By Deborah Borfitz 

July 6, 2023 | Many assumptions have been made about how decentralized clinical trials (DCTs) could help with clinical trial diversity although little “rigorous evidence” exists regarding actual effects on study enrollment. That will require randomized controlled trials to compare DCTs head-to-head with traditional, in-person trials, says Jennifer Dahne, Ph.D., researcher at the Hollings Cancer Center of the Medical University of South Carolina and co-director of the remote and virtual trials program at the South Carolina Clinical & Translational Research Institute. 

As a clinical psychologist whose research program consists almost entirely of DCTs around technology-enabled interventions, she has a few general hypotheses about the impact of the remote method, she says. For one, it probably outperforms the standard approach in some but not all areas. Second, the hybrid model employing some of each tactic would likewise come with some of its own tradeoffs. “We just don’t know.” Her views on the matter were published recently in JAMA (DOI: 10.1001/jama.2023.6982).

Dahne says she’s encouraged by the request-for-information (RFI) issued in March by the National Center for Advancing Translational Sciences (NCATS), part of the U.S. National Institutes of Health, asking for input on critical issues surrounding DCTs. Last month, the Food and Drug Administration also released draft guidance providing recommendations for implementing DCTs where the term refers to studies where some or all of the trial-related activities occur at locations other than traditional clinical trial sites. 

Interest is building in examining DCT methods, embraced as a matter of necessity during the pandemic, to help clinical trials move forward and enroll populations representative of those experiencing the disease under study, says Dahne. For her line of research, she believes DCTs are a promising approach for evaluating technology-based interventions that deliver mental or behavioral health treatments to patient populations who might otherwise not access them at all. 

Some have hypothesized that a hybrid clinical trial design requiring initial in-person contact with individuals prior to going fully remote might promote better trial retention after the point of enrollment—or at least eliminate professional research participants or people trying to enroll fraudulently, she notes.  “But then you narrow the pool of who can get into your trial... to people who are geographically located near your accrual site.” 

Unintended Consequences? 

Dahne says she has grown increasingly curious about which patient populations are best and least suited for DCTs, in her case so that she can think about other treatment approaches for individuals who can’t be reached via technology-based treatment solutions.  

A recent grant from the National Cancer Institute is supporting a study on the delivery of smoking cessation via telehealth to individuals who are residing in the most rural parts of South Carolina, says Dahne, motivated by the unsurprising reality that they are underrepresented in clinical trials as a proportion of all residents in the state. But that still doesn’t answer questions about which trial design or the other works best, on a broad scale, at engaging different populations into studies.  

Finding those answers falls within the scope of research funded by the NCATS. In its recent RFI, Dahne notes, the agency does not use the term decentralized trial synonymously with a reliance on technology-based platforms. It acknowledges that a DCT can also mean bringing a trial to participants by having community health workers go out to people’s homes—as was done for trial enrollment and administration of experimental vaccines during the pandemic—which might increase access to a study but not necessarily for all patient populations.  

The missing evidence could worsen known barriers to participating in clinical research, such as mistrust of academic institutions and clinical research, Dahne says, noting that with DCTs clinical researchers may have less direct contact with individuals and thus fewer opportunities to dispel any misgivings that might exist.  

“We need to be examining the impact of decentralized methods versus traditional methods on each step of the [clinical trial] pipeline,” says Dahne, including recruitment and screening activities, treatment delivery, data collection over the course of the study, and dissemination of results back to participants. “It might be that you get more diverse participant groups enrolled in decentralized trials... but you lose something in data quality because it is all done remotely.” 

More research is needed to determine if the methods and procedures used in DCTs are having the desired effect on diversity, she says. The informed consent process, for example, is probably going to happen on a technology-based platform where information about risks and benefits is web-based and perhaps paired with a phone call, or paper consent forms are mailed out and reviewed telephonically. 

But what is the impact of that mode of consent compared to a face-to-face dialogue between investigators and participants in terms of individuals’ understanding of the protocol? And, following completion of the consent process, will study questionnaires be completed as often in a DCT as in a traditional trial? 

‘Nuanced Story’ 

De-implementing a common practice can be difficult and costly, says Dahne, adding a degree of urgency to properly evaluating DCTs now the pandemic is winding down. “The concern is if the train has already left the station, and we have inadvertently exacerbated health equity issues related to clinical trials, how do we bring it back in?” 

The oft-repeated issues about broadband access in rural areas and technology aversion among older adults may be “over-generalizations,” Dahne says. One of her postdoctoral fellows, (Margaret Fahey, Ph.D.) recently looked at preferences regarding engagement with behavioral health treatments via digital platforms for older adults and found that individuals 65 and up aren’t opposed to technology; they just favor certain platforms and mobile apps with simpler designs that accommodate potential sight and hearing impairments. 

Likewise, certain subpopulations of individuals living in rural communities may be either more or less likely to readily engage with DCTs and technology-based platforms, she adds. “It is likely a nuanced story.”