Challenges to Research and Innovation to Optimize Deceased Donor Organ Quality and Quantity
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Transcript of Challenges to Research and Innovation to Optimize Deceased Donor Organ Quality and Quantity
Challenges to Research and Innovation to Optimize Deceased Donor Organ Quality and Quantity
Peter Abt, MDSandy Feng, MD PhDAmerican Society of Transplant Surgeons
August 28, 2012
Organ Quantity Limits Transplant Opportunities
Primary limitation to transplantation
•Motivates living donor transplantation
Engenders waitlist morbidity and
mortality
Organ Quality Limits Transplant Outcomes
Decrease in ideal donors; increase in
marginal or expanded criteria donors
•Donor quality defined by post-transplant
outcomes according to risk of graft loss
(patient death or need for retransplantation)
Inferior organ quality engenders recipient
morbidity and mortality
The Need for Innovation and Research in Donor Intervention and Treatment
To increase the number of organs available for transplantation
•Mitigate waitlist morbidity and mortality
To improve the quality of organs used for transplantation
•Mitigate recipient morbidity and mortality
Donor
RecipientsThe Long Pathway for Donor-based Research
Authorization/Consent
IRB Approval
Donor hospital“approval”
Protocol dissemination
Waitlist candidate / recipient consent
Impact on allocation and distribution
Recipient and transplant center outcomes
Dissemination of study outcomes
Safety and efficacy analyses
Impact on donation
Obstacles to Research and Innovation in Deceased (Brain Dead) Donors
Scientific
Ethical
Logistical
Regulatory
Investigator
Donor / Donor hospitals
OPOs
Waitlist candidates
Transplant recipients / centers
ProblemCurrent ethical, logistical, and regulatory
infrastructure is inadequate to support effective donor intervention and treatment studies.
The magnitude and complexity of the challenges require guidelines
to facilitate the optimal design and safe execution of
clinical trials in deceased donors.
7/10 7/11 7/12
Initiative advanced by the Scientific Studies
Committee
Form working group to write Working Document
in conjunction with Ethics and Standards/Quality Committees
1st F2F Meeting ATC 2011
ASTS, AOPO, ODRC
Share and Revise Working Document
AST, AOPO, SCCM, ASBH
2nd F2F Meeting ATC 2012
ASTS, AST, AOPO, SCCM, ODRC, and ODTA
Discussions with Key Stakeholders
Timeline of ASTS Efforts
The Legal Basis for Research Authorization in Deceased (Brain Dead) Donors
Organ donation and associated research is based on gift law
•Donation is viewed as gifting, not as an informed decision regarding healthcare by the deceased or his / her next of kin
Specific Circumstances that Require Full Informed Consent
Genetic studies that risk
• Identification of the donor or
•Bears implications for the donor family
Precedent established by the National Disease Research Interchange
•Detailed informed consent related to genomics testing
Does Authorization Achieve Maximal Transparency?
Public perception of donation •The importance of trust in the process
•Lack of awareness that donation may be associated with research
•Potential risk for research to alter the intention of the gift• Varies with specific risk posed by each
specific study
Donor Hospitals
All hospitals are potential donor hospitals
•There may, however, be as few as a single donor participating in any particular donor study
Donor hospitals have a vested interest in the appropriate assessment and conduct of research in deceased donors
•Public relations and perception
• Financial
Regulatory and Logistical Challenges Posed by Donor Hospitals
Most lack a policy for assessing clinical trial protocols in deceased donors
•Precedent of hospital DCD policy
If an investigator must approach each hospital on an individual basis – the current approach – donor-based research would be unfeasible
Regulatory Vacuum Related to Research in Deceased (Brain Dead) Donors
Federal regulations governing research in human subjects do not apply
The role of the institutional review board, if any, in the evaluation of donor intervention / treatment trials is unclear.
• Investigator
• OPO
• Donor hospital
Potential Impact of Donor-based Research on Waitlist Candidates
Organ offers are made to waitlist candidates through their transplant physicians
Transplant physicians, in conjunction with candidates, must decide whether to accept or decline any / all organ offers
The exposure of an organ to an investigational intervention or treatment may impact the decision regarding acceptance or declination
The refusal of an organ secondary to concerns regarding donor research may lead to waitlist morbidity and / or mortality
Issues Related to Informed Consent in the Recipient
Receiving an organ that has been involved in a donor-based research protocol does NOT obligate the recipient to participate in the research
Donor-based research questions the necessity of recipient consent under specific circumstances
• Research with endpoints that relate solely to data derived from the deceased donor
• Research limited to the use of data submitted to the United Network for Organ Sharing and obtained without identifiers
Issues Related to Recipient Informed Consent
The necessity for informed consent depends on whether a person is a research subject
•Will there be interaction between the investigator and the organ recipient related to an investigational treatment?
•Will identifiable data be collected and/or analyzed for research purposes?
What might be the implications for donor intervention / treatment trials if organ recipients frequently decline consent to participate in research?
Logistical Challenges Related to Informed Consent for the Transplant Physician and Transplant Center
Transplant physicians will need to participate in and take responsibility for obtaining informed consent from the recipient for research participation• Imposes an additional burden
The research protocol must be approved by the transplant center IRB•Need for “IRB exemption” if center is not
participating in the specific trial
The Need for Communication Mechanisms
A single repository that provides standardized information
related to all donor-based studies (www.clinicaltrials.gov)
A mechanism to expeditiously distribute detailed
information about study interventions / treatments to the
physicians of all candidates offered an organ from a donor
that has participated in an intervention or treatment trial
• Essential for final decision regarding organ acceptance
• Essential to support informed consent discussion with the
recipient regarding research participation
A mechanism to optimally and safely provide data regarding
the recipient and/or transplant outcomes to the investigator
Impact on Organ Donation
Donor-based intervention and/or treatment trials may impact organ donation
•Negative impact if public perception views research as compromising the intent of the donor/donor family to bestow a gift through transplantation
Impact on Organ Allocation and Distribution
Declining to consider or accept organ offers secondary to donor-based research would alter organ allocation or distribution, respectively
The impact on individual and overall waitlist morbidity and mortality for all exposed organs must be assessed
Impact on Transplant Outcomes for All Exposed Organs
Donor intervention and treatment trials will likely be designed with a focus on collecting and analyzing data related to the outcome of a single organ
•However, multiple organs will likely have been exposed in the donor
The impact on the transplant outcomes of all exposed organs should be examined
Impact on Recipient-based Studies
Participation in a donor-based trial may exclude recipients of exposed organs from participation in other trials designed for transplant recipients
Transplant physicians and programs may harbor concerns about the imposition of these restrictions
Impact on Transplant Center Outcome Metrics
Donor intervention and treatment trials can impact statistics related to waitlist and transplant outcomes for transplant centers• Performance metrics for OPOs and transplant
centers are currently misaligned
These publicly available statistics, in turn, may risk a center’s reputation, accreditation, insurance contracting position, transplant volume, and revenue
What does the Organ Donation and Transplant Recipient Community Need?
The ASTS requests that ACOT recommend to the Secretary that HRSA leadership work with the donation and transplantation community to provide recommendations that address the complex and multi-disciplinary challenges that obstruct the safe and optimal design and execution of innovative clinical trials in deceased brain dead organ donors.