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