Feds Fault Harvard Research Practices

Fifteen studies run by Harvard researchers in rural China failed to inform subjects about risks they took by participating in the research, a federal investigation concluded last week.

The investigation found no evidence that subjects were physically harmed by defects in the studies, which were conducted beginning in the late 1990s and most of which sought genetic and environmental causes for ailments ranging from obesity to schizophrenia.

But the government cited numerous failings by the researchers to disclose key information about their studies to participants.

When one researcher signed up participants for several studies, he did not make it clear to prospective subjects that the studies were voluntary and that they could drop out at any time, according to the federal Office of Human Research Protection (OHRP).

The agency also faulted an internal review board at the Harvard School of Public Health (HSPH) for sloppy oversight that “regularly failed to be substantive and meaningful.”

Additionally, the government criticized two Harvard-affiliated hospitals, the Massachusetts Mental Health Center and Brigham and Women’s Hospital, for inadequate review procedures.

Harvard officials have acknowledged their failure to adequately monitor research carried out in China. They have been working for several years with the OHRP to fix the problems, the officials said.

“There were deficiencies in our procedure and in our oversight, absolutely,” said HSPH spokesperson Robin Herman. “We fully agree with the thrust of the OHRP report.” Eleven of the studies were conducted by one researcher—Associate Professor of Medicine Xiping Xu—whose research in China was suspended by HSPH pending an outside audit commissioned by the school’s administrators.

Some consent forms that Xu used in his studies contained “complex language” that was likely difficult for rural Chinese subjects to understand, the federal report said.

The forms also omitted key information—they failed to describe experimental procedures and identify “risks and discomforts” subjects might be exposed to. And in one case, Xu did not give consent forms to some participants until after the study had already begun.

The federal investigation also cited Xu on a number of instances for beginning or changing studies prior to receiving approval from the HSPH’s Institutional Review Board (IRB).

The federal report made similar criticisms of two other studies directed by Professor of Medicine David C. Christiani, who has already completed the studies, and two run by Cobb Professor of Psychiatry Ming T. Tsuang.

In the wake of the report, HSPH has revamped its procedures for overseeing studies by increasing IRB staffing and creating a monitoring program specifically to oversee consent procedures.

And because of their violations, HSPH will subject any future research by Xu and Christiani to more frequent and stringent review than other researchers at the school.

Xu’s research was primarily sponsored by the National Institutes of Health, as well as Cambridge-based Millennium Pharmaceuticals company and Harvard.

Until current questions are resolved, Xu will not be allowed to submit new research grant applications.

The researchers have offered few public comments in response to the federal complaints.

Christiani wrote in an e-mail that his “commitment to global public health remains as strong as ever, and my research projects will continue to reflect that commitment.”

He declined further comment.

Xu also declined to comment beyond a statement, in which he thanked the OHRP for its “time, effort and thoroughness in its review.”

In addition to the individual researchers, the federal report also criticized the HSPH review board.

The IRB approved studies despite “grave doubts” about whether the research results would be kept confidential. It also “failed to adequately consider whether or not subjects would benefit from this research.”

OHRP began its investigation of the China studies in response to a complaint filed in 1999 by Gwendolyn Zahner, a former assistant professor at HSPH. These questionable research practices were later the subject of a series of investigative articles by the Washington Post.

HSPH’s leader noted the investigation taught the school a valuable lesson.

“International research is of utmost value in promoting human health, but research on human subjects, when carried out in different cultural contexts, introduces great complexity,” said HSPH Dean Barry R. Bloom in a statement.

“We are mindful of how fragile the public trust has become in research involving human subjects, and with this in-depth re-examination and changes in our procedures, we are striving to achieve the highest possible standards to maintain that trust,” he added.