The final workshop panel explored what the future holds for incorporating health literacy into clinical trials from the beginning of the process. Terry C. Davis, professor of medicine and pediatrics at the Louisiana State University Health Sciences Center, moderated the discussion. Each panelist spoke for 5 minutes, giving her insights on the previous presentations and discussions as well as looking ahead. Davis then posed questions and facilitated a discussion with the audience. The panelists were Emma Andrews, senior director in U.S./Global Medical Affairs at Pfizer Biopharmaceutical Group; Monika Mitra, Nancy Lurie Marks Associate Professor of Disability Policy, Lurie Institute for Disability Policy at Brandeis University; Jovonni R. Spinner, senior public health advisor and co-lead for the Outreach and Communications Program at the U.S. Food and Drug Administration’s (FDA’s) Office of Minority Health and Health Equity (OMHHE); and Rebecca J. Williams, acting director of ClinicalTrials.gov at the National Center for Biotechnology Information of the National Library of Medicine (NLM) at the National Institutes of Health.
Emma Andrews, Senior Director, U.S./Global Medical Affairs, Pfizer Biopharmaceutical Group
Andrews began by noting that her remarks represented her own views and not those of Pfizer. She continued by saying that she is passionate about health literacy and that she and her colleagues work throughout her organi-
zation with the goal of bringing breakthrough medicines that can positively impact people’s lives to market. Andrews emphasized that new medicines could not be brought to the market without clinical trials.
Andrews noted, however, that clinical trials could not happen without patients, health care professionals, clinical research investigators, and many others. She said that she would like to expand that list to include, for example, community organizers, teachers, and faith-based leaders. Andrews said that everyone in the community needs to know about clinical trials because there are still a number of myths and misperceptions among people outside of the health care system. She believes that can change through health literacy and clear communication. She also reasserted that health literacy is not about making sure information is communicated in “lay” terms, because everyone could be considered a layperson depending on the topic. Health literacy is achieved by aligning the complexity of health information with the capacity of the intended audience.
Andrews said that, in her opinion, one important area for the future of health literacy in clinical trials is the informed consent process. She likened the process to going to a new restaurant where the food is unfamiliar. The chef may say, “This is an amazing dish,” but upon tasting it a person may not like it. According to Andrews, the informed consent process is similar because patients are being told what the clinical trial experience is like but cannot know for sure until they are enrolled in the trial. Andrews hopes that health literacy practices and improved technology developed with health literacy in mind (e.g., virtual reality headsets) can help people better understand what to expect from a clinical trial and therefore increase the number of people who stay in trials after enrollment.
Monika Mitra, Nancy Lurie Marks Associate Professor of Disability Policy, Lurie Institute for Disability Policy, Brandeis University
Mitra began by saying that she has never conducted a clinical trial and is not a patient advocate. Her expertise is in disability policy and, she said, her purpose at the workshop was to speak about inclusion of people with disabilities (PWD) in clinical trials. Specifically, Mitra asked, how can we use the principles of health literacy to inform our research designs so that we can include PWD more effectively?
According to Mitra, there are approximately 54 million people in the United States with a disability, and they are a diverse group with different levels of functioning and different levels of need. Mitra said they are also a group more likely to have more complex health conditions and chronic conditions in addition to their disabling conditions. She said that as a group, PWD are potentially the greatest beneficiaries of clinical trials and health
services research. They represent about one-quarter of health expenditures in the United States and face significant health, social, and economic disparities. Finally, Mitra noted, they are traditionally marginalized and underrepresented but, in most research and policy settings, they are not recognized as a group that faces disparities. This exclusion also applies to clinical trials research and it occurs because of both explicit and implicit barriers.
Due to strict inclusion and exclusion criteria, Mitra said, clinical trials have traditionally favored healthy, young, nondisabled Caucasians. According to Mitra, clinical trials exclude about 59 percent of the U.S. population because of these inclusion and exclusion criteria. A considerable number in this group are children and adults with disabilities. Mitra referenced a 2014 study by Feldman and colleagues that reviewed 300 randomized controlled clinical trials and looked specifically at the inclusion of people with intellectual disabilities. They found that, out of the 300 studies, only 6 (2 percent) explicitly included people with intellectual disabilities. They also found that 15 percent explicitly excluded people with intellectual disabilities because of explicit barriers. Mitra asked, “What about trials between the 2 percent that were inclusive and the 15 percent that were exclusive, and what are the implicit barriers between the two margins?”
Feldman and colleagues found that 90 percent of the studies that did not mention people with intellectual disabilities in the inclusion/exclusion criteria were designed in a way that excluded people with these disabilities, said Mitra. These implicit barriers included a lack of community engagement, inaccessible materials and information during recruitment, inadequate representation of PWD, and lack of knowledge and disability competence within the research community (Feldman et al., 2014). Mitra noted that these are examples of the implicit bias and unfounded beliefs within the research and medical communities about the competence of PWD. Mitra said that this is why it is important both to be aware of health literacy and to have a holistic definition of health literacy.
All of this is compounded by a paucity of research and limited understanding of what health literacy is within the context of PWD, said Mitra. Current health literacy efforts often systematically exclude PWD, according to Mitra, and this exclusion contributes to the ongoing health disparities and inequities among those who are disabled. Mitra explained:
When framing health literacy in PWD, we should think beyond accessible materials. We should think beyond inclusion and exclusion criteria … we should think about the design and implementation of the studies. We should think of the systemic barriers to communication and the facilitation of access and the meaningful engagement of disabled communities. We should also think about understanding the sociocultural context within which health literacy is experienced within the disability community. And
this framing of health literacy is critical for PWD and for other marginalized communities. It is especially important for PWD given the incredible mistrust between PWD and the medical community.
Mitra went on to explain the concept of universal research design, described by Williams and Moore (2011, p. 1), which “promote[s] routine inclusion of persons with disabilities in mainstream biomedical studies, without the need for adaptation or specialized design.” She explained that “universal design” was later expanded by Rios and colleagues (2016) into “accessible research design,” which sought to broaden the idea of accessible research by considering universal design as one of three levels of implementation, with the second and third being accommodations and modifications, respectively. Agreeing with Rios and colleagues’ analysis, Mitra noted that in order to effectively include PWD in clinical trials, the research community needs to move beyond universal design and think of inclusive and accessible research design. This should include the principles of universal design but also accommodation and modification. The research should be inclusive of PWD in all stages of research from study design to recruitment strategies. Most of all, Mitra concluded, it needs to be founded in the principle of the civil rights mantra “nothing about us without us.”
Jovonni R. Spinner, Senior Public Health Advisor, Outreach and Communications, Office of Minority Health and Health Equity, U.S. Food and Drug Administration
Spinner began by saying that she would be speaking about the perspective of FDA. This perspective, she said, is that the work of improving health literacy in clinical trials starts before the trial begins. Her mission in the OMHHE is to do this by raising awareness about why diversity in clinical trials is necessary. The mission of the OMHHE, according to Spinner, is to create a world where health equity is a reality for everyone, and a key component of health equity is health literacy.
The OMHHE is interested in promoting better informed decision making about FDA-regulated products, said Spinner. Patients should be involved in every stage of the clinical trials process. Spinner said that the OMHHE wants to make sure that racial and ethnic minorities; veterans; youth; lesbian, gay, bisexual, transgender, or queer individuals; and individuals with limited English proficiency and low health literacy have the health information they need in a form they can access and understand. This allows them to make decisions not just about their own health but for their loved ones as well. Improving health literacy among these populations is critically important to reducing health disparities because low health literacy does have an impact on a person’s ability to make decisions about
their health, Spinner added. This can range from knowing how to read a medication label, to knowing how to check one’s glucose, to understanding what that number means. For issues relating to informed consent, Spinner cited some of the questions:
- Do they know that they are eligible for the trial?
- Do they understand what the inclusion and exclusion criteria mean?
- Do they understand the documentation that has been given to them?
As a result, Spinner said, the OMHHE has a very specific focus on making sure that they are creating culturally and linguistically tailored clinical trial health education resources that are written in plain language at all literacy levels so that everyone can understand. Low health literacy cuts across all levels of education and income; even the savviest person can have low health literacy.
Spinner said that the way the OMHHE prepares people at all levels of health literacy is first by working with stakeholders. This allows the OMHHE to understand where they can improve and whether they have adequately conveyed the appropriate message. The OMHHE does message testing with panels of consumers, Spinner added, asking whether the graphics are appropriate and if the information is clear and easy to understand.
With regard specifically to clinical trials, Spinner leads the Diversity in Clinical Trials Initiative, a multimedia campaign to raise awareness about the importance of minority representation in clinical trials. One of the goals of the campaign, Spinner said, is to dispel some of the myths that exist in racial and ethnic minority communities about clinical trials and to introduce positive messages about clinical trials. The initiative addresses myths such as that a person has to be sick to participate in a clinical trial, said Spinner, adding, “Many people think that a clinical trial is a last resort measure.” The initiative also lets people know that research participation is voluntary and that participants can leave at any time without penalty. Spinner said that the initiative also addresses some historical abuses experienced by racial and ethnic minority groups.
According to Spinner, the initiative has produced nine public service announcements (PSAs) so far. The first six feature an African American woman who is an FDA patient representative living with sickle cell disease. Other PSAs and videos feature Spanish speakers, veterans, and other representatives of different populations. It is important to make sure that people see themselves in the material, said Spinner. The initiative is also producing podcasts, social media posts, blogs, newsletters, and a communications tool kit, as well as a number of print materials. Spinner noted that the diversity
of materials is important for health literacy because information should be presented in a variety of ways. She added,
We know that our communities need multiple types of information so we have the videos that are reinforced by the fact sheets, that are reinforced by the social media message, that are reinforced by the stakeholder engagement … we have this multimedia approach to make sure that people can get the messaging in different ways.
Spinner concluded by summarizing the key health literacy strategies of the OMHHE, including
- using plain language and avoiding jargon;
- assessing audience needs; and
- tailoring materials appropriately, including taking care with translating materials.
Finally, Spinner said, it is important to keep the patient at the center of everything they do and to make sure that patients have the information that they need to make decisions about their health.
Rebecca J. Williams, Acting Director, ClinicalTrials.gov, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health
Williams began by saying that in her role at ClinicalTrials.gov she is privileged to sit at the cross-section of the clinical trials enterprise. She noted that the ClinicalTrials.gov website is intended to serve multiple purposes. First, to provide accountability for the way research is conducted and reported but also to be a resource for people who want to find trials and determine eligibility. Having multiple purposes brings tension, Williams added, and dealing with that is part of looking to the future of health literacy in clinical trials.
In order to talk about the future, Williams said, she would need to talk about the past a little. One of the things that they were asked to consider at ClinicalTrials.gov as part of the rulemaking process for the FDA Amendments Act of 2007 (which expanded which trials are required to be reported and added the requirement that investigators had to submit results) was whether the results had to be accompanied by a narrative summary intended for a general audience. Part of this, Williams noted, was determining whether ClinicalTrials.gov could ensure that the summaries were not promotional or misleading, so her office sought public comment
on whether the summaries should be included in the ClinicalTrials.gov database.
According to Williams, her office was particularly concerned about the criterion of ensuring that the summaries are easy to read and not promotional or misleading. They receive 600 new trial registrations every week and post 120 new results records every week, Williams said, so there is no way that staff can have a systematic process for validating information. It is a challenge to ensure that such a massive amount of information is meeting the public’s needs and is independent of bias. According to Williams, they did not receive many comments on methods that could resolve the issue so they decided to defer the decision on posting summaries for the public until they could find a way to ensure the quality of the information. But as this process was being considered, they realized that informed consent documents are intended for non-experts and are reviewed by an oversight body. Williams stated that as a first step they could post informed consent documents publicly on ClinicalTrials.gov to accompany the study record. In addition, when the Common Rule revisions came out, it became a requirement to post the informed consent document if the study was funded by a federal agency and covered by the Common Rule. Now there is a trove of informed consent documents available online, said Williams, and this is an opportunity to evaluate those documents and identify best practices.
Another practice that came out of the rulemaking process, said Williams, is that ClinicalTrials.gov now requires, along with the results information that is being posted, that the full protocol document and statistical analysis be reported to allow for the evaluation of the results. It has also been clarified that when the registration is posted, a brief summary that explains what the trial is about must be posted and written in plain language for a general audience, although Williams noted that guidance has not yet been issued on best practices for writing this content. She added that the registration information at ClinicalTrials.gov is meant to be a representation of the information that is in the protocol document itself, a summary of the information that is considered the most important from the study.
When protocol documents were created, Williams said, no one envisioned that they would become a source of public information about the trial. So the way the protocol document is used has been transformed but the way the documents are written and crafted has not yet been transformed. Williams said she believes there is an opportunity to rethink the protocol document and how it can serve not just the study team but also the general public. Williams also noted that a couple of years ago ClinicalTrials.gov had done an evaluation on their website that included all of their different audiences: patients, researchers, health care providers, etc. They found that even the most frequent and advanced users did not
fully understand everything they could do or get from the website. Some parts of the website were reworked to respond to this evaluation and, as a part of that, the decision was made to prioritize the needs of the patient in revising the content. What they found, Williams reported, was that by prioritizing patients, the needs of other users were not compromised. In fact, she said, the opposite was true, and the revisions seemed to better support all of their users.
Improving Stakeholder Involvement
The first questions from Davis were “How can we do a better job of involving stakeholders? How can we do a better job of identifying who needs to be informed and when and how to inform them?”
Spinner began by noting that the term “stakeholder” is broad and the concept should also be broad. She noted that often people work in silos and do not know who else is working in their space and that it is also beneficial to look for nontraditional partners. For example, she suggested, education, housing, and transportation can all have important impacts on whether people participate in clinical trials. Taking the specific example of transportation, she asked,
How does the person get to the clinical trial site? Is their neighborhood safe enough for them to get to public transportation? Do they have access to their own car? When you are thinking about a person embarking on a clinical trial you need to make sure that all of the other areas of their life are intact … you don’t want their health to fall at the bottom [of the list] because there is a more pressing issue.
The different sectors need to work together, Spinner concluded, so it is important to bring everyone to the table to have this conversation.
Davis then asked, “In developing a clinical trial, how many people outside of the trial need to be involved? How wide do you cast the net?”
Andrews answered that in the field of pharma, they start with an unmet medical need. Once that need is identified, they determine who the patients are, where they live, and how they relate to their communities. After that, she continued, colleagues may work with patient advocacy organizations that will know that patient population and know who the influencers are within that community, such as faith-based leaders and educators. Colleagues ensure that insights from the patient advocacy organizations are shared with the scientists. Andrews concluded by saying that she would challenge health care professionals to think about where patients live and what their communities are like.
Mitra answered that she is currently conducting research on the perinatal health of women who are deaf and hard of hearing. On this study, there are investigators, research staff, and advisory board members who are deaf and hard of hearing, and they have also involved the National Association of the Deaf. In another research study on women with physical disabilities, Mitra said, two of her co-investigators are women with physical disabilities. It is critically important, she noted, to involve people that represent or understand the experiences of those involved in the study, she said.
Williams noted that a challenge of talking about clinical trials is that everyone assumes they are all equal, which is not the case. She added that it is important to determine the individual preferences and assumptions of participants to help them understand whether a trial is right for them.
Balancing Patient, Community, and Funding Needs for Trials
Davis then asked how investigators can balance the needs of patients and communities with the requirements of the funders of clinical trials.
Williams answered that, often, lack of resources is used as an excuse for not being inclusive or taking health literacy into account. She said that that approach should be flipped; the question should ask what resources are necessary to conduct a high-quality trial, and the answer should determine the design, not the other way around. Mitra noted that it is also necessary to “bake it in”; if funders require the involvement of communities, representation, and health literacy then it will happen.
Davis asked about visual images and messaging and how an investigator can know what is appropriate. Andrews answered that investigators must test the materials they are going to use because no matter how carefully the message has been crafted it could miss the mark in terms of messaging. Spinner echoed this comment, saying that testing the message is vitally important. Mitra added that just having pictures of minorities or PWD is tokenism, and inclusion cannot begin and end with pictures in a brochure. Spinner also added that sometimes it is best not to use people but rather graphics that animate a process; it is important to consider the context. Davis followed up by noting that one of the more powerful examples of this she had seen was a video explaining colonoscopies to children that used a teddy bear instead of a child.
Looking Ahead: Potential Key Changes
Davis then asked the panelists, “If there is one thing that you could change, what are some things that you think are key?”
Andrews said that for her it is getting the message out that the stakeholders are not just physicians and clinical investigators, and that we need
to do a better job of educating people about clinical trials. Mitra answered that she thought it was important to build trust and to look at who is not at the table and work for inclusion. Spinner’s answer was that she would like scientists and researchers to look at their terminology and stop using jargon and to be creative about how they are getting information out to participants. Finally, Williams answered that she would want researchers to focus on how they intend to communicate from the very beginning of the trial design and to prepare people to receive that information rather than thinking about it as an accessory. She continued by saying that people rely on a single document (the protocol document) to communicate about a specific trial, but right now that document is not meeting people’s needs.
Christopher R. Trudeau from the University of Arkansas School of Law asked about the user statistics for ClinicalTrials.gov and whether researchers have been mining the data on the website to improve the process or how they do things. Williams answered that it is used by a wide variety of individuals. In general, she said, about half of their users could be categorized as patients and the public, and the other half as researchers, health care providers, and information professionals like librarians. She added that they do have some patient advocacy organizations that help people navigate the site or their own customized sites and find disease-specific trials and information, which is targeted assistance that the NLM cannot provide. By making the data available, Williams continued, they are helping people to use it in ways that work for them.
Jennifer Dillaha from the Arkansas Department of Health commented that she remembered a study from a number of years ago that found that patients’ adherence to HIV medications was strongly predicted by whether they believed the workers at the clinic cared about them. She wondered if adhering to health literacy principles would better communicate to patients that they are cared for. Vanessa Simonds from the University of Montana wondered how researchers and investigators could be held accountable for using health literacy best practices, especially if they do not have a background in health literacy or health communication. Williams noted that this was an important question but she did not know the answer, saying that there should definitely be a discussion around what kind of competencies investigators and researchers should have.
Nicole Holland from the Tufts University School of Dental Medicine asked how researchers can address historical abuses by the research community toward minority communities. Spinner answered that this “dark history” is one of the things they are trying to address with the clinical trials initiative. However, she said, as time passes they have found that it becomes less and less of an issue and that mostly people in underserved communities are not participating in clinical trials because they are not asked. She added that it is important to engage the “gatekeepers of the community” (e.g.,
faith-based leaders) to start building trust. Mitra noted that she has found that for PWD, the way they interact with clinicians is critically important and if they feel stigmatized or disrespected it becomes a cumulative burden. Andrews responded that, for her, transparency and authenticity are key. It is not just about enrolling people in a trial but sharing the results with them and getting feedback on what went well and how things could have been better. Davis summarized that what she was hearing from everyone was that trust is key and the researchers need to be trustworthy, especially for minority communities.
Pettit Nassi commented that there is currently a moratorium against biospecimen collection that began with the Navajo Nation and went to the Cherokee Nation and is now essentially nationwide for American Indians and Alaska Natives (AIs/ANs). She said that this is a challenge because there are very few from the AI/AN population who are enrolled in clinical trials. It does not matter how trustworthy a researcher is, she said, because historically, native populations’ relationship with the federal government has been a challenge. Pettit Nassi said that when we talk about transparency and authenticity, we need to remember that there are still areas—not just AI/AN communities but also small, rural church communities—that have similar challenges, who do not trust the research community. Because of this, a whole population is left behind, she said, adding, “Are the people who make those decisions listening and finding answers to [this problem]?”
Collyar followed up by saying that one thing that could be recommended is that a communication plan must be part of protocol development. She added that there are communication models that are not that difficult to implement and if researchers start to think about communication as a necessary part of developing the plan it would be a fundamental switch.
Duhig asked Williams if there is an opportunity for ClinicalTrials.gov to make a communication plan a requirement or recommend it. He added that smart regulation and requirements like that can have an impact.
Williams answered that she thinks ClinicalTrials.gov might be too late in the process to influence that because people come to them when they have already developed the protocol. However, she said, she does think there are ways to incentivize particular goals, such as requiring certain elements in the document. Andrews responded that she wanted to play devil’s advocate by suggesting that because protocol documents are not intended for patients and the public maybe they should not be the documents relied on for communication purposes. She posited that perhaps a different document is necessary, one that is designed for patients and the public. Williams responded that unfortunately the protocol document is the main source document for dissemination currently but that it is definitely worth thinking about whether that should be the case.
Steve Rush from UnitedHealth Group commented that several years ago, United Health Foundation had a grant program that required a communication plan and adherence to health literacy best practices from applicants, so there is some precedent. Barbara Biesecker from RTI International noted a similar experience in her previous work, where she and the study investigator made a commitment in a multiyear study to give the participants a summary of the results every year in easy-to-understand language. They spent time with stakeholders developing a communications plan, and after that, she said, it was not difficult to adhere to the plan. Getting communication right took work, she said, but “there was nothing complicated about it.”
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