Common Rule tissue changes elicit objections

Collateral damage could be high

One of the more controversial proposed changes to the research Common Rule involves strengthening informed consent protections related to research involving biospecimens. Some researchers predict these changes could shut down much of their work and result in major collateral damage to the research enterprise.

"I think the changes being proposed will have a major impact on our ability to do research," says William E. Grizzle, MD, PhD, professor of pathology at the University of Alabama at Birmingham in Birmingham, AL.

Researchers now can conduct research with existing biospecimens without obtaining informed consent when they've stripped the specimens of identifiers. The proposed changes in the advanced notice of proposed rulemaking (ANPRM), published in the Federal Register on July 25, 2011, would require written consent for research use of biospecimens even when they have been stripped of identifiers.

"They're asking us to consent 30,000 to 50,000 patients a year," Grizzle says. "We estimate it would take three or four fulltime individuals who would do nothing but informed consent, costing us up to $300,000 more to be able to continue doing research at the level we're currently operating."

HHS would be mandating this extra expense at the same time the National Institutes of Health (NIH) has cut its support of research, he adds.

"My budgets now are decreased by 5% to 10%, so we'd have to greatly reduce our service to the research community," Grizzle says.

The U.S. Department of Health and Human Services (HHS) has proposed that researchers obtain consent with a standard short form. It would provide open-ended consent for most research uses of biospecimens, including clinical specimens collected at a hospital.

The rationale behind the change, according to HHS is that changing technology in genomics has increased the amount and nature of information that can be obtained about individuals. Plus, HHS says that surveys show that people want to be able to decide whether or not their specimens can be used in research.

Although HHS' goals may be laudable, some experts commenting on the proposed changes, say the consequence of the proposed change would be dire.

"This would have a calamitous impact on medical research in this country," writes Helen P. Cathro, MBChB, MPH, associate professor in the department of pathology at the University of Virginia in Charlottesville, VA. Cathro submitted a personal comment on the proposal to the Office for Human Research Protections (OHRP). All comments are published online at www.regulations.gov.

Obtaining informed consent from every hospital patient who might have tissue used in research is almost impossible, Cathro says.

"It would cost a huge amount of money," she adds. "We've actually tried to get a hospital to do this, and we've had no success at all."

Most of these patients are facing surgery and already have to read multiple pages of documents, she explains.

"So you have to get someone to explain to them all of the ramifications of what will happen to their tissue," Cathro says. "And unless hospitals are forced to pay for this, it won't happen. Research budgets have no money built in for this expense."

There are huge ramifications for the scope of medical research across the United States, Cathro adds.

Without continued access to thousands of tissue samples, some research publishing will slow, the medication pipeline will grind to a halt, and academic researcher careers will stagnate, she predicts.

"If the general patient population were polled on the proposed measures and educated as to the likely implications for U.S.-based research, I have no doubt that they too would oppose it," Cathro writes in her comment. "Using de-identified tissue for research imposes a minimal risk to patients and provides potential large benefit to the future patient population."

The proposed change will have its greatest impact on research involving remnant tissue, Grizzle says.

"One thing I'm sure [regulators] have not looked at is the issue of how various types of bio-depositories will be affected," Grizzle says. "You have one issue when a biobank or depository has specimens from patients who are part of a cohort or epidemiological study because the biobank has an ongoing relationship with the patient."

Bio-depositories that collect remnant specimens that are left over after a clinical diagnosis and would otherwise be thrown away will have a major problem with this change, he notes.

"A big portion of research today is performed on remnant specimens, and that's where they'll have a problem," he adds.

Everyone in the research world agrees that investigators need to obtain informed consent in clinical trials or during any research in which there is a direct interaction with a patient or the potential of harm, says Christopher A. Moskaluk, MD, PhD, David Harrison Distinguished Teaching Professor of Pathology at the University of Virginia Health System in Charlottesville, VA.

"The issue is for research that is utilizing both archival tissue specimens and clinical data," he says.

"The proposed rule changes will affect both," he adds. "Right now it is possible to use archival tissue specimens and have access to patient's medical records for certain research projects if the IRB reviews them and feels there will be no direct interaction with the patient and no subsequent consequences to clinical care, and no risk of the patients being associated with the study's data."

IRBs can allow a waiver of informed consent in those instances, he says.

These waivers are especially important when investigators are using many different tissue samples or medical records that may involve hundreds of individuals and samples that date back decades, Moskaluk explains.

"The effort to track down individuals to obtain informed consent would take more effort than the actual investigation, and that's why a waiver is allowed right now," he adds.

For instance, suppose a pathologist or researcher suspects a certain biochemical pathway is activated in breast cancer and this hypothesis should be investigated, Moskaluk says.

"The researcher would get a sizable cohort of maybe 100 cases to see if this bio-pathway is activated," he explains. "But trying to get retroactive informed consent from those 100 individuals is quite difficult to do, and HIPAA regulations would prevent you from doing it directly."

Instead, the researcher would have to contact each patient's doctor and ask them to contact the patient.

"It's a quite laborious, multistep process to obtain informed consent for something that would have no direct impact on the patient's care," he adds. "The goal would be to find something that could move the medical knowledge toward finding new drugs and therapies, so it would be for the good of society."

Also, research involving tissue samples has no inherent associated risk, he says.

"Advancing medical knowledge with no impact in terms of subject risk is something that can be done relatively easily with IRB review when they allow for a waiver of informed consent," he adds. "But this won't happen in the future under the proposed Common Rule changes."

HHS says that the proposed informed consent changes would apply only to biospecimens collected after the effective date of the new rules. This grandfather clause is critically important if the rules are approved as written, Grizzle says.

"All paraffin block collections in any institution would no longer be of any use unless they're grandfathered," he says. "Trying to consent those patients would be an impossibility."

The Common Rule changes as written would result in a 30% to 40% decrease in available specimens, Grizzle predicts.

The impact on translational investigation would be negative and unnecessary, Moskaluk notes.

"The waiver of informed consent is not a huge insult to the autonomy of individuals," he says. "How much autonomy should people be granted to be involved in research?"

On the other hand, regulations that create onerous restrictions on research can also create harm, he adds.

"If research really is minimal risk and it uses retrospective materials and data, then having to get informed consent could create a financial and logistical burden that would prevent a lot of this research from occurring, and that is a harm to society."