The US Food and Drug Administration’s (FDA) guidance document on decentralised clinical trials (DCTs) published in September 2024 is a welcomed addition to guidance surrounding the employment of DCTs (1). Their draft guidance has been available to read previously, and this new publication sits nicely with the European Medicines Agency’s (EMA) recommendation paper published in December 2022 (2).
The FDA neatly describe a DCT as a ‘clinical trial that includes decentralised elements where trial-related activities occur at locations other than traditional clinical trial sites’. Decentralised elements as described in my previous blog post include a range of operational adaptions to a trial such as e-consent, telehealth visits or digital health technologies (DHT) to collect data. The interest in these adaptions to trial conduct has several potential benefits such as improved patient diversity and retention, and potential for greener trial conduct. The FDA guidance document summarises their recommendations for implementing DCTs in a positive light, affirming the suitability of their conduct whilst being realistic about the challenges and possible additional considerations needed for their implementation.
My Thoughts
I find these FDA guidelines on decentralisation to be both clear and comprehensive. The language is straightforward, portraying decentralisation in a positive light without veering into overconfidence or unrealistic promises. The guidelines thoughtfully address a range of essential topics and effectively direct readers to additional resources where needed. Importantly, they emphasise that adaptations should be tailored to the specific needs of each trial, encouraging a flexible approach rather than a one-size-fits-all model. It is also important to note that this guidance document is presented as a set of 'nonbinding recommendations,' providing suggestions for stakeholders without mandating specific actions.
However, I noticed there is no mention of routine data sources or electronic health records (EHRs) in the guidance. Given the current push for integrating these resources into trials, this omission seems a missed opportunity, as EHRs offer an excellent example of decentralisation in action. Additionally, although the guidelines frequently mention patients, they appear to lack direct input from patients and public consultations, which could have enriched the guidance with a more comprehensive patient perspective. It would also have been helpful to include recommendations on involving public partners in the trial design process itself, which could contribute valuable insights. Lastly, the guidelines could benefit from a discussion on the role of feasibility studies, either by suggesting their inclusion or by referencing existing studies for further learning.
Overall, I think this resource will be valuable for investigators and trial teams exploring the decentralisation of trial activities and will likely spark productive conversations on feasibility and implementation.
The Recommendations
The guidance document neatly outlines 10 recommendations for implementing DCTs with each section going into the detail of considerations needed for each.
DCT Design and Conduct | |
 | Highlights how there is a need to consider the potential variability in measurements that can be done in the home, but a hybrid model can be adopted in cases where the variability would be too high to control. There is also a useful point about considering the effect size when using data from a trial which was carried out in a traditional manner. |
Remote Clinical Trial Visits and Clinical Trial-Related Activities | |
 | This section describes the range in which clinical trial visits can take place outside of a central site which can vary widely. I think this demonstrates to stakeholders that we are not confined to a binary model or central site and isolated at a participant's home. Another important consideration point in this section is the collection of adverse events and how a successful system needs to be implemented so as to not lose important data. |
Digital Health Technologies | |
 | The guidance refers mainly to another guidance paper; Digital Health Technologies for Remote Data Acquisition in Clinical Investigations. However, it does emphasise the concern of accessibility of the patient population to digital heath technology and if it is appropriate to be used on a trial-to-trial basis based on the population of interest. |
Roles and Responsibilities | |
 | This section is a comprehensive breakdown of the role of the sponsor, the regulator, and the investigator and the delegation of trial-related activities. This is a useful section that can be extracted directly from and amended as per the trial unit which is conducting a trial to clearly list responsibilities. |
FDA Oversight | |
 | The FDA oversight section refers mainly to the FD&C Act and is less applicable outside the USA but may still be of importance when considering multinational sites. |
Informed Consent and Institutional Review Board Oversight | |
 | This section covers what the informed consent process should inform trial participants of including where trial activities will take place. This is an important point, making clear exactly what contact a participant will get within the trial so expectations and understanding of the trial process are clear. |
Investigational Products in a DCT | |
 | Drug and biological products and medical devices are both discussed. Drug and biological products are only to be administered under the supervision of the investigator or sub-investigator which means the feasibility of administration should be considered. However, if the profile of the product is well characterised it could be administered at a local site or in the home which emphasises this sliding scale of how decentralisation can be conducted. Again, for medical devices, the considerations before deciding on the type of decentralisation should be ‘the type of medical device, its intended use, its instructions for use, and the potential risks of the device for participants’. |
Packaging and Shipping of IMP | |
 | Details the documentation and steps required for direct shipment of the IMP to a healthcare professional or the participant |
Safety Monitoring in DCTs | |
 | As highlighted above this section goes into more detail of how safety monitoring should be carried out in a decentralised manner and how this may look different from a traditional trial design. However, we should still be upheld to the same high standard. |
Electronic Systems Used When Conducting DCTs | |
 | This covers a wide range of electronic systems from e-consent and e-CRFs which trial teams are probably familiar with by now to more complex systems like syncing digital health technologies and communication tools. Some regulations are most likely country-specific and need to be adhered to but also trial-specific training for all those involved including participants. |
This research was funded by the NIHR Imperial Biomedical Research Centre (BRC). The views expressed are those of the author and not necessarily those of the NIHR or the Department of Health and Social Care.
1. FDA. Conducting Clinical Trials With Decentralized Elements [Internet]. FDA; 2024 [cited 2024 Oct 15]. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/conducting-clinical-trials-decentralized-elements
2. European Commission. Recommendation paper on decentralised elements in clinical trials [Internet]. 2022 [cited 2024 Mar 20]. Available from: https://health.ec.europa.eu/latest-updates/recommendation-paper-decentralised-elements-clinical-trials-2022-12-14_en
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