Return of Genetic Results in Kidney Research – Emerging Practices Workshop

Event Details

Purpose

While most research participants expect to learn about clinically relevant results obtained through their participation in research studies, implementing the return of results in genetic studies has been challenging. Some notable issues related to the adequacy of consent are the types of results to be returned, such as actionable incidental genetic findings or non-actionable but diagnostic findings, validation of results and the need for genetic counseling and follow-up clinical care. The challenges are augmented in studies involving children and when the knowledge about the clinical implications of genetic findings is only emerging, such as increased risk and polygenic risk scores.

Given the significant variability in study populations, design, and resources, along with the lack of clear standardized guidelines on how to prioritize these often-intertwined issues, we have structured this workshop to broadly touch on some of the key points to consider, along with emerging practices, as related to several NIDDK funded renal diseases consortia. As a platform for an initial discussion, we will review current plans for the return of genetic results for several studies, followed by panel discussions and break-out sessions set around key issues. Our hope is that this workshop will create a general framework to help catalyze further discussions and establish guidelines, moving forward.

Registration Deadline

July 31, 2023

Agenda

July 31, 2023

10:00 a.m. – 10:10 a.m.

Introduction
Afshin Parsa, M.D., M.P.H., and Rob Star, M.D.

10:10 a.m. – 10:30 a.m.

Opening Remarks—Framework and Rationales for Return of Results (RoR)
Ali Gharavi, M.D., and Maya Sabatello, LLB, Ph.D.

10:30 a.m. – 11:00 a.m.

All of Us Research Program Presentation
Anastasia Wise, Ph.D.

11:00 a.m. – 11:45 a.m.

Presentations from Studies Returning Results
CureGN, Neptune, and KPMP Consortia

Moderator:
Ingrid Holm, M.D., M.P.H.

Presenters:
Maya Sabatello, LLB, Ph.D.
Ana Claudia Onuchic-Whitford, M.D.
Bessie Young, M.D., M.P.H.

11:45 a.m. – 12:15 p.m.

Panel Discussion
Issues to cover: Planned workflows for RoR, knowledge of genomics—RoR priorities and requirements/structure for providing RoR

12:15 p.m. – 12:45 p.m.

Lunch

12:45 p.m. – 1:25 p.m.

Special Issues in Returning Results
CKiD (Children), APOLLO (Risk), and eMERGE (Polygenic Risk Score) Consortia

Moderator:
Matthew Sampson, M.D., M.S.

Presenters:
Craig Wong, M.D.
Barry Freedman, M.D.
Krzysztof Kiryluk, M.D.

1:25 p.m. – 1:50 p.m.

Panel Discussion
Issues to cover: Interest and challenges involving RoR to children, genetic risk findings, and emerging genomic results (PRS)—responsibility for validation

1:50 p.m. – 2:20 p.m.

Genetic Counselor Panel—Experience on the Ground

Moderator:
Wendy Uhlmann, M.S., LCGC

Presenters:
Emma Perez, MGC, CGC
Catherine Wicklund, M.S.
Mary-Beth Roberts, M.S., CGC

Issues to cover:  Case studies relating to ACMG medically actionable incidental gene findings, disability, APOL1 in transplant setting, and variants of uncertain significance (VUS)—medical implications, challenges in the process and commonly asked questions

2:20 p.m. – 2:30 p.m.

Break

2:30 p.m. – 3:30 p.m.

Patient Panel and Community Engagement

Moderator:
Glenda V. Roberts

Presenters:
Opeyemi Olabisi, M.D., Ph.D.
Sharon Lagas
Trinisha Williams
Denay Richards
Andrea Alvarez

Issues to cover: Personal experiences, barriers and facilitators related to genetic testing and return of results, prioritization of results, and relevance to family members

3:30 p.m. – 4:25 p.m.

Breakout Sessions

1. Responsibility and Priorities for RoR
   
   Moderators:
   Wylie Burke, M.D., Ph.D., and Nanibaa’ Garrison, Ph.D.
• Process for deciding what results are returned
• Disease specific (i.e., pertaining to study at hand) vs. secondary ACMG 81 actionable and/or clinically meaningful gene findings
• Disease modifiers (e.g., APOL1)
• Polygenic Risk Score
• What are the responsibilities toward participants who dropped out of a study or families of participants who are deceased?
2. Responsibility for Validation
   
   Moderators:
   Clesson Turner, M.D., and Ali Gharavi, M.D.
• Can we return research-level data when unable to obtain Clinical Laboratory Improvement Amendments (CLIA) validation?
• How should resources be prioritized for validation to decide which category of research level data should be returned? Should disease-specific gene variants be studied? Incidental findings? Risk factors? All putative pathogenic variants related and unrelated to study aims?
• Which physician(s) should order—and receive—the CLIA validation (study physician, primary nephrologists, patient’s PCP)?
• Who should cover the validation costs, including a possible reinterpretation of results (e.g., polygenetic risk scores)?
3. Responsibility for Genetic Counseling and Follow-up
   
   Moderators:
   Hila Milo Rasouly, Ph.D., and Meg Hager, M.S., M.P.H., CGC
• What are the responsibilities for pre- and post-test counseling?
• Are the counseling responsibilities different for different categories of variants (e.g., if incidental, does the study need to provide counseling or does adequate referral suffice, or when are printed materials sufficient)?
• What are the responsibilities for follow-up and medical decision-making post-RoR?
• Should the RoR plan be tailored to nephrologists’ genomic knowledge and capacity?
4. Responsibility for Inclusion and Equity
   
   Moderators:
   Carol R. Horowitz, M.D., M.P.H., and Nichole Jefferson
• Cultural appropriateness and diversity
• Responsibility to communities (i.e., not just individuals)
• Pediatric populations
• Accessibility to testing, research and genetic counseling (e.g., rural areas, reservations, access to information, linguistic accessibility, accessibility for people with different abilities)
• Equity in access to follow-up care—how to manage RoR to study participants who may not be able to afford follow up care? What are the responsibilities of the study research team versus clinical health care providers?

4:25 p.m. – 4:35 p.m.

Break

4:35 p.m. – 5:20 p.m.

Report Back and Discussion

5:20 p.m. – 5:30 p.m.

Summary and Closing Remarks

5:30 p.m.

Adjournment

Organizing Committee

• Maya Sabatello, Ph.D., LLB, (Co-chair)
• Wylie Burke, M.D., Ph.D.
• Ali Gharavi, M.D., (Co-chair)
• Nanibaa’ Garrison, Ph.D.
• Ingrid Holm, M.D., M.P.H. (PDF, 87.67 KB)
• Carol Horowitz, M.D., M.P.H.
• Nichole Jefferson
• Afshin Parsa, M.D., M.P.H.
• Glenda Roberts
• Robb Rowley, M.D.
• Clesson Turner, M.D.
  

Moderators

• Meg Hager, M.S., M.P.H., CGC (PDF, 105.42 KB)
• Hila Milo Rasouly, Ph.D., M.Sc., CGC (PDF, 86.34 KB)
• Matthew Sampson, M.D., M.S.
• Wendy Uhlmann, M.S., CGC

Study Presenters

• Barry Freedman, M.D., FACP
• Krzysztof Kiryluk, M.D.
• Opeyemi Olabisi, M.D., Ph.D.
• Ana Claudia Onuchic-Whitford, M.D.
• Craig Wong, M.D.
• Bessie Young, M.D., M.P.H.,FACP, FASN
  

Genetic Counselors Panel

• Emma Perez, M.S., CGC (PDF, 86.52 KB)
• Mary-Beth Roberts, M.S., CGC (PDF, 86.24 KB)
• Catherine Wicklund, M.S., CGC

Patient Presenters and Panelists

The following patients will present and/or participate in panels to share their stories and perspectives:

• Andrea Alvarez,
• John Brandon Bayton, Jr.
• Jennifer England
• Nichole Jefferson
• Jennifer Jones
• Sharon Lagas
• Denay Richards
• Curtis Warfield
• David White
• Trinisha Williams, M.P.H., LM