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Tufts Center for the Study of Drug Development and Biogen recently conducted a study to inform growing interest in improving diversity of clinical trial participation. The results of this research provide insights into increasing the community of minority investigators and study staff and presenting greater access to clinical trials among minority study volunteers.
The development of new therapies is not possible without volunteers to participate in clinical trials. Recruiting study participants is extremely challenging regardless of demographic background. Challenges to potential participants include time away from work and loss of income, travel to a site and reimbursement, and the potential risks of a trial. There are, however, unique barriers for minority and underrepresented populations who participate in clinical trials, including mistrust, inadequate communication, and significant fear of the research process. Some of these barriers are rooted in the ethical failures of the history of clinical trials. Most notably, the Tuskegee Syphilis study conducted between 1932-1972 which promised black male participants free medical care but did not treat them once the cure became available in 1947.1
There is ample evidence in the literature indicating that the primary factor associated with low participation by underserved groups in clinical trials is a lack of trust in research and in the healthcare system.2 Unethical practices, and disclosure and transparency failures are two examples of factors that have led to widespread distrust.3 Poor access to clinical trials and the low relative availability of experienced minority clinical investigators are also cited as barriers to minority patient participation.4,5,6 Recently, significant strides have been made to build the trust between minorities and trial investigators by the National Institutes of Health (NIH), FDA, and among industry stakeholders. The 2019 draft guidance released by FDA on enhancing the diversity of clinical trials reflects the perceived importance of having adequate minority representation in clinical trials.7
Tufts Center for the Study of Drug Development (Tufts CSDD) and Biogen recently conducted a study to inform growing interest in improving diversity of clinical trial participation. Tufts CSDD conducted ten in-depth interviews with investigative site staff during July and August 2019 and co-moderated two advisory boards with 11 clinical research professionals in Atlanta and Phoenix. The primary aim of the advisory boards was to understand investigative site experiences and barriers that hinder minority participation. The results of this research provide key insights into increasing the community of minority investigators and study staff and presenting greater access to clinical trials among minority study volunteers.
The advisory boards noted that trust should exist at both the individual level (e.g., physician, healthcare provider) and the institutional level (e.g., healthcare or medical system) with the coordinator and/or investigator acting as a critical liaison. Advisory board members expressed:
“In dealing with minority populations, the coordinator needs to know how to address the issues of trust and the distrust of the medical system, and distrust in research.”
“You have to know where that fear and distrust comes from, and then you have to know how to address it appropriately.”
“I usually tell them straight out we don’t have enough African Americans in research, and we’re giving you all this information on medications that are not tailored for us. It’s tailored to Caucasians.”
Prior research supports the concept of establishing trust at the individual and institutional level. Trust in a physician or researcher is typically based on the quality of personal interactions, while trust in the medical research enterprise is often based on the reputation of an institution.6One strategy to increase trust at the individual level is through strengthening a patient’s relationship with their healthcare provider.
Establishing trust between a healthcare provider and patient requires recognition of diverse patients’ needs, which commonly involves awareness of language preferences. Unfortunately, many sponsors and study teams often overlook language inequity as a barrier to recruitment of diverse participants. Individuals who speak English “less than very well” are considered to be of limited English proficiency (LEP) and constitute 8.5% of the total U.S.population or 25 million people over the age of five.8 The population of LEP people continues to grow, and research shows this population to be more likely to live in poverty, have poorer health outcomes, and be underrepresented in clinical research.9 Limited participation by LEP patients greatly diminishes the social benefits and generalizability of clinical trial outcomes. The advisory boards noted that the development of culturally and linguistically appropriate educational interventions geared toward LEP communities are critically needed to explain the risks, benefits, and practices of clinical research.
One solution recommended to address language inequities was to recruit bilingual site staff; however, the availability of multi-lingual coordinators is extremely limited and remains an urgent need. To overcome shortages of multi-lingual staff, sites offer cultural competency training and language courses to interested employees. Technology can also be leveraged to translate materials into grammatically correct language. Ad board participants recognized that materials should be inclusive of distinct dialects and languages. Information must be accurately translated to reflect the idiomatic characteristics of the target population. Another common misconception is that someone of Hispanic/Latinx background has the ability to speak one language over another or has the literacy level to understand in their preferred language. Whenever possible, both the English and Spanish versions of materials should be included in one document. Study coordinators related examples of patients who enroll or discontinue studies based on a family member’s advice. Bilingual materials are also beneficial for family members who are involved in the patients’ healthcare and decision-making. As the role of family and tradition are highly valued among diverse populations, including the patient and their family early on in the recruitment process is key to improving participant adherence to the study protocol.
“The thing is, a patient goes home and explains in a way that’s not going to be the same as what was explained to them during their visit because it’s just–they explain whatever they absorbed, and it might not–to the family, it might sound like an experiment, which is what a lot of patients say, versus someone who is trained to explain it to the family member.”
“A lot of times we’ll have a woman come in, we’ll give her the consent form and talk to her about it, and she’ll say, ‘My husband has to read it,’ or ‘I have to talk to my husband.’ Men will do the same thing, ‘I have to talk to my wife.’ Sometimes they’ll bring their wife or their husband. Then it just makes it a little bit easier, because they’re both there.”
Fear of deportation among undocumented immigrants who become involved as research participants was identified by the Phoenix ad board as a source of concern leading to greater mistrust and fear. Participant misunderstandings about what they are committing to may occur due to a potentially limited knowledge of the research process. As a result, there is a critical need during the recruitmentprocess to provide and communicate detailed study policies regarding the reporting of undocumented immigrants. Enlisting the aid of community-based groups and clinics that are trusted by migrant communities help guide these conversations.
“Working with a lot of folks that may have mixed legal status in their family, we had a really difficult discussion around this with our team about our level of comfort of actually having to present that to these families and how much of a deterrent that could be.
“A lot of our folks are working two jobs, have limited transportation. Then if they’re going to show up and be surprised by: ‘You have to fill out this W-9,’ which basically, if you leave this part blank, is saying something about your status, that absolutely is a: ‘I don’t want to participate.’”
In addition to ensuring sympathetic translations, partnering with the community may avoid engendering stereotypes or confusion by researchers or sponsors based on potential cultural, socio-economic (e.g. poverty), or linguistic differences. Successful intersections and engagement include investigators and staff from study participants’ own communitiesto increase rapport and build trust.One participant established an group of community leaders to develop targeted and appropriate materials; and ensure consent forms were written at the sixth-grade level. In addition, the group provided on-the-job training and “lay training” for community board members. The “lay training” served as an alternative to the current CITI training that is geared for training researchers and may pose challenges for a non-researcher. The training provided community members with a better understanding of medical research at all stages, including patient recruitment, enrollment, and retention.
Other strategies that foster community collaboration and facilitate trust are researchers’ active participation in the community,for example, by attending and hosting health fairs, or disseminating the results of prior research studies. A recommendation for sponsor companies is to build lay language results into their patient engagement plans. Contrary to popular belief, churches may no longer be the best form of communication and outreach for minority patients. While churches still play an important role and act as a location for community events, it may have shifted as the main/sole source of communication and outreach as younger generations seek other outlets. Including a variety of community stakeholders from the start to the close of a trial has revealed other recruitment strategies,such as “refer-a-friend,” that may ease the recruitment process of specific subpopulations.
“We’re talking about having that trusted visual in the community. When I go in as a member of a university [in the state of Georgia]. I’m introduced to the community through these entry points, these agents, and the gates are automatically open to me.”
“I’ll notice that more of our Hispanics come from maybe refer-a- friend versus our traditional methods. We have flyers and they’re not putting ‘flyer,’ they’re putting ‘my sister’ or ’my friend,’ things like that. It’s much more refer-a-friend than anything else.”
Participants strongly encouraged the use of technology for overcoming not only language and literacy barriers, but also for broadening the reach of diverse trial participants. Remote or virtual trials have become more common and their usage is increasing across the industry.7 These trials use wearables, mobile apps, videoconferencing,or other tools to ease the burden for both the sponsor and study participants. Despite significant progress made in virtual trial technology over the past decade, research sites continue to play a vital role in moving clinical research forward. One site shared use of an app-based digital storytelling intervention to engage minority groups and facilitate the informed consent process. Sites also offer Uber and/or Lyft ride credits to improve access to participation.
“The app sends push notifications [to their cell phones] and asks patients to answer questions. It prompts them to watch the story they’re supposed to be watching. It’s working really well for us. It’s geared towardsHispanic patients, but everything-the story, the video-is in Spanish, and includes subtitles in Spanish, too. We also have them set to English, so that if you have a mixed language family, everybody can understand, hear, or read it.”
Strategies that consider the culture and diversity of a population are effective among investigators and research staff. The advisory board discussions revealed that sitesdo not feel prepared or equipped to serve underrepresented populations. Providing adequate compensation, resources, and allocation of additional time for investigators (of all backgrounds) to prepare and learn about appropriate strategies for recruitment and retention of diverse participants alleviates “burnout” and improves staff retention to ensure continuity of community interventions.3 Tangentially, providing clinical research education early in an individual’s career increases their awareness and opportunity to be a clinical investigator or study coordinator.
“If you want to design a study, the site should be equipped with all the materials on all the populations of interest (e.g.,Spanish-speaking patients). The sponsor has to be ready to provide that to sites so that they feel prepared for the patients.”
The group noted that additional investments and incentives by institutions (e.g., universities, hospitals) and other organizations (e.g., professional associations) could potentially increase the numbers of diverse investigative site staff and improve minority participation. This investment could be used to stimulate hiring, support underrepresented study coordinators and investigators, and create a supportive and comfortable environment for diverse investigators. Participants offered ideas for incentives and strategies to motivate researchers and investigators to participate, including publication opportunities, promotions, awards and recognition for minority-serving institutions, supportive infrastructure (i.e. mentorship), and carving out time for primary investigators (PIs) to conduct research.
“Need good mentorship (not sure if through the same race or not) and institutional support. The institution must provide a level of security that they can do this work and it won’t all come crashing down if they lose a grant cycle.”
It is widely known that marginalized groups must overcome large barriers in the clinical research process and in order to establish a solid foundation for diversifying trials and research teams, there are critical areas that still need to be addressed. Mistrust of clinical research and of the medical establishment, and low ethnic/racial representation of investigators, site staff, and study volunteers are factors that perpetuate fear and lack of participation in clinical trials. Community-based partnerships with trusted representatives serve to increase awareness of clinical trials and provide extensive information about the process. It was apparent that this group of diverse coordinators and investigators have been working to include underrepresented participants in trials and are willing to forge stronger partnerships with sponsors and other organizations to promote sustainability of their diversity and inclusion efforts.
Greater diversity in research participation is needed to promote justice in clinical research and rectify health disparities. Application of these principles in clinical research will provide meaningful results that are free from bias and represent diverse populations who may use these treatments when they become available.
Yaritza Peña, Research Analyst; Mary Jo Lamberti, Professor and Associate Director; Geraldin N. Batista, Marketing Communications Coordinator;all from Tufts CSDD; Kate Wilson, Patient Engagement Strategy Lead; Narinder Chopra; Director, Patient Feasibility, Enrollment, and Retention; both from Biogen
We would like to acknowledge all of the participants of the interviews and advisory board discussions; they shared valuable insights on the opportunities and challenges of diverse clinical trial recruitment and retention at the ground-level.