Decentralized clinical trials are one tool in the arsenal for upgrading clinical trials. Decentralization may refer to a large variety of tactics and possible aspects, making it difficult to provide a single, complete definition. Even the terminology used to describe the trend has evolved over time, including mobile, virtual, digital, site-less, and remote. Despite the FDA’s stated desire to include and expand such techniques into protocol design, it’s probable that the work to establish the vision has hampered implementation
Decentralized clinical trials (DCTs) are studies that are “conducted via telemedicine and mobile/local healthcare providers, using processes and technologies that differ from the traditional clinical trial model.”
Remote decentralized clinical trials (RDCT) are defined as “an operational strategy for technology-enhanced clinical trials that make clinical trial activities more accessible to [participants] by moving clinical trial activities to more local settings.”
Technology is the foundation. Decentralization, of course, depends on your perspective of view. Certainly, participant-centricity should be at the forefront of our minds when defining and shaping the relative impact of a clinical trial. On the one hand, since participants are not required to visit traditional sites as often, participation extends beyond the trial site. Participants may now engage in clinical studies from the comfort of their own homes or other desirable places, rather than the site acting as a proxy for them in the past. Clinical trial supervision, whether by remote monitoring, fewer clinical investigators, or independent ethical review, are instances of decentralized components that might benefit from greater overt centralization if seen through the eyes of each individual participant—into their house.
However, the life sciences industry is growing. In headlines, the Plato-attributed aphorism “necessity is the mother of invention” is often utilized. But it needs more than a spark of imagination. The public health emergency has also provided the FDA with the opportunity to meet the challenge and provide guidance to level the playing field, rather than relying solely on industry leaders to forge ahead on an as-needed basis, where many were previously hesitant due to perceived regulatory uncertainty.
The FDA defines the conditions under which involved local healthcare practitioners (HCPs) are not considered sub-investigators and are not needed to be declared on the FDA Form 1572. Procedures that are identical to standard clinical practice do not qualify (as opposed to drug response evaluations or procedures performed specifically for the protocol and separate from standard medical treatment), but the overall requirement of “direct and significant contribution to the data” remains in effect.[5] Alternatively, these HCPs must be recorded in site records, such as the delegation log. Of course, the details of the experimental medicine’s administration should be contained in the IRB-approved protocol.
In addition, the FDA emphasizes that investigators must ensure that participants’ medical records are available to necessary documentation, especially if the HCP supplying the investigational product (IP) is not considered a sub-investigator. As a consequence, the investigator need the participant’s consent to access trial-related information from the medical file (such as vital signs and usual symptom rating associated with IP administration). The FDA further urges the investigator to notify the HCP immediately of their intention to seek these materials. The FDA confirms that IP may be shipped directly from a central distribution site to an HCP or — if the risk profile allows — to a participant, provided that such shipping is done under investigator supervision and that procedures are in place to ensure product quality and accountability (i.e., that the protocol’s specified IP storage conditions were followed during shipping and that the IP packaging was intact upon receipt). The FDA also provides advice on how to dispose of remaining intellectual property when there is no direct site involvement.
Furthermore, the FDA has tried to make remote clinical study administration simpler by offering access to the MyStudies platform for electronic consent. Furthermore, the FDA has boosted its efforts to make low-risk digital health devices more widely accessible, especially in the area of mental health.
However, these suggestions, like those provided by several government agencies[14], are often confined by the duration of the epidemic. To maintain acceptability, it is vital to maintain the current pace while using innovation and experience. Consistency in the interpretation and application of standards provides entrepreneurs with a level of comfort in corporate planning, and it is also critical to intellectual property rights. The same may be said for clinical trial planning. In order to meet industry expectations and retain benefits, the regulatory framework after COVID-19 must be clear and consistent. A large retreat, on the other hand, might endanger participants’ confidence in developing decentralized techniques and best practices. Furthermore, it’s unknown what, if any, long-term consequences the epidemic will have on participants’ views toward further exposure and socializing in an environment with practical and safer options.
Clinical trial decentralization is not a panacea for all of its challenges. Yes, these strategies have the ability to remove long-term racial and other inequities in clinical trial participation, boost efficiency, and decrease the entrance barrier. However, as healthcare becomes more decentralized in general, there will be many of the same as well as new barriers to participation in clinical trials; whether these barriers remain in place remains to be seen. Awareness of clinical trials remains a barrier among both patients and clinicians. One of the new difficulties that has emerged is simple identity verification for participants and anybody else who may be present during a telemedicine consultation. Telemedicine laws and payer coverage choices are becoming more accommodating of telehealth as we go toward service and payment parity. This program may enable more healthcare providers to participate in clinical research. More varied investigators and research employees may also boost the diversity of participant populations. Will equal access to clinical trials, as well as parity in service and payment, result in better health? Or, given our limited technical skills, may we create a sifting of the pool of possible investigators and participants, heightening worries about research fairness and equality?
Clinical trials are unquestionably more popular and exciting than ever before, particularly right now. DCTs should have the greatest impact on participant satisfaction, engagement, and retention. Stakeholders should be prepared to continue supporting infrastructure and supplying technology to prospective participants as required to level the playing field in order to fully realize the inclusive potential of DCTs—at least for the foreseeable future.
DCTs are not one-size-fits-all, and a hybrid approach will often be necessary, particularly when applied across many nations with varying demographics, policies, and technological uptake. When hybrid models are utilized, sponsors must carefully assess changes in clinical trial conduct against unnecessary or possibly misleading variability in the data provided. When the decentralized components are optional, the researchers should describe the relative differences to participants (for example, are there unique confidentiality difficulties with a digital health gadget or home health service?). It goes without saying that this complicates planning unless the core processes (such as plans for risk assessment, monitoring, intellectual property responsibilities, training, privacy and security, and so on) are built and verified by transformative experience. As is often the case, including all stakeholders (such as participants, investigators, regulators, and so on) early in the planning phase is the best approach to decrease complexity and ensure efficient DCT implementation.
