Are research subject advocates the future?

NCRR created position, but roles vary

There is a new kid on the block, helping to oversee human subject protections at some institutions and providing some assistance to overtaxed IRBs: the research subject advocate (RSA).

The National Center for Research Resources (NCRR) of Bethesda, MD, decided several years ago that researchers and IRBs needed additional resources when it comes to human subject protection, so NCRR created the RSA position to assist 82 General Clinical Research Centers (GCRCs) that receive funding from five-year National Institutes of Health (NIH) grants.

"I wasn’t at NCRR when the decision was made, but I think from my discussions here that the thought was that RSAs were not to take the place of the IRB or human subject protection offices at institutions, but to help GCRC nurses, participants, lab staff, and principal investigators to understand what was needed," says Elaine Collier, MD, assistant director for clinical research at NCRR.

"The RSA’s task is to represent the voice of the human subject on GCRC, because that’s a voice that’s not there," she adds. "So this is a person who thinks about how the participant would view the study when discussions are made of that study."

Many RSAs work closely with IRBs, and some are members of IRBs. This gives them an insight into what the IRB expects and needs from investigators, and they’ll pass that information on to the investigators often before the protocols are submitted.

"Also, if they have concerns about a protocol they can profess those to the IRB, too," Collier says. "It’s a two-way street."

Although RSAs now are only available at GCRCs, the model could be useful at other institutions, she notes.

Industry-sponsored and other government-sponsored trials could benefit from having an RSA involved, Collier says. "We don’t envision right now moving in that direction, although we see how it would be useful."

Here’s how the position works:

• RSAs vary widely in their duties, but there should be little or no duplication with what IRBs do. "IRBs have an actual statutory responsibility for human research subject protection. We try to assist investigators in meeting IRB criteria," says Theresa O’Lonergan, MA, research subject advocate at the Pediatric General Clinical Research Center at the University of Colorado Health Sciences Center and a biomedical ethicist at the Children’s Hospital in Denver. She also is the president of the Society for Research Subjects Advocates.

"I work with the IRB, and we share a database that they have generously allowed me to access. If I see that an investigator’s [paperwork] is about to expire, I can contact the investigator," O’Lonergan says. "I don’t take on the IRB’s work; I just make sure our principal investigators are doing what they’re supposed to be doing."

Wajeeh Bajwa, PhD, a research subject advocate and regulatory consultant at Duke University Medical Center in Durham, NC, has provided RSA-type services to his institution since 1998, and the RSA model was developed based on his work.

The idea of having a separate regulatory consultant or RSA is that IRBs spend a great deal of resources in handling paperwork related to compliance and consent forms and have little time for hands-on oversight, Bajwa says.

"There’s very little in terms of oversight of manufacturing aspects or clinical trials in terms of doing orders and looking at documentation that each investigator has at his site," he explains. "At Duke, we started providing this service for investigators so they could request a regulatory consultant to help them become fully compliant with good manufacturing practices and good clinical practices."

Once Bajwa began the work, the response from investigators was tremendously positive, he says. "Usually investigators do not have the funds to hire an outside consultant."

Likewise, the Duke IRB was supportive of the role and has always been mutually cooperative, Bajwa says.

"I am a member of the IRB, and some protocols are assigned to me to review, and they are not necessarily related to GCRC," Bajwa adds. "I can stay abreast of what new things the IRB has to cope with, like when they had to modify all consent forms using HIPAA [Health Insurance Portability and Accountability Act] language."

In creating the RSA model, NCRR made the position flexible by giving institutions leeway to turn this into whatever worked best for them. For example, some GCRCs have full-time RSAs, while others may have several people providing part-time RSA work. The people working as RSAs have a variety of degrees and experience, and while some serve on IRBs, others do not because they feel it would be a conflict of interest.

"As you can imagine, we’re an extremely diverse group of people," says Susan Margitic, MS, GCRC research subject advocate for Wake Forest University School of Medicine in Winston-Salem, NC. "Some of us are ethicists, some are clinicians, and some are researchers."

• RSAs often work directly with investigators and research staff. One of the big advantages to having an RSA is that the RSA can work one on one with investigators, both in terms of providing input for the protocol as it’s developed and helping to monitor the safety status of the study, Margitic says.

"Whereas our IRB is responsible for over 1,000 active protocols, our RSA office oversees the safety of about 100 protocols," she adds.

RSAs educate and work closely with investigators as they develop protocols, providing them with suggestions that will ease their application process.

"The main role of the RSA is the training and education of the investigators," Bajwa says. "The IRB is more of a monitoring board, and RSAs can fulfill this role of training and education and answering investigators’ questions on a day-by-day basis."

O’Lonergan typically works with investigators for about four months before they’re ready to submit their protocol to the IRB. "If I help them with the protocol, they typically go through the IRB review with fewer problems, and our review has fewer problems," she says. "I work with them on research design and human subjects protection."

Some RSAs, including O’Lonergan, are involved in the GCRC approval process, and investigators will make changes per the RSA’s suggestions, she notes. "I have a good relationship with investigators; and if I bring up concerns, they know I’m not the only one who has them."

Once a protocol is approved by both the GCRC and the IRB, the RSA still may provide assistance through data safety monitoring, providing guidance during the informed consent or assent process, and training research staff, O’Lonergan says.

"If it’s a problematic protocol I might suggest that I come in and help with the first month or so," she says. "I meet with them at protocol initiation, make sure nurses have no problems in recruiting and know what they are supposed to do."

RSAs may also assist experienced investigators by letting them know when protocol changes need IRB approval and providing some assistance with meeting HIPAA privacy regulations, O’Lonergan says.

"At first, you’re always worried that investigators will think, Why is she bothering me?’" she says. "But I’ve had the good fortune to have investigators say, I didn’t know you could do this — come on over.’"

Basically, RSAs provide investigators with assurance that their protocol applications are submitted properly and that their research meets all regulatory standards.

"The other thing that RSAs do is provide a friendly audit of trials for investigators at GCRCs," Collier says. "So if there are things that need to be improved, the RSA can talk with the investigator about them, and it’s not a compliance audit."

• RSAs may also work directly with research subjects. Bajwa sometimes meets with research subjects to make certain that they understand the informed consent form.

Particularly in the cases of high-risk studies, he will make certain subjects understand all of the risks involved in the study, and he’ll sit down with investigators when they are explaining consent to subjects.

"I monitor how the consent is being given and provided to the research subject, and in one study that can take up to 3½ to four hours," Bajwa reports.

Margitic also observes investigators as they provide informed consent, watching to make certain they engage the person in a dialogue and encourage the person to ask questions.

"We don’t want to see any signs of coercion," Margitic says. "The consenter should take time and not give any indication that they’re rushed."

The whole idea of having an extra person observing and monitoring research projects in a hands-on manner is one that might become a model for many institutions, Margitic says.

"My sense is we are really paving the way," Margitic says. "The RSA serves as a role model that is first of its kind and it may be a pilot for what could be done institutionwide, although we have the luxury of doing the work for a core group of protocols."