Clinical Researcher—April 2022 (Volume 36, Issue 2)
David J. Morin, MD, FACP, CPI, FACRP
2022 Chair of the Association Board of Trustees for ACRP
The definition of decentralized clinical trials (DCTs) varies from source to source, but a central theme involves processes that move data collection and investigational product (IP) administration closer to the study participant and farther from the site as the center of activity. DCTs are a natural evolution of research accelerated by the pandemic, and can provide novel datasets via mobile technology from “real-world” settings and virtual and offsite interactions. They can also broaden participation in research by enhancing researchers’ access to more diverse populations, resulting in a more accurate scientific understanding of future therapeutics.
DCTs, once resisted by many professionals but long preferred by many patients, are here to stay, and site processes and personnel must adapt to new operating procedures while maintaining traditional site-centric methods, which are critical in onsite/offsite hybrid models for conducting trials.
PIs and DCTs: A Healthy Combination?
With the rapid rise of DCTs to such levels of prominence as they are currently enjoying, we find ourselves embarking on an unprecedented experiment with the research process itself—one requiring us to tread thoughtfully in regards to how all stakeholders are affected, lest we run into the law of unintended consequences. Unfortunately, mostly left out of this discussion is how this affects the abilities and willingness of site staff and principal investigators (PIs) to perform the new duties and responsibilities entailed in DCTs.
In the conventional, site-centric model, coordinators and supporting personnel perform most protocol-related tasks under the supervision of the PI. The latter accepts responsibility for the conduct of the study and the safety of participants. When a study participant visits a site as directed by the protocol, all resources are available to complete the requirements and monitor safety. Trust is the main attribute behind the Delegation of Authority by the PI for those deemed qualified by training, education, and experience.
Pending the release of updated U.S. Food and Drug Administration (FDA) guidance on DCTs, the regulatory requirements are the same for DCTs as site-centric studies. In 2009, the FDA released the “Final Guidance Document” on “Investigator Responsibilities.” The document confirmed the PI’s responsibility for study staff directly involved in the conduct of the study, even when they are not under the PI’s employ—in effect, anyone to whom the PI has delegated study duties for which they are qualified.
However, the sponsor is held responsible for “critical aspects of a study performed by parties not involved directly in patient care or contact and not under the direct control of the clinical investigator.” An example provided in the guidance is clinical chemistry testing “commonly done by a central independent facility retained by the sponsor.” It seems, then, that the difference in determining if the PI or sponsor is responsible is whether the individual or party in question is directly involved with “patient” care and has “direct control.”
Who’s On First?
All of this raises the question: Should the PI be held responsible for activities that directly involve “patient” care per the protocol, but in situations under which they have no “direct control”? An example would be an offsite protocol visit conducted by a home healthcare nurse employed by the sponsor. Another would be when an IP is sent directly by the sponsor to the patient’s physician to administer.
In these cases, a regulatory decision to make PIs responsible may affect their willingness to accept a study. DCTs may also require site staff to conduct home visits that raise logistical issues involving time, travel distance, personal safety, IP transport, lab collection, and safety assessments. These will require updates to regulations, oversight, standard operating procedures, budgets, recruitment strategies, training, and organization structure.
Ongoing reviews of how DCTs affect the main goals of broadening study participation, increasing patient diversity, and improving study implementation, as well as their effects on the clinical research workforce itself, are needed. Much of this depends on how regulatory authorities define the roles and responsibilities of sponsors, study teams, investigators, and other new stakeholders. For more background on DCTs, you can visit the ACRP website to download the recent whitepaper on Decentralized Clinical Trials: Perspectives for Clinical Research Professionals developed by expert members of the ACRP Fellows.
In addition to his volunteer duties with ACRP, Morin provides patient care and serves as the Director of Research at Holston Medical Group, a multispecialty practice in Tennessee and Virginia, and is Director of the High-Risk Disease Prevention program for a Fortune 100 company.