Decentralized Clinical Trials Across Europe: Regulatory and Other Practical Considerations
Maya Zlatanova
FindMeCure Ltd.
D

ecentralized Clinical Trials (DCTs) can be an accelerator to increase patient diversity, recruitment, and engagement. The COVID-19 pandemic made decentralization not only a preference but also a necessity for many clinical trials globally whose operations were disrupted due to the complicated healthcare and logistical situation the pandemic caused.

On February 4, 2021, the European Commission published the updated, fourth version of the guideline on the management of clinical trials during the COVID-19 pandemic, i.e., the “Guidance on the Management of Clinical Trials during the COVID-19 (Coronavirus) Pandemic.” Although it is clear that these are temporary recommendations to manage clinical trials while the public health emergency lasts globally (e.g., implementing home health visits, shipping investigational medicinal products [IMP] directly to participants, and conducting remote Source Data Verification [rSDV]), these recommendations are key components deployed in DCTs which make for their global adoption under the current conditions and also in the future after the COVID-19 pandemic is resolved.

Regulatory and geographic factors greatly influence the adoption of DCTs. Compared to the United States, Europe has been highly impacted by local-specific translation of the European Medicines Agency (EMA) recommendations related to the implementation of DCTs. These country-level specifics include adoption of e-Consent, home-health nursing services, direct-to-participant IMP delivery solutions, and data privacy regulations.

E-Consent

In most countries in Europe, e-Consent is still not possible in its full remote format. For example, according to Gergely Béldi, a Hungarian clinical research expert, Hungary has been trying to adopt e-Consent but has encountered some challenges. The barrier is that even if a participant is allowed to read the e-Consent somewhere else and then have a telehealth conversation with the DCT investigator, a wet signature is still required on a paper-based original document. The situation in other European countries is similar. Yet, according to María López, a clinical research and regulatory consultant in Spain, there has been quite a big push in countries like Spain to implement e-Consenting solutions (via phone, web platforms, etc.).

Pavle Medenica, a Serbian clinical research expert, mentioned that the Serbian regulatory authority doesn’t specifically address this topic in their guidelines. Serbia adopted the Law on Electronic Document, Electronic Identification and Trust Services in Electronic Business in 2017. Based on this law, appropriate bylaws have been adopted for its explanation and more detailed application, and one of these is the Rulebook on detailed conditions that must be met by qualified electronic certificates. We can state that the basis for the application and use of the e-Consent process in Serbia has been formally created legally.

Home-Nursing and Home-Drug Delivery Solutions

The pandemic and the inability of many participants to travel to a clinical research site made it essential to implement home-health nursing services and direct-to-participant IMP delivery solutions across all European countries. The positive side is that there are international vendors having local offices and implementation know-how. The western European countries have a bigger diversity of vendors, whereas countries like Russia, Hungary, Bulgaria, or even Poland have fewer options. According to Lukasz Wozniak, a clinical research expert from Poland, what makes DCT implementation in Poland more flexible is not only the existence of vendor solutions but also the fact that there are many specialized Site Management Organizations (SMOs) that are helping the clinical research sites to adapt more quickly to the new environment and provide creative solutions.

During the pandemic, Russian clinical trials were also threatened. Alexsandr Stiblo, a clinical research expert from Global Clinical Trials, shared that since it was impossible at the time for patients to travel to clinical sites, sponsors issued a global memo authorizing telehealth as a means to perform participants’ visits remotely. His organization had to prepare an emergency notification to the Ministry of Health explaining that sites are unable to perform scheduled visits via telehealth without protocol deviations. This means they need an additional regulatory approval.

Data Privacy

All European Union (EU) member states comply with the General Data Protection Regulation (GDPR) requirements for data privacy. Countries like Russia have their own local regulations. In 2018, Serbia adopted the Law on Personal Data Protection which incorporated the principles of the GDPR into the domestic legal framework and harmonized this area with EU standards.

For conducting DCTs, GDPR is a big barrier for rSDV activities. Not many clinical research sites are able to allow sponsors to remotely access their medical records using their own specific systems. For example, in Spain systems such as Teams and Zoom with screen sharing are not considered to properly ensure data protection and privacy according to GDPR requirements.

During the COVID-19 pandemic, central monitoring has been the best approach to ensure a minimum level of monitoring activities in those clinical research sites that did not allow monitoring visits for rSDV purposes. In those investigational sites that allow rSDV, the Clinical Study Agreement must be amended to include:

  • specific fees to cover this activity,
  • documentation of Monitor Confidentiality Agreement, and
  • a secure remote connection protocol.

DCTs can significantly improve convenience for participants to enrol and stay in a clinical trial. Remote data collection is another advantage for the future of collecting real-world data and ensuring better communication with the approval of reimbursement by authorities. At the same time, DCTs are not a panacea, and it all comes down to answering these questions:

  • What motivates participants and how do they deal with the everyday challenges of their illness?
  • What are the administrative and specific regulatory requirements that empower or challenge the adoption of new solutions?
  • What are the surmountable and not surmountable barriers in each DCT that are defined by each protocol?

By answering these questions, sponsors should be able to see the relative potential of full DCTs, hybrid DCTs, or traditional trials. It also means that feasibility needs to go beyond traditional site surveying and competition analysis and combine participants’ needs and scientific questions together on the same roadmap.

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