Ten takeaways from FDA’s DCT Draft Guidance

US Food and Drug Administration issued a draft guidance a couple of weeks ago titled “Decentralized Clinical Trials for Drugs, Biological Products and Devices – Guidance for Industry, Investigators, and Other Stakeholders”. This guidance is now open for comments from various industry stakeholders. This is issued to comply with the FDORA requirement to provide guidance to the industry no later than 29^th Dec 2023.

This blog post is to summarize 10 key takeaways from the draft guidance along with some of my thoughts.

1. Fully Decentralized Vs. Hybrid Trials: Guidance is to use fully decentralized trials for investigational products that are simple to administer, have well-characterized safety profiles, and do not require complex medical assessments.  If not, it is noted that hybrid trials may be more appropriate with the administration of IP or complex medical assessment is performed during a site visit and other follow-up assessments could be done remotely through ePROs, telehealth, in-home visits, or by local HCPs, as appropriate.
2. DCT challenges & planning:
   • Challenges like coordination of trial activities with individuals and facilities across multiple locations that are non-traditional clinical trial “sites”.
   • Plans to conduct DCTs should include:
     • use of local facilities, personnel, etc.
     • visits to patients’ homes
     • distribution of IP to participants, at home
     • Plans are to be reviewed with relevant FDA review divisions before starting.
3. DCT Designs:
   • Need for a physical location, which should be listed on Form 1572 or IDE, where all trial-related records for participants are available and trial personnel can be interviewed.
   • May not be appropriate for a “non-inferiority” study given the variance of assessments across HCPs and thus need to be reviewed with FDA divisions beforehand.
4. Visits & Activities:
   • Telehealth visits can be considered where no in-person interaction is needed and should be specified in protocols.
   • The Adverse Event (AE) reporting process to identify and manage should be specified in the protocol.
   • All documentation (CRFs) is expected for telehealth visits and patient identities should be confirmed.
   • All personnel and patients involved in the study should be trained, as needed, to ensure consistency.
5. Digital Health Technologies:
   • Recommendation from FDA draft guidance titled “Digital Health Technologies for Remote Data Acquisition in Clinical Investigations” to be used.
   • Any technology used in the study should be available and suitable.
   • In the case of BYOD, devices should be provided by sponsors to ensure patients that cannot afford them are not excluded from the study for socioeconomic reasons.
6. Key Stakeholder Responsibilities:
   • Sponsors:
     • Sponsor responsibilities remain the same for DCTs as with the traditional site-based studies.
     • Should strive for Diversity & Inclusiveness in the patient population.Should have a Data Management Plan (DMP).
     • Describe operational aspects of DCT in the protocol.
     • Ensure compliance with local laws, regulations, and licensing requirements.
     • Ensure proper monitoring of the investigation.
   • Investigators:
     • Responsible for the conduct of DCT and oversight of individuals delegated to perform trial-related activities according to the investigational plan, applicable regulations, etc.
     • May use local HCPs, if permitted by the protocol
     • May use technologies like videoconferencing for oversight.
     • Ensure enrollment is aligned with the ability to manage and supervise.
     • Appropriate delegated local HCPs should be listed as “subinvestigators” based on their assigned responsibilities and the significance of their contributions.
     • Ensure consistency of the process, activities, and practices to minimize variability across local HCPs through regular reviews and quality control measures.
     • Designated clinical laboratory facilities should be used, where needed, for critical data that is used to evaluate outcomes.
     • Health records should be obtained from local healthcare facilities, and primary providers for any emergency and/or routine visits, with permission from patients.
7. eConsent & Institutional Review Board:
   • eConsent can be obtained from patients at their remote locations provided all regulatory requirements regarding informed consent are met.
   • FDA recommends using central IRB to facilitate efficient review of the protocol, informed consent documents, and relevant trial-related information.
8. Investigational Products:
   • Should be administered under the supervision of the investigator or the subinvestigator, unless the drug has a well-characterized safety profile and does not require specialized monitoring, post-administration.For investigational devices, should consider the type of medical use, instructions for use, risk profile, etc.
   • Investigational products or devices can be shipped directly to patients based on the considerations documented in the protocol for appropriate handling, packaging, distribution, and use.
   • If any issues arise in the case of remote administration or use of IP, sponsors must discontinue the practice and use FDA or IRB to determine the continuation or stoppage of the trial.
9. Safety Monitoring:
   • Sponsors should implement a safety monitoring plan to ensure the safety and welfare of trial participants in DCT.
   • As with site-based trials, SMP should describe how adverse events will be reported, seek medical help by the participants, and collected and responded to by the investigators.
   • Investigational products or devices can be shipped directly to patients based on the considerations documented in the protocol for appropriate handling, packaging, distribution, and use.
10. Software:
    • Software to run DCTS can be used on a variety of platforms like tablets, cell phones, laptops, etc.
    • Must be 21 CFR Part 11 compliant.
    • Ensure data reliability, security, privacy, and confidentiality.
    • Real-time video interactions and telehealth are considered to be live interactions and hence not subject to 21 CFR Part 11 
    • The software can be used to manage eConsent, reports, eCRFs, visit scheduling, IP shipment tracking, DHT recorded data collection and communication between site personnel and participants.

In conclusion, some of the aspects of traditional clinical trials remain the same while DCTs will provide flexibility in many ways to reduce the site visits and leverage DHTs to collect data directly from patients. The guidance will certainly help all the stakeholders involved in clinical trials to take a measured approach to adopt DCTs. We also need to wait for public comments and feedback and how that will impact the final guidance. This is a great step forward to raise the awareness in the industry of what the FDA is thinking but also to help drive some standardization in how sponsors, sites, patients, technology & software providers, IRBs, etc. think and act to facilitate Decentralized Clinical Trials.

Please note that this post is to summarize the guidance and share some of my thoughts for information purposes. You can read the full guidance at the link provided at the beginning of this post.

iPads, iPhones, Androids, Windows Mobile Phones, Life Sciences and Compliance

Apple has sold millions of iPads in the past 18 months. The adoption of the device in the market is phenomenal. This trend is reflected in Life Sciences & Healthcare industry as well. A mobile Health News article (2012: About 62 percent of physicians use tablets) puts the adoption of tablets by the physicians at 62%. Another report by IDC puts the Smart Devices sales exceeding the combined sales of laptops and desktops. All these trends are indicative of the rate of adoption of mobile and smart devices by the population in general. The healthcare and life sciences industries are no exception to this.

While the adoption is growing in general, the challenges and bottlenecks are numerous for adoption of the devices in an Enterprise/Business setting. To make this even more complex, consider using the tablets and smart phones in a validated environment to capture and manage personal health information of patients.

Some key questions to be asked while considering adoption of Mobile devices in a validated environment are:

• Will the device and application be considered a Mobile Medical Device?
• If so, what should we do to validate the application?
• What are the regulatory requirements and guidance from the agencies?
• Should we consider a native application vs. a web based application?
• If so, how does the validation activities and artifacts differ?
• Would the data be stored on the device or would it be transferred to the server as soon as it is captured?
• Should we make it available offline to enable usage without internet connectivity?
• What are the synchronization challenges?
• How do we handle identity management?
• How do we ensure data security?

While some of these questions are applicable to any enterprise mobile application, they are even more important to consider if the Mobile device is slated to be used in a regulated environment. For customers in the US, one key document to be considered as input, to answer some of the questions, is FDA’s DRAFT Guidance for Mobile Medical Applications.

mHIMSS Policy & Regulatory Implications Workgroup has provided a very good summary of how the guidance should be interpreted with respect to Mobile Medical Applications. You can read the summary here (needs registration).

FDA also provides more useful information on Mobile Medical Applications here.

I look forward to comments and insights into any specific experiences that you might have had with respect to developing Enterprise Mobile Applications in a regulated environment. These applications may or may not be companion applications to devices, but may fall under the MMA purview as defined in the guidance.