By Lisa Seachrist

Washington Editor

WASHINGTON - Finalizing nearly three years of work that has been interrupted by sheep clones and stem cell debates, the National Bioethics Advisory Commission (NBAC) submitted to President Clinton its final recommendations on how to regulate research on stored human tissue samples.

The 23 recommendations in total outline a plan for modifying the "Common Rule" overseeing federally funded biomedical research in a way that addresses research using the vast number of tissue samples that have been stored over the past century. In addition to tissue sample research, NBAC recommended the principles guiding its report be adopted by lawmakers and regulators considering medical records privacy.

Unfortunately, the conclusions reached by NBAC have critics both in academia and industry who are concerned the recommendations won't simply stymie certain avenues of biological research - but block them altogether.

Central to critics' concerns is the definition of what constitutes human subjects research. In its report, NBAC defines both coded samples and identified samples as research on human subjects requiring full informed consent and review by institutional ethics boards.

"The definition of what's identifiable is the crux of the issue," said Gillian Woollett, associate vice president for biologics and biotechnology for the Pharmaceutical Research and Manufacturers of America (PhRMA).

Michael Werner, bioethics counsel for the Biotechnology Industry Organization (BIO), agreed, noting, "The big issue for us is that we think that coded data should be treated as anonymous data. Our sense is that coded data just doesn't raise the same concerns as identifiable data."

Currently, academic and industry researchers use tissue and blood samples to conduct discovery research that can indicate genes and cell pathways that are important in a disease process as well as for other basic research pursuits. Often, they choose to use samples coded to permit names and other identifiers to be removed. A central keyholder can link the samples and the medical records to the patient should further tissue or some medical information prove useful.

NBAC considers these coded samples to be the same as samples with names and addresses on them because the code makes them traceable. As a result, research using those materials would require Institutional Review Board (IRB) review and adequate informed consent.

"We place a tremendous amount of responsibility on the keyholder, not the researcher, receiving coded samples," Woollett said. "[In terms of confidentiality] it doesn't much matter whether a key exists or not if you don't have the key. Those samples should be freely circulated among the research community."

NBAC also calls on the National Institutes of Health's Office of Protection from Research Risks (OPRR) to revise its guidance to make clear that all "minimal-risk" research involving human biological materials - regardless of how they were collected - should be eligible for expedited IRB review.

Now, when a patient signs a consent form for surgery or a biopsy, there usually is a clause permitting the sample to be used for research. NBAC recommends such universal consent be eliminated and patients consent to clinical care and research separately. In addition, it recommended patients be told their decision not to participate in research won't impact their clinical care.

However, Woollett questioned how a patient can give truly informed consent for research when he doesn't know the likely nature of the research.

Requiring researchers to go back to sources to get informed consent could have the effect of stopping certain areas of research altogether. NBAC has recommended several provisions based on the current Common Rule to allow IRBs to waive informed consent when collecting such consent isn't practicable.

However, the chore of going through IRB review, no matter how expedited, and obtaining a waiver for additional informed consent may have the effect of discouraging public-private partnerships. The Common Rule applies only to researchers and institutions receiving federal research funds and research reviewed by FDA. While private researchers often choose to abide by the Common Rule for research that doesn't fall under those categories, they aren't compelled to do so.

"They are essential providing a disincentive for industry and academic collaborations," Woollett said. "The effect on research is potentially quite serious."

NBAC's report doesn't carry the weight of law. Any further action on the issue would need to be initiated either by members of Congress or the Clinton administration.