U.S. Bioethics Panel to Review Clinical Trials Around the World

Prompted by concerns about an unethical U.S.-sponsored study in the 1940s, bioethics advisers to President Barack Obama formed an international panel today that will examine whether current rules adequately protect volunteers in global clinical trials.

A historian at Wellesley College shocked the nation last October with the revelation that, from 1946 to 1948, a U.S. Public Health Service researcher deliberately exposed Guatemalan prisoners, soldiers, and others to syphilis and gonorrhea. The experiments drew comparisons with Tuskegee, the notorious 40-year study in Alabama begun in 1932 in which U.S. researchers allowed hundreds of African-American men with syphilis to go untreated.

In response, President Obama asked his Presidential Commission for the Study of Bioethical Issues to examine whether "current rules for research participants protect people from harm or unethical treatment, domestically as well as internationally." Obama also asked the Institute of Medicine (IOM) to investigate the Guatemala study. But that fact-finding job also fell to the bioethics commission after IOM realized that five of its members had been involved in the study. The commission is chaired by University of Pennsylvania President Amy Gutmann and vice-chaired by Emory University President James Wagner.

Today, Gutmann announced the members of a panel that will look at the "adequacy" of standards "across the field of international research today," she said. The members include four experts from the bioethics commission and 10 others from 10 countries, from Belgium to Uganda to India. The panel will meet three times before reporting to the commission in August. Gutmann's panel will also receive advice from the vice president of Guatemala, José Rafeal Espada, a former cardiothoracic surgeon.

A team of 12 commission staffers and several academic consultants has already begun digging through 477 boxes of documents on the Guatemala studies. They want to answer such "fundamental questions" as who knew about the studies, when they knew it, and what they did about it, said commission Executive Director Valerie Bonham. Her staff members plan to finish its report by summer.

At today's meeting, the commission also heard from various experts on the landscape of international trials. Duke University clinical researcher Robert Califf described a sharp increase in the number of trials in the past decade as companies seek to cut costs and avoid the inefficiencies of U.S.-based trials. He identified payments to patients that far exceed local norms as the most common ethical problem.

University of Washington HIV researcher Lawrence Corey, who heads the U.S.-funded HIV Vaccine Trials Network, described his team's efforts to partner with local researchers so that the community benefits from findings, for example, on male circumcision to reduce HIV transmission.

University of Wisconsin, Madison, historian Susan Lederer briefly reviewed the ethics of medical research in the early and mid-20th century. She said control groups were a novel idea when a team of U.S. syphilogists planned experiments like those in Guatemala and Tuskegee, and researchers didn't always use written protocols. The Guatemala case "is unlikely to be the only such study out there lurking in the archives," Lederer said. (More unethical studies were revealed by the Associated Press yesterday.)

Still, ethicist Dan Brock of Harvard Medical School in Boston said it is "pretty unlikely" that the Guatemala study could happen now. "Everyone now agrees" on what was wrong, he added, suggesting that "doesn't provide much new work for the commission." But Indiana University, Indianapolis, ethicist Eric Meslin disagreed. "It could happen today," even in the United States, he said, because the so-called common rule for protecting U.S. human subjects, doesn't apply to research not funded by the government or submitted to the U.S. Food and Drug Administration.

Guttmann says there is plenty for the commission to do because of the rise in trials and because the common rule hasn't been revised "for decades." The Guatemala studies are "a reminder of historical injustices," she told ScienceInsider. "We have to ask ourselves, as a commission, are there practices that will strike people looking back at today as [being as] unethical as the practices we're looking back on in Guatemala?"

The international panel's charge is to look at only research funded by the U.S. government. But Gutmann says, "We are free to move beyond that" to trials run by drug companies. The bioethics commission will report to the president by the end of this year, Gutmann says.

Yesterday, the commission began discussing the ethics of genetics and neuroimaging, including whether to tell study volunteers about unexpected findings that aren't directly related to the research. The panel "will refine the topic" before its next meeting in May, Gutmann says.