The FDA’s Decentralized Clinical Trials Draft Guidance Explained

The highly anticipated Decentralized Clinical Trials (DCT) draft guidance from the FDA was finally released on 02-May-2023. In this 19-page document, the FDA outlines its current thinking around the concept of DCTs. From the outset of the draft guidance, the FDA makes a clear point on what DCTs can mean for patients and the patient experience: 

By enabling remote participation, DCTs may enhance convenience for trial participants, reduce the burden on caregivers, and facilitate research on rare diseases and diseases affecting populations with limited mobility or access to traditional trial sites. This may help improve trial participant engagement, recruitment, enrollment, and retention of a meaningfully diverse clinical population.

Enabling Diversity-Driven Clinical Trials

At the end of the day,  it’s not about DCT, it’s about diversity-driven clinical trials and enabling clinical trials through a reimagined approach using the CRIO platform. The draft guidance outlines some of the challenges and associated recommendations with DCTs.  Those challenges and recommendations include: 

• What is it going to take to drive diversity and recruit needed patients?

The FDA recommends developing a clear plan which outlines who performs each activity and where. It should also stipulate which activities can be done remotely. This plan should also specify whether you will utilize local healthcare facilities, healthcare providers or conduct in-home visits.

• Can you ship an Investigational Product (IP) to the patient or do they need to come in?

IPs that are simple to administer or that have well-defined safety profiles are likely better suited for a fully decentralized trial approach. A hybrid approach should be considered where the administration of the IP is complex or requires more direct oversight. Additionally, IPs with a less well-defined safety profile should also be placed in the hybrid category. Follow-up assessments could be performed remotely via Telehealth or in-home visits, where appropriate. 

• Does your team, sites and other research personnel know what they are doing?

To have a successful decentralized clinical trial, it is important that all persons who use electronic systems (including digital health technologies (DHTs) receive the appropriate training to enter, review and manage the data collected throughout the trial. Upfront risk assessments can help manage any potential pitfalls for all stakeholders involved. 

FDA Recommendations for Implementing DCTs

DCT DESIGN: 

Different trial activities can take place across a network of locations and remote settings. And investigators must demonstrate central oversight of all those trial activities. A physical location where all trial-related records can be accessed and trial personnel can be interviewed is another key element of this guidance. This may lead to some confusion because there will be additional hurdles in interviewing everyone who helped facilitate the trial. The FDA also states that local health care providers (HCPs) who perform activities which do not require detailed knowledge of the protocol or IP are not considered part of the trial personnel. These activities include performing physical examinations, reading radiographs, obtaining vital signs, etc.

REMOTE CLINICAL TRIALS & CLINICAL TRIAL-RELATED ACTIVITIES:

To make clinical trials more accessible, the FDA recommends that investigators consider Telehealth visits where no in-person interaction is needed. Visits that can be performed remotely via Telehealth should be outlined in the study protocol. 

As for in-person visits, consider options such as in-home visits by trial personnel or visits to the patient’s preferred location. Furthermore, depending on the protocol, the patient could utilize local HCPs outside of the trial personnel to perform trial-related services (e.g., performing physical examinations, reading radiographs, obtaining vital signs). These services should not require a detailed knowledge of the protocol or the IP.

Here’s a key quote from the guidance on how to decide when to use HCPs and Telehealth: 

Trial-related activities that are unique to research and/or require a detailed knowledge of the protocol or the IP should be performed by qualified trial personnel who have been appropriately trained. When applicable, both trial personnel and trial participants should be trained on how to conduct or participate in a Telehealth visit.

Using Digital Health Technologies (DHTs): 

While DHTs can be a key component of a decentralized trial, the FDA points to the dedicated DHT Guidance that was released in December 2021 for questions around selection of DHTs, validation, usability testing and other DHT-related matters. 

To prevent excluding patients from trials based on socioeconomic status, sponsors must ensure that DHTs are appropriate for all participants. One solution is to provide a sponsor provisioned DHT whenever possible. This removes the burden from patients who are unable to afford the specified protocol DHT and are therefore excluded from the trial.

Roles & Responsibilities

The Sponsor and Primary Aims: 

Sponsors of clinical trials should aim for diversity and inclusiveness in trial populations. Engagement, recruitment and retention can all be improved with outreach through local healthcare institutions and by bringing trial-related activities to participants’ homes. Using local healthcare providers close to potential participants’ homes is also suggested. This is aimed at improving participation and reducing cultural or linguistic barriers.

To account for all data points, implement a data management plan. The plan should outline the data flow from creation to final storage. This includes a list of all vendors/systems involved in the acquisition of the data and all potential points of origin (patients, trial personnel, local HCPs, etc). The FDA recommends the use of risk-based monitoring methods and centralized monitoring to proactively identify and address missing data, inconsistent data, data outliers, and potential protocol deviations. These actions can help detect and prevent systemic or significant errors in clinical trials.

The Investigator & Delegation of Trial-Related Activities 

Whether it’s a site-based, decentralized, or a hybrid trial, the investigator is responsible for the conduct of the trial. This includes ensuring that the delegated activities/tasks are conducted according to the investigational plan, applicable regulations and relevant laws. 

There are notable differences between DCTs and traditional site-based trials. Usually, it’s the extent of the adoption of DHTs, Telehealth, remote trial personnel, and local HCPs, just to name a few. To establish consistent implementation and execution, additional training may be required to ensure the tools are understood and workflows are clear between the different entities. Leveraging local HCPs to perform routine tasks that do not require specific knowledge of the protocol or investigational product (IP) can help facilitate access to patients who would otherwise be unable to participate. These routine trial-related activities can include:

• performing physical examinations
• reading radiographs, or 
• obtaining vital signs 

While not required to be listed on the FDA 1572, local HCPs should be listed in a ‘task log.’ This ensures central oversight of who performs actions and tasks in a trial. With different stakeholders involved, maintaining consistency in data collection can be challenging. The FDA recognizes the potential for variability. To that end, it suggests establishing Quality Control measures to help assess the consistency and completeness of the data collected. Depending on the tasks performed, different activities may require different levels of quality control. 

Informed Consent and IRB Oversight: 

The informed consent documentation must describe who has access to the patient’s data. This is particularly important with the involvement of multiple stakeholders. It must also address how the data is used and who to contact for questions during the trial. 

Further, with the prevalence of electronic informed consent, the consent visit itself may also be conducted remotely. If that is the case, investigators need to ensure that all applicable regulatory requirements are met. 

Safety Monitoring Plan: 

It is critical to evaluate and manage AEs  properly – whether they occur at a site, remotely, or at a HCP. Similar to a traditional site-based trial when developing a protocol and the safety monitoring plan, the capture of patient adverse events and any related action taken needs to be considered – especially when there are multiple parties involved (sites, local HCPs and others). Ask yourself the following questions:

• How can the patient report an adverse event?
• Who can/should receive the adverse event notification? 
• What data is collected when an adverse event is reported? 
• How can patients arrange unscheduled visits using Telehealth, for example?

In the event that an AE requires urgent or in-person attention, the protocol must clearly outline how care will be provided.

Software Used in Conducting DCTs: 

The activities outlined in the guidance cannot be effectively conducted without the adoption of software and electronic tools for data capture. Since data can be captured through software apps on cell phones, tablets or computers, anyone using software applications or DCT tools should receive proper software training. Electronic informed consent forms, remote reporting systems for local HCPs, visit scheduling tools or IP tracking software all require a baseline knowledge of those systems.

Notably, software tools that produce and process trial records are subject to the FDA’s 21 CFR Part 11 regulation. The latest draft guidance, issued in March of 2023, includes critical components to consider when implementing software tools and applications that support DCTs, including Digital Health Tools (DHTs). 

Summary & Key Takeaways

In summary, the DCT guidance helps sponsors, investigators and other stakeholders consider the implications of removing some or all of the in-person interactions of a traditional site-based trial. By setting expectations for sites, patients, local HCPs and others – investigators can achieve central oversight of a trial. Software applications and other digital tools help enable precise data capture, the conduct of remote visits (including eConsent), IP shipment and tracking, and even administration. Ultimately, the goal is to have a clear understanding of the capabilities of each software tool and how it can be leveraged throughout the trial.

Software solutions, like CRIO, can help all stakeholders drive toward a reimagined clinical trial approach. Central and paramount to a reimagined approach is the need to drive diversity in clinical trials. Accordingly, sponsors must recruit and retain patients that are a better representation of populations that will use the product in the real world. Key to this diversity is in giving patients options as to how they can participate in a clinical trial. Decentralization carries unique needs. It requires the assurance that investigators have complete oversight over all aspects of the clinical trial conduct and data collection. CRIO is central to this approach. It enables investigators and site staff to ensure this oversight regardless of where the clinical trial tasks are being conducted.   

Discover how CRIO can help you and your organization to reimagine clinical trials. Explore other insightful white papers and blogs at https://clinicalresearch.io/blog/

Read More: Increasing Diversity in Clinical Trials- 3 Steps for Sponsors