Hello, my name is Dr. Susan Taylor. I am the Burnett Johnson Endowed Professor of Dermatology and Vice Chair for Diversity, Equity and Inclusion in the Department of Dermatology at the Perlman School of Medicine at the University of Pennsylvania. It's my pleasure to discuss with you today health equity in clinical trials. So we will first discuss gaps in inclusivity in dermatologic clinical trials. Next, cultural considerations for clinical trials. Then we'll go over to obstacles to clinical trial participation and finally possible interventions. So why is inclusivity in clinical trials important? Well, there's several reasons. There are differences amongst various population groups in clinical phenotypes, in immunologic pathways and endotypes, and they are not, unfortunately, fully elucidated. There's inadequate representation of population groups in clinical trials that can lead to an incomplete understanding of the safety and efficacy of new drugs, devices, biologics and vaccines. And if there's inadequate representation of these groups, this may limit the generalizability of trial findings. Population group data that includes gender, ethnicity and race for most new agents for inflammatory disorders in dermatology, including atopic dermatitis are not always available. And as a result, new medical products may not be beneficial to all populations who need them and existing disparities in outcomes amongst various population groups may remain unchanged or those disparities could worsen and new disparities may arise. Inclusion of different population groups in randomized clinical trials and sub-analysis are of great importance and should be strongly encouraged. Now, the NIH Revitalization Act of 1993 provided guidelines. And those guidelines stated that women and members of minority groups and their subpopulations must be included in all NIH-funded clinical research unless a clear and compelling rationale and justification establishes that inclusion is inappropriate. In 2017, there was a guideline amendment and this requires that recipients conducting applicable NIH-defined Phase III clinical trials ensure results of valid analysis by sex or gender, race and or ethnicity are submitted to clinicaltrials.gov. When we look at the literature of inclusivity in clinical trials, here is a study published in 2022. These authors looked at 103 articles that represented 119 unique clinical trials in acne, atopic dermatitis and psoriasis. What they found in regard to reporting was that women and men of all ages and in regard to reporting was that race and ethnicity were only reported in about 22% of all of these clinical trials. In terms of representation, the proportion of white participants was 77.5%. And this is higher than their population here in the United States at the time of 72.5%. There were lower numbers of non-white and Hispanics in non-topical, that is systemic, Phase III trials as compared to topical agents that were looked at in clinical trials. And here we see from that same study in 2022 that for all trials, only 22% of the study participants were non-white. For acne, it was a little bit higher at 24%. Atopic dermatitis, a little bit higher at 37%. But psoriasis we see is lower at only 15% of non-white participants in those psoriasis trials. Here is another graphic representation that basically shows that in our clinical trials, be it acne, atopic dermatitis, psoriasis, or all of these trials put together, the majority of the population studied were white and blacks, Asians, other races, and Hispanics were not well represented. The same trial also demonstrated that there was a higher proportion of white participants in Phase III trials as compared to Phase I and II trials. So there was a lower proportion of all non-white groups in Phase III trials. They were a little bit higher in Phase I and Phase II trials. The number of Hispanic participants in Phase III trials was also lower as compared to Phase I and Phase II trials. So there were differences depending upon the phase of the trial, I, II, or III. Here is another study that was published in 2023 that looked at inclusivity in clinical trials. They found, they looked at participant data from dermatologic clinical trials completed from 2017 through 2021. Now, there were a total of 246 trials that they looked at. And of those 246 trials, 215 reported racial data and 152 of those trials reported ethnicity data. Now, compared to U.S. census data where blacks or African-Americans, American Indian, Alaska Natives, Hispanic, and Latine population, and two or more races, they were all underrepresented in these clinical trials. When we delve deeper into racial and ethnic differences in inclusivity in those 215 clinical trials from the paper published in 2023, we see that there are variations depending upon the year. For our black and African-American population, in 2019, that was the highest percent at 9.3% of blacks and African-Americans who were enrolled in those 215 clinical trials. Unfortunately, in 2020 and 2021, those numbers decreased. There was also a peak of Native Hawaiian and other Pacific Islanders in studies that were performed in 2018 and 2019 with a decrease in 2020 and 2021. For our Latin Hispanic population in 2017, about 22% of those who participated in clinical trials were Hispanic or Latine. And from that time period on, the numbers have decreased. So again, variability according to the year. We also learned from that study that black patients made up 11.6% of atopic dermatitis clinical trial patients. But this is in comparison to the US population of black patients, which was 13.6% at that time. There were similar disparities in our Hispanic or Latine patients who participated in these trials. These were eczema or atopic dermatitis trials where they made up about 10.3% of the study patients as compared to being 19% of the US population. So we can clearly see that both groups are underrepresented in atopic dermatitis clinical trials. When we look at inclusivity in clinical trials for atopic dermatitis for systemic agents, we clearly see disparities. When we look at abracitinib versus placebo or dupilumab, only 4.2% of the participants were African-American. If you look at the lebrokizumab phase three trial for atopic dermatitis, only 11% of participants in that trial were African-American or black. And if you look at the dupilumab phase three trial for atopic dermatitis, again, only 6.25% of the participants were African-American. When we look at our pediatric population, the prevalence of atopic dermatitis in black children we know is quite high at almost 16%. But black children only made up about 10% of patients in atopic dermatitis trials as revealed from the publication from 2023 by Moscow. White patients made up 60% of all patients in clinical trials, even though the prevalence of atopic dermatitis in white children was only about 10%. Now, the four clinical trials that they looked at included about 65% white patients versus 11% black patients, 16% of Asian patients, so they were over-indexed, and about 17% of Hispanic or Latine patients. When we look at the percent of clinical trials with racial and ethnic representation equal to or greater than the US population, we can see that only about 22% of clinical trials that had blacks or African-Americans equal to or greater than the US population. And if we look at those trials that had equal numbers proportionally to our population of American Indians and Alaska natives, that was only 12%. For Latinos or Latin A population, again, only 28% of the clinical trials had Latin A patients who were proportional, which were proportional to our US population. When we look at our psoriasis trial, the trend continues. Black patients made up only about 3% of psoriasis clinical trial patients, but they consisted of about 13% of the US population. Hispanic or Latin A patients made up about 10%, almost 11% of psoriasis clinical trials. But remember, they make up about 19% of the US populations. So we clearly see from this Mineroff study that both groups, blacks as well as Hispanics, the Latin A population, both groups were underrepresented in psoriasis clinical trials. Let's look at alopecia areata. Unfortunately, the trend continues. Black patients made up about 8% of alopecia areata clinical trials, compared to remember about 13% of the U.S. population. Hispanic and Latine patients made up about 12% of our alopecia areata clinical trials but again they're 19% of the U.S. population so again both groups are underrepresented in our alopecia areata clinical trials. It is critically important that we look beyond gender, race, and ethnicity in regard to clinical trial subjects and their participation. We must take into consideration cultural factors so for example the number of Muslims will nearly equal the number of Christians around the world. Islam is the fastest growing religion here in the United States and Muslims will be the largest non-Christian religion. Upholding faith-based expectations and standards in clinical trials is crucial to counter mistrust so dermatologic concerns of individuals of Muslim faith merit special considerations. So what are some of those cultural considerations? Well when we advertise for clinical trials we should consider including images of individuals with the jobs on our recruitment materials to foster representation. We need to encourage participants to make informed decisions about participating so to do this we must inquire about religious affiliations during the participant's intake to identify those who may need to follow an adjusted protocol for scout photographs. So for example there are some women who are covered who only want to uncover one area of their body at a time as opposed to completely disrobing so we have to take those cultural considerations as an important factor. When we advertise for clinical trials and are recruiting patients it's important to involve Islamic religious leaders and mosques in health promotion strategies. So when we're considering clinical trials procedures it's important to demonstrate for our patients assessment tools and images so they know what to expect particularly with scout photography their dimensions and orientations before or during the informed consent process. It's important to plan for potential protocol adjustments and assessment tools to accommodate religious preferences and standards. We have to consider capturing distinct separate images of various areas to reduce the necessity of removing the hijab. And we want to demonstrate captured images to participants to assess their comfort before storage. We might need to destroy and retake any photo based on an individual's preference. Now there are a whole host of other obstacles to clinical trial participation. There are hidden costs that I'd like to review. In regard to travel there's gas there's vehicle wear and tear there might be tolls and parking fees for your subjects. Airfare and lodging might be a consideration. The cost of food many of our subjects need to eat out while away from home and this might include not only the subject but also their family members. There are costs associated with child or elder care. If our participant has a child they might need to hire a sitter or pay for daycare or day programs for their elders. Employment many of our participants might lose wages or their spouse who must accompany them might lose their wages. And insurance you know if there is an adverse event that occurs and it's not going to be paid for by the study sponsor that individual might be responsible for a co-pay or for the cost of the care. Now this is a study I'd like to review with you of 91 quantitative qualitative interviews at five U.S. cancer centers among four stakeholder groups. Now those that they interviewed were cancer center leaders, principal investigators, research staff, and referring clinicians. It was a diverse group with 67 being white, 11 black, 13 Asian, 15 Hispanic, and a mean of 12 years of trial participants among those four stakeholder groups. All interviews were recorded and transcribed and there were two prominent themes that were identified in regard to obstacles to clinical trial participation. The first was racial and ethnic minorities are influenced by varying degrees of skepticism related to trial participation and this included distrust, discomfort with inherent uncertainty of trial participation, negative connotations of clinical trials, things that they had heard about clinical trials in the past. It included a low education level and language discordance. The second major theme that was identified was potential minority participants often face multi-level barriers that preclude them from being offered an opportunity to participate in clinical trials and this includes unmet transportation needs, inadequate insurance coverage, low education level, language discordance, and competing obligations limiting their time for trial participation. Patient barriers are being identified but less than half of the published studies are reporting on these barriers. Now that we've reviewed some of the barriers I want to discuss a very important study that was published by Clark et al entitled Increasing Diversity in Clinical Trials Overcoming Critical Barriers and these investigators looked at cardiometabolic trials not dermatology trials and they identified the barriers to the trials and they suggested interventions to help patients be more likely to participate. They interviewed investigators who were minority serving physicians and the subjects that they had interacted with 24 were black, 21 were hispanic, and nine were asian patients. When we look at the barriers that were identified mistrust was number one and Clark et al suggested some solutions. They suggested to emphasize to the subject that your number one priority as an investigator is the subject's health and safety. To let them know that there's been extensive research and testing that many people have received the medication if that was indeed the case. We let the subject know that their health will be closely monitored and there is the possibility that the study and the study IP will improve their health. Another barrier that was identified was the lack of comfort with the process and they suggested the following interventions to make sure that the subject had clear understanding that they give enough information for informed decision making that they emphasize that the subject's participation is voluntary that they truly appreciate that the subject participates in the study. It's very important to make sure the study participant knows their main contacts the investigator and the coordinator that they will monitor your their health and will attend to any side effects and the their progress the subject's progress will be closely monitored and they're always available to answer any question the subject that they may have and if the subject gives permission that the investigator will have a close relationship with their PCP. Other barriers lack of information so what are some of those interventions? Well number one which makes sense is to make sure that you provide the subject with all of the information that he or she she needs that you give complete answers to their questions if there's a coordinator who can't answer some of their questions that the subject will be directed to someone who can indeed answer their questions let them know that you will take as much time and give as much information as possible so that the subject feels that they're in complete control. Another barrier was time and resource constraints. A couple of interventions that were suggested in the paper included thanking the subject for considering participation and letting them know that the doctor can monitor their health and safety. To provide within reason some compensation some compensation for their time commitment and transportation as per the IRB approval. In terms of general lack of awareness there are some interventions that were outlined in regard to increasing clinical trial awareness overall in a community. So we have had the ability based on the literature to identify some possible interventions in regard to barriers to participation in clinical trials. Now another important barrier that we have to discuss before we close is the fact that often investigators who have diverse patient panels do not have experience in executing clinical trials. So I want to point out that the Skin of Color Society has developed a leadership development tool to identify training to board certified dermatologists who are underrepresented in medicine who have little or no clinical trial experience. And this mentorship program allows them to participate in a didactic online course and then an in-person eight-hour training and finally longitudinal mentorship experience so that they have the ability to learn how to execute clinical trials. And here you see a link to the Skin of Color Society so you can learn more about this very important mentorship program. And with that I want to thank you for your time and your attention.

health equity

dermatologic trials

underrepresentation

cultural considerations

inclusive recruitment

equitable healthcare