Settlement reached in Gelsinger death 

More IRB oversight mandated

The 1999 research-related death of Jesse Gelsinger achieved one more step toward resolution with the announcement of a settlement between the federal government and researchers and research institutions involved in the case.

U.S. Attorney Patrick Meehan announced the settlement in February. As part of the agreement, two institutions — the University of Pennsylvania and Children’s National Medical Center in Washington, DC — will pay $517,496 and $514,622, respectively, to resolve the government’s allegations. The institutions also agreed to changes in the conduct of their human subjects protection programs.

The three researchers named in the case — James Wilson, MD, PhD; Mark Batshaw, MD; and Steven Raper, MD — will have restrictions placed on their clinical research for several years.

"Perhaps most significant is the impact that these settlements will have on the way clinical research on human participants is conducted throughout the country," Meehan says. "This action covers two major research centers which have instituted important changes in the conduct and monitoring of clinical research on human participants.

"We hope that these settlements will now serve as a model for similar research nationwide."

Gelsinger, 18, was a volunteer in a Phase I safety study examining an investigational drug to be used to treat a deficiency in an enzyme, ornithine transcarbamylase (OTC). Patients with OTC deficiency cannot properly convert nitrogen in the body to urea for excretion as urine. Although severe OTC deficiencies can cause death, Gelsinger had a less severe form of the disorder, which was controlled by medication.

In the study, participants were injected with a genetically engineered adenovirus, which would deliver the OTC gene to the patient’s liver to produce the missing enzyme.

Gelsinger had a reaction to the treatment and died four days later from multiple organ failure.

The government has alleged that the study should have been terminated before Gelsinger’s involvement because of previous problems. The government further alleged that false statements and claims about the study were submitted to the NIH and the FDA.

Both the researchers and hospitals involved deny the allegations and contend that their conduct was lawful and appropriate.

Terms of the settlement require that the University of Pennsylvania increase IRB oversight of clinical research; conduct mandatory training for investigators and staff that includes good clinical practices, informed consent and conflicts of interest; use an independent contract research organization to monitor and oversee research; and create an Office of Human Research to focus on participant safety.

Officials at the University declined to be interviewed, but issued a statement saying that in the past five years, "Penn has established what is now a national model for the conduct of research, including the mandatory training of investigators and staff coupled with a comprehensive internal monitoring program for research involving volunteers."

As part of the settlement, Children’s National Medical Center agreed to increase IRB staff from two to five; increase the IRB’s budget by 50% between 2001 and 2004; add a position of RN quality improvement coordinator; and add a research subject advocate, a bilingual pediatrician/ethicist who would review all pediatric clinical research center protocols and consent forms prior to IRB submission. The advocate also would seek feedback from families and participants regarding recruitment and informed consent.

In its statement, Children’s National defended the hospital and Batshaw, its chief academic officer.

"Despite his complete cooperation with the investigation, and acknowledgement of opportunities for improvement, Dr. Batshaw and CNMC, as participants in the aforementioned studies, deny that the they engaged in any unlawful activity and to the contrary, contend that their conduct was at all times in good faith, appropriate, and in the best interest of the study participants."

Paul Gelsinger, Jesse’s father, says while the settlement addresses the role the institutions and their IRBs played in the study that resulted in his son’s death, it does little to ensure that a similar accident won’t occur at another institution. He did not support the settlement, because it did not require an acknowledgement of wrongdoing or an apology from the institutions or researchers involved.

"While I commend [the institutions] for the improvements that they have made, those improvements should have occurred long ago," Gelsinger says.

He says he would like to see changes outlined in the Institute of Medicine’s book, "Responsible Research," applied to the oversight of clinical research, in particular recommendations to address conflicts of interest.

"It will take legislation with severe financial and criminal repercussions to actually get all of research to pay attention and upgrade their oversight systems," Gelsinger says.

The lesson he believes IRBs should take from the entire matter: "Question the ethics of everything being done. Dig deeply into financial and professional conflicts of interest, no matter the importance of the person conducting the research or the potential benefit to the patient population, knowing that you and the researchers and your institutions will someday be held accountable for the way that the research is conducted."