1. Phase O Trials: Ethical Considerations Holly Taylor, PhD, MPH Department of Health Policy and Management Bloomberg School of Public Health Berman Institute of Bioethics Johns Hopkins University

2. Summary Subject Understanding –Respect for Persons –Empirical Evidence from Phase I Patient Subject Physician Investigator –Moving Forward Voluntariness Disclosure Understanding

3. Subject Understanding Respect for Persons –Informed Consent Elements of Consent –Threshold Competence Voluntariness –Informational Disclosure Understanding –Consent Decision Source: Beauchamp & Childress (2001)

4. Subject Understanding Empirical Evidence from Phase I –Patient subject Majority believe they understand trial but majority unable to correctly state purpose and other details Majority enroll with hope for direct medical benefit Low refusal rates –Physician Investigator Overstate likelihood of benefit Role of language in presentation of options

5. Subject Understanding Empirical Evidence from Phase I –Dynamic Advice of and trust in physician motivating factors for patient subject enrollment

6. Subject Understanding Moving Forward –Voluntariness Appreciate the ‘vulnerability’ of patients who are at end of life and exhausted all treatment options.

7. Subject Understanding Moving Forward –Disclosure No potential for direct medical benefit Physical risks – related to intervention – serial biopsies Benefits to future patients only Potential effect on quality of life Alternatives – Phase I or II trials – Palliative care

8. Subject Understanding Moving Forward –Understanding Implementation of best practices regarding consent process Assessment of patient understanding before and after participation

9. Subject Understanding Moving Forward –Commitment to evidence-based research practice –Apply knowledge to other phases of drug development

10. Individual Risk Benefit Society IRB Risk Assessment: Do the Benefits Outweigh the Risks? Individual

11. Intervention- related Risk Benefit Society IRB Risk Assessment: Do the Benefits Outweigh the Risks? Intervention- related

12. Individual Risk Benefit Society IRB Risk Assessment: Do the Benefits Outweigh the Risks? Individual

13. Summary Subject Understanding –Respect for Persons –Empirical Evidence from Phase I Patient Subject Physician Investigator –Moving Forward Voluntariness Disclosure Understanding