Issues in Organ Donor Intervention Research: Introduction and Context

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1 Issues in Organ Donor Intervention Research: Introduction and Context Peter Abt, MD Associate Professor of Surgery University of Pennsylvania September 2016

2 Acknowledgements IOM Study Committee ASTS, AST, AOPO, ODRC, AASLD, TTS Arnold Foundation NIH, HRSA Gift of Life, New England Organ Bank, One Legacy

3 What is Donor Intervention Research? Intervention performed in the deceased prior to organ recovery Organ specific ex-vivo intervention is a subset of donor intervention research

4 What might be accomplished through deceased donor intervention research? Increase the quantity and quality of deceased donor organs available for transplantation.

5 The Rationale of Donor Intervention: Mitigate Organ Injury Secondary to Brain Death and Transplantation Brain death is physiologic, cellular, and molecular turmoil that compromises organ viability and function The injury sustained in the donor is compounded by ischemia / reperfusion injury in the recipient The injury is mitigated by the underlying health status of the donor

6 Donor Intervention Research is Unique Intervention in a deceased donor Outcome of a study could be in the donor or the organ recipient(s) Donors and recipients can be anywhere in the USA Constricted timeline Impact extends to multiple organ recipients through the donor s organs Wait list candidates Organ recipients Study organs and bystander organs Number and diversity of stake holders

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8 Timeline: First 3 years Initiative advanced by the Scientific Studies Committee Share and Revise Working Document AST, AOPO, SCCM, ASBH Form working group to write Working Document in conjunction with Ethics and Standards/Quality Committees AJT 2/13 7/10 7/11 7/12 Discussions with Key Stakeholders 1 st F2F Meeting ATC 2011 ASTS, AOPO, ODRC 2 nd F2F Meeting ATC 2012 ASTS, AST, AOPO, SCCM, ODRC, and HRSA ODTA ACOT 8/12

9 DMRCC Meeting Crystal City, VA Timeline: Last 2 years HRSA / ODTA EFFORTS DIREP Meeting Crystal City, VA DIREP Meeting Philadelphia, PA 9/13 11/14 5/15 4/14 Initial Contact 6/14 9/14 3/15 DRAFT Statement of Task IOM 7/15 Favorable Reception by Health Science Policy Board Funding secured: Laura and John Arnold Foundation Engaging the IOM

10 Why the IOM? Provide an independent authoritative level of scholarly review Negates conflict of interest Well respected by medical and lay community IOM studies often include recommendations/next steps IOM has a history of providing guidance and clarity to the development of organ donation and transplantation

11 Example of Donor Intervention Research Incidence of DGF in kidney Recipients Hypothermia =28% Normothermia = 39% OR = 0.62, P=0.02

12 Confusion and Misunderstanding: Oversight and Regulation Letter from Public Citizen to the Director of the Office of Human Research Protections. 1) The UCSF IRB determined incorrectly that the research represented nonhuman subjects 2) As a result the investigators failed to obtain informed consent of the subjects of the trial.

13 Research Ambiguity Survey of OPO directors, Transplant Surgeons, IRB members -Variety of research scenarios -Disagreement with regard to recipient consent and the necessity of IRB approval

14 Creating an Environment for Donor Intervention Research Oversight Ethics Regulatory Logistics Recipients DONOR

15 Specific Domains Deceased Donor (A. Glazier) Donor hospital Authorization for research Organ Transplant Recipient (K. Heffernan) Where does the research take place? Are all organ recipients human subjects? Optimal Oversight (S. Feng) Central oversight mechanism Comprehensive ethical, scientific merits, safety

16 Conclusions Donor intervention research has the potential to increase the quantity and quality of organs available for transplant from deceased donors. Nearly all trials (anything other than minimal risk) cannot be conducted due to ethical and regulatory ambiguity. We have an obligation to patients in need of a transplant to create mechanisms that allow the safe conduct of donor intervention research.