The DCT Revolution Is Over… Vive La DCT Evolution!

By Life Science Connect Editorial Staff

“Decentralized clinical trials” (DCTs) probably can be simplified to “clinical trials” at this point, given that nearly every study now incorporates DCT elements. The extent of DCT elements implemented can be impacted by endpoints, patient burden, site capability, home healthcare provider (HCP) availability, and more.  

Most agree the principal goal of DCTs is to balance these variables in a way that emphasizes patient-centricity: minimizing patient burdens while also expanding participant diversity, study access, and study reach. DCT strategies became firmly established in the industry during the COVID-19 pandemic, but today, the DCT ecosystem has matured significantly to include service providers with more real-world experience and advanced tools, plus a mindset of initiative versus reaction.

DCTs Must Be Proactive

Proactive DCT analysis is a critical part of trial planning that fosters patient centricity and helps to create an environment where data flows seamlessly. DCT elements have become better integrated into the protocol visit assessment and are a more significant part of a trial’s narrative in the informed consent form.

The pandemic provided a demanding proving ground for DCT strategies, showcasing the efficacy of some technologies and strategies while revealing the shortcomings of others. As a result, organizations and investigators quickly became adept at evaluating and applying DCT strategies. But expanding and/or altering endpoints after a protocol has been developed can overburden investigators and patients. Trial designers must exercise discipline in outlining the purpose of every DCT element proposed.

Every clinical trial has components that could be designed as remote/digital, but deciding whether to do so means contemplating the intervention, its safety profile, and how data will be captured. For example, Bayer’s DCT experience started with cardiovascular trials, typically requiring long-term outcomes or follow-up. The company identified different DCT challenges at each stage and narrowed its trial design process accordingly: What data must be collected in this stage, why, and how? The company next looked at the design challenges associated with fitting identified DCT components into the overall regulatory structure of traditional clinical trials.¹

In general, it is a best practice to start a DCT assessment by examining the protocol for visits expressly required to take place at the site, for example, because of instrumentation needs, personnel expertise, or regulatory stipulations. Then, discover which data can be collected in a more convenient location for the patient and record the risks inherent in each strategy. The same logic applies to the potential benefits or burdens associated with home nursing visits, drug shipments to patients, wearable devices, etc. Regardless of therapeutic area, the guiding principle of DCT elements is to apply them at the right time for the right patient.

Reduced Patient Burdens Drive Trial Outcomes

Digital biomarkers are a cornerstone of DCTs, and the industry must collect these data in the most unobtrusive/noninvasive way while ensuring data integrity. As advanced DCT tools and strategies enable researchers to more capably reduce patient burdens, attention can shift back to trial optimization. For example, consider a neurology/MS clinical trial. DCT elements, combined with home healthcare strategies, have proven to optimize both data collection and patient experience.

Approaching studies with that mindset, a recent Sanofi collaboration seeks to promote freer engagement between patients and sites through use of an AI-powered mobile app, which also can be used to complete some visit assessments.² Study designers also are exploring the use of photographs to let investigators and participants converse based on images, rather than a site visit (e.g., to examine lesions associated with a dermatology study). And, digital biomarkers are being examined to study actigraphy, i.e., measuring patients’ gross motor activity remotely and non-invasively. In each of these applications, data integrity/flow is being enhanced alongside patient convenience and comfort.

Effective execution of e-consent forms is a popular DCT area of focus. Sponsors want to complete the existing legal document while also making the informed consent process more substantial and more informative for the participant. E-consent sometimes is thought of as a static point in time but, particularly in a trial where DCT elements may be introduced after the trial has begun, it is a living document that presents opportunities to reassess general trial flexibility and data integrity. It also provides valuable touchpoints for patient feedback, creating a communication loop that supports investigators, enabling flexible patient options while maintaining pragmatic trial design and still safely achieving novel endpoints.

Patient Voice Must Be Reflected In Trial Design

Each DCT element’s deployment must keep patient experience, patient safety, and data quality at the forefront.  General study feedback from patient groups is common across clinical trials, but whether that information is relevant and actionable for patients in your trial is hit-or-miss. Thus, more specific, practical feedback from patients and sites must be sought to supplement that imprecise feedback, helping to avoid trial designs that depend on assumptions about the patient.

For example, in a pediatric trial, in-home nursing visits typically are embraced by participants’ families and other caregivers, who are saved travel, trouble, and time. However, some patients or caregivers may be reluctant to welcome a stranger into their home. Similarly, not all patients are comfortable with teleconferences, the use of mobile apps, or body-worn technologies that record and/or transmit their vital signs. Technology shortcomings do not have to be catastrophic to be bothersome to patients or worrisome to regulators. DCT decisions must always weigh the criticality of and accuracy of endpoints against providing patients with greater comfort, convenience, and relief from site visits.  

Toward this end, the Collaborative Institutional Training Initiative (CITI Program) “identifies education and training needs … and provides high quality, peer-reviewed, web-based educational materials to meet those needs.” In addition to helping sponsors identify whether they are developing necessary, novel endpoints using digital health technology, the CITI Program assists sponsors in locating resources to amplify patient voices. For example, the program helps sponsors to determine questions they might want to ask patients and sites during trial design. CITI is just one of several organizations available to help guide study designers in the direction of better patient engagement.

Enable Principal Investigator Oversight

Principal investigator (PI) oversight focused on patient safety and data integrity is a significant DCT concern. The ICH E6(R3) Good Clinical Practice (GCP) guideline’s most recent revision clarifies the extent of study oversight a PI is to have, as well as how the investigator can provide that oversight.

A Sanofi survey of key stakeholders, executed to understand what might inhibit or prevent uptake of certain DCT elements by patients and investigators, identified home nursing as a problem area because of this indemnity factor. As a result, the company ensures each home nurse signs the delegation of duties log, regardless of their employer, to ensure accurate documentation.³

Sponsors are encouraged to engage DCT/home nursing vendors early, creating and maintaining a clear, direct communication channel between the PI and visiting nurses. This creates accessibility and familiarity that support data integrity and positive patient experiences. For example, not all in-home care comprises an “absolute” healthcare visit. A telehealth visit may be conducted by an on-site investigator while an in-home HCP assists the participant, ensuring adequate oversight of the interaction.

For a site to ensure continuity, it is ideal to have a dedicated home healthcare nurse assigned to each participant, and then a backup home healthcare nurse assigned to the site. This strategy avoids cycling through a half-dozen HCPs over the course of the study, which increases stress on the patient and introduces data integrity concerns.

FDA regulators have indicated an openness to the idea of nursing professionals being able to conduct certain DCT procedures, within the scope of their ability, but without the necessary protocol training, and without being on the daily delegation of duties. EU guidelines are similarly forgiving, which has given confidence to sites and sponsors employing these methods.

Numerous guidance documents from various regulators have emerged in recent years, covering not only the application of DCT elements to clinical trials but also informing the use of real-world evidence (RWE), e-consent, and more. Now, the onus is on the industry to provide regulators with clear, actionable feedback so the latter can update perceived gaps or points of confusion in those drafts. Related, ICH E6(R3) is supposed to add a future annex discussing DCT components in more depth, based in part on industry feedback. 

As stated above, though, that type of feedback is reactive. Only so much clarity can be written into a guidance document; being able to interpret and implement that guidance is contextual. Engage regulators and vendors early and often to facilitate submission of a more thorough protocol. If the rationale and use cases for DCT design are not obvious to regulators, it will be problematic (e.g., the EMA now requests a protocol cover letter clearly explaining the trial’s decentralized components.)

Thus, it is important to recognize that patient adoption often is the least challenging part of DCT assessment, because modern patients expect trial sponsors to operate differently. Participants expect sponsors to minimize and eliminate burdens to participation as much as possible — not just obvious burdens, like travel, but additional burdens caused by tacked-on endpoints or difficult-to-use technology. To learn more, watch the recent Clinical Leader Live event exploring DCT creation and implementation, available on-demand through the support of Medable.