The European Medicines Agency’s vision of a single source of truth for clinical trial information forces a major shift in how companies collect and store trial data and documents, explain Stephan Ohnmacht and Werner Engelbrecht.
The Clinical Trials Regulation (CTR represents a milestone on the journey to a more competitive European R&D environment, particularly for multinational studies. Improved trial transparency (for which the European Medicines Agency – EMA – recently opened a public consultation) will make it easier for patients to participate in research. A harmonised approach to clinical trial applications across Europe should lead to faster approvals.
However, companies have been facing challenges in several areas since EU CTR became mandatory three months ago. Sponsors and contract research organisations (CROs) find it difficult to coordinate submissions cross-functionally and meet tight deadlines, partly due to fragmented and time-consuming data collection. Redactions are another sticking point. Disclosures must be fully integrated within the standard clinical trial process yet occur more frequently across the trial lifecycle than before.
Some issues are outside companies’ control and will only ease once the Clinical Trials Information System (CTIS) reaches a steady state. Still, companies don’t need to wait for the next phase of CTIS to improve their oversight of the complete submission file. Changing the resourcing of their regulatory and clinical teams and adapting their data collection, request for information (RFI), and redaction processes will provide much-needed visibility sooner. The benefits are not limited to EU CTR. Clarifying ownership and creating a single source of trial information would also make rest-of-world studies more efficient.
Small single-country studies are usually good candidates for a pilot submission to CTIS and have been used to uncover the limitations of existing processes. Insights from these first submissions have helped sponsors decide on an effective resourcing model for subsequent studies, including whether or not to outsource to CROs.
Sponsors that insource have improved alignment by creating a single EU CTR cross-functional process and team structure, spanning from regulatory and clinical to quality, safety and trial disclosure. In the past, these teams had independent responsibilities. Regulatory managed the submission of health authority approvals while clinical teams handled ethics committee approvals at the site or country level. Condensing regulatory and ethics committee approvals into a single process requires adjustments to team structure and responsibilities.
Companies have set up their centralised submission teams for success by clarifying ownership of the end-to-end process and confirming new responsibilities. Among Veeva customers, there isn’t a consensus on which team should be in the driver’s seat: roughly half point to regulatory while the remainder opts for clinical operations. Irrespective of which team leads, its submission responsibilities are broader than before, extending to regulatory, ethics and disclosures.
The European Medicines Agency has thrown down the gauntlet – and for some companies, this provides a welcome opportunity
As the nominated team is pivotal in collecting trial-related information, its remit should be clearly communicated to the broader organisation. Understanding who is accountable for gathering information from different stakeholders (e.g., quality, regulatory affairs, clinical) is critical, particularly during RFIs from EMA, which require a response within 14 days. A tracker specifying ownership for each task can make it easier to collect RFI answers across the organisation.
Customers are also exploring new ways of working to counter the challenges of fragmented data collection and dynamic redactions. Some sponsors have delegated data entry into CTIS to CROs for outsourced studies, eliminating a few extraneous steps. Similarly, centralising responsibility (whether internally or outsourced) for redactions helps to manage this process more effectively because training, guidelines and standard operating procedures can be implemented in just one dedicated team.
Single source trial information
Some customers are now sufficiently well-versed with the regulation to submit Parts I and II together. Leading companies go further during the initial submission by including many countries under Part II. Submitting multi-country studies in parallel decreases the number of evaluation cycles, reduces the risk to patient recruitment and shortens the overall approval timeline. But it’s a heavier upfront lift, for which easy access to trial-related information is essential.
It may be tempting to navigate a submission with pre-existing data collection processes, but this could prove shortsighted. Currently, CTIS lacks an API capable of receiving data and documents from either sponsor systems or tech partners (including Veeva). However, the next phase of CTIS will probably involve API capabilities, which could make company integrations more straightforward. Doing the hard work now to create a robust data foundation will pay dividends if (and when) the API is introduced by EMA.
Sponsors and CROs that have centralised data entry into one team (resourced with up to 10 people in enterprise biopharma) are already seeing the benefits of the new model. Having one part of the organisation accountable for data entry and upload to CTIS streamlines user access management and reduces the training effort required. However, data entry teams often need external support to create a repository of all the data points for each CTIS submission and then scale this structured approach across the company. This CTIS data collection tracker should be a single source of truth of all reportable data from different systems.
It can also be helpful to reflect on the spirit of the regulation when setting up a process to manage redactions. Companies need to balance disclosure risk with the benefits to patients of greater trial transparency. Usually, the two main types of data anonymisation activities, commercially confidential information and protected personal data, take place using a hybrid approach. Redactions of company information are often centralised because they require legal knowledge and personal data redactions are decentralised, so local teams can apply their national legal understanding.
Modifying redactions can quickly become messy in a hybrid model. Information that is confidential today might not be in a few months when the trial ends. Nor do all redactions involve obscuring text. Some content may need to change or be rephrased. The complexity of managing redactions could hinder patients and sites from enjoying easy access to study-related information envisioned in the regulation. To address these areas, sponsors should work in a system that maintains a close relationship between source and redacted documents so that teams can easily manage changes to content before public disclosure.
Meeting the new standard
A single source of truth for European clinical trial information will benefit patients, who will soon find it easier to participate in ongoing trials. Mandatory use of the same system should enhance stakeholder access to trial information without compromising robust data privacy standards.
However, EU CTR also challenges sponsors and CROs to reconsider how they collect and store trial data and documents for EU and non-EU studies. The European Medicines Agency has thrown down the gauntlet – and for some companies, this provides a welcome opportunity to get their houses in order.
Stephan Ohnmacht is Vice President, R&D Business Consulting at Veeva Systems
Werner Engelbrecht is Senior Director, Strategy, Veeva Vault Clinical Operations, at Veeva Systems