CTIS: Impact, Strategic Considerations, and SanaClis' Experience and Solutions

Introduction

Clinical trials are critical for evaluating the safety and efficacy of new medical products. The Clinical Trial Regulation (CTR) No 536/2014 by the European Union (EU) aims to harmonize and simplify the clinical trial approval process across all EU member states. As part of this initiative, the Clinical Trial Information System (CTIS) was developed. CTIS is an EU-wide electronic system that facilitates the submission, evaluation, and supervision of clinical trial information, enhancing transparency, efficiency, and patient safety.

Definition

CTIS is a cloud-based platform that serves as a centralized database and collaboration tool for managing clinical trials in the EU. It aims to streamline the submission, assessment, and supervision of trial-related information, promoting harmonization and efficiency in the clinical trial approval process.

Clinical Trial Submission Process

The clinical trial submission process is a crucial aspect of medical research and drug development, ensuring that new treatments and interventions are rigorously tested for safety and efficacy before they can be made available to the public. This process involves multiple stages and interactions with regulatory authorities to ensure that the trial is conducted ethically, with patient safety as a top priority. The introduction CTIS has further streamlined this process by providing a centralized platform for electronic submissions and efficient communication between sponsors and regulatory bodies. Let's break down the process step by step:

CTIS interaction with other systems and databases

CTIS interacts with various other systems and databases to ensure a streamlined and comprehensive approach to clinical trial management. These interactions facilitate data exchange, enhance collaboration, and support regulatory oversight. Here are some key points on how CTIS interacts with other systems and databases:

European Medicines Agency (EMA) Databases:

CTIS was developed and is managed by EMA, and it integrates with EMA's existing databases to ensure seamless data exchange. This integration allows CTIS to access and cross-reference relevant information, such as medicinal product databases and safety databases, to ensure accurate and up-to-date trial-related information.

National Regulatory Authorities' Systems:

CTIS interacts with the systems of national regulatory authorities in EU member states. This interaction allows regulatory authorities to review and approve clinical trial applications and related documents submitted through CTIS. It also enables real-time updates on trial statuses and facilitates consistent communication between sponsors and authorities.

Ethics Committees (ECs) and Institutional Review Boards (IRBs):

CTIS facilitates interaction between trial sponsors and ECs/IRBs. ECs review the ethical aspects of clinical trials, and CTIS enables the submission of trial documentation to these committees for approval. This interaction helps ensure that trials are conducted ethically and in line with patient rights and safety.

Sponsor's Systems:

While CTIS serves as the central platform for clinical trial management, sponsors may still have their own internal systems for managing trial-related data. CTIS might offer features to export or import certain data to and from the sponsor's systems, allowing sponsors to maintain consistent records across platforms.

Clinical Trial Management Systems (CTMS):

Some sponsors use CTMS platforms to manage various aspects of their clinical trials, such as site management, patient recruitment, and monitoring. Integration between CTIS and CTMS systems can enhance efficiency by allowing data to flow between the two systems, reducing duplicate data entry and ensuring data consistency.

Pharmacovigilance Databases:

Pharmacovigilance databases track and monitor adverse events and safety data related to medicinal products. CTIS has mechanisms to communicate safety-related information to these databases, ensuring that safety concerns are promptly reported and managed.

Data Repositories:

CTIS may interact with centralized data repositories that store aggregated and anonymized clinical trial data. These repositories can be valuable for post-market surveillance, research purposes, and generating insights from a broader dataset.

Electronic Health Records (EHR) Systems:

Depending on regulatory requirements and trial design, there may be interactions between CTIS and electronic health records systems. This could involve accessing patient medical histories for eligibility assessment and safety monitoring.

The interaction between CTIS and these various systems and databases is crucial for creating a comprehensive and efficient ecosystem for clinical trial management. These interactions enhance data accuracy, reduce redundancies, promote transparency, and support timely regulatory oversight. However, the specifics of these interactions and integrations can vary based on regulatory guidelines, technological capabilities, and the design of the clinical trial ecosystem.

The transition of existing Clinical Trial Authorizations (CTAs) from the EU Clinical Trial Directive (CTD) process to the EU Clinical Trial Regulation (CTR):

Transition from EU CTD to EU CTR:

The EU CTR replaces the previous EU CTD and introduces a harmonized regulatory framework for clinical trials across the EU member states. The transition involves moving ongoing clinical trials from the existing CTD process to the new CTR process.

Timeline of the Transition:

The transition period for moving existing ongoing trials from the EU CTD process to the EU CTR process began on February 1, 2022, and will conclude on January 31, 2025. This three-year period provides sponsors with a defined timeframe to adapt their ongoing trials to comply with the requirements of the new regulation.

Implications and Considerations:

During the transition period, sponsors are expected to take the necessary steps to transfer their ongoing clinical trials from the CTD process to the CTR process. This involves aligning trial documentation, procedures, and interactions with regulatory authorities and ECs according to the new CTR guidelines.

Trial Preparation:

Protocol Development:

The clinical trial begins with the creation of a detailed protocol outlining the study objectives, methodology, patient selection criteria, treatment plans, and assessment methods. This protocol serves as the foundation for the entire trial.

Documentation Preparation: Various documents, such as the Investigator's Brochure, Informed Consent Forms, Case Report Forms, and Clinical Study Reports, are prepared to provide comprehensive information about the trial's design, procedures, and expected outcomes.

Application Submission:

?The process of submission is in EU countries, and non-EU countries varies. In EU countries submission to both Regulatory Authoritieis as well Ethics Committees is performed via CTIS. In non-EU countries the submission process to Regulatory Authorities and ECs is performed separately.

Ethics Committee Review:

In CTIS, the trial protocol and related documents are submitted in parallel to independent ECs or IRBs and Regulatory Authorities for approval. The EC evaluates the trial's ethical considerations, patient consent process, and potential risks and benefits.

Regulatory Authority Submission: The sponsor submits an application to the relevant regulatory authority, such as the Food and Drug Administration (FDA) in the United States or respective Regulatory Authority via CTIS portal in Europe. This submission includes comprehensive information about the trial, its objectives, methodologies, and documentation on safety and efficacy.

Assessment:

Regulatory Review:

Regulatory authorities review the submitted application to assess its scientific validity, patient safety measures, and compliance with regulatory guidelines. This involves evaluating the trial's design, patient recruitment methods, investigational product details,

Communication and Clarifications: During the review process, regulatory authorities may request additional information or clarifications from the trial sponsor to ensure a comprehensive understanding of the trial. This stage involves iterative communication between the sponsor and the regulatory authority.

Approval and Initiation:

Approval Decision: Based on a thorough assessment, the regulatory authority decides whether to grant approval for the clinical trial to proceed. Approval is contingent on meeting all regulatory requirements and addressing any concerns raised during the review process.

Initiation: Once approval is obtained, the trial can commence recruitment and treatment of patients according to the approved protocol. The trial's progress is monitored closely to ensure compliance with the approved procedures and patient safety.

The introduction of CTIS simplifies and modernizes this process by providing a unified platform for sponsors to electronically submit trial-related information to regulatory authorities. CTIS enhances efficiency by facilitating quicker communication between sponsors and regulatory bodies, reducing paperwork, and improving data accuracy. It also offers a standardized format for submission, making it easier for regulatory authorities to assess and review the submitted materials.

?Leveraging SanaClis' Experience and Solutions

?SanaClis, a leading clinical research organization (CRO), has extensive experience in utilizing CTIS and offers innovative solutions to help sponsors navigate the system effectively. By partnering with SanaClis, sponsors can benefit from their expertise and leverage their specialized tools and services.

• CTIS Implementation Support: SanaClis provides comprehensive support during the CTIS implementation process. This includes assisting sponsors with system onboarding, data migration, and ensuring compliance with CTIS requirements. SanaClis's experienced team guides sponsors through the entire setup process, ensuring a smooth transition to the new system.
• Regulatory Compliance Services: SanaClis assists sponsors in maintaining regulatory compliance throughout the clinical trial lifecycle. Their team of regulatory experts stays updated with the evolving CTIS regulations and ensures that sponsors adhere to the latest requirements. They provide guidance on protocol development, dossier preparation, and submission, ensuring sponsors meet all regulatory obligations.
• Training and Support: SanaClis offers comprehensive training programs to educate sponsors on CTIS functionalities and best practices. They provide customized training sessions to sponsors and their teams, equipping them with the necessary skills to navigate CTIS effectively. Additionally, SanaClis offers ongoing technical support, ensuring sponsors have access to assistance whenever needed

Quality Assurance and Audit Readiness: SanaClis assists sponsors in maintaining high-quality standards and audit readiness. They conduct internal audits, identify areas of improvement, and implement corrective actions to ensure compliance with CTIS regulations. By partnering with SanaClis, sponsors can mitigate risks and ensure smooth audits and inspections.

Impact of CTIS on Clinical Trial Management

Elimination of Paper-Based Submissions:

CTIS replaces the traditional paper-based method of submitting clinical trial applications and related documents with a fully electronic platform. This eliminates the need for physical documents to be printed, shipped, and stored, reducing the administrative burden associated with paper submissions. As a result, trial sponsors, regulatory authorities, and ethics committees can collaborate seamlessly through a digital environment.

Reduction of Data Duplication:

With CTIS, trial sponsors can submit trial-related information and documentation electronically in a standardized format. This reduces the potential for data entry errors and duplication of efforts that can occur when information is manually transcribed from paper documents. The system's structured data input ensures accuracy and consistency across submissions.

Real-Time Status Updates:

CTIS provides real-time visibility into the status of clinical trial submissions and reviews. Both sponsors and regulatory authorities can track the progress of the submission, review, and approval process. This transparency fosters effective communication and enables stakeholders to identify and address any bottlenecks or issues promptly.

Streamlined Review Process:

CTIS centralizes the review process by allowing regulatory authorities and ethics committees to access trial-related documents in a standardized format. This facilitates efficient and consistent evaluations of trial protocols, documents, and safety measures. The digital platform enhances collaboration among reviewers, allowing for quicker information exchange and resolution of queries.

Minimized Delays and Accelerated Approvals:

By providing a centralized repository of trial-related information, CTIS reduces the likelihood of delays caused by missing or incomplete documentation. Regulatory authorities and ethics committees can access the required materials in one location, enabling them to perform thorough assessments more efficiently. This streamlining leads to faster review timelines and ultimately quicker approvals for clinical trials.

Enhanced Communication and Collaboration:

CTIS fosters improved communication between trial sponsors and regulatory authorities. Sponsors can interact with authorities through the platform, addressing any queries or requests for additional information promptly. The digital environment also enables easier sharing of documents and responses, enhancing overall collaboration.

?Standardized Data Exchange:

The structured data format used in CTIS ensures that information is submitted in a consistent manner, following standardized formats and terminology. This not only reduces the chances of misinterpretation but also allows for easier data aggregation and analysis across multiple trials.

Efficient Documentation Management:

CTIS provides a secure and organized repository for all trial-related documents, making it easier for sponsors and authorities to access and manage essential information. This reduces the risk of misplaced or lost documents and simplifies the process of maintaining up-to-date records.

Strategic Considerations for Sponsors

• Adapting Internal Processes: Sponsors need to align their internal processes with CTIS requirements. This includes updating data management systems, training staff on CTIS functionalities, and ensuring compliance with relevant regulations.
• Data Quality and Standardization: Sponsors must ensure the accuracy and completeness of trial data submitted to CTIS. Implementing standardized data capture processes and quality control measures will help maintain data integrity and streamline submissions.
• Compliance with Regulatory Requirements: Sponsors should familiarize themselves with the specific regulatory requirements of each member state and ensure adherence to those regulations when submitting trial information through CTIS.

?Helpful Pointers and Suggestions:

• ?Ensure you verify the availability of data related to your study, including all stakeholders, substances, and products, within the OMS (Organization Management System).
• Don't hesitate to reach out to the EMA support desk if you have any questions or require assistance.
• Keep in mind that all documents, except IMPD-Q and financial arrangements, are accessible to the public. Personal data and commercially sensitive information must be redacted. Note that redacting documents can be time-consuming, so it's advisable to establish a well-structured document management process. For example, at the site level, you'll need to submit a minimum of seven documents, including public and non-public CVs, public and non-public Declarations of Interest (DoI), suitability assessments of the facilities (public and non-public), and GCP documentation.
• When preparing Part II application documents, make use of the recommended templates available at the following link: https://health.ec.europa.eu/medicinal-products/eudralex/eudralex-volume-10_en
• Ensure that all submitted documents are named correctly according to the specified naming convention.

?Conclusion

CTIS is a transformative step in streamlining the clinical trial approval process within the EU. Its impact on clinical trial management is significant, enhancing efficiency, transparency, collaboration, and patient safety. Sponsors play a crucial role in leveraging CTIS effectively, requiring strategic considerations to adapt to the system's requirements. SanaClis, with its experience and innovative solutions, provides valuable support to sponsors, enabling them to navigate CTIS successfully and maximize the benefits offered by the system. By embracing CTIS and partnering with organizations like SanaClis, sponsors can streamline their clinical trial processes, accelerate trial approvals, improve data quality, and ensure compliance with regulatory requirements.