EMA’s new clinical trials guideline
This guideline, which ensures regulatory compliance with the requirements of ICH GCP E6, came into effect on 9 September 2023. It introduced a new consolidated framework of standards for computerised systems and electronic data in clinical trials. It is a unique guideline in its thoroughness and extent on the matter. OSP had a conversation with Vesta Marciulioniene, director of regulatory affairs at ICON.
What is ICON’s current experience on the implementation of EMA Computerised systems and Electronic Data Guidance?
With our experience to date we serve our customers both in delivery of standard services, as well as continuous consulting with them on our implementation of the guideline and sharing the lessons learned in specific areas of interest to our customers.
In advance of the guidance being published and given its holistic and forward-thinking approach of the guidance, a cross-functional team at ICON, including representatives from over 30 different groups, assessed the impacts of the EMA guidance which was termed the impact-risk assessment phase. Following this initial phase, the team then moved into the remediation and implementation phase, based on the impacts identified during the initial phase – this was called the impact mitigation phase. Just couple of months into the initiative, approximately 75% of the potential assessed impacts were identified as having no risk or low risk and therefore no mitigation was required. This gave us the high level of confidence we were already in a good compliance position as a company from the very start. To date, we have been methodically working with a focus to close all remaining impacts, mainly related to systems, processes and delivery, and we continue to be on the right track targeting to conclude each outstanding mitigation within a defined timeline.
Can you share any success story on implementation?
In our own experience implementing the guidelines, in addition to supporting customers over the last number of months, successful implementation success stories have some common characteristics:
Clear strategy and methodical approach
The focus from the beginning should be to have a strategic and organised initiative. For us here at ICON, this included well-defined phases, clear tools, effective change management and oversight of the global team. We were also able to immediately identify where further clarifications on the scope and interpretation of the guidance from the EMA was needed. This clarification was sought and allowed us to ensure we had considered the entire scope expected by the EMA, ensuring we were driving towards inspection-readiness.
Cross-functional collaboration
Input from cross functional experts, right across the organisation and from external partners, on impact and mitigation activities is crucial. This collaboration is required to ensure impacts are dealt with quickly and effectively and mitigations are put in place to ensure continued compliance. This allows for deep dive discussions on different aspects of the guidance in order to choose the best course of decisions and actions.
Awareness building
Whilst working through how we can support customers with implementation of the guidance, building awareness of the guidelines and its impact with our customers, investigators, sites and other stakeholders was important. These conversations, which happened in a range of formats, from blogs, whitepapers, articles and webinars to in-depth meetings, were important so that sponsors and investigators could give the due consideration to the guidance. They were also important in driving key decisions to support compliance.
What are the challenges faced?
The challenge from the start has been the short term of six months from publication to the effective date of the guideline, defined by the EMA. The complexity and the multilayered scope of the guideline has not been an easy nut to crack. Two main challenges, underestimated in the release of this guideline, is the time and the investments required to develop and evolve the technology and systems to meet the future-state expectations. This includes many stages to determine, scope, plan, pilot, test, validate and implement. Systems owned or purchased by individual companies or sites are likely to still be in reasonably good control. In the meantime, the variability of governmental, regulatory and site-owned systems used in clinical trials presents significant challenges to the industry and the sites, including aspects of access control, adequacy of functionality, provision of direct access and audit trails.
What steps are taken to overcome the challenges? (meaning prompt for clarification by EMA on interpretation and acceptance of medical health care system standards)?
Not all of the technology systems that may be utilised are in the control of the individual sponsor, CRO or site, for example Electronic Medical Records (EMRs) systems, which may be owned by national or regional institutions. ICON has been working closely with Association of Clinical Research Organisations (ACRO) to open further discussions with the EMA on the concerns when the technology has current limitations to catching up with the expectations of the guideline. As a case in point, there is industry-wide concern of the unintended consequences of the guideline’s application to EMRs, which attempts to address the concerns of these systems owned by national or regional institutions. ICON have developed the concept of a ‘digital standard of care’ approach applied to the technology that is used in normal medical practice. Digital standard of care equates to national/institutional systems used in day-to-day routine healthcare settings and compliant with the national requirements. We await to hear feedback from the EMA on whether this digital standard of care will be applied in a similar way to the usual medical standard of care.
How do sponsors collaborate with CROs on the implementation of the guidance?
Sponsors have had a growing interest on the topic since the guideline was published to gain confidence with the compliance across their own, vendor and site systems. This impacts any sponsor globally where marketing authorisation is expected to be submitted in the EU. ICON has had multiple awareness and collaboration sessions with our sponsors. In addition, this topic is increasingly being asked about during audits, which is starting to bring the compliance to the guideline into strong focus.
What expectations do you have as CRO for investigator sites in implementing the requirements of the guidance?
For site-owned systems and technology or contracted vendors systems, the sites themselves should take full accountability for those to be compliant to the EMA guideline. However, in cases when, for example, EMRs are owned by national or regional authorities, addressing existing system deficiencies and limitations is important for them to continue to be used. Further local debates need to be pushed by sponsors and sites through any available country clinical research associations. All efforts are needed to accelerate the modernisation of the health systems currently not catching up with the guideline. In contrast, the hope is that the EMA will accept the digital standard of care at a site is acceptable for use in clinical research.