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Clinical trials with stem cells

Bernard Lo, M.D.

February 12, 2009

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Questions for class

Anyone know someone with Type I

diabetes?

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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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Induced pluripotent stem cells (iPS 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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Particular barriers to consent

Strong scientific plausibility

Hope, expectations

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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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Questions

2. What are risks of stem cell

transplantation?

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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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Questions

3. How should the consent process be

improved?

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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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Questions

5. Who should be enrolled in Phase 1

trial? Children? Adults?

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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

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