Navigating Decentralized Clinical Trials In the EU and the UK
In the wake of the COVID-19 pandemic there was an increased uptake in decentralized clinical trials (DCTs) in the EU and the UK. DCTs differ from traditional clinical trials in that they incorporate ‘remote’ elements. These enable activities such as consent, administration of the treatment, data collection, and monitoring to take place remotely, for example from the patient’s home. However, DCTs remain subject to all the laws and rules applicable to clinical trials. In Europe, these include the EU Clinical Trial Regulation and the General Data Protection Regulation (GDPR).
Guidance on how to properly conduct DCTs has been recently emerging, both at an EU level and at a national level in EU member states and in the UK. This month, on 13 December, new EU-level guidance in the form of a joint recommendation paper on decentralized elements in clinical trials (the Recommendation Paper) was published by the Heads of Medicines Agencies, the European Commission, and the European Medicines Agency.
The Recommendation Paper and other recent EU and UK guidance have clarified a number of key considerations for DCT sponsors in the EU and UK:
- Patient recruitment and informed consent: Inclusion/exclusion criteria for DCTs should contain provisions relating to the adequacy of the participants’ homes, for example temperature control. Electronic methods may be used for documenting written informed consent, though different countries may hold different positions on the permissibility of electronic consent (eConsent). Any eConsent system used must ensure participant confidentiality is maintained, and source consent documentation must be available for inspection during and after the end of the trial.
- eSignatures: Electronic signatures are increasingly used in the context of DCTs. Some countries require a participant’s identity to be verified via video link when providing an electronic signature. Depending on the risk classification and degree of intervention of the clinical trial, different types of eSignatures may be required, and all eConsents/eSignatures must comply with the GDPR. Often, it is good practice or even required to carry out a data protection impact assessment to assess the risk from a data privacy perspective when using eConsent forms.
- Delivery and administration of investigational medicinal products (IMPs): Any risk assessment of the delivery of an IMP at home should address whether an observation period and emergency plan are necessary, storage conditions, medicine accountability, and the preparation, stability, and robustness of delivering the IMP and administering it at home. The Recommendation Paper suggests limiting transportation steps for the active pharmaceutical ingredient and choosing authorized vendors for delivery. The protocol should account for delivery of the IMP to a participant’s home. Trial participants should be given appropriate training and alternatives to their personal devices for capturing trial data.
- Patient monitoring and telehealth: Details of any monitoring strategy should consider the risks of any tools, locations, and individuals involved in the decentralized elements. The monitoring strategy should not unduly burden the site and should ensure that any adverse events are reported appropriately. Any digital/telehealth tools used must be subject to validation and assessment rules and follow the study protocol.
- Data flows, management, and data integrity: Data collected must follow the same GCP standards as any other method of data collection. Re-monitoring should be considered if there are any concerns about the quality of the data. Further, all personal data processing in the context of a DCT must comply with the GDPR. The key consideration/impact that a sponsor needs to consider in relation to a DCT – as opposed to a traditional clinical trial – is data flows. These will be vastly different in a DCT, with significantly more direct-from-patient data collection and a higher number of actors in the data flow chain. This may have an impact on, for example, data processing/transfer agreements, cyber security and the virtual (remote) exercising of data protection rights.
- Overarching responsibility: Throughout the DCT, the sponsor and investigator remain responsible for fulfilling the tasks laid out in the DCT protocols. The rationale and extent of delegated tasks should be clearly laid out in the protocol and in a written agreement between the responsible party and delegee.
- Equipment retrieval post-trial: Care should be taken to ensure that no equipment provided for the trial could be seen as an incentive to study participants.