January 10, 2023
EMEA Recommendations for Decentralized Clinical Trials: Considerations for Design, Implementation, and Data Integrity
While clinical trials have been incorporating decentralized elements for some time, the EMEA has acknowledged the impact of COVID-19 on the increased adoption of decentralized procedures and more recently the importance of its continued use beyond the pandemic. In December 2022 they issued an updated recommendation paper on decentralized clinical trials (DCTs) focusing on four main areas: clinical trial oversight, eConsent, delivery of investigational medicinal products (IMP), and administration at home. In this article, we will review these recommendations and consider what impact they may have on the future of DCTs.
Leveraging the Expertise of Healthcare Professionals to Enhance DCT Design and Implementation
The EMEA organization highly recommends involving investigators and healthcare professionals in the design, development, and implementation of DCTs. These professionals can provide valuable insights into the potential consequences of reduced personal contact with trial participants and can help develop strategies for managing data collection and ensuring the quality and integrity of the source data. Their expertise and experience are essential for ensuring the success and safety of the trial. Involving investigators and healthcare professionals in the design and implementation of DCTs can help to ensure that the trial is conducted in a way that is safe, ethical, and compliant with regulatory requirements.
DCT Procedures - Site Burden Awareness
It is important to carefully consider the potential benefits and drawbacks of transferring any clinical trial-related procedures to decentralized settings. While decentralization may offer certain benefits, such as increased convenience for trial participants and the ability to reach a wider and more diverse population, it may also introduce new challenges and potential risks that need to be carefully managed. For example, decentralization may increase the burden on trial participants to manage their own care and follow-up, which may not be feasible for some individuals. It may also require new or modified protocols and procedures to ensure the safety and integrity of the trial. Therefore, it is important to carefully weigh the potential benefits of decentralization against any potential transfer of burden and to plan and implement decentralization strategies to minimize any negative impacts.
IMP Integrity and Logistics
It is important to have a contract in place between the logistics provider and the vendor used for logistics in a clinical trial to outline the steps for distributing and/or dispensing the investigational medicinal product (IMP) to the participant's home. This helps to ensure that the IMP is handled and shipped in a way that meets regulatory requirements and ensures the safety and efficacy of the product.
In the contract, the logistics provider should outline the steps they will take to confirm the identity of the IMP, including verifying that the IMP that was dispensed is the same as the IMP that was dispatched and received. This is an important quality control measure that helps to ensure that the right product is being used in the study and that the integrity of the IMP is maintained.
It is also important to inform participants in the clinical trial that their personal data will be used by a third party vendor to ship the IMP to their home. This should be included in the informed consent process, and participants should be made aware of their rights and any potential risks associated with the use of their personal data in this way.
Local Pharmacies Use
It is important to consider the storage and administration of the IMP at the participant's home when designing a clinical trial. Local pharmacies may be used as an alternative to shipping the IMP directly to the participant's home, and labeling requirements should be consulted in this case. The pharmacist handling the participant in the clinical trial should be trained to dispense the IMP according to the protocol.
DTP and Self dispensing / Healthcare Involvement
If the IMP requires healthcare professionals to be involved in its preparation or administration, it is recommended that the IMP be shipped to the healthcare provider rather than the participant's home. If this is not possible, clear instructions for the storage of the IMP prior to meeting the healthcare professional will be needed. If the participant is expected to self-administer the IMP, step-by-step instructions should be provided, and the use of electronic instructions accessible via methods such as QR code scanning may be considered.
Storage at the Patient Home
When designing a clinical trial, it is important to consider how to ensure the appropriate storage conditions of the IMP at the participant's home. This is especially relevant for DCTs where the participant takes the medication home, but it is also important to consider in traditional clinical trials. Inclusion and exclusion criteria should include provisions related to the adequacy of the participant's home for storage of the IMP, such as temperature control and restricted access where necessary. Sponsors should provide clear guidance on storage at the participant's home in a way that minimizes burden on the participant. It is important to ensure that the storage conditions of the IMP are met to maintain the safety and efficacy of the product.
Drug Centric Procedures - Accountability, Returns
It is also important to have accountability, IMP return, and recall procedures in place in case a recall is necessary. If a recall is needed when the medication is stored at the participant's home, it is important to have a plan in place for how this will be communicated and how the IMP will be collected. There are many considerations to take into account when designing a study that involves the administration of IMP at the participant's home.
Regulators are well aware of the challenges and benefits of DCTs and are increasingly open to the use of technology to facilitate these studies. This includes the use of barcodes to allow easy access to participants and quicker updates as needed, as well as the use of interactive response technology (IRT) to help monitor and operate the process while maintaining drug integrity and participant safety as the top priority.
The guidance is a good start and will probably be updated as the industry gains more experience. It is important for sponsors to work closely with regulators to ensure that DCTs are conducted safely and in compliance with regulatory requirements.
In the future, regulators may require more information on the use of central pharmacies and storage and monitoring compliance at the participant's home to mitigate risks in DCTs. Sponsors should be prepared to provide this information and demonstrate how they are addressing these risks in their DCT protocols.
Link to the recommendation letter published in December, 2022: https://docs.google.com/document/d/1iq36_zmq5nR-gu0IG_DEOBCB0BHvvltD/edit
About the Author
Neta Bendelac is the Senior Director of Strategy at 4G Clinical, a leading provider of randomization and trial supply management technology for sponsors and CROs conducting clinical trials. With over 14 years of experience in Clinical Supply Chain Management, including serving as the head of the Clinical Supply Chain department at global Pharmaceuticals companies, Neta is a recognized thought leader in the field.
In her role at 4G Clinical, Neta is responsible for identifying trends, driving innovation, and shaping products to meet industry needs. She has a wealth of expertise in clinical supply chain and decentralized clinical trials, and has developed innovative approaches to managing investigational medicinal products (IMPs) in clinical trials with a patient-centered perspective. Neta’s background is in international supply chain consulting, helping companies worldwide to optimize their supply chains through the use of simulation and optimization tools.
Neta Bendelac is the Senior Director of Strategy at 4G Clinical, a leading provider of randomization and trial supply management technology for sponsors and CROs conducting clinical trials. With over 14 years of experience in Clinical Supply Chain Management, including serving as the head of the Clinical Supply Chain...