There appears to be yet another reason to scrutinize clinical trials - exclusion of lesbians and gay men from clinical trials in the US, particularly those with sexual function as an end point, according to an analysis that was published in theletters section of The New England Journal of Medicine.
A search using the terms "couples," "erectile dysfunction," and "hypoactive" (related to hypoactive sexual disorder), yielded 243 studies, of which 37, or 15 percent, had explicit exclusionary language. The results indicated that industry-sponsored trials, multi-region trials (according to census definitions), and Phase III trials were the most likely to exclude lesbians and gay men, according to researchers at Fox Chase Cancer Center in Philadelphia.
They also examined eligibility criteria in 1,019 studies using 'asthma' as a search term and found these didn't have high rates of exclusionary language, and no asthma trials excluded lesbians and gays. But they did notice an ADHD clinical trial that required participants be "in a reciprocal relationship with a person of the opposite sex."
The researchers wrote that "exclusion of lesbians and gays from clinical trials is not uncommon...and it's likely that most gay and lesbian patients are unaware their sexual orientation is being used as a screening factor for participation in clinical trials." At the same time, there was no indication people running the trials intended to discriminate against gays or lesbians, according to Brian Egleston, one of the researchers who wrote the letter.
It may simply be tnhat boilerplate language is repeatedly used. "This has really become a copy and paste issue," he tells The Philadelpha Inquirer.
Among the 37 trials restricted to heterosexuals, one studied the use of Levitra, to improve erectile dysfunction after nerve-sparing prostate surgery. A spokeswoman for Bayer tells the paper it was limited to heterosexual males because scientists used a standard measure of erectile success that relates specifically to opposite-sex couples. The questionnaire asks, among other things, whether the male was able to insert his penis into the female reproductive organ.
The ADHD study, which was sponsored by Lilly, looked at whether ADHD was alleviated by Strattera, and examined impacts on "family functioning." "The scales used to examine family functioning were designed and validated for use with heterosexual couples," a Lilly spokeswoman tells the paper. "ADHD can occur in anyone, regardless of gender or sexual orientation, and all families can be affected by it. Lilly supports treating ADHD in any setting and with any type of family."
The Inquirer notes that the National Institutes of Health has guidelines to ensure women and minorities are included in trials, except for a medical reason, but none exist for people of various sexual orientations. However, the paper adds the NIH asked the Institute of Medicine to study and identify priorities in research with lesbian, gay, bisexual, and transgendered populations.
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Any drug company receiving an NDA approval based on these kinds of exclusionary criteria should be forced to state in their labeling what types of groups were excluded from the studies. Perhaps the resulting bad PR might shake them up. I tell you what won't work: getting companies to do studies in special populations as Phase IV committments. These are almost routinely requested by Advisory Committies pre-approval, and are just as routinely almost never performed.
I remember seeing a clinical trial recruitment ad [I think it was for something at Johns Hopkins] that was testing a contraceptive for women....and only wanted _right-handed_ women to apply.
Granted, there have been research studies suggesting that hormonal balances in utero might have an influence on handedness, but why on earth should that affect outcomes for a contraceptive study? Are left-handers somehow more or less fertile than right-handers?
I regret to say that some women, not just lesbians have been treated as second class citizens in clinical trials until fairly recently. I once had a boss who told me that all women of childbearing potential had to use a reliable form of contraception at least three months prior to the start of a particular study. I asked if that applied to religious orders that took a vow of celibacy, and he said no exceptions. In fact, we did have several volunteers from a local convent come by the center; very nice people. In this case I allowed a protocol deviation by not requiring contraception nor did I require pregnancy tests on them. I took the heat from my boss for those moves, but I felt that it was better than embassassing the Sisters.
Wow, Pharmavet, unless this was a phase IV study of a drug with a well known (and safe) repro-tox profile, your actions were completely and utterly inappropriate and reckless. Sorry, I had to speak to nuns and explain why the requirement was in place and, despite my very young age at the time and being uncomfortable with the conversation, it was the right thing to do.
That requirement was not about discrimination, it was about safety (nuns, lesbians and abstinent women have gotten pregnant, some because they didn't always quite act in accordance with the label and others due to rape). You put your company at exceptional risk and could have put any pregnancy at risk as well.
Corp counsel? Maybe they should be the ones who speak to the nuns.
Tell me, ol cranky, did you make those nuns, lesbians and celibates undergo monthly serum pregnancy testing in all of your Phase I-III clinical trials? Did you make the nuns list their brand of contraception on the case report forms at every visit? Did the study coordinators remind the lesbians how to use their diaphrams? Do you even KNOW the seven generally accepted means of female contraception in clinical trials? Do you even know which are the acceptable uses of contraception in women to be used in conjuction with a condom? Have all of the drugs you have studies been determined in repro/tox whether they can transmitted in semen? Did your companies do such preclinical testing, and if yes were the findings reported in every Investigator's Brochure your company ever published? I raise these points to illustrate that the compared to the likelihood of a nun or lesbian getting pregnant (which has never happened in my experience), these other types of liabilities are just as likely to occur.
I do know the generally accepted "medically acceptable" methods of contraception and which methods should be considered acceptable are (and should be) based on potential risk.
I have written trials in which we have allowed double barrier method/barrier + contraception, some in which "abstinence" was acceptable, and some in which we limited to something more instrusive (i.e., hormonal contraception, IUD, etc.) and yes, I did work on at least one compound in which we emphasized that men MUST agree to practice barrier method + spermicide because there was some funkiness with sperm production (I can't remember what it was, it was a long time ago).
In most of my IND studies, I have recommended men use a barrier method as a safety precaution. I have worked both at the site level and in industry. In the industry side, decisions about how stringent precautions to require as part of I/E criteria were based on information known from repro-tox data we had (yes, reported in the IB/IND updates at least as long as I worked on those compounds) and potential risk based on class of drug, etc. I can't think of any studies in which a negative pregnancy test (usually serum HCG wasn't a requirement for enrollment/randomization and tests were repeated at various intervals during the study, though I'm sure I've had studies in which we've used urine tests). Part of the reason I have always been so conservative in requiring contraception beyond abstinence is the fact that we often do not have sufficient repro-tox data and it is always better to err on the side of safety, especially when you don't have thousands of subjects worth of exposure.
Working at the site, it was my first study in which I had to ask a nun about contraception. I was bound by the protocol and it is not the place of site staff to put the study sponsor at additional legal risk if an unexpected pregnancy occurred in a study subject (remember, they face potential liability from the mother/father *and* the resultant child). The fact someone at the staff felt they shouldn't be required to follow the protocol because they deemed the risk negligible does not help the sponsor company avoid a lawsuit.
The first nun, in particular, was > 2 years post-menopausal and was able to be screened. Any nun, just like any other woman, of child bearing potential screened for a study in which abstinence was unacceptable was deemed ineligible to participate if they were not using and/or did not agree to use an acceptable method of contraception as defined in the protocol.
The lesbians I have screened/enrolled (for studies in which barrier method was acceptable) were reminded that, as part of the study they agreed to be fastidious with use of contraception if they engaged in sexual activity in which pregnancy was even remotely possible. Just like women who claim they are abstinent, there are women who identify as lesbians (even those in relationships) that do willingly engage in sexual activity with men on occasion (not every gay person is a big fat 6 on the Kinsey scale and, as shocking as it may be, there have been nuns who violated their orders and had sex with a man).
As a woman, while I understand that people (even medical personnel) are uncomfortable having frank discussions about need to avoid pregnancy and the methods required by a particular study with potential study subjects (and/or their parents), I do not understand why some people seem to think this is a political discrimination issue.
As an industry professional who thinks protocol adherence, safety and ensuring we get good, quality data, I am perplexed why another industry professional would decide unilaterally to put their company at risk because they perceive the risk as being smaller than those who approved the protocol and/or the legal department.
Contraceptive failure rate publications consistently make the point that most of the time failure is not due to product defect but due to incorrect and/or inconsistent method of usage. Therefore, honestly speaking how likely do you think that a woman that is being asked to use a contraceptive for the very first time (just to meet the demands of a study protocol with no intention of heterosexual activity) will be to use the product consistently and correctly? Knowing that many women have difficulty with AE's in their first usage of oral contraceptives, I think that infact many first time users will NOT use the product properly; they just won't admit it to the study coordinator.
Therefore while I understand your liability concerns, I think that you're just engendering a false sense of security if you think that all of the first time OC users will use the product correctly and consistently.
There's no false sense of security at all, we're aware of contraceptive failure rates. We do pregnancy routine tests on women of cb potential on a regular basis during study participation despite knowing they're supposed to be compliant with contraception to minimize risk and know when there may be an issue so we can d/c treatment as early as we can to limit embryonic exposure as best as we can.
For the record, I don't put people on contraceptives so they can be enrolled in a study (hence usually requiring them to have been using them at least a month prior to screening) and, when working at the hospital, there were some (very rare) instances in which we had to provide patients (male and female) with some sex ed.
That said, the attitude of "well some people lie, and there's contraceptive failure rates" so there's no reason to try to decrease risk by requiring them is defeatist and does not justify a unilateral decision not to comply with a study protocol. BTW, and this drives me nuts that I have to point this out to some people, if they really abstain from all sexual activity that could lead to pregnancy and remain so during a study that permits use of barrier method/spermicide, the point is moot. The risk of pregnancy in those cases is due to something pretty heinous.
Clinical Trials also represent the last and only avenue for treatment and extending life, for many patients with end stage disease. By excluding Lesbian and Gay patients, clinical trials are preventing access to life saving treatment. Darryl Mitteldorf, LCSW Executive Director Out With Cancer - The National LGBT Cancer Project http://www.lgbtcancer.org