Full or Hybrid decentralized clinical trials (DCTs) are facilitating new treatments through the advancement of clinical development in many therapeutic areas and will likely be incorporated into more trials every year. To make this transition as successful as possible for Sponsors, Sites, CROs, and Study Participants, we need to ensure we’re mindful of all the components that make up a DCT to set everyone up for success
In this blog, we’ll discuss DCT capabilities, study design, and planning considerations to keep in mind while planning a DCT.
What is a DCT?
DCTs are designed to support less physical interaction with participants and more virtual support through various technology platforms like telehealth, wearables, direct to patient drug shipments, remote labs or scans, Electronic Patient-Reported Outcomes (ePRO), Electronic Clinical Outcome Assessments (eCOA), and Electronic Informed Consent (eConsent).
The FDA’s response to DCTs
The FDA has called on CROs and sponsor organizations to increase the diversity in clinical studies. One major way to do this is through decentralized clinical trial elements and platforms.
In November 2020, the FDA published guidelines on DCTs and their hope that future studies will better represent the population that will be using the drugs if they are approved.
In December 2021, The FDA published a draft guidance on digital health technology for remote data acquisition and clinical investigations that speaks to verification, validation, and useability of digital health technology like smartphones and wearables.
You can find a list of all FDA Guidance Documents on Digital Health Content here.
The differences between Hybrid and Full DCTs
It’s common for clinical studies to utilize one or more DCT technologies even if the trial is not fully virtual or remote. We refer to these as Hybrid DCTs. These studies will have a mix of remote and traditional onsite assessments that allow for flexibility in study design.
Full DCTs, however, are fully digital and virtual. They have no, or very limited, in-person tracking from a traditional clinical site.
5 study design factors to keep in mind when considering a DCT
When considering a DCT, whether it’s hybrid or full, there are specific study design factors to keep in mind. Just because you can utilize DCT functionality, doesn’t mean you always should. We’ve summarized these considerations into 5 main points below.
- Complexity and potential challenges: Therapeutic area and Visit Assessments
In traditional trials, drugs are transported and stored at a central research site where storage and stability requirements can be met. However, with full DCTs, the drug would need to be shipped to the individual participant’s home, which can present many challenges. These include:
- A lack of guaranteed stability and storage requirements
- Prevention of unauthorized access
- Detection of drug tampering
- Interruptions of study drug dispensing due to not receiving drug refills on time
These challenges could potentially be addressed with a hybrid DCT, where the visit assessments can be more flexible, and participants can go to the site for investigational product (IP) dispensing or administration.
When specialized tests are required, like MRIs or blood draws, study participants can be offered a choice of going to the clinical site, visiting a local lab or hospital, or a visit from a mobile health unit.
- Targeted age group and potential technology or time barriers
Participants have a direct effect on the successful conduct of your trial. You must evaluate your patient population carefully and consider potential patient challenges that could negatively affect a hybrid or DCT trial.
- Does your patient population have impairments like colorblindness or deafness?
- Are your patients tech-savvy?
- What training will they need to use the technology?
- Are devices to engage with the technology readily available within the target population?
- Will they be able to use the technology independently?
- Will they be comfortable not having any or limited face-to-face interactions?
3. Licensing requirements and timelines
There should be discussions very early on regarding the assessments and data collection tools that will be used, the licensing required to use them, and who will be responsible for obtaining the licensing.
Some ePROs and eCOAs are open source, while others are under strict copyright and licensing that can be costly. Sponsors might need to be made aware of these requirements and might decide to source the development work to a vendor at the very last minute, which will impact timelines.
It should also be decided as soon as possible, who will be responsible for validating the devices and setting up the timelines to validate any integration needed.
Obtaining licenses can take several weeks. Other licensing considerations include the following:
- Sometimes licenses require agreements or payments for different modes of collection (tablet vs. hand-held vs. desktop vs. Bring Your Own Device [BYOD])
- Electronic Capture Validation of the assessment may only be available through preferred vendor platforms.
- If validation is not already done through your preferred platform, it may be available, but could take 4-16 weeks
- Ensure all modes of collection (if multiple) are comparable to each other
- Will paper capture be used as an emergency backup, or if a participant refuses to enter electronically?
- IF BYOD is utilized, how will the participants’ devices be approved?
4. Regulatory Considerations
Regulatory agencies have clear guidance in place for conducting DCTs, so it’s important to understand them as you start study planning activities. Additionally, it’s essential to ensure relevant technologies are used in line with the applicable data protections for each country where a study will enroll.
Early engagement with regulatory authorities is strongly encouraged. Don’t wait until the protocol has been set and changes become difficult.
The MHRA, FDA and Health Canada are clear that they support DCTs. They know that all DCTs will not be the same but expect patient safety and data integrity to be prioritized. Digitally enabled activities must safeguard patients, maintain compliance with good clinical practice (GCP), and minimize risks to trial integrity.
- Infrastructure and technology
There are infrastructure considerations and challenges that might impact the feasibility of using technology in your DCT. For example, you cannot run a DCT trial in an area or country where there is no or limited internet access.
- Plan how to replace lost, broken, or stolen devices
- How will devices be replaced if they are lost/broken/stolen while the participating is away from their home address (for example, on vacation)?
5 considerations for planning a DCT
Once a DCT, Full or Hybrid, has been determined to be in the best interest of all parties, the following outlines some of the considerations for study planning.
- Vendor Selection
Vendor selection should be made as soon as possible. The Digital Data Collection Tools will be your main source of data collection, so they need to be easy to use. Participants are unlikely to tolerate excessive issues or bugs. If your vendor technology is not easy to use, it could result in early withdrawals that might put the success of the trial at risk.
Our recommendation would be to consider using specialist vendors where possible. For example, for drug shipments. This would ensure the IP stability is maintained, confirmation of delivery is obtained, and that the IP is dispensed to a specific participant.
Vendors can be critical as they will be able to guide and assist you in navigating your options and the professional services they can provide, especially when considering specific regional challenges.
- Ensure the protocol, the investigator plan, or any other study document provides detailed descriptions of the use of DCT elements
Everything should be documented. This includes:
- All electronic systems that will be used in the study
- The roles and responsibilities of all stakeholders
- System Validation, backup of technologies, licensing of applications, device provisioning and replacement
- Drug accountability and compliance: the procedures in place for keeping account of the IP and controlling the compliance of trial participants
Ensure all contracts and agreements between stakeholders and 3rd party providers are in place. It’s important to determine where contractual obligations lie within a DCT and who the responsible party is for each element.
- Training
All investigators and sites need to be trained in DCT processes and the use of DCT technologies.
Trial participants need to know what to do, when to do it, how to do it, and even what to do if they don’t know what to do as soon as the study starts. Determine their point of contact and what options will be available to them.
There could be in-person visits for training participants that may include administration of the study drug and use of a telemedicine platform.
- Data Considerations
It needs to be decided and documented how the data will be collected, stored, secured, and tracked. Who will have access to the data? How will you keep track of participant interactions with investigators, health care professionals, call centers, or video telemedicine interactions?
- Audit Trails
Clear documentation must be in place to ensure data provenance. This will include detail of the data flow from source to report, like the source data locations, date collected, data handlers, data protection, data access, data ownership, training, etc.
Patient safety is of the utmost importance, so plan how AE/SAEs will be managed from technologies and how participants will be supported.
In addition to the 10 considerations listed above, a clear risk assessment should be in place for all DCT trials
Regardless of the approach, whether it is a hybrid or full DCT, the investigator and sponsor responsibilities do not change.
There are many challenges associated with DCTs, some examples are mentioned above, and you need to be clear on the expectations to be able to evaluate if a DCT is feasible based on the requirements and conditions set out in the protocol.
For instance, you need to consider whether the endpoints can be measured remotely. What if there is a need for specialized equipment that is not available to the patient at home, like MRI scanning?
What are the benefits of a DCT?
It can be a patient-centric approach.
Decentralization is making clinical trials more patient-friendly and accessible by bringing the trial to the participant. We live in a society where most people have fully packed schedules, and many patients don’t enroll in clinical studies because they can’t fit any more into their lives. The utilization of telemedicine makes it easier for study participants to interact with study personnel at their convenience. eReminders can also be employed to help participants remember to submit important data consistently, in real time.
It could enhance recruitment and diversity.
DCTs can decrease geographic barriers to studies for patients of diverse populations, including the elderly, those living in remote areas, or ethnic minorities. All populations that are currently underrepresented in traditional onsite design. The study design saves time for patients by reducing the travel burden to the clinical site and disruptions in their day-to-day activities.
In addition, DCTs can be used as a means to bridge inclusion in studies in both developed and developing regions. This ultimately means a better representation of the population.
It might reduce site burden.
The technology used in DCTs can make the consent process for a trial more efficient. Sites are better supported, and with reduced on-site visits there’s less of a burden on them. Sponsors may also benefit from reduced costs, less travel time required for monitoring, and enhanced data accuracy.
To learn more about DCT technology like ePRO and eCOA, read our blog covering those topics here.
Email info@mmsholdings.com to talk to a DCT expert.
Learn more about our data management experts here.
By: Krista Bossi, Senior Clinical Data Manager, Ronelle Adlem, Senior Manager of Clinical Data Management, and Doreen van Huyssteen, Associate Director of Clinical Data Management
