Imagine a new disease sweeping across Europe. Scientists rush to launch clinical trials for life-saving treatments, but they’re mired in a bureaucratic swamp of paperwork, technical glitches, and conflicting demands. This isn’t fiction; it’s the reality of the European Medicines Agency's (EMA) Clinical Trials Information System (CTIS).
Launched in January 2022 with the promise of streamlining clinical trial approvals, CTIS has instead become a source of frustration for researchers battling outbreaks. This article explores the experiences of three studies ensnared in the system, revealing the shortcomings that threaten Europe’s capacity to respond effectively to future health crises.
A System Designed to Streamline, But Drowning in Red Tape
Previously, the clinical trial approval process in Europe was a patchwork of national regulations, leading to delays and inconsistencies. CTIS aimed to harmonize this process through a centralized platform. However, the reality is far from the promise. Researchers involved in three multinational studies—EU-SolidAct (Bari-SolidAct and AXL-SolidAct) and MOSAIC—have found themselves grappling with a system that requires extensive paperwork, imposes conflicting requirements from different countries, and presents unexpected technical hurdles.
Data Collection and Management Challenging
When CTIS was launched, there was a clear need for change management regarding data collection and management. Cervantes notes that while some larger organizations have developed internal solutions and defined who will collect the necessary information for submissions, other sponsors are still trying to understand the exact data requirements and processes around Part I and Part II submissions. The new application process has two parts: Part I includes scientific and medical product documents, while Part II contains national and patient-level documents.
With CTIS and the Clinical Trials Regulation (CTR) came increased transparency, resulting in more data being made publicly available. This shift necessitates that sponsors consider the risks related to protecting personal data and commercially sensitive information. “Human oversight is needed to be constantly on top of that and ensuring that the right documents have been redacted and are up to date,” Cervantes explains.
Another challenge is that CTIS lacks direct integration capabilities, meaning data and information must be manually entered into the system, creating a high effort burden. A survey by Phlexglobal reveals that 42% of respondents track CTIS activity manually, often using Excel. Cervantes mentions that over time, the EMA might introduce an application programming interface (API) to facilitate better automation of the process.
However, Khera cautions that while the EMA is likely considering improvements to CTIS, automation remains distant. “You can only automate something when you understand what needs to be automated,” she says.
“CTIS has more advantages than disadvantages, and it is just a matter of time and experience,” Koepke adds. Khera encourages sponsors to seek help, whether through stakeholders familiar with CTIS or from the resources provided by the EMA. “We need to give this new system a chance; it can always be refined with industry feedback,” she emphasizes.
From the end of January 2023, sponsors must use CTIS to submit all new clinical trial applications. By January 2025, EudraCT will be phased out, requiring all new and ongoing studies to transition to CTIS. While this represents a significant management change, the long-term benefits of collaborating with regulatory bodies and achieving better clarity over submission and approval timelines will outweigh the short-term operational inefficiencies.
Delays That Cost Lives
While CTIS has marginally reduced approval times compared to the old system, the process remains agonizingly slow—especially critical during outbreaks. For instance, in the case of MOSAIC, a study on the mpox outbreak, approvals in some countries arrived only after the outbreak had peaked, rendering the research largely irrelevant.
Delays arise from various factors: the sheer volume of required documents, the need to navigate conflicting national demands, and the system's inefficiency in handling modifications. Adding a new study site, for example, can take months due to the need for approvals from both regulators and ethics committees in each country.
Technical Glitches and Kafkaesque Bureaucracy
Researchers also face numerous technical problems with CTIS. System glitches have led to lost data, duplicated work, and unnecessary delays. The process for addressing queries from regulators—known as RFIs—often comes with unreasonably short deadlines and no clear communication channels.
Imagine submitting a stack of documents only to find that a minor error in one invalidates the entire submission weeks later. This Kafkaesque scenario reflects the frustrations researchers encounter with CTIS.
The Price of Progress?
The increased complexity of CTIS has led to a significant rise in costs. Submitting applications or making modifications can be prohibitively expensive, especially for publicly funded academic research. This creates an uneven playing field, favoring large pharmaceutical companies over smaller, independent research groups.
A Call for Urgent Reform
The experiences of these studies paint a troubling picture of a system struggling to meet the demands of outbreak research. While CTIS offers some benefits, such as increased transparency, its flaws far outweigh them. Urgent reforms are needed to address the following issues:
Reduce the Document Burden: Many required documents are unnecessary and contribute to delays without adding value.
Harmonize National Requirements: Conflicting demands from different countries create confusion and extra work.
Streamline the Modification Process: Changes to a study should be quick and straightforward, not a months-long process.
Fix Technical Glitches: The system needs to be reliable and user-friendly to prevent unnecessary delays.
Reduce Costs: Fees for submitting applications and modifications should be reasonable and transparent.
Ethical Implications
Beyond practical challenges, CTIS raises serious ethical concerns. Delays in trial approvals can prevent patients from accessing potentially life-saving treatments. The system’s complexity also discourages crucial research on emerging outbreaks, hindering our preparedness for future health crises.
Conclusion: A Race Against Time
The COVID-19 pandemic and the mpox outbreak have underscored the critical need for rapid, efficient clinical trials. In its current form, CTIS acts as a barrier to progress. Without significant changes, the system risks undermining Europe’s ability to protect its citizens from future health threats.
Researchers behind EU-SolidAct and MOSAIC have put forth concrete suggestions for improvement. It’s time for the EMA to listen and take action. The lives of European citizens may depend on it.
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