Post on 13-Dec-2015
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Goal of session
Design a clinical trial of stem cell
transplantation for Type I diabetes that
addresses ethical concerns
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Rationale for stem cell transplantation
Type I diabetes caused by autoimmune
destruction of beta cells, loss of insulin
Long term complications of Type I
diabetes despite insulin therapy
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Rationale for stem cell transplantation
Shortage of donors for Islet cell
transplantation
Transplant beta cells Derived from stem cells Direct reprogramming of pancreatic
exocrine cells
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Ethical issues in any clinical trial
1. Risk / benefit balance Outcomes are uncertain Participants at risk, but not designed to
benefit them IRB must approve
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Particular concerns about risk
Pluripotent Differentiate into unintended cells Integrate into unintended targets
In vitro manipulation Reprogramming may go awry
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Particular concerns about risk
Limited experience in humans Unexpected adverse events
Long-term adverse effects in chronic
illness
Hard to discontinue intervention
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Ethical issues in any clinical trial
2. Informed consent “Therapeutic misconception” IRB tend to require longer consent forms
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Question
1. Why not let everyone who wants a
stem cell transplant get it?• Available in some countries
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hESC transplants readily available
No information on materials, protocols
No follow-up
No control group
Conflict of interest
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Risks
Might not improve clinical condition Not produce insulin Production without regulation Recurrence of autoimmune destruction
Adverse events Tumors, cancer
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Improving the consent process
Assess comprehension of key features
of trial
Clinical Trials 2008; 5: 517-522
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Key features of RCT
Different than clinical care
Not sure that intervention effective or
safe
May have serious side effects May be unexpected May not be able to reverse the intervention
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Selection of participants
Children May be more effective early in disease Most to lose if severe adverse events Cannot give informed consent to accept risk
Adults
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Questions
6. Who should be enrolled in pivotal
Phase 3 trial? Children? Adults? Someone who gave research funding?
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Questions
7. What should be design of Phase 2-3?• Sham transplant?• Background care in both arms?
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Questions
8. What should be duration of pivotal
Phase 3 trial?
9. At close of trial should control arm be
offered transplantation?
10.How assess very long-term benefits
and risks?
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Recommendations for clinical trials
3.Disseminate results even if negative• Limits of clinical trials databases
Clinical Trials 2008; 5: 517-522
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Take home message
Give trial a catchy NAME
Ethical issues are inherent in clinical
trials
Investigators, referring clinicians,
reviewers, readers need to be aware of
ethical issues and how to resolve them