Researchers planning to set up clinical trials, test new drugs, or develop gene therapy protocols will now have to abide by new federal guidelines concerning human subjects research or face the possibility of stiff financial penalties, according to an announcement made 23 May.

The HHS announcement addresses the following issues with respect to human subjects research:

  • Education and training

  • Informed consent

  • Improved monitoring

  • Conflict of interest

  • Civil monetary penalties

New initiatives designed to safeguard participants of clinical experiments and to better monitor biomedical researchers who establish clinical trials were released earlier this week by U.S. Department of Health and Human Services (HSS) Secretary Donna E. Shalala. Shalala announced several new guidelines that would, among other things, oblige investigators to receive training in ethics and human subjects research. The guidelines also would impose audits on research records, and they call for improved monitoring of clinical trials. But Shalala's announcement didn't end there. The HHS is also pursuing legislation that will enable the Food and Drug Administration (FDA) to levy substantial fines on investigators and research institutions that violate informed consent guidelines.

The HHS stipulation that educators be better trained and educated in ethics comes after the recent and very public revelations of research oversights and financial conflicts, and just 2 days before the Senate public health subcommittee meets to hear about one of those cases--the death of an 18-year-old who participated in gene therapy clinical experiments at the University of Pennsylvania in Philadelphia.

The National Institutes of Health (NIH) will announce next month that, starting this fall, it will be mandatory that recipients of federal funding receive "appropriate research bioethics training and human subjects research training" as a condition of their award or before their research grants are renewed. Belinda Seto, deputy director for NIH's Office of Extramural Research, who played an integral part during the past few months in drawing up the HHS announcement, adds that "the NIH will not assess or evaluate" institutional ethical programs. Seto also says that researchers must recognize that informed consent does not just mean getting participants to sign a document. It is an " iterative process." For example, should any "significant trial-related event" occur during a trial, researchers must "reconfirm" informed consent of its participants.

The NIH will now also require investigators of Phase I and Phase II trials to submit at the time of grant application "clinical monitoring plans" that explain how the trial will be conducted. Seto suggests that to reduce burdens on researchers, large research institutions--such as Johns Hopkins University or the University of California, San Francisco--might want to establish "standard monitoring plan templates" which can be modified or submitted initially.

One of the most important issues that investigators need to address is that of financial conflicts: "Researchers must be more attuned to conflict of interest issues," says Seto, echoing Shalala's comments that "new ethical dilemmas" may be created because biomedical research is becoming more commercial.

Updates and Links

To back up the guidelines, the HHS is pursuing legislation that, if enacted, would punish the violation of informed consent or "other important research practices"--such as conflicts of interest--with fines of up to $250,000 for each offending investigator, and up to $1 million for the offending institution. These "financial penalties," the HHS announcement reads, will provide "additional tools" to "sanction research institutions" and investigators.

To clarify and enhance the informed consent process, the HHS is holding a "widespread review" among members of the public this summer. "Public confidence in clinical trials is essential to the continued advances in medicine we all hope to see in the next century," Shalala states. And those hopes lie with the compliance of clinicians, investigators, and researchers who conduct this work. The ultimate goals, Shalala explains, are to "strengthen government oversight of all biomedical research," such as genetic research, and reinforce "internationally accepted ethical standards and federal guidelines."

Penn Halts Gene Therapy Clinical Trials

Following recent concerns about the management of human subjects research, the University of Pennsylvania announced 24 May that its Institute for Human Gene Therapy (IHGT) will no longer be permitted to conduct clinical trials.

The decision--made by university and institute officials--is one of many actions undertaken to address concerns highlighted in a report by an independent panel, who reviewed mechanisms of oversight and trial monitoring at IHGT. All seven of its clinical trials are "on hold by the FDA," a Penn spokesperson tells Next Wave. Gene therapy research will still be permitted elsewhere at Penn, but under the jurisdiction of the university's Office of Research Administration.

President Judith Rodin agrees with the review panel's suggestion that human clinical trials across the country will now require "increasingly stringent oversight and regulatory compliance."