What factors could be excluding transgender people from oncology clinical trials, and what can we do to make them more inclusive? Dr. Westin discusses this important issue with her guests, Dr. Ash Alpert and Dr. Lola Fashoyin-Aje.

TRANSCRIPT

Dr. Shannon Westin: Hello, everyone, and welcome to another episode of the JCO After Hours podcast. This is when we get down and dirty into manuscripts that are published in the Journal of Clinical Oncology. And I am so excited about our topic today. We are going to be discussing a Comments and Controversies article that was published online in JCO October 27, 2022, and it's entitled "Addressing Barriers to Clinical Trial Participation for Transgender People With Cancer to Improve Access and Generate Data." And please note all authors do not have any conflicts of interest.

It is my great honor to be accompanied today by two of the co-authors on this important manuscript. First is Dr. Ash Alpert, and they are an Agency for Healthcare Research and Quality T32 Postdoctoral Fellow in Health Services Research at Brown University. And I'm so excited to note that they will be joining Yale as an Instructor of Medicine quite soon.

Welcome, Dr. Alpert.

Dr. Ash Alpert: Thank you.

Dr. Shannon Westin: And I'm also accompanied by Dr. Lola Fashoyin-Aje, and she's the Associate Director for the Oncology Center for Excellence at the Food and Drug Administration.

Welcome.

Dr. Lola Fashoyin-Aje: Thank you so much. It's my pleasure to be here.

Dr. Shannon Westin: So we'll get right to it. I'm so excited. I think this is a topic that many of us, almost all of us, are needing a lot of support, needing a lot of education, and I think let's start by level setting. So what we're going to be speaking today is about transgender people. These are persons whose gender identity does not correspond with what is commonly expected for them based on the sex registered for them at birth. Do we have information about how many transgender people will be diagnosed with cancer and what are the most common cancers they face?

Dr. Ash Alpert: So, given many barriers to data collection about transgender people, we actually have very little quality data about transgender people's health outcomes in general and specifically around cancer incidence and outcomes. But what we do know is that at least 0.7% of the US population is trans. And the limited data that we have suggests that transgender people don't have higher rates of cancer than anyone else. So if you look at the numbers for the US, that translates into there being about 2 million transgender people in the US and about 900,000 transgender people who are diagnosed with cancer in their lifetimes.

The other data that we have is that it looks like transgender people who are on hormone therapy and have surgeries, therefore less of a chance of being diagnosed with prostate cancer. If people have had bilateral mastectomy, they have less of a chance of being diagnosed with breast cancer. And it does seem like from retrospective data that it's possible that people on estrogen therapy are more likely to be diagnosed with a breast cancer. So basically, all things that we would expect. And given that about one in 10 transgender people in the US are living with HIV, it's likely that trans people also have higher rates of HIV-associated malignancies.

Dr. Shannon Westin: And I wonder, what about screening? I would think that this could be a real difficulty. If people are misgendered, they may not be offered the appropriate cancer screening. I know I'm getting a little bit away from the crux of your talk, but I think this is so important.

Dr. Ash Alpert: Yeah. So there's a number of barriers to screening, and two of the ones that come to mind immediately are that trans people, in general, have negative experiences with physicians. So one study suggested that one in three transgender people had had a negative experience with a physician in the last year and that given this, about one in four trans people avoid necessary health care. So that automatically means that trans people aren't getting screened. And then I think the other important thing that you're bringing up is that because of the ways that certain types of health care are associated with gender—so, in other words, getting a cervical PAP smear is associated with being a woman in the ways that we talk about those tests—there are many other barriers to trans people getting cancer screenings. And we do have some data from the literature that suggest that trans people have lower rates of cancer screenings than the general population, likely because of these two, if not more, reasons.

Dr. Shannon Westin: I would anticipate that this could potentially impact, obviously, diagnosis, but then also cancer-related outcomes. Do we have data on that? I know that a lot of this is a data-free zone, so I appreciate you kind of just reviewing what we do know.

Dr. Ash Alpert: So Sarah Jackson published a paper that suggested that in some types of cancer, trans people are diagnosed later with more advanced-stage disease and have poorer outcomes. But, again, it's very limited data.

Dr. Shannon Westin: Anything else that you want to talk about on that second question before I move on to the next one?

Dr. Ash Alpert: Yeah. I mean, I think that the question you raised about cancer screening is also true about cancer treatment. And I think we may get into this in the paper as well, that certain types of cancer—like ovarian cancer, prostate cancer, testicular cancer, and endometrial cancer—are often, in the ways that we talk about them and the ways that we write about them in guidelines, associated with specific genders. So it's not just individual oncologists, but all oncologists are steeped in this language that associates specific types of cancer with gender. And so then it becomes not just something that's happening in the language between two people, an oncologist and a patient, but also in the optics of the clinics, the names of our clinics, our titles as physicians, that all may inadvertently and implicitly exclude transgender people from care.

Dr. Shannon Westin: It's interesting. As a gynecologic oncologist, I feel like I was just talking about this with someone, about this idea of women's cancer care areas and these very specific gendered kind of comprehensive cancer centers that are incredibly exclusive to this group of people. So I'm really glad that you highlighted that. It's very timely, too, because I think our group is talking about how do we want to name our center. So I appreciate this.

So this is an area of interest greatly to me is clinical trials just in general and participation in clinical trials and encouraging inclusivity and improving representation in clinical trials. So we've seen this. We've seen this in gynecologic cancers and other cancers that, obviously, clinical trials change the standard of care, but they also provide better outcomes for patients and people with cancer. So do we know—are there any data about the current state of participation of transgender people in clinical trials?

Dr. Lola Fashoyin-Aje: Yeah, I mean, thank you for that question. The fact of the matter is that we don't really know what the current state of participation in clinical trials in oncology is. This is really part of the reason why the Oncology Center of Excellence at the FDA convened the mini-symposium that we're describing in the paper and the reason why we wrote the paper. I think the assumption that we make is often that the numbers are probably not great. But since we do not routinely collect the data that would help us to identify transgender individuals as part of clinical research, even if transgender individuals did participate in a trial, we would have no way, really, of knowing.

We also do not really have great data regarding what the benchmarks for participation would be because, as Dr. Alpert mentioned before, we don't routinely collect this data as part of the epidemiologic surveys that inform our understanding regarding the populations that are affected by cancer or even at the point of care. It's really very heterogeneous, the types of data that we collect and whether the way that it's collected is optimal. So we really have an information and data deficit that is quite significant for this population that really is needed to be addressed in both sort of systemic ways, but also in our individual settings in the way that we collect data and the way we engage with this population.

Dr. Shannon Westin: Are there any interventions or outreach efforts right now ongoing to start collecting these data or even to start raising awareness that these data should be included? Because I'm just thinking of all the NCI trials we do and industry trials and the data that are collected, and you just don't see this, right? This isn't part of the data dictionary typically, right?

Dr. Lola Fashoyin-Aje: Dr. Alpert can speak to some of this as well. We reviewed this as part of the paper-writing process. But there are ongoing efforts to identify the best ways to collect data and identify the opportunities where we could improve upon where some data is already being collected but also making sure that there's sort of structural measures are being taken to ensure that as we collect those data, that we are handling those data appropriately. Because this is a population that really suffers disproportionately bias, discrimination, violence. And so we want to make sure that as we are encouraging folks to provide this kind of information, because we really think that it will help improve their clinical care outcomes as well as clinical trial participation access, but that we are also, at institutional levels, addressing some of the areas that are either explicitly or inadvertently creating barriers and creating environments that are not supportive or that are not safe for this population.

And so there are ongoing efforts. I can say that at a federal level, there's increasing recognition that we really are not doing a great job. And I think there are some recommendations for how to collect these data in surveys, but it may not necessarily be applicable to what we need to know in the clinical trial setting. And so there's so much work to be done still.

Dr. Shannon Westin: Great. Dr. Alpert, do you have anything to add there?

Dr. Ash Alpert: This could be a very long conversation, but I'll briefly say that there are a couple of things that are happening right now that suggest that things are moving along. One is that NCI put out an administrative supplement for NCI-designated cancer centers to apply for, through which they can begin to collect sexual orientation and gender identity data at the cancer centers. So that means that now that that's happened, cancer centers across the country are testing measures with which to collect sexual orientation and gender identity data.

And at Yale, I'm a part of a research team that is beginning to collect data, both based on some national recommendations and also based on some of our individual research and ideas about how to collect this data in a way that really provides transgender people the autonomy to identify and describe themselves in ways that really feel right to them and to us. I think there are exciting things in the works. But I also really appreciate the conversation we just had about safety because in my qualitative research, what I've found over and over again is that often transgender people are put into a very difficult situation where if they come out to their clinicians, they experience stigma and sometimes violence, and when they do not tell clinicians certain things about their medical histories, including that they are on hormone therapy or that they've had particular surgeries or specific information about their anatomy, then they're put in the position where they may not be receiving the best care because their clinicians don't have all the appropriate information. It's a very difficult situation for individual patients and also for those of us who are thinking systemically and structurally about how to improve what we know about cancer epidemiology and how to provide the best care for transgender people with cancer.

Dr. Shannon Westin: I mean, I think that kind of dovetails nicely with my next question, is really trying to understand how some of these structural barriers might impact participation in clinical trials. So what are the barriers that are keeping these people off of these trials? And maybe how can we start to strip those barriers away? All in that, I think, highlighting that highlight of safety and inclusion.

Dr. Fashoyin-Aje: I can start by touching upon some of this. I think one important area has to do with language, the language that we use, the signage that we use. And sometimes it's not even just what is explicitly stated but also what is omitted, what is silent, which may have adverse consequences as well. And that could be even worse because then you're sort of rendering a population invisible or basically really kind of reinforcing this idea that they're just not seen.

So I think one area that is really quite relevant in the regulatory setting has to do with eligibility criteria. And I think often, those are silent with respect to transgender individuals because, number one, people just may not know, so they just could fall off, and they just are not thinking that this is a population that I need to explicitly ensure that they are invited to participate in this trial. And then I think other times, there are a lot of assumptions made about whether or not it is safe, and some of those assumptions may be supported, and some of them are not supported. So I don't want to trivialize whether or not an individual is receiving hormonal therapy, whether or not that may have adverse impact on their outcomes in the clinical trial; that could very well be the case, but we just don't know most of the time, and so we don't explicitly state one way or the other.

I think the other way is just sort of the kind of language that we use. Calling individuals women may exclude certain people; they may not be sure. I think a lot of people when they hear women, they're not thinking about transgender women. So, in the paper, we really highlight opportunities where we could be more specific about the language that we use so that it is clear what we're referring to. So if you are designing a study that is meant to test a drug in patients who have ovarian cancer, say that. You don't need to say "females with ovarian cancer" if you're not really explicitly—there would really typically not be any reason to exclude people just based on that without more information. And often that more information isn't actually collected.

So I think that's sort of part of what we are trying to highlight here, that there are things that can be done at a micro level, but there are things that can be done at a macro level, and really culture change is a really important part of this, this sort of thinking like which of my neighbors might want to be included in this trial? Which one of my children's friends might want to be enrolled in this pediatric trial? And just kind of thinking a little bit out of the box and thinking of ways to be more inclusive and then have reason to exclude rather than to start from a baseline of exclusion and then inviting people.

Dr. Ash Alpert: Yeah, I think we highlighted three main areas of eligibility criteria that may inadvertently exclude transgender people. One was mentioning sex or gender in the inclusion or exclusion criteria when it's unnecessary. The second is mentioning hormone therapy but not specifically and explicitly stating whether hormone therapy used for gender-related purposes would be included in that. So, for example, we, I think, in the paper, describe a prostate cancer trial that excluded people with prior hormone therapy for prostate cancer, but I think it would be very confusing for me if I were a transgender woman on estrogen therapy, whether or not that excluded me from the trial because it's not specifically called out. And then we still see blanket exclusions for people living with HIV despite all the discussion and commentary about this. And that necessarily excludes many trans people because one in 10 transgender people in the US is living with HIV.

And then I think we also, in the paper, highlight that there's actually been qualitative research done with transgender people looking into the facilitators and barriers to participating in clinical trials, and we summarize them just saying that trans people suggest that they're more likely to participate in trials that are led by or staffed by transgender researchers, that explicitly benefit transgender communities, that provide resources, that address financial barriers, barriers to transportation, and that are integrated into health care that transgender people are already receiving.

So I think there are clear ways for cancer centers, principal investigators, to think about revising their trials to ensure that they are accessible to transgender people. And I think one thing that's hinted at in those suggestions is community-based participatory research in order to really ensure that the trials that we're writing are meeting the needs of community members.

Dr. Shannon Westin: I think there's always a huge opportunity to have advocates at every level reviewing our trials and our grants. And I don't know that we always do the best job of being incredibly inclusive of who we invite to the table to review those. So that part of the paper really spoke to me as someone who sits on different—task force for ovarian cancer and through the NIH and others, making sure that we really have a representative group that is reviewing these trials and ensuring that they are appropriately inclusive. So I really always like true action items because I think we all get really frustrated when we talk about a problem and say there's a problem and we wave our hands at the problem, but what we need are really goal-based solutions. And I think that was one of the parts of your paper that really I felt like elevated this paper, and now I think we just need to get it out so that it moves on beyond this workforce, this task force, and actually gets implemented on a day-to-day basis as we're developing these trials.

So I think I have one more question that I think we've kind of highlighted, but I want to make sure to put a pretty fine point on it. And you've talked a little bit about this, but we know that many transgender people are taking hormones so they can align their anatomy and their physiology with their gender. And we talked a little bit about exclusion around this, but I'd love to hear your thoughts about how can we better address this particular issue. And I'm just thinking of gynecologic cancers. We're using hormones constantly as a treatment. Breast cancer, same. So is there a way to align the drug development in this space but allow people that are taking these hormones for a different reason, a non-cancer-related reason?

Dr. Lola Fashoyin-Aje: Yeah, I think, as we discussed, these exclusions can be both explicitly stated in the protocol, like Dr. Ash mentioned before, or it can be silent, where there just isn't information that would direct a provider or investigator one way or the other as to whether or not it is safe to enroll participants on the trial who are transgender and who are receiving hormonal therapy in that context. So addressing this really takes a lot of education for each one of us. And, as I mentioned before, it's a data-free zone. And I think, ultimately, what's going to make some of these recommendations that we made in the paper sustainable is really having data.

When we were preparing the symposium and when we held the symposium, it was quite clear that some of the available data regarding the safety of hormonal therapy—like does it increase the risk of cancer, what are the impacts on an investigational therapy—there's just a lot of inconsistent information, incomplete information. And so we really need a lot of research to be done to fill those data gaps. And that's why in the FDA Oncology Center of Excellence, we actually have an active funding opportunity right now where we're requesting proposals for applied regulatory science research to really understand the factors that affect safety and efficacy of underrepresented populations in oncology therapeutic development. And we specifically call out sexual and gender minorities as part of that because we recognize that that's sort of an area where safety is always sort of invoked. But we just don't know many times if that's actually supported. And so we really do need data.

I don't have a best-practices approach. I think it's important that an investigator or provider ask their patient if they are receiving this and do preliminary basic research about whether or not there's even opportunity for drug interactions, which is something you would be concerned about, or for increasing the risk of developing tumor or tumor progression, depending on the disease. But again, we just don't know. So I think it's really challenging to offer—as a representative of a regulatory agency, it's really challenging for me to offer a best-practices approach here, other than we should just collect the information and do some research to really better understand.

Dr. Ash Alpert: Another thing that complicates this whole conversation is that historically, hormone therapy and surgeries have been used as a surrogate target for transphobia. Oftentimes, trans people have the experience of presenting to care for some symptom that we're having and having that symptom blamed on hormone therapy or surgeries when it's not related. So I think that complicates the ways that we're describing our research. That complicates national conversations about the safety of continuing hormone therapy in the context of a cancer diagnosis and treatment. And it definitely complicates conversations that individual transgender people and their oncologists have about whether or not to continue hormone therapy or how to manage the timing of surgeries in the context of cancer treatment. So that's not to stop or halt these really important conversations in this data gathering, but I think those are important considerations to keep in mind as we describe these questions, collect our data, and describe our findings.

Dr. Shannon Westin: Well, great. Well, this has been amazing, and I think that we wanted to put this podcast together so that we could get your very important findings out. How else can we get this out there? What else do we need to do? What are you all doing at the FDA?

Dr. Lola Fashoyin-Aje: The symposium that we organized was a huge first step, and we are having those conversations internally about what the best approach is that is data-driven approach. But to be quite honest, I think that there are so many barriers to changing the status quo. And I think what's really important is the continued highlighting of these issues at every opportunity to not leave out this population when we're talking about equity and underrepresented populations and to keep making those changes in our own particular settings about how we use language, the recommendations that we give to sponsors. I'm speaking from the FDA now about inclusion.

And our research and policy priorities really have to reflect this as well. And so, at an organizational level, what are you doing to ensure that this population is safe, has access, and that you're really engaging them in determining what—there are so many issues to prioritize. Where do you start? What are the things that are more short term, and what are the things that are longer term? And these are conversations that we have with patients at the FDA, inviting them to talk to us about them in different product development contexts, but also more generally.

Dr. Shannon Westin: Any last thoughts, Dr. Alpert?

Dr. Ash Alpert: I really urge readers to take these issues into consideration in their clinical trials office, to their cooperative groups, and to continue to think about them as they're writing trials. I really appreciate—I think we really appreciate the opportunity to speak on this podcast and to potentially have more people hear about these concerns and think about them.

Dr. Shannon Westin: Well, I really appreciate all the time that you spent, knowing that you are both very, very busy researchers.

Thank you all for tuning in today to JCO After Hours. We've been discussing the Comments and Controversies manuscript "Addressing Barriers to Clinical Trial Participation for Transgender People With Cancer to Improve Access and Generate Data." I am very grateful to all of you for listening. Hope you'll check out other episodes of the podcast, and we'll see you very soon.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.

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Barriers to Clinical Trial Participation for Transgender People

Journal of Clinical Oncology (JCO) Podcast

Barriers to Clinical Trial Participation for Transgender People