Human-research oversight is too lax

Lexington, VA Monday, September 21, 2009

This commentary appeared originally in the Arizona Daily Star on Sept. 21, 2009

Ten years ago last week, Tucsonan Jesse Gelsinger died at age 18, the victim of a medical experiment gone awry. Sadly, Gelsinger's death was the predictable result of an anemic, laissez-fare system of oversight the same one we have today.

The progress of science is important. But the lives of individual participants in scientific experiments are just as important. A single human being cannot be sacrificed to advance the interests of science.

The point of the experiment on Gelsinger was simple: Could a modified virus safely transport genes for an enzyme he lacked? After Gelsinger's death, regulators uncovered troubling decisions. Researchers never disclosed to Gelsinger that monkeys died in prior trials.

Researcher James Wilson owned nearly a third of the biotech company, Genovo, sponsoring Gelsinger's trial, while the University of Pennsylvania owned 5 percent shares valued at millions of dollars.

The researchers eventually took a drubbing. The Senate and the U.S. Food and Drug Administration held hearings on mistakes in the experiment. The Gelsingers sued and settled for an undisclosed sum. The federal government subjected Wilson and co-researchers Mark Batshaw and Steve Raper to years of monitoring.

But much remains unknown about what went wrong.

I asked Gelsinger's father, Paul, for documents collected in his lawsuit. Those documents are included in my new book, "Health Law and Bioethics: Cases in Context," and show that Wilson's financial conflict posed real risks for patients but could have been avoided.

Penn asked its conflict-of-interest committee to review Wilson's arrangement. The committee in months of deliberations raised concerns about Wilson's hefty financial stake. They asked what would happen if a patient died and worried whether Wilson might move too fast. The committee chair suggested that a company controlling Genovo could fund Wilson's research, rather than Wilson's company, eliminating the financial conflict.

Committee minutes indicated that "unusual circumstances" would make Wilson's deal OK a conclusion vigorously disputed by member Louis Girifalco, who later resigned over the "error." Despite strong signals that something was amiss, Penn approved Wilson's deal.

In retrospect, the committee's concerns were prescient. Wilson admits to participating in "team meetings" during Gelsinger's trial. Does Wilson's financial interest explain lapses like the misleading disclosures to Gelsinger about risks?

The form Gelsinger signed said: "We have also tested the safety of this virus in monkeys and have not found toxicity at the doses being used in this study."

This form didn't lie, it just cleverly side-stepped the full truth. An earlier form baldly stated: "In mice and monkeys, high doses of the virus have been associated with evidence of liver inflammation (hepatitis), hepatic necrosis and death."

After Gelsinger's death, oversight authorities inside Penn and the FDA could not explain how disclosures they approved about monkey deaths were subsequently dropped.

Not much has changed in the intervening decade. Disclosure continues to be policed primarily by institutions. Financial conflicts of interest still pervade research.

Oversight of human research rests on little more than trust. We trust that researchers will not consciously or unconsciously act in their own self-interests. We trust that material information about risks will be disclosed. We trust that researchers won't gamble with patients' lives.

When are we going to realize that patient safety is too important to leave to an unchecked honor system?

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