Washington Editor

WASHINGTON - Two highly publicized deaths of clinical trial participants have prompted lawmakers to look deeper into the rules that govern such research.

It all started about two years ago when Jesse Gelsinger, 18, a patient enrolled in a Phase I gene therapy trial at the University of Pennsylvania, unexpectedly died. And then last year, Ellen Roche, a 24-year-old healthy volunteer at Johns Hopkins University, died after inhaling a chemical as part of an asthma trial at the Baltimore university.

These are just two stories, but there are others.

Indeed, Sens. Edward Kennedy (D-Mass.) and Bill Frist (R-Tenn.) held a subcommittee hearing of the Senate Health, Education, Labor and Pensions Committee here Tuesday to collect information and opinions from industry representatives on monitoring clinical trials and protecting volunteer participants. Kennedy reportedly is preparing legislation that would, among other things, require accreditation of the institutional review boards (IRBs) that oversee federally funded clinical trials. Meanwhile, in the House, Rep. Diana DeGette (D-Colo.) also is considering legislation, but hers would give IRBs the choice of gaining accreditation.

Clearly, current laws need reform, Kennedy said during the hearing. “When the original legislation was enacted, clinical trials were conducted on a few dozen subjects at a single institution. Few researchers at universities had financial ties to drug companies - and biotechnology was not yet even a word, much less a national industry,” he said. “But clinical research has changed significantly since then, and those changes have strained our system of research protections to the breaking point.”

According to data from the National Institutes of Health, nearly 7 million people annually are enrolled in research sponsored by the government. The pharmaceutical industry spends $26 billion a year on research (compared to $16 billion for the NIH), so the total number of patients enrolled in the public and private sectors is estimated at about 19 million each year, the NIH said.

After the death of Gelsinger, Frist said he held two hearings to examine the oversight structures in place for ensuring the safety of patients in gene therapy trials. “It became clear that there had been a systemic breakdown of oversight ranging from the investigators to the institutional review boards to the federal agencies responsible for ensuring the safety of patients,” said Frist, a heart surgeon and the only physician in the Senate.

Cherlynn Mathias, a registered nurse and whistleblower who helped shut down a melanoma clinical trial at the University of Oklahoma in June 2000, told Frist and Kennedy that she was haunted by a series of problems she witnessed while working as the study coordinator of the melanoma trial. Among them, she said ineligible patients were enrolled in the study, adverse event monitoring was lacking, an unapproved version of the protocol and informed consent were being used, and patients were led to believe that the vaccine could cure their cancer.

She told Kennedy that the 1,900 IRBs across the U.S. should be forced to receive accreditation. (Members of IRBs are usually faculty associated with universities, bioethicists, physicians, researchers and community members.)

But Marjorie Speers, executive director of the Association for the Accreditation of Human Research Protection Programs Inc. and the former acting executive director of President Clinton’s National Bioethics Advisory Commission (NBAC), said the commission does not recommend mandating accreditation.

“We believe that accreditation should be voluntary,” Speers said. “We believe it works best when an organization makes a voluntary commitment, and it should be done in conjunction with the federal government.”

Charles Johnson, associate director of specialty biotherapeutics at South San Francisco-based Genentech Inc., who addressed the subcommittee on behalf of the Washington-based Biotechnology Industry Organization, said, “BIO is intrigued by the concept of IRB accreditation and would be supportive of exploring the issues involved.”

Advocates of mandatory accreditation would make the argument that organizations likely would not volunteer unless they ran into the troubles faced by Johns Hopkins or the University of Oklahoma.

Speers said last year the NBAC drew up a report, “Ethical and Policy Issues in Research Involving Human Participants,” in which it recommended that the government establish an independent office, the National Office for Human Research Oversight, to lead and coordinate the oversight. Furthermore, NBAC recommended a single federal policy to apply to the research. (See BioWorld Today, June 12, 2001, and Sept. 17, 2001.)

The NBAC’s charter expired in October and was later replaced by a similar committee set up by Bush.

BIO also had supported a single federal policy, saying researchers are subject to a patchwork of different, sometimes inconsistent, state laws. “Although there are extensive federal rules regarding research, state laws govern issues such as the form of review and format of additional documentation of consent,” Johnson said. “This is often problematic for researchers.”

Others have raised concerns about financial conflicts of interest, to which Johnson said there is a perception that private money in the health care setting creates conflicts of interest for researchers that may affect results and the quality of care. “The best way to both protect patients and the integrity of research is to ensure that research protocols are independently reviewed and that all financial interests are disclosed,” he said.

Frist raised his eyebrows when Speers and Mathias informed him that researchers are not required to inform an IRB of any potential financial conflicts.