exploratory Research Groups (2011-2017)

Institution	Lead PI(s)	Study Title	Clinical Focus
Baylor College of Medicine	Sharon Plon, Will Parsons and Amy McGuire	Evaluating utility and improving implementation of genomic sequencing for pediatric cancer patients in the diverse population and healthcare settings of Texas: The KidsCanSeq Study	Pediatric cancer
Brigham and Women's Hospital	Robert C. Green	Integration of Whole Genome Sequencing into Clinical Medicine	Primary care patients, cardiomyopathy patients
Children's Hospital of Philadelphia	Ian Krantz and Nancy Spinner	Applying Genomic Sequencing in Pediatrics	Pediatric patients with one of four conditions - intellectual disability, sudden cardiac arrest/death, hearing loss, and mitochondrial disorders
Dana-Farber Cancer Institute	Levi Garraway and Pasi Janne	The Use of Whole-Exome Sequencing to Guide the Care of Cancer Patients	Lung and colorectal cancer patients
Hudson-Alpha Institute for Biotechnology	Greg Cooper and Richard Myers	Genomic Diagnosis in Children with Developmental Delay	Children with intellectual disability and/or developmental delay
Kaiser Foundation Research Institute	Katrina Goddard and Benjamin Wilfond	Clinical Implementation of Carrier Testing Using Next Generation Sequencing (NGS)	Women and their partners seeking pre-conception carrier testing
University of Michigan, Ann Arbor	Arul Chinnaiyan	Exploring Precision Cancer Medicine for Sarcoma and Rare Cancers*	Patients with advanced sarcoma or other rare cancers
University of North Carolina, Chapel Hill	James Evans, Jonathan Berg and Gail Henderson	NC GENES	Patients from one of five clinical domains - cancer, cardiology, dysmorphology, neurodevelopmental and ophthalmology
University of Washington, Seattle	Gail Jarvik	Clinical sequencing in cancer: Clinical, ethical, and technological studies	Patients who have clinical indications for colorectal cancer/polyposis (CRCP) genetic testing
University of Washington, Seattle	Gail Jarvik	CSER Centralized Support Coordinating Center	The coordinating center is responsible for facilitating the scientific work of the CSER consortium and its working group by providing logistical and scientific expertise. It will also be a key partner in disseminating findings and approaches from the CSER program to the biomedical research community.

Ethical, Legal, and Social Implications-specific Projects (through 2017)

Formerly comprising the Return of Results Consortium

Institution	PI	Study Title	Grant Type
Cleveland Clinic	Richard Sharp	Presenting diagnostic results from large-scale clinical mutation testing	R01
Columbia University	Paul S. Appelbaum	Challenges of informed consent in return of data from genomic research	R21
Columbia University	Wendy K. Chung	Impact of return of incidental genetic test results to research participants in the genomic era	R01
Children's Hospital Boston	Ingrid A. Holm	Returning research results in children: Parental Preferences and Expert Oversight	R01
Children's Mercy Bioethics Center	Jeremy R. Garrett	The presumptive case against returning individual results in biobanking research	R21
Johns Hopkins University	Michelle Huckaby Lewis	Return of research results from samples obtained for newborn screening	R21
University of California, San Francisco	Gloria Peterson, Barbara Koenig, and Susan Wolf	Disclosing genomic incidental findings in a cancer biobank: An ELSI experiment*	R01
Seattle Children's Hospital	Holly K. Tabor	Innovative Approaches to Returning Results in Exome and Genome Sequencing Studies	R01
Vanderbilt University	Ellen Wright Clayton	Returning research results of pediatric genomic research to participants	R21

* Co-funded by NCI

Phase II CSER2 Working Groups

Working Groups Convened in Fall 2017

Clinical Utility, Health Economics, and Policy (CUHEP)

Co-Chairs: Bart Ferket (Mount Sinai) and Heidi Russell (Baylor)

Mission: This transdisciplinary working group includes experts in clinical care, genetic counseling, outcomes research, health economics, cost effectiveness, health policy, health IT systems, and administration. We are studying consortium-wide measures of clinical utility from the perspective of participating physicians’ recommendations and uptake of these recommendations by families. The WG also acknowledges the importance of key outcomes of interest to payers, administrators and policymakers including those related to clinical outcomes, healthcare utilization, and health economics. Initial activities have included planning collaborative cross-consortium analyses informed by common measures of clinical utility and health outcomes to maximize the power of these investigations for usefulness for groups creating genomic medicine guidelines, payers and other policymakers. This working group is committed to reaching out to different professional medical organizations outside of medical genetics as well as with payers and policymakers, to ensure we are including relevant outcome measures.

Education and Return of Results (Edu/ROR)

Co-Chairs: Kate Bonini (Mount Sinai) and Kate Foreman (UNC)

Mission: The mission of this Working Group is multi-faceted:

Explore return of result delivery models for genomic testing across diverse populations and patient care settings including in-person, telemedicine, web platform and written materials.
Collaborate on efforts to educate patients and providers about genomics, genetics and genetic testing methods for returning results. The WG will expand upon existing CSER resources as needed, as well as develop patient and provider education to ensure information is accessible, understandable and actionable for diverse populations.
Investigate the implications of returning diagnostic, secondary and negative genomic sequencing results in collaboration with input from the SADY and CUHEP WGs.
Explore the family communication process following RoR.
Determine participant satisfaction with various aspects of the return of results process including information received, mode of delivery and overall patient experience. The WG will collaborate with other CSER WG to also explore the downstream effects of RoR.

ELSI and Diversity

Co-Chairs: Mary Majumder (Baylor) and Benjamin Wilfond (Kaiser)

Mission: Given the focus on diversity in CSER, issues of diversity potentially fall within the scope of all WGs. This WG, however, intends to tackle social and ethical implications of genomics, with a particular focus on diversity. This mission encompasses the challenges of implementing genomics in diverse populations and how racial, ethnic and socioeconomic diversity might impact informed consent and return of results processes, as well as the delivery and personal utility of genomic medicine more broadly. Although diversity is a major focus, this WG will also take on other ELSI-related issues.

Sequence Analysis and Diagnostic Yield (SADY)

Co-Chairs: John Greally (Mt. Sinai) and Sarah Kalla (Baylor)

Mission: All CSER sites are recording some measure of diagnostic yield, since it provides a proximal measure of clinical usefulness (or at least sets a cap on potential clinical utility). This group seeks to harmonize or at least understand differences among sites to make cross-consortium comparisons, including phenotype/disease categories, sequencing performance metrics, variant calling/annotation/interpretation, case-level reporting criteria, and secondary findings. This WG also addresses issues related to laboratory-provider interactions. In addition, this WG discusses sharing sequencing data and technical improvements among sites, adding founder mutations to databases, and reanalyzing VCFs to assess impact on yield and cost.

Patient, Community, and Clinical Stakeholder Engagement

Co-Chairs: Sara J. Knight (HudsonAlpha) and Amanda Gutierrez (Baylor)

Mission: There are numerous stakeholders at the various CSER sites including patients/caregivers who are likely to represent diverse population, SES, demographic, geographic, and disease groups. In addition, stakeholders encompass patient/caregiver advocates, and clinicians from diverse specialties and clinical settings. Finally, institutional and healthcare stakeholders include IRBs as well as healthcare and payer representatives. Acknowledging the inherent differences between stakeholders, this Working Group aims to provide a forum to identify and discuss stakeholder activities, address common challenges, and highlight outcomes.

Survey Measures and Outcomes (M&O)

Co-Chairs: Jessica Hunter (Kaiser) and Michael Leo (Kaiser)

Mission: Similar to the CSER1 Outcomes and Measures Working Group, this group will focus on patients' and family members' knowledge, attitudes, beliefs, behaviors and psychological outcomes. In keeping with the focus of CSER, we would also study provider knowledge, attitudes, beliefs and behaviors, including diagnostic thinking and management planning. This can include mixed methods-qualitative interviews, surveys, and abstracting clinical records. This WG will also address issues related to patient/providers surveys with input from the CUHEP, ELSI/diversity, and Edu/ROR WGs; common measures related to demographics and socioeconomic status (other than ancestry) with input from the ELSI/diversity WG; and a cross-CSER decliner survey.

CSER Working Groups Running Through 2017

Informed Consent & Governance

Chairs: Paul Appelbaum and Joon-Ho Yu
Mission: Discuss emerging issues and develop new and creative approaches related to informed consent in the context of clinical sequencing; compare and, to the extent feasible, develop standardized consent language and protocols. Discuss and compile experience with institutional governance of genomic data in research and clinical settings; where appropriate integrate governance recommendations with best practice and/or model language for informed consent.

Actionable Variants and Return of Results
Chairs: Laura Amendola and Wendy Chung
Mission:

Define the principles and processes guiding the definition of an 'actionable' gene across the consortium, highlighting common outcomes and the rationale underlying discrepancies.
Explore overlap regarding the classification process of identified variants in these actionable genes, and develop resources to support decisions with respect to pathogenicity.
Coordinate with other CSER working groups to develop best practices for the process of returning genomic findings, including the informed consent process, analysis of sequence variants, storage in the medical record, and communication of results to the patient.

Sequencing Standards

Chair: Nick Wagle and Donna Muzny
Mission: Develop and share technical standards for sequencing in a clinical context (for example, minimum coverage and quality metrics, turnaround time, data formats, CLIA); develop best practices for variant validation.

Electronic Health Records

Chair: Peter Tarczy-Hornoch and Brian Shirts
Mission: Understand and facilitate cross site collaboration nationally around informatics work as related to variant annotation, prioritization, integration into electronic medical record, and integration into decision support.

Outcomes and Measures

Chairs: David Veenstra and Stacy Gray
Mission: Coordinate development of instruments to measure psychosocial outcomes related to returning results.

Pediatrics

Chairs: Kyle Brothers and Ben Wilfond
Mission: Explore and attempt to develop standardized approaches to addressing the unique ethical, legal, and practical challenges relating to returning results in studies involving pediatric populations.

Genetic Counseling

Chairs: Julia Wynn and Sarah Scollon
Mission: Discuss site-specific experiences with issues related to genetic counseling. Work on publications and educational materials, and function as a sounding board to new groups.

Tumor

Chair: Will Parsons and Dan Robinson
Misson: Explore the unique technical, interpretive and ethical challenges and considerations involved in clinical sequencing of cancer genomes (e.g. identification of somatic variants) and to attempt to develop best practices for these tests.

Practitioner Education

Chairs: Sharon Plon and Kelly East
Mission: Develop ideas, tools and resources that can help inform non-genetic medical practitioners of the use of genomic sequencing in the clinic.

Phase II CSER2 Working Groups
Working Groups Convened in Fall 2017
Clinical Utility, Health Economics, and Policy (CUHEP)
Co-Chairs: Bart Ferket (Mount Sinai) and Heidi Russell (Baylor)
Mission: This transdisciplinary working group includes experts in clinical care, genetic counseling, outcomes research, health economics, cost effectiveness, health policy, health IT systems, and administration. We are studying consortium-wide measures of clinical utility from the perspective of participating physicians’ recommendations and uptake of these recommendations by families. The WG also acknowledges the importance of key outcomes of interest to payers, administrators and policymakers including those related to clinical outcomes, healthcare utilization, and health economics. Initial activities have included planning collaborative cross-consortium analyses informed by common measures of clinical utility and health outcomes to maximize the power of these investigations for usefulness for groups creating genomic medicine guidelines, payers and other policymakers. This working group is committed to reaching out to different professional medical organizations outside of medical genetics as well as with payers and policymakers, to ensure we are including relevant outcome measures.
Education and Return of Results (Edu/ROR)
Co-Chairs: Kate Bonini (Mount Sinai) and Kate Foreman (UNC)
Mission: The mission of this Working Group is multi-faceted:
Explore return of result delivery models for genomic testing across diverse populations and patient care settings including in-person, telemedicine, web platform and written materials.
Collaborate on efforts to educate patients and providers about genomics, genetics and genetic testing methods for returning results. The WG will expand upon existing CSER resources as needed, as well as develop patient and provider education to ensure information is accessible, understandable and actionable for diverse populations.
Investigate the implications of returning diagnostic, secondary and negative genomic sequencing results in collaboration with input from the SADY and CUHEP WGs.
Explore the family communication process following RoR.
Determine participant satisfaction with various aspects of the return of results process including information received, mode of delivery and overall patient experience. The WG will collaborate with other CSER WG to also explore the downstream effects of RoR.
ELSI and Diversity
Co-Chairs: Mary Majumder (Baylor) and Benjamin Wilfond (Kaiser)
Mission: Given the focus on diversity in CSER, issues of diversity potentially fall within the scope of all WGs. This WG, however, intends to tackle social and ethical implications of genomics, with a particular focus on diversity. This mission encompasses the challenges of implementing genomics in diverse populations and how racial, ethnic and socioeconomic diversity might impact informed consent and return of results processes, as well as the delivery and personal utility of genomic medicine more broadly. Although diversity is a major focus, this WG will also take on other ELSI-related issues.
Sequence Analysis and Diagnostic Yield (SADY)
Co-Chairs: John Greally (Mt. Sinai) and Sarah Kalla (Baylor)
Mission: All CSER sites are recording some measure of diagnostic yield, since it provides a proximal measure of clinical usefulness (or at least sets a cap on potential clinical utility). This group seeks to harmonize or at least understand differences among sites to make cross-consortium comparisons, including phenotype/disease categories, sequencing performance metrics, variant calling/annotation/interpretation, case-level reporting criteria, and secondary findings. This WG also addresses issues related to laboratory-provider interactions. In addition, this WG discusses sharing sequencing data and technical improvements among sites, adding founder mutations to databases, and reanalyzing VCFs to assess impact on yield and cost.
Patient, Community, and Clinical Stakeholder Engagement
Co-Chairs: Sara J. Knight (HudsonAlpha) and Amanda Gutierrez (Baylor)
Mission: There are numerous stakeholders at the various CSER sites including patients/caregivers who are likely to represent diverse population, SES, demographic, geographic, and disease groups. In addition, stakeholders encompass patient/caregiver advocates, and clinicians from diverse specialties and clinical settings. Finally, institutional and healthcare stakeholders include IRBs as well as healthcare and payer representatives. Acknowledging the inherent differences between stakeholders, this Working Group aims to provide a forum to identify and discuss stakeholder activities, address common challenges, and highlight outcomes.
Survey Measures and Outcomes (M&O)
Co-Chairs: Jessica Hunter (Kaiser) and Michael Leo (Kaiser)
Mission: Similar to the CSER1 Outcomes and Measures Working Group, this group will focus on patients' and family members' knowledge, attitudes, beliefs, behaviors and psychological outcomes. In keeping with the focus of CSER, we would also study provider knowledge, attitudes, beliefs and behaviors, including diagnostic thinking and management planning. This can include mixed methods-qualitative interviews, surveys, and abstracting clinical records. This WG will also address issues related to patient/providers surveys with input from the CUHEP, ELSI/diversity, and Edu/ROR WGs; common measures related to demographics and socioeconomic status (other than ancestry) with input from the ELSI/diversity WG; and a cross-CSER decliner survey.
CSER Working Groups Running Through 2017
Informed Consent & Governance
Chairs: Paul Appelbaum and Joon-Ho Yu
Mission: Discuss emerging issues and develop new and creative approaches related to informed consent in the context of clinical sequencing; compare and, to the extent feasible, develop standardized consent language and protocols. Discuss and compile experience with institutional governance of genomic data in research and clinical settings; where appropriate integrate governance recommendations with best practice and/or model language for informed consent.

Actionable Variants and Return of Results
Chairs: Laura Amendola and Wendy Chung
Mission:
Define the principles and processes guiding the definition of an 'actionable' gene across the consortium, highlighting common outcomes and the rationale underlying discrepancies.
Explore overlap regarding the classification process of identified variants in these actionable genes, and develop resources to support decisions with respect to pathogenicity.
Coordinate with other CSER working groups to develop best practices for the process of returning genomic findings, including the informed consent process, analysis of sequence variants, storage in the medical record, and communication of results to the patient.
Sequencing Standards
Chair: Nick Wagle and Donna Muzny
Mission: Develop and share technical standards for sequencing in a clinical context (for example, minimum coverage and quality metrics, turnaround time, data formats, CLIA); develop best practices for variant validation.
Electronic Health Records
Chair: Peter Tarczy-Hornoch and Brian Shirts
Mission: Understand and facilitate cross site collaboration nationally around informatics work as related to variant annotation, prioritization, integration into electronic medical record, and integration into decision support.
Outcomes and Measures
Chairs: David Veenstra and Stacy Gray
Mission: Coordinate development of instruments to measure psychosocial outcomes related to returning results.
Pediatrics
Chairs: Kyle Brothers and Ben Wilfond
Mission: Explore and attempt to develop standardized approaches to addressing the unique ethical, legal, and practical challenges relating to returning results in studies involving pediatric populations.
Genetic Counseling
Chairs: Julia Wynn and Sarah Scollon
Mission: Discuss site-specific experiences with issues related to genetic counseling. Work on publications and educational materials, and function as a sounding board to new groups.
Tumor
Chair: Will Parsons and Dan Robinson
Misson: Explore the unique technical, interpretive and ethical challenges and considerations involved in clinical sequencing of cancer genomes (e.g. identification of somatic variants) and to attempt to develop best practices for these tests.
Practitioner Education
Chairs: Sharon Plon and Kelly East
Mission: Develop ideas, tools and resources that can help inform non-genetic medical practitioners of the use of genomic sequencing in the clinic.

Events

eMERGE & CSER: Genomics and Medicine January 17-18, 2019
eMERGE & CSER: The Convergence of Genomics and Medicine February 2, 2017
CSER2 Webinar June 15, 2016
Integrating Genomic Sequencing into Clinical Care: CSER and Beyond September 28, 2015

Events
eMERGE & CSER: Genomics and Medicine January 17-18, 2019
eMERGE & CSER: The Convergence of Genomics and Medicine February 2, 2017
CSER2 Webinar June 15, 2016
Integrating Genomic Sequencing into Clinical Care: CSER and Beyond September 28, 2015

Funding Opportunities

Program Staff

Dave Kaufman, Ph.D.

Program Director
Division of Genomics and Society

Last updated: July 9, 2024