New HHS research committee plans to clarify and define some regulations

Initial focus on accreditation, children

IRBs and the research community soon may have new guidance in defining and clarifying some of the gray areas in regulations of human subject protection.

The Department of Health and Human Services (HHS) created the Secretary’s Advisory Committee on Human Research Protections (SACHRP) to replace the National Human Research Protections Advisory Committee.

"We have been charged by Secretary Tommy Thompson in a charter to advise him on protection of human subjects with particular emphasis on special populations," says Ernest Prentice, PhD, SACHRP chair, and the associate vice chancellor for academic affairs at the University of Nebraska Medical Center of Omaha.

SACHRP has ex-officio members from various federal agencies, including the National Institutes of Health (NIH), the Department of Justice, the Food and Drug Administration (FDA), the Department of Education, and others, he notes.

"So we’re getting input from all official branches," Prentice says. "That means NIH can advise the committee about their concerns, and we can address them."

HHS has asked the committee to provide guidance on research that involves the following populations and issues:

  • special populations, such as neonates and children, prisoners, and the decisionally impaired;
  • pregnant women, embryos, and fetuses;
  • individuals and populations in international studies;
  • populations in which there are individually identifiable samples, data, or information;
  • investigator conflicts of interest.

The committee’s responsibilities also include the review of ongoing work and activities of the Office of Human Research Protections (OHRP), including a review of assurance systems, minimal research risk standards, the granting of waivers, OHRP’s educational programs, and the monitoring of IRBs and institutions that sponsor research.

"That’s a fairly broad charter, and obviously we can’t tackle all of those issues simultaneously," Prentice says. "So we have chosen to identify some initial challenges and tasks that we’re going to work on as a committee."

SACHRP has formed three subcommittees to further examine the areas of IRB and research institution accreditation, research protections for children under the regulation Subpart D, and research involving prisoners.

"We’ve also appointed individual members of the committee to spearhead discussion on some issues, including adverse event reporting, litigation, and international research," Prentice says.

When the subcommittees complete their reports and the full committee has discussed and accepted these reports, the committee will give its final report to HHS, and it may form several different subcommittees, he notes.

"I’m optimistic the work of the committee will result in significant products, will assist in ensuring appropriate protection of human subjects, and, at the same time, will facilitate important research," Prentice says.

For him and other leaders in the research community, a big concern is the public’s loss of trust in human subjects research.

"It’s very important that we maintain the public’s trust in clinical research so they know their rights come first, and that they know there is a staffed IRB that will work with investigators to ensure appropriate protection, and that they know the institution is committed to this endeavor," Prentice says.

Accreditation a hot issue

Here is a thumbnail look at the issues being addressed by SACHRP’s subcommittees:

• IRB accreditation: "As a committee, we want to look at ways to motivate institutions and look at the impact of accreditation and whether or not the federal government ought to be involved in certifying accreditations," Prentice notes.

"We think as a committee that [human subjects research] accreditation is something that’s long overdue," he says. "They’ve had animal research accreditation since the 1960s, so it’s incredible that we’ve chosen to accredit animal research and only now look at human research accreditation."

The accreditation subcommittee is looking at the pluses and minuses of accreditation and the issue of whether the federal government should be in the business of encouraging accreditation, says Thomas L. Adams, CAE, a member of SACHRP and the accreditation subcommittee. Adams also is the chief executive officer of the Alexandria, VA-based Association of Clinical Research Professionals (ACRP), an 18,000-member association that provides training and education for people involved in clinical research.

Specifically, the subcommittee will assess existing impediments to accreditation and identify ways to reduce impediments and, perhaps, enhance inducements, he says.

"As a general rule, I personally believe accreditation is a good thing," Adams adds.

"The types of things we’re looking at are not necessarily covered under the current rules and regulations, but may further be fleshed out by either a legislative or regulatory initiative in the future," he says.

The two nongovernment organizations that currently provide accreditation services for IRBs will have an opportunity to meet with the subcommittee to explain how the programs are working, Adams says.

"Accreditation is an important way to ensure patient protections," he notes, adding that another part of the trend toward ensuring quality in human subjects research is certification.

ACRP provides certification for research professionals and has just begun a program for principal investigators, Adams says.

More information about the certification program can be found on the organization’s web site at www.acrpnet.org.

Focus on risks

• Research involving children: SACHRP and a subcommittee focusing on the Subpart D regulations will advise HHS on appropriate interpretation of the regulations that apply to additional protection of children, Prentice reports.

This is an area that has caused some confusion among IRBs for 20 years, and the issue is further problematic when the FDA’s parallel regulations are considered, he adds.

The subcommittee will work on defining some of the terminology that has troubled IRBs and investigators over the years, says Celia B. Fisher, PhD, a SACHRP co-chair of the pediatric research subcommittee. Fisher also is the Marie Ward Doty university chair and the director of the Center for Ethics Education at Fordham University in Bronx, NY.

For one thing, the subcommittee will attempt to provide guidance for what constitutes minimal risk in research that involves children, she notes.

"In the federal guidelines, minimal risk is defined in terms of the everyday experiences of the child," Fisher says. "And one of the issues that has been confounding IRBs and investigators is whether everyday experiences should be defined relative to the healthy child or the vulnerable child."

Minimal risk needs to be thoroughly examined from all angles, including psychological and social-behavioral, she says.

An example would be a social-behavioral research that asks children in a school setting about depression, suicide, trauma, sexual activity, or drug use, Fisher adds.

"This is where IRBs are having tremendous difficulty figuring out whether this is minimal risk, or whether this is in some sense risky just to read the question and ask for answers," she says.

For biological research, a blood draw might be viewed as minimal risk, but if the child is a hemophiliac, it no longer can be considered a minimal risk, Fisher adds.

"At the same time the federal guidelines and recommendations can’t absolutely define this issue because every child’s population is different," she says. "So what needs to be done is to provide guidelines for how to assess whether a research design presents minimal or greater than minimal risk."

Another clarification involves when the regulations permit pediatric research that is a minor increase over minimal risk with no direct benefits, Fisher says.

"You are allowed to do this research if it has direct relevance to the child’s condition," she notes. "But defining the child’s condition can be very confusing."

For example, is being a child a condition in itself or does "condition" only refer to illness? Also, is a child’s poverty a condition? Is minority status a condition? Or if the child has been abused is that a condition? Fisher asks.

"It’s very difficult to narrow the definition because there may be instances where simply being a child is important to doing the research," she says.

The subcommittee also will address the controversies involving 407 reviews of which the most notable review this past year involved the proposed pediatric smallpox clinical trials, Fisher says.

Clinical trials of vaccines to prevent illness are examples of studies where it’s necessary to have children as subjects, she explains.

"But there are other times where you do not want to simply use children because you want to test [a drug or device] that will be largely used by adults," Fisher adds.

• Research involving prisoners: SACHRP and the prisoner research subcommittee will address the Subpart C regulations to determine whether additional protections are appropriate for protecting prisoners involved in research, Prentice says.

The regulations were issued more than 20 years ago, and a great deal has changed since then, he notes.

"We know that the regulations are very restrictive, and we know that prisoners are often deprived of an opportunity to participate in clinical research because the regulations are so restrictive," Prentice explains. "While we understand that individuals in prison are in a potentially coercive environment, nonetheless, this becomes a matter of justice, and we want to make sure the research is appropriate for the times."