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Are gays and lesbians being unfairly excluded from your clinical trials?
IRBs should ask: Are there valid scientific reasons?
A recent analysis of clinical trials showing that gays and lesbians have been excluded from certain types of studies is causing reverberations within the research community and beyond.
The analysis, whose results were recently published in a letter to The New England Journal of Medicine, has led to a call from five U.S. senators for an investigation by the U.S. Department of Health and Human Services.1
"This is more than an equality issue it raises huge questions about the quality of medical information from flawed trials," Sen. John Kerry, D-Mass., said in a statement that accompanied an April letter to HHS Secretary Kathleen Sebelius.
Brian Egleston, PhD, a biostatistician at Fox Chase Cancer Center in Philadelphia, was the lead author of the letter. He said his interest in exclusions of gays and lesbians from trials was prompted by his service on Fox Chase's research review committee, a scientific review panel that looks at protocols prior to their submission to the institution's IRB.
"I saw a couple of protocols with language that studies were restricted to people in heterosexual relationships," Egleston says. He says one of the studies concerned couples counseling and the other was related to treatment for prostate cancer.
After he and another member raised questions about the two protocols, "it actually was something that research review asked the investigators to explain ...before they approved the protocols."
This led Egleston and his colleagues to do searches of the ClinicalTrials.gov database looking for specific inclusion and exclusion criteria that limited participation in trials to heterosexuals.
When his group looked at studies containing the words "couples," "erectile dysfunction" or "hypoactive" (referring to hypoactive sexual disorder), they found 37 studies 15% of all studies that included those words that had language that in some way excluded gays and lesbians. For example, there might be a requirement that the participant "be in a reciprocal relationship with a person of the opposite sex."
Lack of validated measures
Egleston says the most common reason given by researchers for such exclusion criteria is a lack of validated measures of sexual functioning endpoints for gays and lesbians. He says commonly used surveys of sexual functioning have questions that are related to heterosexual relationships. But he says there are methods that can be used in both gay and straight populations, including the so-called "stamp" test, an older measure that is appropriate for men of any orientation, including men who are currently not in a sexual relationship.
Egleston says that the research community at Fox Chase has become educated about this issue and investigators are more often using study designs that can accommodate a diverse population.
Fox Chase's IRB now takes a close look at such exclusions as well, when they come up in review, says its vice-chairman, Clifford Perlis, MD, MBE.
"If there are compelling scientific reasons for excluding one group or another, that's reasonable, the same way you would deal with any other population," Perlis says. "But we basically put the burden on the principal investigator to justify any exclusions on a scientific basis, not just a convenience basis."
Perlis says that the exclusions he's seen don't seem to be caused by bias or malevolence against gays and lesbians.
"It's more often omission, rather than commission assuming that someone is in a heterosexual relationship," he says. "Gradually, as times change, we're coming to the recognition that not only may someone's partner not be a spouse, it may be someone they just live with. And furthermore, it may not necessarily be someone of the opposite sex."
Egleston says he believes some of the trials simply use boilerplate language from previous trials on similar topics, perpetuating the exclusions.
Generalizability, equal access
Perlis and Egleston say there are instances when it's scientifically justified to focus on a targeted population for example, an HIV prevention trial that Egleston found in his analysis.
"There, you can make a good case that the method of transmission of HIV is just so different between heterosexuals and gays and lesbians that you might need separate trials," he says.
But in many cases, he says, such separation isn't necessary. To focus only on heterosexual responses to sexual functioning raises two concerns, Egleston says it may make the research less generalizable and creates an issue of unequal access to trials.
While the situation is similar to past concerns over exclusions of women and ethnic minorities from clinical studies, Perlis says he doesn't believe the scope of this problem is as large.
"I think Dr. Egleston's study shows that it is pervasive in certain types of studies," he says. "His letter is important because it highlights these differences and really forces the research community to ask important questions and say, 'Wait a minute is it only heterosexual men who have erectile dysfunction? Or is this also a problem in some homosexual men?'"
He says the most important question an IRB should ask when presented with this kind of exclusion is: Is there a scientifically valid and meaningful reason for that exclusion?
Egleston expects more repercussions from his findings, based on what he's heard from gay and lesbian advocacy organizations.
"Some groups are trying to get the (National Institutes of Health) to put together some guidelines about this, as they did with women and ethnic minorities," he says.
But Perlis says his own IRB hasn't created any formal procedures for dealing with exclusions of gay and lesbian participants.
"It's been incorporated more under the general idea that we don't want to make a distinction unless there's a rational scientific basis for doing it," he says. "It's a little bit of common sense and a little bit of sensitivity and not necessarily a whole lot of new regulations."