Industry efforts to increase diversity in clinical trial populations are starting to pay dividends.
It is commonsensical that a patient population in a clinical trial should reflect the general patient population, yet matching levels of diversity – especially gender and ethnicity – in trials has been a thorny issue. “Most physicians and scientists are informed by research extrapolated from a largely homogeneous population, usually white and male.” This is the conclusion of a paper published in PLOS Medicine late last year. The authors warn that ignoring the racial/ethnic diversity of a population is “a missed scientific opportunity to fully understand the factors that lead to disease or health.”
The numbers on ethnicity speak for themselves. In the US, for example, black Americans comprise 13.2% of the population and Hispanics 16%; they make up just 5% and 1% of clinical trial participants respectively. In Europe, a 2006 review of 72 cardiovascular cohort studies found that just 15 studies were able to compare different ethnic groups, all of which were carried out in the US (none of the 41 studies in Europe were able to compare data by ethnic group). The picture is just as murky with gender. A 2014 study from Brigham and Women’s Hospital and George Washington University found that medical research in many disease areas, including cardiovascular disease, which kills more women than men, often included few women subjects or didn’t report results by gender. Key findings were that only one-third of subjects in cardiovascular clinical trials were female and in depression, which is more prevalent in women than men, brain studies in male animals outnumbered those in female animals five to one. It is no wonder that the authors of the 2015 paper argue for a more comprehensive view on diversity-sensitive clinical evidence – one that “takes heterogeneity as a starting point”.
Why is diversity important?
The fact that minorities, women, the poor and the elderly are underrepresented in clinical studies hasn’t gone unnoticed; indeed, the FDA heralded 2016 as the “year of diversity in clinical trials”. According to FDA Commissioner of Food and Drugs, Robert Califf: “Moving from the result of a clinical trial to applying it in practice is complex. But it’s generally agreed that the composition of the population enrolled in a trial should help FDA reviewers, clinicians, or policy makers to have confidence that the trial results will apply to future practice.” In response, the FDA has engaged in a number of activities to push for more diverse populations in clinical trials, such as providing information to underrepresented groups as well as launching Diverse Women in Clinical Trials, a multipronged effort to raise awareness and share best practices about clinical research design, recruitment, and subpopulation analyses. TransCelerate, the non-profit organization that works across the biopharmaceutical research and development community, has sponsored an initiative on Clinical Trial Diversification. It aims to assess the problems and develop guidance for sponsors and clinical trial sites on better practices and processes for minority recruitment.
Our hope is that by increasing minority physicians’ participation, we will be able to increase the diversity of clinical trial participants and improve clinical research.
Industry has also played its part with US pharma trade body PhRMA, launching the ‘I’m In’ campaign in 2014 in a bid to increase diversity and encourage minorities to become involved in clinical research. “The people we most need to study may be the very ones that have been historically underrepresented in clinical trials, such as African Americans, Asian Americans, and Hispanics,” notes the campaign, which is now run by the National Minority Quality Forum. “We know that, historically, people from minority populations have been reluctant to participate in clinical trials,” says Andrew Powaleny, Senior Manager, Science and Regulatory Advocacy Communications at the Association. “Motivations differ from person to person and we recognize that. Our position is to raise awareness and to seek greater participation, and for people to have a full appreciation of why clinical trials are important.”
Lack of trust?
The obstacles to true diversity mirror those of trial recruitment at large, although access to trials, lack of awareness and lack of trust are more pronounced in some populations. According to Ann Van Dessel, SVP and Global Head of Clinical Operations at Janssen, awareness a crucial barrier. “Awareness of clinical trials as a potential treatment option is low, especially with minority populations. When there is awareness of a clinical trial option, there may be misconceptions about what is involved with clinical trials.” Lack of access to medical treatment can also be a significant barrier to learning about clinical trial options, an issue that disproportionately affects patients from lower socio-economic strata, she says. Van Dessel points out that studies are conducted, for the most part, in the developed world. “These trials represent certain regions and ethnicities and, in particular, men. Women are usually under-represented for multiple reasons like pregnancy and breastfeeding, which are important, but the real world setting is not reflected. “Often clinical trial sites are the conduit to find patients and then provide this education. If sites don’t have diverse populations, then finding the ‘right’ patients and participants can be a difficult task,” she says. There may be other considerations, such as family input, transportation challenges, or time burdens, which act as deterrents for individuals. “The ability to connect with potential trial participants, in a way that is meaningful to them and from a source that is considered to be trustworthy in the eyes of that person, is imperative to participation success,” says Van Dessel.
Janice Chavers, Director of Diversity and HR Communications at Eli Lilly and Company, says that a general lack of trust around medical research is also a major issue. In addition, Lilly has identified another less obvious barrier – the lack of minority investigators. To help address the issue in oncology, they have partnered with the Center for Drug Development and Clinical Trials at Roswell Park Cancer Institute and are conducting workshops to train minority physicians to become clinical trial investigators. The training programs, which are the first of their kind in the pharmaceutical industry, “aspire to develop a broader base of diverse investigators who understand the principles of good clinical trial design and have the tools to conduct trials that are relevant to underrepresented populations”, says Chavers. “Our hope is that by increasing minority physicians’ participation, we will be able to increase the diversity of clinical trial participants and improve clinical research.”
Janssen is making similar efforts, says Van Dessel. “Research has shown that minority patients often look to be treated by physicians of their own race, so identifying diverse investigators and site staff is critical to reach diverse populations. Our processes for site identification and site staff training at Janssen include considerations to increase engagement with sites treating diverse subject populations.” Janssen’s clinical trial recruitment data is analyzed to evaluate progress and identify opportunities for achieving representative population, based on the indication and disease researched. Lilly is currently engaged in a major research project with by the National Center for Bioethics in Research and Health Care at the historically black Tuskegee University. The collaboration, which includes research, education, and community engagement, forms part of Lilly’s wider clinical trial diversity strategy.
For Chavers, it’s a means to justify an end. “The ultimate goal of our clinical trial diversity strategy is to improve health outcomes for individual patients. The issue at hand is that responses to medicines can vary depending on a number of factors, including someone’s genetic background, ethnicity, sex, and lifestyle. This is why it’s critical for Lilly to have diverse representation in clinical trials—to gain the insights necessary to make medicines that will be the most effective for all people who use them,” she says. Janssen is raising awareness of the issue internally and taking steps to increase diversity in clinical trials, while, externally, it is partnering with the Society for Clinical Research Sites (SCRS) to develop an awareness and best practice program for clinical trial sites. This program will include tools, webinars, and live seminars to assist clinical research site leaders in best practices for diverse patient engagement in clinical research “Global Public Health – a department of Janssen that focuses on developing drugs and increasing access to our drugs to non-Western countries – is conducting trials in parts of the world where trials haven’t been routinely conducted, like sub-Saharan Africa and other developing countries,” says Van Dessel. “We are also working to recruit more women into trials and generating real-world evidence to help fill the data gaps from the phase 3 studies.”
The patients we serve
The ‘year of diversity’ in clinical trials is almost over so has industry finally begun to make concerted efforts towards greater inclusiveness? “I can’t speak for others, but we certainly have made progress,” says Chavers. “While we’ve made progress, we still have more to do.” Van Dessel agrees. “It is critical for pharma to address this; we need to better understand the patients we serve, be that genetic diversity or gender, or even the social issues people face will have an impact on the treatments we develop.”