Clinical Trials Join the Remote Work Revolution: FDA’s New Draft Guidance on Decentralized Clinical Trials

On May 2nd, FDA released a new draft guidance with recommendations for decentralized clinical trials (DCTs) for drugs, biologics, and devices.  A DCT is a clinical trial where some or all of the trial-related activities, such as administration of the investigational product, data collection, or safety monitoring, occur at locations other than traditional clinical trial sites.  In a DCT, trial-related activities may occur in trial participants’ homes, at local health care providers’ offices, or in local clinical laboratories.

DCTs became more common during the COVID-19 public health emergency, when sponsors were motivated to conduct more clinical trial activities remotely in order to avoid in-person interaction.  This draft guidance builds on recommendations that FDA initially developed early in 2020, in response to the COVID-19 challenges (see our blog post on these recommendations here).

Section 3606(a) of the Food and Drug Omnibus Reform Act (FDORA) directed FDA to “issue or revise draft guidance that includes recommendations to clarify and advance the use of decentralized clinical studies to support the development of drugs and devices,” not later than December 29, 2023.  This draft guidance was published in response to this statutory mandate.

The draft guidance notes that DCTs may not be feasible for all study designs.  Notably, the draft guidance explains that variability of the data obtained in a DCT, compared to a traditional clinical trial, could affect the validity of finding non-inferiority but would not affect the validity of a finding of superiority.  For example, in a non-inferiority trial where the effect size of an active control drug has only been determined in a traditional clinical trial, the same effect size may not be seen for the active control drug in a DCT.

With regard to clinical trial visits and activities, the draft guidance provides examples of the types of approaches that may be possible with a DCT.  Study visits can be conducted using telehealth visits if in-person interaction is not necessary.  Trial personnel can also be sent to participant’s homes.  Visits can also potentially be conducted by local health care providers close to a participant’s home, rather than clinical trial personnel.

DCTs often include the use of digital health technologies (DHTs), which is technology that can be used to remotely capture and transmit health care information.  DHTs include monitoring instruments (e.g., activity trackers, glucose monitors) and software (e.g., mobile applications to capture patient-reported outcomes through questionnaires).

The draft guidance is part of a larger FDA initiative related to DHTs.  For example, in March 2023, FDA issued a Framework for the Use of Digital Health Technologies in Drug and Biological Product Development, which noted that FDA would publish guidance on the use of DHTs in both traditional and decentralized clinical trials.  FDA has created a DHT for Drug Development website and an email address for questions related to DHT-derived data (dhtsfordrugdevelopment@fda.hhs.gov).  FDA has also launched a series of five public workshops on issues related to DHTs in regulatory decision-making.

The draft guidance cautions that any DHTs used in a DCT should be “available and suitable” for all trial participants.  If participants are permitted to use their own DHTs, sponsor-provided DHTs should be available as an option to avoid excluding participants from the trial due to lack of available technology.  In a CDER Conversation regarding DCTs and DHTs, Leonard Sacks, Associate Director for Clinical Methodology in CDER’s Office of Medical Policy, noted that there is a risk that technical hurdles could skew a trial population to a “younger and more tech savvy” population compared to the actual patient population.

DCTs also have the potential to increase diversity and inclusiveness in trial populations.  The draft guidance states that the use of local health care providers, for example, may “improve engagement, recruitment, and retention of diverse participants” and “may reduce cultural or linguistic barriers.”  Dr. Sacks also explained that DHTs and DCTs may “open access to research” for older individuals and people with disabilities who are not able to travel to clinical trial sites, but could participate from home or a nearby clinic.

The draft guidance outlines some of the practical considerations for DCTs with regard to recordkeeping and clinical trial operations.  For example, the draft guidance notes that the trial’s data management plan should include information about the multiple sources of data collection.  Additionally, the draft guidance describes when local health care providers may be considered sub-investigators for purposes of completing Form FDA 1572 (for drugs) or the list of investigators in an investigational device exemption (IDE) (for devices).  Investigators should also maintain a task log of all local health care providers who perform trial-related activities.

The draft guidance also states that informed consent can be collected remotely or electronically as part of a DCT, so long as there is institutional review board oversight.  The informed consent process should inform participants whom they should contact with questions.

The draft guidance describes situations when an investigational product should be administered with in-person supervision by an investigator at a trial site versus shipped to a patient’s home.  Investigational products that involve complex administration procedures or have a high-risk safety profile may require in-person supervision, while products for which the safety profile is well-characterized and do not involve specialized monitoring could be administered at home without direct supervision.  The stability profile of the product must be considered when a product is shipped to a participant’s home.

The draft guidance provides recommendations related to the safety monitoring plan in a DCT.  The safety monitoring plan should ensure that all adverse events are appropriately captured and addressed despite the decentralized nature of the trial.  There should also be a plan in place for responding to adverse events, including how participants are expected to seek medical assistance locally when necessary.

Finally, the draft guidance addresses the use of software in a DCT.  All parties using software should be trained on how to use it properly.  Any software that is used to produce or process trial records must be compliant with the requirements in 21 C.F.R. Part 11.  FDA considers real-time video interactions to be a live exchange of information between trial personnel and trial participants, so these interactions are not subject to Part 11, though local laws regarding telehealth may apply.

FDA is accepting public comment on the draft guidance until August 1.