7. Decentralized Clinical Trials

7.1 Do the country regulations allow Decentralized Clinical Trials (DCT) elements (e.g., eConsent, ePRO administration, remote investigator site, etc.)?

Yes.

7.2 Is there any specific regulation/guidance on the use of DCT elements within a clinical trial?

Yes. In May 2023, the FDA released a draft guidance for public comment on “Decentralized Clinical Trials for Drugs, Biological Products, and Devices”.

In Dec 2023, the FDA published the final guidance on “Digital Health Technologies (DHTs) for Remote Data Acquisition in Clinical Investigations”.

In 2016, the FDA published a guidance in the form of Questions & Answers, titled “Use of Electronic Informed Consent”.

7.3 What is the overall acceptability of DCT elements by the US Regulatory Authorities and Ethics Committees?

The overall acceptability is very good; many DCT studies are being currently conducted in the U.S.

7.4 Has a fully virtual trial (DCT) been conducted in the country yet? If so, please provide an example including the registration number and any link to it, whether COVID/non-COVID trials.

Yes, see below just a few:

• ClinicalTrials.gov ID NCT05098938
• ClinicalTrials.gov ID NCT06247085
• ClinicalTrials.gov ID NCT06237452
• ClinicalTrials.gov ID NCT05869773
• ClinicalTrials.gov ID NCT05822427
• ClinicalTrials.gov ID NCT05765578
• ClinicalTrials.gov ID NCT05686369
• ClinicalTrials.gov ID NCT04471623

7.5 Are there any non-regulatory DCT initiatives in the country, such as where the investigator sites and local CROs founded an alliance?

Yes, there are currently many associations supporting DCT. For example:

• ACRO conducted an initiative in Decentralized Clinical trials in 2019. The result has yielded very useful material, which is often referred to by global regulatory authorities.
• DTRA (Decentralized Clinical Trial Alliance) focuses on priorities and initiatives on advancing decentralized trials and research.
• CTTI (Clinical Trials Transformation Initiative) has been for many years supporting the DCT model. Under their “Digital Health Trials” page, they have available supporting materials and guidance.

7.6 Are there any general considerations when using DCT elements in a study?

The FDA Draft Guidance on “Decentralized Clinical Trials for Drugs, Biological Products, and Devices” states that “FDA’s regulatory requirements for investigation of medical products are the same for DCTs and traditional site-based clinical trials”.

It goes further indicating that:

“Fully decentralized trials may be appropriate for investigational products (IPs) that are simple to administer or use, have well-characterized safety profiles (see section III.F), and do not require complex medical assessments. Alternatively, hybrid decentralized trials may be more appropriate in cases where the administration of an IP or a complex medical assessment needs to be performed at a clinical trial site and some follow-up assessments could be performed remotely through online patient-reported outcome measures, via telehealth or in-home visits, or by local  health care providers (HCPs), as appropriate.” 

“Challenges related to DCTs may include coordination of trial activities with individuals and facilities in multiple locations that are not traditional clinical trial sites. DCTs generally include specific plans to facilitate the decentralization of the trial. These plans should include, as appropriate, the use of local health care facilities, local HCPs, and local clinical laboratory facilities; visits to trial participants’ homes; and direct distribution of the IP to trial participants at their locations. Specific issues related to the feasibility, design, implementation, or analysis of a DCT should be discussed early with the relevant FDA review divisions. Appropriate training, oversight, and up-front risk assessment and management will be key to implementing a DCT successfully.”

Below are some recommendations obtained from the DRAFT guidance:

“For inspectional purposes, there should be a physical location where all clinical trial-related records for participants under the investigator’s care are accessible and where trial personnel can be interviewed. This location should be listed on Form FDA 1572 or for investigational device exemption (IDE) applications must be included in the IDE application. 

Roles & Responsibilities:

Sponsor

Sponsor responsibilities are the same for DCTs and traditional site-based clinical trials. Because DCTs may involve many contracted services, sponsors should ensure proper coordination of the decentralized activities (e.g., use of mobile nurses for at-home visits, use of local HCPs, direct shipping of IP to participants) (see sections III.B and III.G). 

• Sponsors should strive for diversity and inclusiveness in trial populations. Outreach through local health care institutions (e.g., pharmacies, clinics) may facilitate recruitment of diverse participants in areas where there are limited or no traditional clinical trial sites. Bringing trial-related activities to participants’ homes, including through the use of DHTs, may reduce the need for travel and improve engagement, recruitment, and retention amongst potential participants with challenges accessing traditional clinical trial sites. The use of local HCPs close to potential participants’ homes may improve engagement, recruitment, and retention of diverse participants (e.g., race, ethnicity, age, sex, and geographic location). Further, the use of local HCPs may reduce cultural or linguistic barriers to participation in clinical trials.
• To account for multiple sources of data collection in a DCT, the sponsor should include at least the following in a data management plan (DMP): 
  • Data origin and data flow from all sources to the sponsor (see section III.I) (e.g., a diagram that depicts the flow of data from creation to final storage) 
  • Methods used for remote data acquisition from trial participants, trial personnel, and contracted service providers (e.g., local clinical laboratory facilities and local HCPs who perform trial-related activities) 
  • A list identifying vendors for data collection, handling, and management
• Sponsors should describe in the trial protocol how operational aspects of the DCT will be implemented. This description should cover, but may not be limited to, the following:
  • Scheduled and unscheduled clinical trial visits (remote and in-person, as applicable) 
  • Transmission of reports on activities performed at different locations (e.g., 217 medical imaging; clinical laboratory tests; and procedures performed at trial participants’ home, work, or other local facility) 
  • Delivery of IPs to trial participants, if applicable, and accountability for IPs 
  • Safety monitoring and management of adverse events
• Case report forms should identify when and where data were collected and by whom.
• Sponsors must comply with relevant local laws, regulations, and licensing requirements governing medical practice and IP administration when conducting a DCT. This may involve addressing laws in multiple U.S. States, territories, and other countries.
• Sponsors must ensure proper monitoring of an investigation. As with any trial, sponsors may use a variety of approaches to monitor DCTs, and the monitoring plan for a trial should be based on the sponsor’s risk assessment. A trial monitoring plan should (1) describe how monitoring will be implemented to assess protocol compliance and data quality and integrity, (2) specify the frequency with which trial records and source documents will be reviewed, and (3) note any unique aspects related to the DCT procedures. FDA encourages risk-based monitoring approaches and use of centralized monitoring to identify and proactively follow up on missing data, inconsistent data, data outliers, and potential protocol deviations that may be indicative of systemic or significant errors.

The Investigator and Delegation of Trial-Related Activities

Investigators are responsible for the conduct of the DCT and the oversight of individuals delegated to perform trial-related activities, including ensuring that these delegated activities and/or tasks are conducted according to the investigational plan, applicable regulations, and relevant laws. A key difference between DCTs and traditional site-based clinical trials is the extent to which the investigator uses telehealth, trial personnel working remotely, local HCPs, and/or DHTs in the conduct of the trial. Whether the trial can be conducted entirely using remote visits or a hybrid trial design is appropriate depends on the types of assessments and procedures needed to collect endpoints and monitor safety. The decentralized features of the trial may necessitate additional training, coordination, and standard operating procedures to ensure consistent implementation.

When permitted by the trial protocol, investigators may delegate trial-related activities to local HCPs to perform trial-related procedures that require in-person interactions with trial participants (e.g., physical examinations and other medical procedures). These procedures may take place at participants’ locations or other local health care facilities as specified by the trial protocol. 

• Videoconferencing and other technologies may be useful to allow investigators to oversee trial personnel performing activities described in the trial protocol (e.g., photographing lesions, fitting wearable sensors) at participants’ locations. 
• Investigators should enroll only as many trial participants as they can appropriately manage to ensure adequate supervision of DCT-related activities. 
• As for any drug trial subject to 21 CFR 312.53, Form FDA 1572 must be completed by all investigators. The decision to include individuals as sub-investigators in a DCT should be based on their assigned responsibilities. - When trial personnel contribute directly and significantly to the trial data, they should be included on Form FDA 1572 as sub-investigators. - Local HCPs contracted to provide trial-related services that are part of routine clinical practice (e.g., performing physical examinations, reading radiographs, obtaining vital signs) and where a detailed knowledge of the protocol, IP, and the investigator’s brochure is not necessary should not be listed on Form FDA 1572 as sub-investigators. However, local HCPs should be included in a task log (as described below in this section). 
• For device investigations, investigator responsibilities under 21 CFR part 812 include the requirement that there be a signed agreement between the investigator and sponsor (see 21 CFR 812.43(c)(4) and 812.100). A list of all investigators in the study is also required as part of an IDE application (see 21 CFR 812.20 and 812.150(b)(4)). Local HCPs contracted to provide trial-related services that are part of routine clinical practice and where a detailed knowledge of the protocol or the IP is not required are generally not considered investigators and should not be included in the IDE list of investigators. However, these local HCPs should be included in a task log (as described below in this section).
• A critical consideration in a DCT when delegating trial-related activities to local HCPs is the potential for variability in the approach across different practices (e.g., documenting vital signs, physical examinations, and evaluation of adverse events). Quality control measures should be in place to help reduce variability, including regular review by investigators of participant data entered by local HCPs, to assess consistency and completeness of the required procedures. The type and scope of quality control measures should be tailored to the criticality of the data and the complexity of procedures done by the local HCPs. 
• As part of preparing and maintaining adequate case histories, investigators must maintain a task log of local HCPs who perform trial-related activities.
  • The task log should include (1) the names and affiliations of the local HCPs, (2) a description of their roles and assigned tasks, (3) the dates these local HCPs are added to the log, and (4) the locations where these activities are conducted.
  • The task log should be dated and signed by the investigator when initially created and updated when new local HCPs are added. The task log should be available to FDA during inspections.
  • Other health care professionals not involved in the clinical trial who deliver care to trial participants but not as part of the trial should not be listed on Form FDA 1572, the task log, or a medical device sponsor’s current list of investigators. These professionals may include emergency room personnel, hospital personnel, family physicians, and nurses providing routine care for trial participants with emergent or existing conditions.
• Some trial protocols will include designated clinical laboratory facilities to perform activities required by the protocol (e.g., phlebotomy, x-rays). Other trial protocols may permit the use of a variety of clinical laboratory facilities close to the trial participant to perform these activities. Generally, designated clinical laboratory facilities are preferable to minimize variability, particularly for critical data such as those used to evaluate outcomes, and to perform investigations and tests that are specialized. If appropriate, specimens from trial participants (e.g., blood, sputum) may be collected by remote trial personnel, local HCPs, or clinical laboratory facilities and sent to designated facilities for processing. Local clinical laboratory facilities may be adequate for routine clinical tests that are well-standardized.
• All clinical laboratory facilities should be listed on Form FDA 1572 or in the investigational plan for device studies under an IDE. 
• Technicians and other personnel working for clinical laboratory facilities should not be recorded on the task log or Form FDA 1572. However, for certain device studies (e.g., in vitro diagnostic devices), it may be necessary to identify the responsible individual at the laboratory facility where device testing is done in the task log or IDE application.
• As in any trial, trial participants experiencing any health emergency (e.g., hypoglycemia or abnormal cardiac rhythm) should seek medical attention at local health care facilities (such as an emergency room), as appropriate. With the permission of trial participants, investigators should attempt to obtain reports from these local health care facilities, and investigators should also attempt to obtain reports from primary providers of routine health care when activities take place that are relevant to the trial (e.g., change in concomitant medications).”

7.7 Considerations/Requirements for the Use of eConsent/Remote Consent

The FDA Draft Guidance on “Decentralized Clinical Trials for Drugs, Biological Products, and Devices” provides the following recommendations on eConsent and the oversight by the IRB:

“Obtaining informed consent remotely may be considered as part of a DCT. Institutional review board (IRB) oversight is required to ensure the process is adequate and appropriate.

• Investigators may obtain electronic informed consent from trial participants at their remote locations provided that all applicable regulatory requirements regarding informed consent are met. The process of obtaining electronic informed consent remotely may include a remote visit if needed.
• With a DCT, the informed consent process must include notifying participants of whom to contact for answers to pertinent questions about the research and research subjects’ rights and whom to contact in the event of a research-related injury to the subject.
• The informed consent should describe who will have access to the trial participant’s personal health information obtained during the DCT. 
• FDA recommends the use of a central IRB in DCTs to facilitate efficient review of the protocol, the informed consent documents, and other relevant trial-related information.”

It is worth to take into consideration the recent FDA DRAFT Guidance “Key Information And Facilitating Understanding in Informed Consent” which was released for public comment in March 2024. This draft guidance provides key recommendations that apply to any type of consent (e.g. written, oral, or electronic) in order to enhance the informed consent process.

7.8 Considerations/Requirements for the Use of eSignatures

In March 2023, the FDA published draft guidance entitled “Guidance Document - Electronic Systems, Electronic Records, and Electronic Signatures in Clinical Investigations: Questions and Answers”.

The draft is coupled with the provisions of 21CFR11.50.

FDA’s draft guidance “Use of Electronic Informed Consent in Clinical Investigations – Questions and Answers Guidance for Institutional Review Boards, Investigators, and Sponsors” (December 2016) provides that:

“The regulations found at 21 CFR part 11, permit a wide variety of methods to create electronic signatures, including using computer-readable ID cards, biometrics, digital signatures, and user name and password combinations. FDA does not mandate or specify any particular methods for electronic signatures, including any particular biometric method upon which an electronic signature may be based.”

See also 21CFR11 which includes the statement:

“Where electronic signatures and their associated electronic records meet the requirements of this part, the agency will consider the electronic signatures to be equivalent to full handwritten signatures, initials, and other general signings as required by agency regulations, unless specifically excepted by regulation(s) effective on or after August 20, 1997.” 

The general requirements for electronic signatures are set out in 21CFR11.

7.9 Considerations/Requirements for Electronic Patient Reported Outcome (ePRO)

FDA’s draft guidance “Electronic Systems, Electronic Records, and Electronic Signatures in Clinical Investigations- Q&As” (March 2023) states the following:

“For each clinical investigation protocol, the sponsor should describe the electronic systems (e.g., IRT system, EDC, eCOA) used to collect clinical investigation data as well as the electronic systems used to create, modify, maintain, archive, retrieve, or transmit pertinent electronic records. Sponsors should create a diagram that depicts the flow of data from creation to final storage.”

FDA’s draft guidance on “Decentralized Clinical Trials for Drugs, Biological Products, and Devices” (May 2023) provides general remarks on DHTs: 

“Sponsors should ensure that DHTs used in a DCT are available and suitable for use by all trial participants. When a trial permits participants to use their own DHTs, sponsor provided DHTs should be available as an option to ensure that participants who do not have a protocol-specified DHT are not excluded from the DCT for that reason (e.g., lower socioeconomic groups who cannot afford the DHT).”

FDA’s final guidance on “Digital Health Technologies for Remote Data Acquisition in Clinical Investigations” (Dec 2023) indicates “DHTs may be used to measure biomarkers and to administer COAs, such as patient-reported outcomes and /or performance outcomes. Compared to intermittent trial visits, the use of DHTs to remotely collect data from trial participants may allow for more frequent or continuous data collection. This may provide a broader picture of how participants feel or function in their daily lives.” This guidance provides very detailed considerations which sponsors need to take into account when using DHTs in clinical investigations, such as:

• Selection of DHT and Rationale for use in a clinical investigation. Sponsor should consider the clinical event or characteristic of the disease or condition of interest that is that to be measured, identify appropriate technical and performance specifications and consider the proposed trial population who will be using the DHT.
• The design and operation of the DHT and other technologies should be considered to determine that the DHT is fit for purpose, such as design, power needs, operational specifications, easy to use, any alerts, environmental factors that may affect the performance of the DHT, availability and capacity of participant and sponsor network system, and must have safeguards in place.
• Sponsors should evaluate the advantages and disadvantages of allowing participants to use their own DHT and other technologies for remote data acquisition.

7.10 Considerations/Requirements for Home Health Care (HHC)- Home Nursing

FDA’s draft guidance on “Decentralized Clinical Trials for Drugs, Biological Products, and Devices” (May 2023) provides the following recommendations:

“Remote clinical trial visits and clinical trial-related activities are important strategies to make trials more convenient and more accessible to trial participants. The following should be considered when planning remote clinical trial visits or clinical trial-related activities: 

• In general, investigators can consider telehealth visits instead of in-person visits with trial participants if no in-person interaction is needed. The protocol should specify when a telehealth visit with a trial participant is appropriate and when a participant should be seen in person. 
• In-person visits and trial-related activities can be conducted by trial personnel who are sent to participants’ homes or preferred locations. 
• Depending on the trial protocol, in-person visits and trial-related activities may also be conducted by HCPs who are located close to trial participants’ homes but are not part of the trial personnel. These local HCPs (such as doctors or nurses) may be used by sponsors or investigators to perform certain trial-related activities; for example, on a fee for-service basis. The trial-related services that they provide should not differ from those that they are qualified to perform in clinical practice (e.g., performing physical examinations, reading radiographs, obtaining vital signs). These services should not require a detailed knowledge of the protocol or the IP. 
• 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.”

7.11 Considerations/Requirements for HHC - Home Lab Collection

FDA’s draft guidance on “Decentralized Clinical Trials for Drugs, Biological Products, and Devices” (May 2023) does not provide any considerations on home lab collections, apart from the general recommendations listed under Section 7.10 above. However, there are a few points that should be considered:

• Home Health Care professionals should have adequate training for the tasks that are delegated to conduct, important to consider that state licensing requirements may apply to HHC.
• Considerations on the equipment to be used by the HHC, as it will need to have all the calibration and maintenance requirements.
• HHC may require additional training such IATA for handling dangerous goods.

7.12 Considerations/Requirements for Direct-to-Patient Study Product Delivery

FDA’s draft guidance on “Decentralized Clinical Trials for Drugs, Biological Products, and Devices” (May 2023) provides the following recommendations:

“Drugs and Biological Products

An investigator must administer an IP only to participants under the investigator’s personal supervision or under the supervision of a sub-investigator responsible to the investigator. The nature of the IP should be considered when determining whether administration outside of a clinical trial site in a DCT is appropriate. IPs that involve complex administration procedures; have a high-risk safety profile, especially in the immediate post-administration period; or are in early stages of development such that the safety profile is not well defined may need in-person supervision by the investigator at a trial site.

For IPs for which the safety profile is well-characterized and that do not involve specialized monitoring during the immediate period following administration, it may be appropriate for local HCPs or trial personnel working remotely to administer the IP at local health care facilities or participants’ homes. Hybrid DCTs may be designed for drugs that require supervised but infrequent (e.g., monthly) administration when administration can be done at trial sites with follow-up done remotely.

Depending on the safety profile of the IP (e.g., a class of drug with a risk of hypersensitivity, abuse potential) and the type of trial (e.g., dose escalation trial), sponsors should estimate the urgency and complexity of care that may be needed based upon risks related to the IP and the participant’s underlying condition. Investigators should take steps to help ensure that participants have access to an appropriate level of local care. 

Drugs best suited for direct shipment to the participant’s home include those with long shelf lives and those with good stability profiles. Drugs that involve specialized handling, shipping, and storage conditions may not be suited for direct shipment to locations outside the trial site.

Packaging and Shipping of Investigational Products

Generally, DCTs may allow for the direct distribution of investigational products to trial participants at their locations. The sponsor should consider the following recommendations regarding packaging, shipping, and storage of IPs in a DCT: 

• The protocol should describe how the physical integrity and stability of the IP will be maintained during shipment to trial participants, including appropriate packaging materials and methods (e.g., temperature control). Shipping containers should include clear instructions for handling and storing the IPs and instructions for returning unused IPs. 
• When relevant, DCT personnel should be trained on procedures and appropriate documentation for handling, packaging, shipping, and tracking Ips.
• A central distribution service could be used to ship the IP directly to trial participants. The investigator or delegated trial personnel must control the release of the IP by the distributor; monitor receipt and use by trial participants (or participants’ legally authorized representatives), according to procedures described in the protocol; and monitor the return or disposal of any unused product as directed by the sponsor. 
• The protocol should describe how investigators will track and document that trial participants (or participants’ legally authorized representatives) receive IPs. 
• The protocol should describe procedures that investigators or participants (or participants’ legally authorized representatives) should use to return or dispose of unused IPs and how this will be documented. 
• Sponsors and investigators must comply with applicable Federal, State, and international laws and regulations that address shipping IPs in their respective jurisdictions.”

7.13 Considerations/Requirements for the Use of Telemedicine

FDA’s draft guidance on “Decentralized Clinical Trials for Drugs, Biological Products, and Devices” (May 2023) provides the following recommendations:

• “In general, investigators can consider telehealth visits instead of in-person visits with trial participants if no in-person interaction is needed. The protocol should specify when a telehealth visit with a trial participant is appropriate and when a participant should be seen in person.
• …When applicable, both trial personnel and trial participants should be trained on how to conduct or participate in a telehealth visit.
• Case report forms and other documentation should be completed for telehealth visits, including the date and time of the visit.
• It is the sponsor and investigator’s responsibility to ensure that remote clinical trial visits conducted via telehealth comply with laws governing telehealth in the relevant U.S. States or territories and other countries, as applicable.
• A telehealth visit may be appropriate if an assessment in that setting does not pose significant risk to trial participants and, in such settings, adverse events can be (and are) properly assessed and documented.
• The monitoring plan should prespecify if and when telehealth visits or in person visits (e.g., physical examinations) will be scheduled with trial personnel or local HCPs to collect safety data.
• Trial participants should be able to arrange for an unscheduled visit using telehealth or an in-person visit, as appropriate.
• FDA considers real-time video interactions, including telehealth, as a live exchange of information between trial personnel and trial participants. These live interactions are not considered electronic records and, therefore, are not subject to 21 CFR part 11, but local laws governing telehealth may apply. Privacy and security of these real-time visits should be ensured, and the visits must be documented. If this documentation is captured in electronic form, such documentation is subject to 21 CFR part 11.”

7.14 Considerations/Requirements for the Use of Wearables

FDA’s final guidance on “Digital Health Technologies for Remote Data Acquisition in Clinical Investigations” (Dec 2023) provides a detailed description of the verification, validation, and usability evaluation of digital health technologies used within a clinical trial, including wearables.

“There is a large spectrum of DHTs available for potential use in a clinical investigation. DHTs for remote data acquisition in clinical investigations can include hardware and/or software to perform one or more functions. Appendix A includes examples of DHTs that can be used for remote data acquisition in clinical investigations, such as wearables and software applications (including mobile apps). Depending on the intended use of a DHT, the DHT may meet the definition of a device under the Federal Food, Drug, and Cosmetic Act (FD&C Act).”

Based on the above, it is very important to categorize the type of wearable to be used, if it is an approved/marketed medical device, if it will be used within the study as per approved intended use or a different one. 

7.15 Considerations/Requirements for Remote Monitoring

FDA’s draft guidance on “Decentralized Clinical Trials for Drugs, Biological Products, and Devices” (May 2023) provides the following recommendations:

“Sponsors must ensure proper monitoring of an investigation. As with any trial, sponsors may use a variety of approaches to monitor DCTs, and the monitoring plan for a trial should be based on the sponsor’s risk assessment. A trial monitoring plan should:

(1) describe how monitoring will be implemented to assess protocol compliance and data quality and integrity, 

(2) specify the frequency with which trial records and source documents will be reviewed, and 

(3) note any unique aspects related to the DCT procedures. FDA encourages risk-based monitoring approaches and use of centralized monitoring to identify and proactively follow up on missing data, inconsistent data, data outliers, and potential protocol deviations that may be indicative of systemic or significant errors.”

In April 2023, the FDA released the guidance for industry “A Risk-Based Approach to Monitoring of Clinical Investigations - Questions and Answers” which supports remote monitoring of clinical trials.

7.16 Considerations/Requirements for Digital Health Technologies (such as Platforms)

FDA’s draft guidance on “Decentralized Clinical Trials for Drugs, Biological Products, and Devices” (May 2023) provides the following recommendations:

“Software Used in Conducting DCTs

Sponsors should consider the following regarding software used in a DCT: 

• Software to support the conduct of DCTs can be run through a variety of platforms (e.g., tablets, cell phones, personal computers). Software can be used to perform multiple functions to manage DCT operations, including:
  • Managing electronic informed consent (e.g., maintaining approved versions of informed consent, documenting IRB approval, archiving signed forms) 
  • Capturing and storing reports from remote trial personnel, local HCPs, and local clinical laboratory facilities
  • Managing electronic case report forms (eCRFs)
  • Scheduling trial visits and other DCT-related activities 
  • Tracking IPs that are shipped directly to trial participants
  • Syncing information recorded by DHTs
  • Serving as communication tools between DCT personnel and trial participants
• Training should be provided to all parties (e.g., trial personnel, local HCPs, and trial participants) using software to support the conduct of DCTs.
• There are several ways local HCPs can submit trial-related data for inclusion in clinical trial records, including but not limited to the following:
  • If the local HCPs have access to the eCRF, they can enter trial-related data directly into the eCRFs.
  • Alternatively, local HCPs can upload forms or documents by using methods of 516 secure data transfer to investigators. Investigators or other trial personnel are then responsible for entering these trial-related data into the eCRF.
• Remote trial personnel or local HCPs submitting trial data directly into the eCRF should be included in the sponsor’s list of authorized data originators.
• Software programs that are used to produce and process trial records required by the FD&C Act and FDA regulations are subject to 21 CFR part 11. These programs must ensure data reliability, security, privacy, and confidentiality.
• FDA considers real-time video interactions, including telehealth, as a live exchange of   information between trial personnel and trial participants. These live interactions are not considered electronic records and, therefore, are not subject to 21 CFR part 11, but local laws governing telehealth may apply. Privacy and security of these real-time visits should be ensured, and the visits must be documented. If this documentation is captured in electronic form, such documentation is subject to 21 CFR part 11.

FDA’s final guidance on “Digital Health Technologies for Remote Data Acquisition in Clinical Investigations” (Dec 2023) provides a detailed description of the verification, validation, and usability evaluation of digital health technologies used within a clinical trial.

Additionally, the FDA “Policy for Device Software Functions and Mobile Medical Applications” (28 Sept 2022) provides clarity and predictability for software manufacturers.