Decentralized Trials

The format of decentralized trials was developed originally developed to serve resource constrained researchers across a growing network of sites and really expanded during the pandemic when traditional in-person visits and activities, simply were not possible.

In a decentralized clinical trial (DCT), some or all of a clinical trial's activities occur at locations other than a traditional clinical trial site. These alternate locations can include the participant's home, a local health care facility, or a nearby laboratory.

For patients, this provides levels of increased flexibility and allows for enrollment of patients who may live further away and/ or have travel or cost related issues associate with coming on site.

Image caption: Modes of decentralized options and methods can be used at almost all stages of a clinical research study . Alt text- image of flow chart of decentralized trials, listing tools and methods to be used at each step of a clinical research study.

Decentralized trials also allow for an increase in the volume and types of data that can be collected.  In a centralized trial, data is manually collected during the in-person appointment at a single point in time; however, in a DCT, large amounts of data are collected at multiple points in time, revealing previously unknown relationships in data.

Decentralized trials leverage virtual tools such as trial matching, telemedicine, sensory based technologies, wearable devices, home visits, patient driven virtual health care interfaces and direct to home delivery of study drugs, materials. . In a fully decentralized clinical trial, subject recruitment, delivery and administration of study medication, and acquisition of trial outcomes data all proceed without involving in-person contact between the study team and the patient/subject. Currently, clinical trials for drug approval often already include decentralized elements, and DCTs often incorporate traditional design with decentralization of the patient/subject interaction.

From a trial matching standpoint, electronic medical record data can be accessed in ways by sponsors, in aggregate counts to determine if a site will be a successful candidate for a clinical trial. The data can be shared with site and the site team can work to reidentify those patients once they have trial approval. Besides improved feasibility, using real world data from the EMR to both inform site selection and recruitment, has also been shown to lead to more successful and generalizable trials.

Study start up activities- such as sending drug, supplies, materials, etc. can now be conducted virtually as can most site initiation visits and training on things like electronic data capture, telemedicine visit technology, digital signature logs. This allows for more geographically representative sites to collaborate and participate on studies.

Recruitment can now be conducted largely through online technologies like emails and patient portal messaging. Potential subjects can find trial opportunities on social media or websites and connect with study teams. Study teams can also use EHR data to find a cohort that matches inclusion exclusion criteria and recruit them for a trial. Newer technology allows cohort specific messaging in patient portals, which allows patients to identify their own study cohort, e.g. enrolled verses screening.

Consent can be performed virtually via visit and an electronic consent filed.

Many trials now use virtual visits for some to all of the site visits. Telemedicine visits can be conducted virtually between a participant and research team. This involves less, cost, travel and more frequent interactions. The research teams do need to ensure they are using a HIPAA compliant tools for the visit and that they have a documented, and followed process to confirm the patient identity.

Ongoing compliance can be monitored largely remotely, if not entirely. Monitors can view source and data view electronic means negating the time and travel to come on site. Additionally standard data capture forms can be built in the EMR or an electronic data capture system and shared with all sites by the sponsor. Data can also be captured directly from subjects through wearable devices, sensors, apps may be downloaded and used for data collection, etc.

Some things to consider though with virtual visits are:

  • Telemedicine– if there is any provision of care during the visit (physical exam, assessment or rash or AEs, etc.) then the provider needs to be licensed in the state in which the telemedicine visit is taking place. They cannot conduct telemedicine visits on patients out of state licensure.
  • With so much electronic documentation, for FDA regulated trials, part 11 compliance becomes even more important. Part 11 standards dictate that the data is validated and the equivalent of any written documentation or wet ink signed documentation.
  • Any digital medium being used will require both staff and patient training. The patients or subjects need to be fully trained on the tools they are using and have a clear-cut path to ask questions or get help. They also need to confirm their identity using two factor authentication or other approved methods. 
  • DCTs reduce travel and cost barriers for participants but they also increase reliance on technology, and often smart phones. This can serve as a barrier to certain populations and should be considered during trial development. A reasonable number of mixed methods should be considered for trials. Sometimes smart phones or other technology options may be provided to participants by the trial team.