A new EU-level recommendation paper (“Paper“) sets out wide-ranging recommendations for sponsors of decentralized clinical trials (DCTs). The Paper is great news for sponsors facing an array of grey areas and gaps in regulatory guidance around DCTs. It provides guidance on common issues in designing and implementing DCTs: from documenting the delegation of tasks to digital service providers, to obtaining e-consents and how investigators should manage new streams of incoming data. The recommendations are not legally binding, but the Paper nevertheless represents a vital step towards a common basis for implementing DCTs across the EU.
DCTs focus on bringing an increasing proportion of a trial’s activities to the patient’s home, rather than bringing the patient to a trial site. The ultimate aim is to improve the patient experience and meet patient needs, and the key to achieving this is technology, i.e., e-consents, telehealth solutions and wearables that facilitate remote monitoring. When it comes to DCTs, the key to achieving regulatory compliance is the core principle of ensuring the rights, safety, dignity and well-being of trial participants. The Paper also emphasizes the importance of involving trial participants and investigators from the early stages of the design and implementation of DCTs.
We’ve set out our top six takeaways from the Paper:
- The roles and responsibilities of the sponsor, investigator and service providers: The Paper lays out core principles around how sponsors and investigators should document the delegation of trial-specific tasks to service providers. The protocol must clearly document this delegation, the rationale for the involvement of service providers, and how the sponsor and/or investigator will achieve oversight of service providers. Any trial-specific task that is delegated to a service provider should be specified in a written agreement between the responsible party for the task and the service provider. The Paper also discusses how sponsors should document the delegation of tasks to service providers, where those tasks are under the investigator’s responsibility. This includes how to ensure the investigator may effectively consent to the use of service providers for specific tasks related to the medical care of trial participants.
- Oversight of incoming data: Using digital tools often results in an increase in the amount of incoming data, and it will be challenging for investigators to monitor this constant flow of data. The Paper sets out several recommendations on how to approach this issue. It discusses the underlying principle that the review frequency of incoming data should be based on the relevance of the data for efficacy, and to the safety and well-being of the trial participant. The review of safety data should involve a risk-based assessment, which may include the IMP’s safety profile, indication, known potential risks, and use of notifications and alerts. The Paper recommends using notifications and alerts to ensure timely assessment of Serious Adverse Event (SAE) related data.
- Electronic informed consent: Where the informed consent process is conducted remotely, it should be described step-by-step in the clinical trial application to ensure appropriate ethical review. Informed consent interviews should generally be conducted in-person, but conducting these remotely may be justified in certain circumstances. Where these are conducted remotely, the Paper sets out recommendations, including ensuring there is an opportunity to ask questions and checking the identity of participants not already known to the investigator. The Paper also addresses obtaining an informed consent signature by remote means. For example, when using electronic methods, trial participants should be able to download an electronic copy of the signed and dated informed consent form, or to receive a print-out of the electronic copy.
- IMP delivery and administration at home: This is an area that is subject to a high degree of variation at the member state level, but the Paper sets out a general recommendation that a risk assessment should be completed to determine if this is appropriate. This should take into account a range of factors, including the IMP’s safety profile, the route of administration, the need for emergency plans, its stability, the storage conditions, and the robustness of the IMP’s delivery logistics. When delivering the IMP, it should only be handed over to the trial participant (or a representative, if applicable), or a present healthcare professional involved in the trial. Sponsor procedures should be in place covering delivery and receipt of the IMP, as well as IMP return from the trial participant’s home and destruction of the unused IMPs.
- Trial-related procedures at home: For trial procedures performed at home, the investigator will need to consider the suitability of the patient’s home. At-home procedures should not cause additional risk to the trial participant or to the reliability of the data. If trial participants perform trial-related tasks, they should receive appropriate training. Importantly, the insurance or indemnity arrangements should cover any damage resulting from trial-related procedures performed at home.
- Data management and monitoring: DCTs are characterized by a shift in the burden of data collection from the investigator/site to others, such as the trial or service providers (e.g., home nurses). To add more complexity, there are multiple systems and parties that require adequate oversight. To manage these issues, the Paper recommends including a data flow diagram in the protocol and ensuring all parties have oversight of these data flows. It also discusses steps to ensure security, such as encryption and access rights.
The Paper acknowledges that despite EU efforts, many aspects of the implementation of DCTs are jurisdiction-specific. The Paper sets out an overview of national provisions in each member state relating to the DCT topics addressed in the Paper. It also includes a reminder that it is at the discretion of the member state assessing a clinical trial, as to whether the use of certain decentralized elements is acceptable in that trial. Ultimately, the Paper is a useful step in the right direction, but more is needed to ease the rollout of multi-country DCTs across the EU.