EU drug agency proposes permanent clinical trial flexibility framework for crisis times

The European Medicines Agency (EMA) has published a draft guidance on the conduct of clinical trials during public health emergencies and opened it for consultation until 30 April. It explains how new and ongoing trials should be initiated, adapted and overseen once the European Commission has declared an EU‑level public health emergency. 

The draft draws heavily on experience from the Covid‑19 pandemic, where many small national studies and widespread compassionate‑use schemes did not deliver the level of evidence regulators needed. In doing so, the EMA looks to build in more consistent, risk‑proportionate flexibilities for future crises while keeping good clinical practice (GCP) and data integrity at the centre.

​The guidance sits alongside the EU clinical trials regulation (CTR) and recent standard updates from the International Council for Harmonisation of technical requirements for pharmaceuticals for human use (ICH). It is intended as a standing framework rather than a one‑off crisis document, with the EMA signalling that the guidance will be updated once the proposed European Biotech Act amendments to the CTR are agreed. As a result, the regulatory update matters for any sponsor, CRO or investor planning or running EU trials that could be disrupted by future cross‑border health threats.

New trials during EU emergencies

The guidance applies to two broad categories of studies. First, trials initiated in response to the emergency to evaluate preventive or therapeutic interventions relevant to the event itself. Second, other serious or life‑threatening indications and ongoing development programmes that can safely continue during the crisis. In all cases, the rights, safety and wellbeing of participants must take precedence and the generation of scientifically reliable evidence must remain central to any decision to initiate or continue a trial.

​During a public health emergency, national competent authorities are expected to prioritise assessment of trials that are essential to understanding, mitigating or addressing the emergency and, where necessary, to place less urgent trials temporarily on hold to safeguard regulatory capacity.

Sponsors are encouraged to seek scientific advice from the "Emergency Task Force", an EMA coordination and advisory body established under regulation (EU) 2022/123 specialised in public-health emergencies such as pandemics.

The guidance also steers sponsors towards efficient trial designs. For widespread outbreaks, large‑scale platform or adaptive designs are highlighted as appropriate to generate meaningful data quickly, whereas smaller or localised emergencies may call for more focused approaches. Sponsors should assess logistical feasibility, participant safety and evidence generation before filing, including site capacity under movement restrictions, continuity of investigational medicinal product (IMP) supply chains, maintenance of safety oversight and opportunities to integrate with existing coordinated trial infrastructures.

Changes to ongoing EU trials

The EMA explicitly encourages sponsors to consider adapting already authorised trials to investigate prevention or treatment of conditions related to the public health emergency, where this would be more efficient than starting from scratch. Examples include modifying endpoints, adding relevant cohorts, inserting new treatment arms, suspending non‑relevant arms, changing randomisation to reflect emergency priorities and expanding recruitment to shorten time to analysis. These substantial modifications are to be assessed on an expedited basis through the Clinical Trials Information System.

​The guidance describes a menu of adaptations that may be needed simply to keep trials running under constrained conditions. Acceptable changes include adjustments to the informed consent process (for example, moving to remote consent), altering visit schedules, temporarily halting some or all sites, relocating participants to lower‑risk sites or extending trial duration. Such measures should be limited to what is essential for continuation of the trial during the emergency. They are intended to minimise bias and preserve safety, data integrity, reliability and personal data protection.

​The EMA does, however, draw a clear red line around certain adaptations, which remain unacceptable even in crisis conditions.

For example, disproportionate or non‑essential protocol changes unrelated to the emergency, prospective protocol waivers, waiving scientifically validated eligibility assessments, waiving the obligation to obtain and document informed consent or omitting ethics committee evaluation would not be permissible.

Sponsors remain responsible for determining whether a modification is substantial and for documenting a risk‑based justification, drawing on the EMA's CTR guidance. Communication with authorities and Ethics Committees before implementation is encouraged where the classification is unclear.

Digital tools and electronic processes

The guidance gives formal cover to a range of digital and remote tools that became widespread during the Covid-19 pandemic, particularly around consent, safety monitoring, IMP management and monitoring.

On informed consent, the EMA confirms that remote electronic consent is acceptable and that ICH guidance E6(R3) explicitly supports such approaches as a mitigation measure in emergencies. The consent discussion should occur via secure, real‑time audio‑visual communication, allowing questions and ensuring confidentiality, with consent materials provided in digital formats and signatures captured through secure applications on phones, tablets or computers.

​Sponsors must be able to verify the identity of both participants and those conducting the consent interview and the full process – including any adaptations under emergency conditions – should be described in the protocol or related documents for ethical and regulatory review. In addition, participants must receive appropriate information about the processing of their personal data, including the categories of data collected, the purposes and the parties with access and their rights, with technical and organisational measures in place to safeguard confidentiality and security.

​For safety monitoring, the EMA acknowledges that scheduled on‑site visits may be reduced or cancelled during an emergency and expects investigators to continue collecting adverse events through alternative means (for example, telephone, telemedicine visits and electronic reporting).

Digital health technologies are explicitly endorsed for fit‑for‑purpose safety data collection, in line with ICH guidance E6(R3). Safety information collected remotely must still be appropriately recorded and transferred into case report forms or medical records.

​Digitalisation also extends to trial management and oversight. The EMA describes remote monitoring, including remote source data verification (SDV), as a suitable alternative to on‑site monitoring when technical capabilities exist at sites. It further sets out conditions for sharing pseudonymised source documents in exceptional cases where sites cannot support direct remote access. Centralised monitoring using electronic case report forms, central laboratory data, imaging and electronic patient‑reported outcomes is presented as a way of supplementing or temporarily replacing on‑site monitoring through central, near real‑time review of cumulative data.

Decentralised trial conduct

Beyond digital overlays to traditional site‑based trials, the guidance endorses more structural decentralised elements, particularly trial‑related procedures carried out at a participant’s home or in local healthcare settings. The EMA notes that decentralised conduct may be used to mitigate risks associated with continuing on‑site activities or where site visits are no longer feasible. This dovetails into the EMA's earlier recommendation paper on decentralised elements in clinical trials which includes detailed operational guidance.

​Under the draft guidance, sponsors should ensure that participants receive clear instructions, potentially via electronic step‑by‑step materials such as online tutorials or visual aids and that any additional equipment needed for safe administration and destruction of the IMP is provided. These requirements should be described in the protocol or pharmacy manual.

The EMA clarifies that the intention to either ship IMP to participants’ homes or to redistribute IMPs between sites or supply participants transferred to other sites, should be notified as a substantial modification.

​Participant transfer is itself treated as a decentralising measure. Where some regions or countries are more heavily affected by the emergency than others, sponsors are encouraged to arrange transfer of participants to sites within the EU/European Economic Area that remain operational. However, this is only possible when epidemiological risks are manageable and receiving sites can assume full medical responsibility. Data collected to date must be available at the receiving site, data‑collection tools must operate correctly and sample management must avoid unblinding. Importantly, renewed informed consent is required for continuation at the new site and any contractual changes with investigators or institutions should be addressed.

Inspections and oversight

The guidance recognises that both sponsors and inspectors will face unusual constraints during a public health emergency and signals a proportionate approach.

On auditing, it states that on‑site audits should be rationalised to minimise burdens on clinical trial staff and to protect the safety of all involved where the emergency is associated with social‑distancing restrictions. Remote audits are permitted for critical trials or higher‑risk sites, provided they are considered essential and agreed with investigators; for example, where serious deviations from protocol or legislation must be investigated.

​On monitoring, the EMA reiterates that any changes to the monitoring strategy should be driven by protection of participants and data integrity, using a risk‑based approach to focus on critical sites, data and processes. Adjusted monitoring plans should be reflected in trial documentation and their outcomes summarised in the clinical study report.

​Alignment with the EMA's existing position on remote GCP inspections during public health threats, emergencies and crisis situations will be important for sponsors. In practice, they would need to read the new guidance together with that existing remote‑inspection framework to understand how their documentation and systems may be reviewed during and after an emergency.

Osborne Clarke comment

The EMA’s draft guidance turns much of the ad hoc problem‑solving seen during Covid‑19 into a more structured playbook for future public health emergencies. Instead of isolated national approaches, it points sponsors towards a common set of tools and boundaries for adapting EU trials when conditions suddenly change. For organisations already running multinational studies, it can also help align internal expectations about how far regulators are prepared to stretch in a crisis – and where they are not.

In practical terms, many sponsors may treat the guidance as part of their emergency‑preparedness planning once it is final.

They can, for example, update risk management plans, protocol templates and site guidance so that options like remote consent, telemedicine safety visits, direct‑to‑patient IMP shipment, remote SDV and centralised monitoring are described in advance, together with clear criteria for pausing sites, transferring participants or adapting endpoints. Having those routes mapped out up front then makes it easier to explain, document and implement changes quickly if an EU‑level emergency is declared.

At the same time, the EMA is clear that flexibility has limits.

Over‑reliance on emergency arguments for changes that mainly address operational convenience or cost‑saving – especially where eligibility criteria, core safety assessments or informed consent documentation are affected – may well attract closer regulatory attention. The emphasis on ethics committee involvement and on maintaining robust documentation, including in the trial master file and substantial modification justifications, also suggests that post‑hoc review of emergency‑driven decisions is likely.

Sponsors that already rely heavily on decentralised and digital trial models may see value in contributing to the consultation phase by submitting comments before 30 April, so that practical experience from recent years can be reflected in the final text.