Organ transplant research: Do we need a central IRB?

Nationwide IRB may facilitate studies

A patient needing a transplant for a vital human organ often waits months or even years before one becomes available. Advocates for transplant research contend that someday, that wait could be shortened by new research into ways to better keep organs viable for transplant to improve their function.

But for that to happen, IRBs must allow research with organs currently being transplanted into patients, a practice that raises ethical and practical issues.

Eric Grossman, MD, FACP, medical director of the New York Organ Donor Network, New York City, spoke to an IRB conference earlier this year about his concerns that transplant research could be stymied by the process by which organs are distributed across the country and the necessity of obtaining individual IRB approval at those sites.

Grossman says there has been a great deal of research done on post-transplant interventions such as the use of immunosuppressive drugs by recipients. However, he says interventions that take place with the donor or with the pre-transplant organ pose unique problems.

A hypothetical example might involve a drug given to a patient after brain death has occurred to improve the donor's liver function. The patient's family gives permission for the administration of the drug and the donation of the liver.

"The drug is given and then the organ is allocated to a person after that point," Grossman says. "Often it takes hours to allocate an organ, because we have a list, and we have to communicate with each surgeon for each patient on that list.

"So now, you have a recipient, who has been waiting for an organ, maybe for months, maybe for years," he says. "And you're offering them an organ, but the organ has had an intervention. The question is: How is appropriate informed consent obtained?"

In some cases, the recipient must be told that his or her organ may have had the intervention or may have had a placebo instead.

A recipient in any state

Grossman notes that because of the way organs are distributed throughout networks, the organ could end up with a recipient in any state in the country.

"It is practically difficult to obtain IRB approval from every transplant center in every state in the U.S.," he says.

In the past, this type of research may have occurred without seeking such approvals. But in this era of IRB review, Grossman says he believes promising research is being hampered.

"I think what's happened, by and large, is that the research hasn't occurred," he says.

Grossman notes that nearly 100,000 people are currently on a waiting list for an organ transplant, while only 29,000 deceased-donor transplants were accomplished in 2006.

According to the United Network for Organ Sharing, about 17 people die each day waiting for a transplant of a vital organ, such as a liver, heart, lung, or kidney.

"And the type of research that we're talking about potentially could increase the number of donors by allowing them to survive long enough to the recovery procedure," Grossman says. "It could increase the number of organs that could result by interventions that improve organ function while they're still inside the donor or once they're removed from the donor.

"That's why it's really critical that we figure out how to make this research happen," he says.

During his presentation at Columbia University's annual IRB education conference, Grossman says participants discussed some possible solutions to the problem of obtaining IRB review of transplants throughout the country.

Most promising, he says, was the suggestion of a nationwide IRB devoted solely to transplant protocols. He acknowledges that the challenge would be gaining acceptance for such an over-arching IRB by all of the IRBs at the various transplant centers across the country.

Joel Frader, MD, a professor of medical humanities and bioethics at Northwestern University's Feinberg School of Medicine in Chicago, is a member of the Chicago Transplant Ethics Consortium.

He says there are existing models for centralized IRBs, including the National Cancer Institute's Centralized IRB program, which allows for facilitated review of multisite studies.

"IRBs can sign on to the process and say 'Yes, we'd like to participate.' They get a copy of the central IRB's review when the protocol is submitted to the local institution," Frader says. "One person at the local IRB is responsible for reviewing what the central IRB has done and saying, 'Yes, we accept this,' or 'No, it requires full IRB review.'"

He says many local transplant centers' IRBs probably would be comfortable with a central IRB associated with a well-known organization such as UNOS. But Frader worries that even a central IRB with impeccable credentials raises the potential for conflict of interest.

"Whether we're talking about the NCI or a hypothetical UNOS IRB, these obviously would be review boards that would have a stake in having this research conducted and whether they could over time retain objectivity is an open question," Frader says.

Putting protocols on-line

Grossman says another possibility to aid — and speed — informed consent in transplant research would be to make the various protocols available on-line to potential recipients on the waiting list, so that they have a chance to review them before faced with the life-or-death decision of accepting or rejecting an organ. Patients could be reminded by their physicians during medical visits to review the protocols.

"It would take a lot of commitment on the part of each transplant center," he says. "There are a lot of other things that need to occur at those (medical) visits and we would have to develop a real commitment on the part of the transplant centers to do that. It would require a real cultural change."

The actual decision of whether to accept an organ that has undergone an experimental intervention, Grossman says, isn't all that different from other decisions recipients often must make. Some recipients, for example, must decide whether to accept an organ from a donor who had a disease such as hepatitis B or hepatitis C, which could affect the function of that organ.

Grossman says that many organizations involved in improving organ transplants are anxious for a resolution that will better enable transplant research. He hopes that outreach efforts such as his will help push the issue into wider discussion and bring about a faster solution.

"I think given how many people's lives are held in the balance, how much money is spent in procuring organs and in transplanting organs, that we ought to make whatever additional investment it would take to solve this issue," he says. "The amount would be minuscule compared to the amount that's spent in this area.

"If leadership is shown, people will respond to that. I think people will be receptive if we lay out a road map."