Managing the New EU Clinical Trials Regulation 536/2014 – Guidance for Navigating the Clinical Trial Information System (CTIS)
Staying on top of global regulatory guidelines and compliance is challenging for every organization working in the clinical research industry. Leaders from THREAD recently attended a comprehensive training session around the new Clinical Trial Regulation 536/2014 held by the European Medicines Agency (EMA) in order to help our global customers effectively navigate the changes associated with the new guidelines. In a previous piece, we discussed the changes brought about by the regulation in total. Based on our knowledge of the new regulation, along with our years of experience helping our customers conduct global decentralized clinical trials, the following are our recommendations for how to successfully access and use the new Clinical Trial Information System (CTIS), a critical piece of the new EU regulation.
The CTIS is a centralised, single-entry EU portal and database that will become mandatory for new clinical trials under the clinical Trial regulation after the 31st of January 2022. The aim of the CTIS is to standardise the application, authorisation and supervision processes, improve coordination and increase transparency throughout the Lifecycle of all Clinical trials conducted throughout the European Economic Area (EEA). Its intent is to generate a societal and economic benefits by facilitating large-scale trials to address key health issues, enable knowledge sharing and expert collaboration and ensure the EEA remains an attractive clinical research landscape globally.
The single- entry CTIS portal will support sponsor companies and Contract Research Organizations (CRO’s) by facilitating the:
- Authorisation of clinical trials in up to 30 EEA countries with a single application
- Submission of substantial and non-substantial modifications in a single application
- Addition of new members states to an existing clinical trial application
- Respond to requests for additional information (RFI)
- Submission of notifications e.g., serious breaches, trial start dates
- Submission of annual safety reports in one single submission
- Publication of a Clinical trial
Sponsors will no longer have to submit clinical trial applications separately in each EEA country but can apply through CTIS, the single-entry point for clinical trials submissions. In addition, CTIS harmonizes submissions to Member State national competent authorities and ethics committees within a single application, and provides public registration of each clinical trial, all within the same process. Sponsors and CRO users must undertake preparatory steps before it is possible to use CTIS and should avail of the comprehensive online training and sandbox environment provided by the European Medicines Agency (EMA) to ensure they are competent in the use of the CTIS when it becomes live on the 31st of January 2022
Below THREAD have set about providing some guidance for sponsor and CRO customers on how to access CTIS and on the management of user personae and role allocation within CTIS.
What do Sponsor/CRO companies need to do to access CTIS?
CTIS is structured in two restricted and secured workspaces (sponsor workspace and authority workspace) and a public website. Access to the secured workspace will require valid EMA credentials. The sponsor workspace provides clinical trial sponsors with the functionalities for submission of CTAs to Member States and management of information throughout the life cycle of clinical trials (Diagram 1)
Diagram 1
Resource: https://www.ema.europa.eu/documents/newsletter/clinical-trials-information-system-ctis-highlights-june-2020_.pdf (1)
Access to CTIS. Sponsors/CRO’s are required to complete the following steps to ensure they are registered to make a clinical trial application for authorisation on CTIS.
Register for a user account in EMA Account Management portal
- In order to gain access to the CTIS sponsor workspace, all users will require to have an active EMA account. Users who already have access to other EMA applications e.g., Eudralink, Eudravigilance can access the CTIS system using their existing EMA account credentials.
- If a user does not already have an active EMA account, they will need to create one, by self-registering on the EMA Account Management (IAM) home page.
- Having an EMA account with a Substances, products, Organizations and Referentials (SPOR) user role is necessary step before registering your organization.
- User registration in the EMA Account Management portal can be completed at any time, however users will not be able to access CTIS until the system is live.
- Users can also register for an EMA account using the ‘Register New User’ link on the CTIS Workspace login page
Register your organization
CTIS consumes organization data from the Organization Management portal (OMS). OMS provides a single source of validated organization data that can be used as a reference to support EU regulatory activities and business processes. It stores master data comprising organization name and location address for organizations such as marketing authorization holders, sponsors, regulatory authorities, trial sites and manufacturers. (2)
- If an organisation has already been successfully registered in OMS, a user can retrieve its details within CTIS to populate the clinical trial application, submit notifications or to use it for other sponsor-related activities in CTIS (e.g., populate employer’s details in personal profile).
- If an organisation is not yet registered in OMS they should go to the EMA’s Substance, product, organization and referential (SPOR) portal and log in with their EMA account.
- Before submitting a request to register an organization via OMS, the user must search the available records for their organisation by clicking on the Organizations tab.
- If the user cannot find their organization by name and country, they can request creation of a new organisation from the search page or from the View Organisation/Location Details page.
- Supporting documents must be submitted which allow the EMA to validate the request.
Next steps- What user Management approaches exist on CTIS and what’s the difference?
The CTIS contains two user management approaches which enable an organization to manage their users according to their company needs and resources:
The Organization-centric approach
In which a high-level administrator e.g., Sponsor Administrator, previously validated by the EMA is required. This approach is necessary for big organizations managing a high number of users and Clinical Trials (CTs). This approach is established automatically on the system once the sponsor assigns a high-level administrator via the EMA account management. Users will need to have roles assigned by the high-level administrators or delegated medium-level administrators to perform any action in the system. This approach requires formal registration of an EMA validated high level administrator, but will provide the opportunity to manage access and roles across trials and have good visibility of an organization users and workload.
The Trial centric approach
Is expected to be used by non-commercial sponsors managing a small number of users and Clinical Trials (CTs) on CTIS. This approach is assigned automatically if the sponsor for which a Clinical Trial application (CTA) is created does not have a high-level administrator registered in OMS. The user will be automatically assigned as the Clinical trial administrator for that specific trial only. The management of users under this approach is done by the CT Admin role, which is automatically created at the trial level. This approach Allows a faster and less complex process when submitting a first initial application, as no validation process is required however it becomes less convenient when an organization applies for or runs multiple trials
How to register a High-level Administrator for an organization-centric approach
A high-level administrator role (Sponsor Administrator) must be validated/approved by the EMA following the submission of the ‘Affiliation Template Letter” as proof of the authority to represent their organization.
- High-level administrator CTIS roles (e.g., Sponsor Admin) must be requested via EMA Account Management by logging into the EMA account.
- EMA will need to validate the request to become a high-level administrator.
- When the high-level administrator role has been assigned, it can be seen in the EMA Account Management portal.
- EMA will only be involved in granting high level administration roles to one high level administrator. Any new requests for high-level administrators will then be managed by the existing high-level administrator of the organization
- All administrator roles can assign other roles within CTIS. All roles will have predefined permissions that users can perform on data and documents within CTIS (Diagram 2)
Diagram 2
What are permissions within CTIS?
Permissions are actions that are already predefined within CTIS that users can perform on data and documents. Three types of permission are available in CTIS
- User Management permissions- allows administrator users to manage users with a CT or an organization.
- Task Management permissions- allows business users with the role of CT Coordinator to assign business tasks to member state (MS) users. This role is specific to MS users
- Access Level permissions- Allow business users to perform actions on data and documents stored within CTIS i.e., view prepare or submit for a specific trial or all trials within their organization.
What roles can Sponsor users have within CTIS?
Sponsor organizations users can have high-level administrator roles (sponsor admin), medium- level administrator roles (CT admin) and business roles which include viewer, preparers, and submitters for part 1, part 2 of the CT application and notifications and CT results.
What is the Sponsor workspace in CTIS?
The sponsor workspace within CTIS is a dedicated space where Sponsor users can manage all their clinical trial activities in one spot. In this workspace they can submit an initial clinical trial application, substantial and non-substantial modifications, in addition to adding new member states to an existing clinical trial application. They can also submit additional documentation to update a clinical trial dossier, reply to requests for additional information from the reporting member state of a clinical trial and submit notifications e.g., start of a trial, start of recruitment, serious breaches, and summary of results. The search functions within the sponsor workspace in CTIS are outlined in Diagram 3
Diagram 3
Resource: https://www.ema.europa.eu/documents/newsletter/clinical-trials-information-system-ctis-highlights-june-2020_.pdf (1)
Take Home Message
Sponsor organizations should prepare now for the CTIS becoming live in January 2022 by ensuring they understand the requirements for accessing and using the system. THREAD has provided an overview of the requirement in this article for using the CTIS system but Sponsors and CRO’s should also avail of the comprehensive online training programs provided by the EMA to ensure all users are trained and practice in the sandbox environment to ensure proficiency in its use. Understanding the roles and permissions within CTIS is fundamental in managing resources and getting your organization off to a good start.
Sponsor companies and CRO’s should prepare now
For additional information on how THREAD can help you optimize your clinical trials, visit THREADResearch.com.
Caroline Kelly
Senior Manager, Consulting, THREAD
Caroline brings extensive knowledge and experience in clinical research study design and conduct having worked in the field for the past 24 years. She is a qualified Nurse with a Post Graduate diploma and master's degree in Health Science with most of her career working at site level in Clinical Research.
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