Cinnamon S. Bloss, Ph.D. Director of Social Sciences & Bioethics Scripps Translational Science Institute

@CinnamonBloss

Future of Genomic Medicine VI

What Data to Give Back & How

Learning from Idiopathic Disease Sequencing Case Studies

1. Who are the patients (and physicians)?

Unique, not representative of all who may benefit.

2. What are their attitudes and expectations? Expect access to data beyond the presenting condition.

3. How well do physicians return results? Physicians, as a group, may need help with this.

Main Points of Interest

Idiopathic Diseases of huMan

Study Criteria: 1.Condition serious and undiagnosed

2.Sequencing may be informative

3.Physician Champion to return results

Sequencing for Diagnosis & Treatment of Idiopathic Diseases

Clinician-Scientist Panel Review

Enrollment

Seq, Analysis & Report

Return 1° Results to Phy Champ

Screening

IDIOM Procedures

Psychosocial / Ethics

Psychosocial / Ethics

Phy Champ Returns to Patient

Fall 2011 7th Patient Enrolled N=5 Data Available

Neurology, Rheumatology, Internal Medicine, Allergy/Immunology, Cardiology, Medical Oncology/Hematology, Gastroenterology, Hepatology, Psychology,

Bioinformatics/Genetics, Medical/Bioethics, Nursing, IRB

IDIOM Scientist-Clinician Review Panel

Quarterly Evening Meetings

Domain Instrument

Patient Characteristics Quality of Life WHOQOL Grp (1998)

Genetic Knowledge Calsbeek et al. (2007)

Physician Characteristics Diffusion of Innovations Armstrong et al. (2003)

Attitudes Towards Sequencing

Whole Genome Sequencing Ques Ormond et al. (2012)

Secondary Findings Mayer et al. (2011)

Personal Involvement Inventory Zaichkowsky (1994)

Physician Communication Medical Communication

Competence Cegala et al. (1998)

Impact of Sequencing Decision Regret Scale

Brehaut et al. (2003)

Impact of Events Scale Horowitz et al. (1979)

Psychosocial / Ethics

Pre- and Post-Seq Structured Patient Interviews

IDIOM Referrals

N = 68

Ineligible Panel Reviewed p

N 47 21 (31%) -

Age (years) 47 26 <.001

Physician Referral 36% 71% .04

Top 3 Medical Specialties

Cardiology Internal Med Neurology

Allergy/Immun Oncology

Neurology .046

Panel Review

Enrolled 10% of Referred Cases

Enrolled Case Studies

Characteristics Cases 1 - 5

Age 14 - 35

Gender 80% Female

Ethnicity (self-report) 80% European

Quality of Life Z-scores

Physical -2.3 (severe imp)

Psychological 0.6 (average)

Environmental 1.8 (superior)

Genetics Knowledge 0.6 (high avg)

Patients

Physical vs. Environment, p=.02

Characteristics Cases 1 - 5

Graduation Year 1991 - 2007

Specialties

Neurology Hem/Oncology

Gastroenterology Allergy/Immunology

Time Caring for Patient 7 – 90 Months

Personal Innovativeness 12 (average)

Physicians

70% 60% 60%

90% 80% 80%

100% 100% 100%

Screen/ Treatment None

Childhood Onset

Adult Onset

Preferences for Secondary Findings

100%

60% 60%

Physicians

Patients

Parents

How would you grade your physician? Communication

Knowledge

Explanations

Solicits Ques

Spends Time

Repeats Info

Overall

A

B

B-

C

B

B-

-30

-20

-10

0

10

20

30

40

50

60

Patient-Physician Discrepancy

p=.04

Physician “Self-Grading”

Case 1 Case 2 Case 3 Case 4

Pre-seq Patient Grades Physician

Post-seq Patient Grades Physician

Post-seq Physician Grades Self

Medical Communication Competence Scale

B

B-

F

A

A+

-3

-2

-1

0

1

2

3

Return of Results Discrepancy

Strongly Agree

Agree

Slightly Agree

Neither

Slightly Disagree

Disagree

Strongly Disagree

Ensured patient

understood

Knowledge about

genetics

Knowledge about WGS

Reviewed or repeated important

information

Encouraged patient to

ask questions

Spent enough

time explaining

Adequately explained

WGS results overall

Explained what the results were

Mother

Father

Physician

Miscommunication = Mistakes, Misunderstandings & Frustration

Post-Sequencing "We took several hours post-[testing to discuss results] which is not feasible in general practice.” - Physician Case 1 "Make it faster so it's more relevant.” - Patient Case 2 "Do not depend on [a] child's doctor to…transfer such important information.” - Father Case 3

• Mild to no sequencing-related distress, little to no regret • 75% physicians & 50% patients suggest added clinician

Barriers

Cost Efficiency, Privacy Concerns / EMR, Turn-around Time, Few Genetic Counselors, Secondary Findings,

Return of Results, Physician Training

University/Medical School Year Program Description U of Rochester School of Medicine 1999 Double Helix Curriculum

U of Miami Miller School of Medicine 2005 Pathway in Human Genetics and Genomics

U of Pennsylvania School of Med 2008 Personalized Medicine Course

Johns Hopkins School of Medicine 2009 Genes to Society Curriculum

Tufts University 2009 Personal Genomics Course

Ohio State University 2010 P4 Scholar’s Program in Personalized Med

Stanford University 2010 Genomics and Personalized Medicine Course

Georgetown Univ School of Medicine 2010 Molecular and Human Genetics Module

SUNY Upstate Medical Univ 2010 Personalized Medicine Elective

Baylor College of Medicine 2011 Genetics Track Curriculum (undergrad)

New York University 2012 Practical Analysis of Your Personal Genome

Beth Israel Deaconess Medical Ctr 2012 Pathologist Genomics Training Program

U of Florida 2012 Genetics Training Program with Avatars

U of Miami Miller School of Medicine 2013 MD/MS in Genomic Medicine

U of Iowa 2013 Personal Genomics Honors Seminar

U of Illinois, U of Texas, & Duke Univ 2013 Personal Genetics Course (undergrad)

Genomic Medicine Education Initiatives

University/Medical School Year Program Description U of Rochester School of Medicine 1999 Double Helix Curriculum

U of Miami Miller School of Medicine 2005 Pathway in Human Genetics and Genomics

U of Pennsylvania School of Med 2008 Personalized Medicine Course

Johns Hopkins School of Medicine 2009 Genes to Society Curriculum

Tufts University 2009 Personal Genomics Course

Ohio State University 2010 P4 Scholar’s Program in Personalized Med

Stanford University 2010 Genomics and Personalized Medicine Course

Georgetown Univ School of Medicine 2010 Molecular and Human Genetics Module

SUNY Upstate Medical Univ 2010 Personalized Medicine Elective

Baylor College of Medicine 2011 Genetics Track Curriculum (undergrad)

New York University 2012 Practical Analysis of Your Personal Genome

Beth Israel Deaconess Medical Ctr 2012 Pathologist Genomics Training Program

U of Florida 2012 Genetics Training Program with Avatars

U of Miami Miller School of Medicine 2013 MD/MS in Genomic Medicine

U of Iowa 2013 Personal Genomics Honors Seminar

U of Illinois, U of Texas, & Duke Univ 2013 Personal Genetics Course (undergrad)

Genomic Medicine Education Initiatives

16 Initiatives

but…

141 AAMC Accredited Schools

Exomes for Primary Care Physicians

56 Physicians / 78% Family Medicine / Median Year Graduation 1995

Observations

1. Physicians, as a group, may need help with genetics (and in some cases might not know it)

2. Patients, families & physicians, would often choose to receive some secondary findings

3. Patients in early studies do not represent all who may benefit – need to ensure access

Main Points Revisited

Ali Torkamani, PhD Nicholas Schork, PhD Eric Topol, MD

Funders NIH/NCRR flagship CTSA grant (Eric Topol, MD) Scripps Genomic Medicine Division of Scripps Health Schaeffer Family Foundation / Warren Foundation / Zarrow Foundation

Acknowledgements Sarah Topol, RN, BSN Burcu Darst Sharon Haaser, RN Philip Pham Bill Shipman, MS Galina Erikson, MS

Andrew Carson, PhD Guangfa Zhang, PhD Philip Pham Erick Scott, MD Glenn Oliveira Lauren Ariniello Janel Lee Nikki Villarasa Sam Levy, PhD Ashley Van Zeeland, PhD Mike Alcorn, MBA

IDIOM Families & Physicians With Special Thanks to “IDIOM #1” Lilly, Gay and Steve Grossman Jennifer Friedman, M.D.

Clinician Review Panel Members Ron Simon, MD, Brad Patay, MD, Kelly Bethel, MD, Paul Pockros, MD, Gary Williams, MD, James Mason, MD, Christy Jackson, MD, Michael Kayser, MD, Raj Belani, MD, Joel Diamant, MD, Nelson Hwynn, MD, Erick Scott, MD

Scripps IRB Barbara Bigby, MA, CIP

Reproduced with permission