Table 1 A list of DCT potential components categorized by the different aspects of a clinical trial
COMPONENTS | FULLY DECENTRALIZED | HYBRID | SPECIAL ATTENTION FOR PEDIATRIC COHORT |
|---|---|---|---|
Site activation | Â | ||
Site selection and activation | Can be done remotely through teleconference. | Similar to a fully decentralized trial | Appropriate settings for recruiting children may include schools, childcare centers, and other common settings for children. Researchers should ensure that the data collection site is safe, convenient, and child-friendly |
Enrolling trial participants | Â | ||
Recruitment | Recruitment can be conducted by web-based methods, social media, physician referrals, patient advocacy groups. | TV, radio, newspaper, physician referrals, posted fliers, mailings, cold calls, and the internet. | Risks and benefits need to be more properly explained (especially when there are no direct benefits) |
Consent | Potential participants review required study documents and provide a digital signature for consent remotely. We need to ensure that participants are comfortable interacting with staffs. | Similar to a fully decentralized trial | A dedicated team to address parents’ and children’s question before signing the consent and assent in a timely manner (24 − 7, same day, or at least next day availability) |
Trial conduct | Â | ||
Pre-screening and clinical visits | Televisit: Investigator-Participant interactions can be connected by bilateral communication (via the mode of Face-to-face, Telemedicine, Text, Chat, Telephone, etc.) Home health visit: Trained mobile healthcare providers (e.g., nurses, physicians, phlebotomists) conduct in-person evaluations at a time and location convenient to the participant. Mobile healthcare professionals (HCPs) perform safety procedures, such as blood collection, vital sign review and other required study evaluations. Mobile HCPs provide supplies and instruct the participant the ability how to collect urine, saliva, and stool samples in their own home to be sent to the central lab for analysis. | Trials with complex imaging needs, radiographic and surgical procedures (e.g. biopsies) require on-site visits. Remote visits, as appropriate, can be considered for follow-up. Some decentralized activities may only be accepted (e.g. culturally or per local regulations) in some countries and/or patient populations and may necessitate another type of hybrid approach. | For televisit, the investigators need to ensure that the children are willing to compliant with the directions via telemedicine, chat, etc. |
Data collection | A clinical outcome assessment (COA) can be administered on a general-purpose computing platform (e.g. mobile phone, tablet, or smart watch) and is then referred to as an electronic COA (eCOA). Types of COA include clinician-reported outcomes, observer-reported outcomes, patient-reported outcomes, and performance outcomes. Continuous monitoring of vital signs and other status assessments by Digital Health Technologies (DHTs) are considered as one of the major data sources. During the home health visit, the mobile HCPs can input participant study data directly into eSource data (e.g., electronic Case Report Form) which feedbacks to the site or directly feed into the Electronic Data Management. | Similar to a fully decentralized trial | eCOA and ePRO need to be fit-for-purpose for the pediatric cohort’s age and knowledge. For example, sometimes emoji-based responses are more interpretable than text-based responses. If DHTs are used, their form factors should be accepted by the pediatric patients. For example, a common size apple watch may be inconveniently big for a preschooler. Sometimes, color watchbands and those with animals’ figures can be more welcome for younger children. A pre-study feasibility and user acceptability test may be called for. |
Safety Monitoring | Train investigative staff on processes that are unique to DCTs, such as remote safety monitoring and procedures needed to support documentation. A list of approved local health care facilities and/or clinicians for emergent issues help the participants at a remote location with questions about possible adverse events. Investigators must coordinate facilities/clinicians near the trial participant’s location. | Can be similar to a fully decentralized trial | A 24 − 7 team who understand the common safety concern and safety monitoring should be ready to answer questions. A regular email or text check-in may be called for. |
Clinical supply | Samples, supplies, and unused investigational medicinal products (IMPs) can be directly shipped or collected from the participant’s home or to home nursing agencies, which can be managed by investigational products accountability tracking system. | Trials with complex investigational product administration (e.g. gene therapy) require on-site visits | Children’s school and other care-related schedules need to be considered when an on-site visit is called for. |
Trial closeout | eTMF (electronic Trial Master File) is the trial master file in a digital format. The EMA and the FDA have released regulations, policies, and guidelines to follow for validating the use of this electronic format, the most widely followed being CFR 21 Part 11. | It has become standard in the pharmaceutical and biotechnology industries to use an eTMF, a good option for both hybrid trials and traditional trials. | eTMF is the standard practice. |
Data monitoring | Tools of centralized monitoring (e.g. remote evaluation of clinical data) can be developed to identify key quality and risk indicators early (e.g. missing data status) and monitor them throughout the study. Remote source document review provides site monitors remote access to physical sites so that they can continue to monitor source data and documents. Clinical research associates (CRAs) can work remotely, even completing source document review or full site visits from home using the same types of technology that patients use for virtual visits. | Centralized monitoring is still a critical component for hybrid mode because direct access to clinical sites and patients is reduced. | Monitoring related pediatric-specific methodological training will be needed. For pediatric studies, the items to be closely reviewed can be prespecified. |
Trainings | Technology should support adequate training for all stakeholders involved in the DCTs. This includes but is not limited to, participants, site staff, call centers, sponsor staff and provision of insight to regulators and EC/IRBs. | Can be similar to a fully decentralized trial. | There should be specialists available to address issues related to pediatric patients using technologies, such as DHT device placement. |