Diversity and ePROs: Still siloed concepts in the era of DCTs?

ePRO is a health outcome that is directly reported by the trial participant and collected by an electronic method. Credit: Irina Strelnikova via Shutterstock.

Decentralised clinical trials (DCTs) are often pinned as a silver bullet to increase a trial’s footprint and reach various populations that otherwise would not participate in research. But as the industry takes off its rose-tinted glasses after a few years of hype surrounding DCTs, it is time to evaluate whether decentralisation actually helps improve diversity.

One of the most patient-centric methodologies in the DCT toolbox is electronic patient-reported outcomes (ePROs). According to the glossary by the Decentralized Trials & Research Alliance (DTRA), ePRO is a health outcome that is directly reported by the trial participant and collected by an electronic method.

Only in the past couple of years have non-electronic PROs taken a more prominent place in clinical trials, as sponsors are using them as primary and secondary endpoints, and not just as exploratory endpoints, says Florence Mowlem, PhD, vice president of science at virtual research organisation ObvioHealth. This was enhanced by several recent guidance documents on patient-focused drug development by the US Food and Drug Administration (FDA).

As traditional PROs have only recently been added to the clinical trial toolbox as significant endpoints, the use of ePROs is even newer. The use of ePROs in US-based DCTs is very low compared to another popular DCT tool—telemedicine. According to a data analysis carried out by Clinical Trials Arena, only 1% of DCTs use ePROs, while 52% of US-based DCTs use telemedicine.

However, it is not the case that ePROs are yet to secure their place in DCTs, but rather an issue of disclosing if data was collected via an electronic device or not. Mowlem says sponsors need to specify when PRO data was gathered electronically because it creates a standard in the industry on what is the best way to collect specific data. 

Alongside the rarely reported use of ePROs, sponsors are also sparing when it comes to reporting diversity data. According to the analysis, only 35% of US-based DCTs that use ePROs disclose the race and ethnicity of the participants, while 54% of US-based DCTs that use telemedicine report it. Clinical trial data reporting has been a constant pain point. While there has been significant improvement over the past couple of decades, the industry still has more work to do, as recently reported by Clinical Trials Arena.

The data analysis, part of the quarterly update of DCT Tracker, relied on an exclusive taxonomic approach, which involved the review of thousands of public drug trial records from 2010 to date, as curated in the Clinical Trials Database by GlobalData, the parent company of Clinical Trials Arena. 

The absolute number of DCTs reporting race and ethnicity data remains significantly low despite the buzz around data transparency. While it is difficult to extract trends from such low numbers, homing in on the ones that do report diversity data, the analysis shows the few DCTs that use ePROs or telemedicine recruit a similar percentage of participants with different racial backgrounds. However, participants from white racial backgrounds still form the majority.

It is also not clear if DCTs are improving diversity data reporting. According to the data analysis, there was a 38% year-to-year decrease from 2020 to 2021 in US-based DCTs that used telemedicine and reported race and ethnicity data. In 2022, US-based DCTs that used telemedicine and reported diversity data dropped further by 85%.

As previously reported by Clinical Trials Arena, DCTs are yet to prove if they can significantly improve participant diversity, especially because the use of tools like telemedicine and ePROs can exacerbate the issue, as some people may not have access to the internet or devices. Jena Daniels, vice president of patient success at technology provider Medable, says sponsors need to think about providing internet access for provisioned devices. Also, while provisioning devices, sponsors and vendors should be aware of what patients might be accustomed to using. For example, if an iPhone-savvy participant received an Android phone, it might be difficult for them to operate it. “In addition to provisioning these devices as an opportunity to meet that gap, we also need to make sure that we're onboarding materials,” Daniels adds.

However, sponsors should also look into if device provision is the best option for the participant. Mowlem says there has been a recent trend of allowing participants to use their own devices, also known as bring your own device (BYOD). This way, there may be less burden on the participant to take care of several devices at once.

The type or format of an ePRO also matters as the preference may depend on the participant’s academic background. A study in 2020 showed that there was variability in preference for mobile-based versus website-based methods of ePROs amongst Black and white populations of those with cancer. A small number of Black participants preferred paper methods as they felt there was more time to think about the question, while some found it difficult to understand the paper symptom summary report.

Natalia Husby, solutions manager at CRO Curavit, explains that academic education may play a role in the difficulties experienced with interpreting the summary report. “This finding also highlights the importance of creating study materials that are accessible to people of varied academic backgrounds,” she adds.

When developing and tailoring questions for ePROs, sponsors and vendors should interact with patient communities to understand their experiences. “If it's not relevant or salient to them, it's going to be more difficult to recruit and retain,” Husby says. Indeed, improvement in quality of life could mean completely different things across various populations and regions, Mowlem adds.

If sponsors or vendors do not combine their ePROs with user experience, the technical brilliance of a product will not matter. Daniels explains that to improve the understanding of participant diversity, it is important to include patients in the protocol writing or run simulation studies to see if certain populations struggle with some of the questions in the ePRO. “If you can have technology that can adapt to different communities, that is where the culture and the product come together,” she says.

Decentralisation and all its methodologies have many features that could improve diversity in clinical trials, but now it is time to show the evidence for it, Mowlem says. Indeed, the data analysis shows that globally, only 27% of DCTs report data on race and ethnicity. “If we don't report it, we can't show that we're improving diversity,” she adds.

The situation is better in the US, with 45% of US-based DCTs reporting diversity data. Yet, Mowlem says this is still quite low. The higher reporting proportion in the US compared to global DCTs may be attributed to the FDA’s effort to increase diversity. However, other regions are not at the same level as the US agency. While the European Medicines Agency (EMA) has a recommendations paper on DCTs, it does not offer much guidance on diversity inclusion, she notes.

From a global perspective, the way race and ethnicity are described and reported may pose another challenge in understanding global inclusion trends. “The bigger question is how do we standardise it across different populations all over the world,” Husby highlights. But on the other hand, diet, culture and geography also play an important role in how a treatment affects a patient and these factors should also be taken into account, she adds. 

However, diversity should go beyond race and ethnicity. Mowlem says the implementation of electronic measures should also cover cognitive and visual impairments, and sponsors need to shift focus from maintaining measurement properties to optimising electronic data capture and patient experience. Daniels suggests including demographic factors such as age, gender identity, and sexual orientation, as well as mental health.

“We need to take a step back and think about diversity in bigger buckets,” Daniels says.