Protecting uninsured participants in research

How will subjects be treated if something goes wrong?

Nearly 47 million Americans lack health insurance, leaving them without regular access to health care — and making them a potentially vulnerable population in health care research.

From the possibility of undue influence to how to deal with research-related injuries, uninsured subjects raise ethical issues that IRBs must consider when reviewing protocols, says Daniel Vasgird, PhD, CIP, director of research compliance services for the University of Nebraska-Lincoln.

Vasgird says the Belmont Principles of beneficence and justice underlie IRBs' responsibility to subjects who lack ready access to health care.

"You have a moral obligation there to make sure that the individual would benefit from the specific study — that it's not just something that you can rationalize out and say you're doing it for the greater benefit of mankind," Vasgird says.

According to the U.S. Census, 15.8% of all Americans reported being uninsured during 2006, the highest percentage since 1998. For some groups, the percentages are even higher: 20% of African-Americans and 34% of Hispanics reported being uninsured during 2006.

Important subject pool

In his previous position as chair of the IRB at the New York City Department of Health, Vasgird saw many uninsured patients.

He says the department was an inviting place for researchers, particularly during the 1990s, when the HIV epidemic was in full swing and tuberculosis cases were on the rise.

"The department has well over 100 clinics scattered throughout the city, with tens of thousands of people receiving treatment in those clinics — STD clinics, tuberculosis clinics, and the like," Vasgird says. "Researchers want to have access to that subject pool, so the Department of Health IRB is an important one."

He says his interest in uninsured research subjects was piqued by a study his IRB reviewed that sought to look at the effectiveness of quinolones, a class of powerful antibiotics.

"An individual had gotten funding from a pharmaceutical company and wanted to use the tuberculosis and STD clinics to recruit subjects," Vasgird says. "Some of [the quinolones] have some very extreme side effects, and as I was reading through the protocol and consent form, I realized after I got to the end, that there was no provision made if anybody was injured, or if they had serious side effects."

Vasgird says he consulted physicians on his board, who all advised that the IRB should require the sponsor to provide free medical care or compensation if subjects were injured in the course of the study.

But the researcher balked at the idea, pointing out that the federal regulations require only that participants be told whether health care is available, not that it be mandated.

"In other words, all you have to do is let people know that they're not going to be cared for if something goes wrong — it's a very, very minimal standard," Vasgird says. "We told him yes, we're aware of that, but I pointed out to him that the IRB can raise the bar, if they feel it's ethically necessary to do it. In this case, we felt it was ethically necessary."

Ultimately, Vasgird says, the researcher and sponsor agreed to the provision and the study went forward.

He says an IRB faced with a study that presents more than minimal risk to subjects should take similar steps to ensure that uninsured subjects are protected in case something goes wrong.

Not every study deserves such stringent requirements, Vasgird says. He says it's up to IRBs to do the risk-benefit analysis and decide whether it's necessary.

"If the risk is low, then in those kinds of cases, you don't have to stipulate it," he says. "You don't have to make a federal case out of every single study. But the board should have that stipulation within its portfolio — it should be ready to say that you have to do this when it's pretty obvious that the physical risk is relatively high."

He notes that in some cases, health care for those injured in research is paid for through the institution's liability insurance.

"So my first word of advice to any IRB is to double-check with your general counsel to make sure that you don't have those provisions in place in an insurance policy."

Other ethical issues

Beyond concerns about research-related injury, the inclusion of uninsured subjects poses other ethical challenges, Vasgird says:

• Undue influence. Vasgird says some uninsured subjects may be signing up for clinical trials because they are trying to receive health care and medication that they can't get elsewhere.

"Their income levels are modest at best," he says. "So they're more susceptible to coercion. It's possible that people would be making a decision to be involved in a study that they normally wouldn't do. They're not thinking seriously about what it could mean for them down the line in terms of their well-being."

He says IRBs should be alert to that possibility when reviewing protocols that are likely to recruit a large number of uninsured patients.

• Post-trial benefits. Vasgird says vulnerable groups such as uninsured patients shouldn't be expected to contribute to research that can't benefit them later, if they're unable to access the study drug because of lack of health insurance.

It's a concept that applies not only to uninsured subjects in this country, but increasingly, to research subjects in developing countries.

"If at all possible, you're supposed to provide so the individual can receive care," he says. "Certainly from the standpoint of the developing countries, they want to make sure that the medical care and other things are going to be provided after the people leave."

Vasgird says that IRBs that routinely deal with uninsured subjects should take special care to involve representatives from that community on the board.

"You should try to make a point of not just having somebody unaffiliated," he says. "You should be going beyond that to find individuals who can really be representatives for these particular groups — a minister, a social worker, a principal, or teacher who comes from that community and who can speak for them."