COMBACTE Magazine: A Decade of Impact

thanks to all our colleagues!

We would be nowhere without the commitment and hard work of the people involved in our projects. Thanks to them, over a decade, COMBACTE has achieved crucial milestones.

Perhaps the most precious gift COMBACTE has offered Europe is Ecraid. This new organisation gives the networks that were built in COMBACTE a robust and sustainable future

Read all about Ecraid on pages 34-37

Irene Norstedt

In the past decade, the COMBACTE projects have provided a critical infrastructure to tackle bacterial infections. I am impressed by how this large clinical and laboratory research network of over 1,200 hospitals and over 900 laboratories has contributed to the knowledge of bacterial infections and their control in Europe. Congratulations to all those involved!

With over 35,000 annual deaths due to antimicrobial resistant infections in the EU/EEA1, and with antimicrobial resistance (AMR) forecasted to become a devastating global pandemic, our efforts to fight this threat need to continue. Since the adoption of the EU One Health Action Plan against AMR2 in 2017, several initiatives have contributed to further strengthening the EU response to AMR, such as the Pharmaceutical Strategy for Europe3 and the new proposal for a Council Recommendation.

It is within this context that we have supported the creation of a European-wide sustainable clinical research network for infectious diseases, which eventually evolved to the establishment of Ecraid early last year. Ecraid will allow us to continue and further build on the achievements of the COMBACTE projects and networks, leveraging the significant investments made, with new valuable clinical research on antimicrobial resistance.

Expectations are high for Ecraid to continue being a critical actor in this field. We hope that its success can be expanded to other infectious diseases as well, particularly in the context of pandemic preparedness and response.

“Our efforts to fight the threat of AMR need to continue”

Issued by the COMBACTE Consortium, April 2023

Chief Editor and Project Management

Adelina Prioteasa

Claire-Marie Martis COMBACTE Communications Office

Concept COMBACTE

Communications Office

Ecraid

Today JCM Context

Design

Today

Copywriting COMBACTE

Communications Office

JCM Context

Photography Eric Mclean

Frans Hofmeester

Getty Images

Marijn de Wijs

Michiel Spijkers

Ovidiu Udrescu

Personal Archives

Producciones Singulares

Shutterstock

Printing Platform P

Contact

Questions or suggestions are welcome at info@combacte.com.

Please let us know if you would like to acquire additional copies of COMBACTE Magazine.

For Marc Bonten

COMBACTE is all about collaboration – working together as a team. So he is a bit cautious about being in the spotlight. But it’s impossible to neglect the man who, as a scientific coordinator since the beginning, breathes COMBACTE and now leads the organisation that can be seen as COMBACTE’s long-term successor: Ecraid. We had a conversation with Marc about his view on the impact and lessons learned over ten years of COMBACTE.

What did you learn from COMBACTE?

“Before COMBACTE I thought being a smart scientist is enough to successfully design and execute trials. But these ten years have taught me the complexity of executing trials. Especially with the state-of-the-art research we do. It’s a real multidisciplinary team effort, in which each role is important, beginning with the study lead and up to the research nurse who is talking to patients’ relatives in the ICU. Trials in the field of infectious diseases are now much more solid than ten years ago.”

Looking back on these ten years… what impact comes to mind first?

“At the top of the list is the collaboration we established. Between scientists in Europe, and between pharma and academia. This also resulted in the infrastructure we built for studies on infectious

Interview with Marc Bonten, Scientific Coordinator of all four COMBACTE projects

“

We take bigger steps together”

diseases throughout Europe. Like the network of hospitals and laboratories. But also, the network of experts in EPI-Net (epidemiological network) who worked together to improve the understanding of the epidemiology of AMR. It’s this collaboration and infrastructure that is the cornerstone of the new organisation Ecraid. We build on the foundation laid by COMBACTE.”

Can we measure the improvement of COMBACTE on people’s health?

“It’s very difficult to measure such a direct impact. Developing treatments in the field of antimicrobial resistance and infectious diseases takes a long time. That was one of the reasons why COMBACTE was developed in the first place. To encourage pharma to invest in long-term solutions. New treatments are developed step by step. Scientists use publications to take a next step. In this sense we had real impact, with over 150 published articles and other publications. And there is a small number of candidate treatments that are now in phase III trials of which we have good expectations that they will make it to the end.”

How did you experience collaborating with pharma?

“Trust has been built during these years, and there is a wish to continue this collaboration. We aim for the same goals. There were times I had to acknowledge that a pharmaceutical company can have its own agenda, which has not always made it an easy process. In the end the collaboration in general has worked out better than I had expected. Together we are taking bigger steps in the fight against infectious diseases.”

Collaboration seems a keyword in your view on ten years of impact. Is academia ready for it?

“Researchers can sometimes also be seen as competitors. This is due to a system that stimulates doing a small trial on your own more than doing a large trial with a bigger group. Even though a large trial is much more effective. In many countries researchers are judged on their individual publications. This is a serious hurdle for collaboration. But I notice an increasing trend in which people are more open to collaboration. There is a kind of togetherness, an awareness that we can be more successful if we collaborate. REMAPCAP (Randomised Embedded Multifactorial Adaptive Platform trial for Community-Acquired Pneumonia), for instance, has issued publications without lead authors, but with 200 co-authors – to me this is the new way of working. COVID-19 has also made clear that large trials have much more impact. We’re on a positive path.”

The EU invested in COMBACTE. This means you also had to collaborate on that level.

“Yes, COMBACTE was funded by both industry and public European funds, more specifically the Innovative Medicines Initiative (IMI). We worked together very well. Nathalie Seigneuret has been our IMI Scientific Project Manager all these ten years. I really appreciate her involvement. We had regular contact, and she joined our General Assemblies. Investing in clinical trials was also something new for IMI, and it comes with risks.”

One of the principles of COMBACTE was also diversity. What does that mean? And are you satisfied?

“We wanted to make it a real European project, not only focusing on western or eastern Europe. This is especially important because some resistant pathogens are more prevalent in eastern and southern Europe. Which is why you need good coverage to include as many patients as possible in different studies. And that is what we did.

But diversity also relates to people. The core group that worked on COMBACTE has done so for ten years. More young researchers are now coming in. The balance in terms of age and gender is improving. As the older generation, we must invest in guiding and making room for the younger generations. And we must offer opportunities. This is also something we will facilitate in Ecraid. Young researchers nowadays are much better educated than my generation was. They learned a lot more about clinical epidemiology and data analysis. We need them.”

“WE MUST INVEST IN GUIDING AND MAKING ROOM FOR THE YOUNGER GENERATIONS”

1,238 hospitals

42

European countries

1,455 laboratory contacts

4,055 hospital contacts

925 Laboratories

32,000 Microbanks

97,500 sample kits

9,400 strains collected

109,000 specimens collected

Eastern Europe’s Potential in High-Quality Clinical Research

For a long time, eastern Europe has been a blind spot for clinical research in infectious diseases. The results of COMBACTE-NET’s HONEST-PREPS suggest that this might be a missed opportunity.

HO spital NE twork STudy – Preparation for a Randomised Evaluation of anti-Pneumonia Strategies (HONESTPREPS) aimed to build an infrastructure to prospectively enrol patients at risk of hospital-acquired or ventilatorassociated pneumonia (HAP/VAP) in the intensive care unit (ICU). It also aimed to determine the incidence, microbiological etiology (including antimicrobial resistance), management and outcome of HAP/VAP in the ICU.

Primarily eastern European sites

Within two years, 2,165 patients were included at 12 hospital sites located primarily in eastern Europe. This choice was deliberate, explains Project Manager Lina Gurskaite (University Medical Center Utrecht): “Eastern Europe is interesting for infectious disease research due to untapped talent, population characteristics and a prevalence of antimicrobial resistance. However, the infrastructure for conducting clinical research there is still developing. When setting up a clinical study, site selection preference often goes to more experienced hospital sites in western and southern Europe.”

Helping sites develop their capabilities

“With HONEST-PREPS, we set out to support promising sites in Serbia, the Czech Republic, Romania, Croatia and Albania to further develop their capabilities”, says Lina. “For example, we asked the sites to handle ethical submissions by themselves, which enhanced their knowledge of the process. We also encouraged them to select a dedicated study coordinator to assist the local principal investigator with day-to-day study tasks.” In addition, complimentary Good Clinical Practice training was offered to all local team members, while the LAB-Net team helped to identify gaps in sampling processes and microbiological procedures and provided training.

Overwhelmingly positive response

The benefits of this hands-on approach can be seen in the study’s outcomes, but also in the sites’ feedback. Lina: “The local research teams were very encouraged by the attention and support we provided. Many indicated their intention to use the results to improve their own hospital’s approach to diagnosing HAP/VAP. We hope that the success of the innovative approach

used in the HONEST-PREPS study will encourage more studies to appreciate eastern Europe’s potential for highquality research.”

Overall, 13% of enrolled patients  were diagnosed with HAP/VAP, with Staphylococcus aureus, Acinetobacter baumanni, Klebsiella pneumoniae, or Pseudomonas aeruginosa detected in over half the cases. “HONESTPREPS delivered relevant information about the epidemiology of HAP/VAP from a region in Europe that is often underreported”, says coordinating researcher Henri van Werkhoven.

Continuing in ECRAID-Base

Although HONEST-PREPS has now reached completion, 8 of the 12 sites have transitioned to ECRAID-Base’s POS-VAP. This Perpetual Observational Study on Ventilator-Associated Pneumonia aims to activate 40 ICU sites in 15 European countries and enrol 20,000 patients in four years. It is part of the EU-funded ECRAID-Base project which is building on COMBACTE’s extensive infrastructure to establish a self-sustainable not-forprofit pan-European clinical research network: Ecraid.

Drieke Vandamme

• PMO lead COMBACTE-NET and clinical project manager COMBACTE-NET WP6E, academic clinical project manager and contracts manager

• Associate director clinical operations Aridis Pharmaceuticals Inc.

“COMBACTE had a very big impact on my career. I started at CHU Limoges as a clinical project manager and always worked as the interface between public and private partners. I learned a lot from both sides and met many people in the field. Although I moved to a private partner, Aridis, I still contribute to that same interface within COMBACTE, working collaboratively on the development of exciting new and novel therapeutics.”

Fleur Paling

• Former coordinating investigator ASPIRE-ICU

• GP and member of the Dutch Association of GPs (NHG) working on Guideline Development, with expertise in Infectious Diseases

“COMBACTE was the platform where I (as part of a larger team) had the opportunity to coordinate an international multi-centre study, from design to publication. This being quite the task, I learned as much about epidemiology and statistics as I did about flexibility and perseverance. I met many, many nice people, and I still cross paths with quite a few of them.”

My COMBACTE Takeaway

Tomislav Kostyanev

• Former Medical Microbiologist, University of Antwerp

• Postdoc, medical microbiologist, Technical University of Denmark

“COMBACTE has built a huge clinical trial network that has supported many clinical studies. Joining the organisation at its very beginning in 2013 and being a part of it for almost nine years has had a significant impact on my career, including obtaining my PhD degree. It is a once-in-a-lifetime experience from which one can learn a lot.”

Frangiscos Sifakis

• Former EFPIA Partner of COMBACTE-NET

Ram Venkatachalam

• Team Lead Grant Management & Advice, UMC Utrecht/Ecraid

“The COMBACTE projects introduced me to the world of antimicrobial resistance research, and the nuances of public-private partnerships. The challenges and bottlenecks I faced during the execution of the COMBACTE projects helped me hone my grant and financial management skills and knowledge. Consequently, COMBACTE projects served as a launching pad for my grant management leadership career at UMC Utrecht and Ecraid.”

• Vice president Real-World Evidence –Gilead Sciences

“When I reflect upon the enormity and complexity of the COMBACTE endeavor, I find it is extraordinary what can be achieved when true leadership, genuine commitment, diverse expertise, and a clear collective purpose come together to take on one of the greatest challenges facing public health. COMBACTE is a real-life demonstration of what is possible.”

Nathalie Seigneuret

COMBACTE-

The project

“COMBACTE-NET was among the very first projects that were launched as part of IMI’s ND4BB programme, which aims to counter antimicrobial resistance by strengthening everything from basic science and drug development to clinical testing and finding new business models. The COMBACTE-NET project was tasked specifically with building a European network of research clinics, laboratories, and investigators that can be utilised to rapidly evaluate novel antimicrobial agents. In addition, COMBACTE-NET was set up to employ that newly created network by conducting various highquality clinical trials that tested the safety and efficacy of some specific candidate drugs. Today, ten years after its work commenced, it can safely be concluded that the public-private consortium has delivered on its goals.”

The results

“First and foremost, the project did create a vast and powerful pan-European infrastructure that is able to rapidly evaluate potential novel antimicrobials. That infrastructure includes CLIN-Net, a network of over 1,200 hospitals that can quickly and reliably recruit patients for inclusion in multinational, multi-centre trials. It also includes LAB-Net, a network of over 900 microbiology laboratories that can quickly deliver reliable, standardised data on microbial strains and their resistance against existing antibiotics.

Tying together these two capabilities is essential for conducting trials in which critically ill patients need to be diagnosed, recruited, appropriately treated, monitored, and evaluated.

netCOMBACTE-NET’s networks have delivered on their promise. They have proved capable of conducting not just observational studies but Phase I, Phase II and Phase III clinical trials as well, even in complicated clinical settings such as mechanically ventilated patients in intensive care.

COMBACTE-NET proved effective, for example, in a Phase II study of suvratoxumab, a novel monoclonal antibody targeting alpha toxin from the Staphylococcus aureus bacteria to protect highly vulnerable, critically ill patients from developing lifethreatening infections. These capabilities and infrastructure created by COMBACTE-NET were utilized effectively for other projects such as the Phase II study of gremubamab, an antibody against Pseudomonas aeruginosa, also studied in critically ill patients at risk for serious life-threatening infections.

Another one of COMBACTE-NET’s key contributions was generating data in support of novel methodological trial approaches (for example, the use of composite endpoints). Those data informed discussion with regulators about how to use innovative study designs to make future clinical trials more time-efficient.

COMBACTE-NET’s broad-based infrastructure even proved extremely useful outside the realm of novel antimicrobials. During the COVID-19 pandemic, rapid molecular diagnostic capabilities, strengthened across Europe through the CLIN-Net and LAB-Net frameworks, proved critical in the fight against SARS-CoV-2.

In all, COMBACTE-NET’s numerous impacts have been substantial, and thanks to Ecraid they will continue to be felt for years to come.”

IHI Scientific Project Manager for the COMBACTE Projects on

COMBACTE-NET):

“COMBACTE-NET has changed the paradigm for clinical research in infectious diseases, not only in Europe but globally. Infectious disease research had long lacked high-quality networks of accomplished clinical research centers and laboratories, and COMBACTENET fulfilled that unmet need.”

Elodie Pfender (CHU Limoges)

“In COMBACTE-NET, academia and industry have learned a lot from each other.”

COMBACTE-NET):

“COMBACTE-NET has created a huge multidiscliplinary community of medical experts in infectious diseases including biologists, statisticians, project managers, industry partners, and so many more who have collaborated over a period of ten years.”

Hasan Jafri (Aridis Pharmaceuticals Inc.): “COMBACTE-NET can serve as a blueprint for successful public-private partnerships, leveraging respective and collective strengths of academic and pharmaceutical industry partners.”

Elodie Pfender (Academic Partner, CHU Limoges, Project Management Office

Hasan Jafri (EFPIA Partner, Aridis Pharmaceuticals Inc., Management Board Member and EFPIA Coordinator

ASPIRE-ICU: Preventing infection more efficiently

Like other studies within COMBACTE-NET, ASPIRE-ICU (Advanced understanding of Staphylococcus aureus and Pseudomonas aeruginosa Infections in EuRopE) served a dual purpose. It helped build a sustainable network of ICUs, but it also had a clear scientific aim: to advance the understanding of Staphylococcus aureus and Pseudomonas aeruginosa infections in Europe to prevent infections and reduce antibiotic use.

We spoke with Fleur Paling, Coordinating Investigator for ASPIRE-ICU (S. aureus), Claudia Recanatini, Investigator for ASPIRE-ICU (P. aeruginosa), and Frangiscos Sifakis, at the time EFPIA Lead ASPIRE-ICU, about their work and ASPIRE-ICU’s impact.

Understanding the occurrence of SAIP

“Our goal was to quantify associations of patient-related and contextual factors, including S. aureus colonisation status, with the occurrence of S. aureus ICU pneumonia (SAIP)”, says Fleur. “SAIP was defined as any pneumonia that developed during an ICU stay 48 hours or more after admission with S. aureus isolated from lower respiratory tract specimens or blood samples. The incidence of SAIP was derived in the study cohort and estimated on the weighted incidence calculation for the originating overarching population, while taking competing events into account.”

Positive impact on clinical practice

In P. aeruginosa research, substantial data and samples were analysed to provide insights into the prevalence and incidence of P. aeruginosa colonisation during an ICU stay. “ASPIRE-ICU yielded a number of interesting findings”, says Claudia, “for example, reducing colonisation by P. aeruginosa could be a way to reduce the risk of lung infection in ICU patients.” The study described the incidence of P. aeruginosa infection in ICUs across Europe and found that the incidence of P. aeruginosa ICU pneumonia (PAIP) was higher in colonised patients, and that different rates exist in different regions in Europe. Claudia: “So the results identified patients with higher risk of PAIP, highlighting targets for future interventions to prevent infection more efficiently, both in clinical practice and when designing clinical trials.”

Fruitful collaboration academia and industry

Asked for the impact and lessons of ASPIRE-ICU Frangiscos points at the

collaboration in the project. “I learned that collaboration between academia and industry can be very fruitful and rewarding, as was definitely the case with ASPIRE-ICU. A critical part was the trust and camaraderie developed early on, which built a strong foundation for the scientific discourse to be productive. On a personal note, my time with ASPIRE-ICU helped me grow as a scientist and as a person. I miss all my colleagues fondly and reflect back on that time as truly special.”

For future health needs

Claudia explains that ASPIRE-ICU’s study results presented a clear picture of infections in Europe and identified specific biological targets and target populations for future preventive interventions. “Beyond the scientific results, it created a coordinated and expert capability for how to design these types of studies, which can be quickly leveraged for future health needs. We can now recognise high-risk patients and focus the application of preventive interventions on them.”

About ASPIRE-ICU: ASPIRE-ICU was a prospective, obser vational, multicentre, epidemiological cohort study that was nested within routine surveillance among ICU patients across Europe. Conducted at 30 sites in 11 European countries, ASPIRE-ICU enrolled 2,000 patients who were recruited upon ICU admission. This study cohort facilitated active sampling and elaborate data collection. Bacterial isolates and serum samples were collected for in-depth microbiological and immunological testing, which was a nice collaboration with LAB-Net.

ASPIRE-ICU aimed to better predict the risk of infection and to estimate the incidence of S. aureus and P. aeruginosa ICU pneumonia, especially ventilatorassociated pneumonia (VAP), during an ICU stay. It assessed its association with patientrelated and contextual factors, for example comorbidities, colonisation status, and relevant biomarkers. With this information, a risk prediction model was developed to quantify the risk of acquiring S. aureus or P. aeruginosa pneumonia during an ICU stay.

“ Reducing colonisation by P. aeruginosa could be a way to reduce the risk of lung infection in ICU patients”

Coordinating Investigator Fleur Paling presenting preliminary ASPIRE-ICU results at ECCMID 2019 in Amsterdam.

IMPORTANT PIECES of a puzzle

There is little awareness about Invasive Escherichia coli Disease (IED), despite the important burden and treatment challenges associated with it. Back in 2018 Janssen Vaccines & Prevention began its collaboration within COMBACTE-NET, through the two observational and epidemiological EXPECT-1 and EXPECT-2 studies. The results provided impor tant information for designing and executing a cur rently running phase III clinical vaccine efficacy trial called E.mbrace*.

We spoke to Janssen Vaccines & Prevention about the collaboration between them and COMBACTE-NET.

Creating evidence

Jan Poolman: “Vaccine development is a publicprivate partnership activity. To understand the epidemiology, the public health impact of a vaccine, vaccine companies collaborate with public health organizations. The network that COMBACTE-NET provided was a great fit for us to learn more about IED and what the impact of IED is on patients. Especially considering our plan to eventually run a phase III vaccine efficacy trial.”

Jeroen Geurtsen: “One of the issues is that the overall awareness of IED in the public domain is low. However, if you look at the scientific data, IED poses an important burden with E. coli being the number-one bacterial pathogen associated with invasive disease, including potentially lifethreatening bacteremia and sepsis, as well as the number-one bacterial pathogen associated with antimicrobial resistance-related deaths. Generating further evidence and data supporting the health impact both at patient level as well as at population level is of critical importance. Collaborating with healthcare providers across Europe provided an important opportunity to increase knowledge on the disease and raise the awareness on the disease burden.”

Transfer of knowledge

Jan Poolman: “What we brought to the table was a focused approach on how to develop a vaccine against IED in the future”.

Jeroen Geurtsen: “I believe an important contribution from Janssen has been the transfer of knowledge into the COMBACTE-NET consortium. The experience acquired by the network on the clinical profile of the disease as well as analysis of the associated clinical isolates can be applied in case future vaccines or other preventative strategies may become available.”

Benefits

Jeroen Geurtsen: “Both the population and the scientific community benefit from collaborations like this. The two observational and epidemiological studies provided important information for designing and executing a currently running phase III clinical vaccine efficacy trial called E.mbrace*. The studies helped us further shape and test the clinical case definition for IED and better understand the impact of the disease at individual patient level. An important result from the collaboration was the operational infrastructure that is now also partially embedded in our phase III study. Some of the sites and principal investigators that participated in the EXPECT studies are now also participating in E.mbrace*. Through the manuscripts that should soon be published, we aim to raise further aware ness on IED in the public domain, and among healthcare professionals.”

Jan Poolman: “E.mbrace* is an event-driven study. That was another important aspect the consortium looked at in EXPECT-1: capturing the IED cases as efficiently as possible. What systems can be used, how fast are they, how is the information flowing – and applying that in the phase III trial. Every case you miss can cause delays down the road and can impact your study.

The takeaway is that COMBACTE-NET contributed to the development of novel preventive strategies, such as vaccines. It contributed to raising the overall awareness of the importance and impact of IED, especially at a patient level. What does it mean for a person to suffer from IED? What happens to them in the hospital? What do the E. coli isolates that caused the disease look like?”

Jeroen Geurtsen: “The road to a phase III vaccine efficacy trial, and a phase III trial itself, is very complex. Like a thousand-piece puzzle, in which COMBACTE-NET has provided several important pieces.”

*ClinicalTrials.gov Identifier: NCT04899336

“ Vaccine development is a publicprivate partnership activity”

helped me take

Collaboration was key to the success of COMBACTE-MAGNET. Hundreds of researchers enjoyed the opportunity to join forces with colleagues all over Europe and make a difference in the field of antimicrobial resistance (AMR) research. Dr. Nithya Babu Rajendran was one of them.

What made you choose to work as a researcher?

“I had a general interest in science as a child, particularly in biology and physics. As I grew up physics became more abstract whereas biology started to provide answers to questions I had about life and human existence. While knowledge and techniques advanced, I found myself drawn to molecular biology and biotechnology. I eventually obtained my masters in

molecular biology and biotechnology, and a PhD in molecular microbiology.”

What was your role in COMBACTE?

“For the last eight years, I worked on EPI-Net,  one of the four pillars of COMBACTE, part of COMBACTE-MAGNET. The overall objective of the network was to create a platform for researchers and experts on AMR to work together and improve

“We developed nine consensus documents and published 21 peer-reviewed journal articles”

Nithya Babu Rajendran

“COMBACTE-MAGNET has

my management skills to the next level”

our understanding of the epidemiology of AMR. This was a complex endeavor with several studies and projects running in parallel focused on different research questions. My role was multifaceted, I wasn’t only doing research, but was also in charge of coordinating and managing all the different activities taking place in EPI-Net. I thus project managed, ran studies, and coordinated communication.”

What has been your contribution to AMR research?

“I’ve been very lucky to be a part of this project and all the contributions are the result of great team effort. We’ve achieved a lot together, and I’m particularly proud of the EPI-Net website that we built as a central data repository for epidemiological data on AMR. It’s a unique platform and is incredibly useful for AMR research now and into the future.”

What did you enjoy most about your work in COMBACTE-MAGNET?

“Our main goal was to improve patient health outcomes, future trials and clinical research. It was a one-of-a-kind project with high ambitions. I enjoyed the challenge, and what was really interesting for me was the atmosphere of cooperation. We worked closely with academic and EFPIA colleagues from within and outside the COMBACTE’s consortia. By building strong partnerships with other European and global initiatives, we were able to share knowledge and experience, reducing duplication of work and increasing efficiency.”

What was the personal impact of your work experience in COMBACTE-MAGNET?

“It allowed me to look beyond scientific research

and delve deeply into the concepts and techniques of project management. Among others, I gathered extensive experience in team leadership and communication, effective budget and staff planning, risk mitigation, internal and external stakeholder liaison, as well as intercultural competence. Skills that not only help to run trials in an academic environment but can be applied in any other profession. My work in COMBACTE-MAGNET has helped me take my management skills to the next level.”

How did you experience the collaboration with pharma?

“It was a unique experience in that you meet these interesting individuals who bring in a completely different perspective to academic research, one that is less traditional and that focuses on sustainability.

For them, it was vital that we developed tools that had longevity. For example, pharma was interested in a business plan for EPI-Net. We built a lot of infrastructure in COMBACTE not to mention tools, which lead to EPI-Net being sustained in Ecraid.”

What do you see as concrete results of COMBACTE-MAGNET?

“In a nutshell, I would say strategic resources in the battle against AMR and infectious diseases. As part of EPI-Net, for example, we developed nine consensus documents and published 21 peer-reviewed journal articles. We also established two public service tools, the EPI-Net website which brings in data on AMR which is easily accessible to anyone around the world, and there’s the AMR Travel Tool which is designed to reduce the spread of AMR through travel.”

“WE WERE ABLE TO SHARE KNOWLEDGE AND EXPERIENCE, REDUCING DUPLICATION OF WORK AND INCREASING EFFICIENCY”

COMBACTEmagnet Nathalie

The project

“COMBACTE-MAGNET focused on finding new clinical options for a highly vulnerable group of patients: those who are critically ill, undergoing intensive care and at risk for or fighting infections by Gram-negative bacteria such as Pseudomonas aeruginosa. The project delivered on its objectives.”

Seigneuret

The results

“The project was set up, first, to gather and analyse epidemiological data about microbial threats, drug resistance and treatment patterns across Europe. To that end, it created an epidemiological network called EPI-Net in which existing surveillance systems were connected. Various centres of excellence were created. The goal was being able to better monitor the spread of antibiotic resistance and the prevalence of healthcare-associated infections.

At the patient level, it sought a better understanding of how infections affect patients’ bodies, which biomarkers reliably predict infection progress and treatment response, and why some patients respond better to treatments than others.

Such knowledge allows for designing more rapid clinical trials to test innovative candidate drugs against multidrug-resistant Gram-negative bacteria, and to do so where ICU patients are most at risk.

Finally, it set out to actually conduct some clinical studies to test the safety

and efficacy of an antibody that might help prevent ventilator-associated pneumonia in vulnerable ICU patients, as well as that of a novel antibiotic compound.

The project delivered on its objectives. The epidemiological work carried out through the EPI-Net network and its newly created centres of excellence produced insights that will continue to support antimicrobial drug development and designs of trials using statistics and new diagnostics. The new EPI-Net surveillance database now provides upto-date, Europe-wide information on the prevalence and incidence of hospitalacquired infections and the spread of antimicrobial resistance. An online AMR Travel Tool now helps international travellers, travel clinics, and infectious disease specialists navigate antimicrobial resistance risks at travel destinations and find ways to mitigate them.

The observational studies provided important new insights into current clinical management, treatment outcomes and related healthcare costs of patients with complicated Gram-negative urinary tract infections, especially in high-risk countries. Highlighting the need for strengthening patient input

IHI Scientific Project Manager for the COMBACTE Projects on

at all levels of the research, a toolkit was developed that provides guidance on when and how to involve the public in research and development of antimicrobials.

An important achievement was the completion of the EVADE Phase II trial of gremubamab for patients with Pseudomonas aeruginosa in their respiratory tract who need mechanical ventilation. Enrolling patients and convincing doctors to test a preemptive treatment ahead of a potential pneumonia diagnosis posed a challenge that was fully met. Although this particular trial ended up not finding a reduced incidence of nosocomial pneumonia, demonstrating an ability to test such approaches rapidly is a key project outcome.

The COMBACTE-MAGNET consortium had to adapt to various surprises along the way that affected its original workplan. Despite not being able to do all trials as initially planned, it proved how transparency and trust among all public and private partners will ultimately be the key to success.

EPI-Net’s achievements will be sustained and expanded in Ecraid.”

DRIEKE VANDAMME

(at the time, Academic partner, CHU Limoges, Project Management Office COMBACTE-MAGNET):

“To me, COMBACTE’s pan-European clinical network stands out as an example of how fragmentation can be reduced in clinical research. With that network having been preserved in Ecraid, future trials will continue to run better and faster, and enable new treatments to hit the market sooner.”

Mark Esser (EFPIA Partner, AstraZeneca, Management Board Member COMBACTE-MAGNET):

“While it did not lead us yet to new medications, we showed that we could design and run epidemiology and clinical trials to better understand anti-microbial resistance. We also identified risk factors and biomarkers for inflammation in urine and blood, revealed the role of the gut as a reservoir for lung infections, and developed models to measure the benefits of different interventions.”

PPI: THE ADVANTAGES OF Involving Patients in Clinical Research

One of the most crucial factors for success in clinical research is the patient. In work package 6i of COMBACTE-MAGNET the patient was the focus. A Bristol-based team delivered a Patient and Public Involvement (PPI) Toolkit.

Andy Gibson, Associate Professor in public involvement in research, based at the University of West England: “The importance and prevalence of PPI has grown over the years, particularly in the UK, but drug development and anti-microbial research is still an area where PPI is rare.”

Advantages

“PPI can help ensure that the research questions address the needs of the patients. It can help in designing interventions by maximising their benefits to patients while minimising any disadvantages. This can be true of any intervention from a drug to a new therapy to a different way of running a service. PPI can also help ensure that any outcome measure chosen has real-world relevance. All this can contribute to more patient-centric clinical trial designs which in turn can lead to better recruitment and retention and a greater chance that the work will have an impact on real-world healthcare and patients.”

PPI Toolkit

“The PPI Toolkit is a useful resource for developing PPI in all stages of the medicine development life cycle. I think more people are becoming aware of PPI and are interested in trying it out but are unsure how to start. We hope the toolkit will help with that. On a larger scale I think it’s important that research funders start requiring proof of PPI in bid development as a pre-condition for funding. I also think relevant patients and members of the public should be members of funding panels to review PPI plans and assess the potential patient benefit of new research.”

The Toolkit consists of:

- A Practical Guide: this document sets out the practical steps of doing PPI.

- The main Toolkit: this document describes the content of the Practical Guide in more detail, providing case examples and evidence to support the practical steps recommended.

To download the PPI Toolkit, visit the COMBACTE Publication Library.

Academic papers

“We wrote several academic papers exploring different aspects of public involvement, including the experiences of principal investigators doing PPI, differing practices in public involvement across Europe and our own experiences of setting up the public advisory group for COMBACTE-MAGNET. We hope these papers together with the Toolkit will provide resources which will support researchers to embark on public involvement.”

“ There are positive signs that PPI is becoming more commonplace in clinical research across Europe”

Principal Investigators’ experience with PPI

“Go into it (PPI) with an open mind and be prepared to be surprised about how valuable it will be.”

Aina Gomila Grange

• Former clinical researcher for COMBACTE projects

• Infectious Diseases consultant and antibiotic stewardship referrer Parc Tauli Hospital Universitari, Barcelona

“COMBACTE was for me the first contact with multi-centre studies at the European level. My experience there allowed me to appreciate the methodology behind COMBACTE and I made invaluable contacts among well-known researchers from all over the world. It was a very enriching experience where I was able to hone my research skills, which has undoubtedly helped me afterwards. It also helped me to more deeply specialise in healthcare-associated infections.”

Seamus O'Brien

• Former EFPIA Coordinator COMBACTE-CARE

• R&D Director for GARDP

“My role in leading the development of the COMBACTE projects with industry partners and the public consortium demonstrated the potential to both come together to address shared goals related to the development of antibiotics for patients and to ensure substantial outcomes for European research capability. The experience I gained from COMBACTE is now core to how I approach partnerships to address development and access of antibiotic treatments as R&D Director for GARDP.”

Cuong Vuong

My COMBACTE Takeaway

• Former EFPIA-Deputy Coordinator of the COMBACTE-MAGNET consortium, EPI-Net EFPIA lead, and Scientific Lead for AiCuris Anti-infective AG

• Director Bacterial Infectious Disease Discovery

Janssen Pharmaceuticals NV

“The COMBACTE framework provided me with an excellent opportunity to extend my network and meet key opinion leaders, as well as deepen my knowledge in antibacterial R&D. The impact was beyond the professional and corporate level. Within COMBACTE, members of SMEs and large pharma were able to collaborate and to share expertise in a fashion which would not be possible outside of such a framework created by IMI and EFPIA.”

Sally Grier

• Former Programme Manager COMBACTE North Bristol; Patient and Public Involvement (PPI) Coordinator

• Retired in 2021 doing voluntary work as a debt coach; member of the PPI panel in North Bristol for COMBACTE

“It was a joy to be a part of COMBACTE. The opportunity to share knowledge and experience across professional disciplines and national borders enhanced the quality of the work, as evidenced by the RESCUING study. Another highlight was the Patient and Public Involvement project, which strengthened our own practice and raised its profile. The PPI panel is consulted by many local infection researchers and their involvement demonstrates the value of this more laboratory-based side of medicine.”

REVISIT

A Novel Tool to TreatResistantHighlyPathogens?

We spoke with Dr. José Miguel Cisneros Herreros (Hospital Universitario Virgen del Rocio, Seville, Spain) and Pfizer’s Lisa Grimsditch and Rienk Pypstra about the impact of REVISIT. “If successful, REVISIT could optimise the care of patients with complicated intra-abdominal infections and hospital acquired pneumonias”, says José Miguel. He adds: “The design, implementation and application of the study protocol has the potential to improve the care of future patients, the communication flows including the detection of potential candidates, the systematic sampling for microbiological diagnosis, and more timely administration of antimicrobials.”

New antibiotic combination: BL/BLI

Rienk says: “We set out to demonstrate the activity of this new Beta-Lactam/ Beta-Lactamase Inhibitor (BL/BLI) combination, and we have now completed patient recruitment. We were able to do so with the collaboration that was on offer through this consortium.” If the study demonstrates the safety and efficacy of this new BL/BLI combination, and if approved, ATM-AVI will allow physicians to have a simple and straightforward solution to a problem that currently requires various combinations of antibiotics. Rienk: “This would be a huge benefit that REVISIT will have brought to the community.”

Solid collaboration every step of the way “The collaboration between academia and pharma was one of the most outstanding features of the REVISIT clinical trial, and in my opinion has been key to its success”, says José Miguel, who cites increased commitment and

motivation among the investigators as a factor leading to successful patient recruitment. It’s a similar story from Pfizer’s perspective who outlined that a much closer collaboration, frequent contact and working together as partners made for a different mindset and an evolved relationship. According to Lisa, this collaboration is a really strong theme running throughout COMBACTE-CARE, not just in science and clinical efforts, but also in project management and management boards. “Solid collaboration was there every step of the way leading to everyone coming together to solve problems.”

Rare but highly resistant

For Pfizer, a COMBACTE-CARE industry partner, testing the safety and efficacy of ATM-AVI was paramount. Antimicrobial resistance (AMR) is one of the biggest threats to global health today and urgently needs to be addressed, a concern that Pfizer takes very seriously. Rienk: “Patients and clinicians need new therapeutic modalities to treat infections caused by these rare but highly resistant pathogens. It’s why we are involved.”

Selecting the right sites is key

Aside from the pending clinical study results, much has already been learnt from the REVISIT study, including how important selecting the right sites and investigators is, and how key it is for efficient and high quality recruitment. The fulfilment of the target sample size despite the pandemic is a major achievement. For José Miguel, “the most important benefit has been the creation of a multidisciplinary team, with an active involvement of surgeons, nurses, microbiologists, pharmacists and

infectologists, along with the challenge of carrying out the project in the hospital and leading it in our country.”

Unique site relationship-building opportunities

Rienk says that Spain was a particularly good example in relation to recruiting patients who are difficult to find for a combination of reasons. Collaboration between pharmaceutical companies and academic centres is vital and allows for knowledge sharing and encourages unique site relationship-building oppor tunities. Rienk: “Together with our academic partners we selected high-potential sites, and offered support to help ensure high quality standards. With this endeavour COMBACTE- CARE has established a high-quality clinical trial network in Europe: European Clinical Research Alliances on Infectious Diseases (Ecraid).”

Lisa believes that the willingness of the academic partners was inspiring. “A specific example is the support for the study sites, which was designed to provide investigators with support through a 24/7 global support line with national leads offering advice. It exem plified how people came together to ensure that the study progress, the data quality, and future patient benefits were at the forefront of the minds of all involved.”

REVISIT is one of the studies in COMBACTE that offers an important contribution in the battle against AMR. With academia and pharma shoulder-to-shoulder on the frontline, REVISIT studied the efficacy and safety of a fixed combination of aztreonam and avibactam (ATM-AVI) in a Phase III randomised, open-label, comparative clinical trial.

“

The data quality, and future patient benefits were at the forefront of the minds of all involved ”

Nathalie

Seigneuret IHI Scientific Project Manager for the COMBACTE Projects on

The project

“COMBACTE-CARE was set up to address a specific challenge: infections with carbapenem-resistant Gram-negative bacteria, which are often resistant to most other antibiotics as well. The project was designed to lay the groundwork for multicentre trials of new compounds that can help counter that challenge. Although the project is in its final stages, with a couple of more months to go, we can already safely conclude that the consortium has delivered on its main objectives.”

Rienk Pypstra (EFPIA Partner, Pfizer, Project Management Office Lead COMBACTE-CARE):

“The close collaboration between Pfizer and the COMBACTE-CARE team was key for selecting the best study sites for this Phase III trial. Pfizer helped select qualified investigators and a diverse population of patients from world regions with high CRE infection rates, while COMBACTE-CARE provided a global footprint and vast experience of infectious disease experts.”

“COMBACTE-CARE has demonstrated how well a publicprivate partnership can work.”

Lisa Grimsditch (EFPIA Partner, Pfizer, Project Management Office Lead COMBACTE-CARE):

The results

“First and foremost, the EURECA study has generated, gathered, and analysed large amounts of observational clinical and epidemiological data on risk factors for serious carbapenemresistant Enterobacterales (CRE) infections and determinants of outcomes for the currently available treatment options. The results have provided us with important new insights. It has also informed the design of future randomised trials testing candidate CRE-fighting drugs.

For example, how important it is to recruit patients from diverse populations. It has built a framework that helps us select the right study sites and find the right investigators, which helps to quickly maximise and optimise the sample of patients that are recruited into the trial. And it demonstrated the added value of setting up an innovative 24/7 support line because trials

like these generally involve clinically complex patient populations.

Using those and other important lessons, the project completed a Phase II study (REJUVENATE) ahead of schedule and also completed patient recruitment for a Phase III study (REVISIT), the final results of which will hopefully be announced soon.

Together, these studies evaluate the efficacy and the safety of aztreonamavibactam (also called ATM-AVI) for the treatment of serious infections with Gram-negative bacteria, including metallo- β -lactamase producing multidrug-resistant pathogens.

off availability, possibilities and priorities of investigators, hospital staff and other infectious disease experts.

This feat can be seen as a testament to the efficient collaboration between investigators from a pharma company, academic institutions, and a contract research organisation (CRO). Together, they were able to take effective measures that helped increase patient recruitment and managed to keep the study mostly on track.

Rienk

Completing recruitment in Phase III was all the more impressive because of the added challenges posed by the sudden outbreak of the Covid-19 pandemic. Like in some other COMBACTE-related trials, recruitment of patients advanced less swiftly than was anticipated beforehand because the pandemic siphoned

Now, we all look forward to learning about REVISIT’s outcomes. Hopefully, they will show robust benefits of ATMAVI, which could support an application for marketing authorisation in Europe. That in turn could add a treatment option for patients with serious Gram-negative bacterial infections, for whom at present such options are limited or non-existent.

In all, COMBACTE-CARE has delivered on its promise to make important progress towards developing this and future new options for the benefit of patients at high risk.”

Pypstra

(Pfizer) “COMBACTE-CARE has made an invaluable contribution by integrating knowledge and capabilities of industry and leading clinical and microbiology academic research groups from across Europe to meet challenges of crucial observational and interventional clinical studies.”

Lisa Grimsditch (Pfizer)

“There was a great sense of community in COMBACTECARE generally, and frequent communication ensured that everyone was up to date.”

Nathalie Seigneuret (IHI):

“The close collaboration between pharma, academia, and clinical research organisations managed to counter disruptions caused by the Covid-19 pandemic. Their experiences and this model of collaboration offer critical lessons for Ecraid and the design and execution of future trials.”

European Coverage

NUMBER OF TRIALS PER COUNTRY

Albania 2 , Austria 1 , Belgium 4 , Bulgaria 3 , Croatia 4 , Czech republic 7, Estonia 2 , France 8 , Germany 4 , Greece 7, Hungary 5 , Ireland 2 , Israel 4 , Italy 4 , Kosovo 1 , Latvia 1 , Montenegro 1 , Netherlands 4 , Portugal 3 , Romania 6 , Switzerland 1 , Serbia 4 , Spain 10, Turkey 5 , United Kingdom 4

Nathalie Seigneuret

IHI Scientific Project Manager for the COMBACTE Projects on

The project

COMBACTECDI

“COMBACTE-CDI was dedicated to developing a detailed understanding of both the clinical impact of Clostridioides difficile infections (CDI) for patients and its epidemiology across Europe. It was meant to help assess not just the scale of the problem in terms of patient morbidity and mortality but also of the impacts it has on entire healthcare economies – which has never been done before in Europe or the rest of the world. It was the last project that was launched under the IMI2-ND4BB programme, and it successfully delivered on its objectives.”

The results

“Traditionally, research into CDI has focused on hospital-associated infections. COMBACTE-CDI also looked at the interplay between hospital infections and the community, including bacterial strains that can be found in animals and food-products.

Among the project’s most notable outcomes are significant new insights into the burden undetected CDI has on healthcare systems in Europe. Those insights include better estimates of infection incidence, distribution, recurrence, and transmission, as well as associated morbidity and mortality and wider impacts on the healthcare economy.

The project established, for example, that the largest burden in terms of healthcare costs derives from the 25-30% of patients who experience recurrent Cdiff infections. In such patients, every recurrence increases the chance of subsequent infections, which places them on a kind of ‘recurrence escalator’.

This insight points to focusing treatment and prevention actions on reducing the recurrence of infections more than on treating all primary infections.

The outcomes also highlight the need for increased awareness of CDI both among healthcare professionals and the wider community, such as adults with known predisposing risk factors or in those with prolonged days

of diarrhoea. Increased awareness can reduce transmission rates and thus reduce the potential for further healthcare burden.

The team also discovered that European countries are not all the same. Those that did little testing for CDI tend to have higher infection levels and low strain diversity, whereas those that test intensively have lower infection levels and huge diversity in strains. That suggests that the latter are not dealing with outbreaks but with sporadic cases. Testing, in other words, seems to be effective in reducing transmission and outbreaks.

Following existing treatment guidelines by hospitals also proved to be associated with lower burdens of CDI.

All those insights will have important impacts on prevention strategies such as educational and testing efforts and programmes. They will no doubt also support the development of novel diagnostic and therapeutic options and open the door to further research for instance on the role of food products in C. diff transmission.”

COMBACTE-CDI, University of Leeds: “I have been surprised by the high level of openness and honesty between the academic consortium members and the industrial partners, GSK and bioMérieux. It was a really great experience working as true partners to deliver what we all wanted to deliver.”

Nathalie Seigneuret (IHI)

“COMBACTE-CDI has connected top experts in CDI to the CLIN-Net and LAB-Net networks. That has expanded the expertise of those networks as they transit to Ecraid.”

Kerrie Davies, University of Leeds: “The biggest finding of the study for me was that 50% of C. diff cases in the community are undiagnosed. This means there are large numbers of patients out there not getting the treatment they need.”

Kerrie Davies, University of Leeds: “COMBACTE-CDI has managed to use a single source of data for making many different analyses. It’s an example of how, if you set up a study correctly, you can use the data for multiple purposes and gain multiple insights, maximising the benefits for research and patients.”

Kerrie Davies

University of Leeds:

“COMBACTE-CDI’s novel and unique approach has provided a much broader picture of what is out there in terms of C. diff infections and what exactly might be causing the biggest problems.”

Kerrie Davies, Scientific Coordinator

FUTURE SUSTAINABLE ECRAID

Next-generation collaboration

Perhaps the most precious gift COMBACTE has offered Europe is Ecraid. This new organisation gives the networks that were built in COMBACTE a robust and sustainable future, and continues the collaboration that so many enjoyed during ten years of COMBACTE.

Ecraid’s purpose is to reduce the impact of infectious diseases, which affects both individual health and society as a whole. A pan-European network conducting clinical research is at the core of Ecraid. With over 1,200 hospitals participating in 42 countries, it has a unique network, supported by the best academic experts in infectious disease that Europe has to offer. Because of its warm-base network Ecraid can execute trials faster and more efficiently, with high quality, making it attractive for both investigator and industry- driven research.

A movement

However, Ecraid is much more than an organisation aimed at carrying out clinical trials. Ecraid is also a movement dedicated to reducing the impact of infectious diseases. A movement where knowledge of infectious diseases can be shared and new methods of clinical research can be developed together. It is a movement where young talent and experienced experts – from both academia and industry –connect to collaborate and learn. With its headquarter in Utrecht, the Netherlands, Ecraid is committed to remaining a real European movement with a Coordinating Committee consisting of European top experts.

Prepared for the next pandemic

What if another pandemic were to break out? How can we be prepared and swiftly respond? These questions led to the establishment of the PREPARE project in 2014, which together with COMBACTE is the predecessor of Ecraid. PREPARE demonstrated its value with the RECOVER program during the COVID-19 outbreak, and Ecraid will be able to do the same during the next potential pandemic.

With its specialised warm-base network Ecraid can respond faster to an outbreak. Ecraid will use any resources to accelerate research in case of an emerging pandemic.

5 advantages of CLIN-Net

1. Single point of access

Direct access to over 1,200 sites via one central point.

2. Operational readiness

When time is of the essence Ecraid is prepared.

3. Focused experience

Specialised in research on infectious diseases.

4. Uniform quality standards

Standardised templates, processes and trained staff.

5. In-depth site knowledge

Data available on all sites and their prior performance.

CLIN-Net – part of Ecraid’s warm-base network

Ecraid provides access to three expanding warm-base networks: LAB-Net with over 900 laboratories, a Primary Care network with over 250 GPs and CLIN-Net. This last network spans over 1,200 clinical sites across 42 countries. It delivers rapid, cost-efficient, high-quality clinical research services to public and private partners. From regular hospital wards to emergency rooms (ER) and intensive care units (ICUs). CLIN-Net’s unique clinical research infrastructure has already enrolled over 47,000 patients in 47 studies.

Unique to CLIN-Net is its number of sites and the CLIN-Net team that oversees the collection of data from the sites, maintains the relationship with them, and coordinates the execution of trials. The team makes sites feel connected and keeps them well-informed when

participating in a study. During a study they monitor a site’s performance and use this information when a new site selection occurs. Changes such as offering new investigators may be administered, so CLIN-Net’s information is always up-to-date.

Augmenting capabilities

Because Ecraid continuously involves existing sites in new clinical studies it can consolidate the network and maintain it as a real warm-base network. The team helps less experienced sites to develop their potential for clinical research, thus expanding the number of experienced sites and augmenting the capabilities of the network to conduct more studies in parallel.

European coverage

Ecraid strives to create real Europe-wide coverage of its network, aggregating the potential European academia has to offer in research on infectious diseases. A broad European coverage (see map page 30 and 31) also gives access to specific populations where the prevalence of antimicrobial resistance is high. This shortens the time in which enough patients are included for a trial.

Ecraid Services

Ecraid provides the full breadth of clinical studies on infectious diseases: observational studies and interventional studies in all four trial phases (I, II, III and IV), for both investigator- and industry-driven research. We do this from the study design to protocol development, to site selection, and finally, the clinical study report.

Pharmaceutical companies have shown keen interest in Ecraid, especially in Ecraid’s site selection services. The site selection team knows every site and their research track record, and they are able to rapidly

select the most appropriate sites for a trial. Even when it seems difficult to identify the right hospitals, the best hospitals are always within reach with one point of contact through Ecraid.

Supporting services

• Laboratory research and bio-banking

With a network of 900 laboratories

Ecraid can provide state-of-theart laboratory research services, in close collaboration with its clinical research services.

• Epidemiological research

With the use of the EPI-Net infrastructure built in COMBACTEMAGNET, patient-level and regional data on emerging infectious diseases and AMR can be collected and analysed. This supports targeted site selection for fast patient inclusion.

• Statistical analyses

Ecraid can provide both standard and innovative statistical support to improve efficiency and quality of studies. This service is built upon the STAT-Net activities in COMBACTE-NET.

Current Study Portfolio

SOS COVID

SARS-CoV-2 Observational Study of community acquired-acute respiratory tract infection.

REMAP-CAP

Randomised, Embedded, Multi-factorial, Adaptive Platform trial for Community-Acquired Pneumonia.

POS-VAP

Perpetual Observational Study among patients at risk for developing VentilatorAssociated Pneumonia.

POS-Disease X

Perpetual Observational Study among patients with unexplained febrile illness.

POS-cUTI

Perpetual Observational Study among patients with complicated Urinary Tract Infections.

POS-ARI-ER

Perpetual Observational Study among patients with Acute Respiratory infections.

POS-ARI-PC

Perpetual Observational Study among patients with Acute Respiratory infections.

ECRAID-Prime

Primary care adaptive platform trial for epidemics and pandemics.

A continuous flow of studies

To maintain a warm-base network you need a continuous flow of studies. Only then sites can get used to working with the standardised processes and procedures and are able to start up quickly with well-trained staff. In the past years the Ecraid network has already included 47,000 patients.

Ecraid has multiple studies running in which sites from its own network participate. Among the studies being executed are the Perpetual Observational Studies (POS). These are multicentre observational clinical studies that include patients on a perpetual basis, receiving standard-of-care for a defined infectious disease and using harmonised diagnostic treatment and followup methods. With the present set of POS, data and clinical samples are systematically collected. Partners can make use of this data or plug in their own questions.

With its perpetual character POS enables continuity in clinical research. This also applies to the even more innovative concept of Adaptive Platform Trials (APT). This concept offers a new approach to studying multiple therapeutics

simultaneously. Ecraid has experience with APT through REMAP-CAP and ECRAIDPrime. REMAP-CAP showed the value of APTs during the Covid-19 pandemic. APTs also make it easier to create a continuous flow of new studies.

Be part of the solution Join the movement

Clinical research on Infectious Diseases