Research geared toward specific groups/individuals
One drug was approved for one race
As studies become geared toward narrow research questions, targeting specific groups, IRB members will have an even more challenging time resolving ethical dilemmas and weighing risks and benefits.
Going back to the Belmont Report, one of the tenants of research is that society as a whole will share in the risks and benefits of studies, says Heather Butts, JD, MPH, regulatory specialist at Columbia University in New York, NY.
At the same time, investigators have been wary of including vulnerable populations in research, Butts says.
It's a balancing act between the fear that there could be greater risks or the understanding that these same individuals should not be excluded from research that might benefit them.
But that is the old dilemma. The new one has even more ethical questions, such as this one: How do IRBs use the old risks-benefits measures when confronted with research that specifically targets one ethnic group, Butts says.
The drug BiDil, which treats heart failure, is the first drug that's been approved for one specific ethnic group. It was approved on June 23, 2005, by the FDA for use with African-Americans, Butts says.
The FDA issued a press release when the drug was approved, saying it represented "a step toward the promise of personalized medicine."
"It caused some controversy because there are questions in terms of what was their thinking behind this decision," Butts says. "What are the genetics and biophysical aspects of this drug that make it seem to work better in African-Americans than in other populations?"
Two clinical trials of BiDil among the general population found no benefit from the drug, the FDA media release says.
"The approval of BiDil was based in part on the results of the African-American Heart Failure Trial (A-HeFT)," the FDA notice says. "The study, which involved 1,050 self-identified black patients with severe heart failure who had already been treated with the best available therapy, was conducted because two previous trials in the general population of severe heart failure patients found no benefit, but suggested a benefit of BiDil in black patients."
The self-identified black patients in the A-HeFT study had a 43 percent reduction in death and a 39 percent decrease in hospitalization for heart failure when compared with placebo, the FDA notice says.
When Butts spoke about this drug at a national IRB conference, one doctor said that he has a white patient in his mid-50s who takes the drug and does well with it. The doctor felt obligated to let the patient know that the drug was approved only for use in African-Americans, and the patient was fine with this disclosure, Butts says.
"The doctor was essentially telling the patient, 'I'm prescribing this to you off-label, and I think it will be of benefit for you because other things aren't working,'" Butts says.
But questions still linger about how the research data came to the conclusion that it was the demographic of being African-American that made the difference, rather than some other item, such as a comorbidity, Butts says.
"Another issue is that there's a question of whether the drug interacts interestingly with patients with diabetes and congestive heart failure, and a lot of African-Americans have diabetes," Butts explains. "So one thought is that the drug works better with the comorbid illness of diabetes than if someone doesn't have diabetes."
However, in the case of BiDil, it was the Association of Black Cardiologists who linked with BiDil's sponsor, NitroMed of Lexington, MA, to conduct the A-HeFT trial to see whether the fixed dose of isosorbide dinitrate and hydralazine benefited blacks, who were selected based on self-identification, Butts says.
"What an IRB should do is be vigilant that groups of people aren't being stigmatized based on what a study describes," Butts says. "For example, if an IRB saw a protocol like the BiDil one, they should ask: Given what the outcomes of this study might be, how will this impact XY people, and will they be looked upon in a certain way that's not favorable?"
Other questions for IRBs to ask are:
- Will there be untoward societal or legal or employment impacts because of the information being sought? "That's especially important in genetic studies," Butts says.
- Are there risks this group of people could suffer based on what you study, and are these balanced by the potential benefits?
- What are the risks you want to take into account as the study progresses?
- Should the study be monitored more frequently because these people may be harmed in ways that cannot be imagined yet?
"The area of genetic research is ever evolving, and there are certain risks you can't wrap your head around in 2006, that you might see later," Butts says.
The medical community and researchers are becoming more aware of what causes certain diseases, including genetic components and comorbid factors, she notes.
"There's a whole area of medicine that looks at the rate at which individuals metabolize drugs," Butts explains. "For example, if you have certain different pain medications and people metabolize them differently, then what works on one person might not work as well for another."
Future medical research will be increasingly geared toward individualized medicine, and this includes individualized according to ethnic group, although it's not clear whether that is an answer or a crutch, Butts says.
"Race may be a pretext for less vigorous examination of why people respond to a specific treatment of drugs," Butts says. "It may be easier to say people respond because of gender, race, and ethnicity."
As studies become geared toward narrow research questions, targeting specific groups, IRB members will have an even more challenging time resolving ethical dilemmas and weighing risks and benefits.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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