# Rapid-sequence clinical research before and during a pandemic: Lessons learned and the way forward

Florence Ader, Éloïse Aubret, Nathalie Bergaud, Maude

Bouscambert-Duchamp, Sophie Circosta, Sandrine Couffin-Cadiergues, François Danion, Christelle Delmas, Alpha Diallo, Emmanuel Faure, et al.

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## ► To cite this version:

Florence Ader, Éloïse Aubret, Nathalie Bergaud, Maude Bouscambert-Duchamp, Sophie Circosta, et al. Rapid-sequence clinical research before and during a pandemic: Lessons learned and the way forward. Infectious Diseases Now, 2025, 55 (7), pp.105135. 10.1016/j.idnow.2025.105135. hal-05390594

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Submitted on 3 Dec 2025

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Original article

# Rapid-sequence clinical research before and during a pandemic: Lessons learned and the way forward

The OPEN-ReMIE steering committee

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## ARTICLE INFO

**Keywords:**

OPEN-ReMIE

Emerging infectious diseases

Preparedness

Platform trial

Proact EU-Response

## ABSTRACT

In the aftermath of the COVID-19 pandemic, the structuring of a nationwide research network for preparation and response to emerging infectious diseases (EID) with epidemic or pandemic potential has become increasingly essential.

A nationwide EID operational research network (OPEN-ReMIE), is funded for five years through the France 2030 program and run by the French national research agency (ANR). Its primary missions are to accelerate hospital-based clinical research under epidemic or pandemic conditions with academic or industrial sponsors, and to pursue this effort in international research networks. OPEN-ReMIE governance is geared to steering this network and to guaranteeing its operability in inter- as well as crisis modes. It will be the point of entry for key international trial platforms, academic and private sponsors, regulatory agencies, associations of citizens and patients, and think tanks committed to promoting scientific integrity.

OPEN-ReMIE encompasses six work packages: (i) regulatory affairs, sponsoring, fast-track procedures and contracts; (ii) clinical site network management; (iii) methodology and management centers to provide methodological expertise (generic master protocols, sets of core and extended variable catalogs, electronic case reports form templates, data management and interoperability, monitoring...); (iv) laboratory and biological resource center management; (v) drug supply and pharmacovigilance supervisory board; (vi) training programs and communication plans for various stakeholders: research teams, healthcare professionals, students, associations of citizens and patients and, increasingly, civil society actors.

All in all, OPEN-ReMIE is a nationwide “preparedness task force” embedded in a large-scale European consortium for EID clinical research and working with other international EID clinical research platforms.

## 1. Introduction

Following the initial reports of cases of acute pneumonia of unknown origin in China at the end of 2019 and in early January 2020, on 30 January 2020 the World Health Organization (WHO) declared the new disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a public health emergency of international concern. The pandemic prompted the adoption of new approaches to “real-time, real-world” clinical research aimed at urgently developing treatments and vaccines. Adaptive designs such as platform trials, are well-suited to the pandemic context. These designs offer: (i) a high level of evidence, similar to that of randomized controlled trials; (ii) flexibility, as interventions can be added or withdrawn according to their risk–benefit ratio; (iii) efficiency, i.e. optimization of human and financial resources in the scope of a single trial; (iv) an accelerated, interim, results-driven decision algorithm, so that further treatment candidate(s) can be added;

(v) an ethical advantage, especially insofar as the control treatment can be adapted as knowledge improves [1,2]. However, these designs are likely to have biases from temporal trends (e.g., changes in the standard of care, the emergence of variants, the introduction of vaccines, the seasonal effect...), which can lead to non-comparable groups and inaccurate estimation of treatment effects [3,4]. Selection bias due to unblinding may also occur. To address these biases, statistical modelling may be required.

Initially a WHO Solidarity add-on, multi-arm adaptative trial [6,7], the DisCoVeRy trial [5], was first launched in France in March 2020 thanks to seed funding from INSERM REsearch and ACTion targeting emerging infectious diseases (REACTing), and subsequently to funding from the French national clinical research program. More than 30 inclusion sites were opened in France, followed in July 2020 by expansion to other EU member states and associated countries (Belgium, Portugal, Ireland, Austria, Greece, Luxembourg, Czech Republic, Slovakia,

<footnote>* Corresponding author at: Département des Maladies infectieuses et tropicales, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, 104 Grande-Rue de la Croix-Rousse, 69317 Lyon cedex 04, France.</footnote>
Poland, and Norway) through the EU Horizon 2020-funded program. As of now, the DisCoVeRy trial has included 1545 patients for evaluation of COVID-19 therapy. It was the steppingstone for the EU-RESPONSE clinical trial network (https://eu-response.eu/), and paved the way for the launching of EU-SolidAct, a second-generation pan-European platform trial initially focused on Covid-19 and currently contributing to the EU's pandemic preparedness strategy regarding emerging infectious diseases (EIDs) [8].

We are now entering a phase requiring the long-term organization of a nationwide research network to prepare for and respond to potentially pandemic EID epidemics [8]. This is critical because the current context of globalization means that it is a matter of when, not if, a new pandemic will occur. As part of the France Relance 2030 programme, we have submitted a project designed to create a nationwide network dedicated to clinical research in the context of EID epidemics or pandemics: OPEN-ReMIE (Réseau Opérationnel National de Recherche pour les Maladies Infectieuses Émergentes / nationwide operational network for emerging infectious diseases). The network's primary missions are to organize and accelerate nationwide clinical research responses to EID and to pursue these efforts in international networks such as PROACT EU-RESPONSE, a spin-off from EU-RESPONSE that aims to build on the progress accomplished during the COVID-19 health crisis. The second mission of OPEN-ReMIE is to consolidate and sustain this network over time, before passing it on to the next generation of healthcare professionals.

## 2. Some feedback on difficulties and drawbacks during the COVID-19 crisis

### 2.1. The difficulty of starting from scratch

Getting a large-scale randomized controlled trial started and running requires: (i) an agreed-upon master protocol, (ii) approvals by institutional review boards and regulators, ideally by means of a fast-track procedure, (iii) adequate funding(s), (iv) suitable study sites, (v) contracting, (vi) providing training for these study sites, (vii) sufficiently qualified human resources in research, (viii) identification of the drug delivery system, (ix) data management and statistical analysis plans, and (x) a referent biology laboratory network (e.g., microbiology, immunology, and pharmacology laboratories), as well as bi collection centers. This process usually largely exceeds a year. Table 1 lists the positive points, hurdles, and drawbacks that the DisCoVeRy core management team has faced during the crisis, and summarizes how OPEN-ReMIE will circumvent the hurdles and address the drawbacks. To complicate matters, with regard to a new disease motivating many ongoing studies, the standard of care (SoC) can rapidly change, necessitating the adaptation of interventions through protocol amendments. Hence, having pre-established structures and procedures to facilitate a rapid, large-scale clinical research response to a pandemic is of critical importance.

### 2.2. "National research Priority" mechanism activation

According to data from the COVID-19 Trials Tracker project [9], the number of clinical studies in COVID-19 up to November 2020 was 6416, of which 3663 were also registered with [ClinicalTrials.gov](https://ClinicalTrials.gov). Entries from the USA (n = 892), China (n = 855), India (n = 711), France (n = 566), Iran (n = 417) and Germany (n = 328) were preponderant. A review has shown that the vast majority (95%) of registered trials worldwide were inadequately designed to yield actionable actions [10]. In this context, the French *ad-hoc* national steering committee for therapeutic trials and other research on COVID-19 (CAPNET) was activated at the end of 2020 to prioritize high-potential studies. The "national research priority" label awarded by this committee led to an accelerated assessment procedure for regulatory authorizations, valorization of the inclusions via SIGREC (Système d'Information et de Gestion de la Recherche et des Essais Cliniques) and access to potentially additional institutional

funding. That said, CAPNET was activated at a time when the "first wave" was coming to an end, and many research projects, especially on a regional scale, had already been initiated, resulting in a fragmented nationwide trial landscape. These studies were often observational in design, exposing a high proportion of patients to compassionate drug use without adequate data collection. Most RCTs focused on a single treatment, were underpowered and/or under-funded, and finally never provided the evidence needed for treatments to be implemented. This raises ethical questions about patient participation in ineffective trials, as well as concerns about the wastefulness of research that fails to produce a proportional benefit in terms of social and scientific value in exchange for human and material costs [11]. In addition, competition between large-scale RCTs and numerous nationally or regionally funded clinical trials likely hampers enrollment [12].

### 2.3. The sociocultural context has made it challenging to conduct large-scale randomized clinical trials

Patient adherence, family support and "buy-in" to public health advice and policies are critical to controlling a pandemic [13]. Excessive mediatization, disinformation campaigns, conspiracy theories, an overabundance of information (infodemic) [14], social media-driven polarization, cyberbullying [15,16] and political bias have added another level of complexity to reaching target recruitments in large-scale RCTs. The controversies surrounding certain drugs have obstructed randomization in many countries. Hence, social influences may have encouraged non-adherent behaviors to pragmatic research strategies.

### 2.4. How were other major pan-European platform trials operating?

In the RECOVERY trial (https://www.recoverytrial.net/), a platform trial conducted in over 175 hospitals in the UK National Health Service (NHS) and in 15 countries abroad, a key element has been the preexistence of an embedded clinical research capability in the National Institute for Health Research (NIHR) providing staff, infrastructure, and funding for national health research priorities, in accordance with the concept of Urgent Public Health (UPH) research elaborated following the 2009 H1N1 influenza pandemic. RECOVERY was one of the first trials to be given UPH status in a single UK-wide process, in which only studies with the UPH designation would be eligible for NIHR support. On March 16, 2020, the Chief Medical Officer for England asked all NHS hospitals to "provide your fullest support for implementation of the RECOVERY trial" [17]. A standard contract was issued to sites with a "take it or leave it" approach. Extensive linkage to routine electronic clinical and vital statistical data sources was used to minimize data collection by front-line health-care staff. The first patient was enrolled on March 19, 2020, nine days after the protocol was written and two days after approval. The first 1000 patients were enrolled in 16 days, and enrollment in the trial was soon exceeding 500 patients/day. The "game changer" benefit of dexamethasone was reported on June 16, 2020, based on the results achieved from 6425 enrolled patients [18,19]. All in all, the RECOVERY trial included 48,638 patients (more than 46,000 in the UK), and led to comparison between COVID-19 therapies.

The REMAP-CAP platform trial (https://www.remapcap.org/) has been funded through the EU since 2018; in 2014, the PREPARE program got underway for community-acquired pneumonia (CAP); it was primarily deployed in intensive care units involving more than 200 inclusion sites (143 in the UK) in 16 European countries. On March 3, 2020, a pandemic stratum was added to the protocol to allow enrollment of COVID-19 patients, and REMAP-CAP was given UPH status in the UK. Additional funding was obtained via the EU H2020 program RECOVER. On September 2, 2020, REMAP-CAP reported its first conclusion on the benefits of hydrocortisone [20]. All in all, the REMAP-CAP trial included a total of 18,592 patients and likewise led to for comparisons between COVID-19 therapies.
<table><caption>**Table 1**
Positive points and barriers to implementing and sustaining the DisCoVeRy platform trial; possible corrective measures.</caption><thead><tr><th></th><th>Positive points</th><th>Hurdles and drawbacks</th><th>Corrective measures</th></tr></thead><tbody><tr><td>Human resources in the core team</td><td><ul><li>Rapid and significant mobilization of human resources from various networks: Inserm, REACTing, ANRS-MIE, specific competencies in university hospitals.</li><li>Pooling of "know-how".</li><li>Adaptability of human resources: ability to work in degraded mode and around the clock.</li></ul></td><td><ul><li>Impossibility of recruiting new human resources at the height of the pandemics due to lockdowns and suspended administrative procedures.</li><li>Working contracts of research staffs did not include the possibility of working overtime or weekend, thereby precluding legal financial compensation.</li><li>Exhaustion of front-line staff</li></ul></td><td><ul><li>Audit each first-circle inclusion site to assess the human resources qualified for EID research and identify the key leaders and stakeholders in each clinical research department.</li><li>Hire qualified personnel under the umbrella of OPEN-ReMIE and ANRS-MIE in understaffed first-circle inclusion sites.</li><li>Train through participation in nationwide and international EID trials, implement appropriate procedures, simplify process whenever possible, organize feedback sessions.</li><li>Centralize fundings so as to endure and/or reinforce broad-based support</li></ul></td></tr><tr><td>Fundings</td><td><ul><li>Rapid seed funding through REACTing</li></ul></td><td>Lack of financial flexibility: multiple sources of funding dedicated to specific tasks with no way to merge certain fundings, to fluidify/facilitate financial operations and to transfer them from one task to another.</td><td></td></tr><tr><td>Institutional review board and regulators</td><td>Support from the nationwide ethics authorities to enable rapid delivery of authorizations: "fast-track Covid-19" procedure</td><td>Non-availability of the CTIS portal has caused substantial delays or has prevented trial openings in some participating EU countries.</td><td>The EU CTIS portal is currently altogether functional.</td></tr><tr><td>Collaborations</td><td>Partnership with the nationwide clinical research network for infectious diseases RENARCI, which has supervised several tasks:<ul><li>selection of investigation centers (feasibility questionnaire);</li><li>collection of documents for regulatory submission (curriculum vitae, good clinical practice certificates, contact lists);</li><li>contact with study sites.</li></ul></td><td></td><td>RENARCI will operate the engagement of second-circle inclusion sites throughout France and will remain a member of the OPEN-ReMIE scientific steering committee</td></tr><tr><td>Safety procedures and safety team</td><td><ul><li>Centralized pharmacovigilance circuit with development of dedicated standard operating procedures (safety management plan, safety communication plan, working safety instructions...).</li><li>Identification of a local safety officer to assist in pharmacovigilance management.</li><li>Strong and immediate mobilization of the sponsor's complete safety department.</li></ul></td><td><ul><li>Good clinical practice requirements for labelling investigational medicines were not waived for routinely used, repurposed and retested drugs, resulting in lengthy regulatory procedures.</li><li>Collection of all serious adverse events in intensive care units has resulted in a massive number of declared events.</li><li>Synchronization issues concerning e-CRF, safety events and monitoring procedures.</li><li>Overly comprehensive collection of serious adverse events by front-line research staff, with "snags" generating numerous queries.</li><li>One center was challenged by a massive workload.</li></ul></td><td>Contact with French medicine agency (ANSM) so as to facilitate procedure implementation in a crisis context for investigational, particularly repurposed drugs.</td></tr><tr><td>Methodology and data management center</td><td><ul><li>Kickoff by WHO blueprint master protocol</li></ul></td><td></td><td><ul><li>No less than five methodology and management centers are involved in OPEN-ReMIE.</li><li>Production of master blueprint protocols according to different scenarios.</li></ul></td></tr><tr><td>Monitoring</td><td><ul><li>Substantial operational resources</li><li>Collaboration between public and private actors</li><li>Constant adaptation to the context of the level of monitoring</li><li>Centralized management of research documents</li></ul></td><td><ul><li>Inadequately harmonized monitoring practices.</li><li>No possibility of online consent.</li><li>Lack of synchronization between e-CRF and monitoring through centralized management.</li><li>No possibility of remote monitoring.</li><li>Lack of synchronization between data management plan and monitoring to optimize data quality.</li></ul></td><td><ul><li>Mapping of the existing initiatives in the French clinical research community regarding simplification of enrollment and monitoring procedures.</li><li>Constitution of working groups to set up e-consent while instituting and/or improving e-monitoring.</li><li>Constitution of working groups on harmonization of data management and data interoperability.</li></ul></td></tr><tr><td>Site commitment</td><td>Massive involvement of front-line health care workers and research staffs to start the trial and enroll patients, at a time (first surge) when all other activities were interrupted.</td><td><ul><li>Need for tough negotiations with sites regarding heightened overheads.</li><li>Preexisting research contracts did not authorize night and weekend shifts, a limitation resulting in lack of overtime compensation for research staffs.</li><li>Simultaneously running competitive trials mitigate inclusion capacity and generate a dispersion effect.</li><li>Exhaustion of on-site efforts, potentially resulting in mitigated commitments over time.</li></ul></td><td><ul><li>Create standard contracts for inclusion sites allowing for minor adjustments. No financial negotiations permitted.</li><li>Hiring of qualified research personnel in inclusion sites under the umbrella of ANRS-MIE</li><li>In a major crisis, activation of a nationwide steering committee for therapeutic trials, the objective being to prioritize high-potential studies granted a "national research priority" label.</li></ul></td></tr></tbody></table>

Abbreviations: INSERM, Institut national de la santé et de la recherche médicale; REACTing, Inserm REsearch and ACTion targeting emerging infectious diseases; ANRS-MIE, agence nationale de la recherche pour le VIH, les hépatites et les maladies infectieuses émergentes; e-CRF, electronic case report form; CTIS, clinical trial information system; RENARCI, réseau national de recherche clinique en infectiologie; WHO, World Health Organization.
### 3. The future: OPEN-REMIE and PROACT EU-RESPONSE

OPEN-REMIE was launched on March 1, 2025, almost exactly five years after the launch of DisCoVeRy (March 22, 2020), and is funded for five years. It includes the six operational work packages (WPs) listed in Fig. 1. These WPs will work closely with the other partner national networks: EMERGEN 2.0 (platform for molecular surveillance and research on infectious diseases caused by EMERging pathogens through GENomic sequencing); I-REIVAC-EMERGENCE (Innovative clinical REsearch network In VACcinology-Emergence preparedness); and SUM'EAU (national platform for research and development in the epidemiology of wastewater) through an inter-platform committee. A tripartite governance structure will steer the network, including a core development team, a scientific steering committee and an independent scientific and ethic advisory board (SEAB). The development team will coordinate the daily tasks of the WPs and will be the initial point of entry for research application proposals from investigators and sponsors. The scientific steering committee will be the pivotal decision-making body and will interface with: other international trial platforms; the academic and private sectors (as major providers of R&D and innovations); institutional agencies (e.g., ANSM, CNIL, EMA); and associations of citizens and patients or think tanks dedicated to promoting scientific integrity in the framework of high-quality open science designed for wide dissemination. OPEN-REMIE will function with academic as well as private sponsors, at the nationwide level, or in international platform trial consortiums. From the very outset, the network will operate within the new EU framework through the Clinical Trial Information System (CTIS) portal (WP1). Each site will include a pair of infectious disease and critical care units (WP2) tasked with applying shared, simplified and adapted procedures and protocols. The sites will be divided into first and second-circle hospitals. The first circle will include national reference centers for epidemic and biological risks [ESR, Etablissements de Santé de Référence] and regional ESRs with equipped medical facilities enabling them to promptly address sporadic imported EID cases or bursts of epidemics across France. This circle will maintain trained staff

and facilities able to optimally implement clinical trials adapted to various EIDs. A second circle of clinical sites will be placed on hold and activated only when epidemic expansion or pandemics occur. The DisCoVeRy team's experience with clinical trials during the COVID-19 pandemic clearly demonstrated that administering contracts with sites and stakeholders was one of the key operational challenges. With this in mind, OPEN-REMIE will develop a standardized contract template to be approved by all network members. Use of this common and unchangeable template will be encouraged as best practice aimed at streamlining collaboration and ensuring consistency between sites. It may also serve as a criterion for prioritizing sites for early inclusion in trials (WP1 and 2). Five methodology and management centers (MMCs) will provide methodological expertise (WP3). They will generate generic platform trial protocols (master protocols) adapted to specific EIDs. They will also consider other methods, some examples being trials embedded in cohorts, hybrid trials combining conventional trial data and either external data for enrichment or remote (at-home) data, and pragmatic clinical trials using routinely collected health data to generate real-world evidence (Table 2). A set of core variables will be generated as block components to create a common electronic case report form (e-CRF) template so as to speed up development phases and facilitate data management and interoperability. Several sets of accessory variables adapted to specific pathologies can be added accordingly (e.g. drug susceptibility testing, imagery...). All the data generated by these studies will be available in a standardized data format, ready to be shared upon trial initiation in accordance with predefined data transfer conditions. One challenge will be to progressively organize the collection and storage of generated multi-omics datasets obtained through artificial intelligence. Lastly, the MMCs will focus on quality assurance for data in a crisis context, thanks to an adaptive, dematerialized monitoring plan drawing upon the experience acquired by DisCoVeRy [21]. OPEN-REMIE will rely on a network of analysis laboratories specialized in microbiology (the EMERGEN 2.0 network), pharmacology, and immunology (WP4). A centralized biological resource center will enable storage of biocollections. The immunology network will offer

<figure><img src="image_4.png" /><figcaption>**Fig. 1. OPEN-REMIE organization chart.** Abbreviations: ANSM, agence nationale de sécurité du médicament et des produits de santé; ANRS-MIE, agence nationale de la recherche pour le VIH, les hépatites et les maladies infectieuses émergentes; CNIL, commission nationale de l'informatique et des libertés; CTIS, clinical trial information system; EMA, European medicines Agency; F-CRIN, French clinical research infrastructure network; RENARCI, réseau national de recherche clinique en infectiologie.</figcaption></figure>
<table><caption>**Table 2**
Key features of innovative trial designs.</caption><thead><tr><td>Trial Design</td><td>Brief description</td><td>Data Sources</td><td>Strengths</td><td>Limitations</td><td>References</td></tr></thead><tbody><tr><td>Hybrid Trials</td><td>Combine conventional clinical trial procedures with external or remote data collection methods.</td><td>Trial data (electronic case report forms) + routinely collected data (e.g., electronic health records, registries, administrative databases) ± patient-generated data (wearables, apps).</td><td>Greater generalizability; richer data; flexibility in data collection; cost reduction.</td><td>Complex data integration; data harmonization challenges; data privacy and regulatory issues.</td><td>[23]</td></tr><tr><td>Pragmatic Randomized Trials</td><td>Evaluate interventions under usual care conditions -broad eligibility criteria and routine follow-up- to inform healthcare decision making.</td><td>Partially or fully based on routinely collected data (e.g., electronic health records, registries, administrative databases)</td><td>High external validity; directly applicable to clinical and policy decisions; lower operational burden.</td><td>Potentially reduced internal validity due to limited control over interventions, measurement bias, and reliance on data not originally collected for research purposes (missing or inconsistent data)</td><td>[24,25]</td></tr><tr><td>Trials Embedded in Cohorts (also known as Trials within Cohorts: TwiCs</td><td>Use an existing cohort for recruitment and follow-up. When an intervention is tested, eligible patients from the cohort are identified and randomized. Only those randomized to the intervention are informed and offered the treatment.</td><td>Longitudinal cohort data (e.g., medical records, questionnaires, registries)</td><td>Efficient recruitment; reduces attrition and disappointment bias; cost-effective; allows multiple trials within the same cohort.</td><td>Cohort setup is resource-intensive; ethical concerns (non-disclosure to controls); risk of contamination; generalizability depends largely on cohort population.</td><td>[26]</td></tr></tbody></table>

a catalogue of assays for intervention-related evaluations (e.g., antibody response, sero-neutralization assays), along with mechanistic studies based on the storage in selected sites of plasma, sera, and peripheral blood mononuclear cell samples. The ANRS-MIE pharmacovigilance department will support OPEN-ReMIE safety activities in accordance with current regulations by providing expertise and management through trials based on our recent experience (WP5) [22]. A working group with medicine agencies will be set up to fluidify the processes related to supply and use of investigational drugs in an EID setting. In the context of WP6, OPEN-ReMIE will develop a website and a communication plan to disseminate the project's results to various stakeholders, thereby maximizing network impact. Another part of the communication plan is aimed at the general public. We believe that combatting misinformation cannot rely solely on reactive strategies, and that the inter-crisis period must be used proactively to build knowledge, strengthen trust, and cultivate a research culture that will be essential when the next health emergency arises. To this end, we plan to implement a comprehensive training program in clinical research, focusing on the specific challenges of conducting research during health emergencies or EID outbreaks. The program will be open to a wide-ranging audience, including research teams, healthcare professionals, medical and nursing students, and the public. To avoid duplicating existing efforts, we will first assess and centralize current training resources, thereby ensuring that this content is effectively disseminated to all relevant audiences. With this in mind, we will leverage all available communication channels, including social media, by sharing or developing content specific to the best practices of each platform. Our overarching objective is to lay advance groundwork by informing and training both professionals and future research participants. This will reduce resistance from patients and healthcare workers when clinical research needs to be rapidly deployed during an emerging health crisis.

As the French clinical research network for EID, OPEN-ReMIE will be the entry point for PROACT EU-RESPONSE, as well as other international research consortia such as STRIVE (Strategies and Treatments for Respiratory Infections and Viral Emergencies funded by the US National Institute of Health) and RECOVERY. With a planned focus on clinical therapeutic platform trials in inpatient hospital settings across Europe, PROACT EU-RESPONSE was launched on January 1, 2025, and is funded for five years under the umbrella of Horizon Europe 2024. Its overarching goal is to prepare Europe for future diseases of epidemic or pandemic potential by strengthening and building upon existing civil society and expert networks.

PROACT EU-RESPONSE is embedded in a larger platform trial network called BE-READY+, which will act as a general coordinator at the EU level. It will provide capacity, in the event of an outbreak, to rapidly pivot toward large-scale, multi-country platform trials investigating diagnostic tool performance and drug efficacy. Sustained patient and public involvement underpin the shared approaches of OPEN-ReMIE and PROACT EU-RESPONSE. Indeed, civil society and the community at large are presently engaged in planning trials, in promoting communication and information for the public about health threats, and in showing how to avoid disinformation, particularly during an epidemic or pandemic. The inclusion of social scientists strengthens this ambition. Furthermore, the two networks will engage in capacity-building activities and derive benefit from their respective accomplishments in the regulatory field.

## 4. Discussion

OPEN-ReMIE provides a unique opportunity to be seized by the French medical community involved in EID management. Based on the operating methods of partner networks and on our own experience, our goal is to pursue strategic and pragmatic development that will enable us to coordinate tailored clinical research in crisis situations without compromising quality and safety. In addition to the financial resources required to upgrade the network, we urgently need to convince our institutions and governmental regulators to support us with regard to the regulatory issues that are significantly slowing down the deployment of rapid- sequence clinical research. These are concerns for all sectors potentially affected by an EID-related health crisis: ministries, regulatory agencies, research funding bodies, research departments of French hospitals... We are convinced that it is possible to develop mechanisms to simplify and accelerate high-quality clinical research in crisis situations. Preparedness and training in the inter-epidemic period are essential. At the international level, it will be important to participate in large-scale observational cohorts and randomized clinical trials. At the nationwide level, our aim is to strengthen capacity-building by conducting clinical trials to test therapeutic responses to seasonal epidemics and outbreaks of emerging pathogens, thereby facilitating the training of qualified, well-sized staff, who will rely on "tried-and-true" procedures. As exhaustion of caregivers and research staff is a major factor in the failure of large-scale, long-term research initiatives, appropriate training is the best guarantee that, in the event of a major crisis, frontline healthcare staff will maintain a decent quality of life. However,
this cannot be achieved without broad-based consultation with stake-
holders and governing institutions to ensure that the relevant laws
proactively evolve and that practices are suitably adapted. On this score,
the COVID-19 crisis awakened a generation of infectious disease phy-
sicians to the urgent need to train future generations in pandemic crisis
management and to leave them with dedicated tools for education and
research. Integration of a clinical intervention research training module
for EIDs should be considered as part and parcel of the curriculum for
health care professionals in infectious disease departments.

Above all, there needs to be a paradigm shift in public understanding
of EID clinical research. It is important to convey the message that
clinical research in crisis situations does not diminish the quality of
standard individual care, and that, quite on the contrary, it ultimately
improves the quality of collective care by promptly evaluating and
rapidly validating the potential benefits of new therapies and vaccines.

Author contributions

FA is the project initiator. FA and KL contributed to the conception and contents of the mini-review; together, they drafted the manuscript, and both of them approved the final version. All of the authors read the manuscript and contributed to its finalization with substantial suggestions and amendments. All of the authors approved the final manuscript

Fundings

OPEN-ReMIE is funded by the French National Research Agency (ANR) (France 2030, grant ANR-24-MIEM-0003). The DisCoVery trial was funded by the national Programme Hospitalier de Recherche Clinique (PHRC-N-20-0351, Ministry of Health), from the DIM One Health Île-de-France (R20117HD), and by seed funding from REACTing, a French multi-disciplinary collaborative network working on emerging infectious diseases. EU-RESPONSE has received funding from the European Commission (Horizon H2020 program, EU-Response grant 101015736). PROACT EU-RESPONSE is funded by the European Commission (Horizon Europe program, grant 101156304). We thank these different entities for supporting our action.

Declaration of competing interest

The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
the work reported in this paper.

References

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[3] Proschan M, Evans S. Resist the temptation of response-adaptive randomization. Clin Infect Dis 2020;71(11):3002-4.

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