With decentralized clinical trials (DCTs), what responsibilities fall under sponsor oversight?
At the Society of Quality Assurance 2022 Annual Meeting in Palm Springs, Calif. FDA Office of Regulatory Affairs Bioresearch Monitoring Division I Director Anne Johnson provided FDA’s perspective on DCTs in a presentation titled, “Sponsor Oversight of Decentralized Clinical Trials.”
[Related: What can inspection data tell us about regulatory enforcement trends involving clinical investigators? Click here to view the webinar, “FDA GCP Inspection Trends Identified Using AI.”]
Part I of this report on Johnson’s presentation at SQA covered the background and an overview of the regulations covering clinical trials, and the elements of DCTs, including the design, benefits, and challenges.
In this second part, we cover sponsor oversight responsibilities for DCTs regarding:
- Electronic informed consent
- Remote visits
- Electronic data considerations
Part III provides the agency perspective on risk-based monitoring and FDA guidance that directly impacts DCTs, and Johnson’s advice to sponsors in the form of “points to consider.”
Electronic Informed Consent
Johnson characterized the process of obtaining electronic informed consent as “a very important aspect to consider because essentially this is where and when the study starts.” The process, she emphasized, must enhance the subject’s understanding of the study and allow adequate opportunity for the participant to ask questions and consider whether to participate in the study.
Documentation of informed consent must include not just the participant responses and their decision along with the information that was provided to them, but which clinical trial staff members were involved. The electronic informed consent data obtained need to include the template used and site-specific versions of the electronic informed consent.
The materials are submitted to the Institutional Review Board (IRB) for review and approval, including all amendments to the informed consent template. The required elements have to be present in the electronic version that is used during the consenting process.
Pay special attention, Johnson said, to how the signature is acquired. Is it an electronic signature? It must include the date that the subject or their legally authorized representative signed the electronic informed consent.
Figure 1 shows the ways that informed consent can be obtained.
Regarding electronic informed consent, Johnson commented, “as you can see, nothing here is new. These have always been in existence. It is just that we are seeing them used more often. The most important things though are to assure patient privacy, confidentiality, and any rights as far as their medical information and who has access to it.”
The processes, procedures, and training need to be in place for electronic informed consent to ensure documentation of the identity of the subject and the staff involved, a review of the document by the subject with the staff, and who was involved.
Processes and procedures and training need to include a confirmation of the questions and how they were answered, as well as whether the subject wants to participate or not.
“It is also very important to recognize that you must find a way to authenticate the identity of the individual who is providing consent and making sure that that is the same individual that is participating in the study,” Johnson pointed out. “You might include things such as some sort of a government-issued ID or a password, a username and password combination for electronic signatures.”
Finally, be sure to consider the elements of 21 CFR 50 for informed consent along with any applicable sections of 21 CFR Part 11.
[Related: Did you know there were 173 FDA 483 observations issued to clinical investigators involving informed consent over the past 15 years? For more clinical investigator insights, contact us for a walkthrough of our platform.]
Remote DCT Visits
Remote visits can employ various remote and electronic components. The standards are the same regardless of whether the visits are traditional or remote. This includes the following, Johnson stated:
- The visits need to be conducted by delegated staff with the appropriate experience, knowledge, and training who evaluate whether the protocol and all the resulting documentation that is required is clear.
- The clinical investigator needs to be involved in the site training, the initiation, and the conduct of the trial. When the clinical investigator reviews electronic records there should be a means to record their review and any comments that they have.
- FDA expects that the DCT has a participant-centered approach, which is needed for this kind of approach to work.
- The processes and procedures, especially if they are hybrid, should be designed for both in-person and remote electronic use.
- Observe local requirements and the variations in state laws and jurisdictions.
- Understand the legality of telemedicine or telehealth, the distribution of investigational product, and local requirements regarding dispensing or prescribing.
Electronic Data Considerations
It is important to pay special attention to electronic sources of data, Johnson emphasized. i.e., data that are first recorded in an electronic format, and the way the source documents are recorded and stored. These include electronic health records, electronic medical records, medical images, and electronic diaries that are completed by study participants.
The following are “especially important” she stressed:
- The source data must be “ALCOA+” – attributable, legible, contemporaneous, original, accurate, complete, consistent, enduring, and available.
- There must be controls to protect blinded information.
- The informed consent documents need to be consistent with how they are supposed to be used.
- Consider the extra burden that might be placed on a trial site to obtain and retrieve information, scan, send, or track, or even facilitate access during a monitoring visit, an audit, or an inspection.
- Compliance with part 11.
- Any modifications or corrections must not obscure original entries, whether it is in an audit trail or in metadata. Overwriting is not acceptable.
- When there are significant delays in saving data, such as long session times, look at when the data has been electronically input and when it was written to the audit trail.
Sponsors should include information about their intended use of electronic systems, a description of any of those security measures, and a description of the diagram or the data flow in a protocol, investigational plan, or in a data management plan.
Regarding electronic data, the FDA Division Director said, “I cannot stress enough the importance of establishing processes and procedures for electronic source data and systems that are used to create, to modify, to maintain, to archive and store, to receive and to transmit data.”
Part III examines FDA’s expectations for risk monitoring of DCTs.
An FDA Perspective on Decentralized Clinical Trials: Part I
Data Integrity and Your Clinical Investigator: What the Data Shows
The Components of “Responsibilities of the Investigator” Observations
Extracting Specific Protocol Violations from Warning Letter Citations
Five FDA Warning Letters Issued in Four Years for Fraudulent Cancer Drug
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