'Sled dogs' haul research into unmapped territory

Collaborative RECS take IRBs to far destinations

There are a variety of models for research ethics consultation services (RECS), but a common factor that has made these new ethics boards appealing to top U.S. health officials and foundations is the idea that they can work collaboratively with IRBs to improve human subjects protection, an expert says.

Larger research institutions, especially those that deal with genetic and embryonic research, have begun to form RECS, sometimes self-funding them and sometimes obtaining grant funding.

RECS often are charged with going into uncharted ethical and research territory, handling issues that are beyond the typical IRB purview, says Jim Lavery, MSc, PhD, a research scientist at Saint Michael's Hospital in Toronto, Canada, and an assistant professor at the University of Toronto. Lavery is a co-principal investigator on a grant funding the RECS, called the Ethical Social and Cultural Program for the Bill and Melinda Gates Foundation Grant Challenges in Global Health Initiative.

One luxury RECS have is they typically do not deal with IRB-type issues, such as ensuring regulatory levels of compliance, he notes.

"RECS handle issues that are super regulatory," he explains. "These are issues we don't have answers for, and there's not a lot of literature on these issues."

For example the Gates Foundation-funded RECS have addressed the ethical and cultural issues related to a Chinese scientist's research into developing a mouse model for the human liver for vaccine testing, Lavery says.

"Our challenge was seeing if this could be done by emerging international standards in a country that didn't have rules that are the same as in the United States," Lavery explains. "So we developed a customized oversight system for that project."

The Gates Foundation wanted an ethics consultation service that would bring expert knowledge to the table on emerging international standards, U.S. standards and current governmental policy, as well as research ethics' history.

"In our program we proposed we develop an advisory service with the objective of working very closely with scientists," Lavery says. "We have a stable of topics that research ethics people talk about."

A different perspective

The idea is to help scientists look at their cutting-edge and novel research with a research ethics perspective. A mouse model for the human liver might be a breakthrough way to develop products that could save thousands of lives. But from another perspective it could raise political and ethical red flags.

The key is to design studies and conduct them in ways that are sensitive to ethical concerns.

"We can say to an investigator, 'If you don't get this right then no one will use the product from your research, and all of this work will be a complete waste of time,'" Lavery says. "We're here to shepherd this process so you don't miss important issues."

For instance, a RECS member might visit a collaborating hospital where embryos are procured to see that the process meets National Academy of Sciences standards, he adds.

If IRBs are the watchdogs of human subjects research, then RECS are the sled dogs, Lavery says.

"Someone came up with the analogy of how we're not watchdogs; that's not our goal here," Lavery says. "But we're not lapdogs either; we're not just going to give some ethical stamp of approval to someone doing something controversial."

Likewise, RECS are not the guide dogs because researchers do consider and care about ethical issues and give these consideration when they develop protocols, he adds.

"So we settled on sled dogs, a Canadian analogy," Lavery says. "There's a bunch of terrain that' s a little more unfamiliar to you, and we probably have more experience with crossing that terrain, and so we'll sort of hitch ourselves together and work collaboratively with you to get to wherever the destination is."

The hallmark of a RECS program is to be as integrated in the clinical research process as is possible, he adds.

RECS are not replacing IRBs, since both have necessary roles as science advances.

"No one wants to run a RECS and leave the impression that IRB folks can't handle these issues," Lavery says.

Establish RECS within the context of the existing human subjects protection program and collaborate with IRBs, he says.

"The key to me is that IRBs have a clear cut responsibility to make sure investigators are compliant with federal regulations and good ethical practice in general," Lavery says. "But IRBs, especially in the United States, are not well-equipped with staff and resources because of regulatory demands, so this makes it harder for IRBs to deal with emerging challenges."

RECS can shepherd ethical discussions between IRBs and investigators.

"One thing we try to do is broker that relationship," Lavery says. "We tell investigators, 'This has nothing to do with IRBs, but these kinds of issues are things your IRB would like to know about, and we can help structure that conversation.'"

Some of the issues RECS deal with are exotic and so far outside known research ethics territory that IRBs probably shouldn't spend much time on them, he notes.

"But any work we do should help IRBs get a sense of what's done and what's on the horizon," he adds.

Encouraging biomedical innovation

Research institutions that charge IRBs with handling all issues, including gray areas of research that only marginally could be considered human subjects research, run a risk of having judgments that discourage biomedical innovations.

"The Common Rule requires IRBs to make judgments, but we're so far beyond that now," Lavery says. "IRBs are terrified of making any kinds of judgments, so what I'd be worried about is if RECS are not rolled out properly then that could reinforce the notion that IRBs have only this very narrow mandate."

Instead, institutions should develop RECS to draw IRBs into new and emerging issues that they don't have very good guidance for, Lavery says.

"This will give them some confidence and the tools they need for making judgments," he adds.

There are three reasons why IRBs should not be left alone to weight the ethics of super-regulatory issues, he says. They are as follows:

  • The first is that IRBs have very heavy workloads and do not have time to explore super-regulatory issues.
  • Then there is the fear that their institutions will be shut down if, even on the surface, they have very technical departures from the regulations, Lavery says.
  • And, third, there's a high degree of variability amongst institutions that perform research, he adds.

"If you are at a major research institute and working on cutting-edge issues with the immune system to combat cancer, then you will deal with entirely different issues than a small IRB at a hospital in the Midwest," Lavery says. "What you see on your desk will be different each day."