The urgent need for more diversity in clinical trials was a common refrain at this year’s American Society of Clinical Oncology (ASCO) Annual Meeting. Although many study sponsors are broadly aware of this concern, most still struggle to implement specific, structural changes that will help trials better represent the wider population.
To understand where trials are falling short, sponsors must first report information on the race and ethnicity of clinical trial subjects. But so far, most sponsors fail to do so.
In fact, among Phase III cancer trials completed in the past five years, most did not publicly reveal data on race and ethnicity. Less than half of pharma-sponsored trials, and only one in 10 institution-sponsored trials, reported on the race or ethnicity of their enrolled patients, GlobalData’s Clinical Trials Database shows. GlobalData is the parent company of Clinical Trials Arena.
Even still, collecting data on race and ethnicity is only the bare minimum. “If we're really serious about trying to recruit more diverse trials, we have to pay attention to the social determinants of health,” notes Dr Al Benson, oncologist at the Feinberg School of Medicine and an author of ASCO’s guidance for increasing trial diversity.
Data on social determinants of health can unearth why trials underrepresent certain races and ethnicities, which can prompt strategies that address these underlying failures, experts say. Population health data can help sponsors build more representative inclusion and exclusion criteria and engage with community-based sites that better reflect their target indications.
Addressing diversity in trials is critical, as it allows sponsors to learn how their treatments could work in a real-world setting. With ASCO and the Association of Community Cancer Centers (ACCC) publishing a joint guidance on increasing diversity in clinical trials shortly before the marquee oncology conference, the onus falls on sponsors to take meaningful action.
Collecting participant data proves key
Data collection can help sponsors understand when they lose potential trial participants during various stages of the study process, notes Reify Health vice president of site growth and adoption Jai Singh.
For example, in an analysis of 13,000 patients across multiple trials, Reify found that Black research candidates were just as likely as other candidates to move into pre-screening, Singh says. But they were 21% less likely to schedule the first visit after pre-screening, and from there, 19% less likely to move into screening. This type of data-driven insight, Singh says, can help sponsors determine where they should direct their resources to increase clinical trial diversity.
Data on social determinants of health, including income, education, and healthcare access, can help sponsors understand why their trials lack diversity, Benson says. For example, sponsors may find that factors such as inadequate transportation are preventing more diverse patients from enrolling, Singh adds.
Sponsors can then use this data to proactively counteract recruitment challenges, such as subsidising transportation, he notes. Even very basic steps, such as distributing patient consent forms in multiple languages, can foster a more inclusive clinical trial, adds Ariel Katz, CEO of healthcare data firm H1.
Data on social determinants of health can also shed light on the implications of clinical trial results in real-world settings, Benson adds. Healthcare insurance can directly impact survival rate, and therefore should be included as part of a multivariable analysis of trial results, he notes.
In addition, sponsors should work to retain diverse populations in long-term follow-up studies to see how a treatment’s extended safety profile measures up in a more representative population, adds CMO of CVS Health’s Clinical Trial Services (CTS) Dr Owen Garrick. Any effort to bridge gaps in diversity at an individual trial level should be supplemented by adaptations at an institutional level, he adds.
Inclusion criteria can exclude
Clinical trial inclusion and exclusion criteria have become increasingly lengthy and complex, causing some trials to exclude health conditions that are more common in Black and Hispanic patients, Singh says. Among the roughly 1,000 Phase III oncology trials completed in the past five years, 35% included blood pressure (BP) and 16% included body mass index (BMI) in their inclusion or exclusion criteria. Strict requirements for BMI, BP, and hemoglobin A1C (HbA1c) are among the exclusion criteria that can lead to less representative trials, Garrick adds.
Specific BMI and BP parameters are useful in some types of trials, but sponsors should not arbitrarily set them based on historical standards, Garrick says. In many cases, raising these baselines would better align with real-world averages for different patient demographics without adversely affecting the strength of clinical trial data, he explains.
In addition, many trials include one subjective exclusion criteria that asks investigators to broadly determine if a patient is a good fit for the trial, Singh says. Reify’s research has found Black patients are excluded on this basis more so than white patients, he notes. More robust data collection can make sponsors aware of which criteria are excluding underrepresented patients so they can amend trial protocols accordingly, he explains.
Deeper pool of sites can increase diversity
To increase the pool of potential patients, sponsors can direct some attention away from traditional academic medical centers (AMCs) to pursue trial sites at smaller community centers, Katz notes. But this can be challenging, as building community trust with smaller centers takes time and cannot be established overnight, Garrick notes. Sponsors should ensure frictions over budgeting do not interfere with their relationship with smaller trial sites.
To measure whether a site is meeting diversity standards, sponsors can compare county-level demographic data to a specific site’s enrolment trends. Each year, trial sites should release data on the “funnel” of recruitment from reach-out all the way to retention, making clear whether progress to diversity is occurring on a yearly basis at each site, Singh says.
Indeed, a myriad of factors can contribute to faltering clinical trial diversity, making it essential to create a more inclusive study. “You want your clinical trial participant population to be a scaled down clone of the epidemiology of your target condition,” Katz says. “Most trials today do not have adequate representation. It’s a public health issue.”
- In addition to recording data on race and ethnicity, clinical trial sponsors should collect data on social determinants of health. This can help sponsors understand and address the underlying causes of low trial participation and where drop-offs in participation occur.
- Clinical trial sponsors should ensure their inclusion and exclusion criteria reflect the real-world populations of their indication. Arbitrary or historic standards, as well as undefined leeway for investigators to exclude patients, can severely hinder trial diversity.
- Clinical trials should include community-based sites outside of academic medical centers to recruit from a deeper, more diverse pool of patients.