Advancing Gender Equity in Biomedical Research with Nicole Woitowich, PhD

[00:00:00] Erin Spain, MS: Welcome to Science in Translation, a podcast from NUCATS, Northwestern University Clinical and Translational Sciences Institute. I'm your host, Erin Spain. It has been 30 years since the NIH revitalization act was signed into law. The landmark legislation passed by Congress in 1993, required the inclusion of women and minorities in federally funded research. Today we have Dr. Nicole Woitowich joining us to discuss the impact of the NIH revitalization act on women's health research. She is the executive director of the NUCATS Institute and also a research assistant professor of medical social sciences at Northwestern University Feinberg School of Medicine, where she has studied the implementation of the national institutes of health sex as a biological variable policy. She joins us today to discuss her research and share insights into the progress made and the challenges still faced 30 years after the NIH Revitalization Act. Dr. Woitowich, thank you so much for joining me today.

[00:01:10] Nicole Woitowich, PhD: Thank you for having me, Erin.

[00:01:12] Erin Spain, MS: Well, tell us a little bit about you. You've held different roles here at Northwestern. You're both a scientist and an administrator. Tell me about you and your work.

[00:01:21] Nicole Woitowich, PhD: I'm formally trained as a biochemist, and while I loved being at the bench, I quickly realized that one of the things I loved more than perhaps western was talking about science. And so early on in graduate school, I started exploring different opportunities that would give me experience and expertise related to science communication. And I really fell in love with science policy, public engagement with science. And at the same time, I was doing a lot of work related to the advancement of women in science and medicine. And I had developed a program for middle school and high school girls to get involved with science up in Lake County. And so some of this work really kind of led me to what we would say in the old days was a non-traditional career path, and I hate calling it that, but at the time that's what it was. And so, I actually came to Northwestern in taking a very administrative role where I got to continue some of the research I was doing and the work I was doing surrounding women's health, the advancement of women in science and medicine, and also science policy. And so I've been able to fuse over the past several years this really unique career opportunity where I get to bring my expertise as a scientist and really my love for administration together. And I get to bring my whole self to work at Northwestern. And over the past several years, I've worked in several different units. And most recently in this past summer, I joined NUCATS as its executive director, where I oversee our centers and programs. And I get to work with a really terrific group of investigators and a wonderful staff that helps advance and accelerate clinical and translational science here at the university.

I would love for you to tell us a little bit more about your research.

So some of the research I do I broadly consider myself falling under the umbrella of the science of biomedical science. So what that means is we use scientific tools and methodologies to examine the scientific workforce, the research questions we ask, the policies that impact it. But all of mine focus on biomedicine and typically academic medical institutions. I've done some work that relates to public engagement and how scientists communicate with non-experts. I've done work related to gender disparities in the biomedical workforce. And one of the things that I'm really excited to talk to you about today is I've done a lot of work looking at the implementation of the National Institutes of Health Sex as a Biological Variable policy.

[00:03:50] Erin Spain, MS: Yes, we are going to talk about that today. This marks the 30th anniversary of the NIH Revitalization Act. Can you paint a picture for me of what it was like before this act for women in research and what's happened since.

[00:04:05] Nicole Woitowich, PhD: Of course, so in the late 1970s, the Food and Drug Administration released guidance that women of quote "childbearing potential" should be excluded from phase one and phase two clinical trials. And this was at the time in response to the thalidomide tragedy of the late 1950s and early 1960s, where along with several other drugs, it was discovered to cause severe birth defects. Luckily, this drug never went to the market in the United States due to the heroic efforts of a famous woman physician, Dr. Frances Kelsey. But despite this policy being well intentioned and enacted in order to prevent harm to some of the most vulnerable populations, it actually had a lot of significant unintended consequences. And so then in 1985, after the FDA put this ban in place the U. S. Public Health Service generated a report, and they found that really this was detrimental to women for excluding them from these studies, and that biomedical and behavioral research should be expanded to include conditions and disease related to, or more prevalent in women across age groups.

 And so then in 1986, in response to that, the NIH adopted language saying that women should be included in clinical research. However, a 1990 government accountability report found that the NIH had made very little progress in the area and said that the policy wasn't well communicated or understood within the research community. So that's what really prompted the National Institute Institutes of Health to take action. They established the Office of Research on Women's Health under the directorship of Dr. Vivian Pinn with the charge of ensuring that women's health is appropriately represented across NIH funded research. But it really wasn't until 1993 when it became law that women were included in clinical research. And the law stated that " it was to ensure that trials are designed to be carried out in a manner to provide valid analysis of whether the variables being studied in trials affect women or members of underrepresented minorities." So I want to keep that language in mind as we kind of talk through what the future holds after this policy was put in place, because some of the same language we are hearing again today in 2024.

[00:06:27] Erin Spain, MS: Well, from a translational science perspective, what advances in women's health do you think can be attributed to this mandate that happened in 1993? Have those advances translated into policy or actual medical practice?

[00:06:42] Nicole Woitowich, PhD: So I think there have been a lot of tremendous advances in biomedicine in the past 30 years. And I do think we have specifically developed more targeted studies and acknowledge the gaps in women's health that exist. That I will say has been really great. However, where I think there has been a challenge is the timing and pace of progress. I think that it's taken a very long time for us to see the results of that law come to fruition. And I'll give an example of where, even though this took place and was put into law in 1993, today we are still having some gaps. One of the major things I would say is during the COVID-19 pandemic, it was a really tremendous opportunity for the biomedical research community to come together and quickly develop a vaccine. And one of the most interesting things to me was that when the COVID-19 vaccines were developed, while women were included in the studies, their data was rarely analyzed by sex. And then, once the vaccines were rolled out, we didn't have any guidelines for women who were pregnant or breastfeeding because those women were excluded from the phase one and phase two clinical trials. So we've still got some lingering issues from the history of biomedicine. So we are still very protective of women who are of "childbearing potential", right? So even though we're including women, a lot of studies will still exclude pregnant and breastfeeding women as part of their criteria. And so when we launched the vaccine during the pandemic, a lot of women didn't know what to do, if it would be safe for them, and because we had such little data, a lot of myths then and misinformation came of that, stating that it might cause infertility, et cetera. So I think that's one area, where if we just had included those groups of women from the get go, we wouldn't have had this issue. Because we already have so much data that vaccines are generally safe and tolerable in pregnancy, there wasn't a good excuse to exclude them. We had another issue with the COVID-19 vaccines where after receiving them, women were reporting experiencing disruptions in their menstrual cycles or changes in their menstrual cycles that were pretty significant. And instead, we had this outpouring on social media, sharing of information, trying to understand, is this normal? Did you experience this? We didn't have that information because data regarding menstrual health was not included or evaluated. And so then the NIH had to backtrack and issue, you know, calls for funding and research on this topic after the fact, when we're not even thinking about it. Like, that should just be a part of our normal study design to capture the experience of women throughout their lifespan. And that includes when they're menstruating, if they're pregnant, if they're lactating, like we've got to be able to capture that in data or else we're doing half the population a disservice?

[00:09:52] Erin Spain, MS: So some of your work has been following up on the implementation of the revitalization act, as well as subsequent policies from the NIH relating to this original mandate. Tell me about this.

[00:10:04] Nicole Woitowich, PhD: So even though the 1993 Revitalization Act required the inclusion of women in clinical trials, it did not speak to other research studies that involved, say, mice or animals. And in response to that, a lot of the work that was done historically in the basic sciences used only male mice or cells. So a lot of the things in our drug development pipeline and developing discoveries for therapies and novel treatments, those fundamental studies were done exclusively, almost exclusively in males. It wasn't until the NIH implemented a policy in 2016 that required federally funded investigators to "consider sex as a biological variable," or the SABV policy. And so what this policy does is it asks that investigators consider how sex can be integrated into experimental design, analyses, or reporting.

[00:11:02] Erin Spain, MS: You found that there's room for improvement, that scientists could be doing more with this policy. Tell me about that.

[00:11:10] Nicole Woitowich, PhD: So some of the work that I've done kind of as a follow up to this policy is to see how we're doing. Are we considering sex as a biological variable? And so when we looked at some publications, we found that, while scientists are including, compared to over a decade ago, we are including both sexes in our research, which is great, we're still failing to analyze data by sex. And that's a real problem. And not only are we failing to analyze data by sex, there was an even more worrisome trend to me that I saw was that in some publications, scientists were not even reporting the number of subjects they used by sex. They would say, we used both male and female mice, but they wouldn't tell you how many. And so this becomes an issue of rigor and reproducibility. So if you go to replicate a study that I did and I said, oh, we, we use both sexes. Well, you don't know if I used nine male mice and one female mouse, or if I used, you know, 25. So, if I go to repeat that and I can't get the same data as you, I'm beginning to question if it's the way I did the study, if it's with my reagents, leading to increased time, number one. But then use of resources. And so this is, our work is, the majority of it is funded by the U. S. taxpayer. And so I think that without being really intentful and having that clear reporting and transparency, we're doing the taxpayers a disservice and our colleagues who are going to try to build upon our work a disservice as well, when we fail to include the most basic information.

[00:12:39] Erin Spain, MS: There's another group of women that I want to talk about in the NIH Revitalization Act, it also specifically addresses equitable inclusion of minorities in medical research. Talk to me about that intersectionality in women's health and how has this legislation impacted women of color?

[00:12:56] Nicole Woitowich, PhD: Oh, this is a great question. I think there are a lot of underrepresented groups in clinical research. And when we talk about women being underrepresented, we also need to think that even that's even much more of a barrier for women of color and women who have been historically marginalized by the biomedical research community and who, for good reasons, have hesitancy and trust in engaging in clinical research studies. And so we know a lot now about the social determinants of health and how your health and well-being can be ascribed by your zip code and where you grew up, where you live, the environmental factors. So I think by not engaging all communities and populations of people, we're doing ourself a disservice. Women are not monolithic, you know. We all have different backgrounds, and we need to be able to capture those experiences and variables in our data. So I think one of the things that we really need to work on is building up trust in biomedical research again. And the pandemic didn't do us many favors either, but I think we have opportunities to really expand and learn from the pandemic and what worked and what didn't work in engaging different groups, engaging people who are marginalized, underrepresented and in hopes of kind of building those bridges, but it doesn't come easy or without a lot of work to really establish relationships and bi-directional communication.

[00:14:24] Erin Spain, MS: I mean, it's true that female participation rates in some studies remains very low. Can you talk to me a little bit about that? You know, why is this happening? Do you think it is an outreach issue or is there something else going on?

[00:14:37] Nicole Woitowich, PhD: So there's a multitude of reasons why women's participation in research --, there are barriers to that, right? One is time. Participating in research, depending on the type of study, it requires you to invest time, time that women might not otherwise have. It requires some level of proximity in certain cases, which is why a lot of research studies out of major academic medical centers come from people surrounding it in the region, which is why it's really important that we think about rural communities and rural health and how we engage those who live maybe not within a 20 mile radius of, say, a Northwestern and how they can participate in studies. And while we've had the advent of, you know, more digital opportunities to advance health, there are still things that require in person participation. So some of that is not having appropriate, you know, access to child care to be able to then come to a site to participate in a study not having access to transportation. So I think there's a lot of things that we can do as a research community, which I think depends on federal investment in those resources so that people can fully participate.

[00:15:47] Erin Spain, MS: What about at the level of NUCATS members? What can folks who are members of NUCATS do when they're implementing their studies and designing studies to be thinking about women and minorities and including them in the research?

[00:16:00] Nicole Woitowich, PhD: I think one of the aspects that I would hope that most people are doing is, first of all, capturing data using best practices. So, right? Sex and gender are two different things. Sex is a biological variable, and gender is a social construct. And so, we want to be capturing data on sex, but if you, especially if you are working with human studies with people, gender is a spectrum. It's fluid and it's non binary. So capturing that data is important. And also we want to consider how when breaking down our data, when disaggregating our data, that we take a look at studies by sex and by gender, because those could be two different things. But one of the, I guess, pleas to the research community that I have is analyzing data by sex. I mean, that will start to give us clues about if there are differences in diseases, disorders, treatments, therapies. We have to start there. And I use this as an example whenever I talk about sex differences, that there was a study that came out a couple years ago that looked at different treatments for glioblastoma, which is a really deadly form of brain cancer. And they ended up just deciding to, let's just break down our data by sex and look at the treatment response by males and females. And what they found was that women actually had a much greater response to treatment. And so that kind of prompted them to think, well, how can we develop a better therapy then? If this is working for women, that's great, but why is it not working for men? And what is the biological mechanism which we can exploit to figure out how this can work better in men? So a lot of people think when we talk about studying sex differences or gender differences that it's all related to women's health. It's not. It's to help us develop better treatments and therapies for everyone. And sometimes there are differences based on sex. And so figuring that out really helps everyone, not just women.

[00:17:55] Erin Spain, MS: Another thing I wanted to ask you about, because this is a field that you study, women and women of color generally are not well- represented in the biomedical workforce, especially in leadership roles, and this is something that you study. As a woman yourself in the field, what impact do you think this underrepresentation has in light of women's health, and what progress has been made or needs to be made?

[00:18:19] Nicole Woitowich, PhD: This is a fantastic question, and I think it underpins a lot of what we're talking about. So historically, the biomedical research enterprise was led by men. You know, even healthcare. Everything we know about science and medicine really was built on generations of data from men. And now that women are approaching parity in medical school, maybe even more than 50 percent of biomedical PhDs are women. Yet in leadership roles, there is still that major gap. And in those leadership roles, that's where you're making research priorities, you're leading the investigations, determining the appropriate analyses, etc. And so, what we've begun to see in some of the data is that there is a gender difference in the way scientists analyze data by sex and gender. That women are more likely to analyze their data by sex than men. So you've got that component of that, but it also bleeds over into patient care where there's gender concordance that patients, women in particular, have better patient outcomes if their physician is also a woman. And so I think this becomes a question of, do women study this and analyze their data by sex more frequently because they're more acutely aware of the conditions that impact them? Or are some of these concerns not on the radar of men? And you'll see women are often the ones driving forth a lot of research in this area.

[00:19:49] Erin Spain, MS: And how does the underrepresentation of women and women of color in clinical research leadership roles impact funding opportunities as well?

[00:19:58] Nicole Woitowich, PhD: We need more funding opportunities for women's health research. So this is the question, is it the chicken or the egg? Who comes first, right? And if there are dedicated funding mechanisms that look at sex and gender and look across the lifespan and health of women, then, if there's an opportunity, even beginning with K and T awards that are specifically focused on that, I think we'll begin to develop a career path and more of a workforce bench for people who are really dedicated to this area of research. But, if there's no funding, we're not going to have people coming into this area, right? They'll go where there is funding available to advance and succeed. I think that's part of the issue is having funding mechanisms available. And I will say the Office of Research on Women's Health at the NIH has really done a tremendous job of trying to provide those opportunities, but I think we should ask for more because I think we're still at a disadvantage when it comes to this. A report by the Women's Health Access Matters Group, WHAM, found that if you just double the budget of what's currently being invested in women's health right now by the NIH, you can generate over 14 billion in the U. S. economy. So, it extends beyond just a research issue. It is an economic issue because the more we know about women's health, the more we can preserve their health, help promote their ability to stay in the workforce, reduce cost to the healthcare system. I mean, it's not just an isolated data point.

What resources are available to NUCATS researchers who want to make sure that they are following the policy, not only that, but exceeding expectations? What resources are available?

So one of the ways I think that NUCATS can help investigators in considering and examining sex and gender in their research. First we have the Biostats Collaboration Center led by Dr. Leah Welty. Her and her team can really advise investigators on the most appropriate way to analyze their data by sex or gender. Then we also, through our affiliation with the CTSA Network, have recruitment resources as well as opportunities to connect with different groups of people across the nation, across Chicagoland, in making sure that our recruitment strategies are really driven by best practices and put the people at the center of participants. and, I think this is an area that's tremendously important to ensure that we have gender equity and parity within the workforce. But really I think the retention and advancement is, I think, what's key right now. So, how can we promote women in leadership? How can we help support trainees as they are developing their career and promoting them through different pathways? And I think, you know, NUCATS has several different training mechanisms where we support Individuals in the translational workforce, so that's another important area, as well as increasing the representation of women clinical trialists, because I think that's really important to have that perspective when ensuring that our design and our analyses for clinical trials are incorporating the perspectives of women across the lifespan.

[00:23:13] Erin Spain, MS: As you mentioned, gender diversity is also important. The fact that there are categories that are not just man or woman. How do you think researchers are handling this now? And where do you see room for improvement?

A lot of the data we're looking at is based on a binary gender system where it captures gender as men or women with not actually considering the perspective of gender diverse individuals. And so I think that's another area that we really need to consider when we are evaluating and assessing data by gender, making sure we're capturing the representation of gender diverse individuals and making sure that their data isn't erased. Because sometimes when you go to evaluate your data, those data can get collapsed into different categories. And so, finding ways that we can make sure either through merging of data sets, making sure that the representation of gender diverse people are incorporated. I think we're seeing that investigators are, especially in quantitative study design, making sure that they're asking questions that capture the diversity there are in genders. So, not just asking man or woman, they're asking about gender non conforming, transgender. They're asking questions about biological sex at birth and asking about if you're taking different hormone supplements or are under hormonal treatments depending on the different stage of your life. So I think that this is really important to capture. As we wrap up today, if there's one thing that you would like NUCATS investigators to take away from this 30th anniversary that just passed of the NIH Revitalization Act and thinking of what we could be doing going forward, what would you like them to remember or to think about?

[00:24:53] Nicole Woitowich, PhD: I think it's really helpful that we consider that women's perspectives are included in our data, and that's through data analyses and reporting and transparency in that. I also think it's really helpful to get the perspectives of women if you are designing studies that involve having to have people come in to participate in studies in an office or for even a virtual setting. Get input. Get some feedback. There's resources and experts available who can talk you through this and figure out the best way to design your studies, your analyses, so that the perspectives of women and gender diverse people are included, and that your data is analyzed appropriately and that it's transparent and rigorous, and that we can all work together to advance biomedical research enterprise. We don't have to do this alone. Resources are available. I think by considering sex and gender in our research, we're opening up new avenues of exploration. So I think a lot of new discoveries and learning will come from there, and ultimately, I think we'll have the potential to directly benefit patient care and lead all people to healthier outcomes.

[00:26:03] Erin Spain, MS: Well, that is a great message to leave us with today, and I want to thank you for your time and all the work you've been doing on this topic. Thank you so much.

[00:26:10] Nicole Woitowich, PhD: Thank you so much, Erin. I really appreciate it.

[00:26:12] Erin Spain, MS: Subscribe to Science in Translation wherever you listen to your podcasts. To find out more about NUCATS, check out our website, nucats.northwestern.edu.