Decentralized Clinical Trials (DCTs) FAQs
November 2024
General Considerations
Q1. What is a DCT?
A1. DCTs are defined as studies “executed through telemedicine and mobile/local healthcare providers, using processes and technologies differing from the traditional clinical trial model”.1 Also, in a decentralized clinical trial (DCT), some or all of a clinical trial’s activities occur at locations other than a traditional clinical trial site. These alternate locations can include the participant’s home, a local health care facility, or a nearby laboratory.
Q2. Should there be a central location/physical location in a DCT?
A2. It is recommended that there be a physical location for inspection purposes where inspectors or monitors can centrally review trial related records whether they are stored in a secure electronic location or at a physical site. For study records stored electronically, processes should be in place to allow monitors or inspectors to review the records remotely.
Q3. What are some participant factors and potential challenges 2 that should be considered when designing a DCT?
A3. When designing a DCT, an investigator should think about the following domains 3 from the participant perspective:
- Communication: The DCT should include procedures to assure that robust communication is maintained among participants, third-party vendors, and the investigator.
- Orientation/Training: The investigator should have provisions in place to orient and/or train participants about their responsibilities in the study, including completing study procedures, uploading study data, using technology for the study, etc.
- Digital and Mobile Technology: The investigator should be aware of technologies being used in the study (e.g., “wearable” ECG cardiac monitors) and consider participant abilities to understand how to use them. The investigator may also need to consider if devices used by participants will be provided by the study, or of the participant uses a personal device (e.g., their own cell phone, or tablet) for study procedures. Further, if any of the study devices require an internet or cellular connection, the investigator may need to consider access concerns that may be insufficient in some areas where participants live. The investigator should also plan for how enhanced connective services man be needed for some participants.
- Personal Privacy/Data Confidentiality: Participants should understand that the investigator will implement all available protections to protect participant identity and their personal privacy, and the confidentiality of their data. The investigator will need to inform participants that study or identifiable data that may be transmitted via various communication platforms and technologies, which may not guarantee confidentiality.
- Safety: The DCT should be designed and conducted in a manner that maximizes safety and well-being for participants. Specifically, participants should be aware of adverse event (e.g., acute side-effects) response procedures, such as contacting 911. The investigator should consider how participants can communicate their research status to EMTs, the Emergency Department, or their primary care provider. If a third-party contractor (e.g., a home health aide) is utilized, training for the reporting and response to participant safety events is essential.
- Costs: The participant in a DCT should be informed if any costs could be incurred during their time in the study. For example, if participant’s cellular data plan is limited, the participant should be notified of this possibility and any financial responsibility.
- Culture/Socio-Economic factors: In a DCT, participants may be enrolled with diverse cultural backgrounds and represent different socio-economic strata. For example, if persons may be enrolled that speak a language other than English, to improve diversity, the investigator should consider in the DCT design means to include these persons by utilizing technological resources or contracted third-party entities who speak the language of those participants. For persons for which study participation might pose a financial burden, the investigator may consider means to provide financial assistance (e.g., furnishing a participant with a tablet to complete study diaries).
- Special Populations and Specific Needs: If children or other vulnerable populations are to be enrolled in a DCT, special considerations may need to be designed into the research to engage parents or Legally Authorized Representatives (LARs). If persons with certain disabilities are to be recruited, the DCT should be designed to accommodate them, if appropriate (e.g., smart phones for the visually impaired, or TTY/TRS phones for people with hearing impairment).
Note: Many of the answers to the FAQs are directly from the following FDA guidance: Conducting Clinical Trials with Decentralized Elements Guidance for Industry, Investigators, and Other Interested Parties (fda.gov)
1 Clinical Trial Transformation Initiative, CTTI Recommendations: Decentralized Clinical Trials 2 (2018), available at https://www.ctti-clinicaltrials.org/sites/www.ctti-clinicaltrials.org/files/dct_recommendations_final.pdf.
Considerations for Remote Clinical Trial and Clinical Trial-Related Activates
Q4. What should be considered for remote clinical trial and clinical trial-related activities in a DCT?
A4. Please see the following for recommendations: Conducting Clinical Trials with Decentralized Elements Guidance for Industry, Investigators, and Other Interested Parties (fda.gov)
Special consideration should be given to account for logistics in the conduct of the trial e.g., participant safety; privacy, confidentiality, and security; risks to non-subjects; vulnerable populations; adequate oversight; compliance with relevant laws, regulations, and local requirements (for example, investigational product shipment, prescribing, telemedicine, etc.).
Digital Health Technologies
Q5. What are Digital Health Technologies (DHT)?
A5. A DHT is a system that uses computing platforms, connectivity, software, and/or sensors for health care and related uses. These technologies span a wide range of uses, from applications in general wellness to applications as a medical device. They include technologies intended for use as a medical product, in a medical product, or as an adjunct to other medical products (devices, drugs, and biologics). They may also be used to develop or study medical products. Please see: Guidance for Industry (fda.gov)
Q6. What should be considered when using DHT?
A6. DHTs used in a DCT should be available and suitable for use by all trial participants. When a trial permits participants to use their own DHTs, 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, such as access to a Smart Phone).
The trial protocol should include consideration of issues such as privacy, confidentiality, security, data breaches, third-party use of personal data, terms of service, and potential harm (both physical and non-physical).
There should also be consideration given to account for and minimize risks regarding the data management plan, and software programs included in the protocol.
Role of Sponsors and Investigators
Q7. What is the role of the Sponsor in a DCT?
A7. Sponsor responsibilities are the same for DCTs and traditional site-based clinical trials. Please see the following guidance for a list of the Sponsor’s role in a DCT: Conducting Clinical Trials with Decentralized Elements Guidance for Industry, Investigators, and Other Interested Parties (fda.gov)
Q8. What is the role of the Investigator in a DCT?
Third Party Collaborators
Q9. Do third party collaborators who participate in a DCT require IRB oversight?
A9. Any third party collaborators that are engaged in research require IRB oversight. Common examples of engagement are a survey firm/third party platform delivering a survey to participants for research purposes and/or a home health care agency conducting research. Please review this JHM IRB guidance for additional information: Sponsor Contracted Third-Party Collaborators
Remote Consent
Q10. Can remote consent be used in a DCT.
A10. Yes, investigators may obtain electronic informed consent from trial participants at remote locations provided that all applicable regulatory requirements regarding informed consent are met. The JHM IRB must approve use of an electronic consent model either as part of the initial application or via a Change in Research. Please see the following guidance: Electronic and Remote Consent
Monitoring
Q11. Is the sponsor required to ensure there is proper monitoring in a DCT?
A11. Yes, The sponsor is required per regulations to ensure proper monitoring of the investigations and to ensure that the investigations are conducted in accordance with the general investigational plan and in accordance with applicable FDA IND or IDE regulations. Sponsors should implement a safety monitoring plan to ensure the safety and welfare of trial participants in a DCT.
Software
Q12. Should the sponsor consider what software to use in a DCT?
A12. Yes. The sponsor should consider what software to use in a DCT. The software used will need to meet considerations for data reliability, security, and privacy. Please see the following for recommendations: Conducting Clinical Trials with Decentralized Elements Guidance for Industry, Investigators, and Other Interested Parties (fda.gov)
Investigational Products
Q13. What should be considered when a DCT involves an investigational product (IP)or biologic?
A13. The administration of an IP to participants must be performed under the supervision of the investigator or sub investigator responsible to the investigator. The investigator shall not supply the investigational drug to any person not authorized to receive the IP under21 CFR part 312. Sponsors should consider the nature of the IP when determining whether administration outside of a traditional clinical trial site in a DCT is appropriate. Administration of IP that has a high-risk safety profile, especially in the immediate post-administration period; that is in early stages of development such that the safety profile is not well defined; or that requires complex preparation, administration, or medical assessments may need in-person supervision by the investigator at a traditional clinical trial site. Alternatively, it may be appropriate for local health care providers or trial personnel working remotely to administer an IP at, for example, local health care facilities, mobile research units, or participants’ homes if the safety profile of the IP is well characterized and specialized monitoring during the immediate period following administration is not needed.
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 underlying condition in the population being studied. 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 good stability profiles. Drugs that involve specialized handling, shipping, and storage conditions may not be suited for direct shipment to locations outside the traditional clinical trial site. Please see: Conducting Clinical Trials With Decentralized Elements Guidance for Industry, Investigators, and Other Interested Parties (fda.gov)
Q14. What should be considered when a DCT involves an investigational medical device?
A14. When determining the appropriate use or administration of an investigational device in a DCT, sponsors should consider the type of medical device, its intended use, its instructions for use, and the potential risks of the device for participants.
Investigational devices intended for home use may be appropriate for use by trial participants without the investigator’s direct oversight when such direct oversight is not needed to mitigate potential serious risks to trial participants. Investigational devices that are not intended for self use (i.e., devices used in hospital or ambulatory care settings) should be used or administered by qualified trial personnel with investigator oversight. An investigator shall not supply an investigational device to any person not authorized under 21 CFR part 812 to receive it. Certain follow-up assessments or procedures needed after using the investigational device or after surgical implantation of the device in trial participants may be performed by appropriately qualified and trained local health care professionals or trial personnel via telehealth visits, at the homes of trial participants, or in local health care facilities. A telehealth visit may be appropriate if an assessment in that setting does not pose significant risk to trial participants and if there are plans in place to ensure that adverse events identified during such visits will be properly assessed, managed, and documented. Please see: Conducting Clinical Trials With Decentralized Elements Guidance for Industry, Investigators, and Other Interested Parties (fda.gov)
Q15. What to consider when shipping an IP in a DCT?
A15. In some cases, DCTs may involve the direct distribution of IPs to trial participants or local health care providers. In these cases, investigators must remain responsible for supervising the supply of IP to trial participants or local health care providers.When applicable, trial personnel should be trained on procedures and appropriate documentation for handling, packaging, shipping, and tracking IPs. When IPs are directly distributed to trial participants or local health care providers, such as through a central distribution service, the investigator must authorize the release of the IP by the distributor; ensure receipt by trial participants or local health care providers, which should be done according to procedures described in the investigational plan or other trial-related documents; and document the return or disposal of any unused product as directed by the sponsor. When IPs are shipped directly to participants, investigators should ensure participants have appropriate instructions and training for use of the product.
Sponsors should address the following in trial-related documents:
• How the physical integrity and stability of the IP will be maintained during shipment including appropriate packaging materials and methods (e.g., temperature control).
- Appropriate labeling and instructions for recipients who are handling and storing IPs
• How investigators will track and document receipt of IPs by participants or local health care providers
• How unused IPs will be returned to the sponsor or disposed of and how this will be documented.
FDA Oversight
Q16. How does the FDA conduct oversight of DCTs?
A16. FDA uses a variety of tools to conduct oversight of regulated entities (e.g., sponsors and clinical investigators). This includes inspections conducted under sections 704(a)(1) or 704(a)(5) of the FD&C Act 35 and, when appropriate, remote regulatory assessments. Please See: Conducting Clinical Trials With Decentralized Elements Guidance for Industry, Investigators, and Other Interested Parties (fda.gov).
Submitting a DCT to the JHM IRB for Review
Q17. Where should I indicate in the eIRB application that my study has a DCT component?
A13. You should indicate “Yes” in section 10 (Study Location) item 3 of the eIRB application. Per JHM IRB Guidance, some DCT components may require external IRB approval, if they are engaged in trial-related activities. This approval should be uploaded to Section 20, question 2.
Q17. Should my protocol describe the de-centralized components of the study?
A18. Yes, the protocol should clearly describe the de-centralized components of the research and address the considerations above for how the de-centralized aspects of the trial will be managed. The protocol should be uploaded to section 6 (Protocol Information) item 2 of the eIRB application.
Q19. What if the decentralized component of the study involves sharing Johns Hopkins Medicine person-level data with outside partners?
A19. If you will share Johns Hopkins Health System or School of Medicine person-level date with outside partners, you must fill out section 36 (Data Confidentiality) of the eIRB application as follows:
- Please indicate “Yes” in section 36 item 2 and answer the items that appear
- Please answer item 5 on the Risk Tier Worksheet
As a note, the consent form should disclose who may access participant information.
Q20. Who should I contact to discuss questions concerning DCTs?
A20. You can request a consult and a member of the Office of Human Subjects Research team will reach out to you.