This document discusses developing an ethical framework for communicating information about an ocular gene transfer clinical trial for choroideremia to patients and families. It summarizes perspectives from patients, clinicians, and advocates about risks, benefits, and timelines for treatment. It also analyzes media coverage of gene therapy and finds that most articles do not mention risks and conflate research with treatment. The document recommends avoiding therapeutic misconceptions, managing expectations rather than messaging, and positioning timelines in the context of clinical trial phases to ensure responsible communication with vulnerable patients.

1. Ocular gene transfer:
Developing an ethical framework to
communicate clinical trial information to
patients and families
Ian MacDonald
Mar. 6, 2015

2. Outline
• A culture of media hype around gene
“therapy”
• Stakeholder and patient perspectives
• Media communications
• Recommendations

3. Gene Transfer
“…attempts to treat genetic disease at the
molecular level by correcting what is
wrong with the defective gene”
–NIH

4. Research Question
How can stakeholders in a novel ocular gene
transfer, clinical trial, ethically communicate
the risks and benefits associated with the
research in light of a perceived ‘cure’, while
avoiding the hype that has been linked to this
field of translational medicine?

5. Choroideremia (CHM)
Men:
Field loss in linear fashion after age 20
Central loss rapid after age 40-50

6. Methods- Perspectives
• 20 patients with choroideremia
• 15 clinicians
• 6 patient advocates
• Semi-structured interviews about expected
therapeutic benefits, perceived risks, and
timeline of hopes for clinical implementation

7. Visual Outcome Perspectives
CurePartial
reversal of
lost vision
Slowing
down vision
loss
Halting
vision loss
Least
Therapeutic
Most
Therapeutic
Patient perspectivesClinician perspectives
No visual
benefit
Patient advocate perspectives

8. Patient - Benefits
• Description of aspirational and collateral benefits
• Direct benefit most prominent
“If there was a therapy…that would be a dream come
true, that would be unbelievable, having full sight now,
not having to worry about being blind in the future,
being able to see at night which to me would be almost
like a superpower because I have never seen at night
before. I would feel like an X-man if I could see at
night”
–Patient

9. Patient - Risks
• Patient “no risk”
perspectives
• Trust in researchers/
science
• Main concern: access

10. Patient - Urgency
“The treatment is not available fast
enough…There’s a real sense of urgency…I
know everybody wants to…do it…in a careful
way and not hurt anybody or make them
unhealthy in some way; but for me, I’d rather
take the chance and save my eyes.”
- Patient

11. Time Frames
• Patients and patient
advocates were
confused and frustrated
• Some clinicians refused
to provide estimates
• Clinician estimates
ranged between 3-10
years

12. Methods- Media
Newspaper articles about ocular gene transfer:
– 26 Canadian , 55 American , and 77 British
20 CHM patients
• Semi-structured interviews about:
1. Perspectives on general gene transfer media
2. Responses to YouTube clip about Leber
congenital amaurosis trial

13. Tone
0
20
40
60
80
100
120
140
Positive Neutal Negative
Frequency
Tone
Tone of ocular gene transfer newspaper coverage in Canada,
United Kingdom and United States

14. Risk and Benefit Representations
• 57% of all articles didn’t mention risks
• Benefits were widely discussed
• Most common benefit= direct visual benefit,
discussed in:
– 100% of Canadian
– 91% of UK
– 87% of US

15. Visual Benefit Representations
0
20
40
60
80
100
120
140
Slow vision loss Halt vision loss Improve vision Cure
Frequency
Visual outcome representation
Ocular gene transfer visual outcome representations in
Canadian, British, and American newspapers
United States
United Kingdom
Canada

16. Research/Treatment Conflation
“To hear such quick progress in a gene
therapy treatment is fantastic. We hope
this success will lead to more funding of
gene therapy research into conditions
that currently have no cure or
treatment.”
Sample, I. (May 2, 2007). Gene therapy aimed at restoring
sight for 30,000 people, The Guardian.

17. Patient Perspectives- LCA trial
“I could empathize with [Corey’s] mother and
her tears when she recalled the diagnosis, and
[it] reminded me of my tears when I got told I
shouldn’t drive anymore, reminds me of my
mother’s tears when she thinks about her role
in passing the gene onto us.”
—Patient 16
Humanintereststories

18. Patient Perspectives- LCA trial
“It gives hope where there was none…because before the last
10 years, the prognosis was - there’s no treatment. So it’s
certainly hopeful and encouraging to see the doctors coming
this far and with trials just around the corner, and knowing
that Leber trials went well and proved safe.”
—Patient 3
“[Media coverage made me feel] hopeful, but at this stage of
life, I’m hopeful and I try not to get myself too excited because
I’ve been let down before. I want to be hopeful, but I don’t
want to be hopeful because I don’t want to get too excited
and be disappointed again.”
—Patient 17
VulnerabilityHope

19. Patient Perspectives- LCA
“After seeing pieces like that [LCA video]…it
gave me a realization…of…the power of gene
therapy. And pieces like that…remind you that
this is real science and people are doing real
things with it…and if the opportunity arises,
think about getting involved [in a gene
transfer clinical trial].”
—Patient 19
Access

20. Patient Perspectives- LCA
When asked how the video makes them feel
about participating in a gene transfer clinical
trial, patients responded:
“I’ll do it tomorrow.” —Patient 2
“I want to find out where to sign up.” —Patient 11
Access

21. Research NOT Treatment
Therapeutic misconception
• Hope for direct benefit present among all
stakeholders
• Media described therapeutic benefit in most
articles
• Media shifted between research and
treatment terminology

23. Treatment NOT Cure

24. Time Frames
• Media, clinicians, and patient advocates
provide vague time frame estimates
• Generally: 10-14 years from phase I to market
approval of drugs
• Positioning in context of closest analog
– LCA:
• Phase I/II studies initiated in 2007
• 2013 phase III underway

25. Respecting Patient Critical Thinking Skills
• Patients are vulnerable to promotional
communications
• Important to tailor communications in light of
patient vulnerability
• Recognizing critical thinking capacity and
expertise of patients
• Managing messaging, not patient
expectations!

26. Conclusion
• Choroideremia patients are exposed to
promotional communications about gene transfer
• Onus on clinical investigators, clinicians, and
patient advocates to ensure responsible
messaging
– Avoid: therapeutic misconception
– Avoid: therapeutic misestimation
– Position time frames in context of clinical trial phases

27. Creating perspective

28. Health Canada
approval
Clinical Trial
Application
Funding
•FFB
•CRFC
•CIHR
•Alberta Innovates
Lab/office prep
• Database setup
• Equipment
• Personnel
• Record keeping
system
Protocol
UA
Sponsorship
Detailed
Protocol
AHS operational
approval
Preclinical
and clinical
data
Phase 1 Trial begins
GMP facility
• Purchase agreement
• Vector development
records
• Site visit
Pre-Trial Activity
HREB
approval
Audits

29. www.chmgenetherapy.ca
• Communication
• Timeline estimates
• Education
• Encourage realistic
expectations

30. Acknowledgements
• Research participants
• Shelly Benjaminy
Queen Elisabeth II Graduate Scholarship