Increasing diversity in clinical trials is important for reasons such as advancing social justice and building trust with previously underrepresented groups. Diverse trial populations will also lead to more meaningful study results and effective treatments for a greater number of people.
In this post, we explore the ramifications of homogenous trials and what recruiters and sponsors can do to make trials more inclusive.
Let’s begin with the legal structures in place to make trials more diverse.
In 1993, the National Institute of Health (NIH) Revitalization Act was enacted so trial managers would include more minorities and women in all NIH-funded research studies.
Many years later, the FDA named 2016 “The Year of Diversity in Clinical Trials” as highlighted by commissioner Dr. Robert M. Califf. The intention: “a wide range of people should have the opportunity to participate in trials, both for access to new therapies and to have the chance to contribute to better treatment of everyone.”
Two years before that, the FDA launched Drug Trials Snapshots, a section of its website that shows the demographic data in clinical trials for new drugs. Differences in benefits and side effects among groups divided by age, sex and race are highlighted. The aim is for greater data availability and transparency.
For instance, the 2015-2016 summary report showed that in 2015 and 2016, African American patients accounted for only 5 and 7 percent respectively of study participants. These numbers show much room for improvement but also support the very reason Drug Trial Snapshots was launched, according to the FDA’s Dr. John J. Whyte.
Writing at Clinical Leader, Whyte argues that this transparency into patient demographics encourages discussion about participation in trials and variability in drug responses.
One such argument is that trial recruitment should show proportional representation matching the larger population. Whyte maintains that while proportional representation may have arisen from a valid social justice perspective, it’s also important from a scientific perspective in order to reach “sufficient statistical power...to perform relevant subgroup analysis.”
People might respond differently to investigative treatments based on their sex, age, diet, medications, genetic traits, race and ethnicity, so trials should ensure all these demographic factors are included in their trial populations.
If the treatment drug is likely to affect different groups in different ways, Whyte says, sponsors need to show clear strategies and testing within the trial setting to capture these differences.
A major problem with clinical trials that use a homogenous patient base is a lack of knowledge of how a treatment drug will affect other populations.
Science writer Sony Salzman at Center Watch reminds us of Sanofi’s blood thinner Plavix — approved in 1997 but with a boxed warning added in 2010 — which could not be processed by around half of the Asian and Pacific Islander populations.
The industry has progressed since that time, Salzman says, citing industry-led efforts such as:
The progress the industry has made is also noted by Wendy Tate, Ph.D. at Forte Research. She reminds us that of the 31,468 patients participating in clinical trials in 2016 (which led to 22 new drugs approved by the FDA), 48 percent were women and 24 percent non-white.
Just one year earlier, those percentages were 40 percent women and 21 percent non-white.
Tate does not conclude that this is enough though and laments, as an example, how pregnant women are often still considered a “vulnerable population” which leads to their alienation.
When it comes to criticism of current practices, a lack of resources is often at the root of it.
This is the charge levelled by Maxine Bookbinder at Clinical Informatica News. She argues that low enrollment in trials can stem from those trials usually being conducted in larger city hospitals rather than smaller community hospitals at which minority patients often seek treatment.
Another major problem is that many doctors are time-strapped and under-resourced so they cannot devote time to assessing available trials. The solution, Bookbinder writes, is a one panel database for patients data, which can be compared with trial eligibility requirements.
Other problems might be more mundane such as distance to travel and perceived associated costs, which can act as hindrances to participation. Sponsors can help overcome these issues, by budgeting for overnight stays and long-term parking compensation, and obtaining agreement from insurance companies to cover the trials.
Prioritizing transportation and housing is vitally important, but before that point, trial outreach coordinators need to tailor their recruitment messages for their chosen audiences. This will likely vary according to gender, ethnicity, age and income, says patient recruitment and project management expert Ashley Tointon.
Once trial outreach personnel know their audience, they will be able to determine the most efficient medium and message to use to engage them. This is particularly true with social media’s potential focused reach.
After understanding who the target is and where to find them, trial managers need to focus on the question of credibility, Tointon explains. Many minority patients distrust pharma and clinical trials in particular. In a grim reminder of the past, Tointon recalls the sterilization of Native Americans in the 1970s and the Tuskegee syphilis experiment on rural black men, which led to many deaths.
Consider how legitimacy is earned when a potential patient hears about a trial from a trusted source such as “the National Black Church Initiative, a Sorority/Fraternity group or even a trusted radio personality,” Tointon writes.
A holistic approach to patient and public health needs is required, says health content strategist Tina Pavane. She notes the importance of educating patients in this regard and lays the responsibility on the shoulders of doctors and trial sponsors.
However, these educational outreach programs can find homes in churches, schools, town hall meetings and community centers too. The more diverse the better as it will ensure a broad population is recruited by generating awareness of clinical trials to all communities.
Engaging prospective patients in familiar and safe places is what Bernadette Tosti urges at Applied Clinical Trials. Not only does the setting make people feel more comfortable but it also allows for better in-person engagement. There is the opportunity to ask questions and have trial recruiters answer them, discussing fears and benefits of enrolling in a trial.
Organizations have to change so that they consider diversity at the outset of trial planning, argues Melva Covington, Ph.D., the director of health economics and outcomes research at Orion.
This mindset should be translated into behavior, which encourages diverse recruitment, trial operations and analysis of results. Diversity, Covington argues, is not just about ethnic backgrounds but also gender and geographic distribution, among other factors.
She calls for due diligence and strategic thinking to favor diversity. If a condition affects a diverse racial or ethnic patient population, trial managers should ensure this group is adequately represented. This begins in the early recruitment and retention planning processes.
The overarching theme is better patient engagement to help understand patient needs and allow patients to become “co-designers of solutions.” Cultural competence and authentic interactions are the foundations of proper patient engagement, Covington says.
All of the above will be better executed if the relevant personnel in the clinical trials industry work together to communicate the availability of trials to people of all races and ethnicities, says ePatientFinder CEO Tom Dorsett.
Encouraging physicians to get more involved in the recruiting process is a good place to start. This is a far more effective recruitment option than direct-to-consumer marketing as patients are more likely to participate if their doctors have told them about a trial.
Part of this comes down to trust. Clinical trial managers should make use of electronic health records (EHRs) for easier identification of protocol-eligible patients. Physicians can then identify patients and work with patient outreach coordinators to connect patients with trial sponsors.
The value of this targeted approach becomes more obvious with non-native English speakers. Often deterred or left unreached by linguistic barriers, having primary physicians discuss trial opportunities directly with those patients can increase enrollment. Clinical outreach coordinators can ensure screening questionnaires are prepared in languages other than English and hire multilingual trial staff.
At the outset of this article, we noted how laws were enacted to encourage diversity. While valuable, the problem runs far deeper, argues Dr. Otis W. Brawley, chief medical officer at the American Cancer Society.
Participation of minorities should not be achieved simply because the law dictates this. Rather, increased diversity should happen because these patients receive better quality healthcare from doctors who encourage them to participate for the sake of their health.
As Brawley says: “There are huge numbers of blacks in the United States who get less than good health care, yet we fixate very frequently on blacks going into clinical trials. Maybe we should focus on blacks getting adequate health care.”
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