The European Medicines Agency (EMA) has updated its Q&A for good clinical practice (GCP). The update acknowledges that the sponsor may support the investigator by identifying or contracting service providers in the conduct of the clinical trial. This update reflects the leading role of sponsors in interaction with contracting service providers when trial activities are conducted remotely during decentralized clinical trials (DCTs). The GCP Q&A also addresses the use of productivity software in clinical trials, and it provides important considerations for when direct remote access to identifiable personal and health data is required in a clinical trial. These updates are the result of discussions and agreements within the GCP’ Inspectors Working Group intended to further coordinate GCP activities in the European Union.
Sponsor role in contracting service providers for trial-related tasks
In clinical trials, the investigator carries the responsibility of protecting the rights and welfare of trial subjects. However, in DCTs, trial activities are conducted remotely, implying a leading role for sponsors in related contracting services. The update acknowledges this reality, but stresses that the separation of the respective responsibilities of sponsors and investigators must be safeguarded. Their division of roles is elaborated in the Head of Medicines Agencies’ Recommendation Paper on Decentralized Elements in Clinical Trials. Accordingly, the update provides that the following conditions must be respected where sponsors identify or contract with service providers for trial-related tasks that are the responsibility of the investigator:
- There must be compliance with the applicable EU laws and the requirements of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use E6 guideline.
- The investigator retains the final decision on whether the service provider is appropriate, their supervision and ultimate responsibility for tasks involving trial-related medical decisions.
- A written agreement should be concluded between the sponsor and the service provider.
- The written agreement between the sponsor and service provider, as well as that between the sponsor and investigator, should clearly state that the investigator maintains adequate control and oversight over the tasks contracted by the sponsor.
- As a general principle, whenever agreements are concluded with service providers, a clear division should be maintained between tasks that are mutually exclusive or that lead to potential conflicts of interest (e.g., issues may arise when the service provider performs both the quality control function and the related task, or when the service provider performs tasks for the investigator and the sponsor even though independence in the tasks is required).
Productivity software
Productivity software is used in clinical trials to support the conduct of clinical trial processes and to record, track, and evaluate events that occur as part of a trial. However, the data generated often lacks traceability, as well as the means to attribute entries and changes. The updated Q&A proposes risk evaluation and, where appropriate, mitigation measures to offset these common shortcomings in areas where data integrity principles apply and prevent negative impacts to the risk-benefit balance of the clinical trial. Mitigation measures to ensure attributability and traceability may include, for example, additional programs or customizations that compensate for application deficiencies, restrictions on the use of the software itself or additional controls in the application environment.
When identifying clinical trial sites, sponsors should assess the impact of the sites’ use of productivity on the safety and integrity of data, as well as the safety and rights of potential clinical trial participants. If the sponsor identifies deficiencies, the site should only be selected if the shortcomings are appropriately justified, and the related risks are mitigated.
The updated Q&A specifies that productivity applications permitting specific configurations and customization of software functions should be subject to validation before use. The appropriate level of validation will depend on the use case and the corresponding risk that may be associated with the process. In addition, any modification of a productivity application should be performed only by qualified and trained personnel. Specific configurations and customizations of productivity application also should be taken into account in the clinical trial archiving strategy.
As a result, the suitability of the use of a productivity application should be assessed and determined on a case-by-case basis in light of the specificities of a clinical trial. To allow competent authorities to assess the appropriateness of mitigation measures, the use of productivity applications requiring mitigation measures, and the adopted mitigation measures, should be detailed and justified in the clinical study report.
Direct remote access
Direct remote access concerns access to data from an access point that is not under the control and supervision of the clinical trial investigator or site. This provides sponsor-appointed trial monitors or regulatory inspectors with remote access to identifiable personal and health data of clinical trial participants. The updated Q&A provides important considerations concerning direct remote access, in addition to national provisions on direct remote access. The considerations include:
- Informed consent of patients relating to any direct remote access to their confidential health records.
- The requirements provided in Annex 1 to the Clinical Trials Regulation regarding the content of the clinical trial protocol.
- Other technical considerations to identify and manage risks associated with accessing or viewing documents remotely.
Authors
Alix Vermulst
