by Anette Breindl, PhD
Twenty-four years after the National Institutes of Health (NIH) established the Office of Research on Women’s Health, and 21 years after the NIH Revitalization Act of 1993 first required that women be included in clinical trials, certainly the letter of the law has been achieved. Women are now the majority of participants in NIH-funded trials.
The whole picture, though, is much more complex, and more uneven. Increased participation has led to gains in some areas. But in other areas, far too little is known about whether and how drug responses and optimal treatments differ for men and women.
Not very long ago at all, the lack of women in clinical trials was due to outright discrimination. In 1977, the FDA barred women of childbearing age from participating in most early stage clinical research, a ban that was officially recognized as detrimental to women’s health in the mid-1980s, when the NIH first adopted guidelines (that remained widely ignored until the NIH Revitalization Act of 1993) encouraging the inclusion of women in clinical research.
These days, the issue, as it often is with women’s issues, is more complex.
It is clear that there has been progress. But it has been uneven, and perhaps surprisingly, there is no obvious relationship between the success and whether a condition is specific to females or not.
Breast cancer, which is overwhelmingly a women’s disease, was singled out in a 2010 Institute of Medicine report on women’s health research as a condition where there has been much progress. Ovarian cancer, on the other hand – which can be due to the same underlying genetic factors in some cases – has seen little progress.
In diseases that can affect both men and women, progress has been equally mixed. The treatment of cardiovascular disease has made strides in women; of lung cancer, not so much.
And even in trials in which women are equally represented, the data generated on their unique responses often goes to waste.
Only a minority of trials analyze their subgroups separately – and so even if a treatment has different effects in men and women, they may not be recognized if such subgroup analysis is missing.
The Society for Women’s Health Research (SWHR) is one organization that is pushing to make such subgroup reporting mandatory in practice. At an April FDA hearing on issues and challenges with the collection, analysis and availability of demographic subgroup data, SWHR president and CEO Phyllis Greenberger urged the FDA to “enforce existing regulations and guidance that require subgroup reporting and analysis be submitted by sponsors for the safety and effectiveness of all medical products … The FDA should finalize draft guidance for sex-specific analysis they proposed in 2011 and issue similar guidance for race and ethnic minorities and the aged.”
The SWHR has long lobbied for the inclusion of women – and minorities – in medical research as part of a broader focus on “transforming women’s health through science, advocacy and education,” according to the organization’s mission statement.
Overall, the FDA and NIH “have improved a lot,” Phyllis Greenberger told BioWorld Today. “If nothing else, they have improved in the recognition that it’s important.” And that improvement has been accelerating. “In 2014, we have probably made more progress than in the 24 years leading up to it.”
But just how much progress has been made remains impossible to know.
For one thing, the NIH has “never broken down the trials by diseases,” Greenberger pointed out. There is the real possibility that an overall participation rate of 50 percent may be the net result of a few large trials that are made up exclusively of women, plus many trials where women are still underrepresented.
Breast cancer, for example, is a very active trial area – much more active than its closest male-specific pendant, prostate cancer – and so breast cancer trials alone may contribute disproportionately to the overall number of women in trials.
With the passage of the 2012 FDA Safety and Innovation Act (FDASIA), Congress mandated that the FDA issue a public report on the extent to which demographic subgroups including sex, age, race and ethnicity, are included in new drug applications.
In late November, as part of that effort towards greater transparency, the FDA released demographic “snapshots” of demographic information for the trials that led to the approval of six drugs in May and June of 2014. If they are snapshots, they are the equivalent of an embarrassing Instagram post.
While the majority of the trials did include separate analyses for men and women, patients above and below 65, respectively, were only analyzed separately in half of the trials.
And the analysis of racial subgroups was simply dismal. In only one of six trials – that for Jublia (efinaconazole, Dow Pharmaceuticals Inc.), approved in June 2014 for the treatment of onychomycosis or toenail fungus — was minority participation sufficient to enable a separate analysis of different ethnic subgroups. That analysis found a trend towards greater efficacy in Asians, either because there was no difference or because the groups were too small – the data can’t say. And according to the FDA snapshots web site, “difference in side effects by race was not evaluated.”
The data prompted the Society for Women’s Health Research to issue a press release stating that “We commend the FDA for the effort in collecting and releasing these data to the public and we believe it is an initial first step towards reducing the disparities and lack of information on sex and ethnic differences. But as is evident, the percentage of minority participation is dismal and while there are women in all of the trials, the numbers are not statistically significant to reach any clinical relevance.”
Not all trials are NIH-sponsored, either. Data from industry trials is largely confidential, but what data there is suggests that women are still underrepresented.
Industry, too, at least has an awareness of the problem. “Diversity in trial enrollment is something that we constantly worry about,” Jesse Berlin, vice president of epidemiology at Johnson & Johnson, told BioWorld Today.
