By David J. Morin, MD, FACP, CPI, FACRP, Association of Clinical Research Professionals
As a physician, I consider our profession to consist of a broad collection of independent-minded spirits with one goal: to deliver the best possible care to patients. However, as a principal investigator (PI), I belong to a subset of physicians with a unique purpose and responsibility – to safely supervise the consenting study participant's journey through the clinical trial and provide the sponsor with valid and complete study data. PIs take this responsibility very seriously since the health and well-being of our study population and the public depend on it. It's not only a sacred trust but also a contract we make with the regulatory authorities to be held accountable should we stray from that commitment. This supervision provides verifiable trust, which is essential from a public perspective. Our willingness to accept responsibility stems from our confidence in those to whom we delegate authority to assist us in implementing study processes.
As we all know, the complexity of clinical research studies requires a team of highly skilled and knowledgeable professionals who work to implement the study activities under the supervision of the PI. Historically, the study visit almost always occurred at a research site or medical facility, but that is changing. The pandemic presented an existential threat to thousands of studies worldwide. It required the rapid adoption of processes that brought the study to the patient via virtual and off-site practices. Decentralized clinical trials (DCTs) move the study visit to the patient and away from the site as the center of activity. Hybrid trials use a combination of on-site and off-site processes. The goals are to broaden access and participation in clinical studies and increase the diversity of study populations. In addition, this process encourages novel data sets through mobile health technology, yielding a better understanding of the safety and efficacy of investigational products (IPs). These changes should well serve the public.
As we work to harness the benefits of hybrid and DCTs, sites and investigators must have processes that allow for the acceptance of DCTs and successful implementation. As these policies are under development, the vital viewpoints of sites and PIs are largely overlooked in this discussion. Existing guidance may not adequately cover the DCT processes I have seen proposed, namely, study visits conducted in the patient's home by a health nurse provided by the sponsor or by the site staff or when IP is delivered directly to the patient's primary care provider. The ability and willingness of PIs to accept these responsibilities rest on our collective trust that the process adequately addresses our shared concerns.
Pending updated FDA guidance documents on DCTs, the regulatory requirements are the same for DCTs as for site-centric studies. In 2009 the FDA released its final guidance on investigator responsibilities. The document confirms the PI's responsibility for qualified study staff directly involved in the conduct of the study to whom they have delegated study duties. 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 was clinical chemistry testing "commonly done by a central independent facility retained by the sponsor." The difference in determining if the PI or sponsor is responsible is whether that individual or party is directly involved with “patient care” and has “direct control.” But should the PI be held responsible for activities that directly involve “patient care” per protocol but where they have no “direct control,” and how does this apply to the new DCT process I noted? Let's explore these in order.
1. Study visits conducted by a sponsor-provided home health nurse (HHN).
Provided there is mutually acceptable documentation of the HHN's qualifications and training, the PI may be willing to accept responsibility for the HHN's actions and delegate authority. However, since the HHN is not under the direct control of the PI and will be performing services off-site, it may be very challenging for the PI to provide "adequate supervision and oversight," resulting in the PI's unwillingness to delegate authority. Also, even though there will be additional complexities and site processes and time in managing oversight and data entry, the sponsor's contribution to study personnel may adversely affect the site's study budget. Furthermore, sites have varying organizational structures, experiences, and physical layouts, which may require the sponsor to provide some flexibility in the study design (i.e., make the HHN visit optional).
2. Home health visit conducted by the site staff.
DCTs may require site staff to conduct home visits that raise logistical issues involving time, travel distance, personal safety, IP transport, lab collection, liability concerns, and safety assessments. Sites may exclude consideration of potential subjects who fall outside a certain distance from their location by creating a geofence. From a business perspective, it may not be financially feasible for a site to see patients outside a certain radius. Restricting access to a trial based on the geographic distance from the site runs counter to DCTs’ goal of broadening access and may also affect study diversity. Proper planning between the sponsor and the site may minimize both of these unintended adverse consequences by ensuring the budget accounts for the travel time incurred.
3. Direct delivery of IP to the study participant's primary care provider (PCP).
Direct delivery to the patient's non-study PCP or the study participant is a “critical aspect of the study involving patient care” but is “not under the direct control of the PI.” To be feasible, it would have to be a stable, low-risk IP with simple administration. Issues include documentation of patient compliance (perhaps with novel technology), IP storage, drug accountability, off-site monitoring, and PCP willingness and training. But would a PI delegate authority to a non-study PCP in this case or would the responsibility rest directly with the study sponsor?
These are just three scenarios that will require updates to regulations, oversight, standard operating procedures, budgets, recruitment strategies, training, and organization structure. In addition, a prospective analysis of how DCTs affect the main goals of broadening study participation, increasing patient diversity, improving study implementation, and their effects on the clinical research workforce is warranted. Finally, how we evaluate the impact of DCTs on patient safety, data integrity, and the research workforce depends on how regulatory authorities redefine the roles and responsibilities of sponsors, study teams, investigators, and other stakeholders considering these new expectations. In my opinion, engaging sites and investigators in this process is vital to realize the full potential of DCTs.
For more background on DCTs, you can visit the ACRP website to download the recent white paper on Decentralized Clinical Trials: Perspectives for Clinical Research Professionals developed by expert members of the ACRP Fellows.
About The Author:
David Morin, MD, FACP, CPI, FACRP, is the 2022 chair for the Association of Clinical Researchers Board of Trustees. He provides patient care and serves as the director of research at Holston Medical Group, a physician owned multispecialty practice in Tennessee, Virginia, and North Carolina. In addition, he is the director of the High-Risk Disease Prevention program for a Fortune 100 company.