The Heart of the Matter

Posted on 5th January 2022

The world of research is built on collaboration, but finding the space for that collaboration is not always easy. When the European Cardiovascular Research Institute (ECRI) was founded, it was to perform various studies into the field of cardiology. In Acquisition International’s Global Excellence Awards, the organization was given the 2021 Award for Excellence in Cardiovascular Clinical Studies – Europe. We take a closer look at their fascinating work to see what they do, and how they’ve achieved such amazing success.

Founded in 2012, the ECRI was designed to act as a collaborative base of operations for scientists and experts from across Europe to explore the field of cardiology, specifically the performance of investigator-initiated studies. These studies have the potential to revolutionize our understanding of this specialized branch of medicine, opening the doors to a whole new world of opportunity. This non-profit has transformed the way in which cardiology is seen by the world at large, pushing the boundaries of what can be done continually forward.

The benefits of ECRI come from the structure of the organization. Through the various processes and systems established, teams can facilitate the design and conduct of clinical trials according to ICH/GCP/ISO guidelines and standards. ECRI uses a great deal of expertise in these trials, looking to Cardialysis, an established academic and contract research organization, which has executed over 400 clinical studies, in Europe and around the world. The combination of both organizations creates an opportunity for multi-center, multinational investigator-initiated studies. Several multi-center randomized clinical trials with ECRI acting as trial sponsor are currently being conducted by means of scientific grants form leading industries.

As a sponsor of clinical trials, there are four clear responsibilities that make ECRI an innovative partner. These four attributes are what the team focuses on to ensure their work is consistently of the highest quality possible. Firstly, patient safety is paramount. The team carefully designs their clinical trials with expert input from established clinicians and scientists. Prestigious clinical centres and investigators are selected to treat patients to guarantee this, with a system of highly regulated safety reporting procedures.

Secondly, the value of data is obvious to a research organization, and to ensuring its integrity is a top priority. ECRI continually monitors the quality and timeliness of data entry, and ensures the continuity of protected databases by hosting these in professional organizations which follow regulations on maintenance of clinical databases. 2021 saw a breakthrough in this respect, making its publication policy public, and therefore a process which can be scrutinized by professionals and specialists from around the world.

Thirdly, the team ensures its results are reliable by highly controlled procedures designed to prevent bias among the investigators. By taking deliberate decisions at the start of the research process, it’s possible to bring about a much more independent decision making process. A clear example of this in action is the way in which a clinical trial is monitored by an independent data and safety monitoring board. These expert board assesses the overall safety of a project. It is typically construed by three members, is independent of the ECRI and provides its advice to continue or modify a protocol to the Steering Committees of a study.

The final aspect that drives ECRI forward is the timely execution of clinical trials within allocated budgets. Science must lead the research industry forward, but careful management and planning are crucial to reach targets and to generate data that can reliably answer the research questions addressed by a particular clinical trial. Some organizations take a cavalier attitude to this, but the team at ECRI ensures that their work is focused specifically on getting good data in a specific field. The team’s close collaboration with Cardialysis, and with other organizations occasionally participating in ECRI trials, is key to this success.

The challenges faced by the medical industry as a whole are numerous, and the work of ECRI contributes to ensuring that cardiovascular clinical studies do not fall behind. As there is less funding currently available, combined with regulatory requirements and company standard operating procedures that make clinical trials expensive to execute, it’s little wonder that many struggle to explore some of the more interesting areas of the industry. Even many interesting study ideas from individual Investigators will not be funded due to budget limitations. ECRI acts as an intermediary between thought leaders and supporting industry, building collaboration not just into the way a study is run, but into the very fabric of its being from the outset.

When the team at ECRI work with their clients, they see them as partners to work closely with to ensure success. Every cardiovascular randomized clinical trial that the team conducts is an enormous endeavour that typically lasts for 5 to 7 years. This means that commitment and passion are critical from all parties. The core of an ECRI project is made of four basic components, starting with the ECRI managing director. This person acts as the sponsor representative for the trial. There are also the Principal Investigators and Steering Committee, who offer the scientific and medical leadership to the trial, the Grant-Givers who support the execution of the investigator initiates through restricted research grants, and finally Cardialysis, to which ECRI outsources all clinical trial and core laboratory execution activities. Often, more than one contract research organization is involved in ECRI trials sharing responsibilities with Cardialysis, either due to band width or geographic distribution. These parties are qualified and compliant ECRI and Cardialysis vendors.

ECRI functions as independent sponsor for clinical trials, drastically reducing the workload to lead investigators, who would otherwise take the sponsor responsibilities at their academic institutions. ECRI utilizes Cardialysis, its sister organization, from which it sources critical capabilities for sponsoring clinical trials. Its operational activities draw on almost 40 years of clinical trial expertise at Cardialysis. The culture of ECRI is the culture of Cardialysis. Both are proudly knowledge-based professional organizations, with regulatory-compliant processes, and top commitment for quality in clinical research.

Over the years, ECRI has become characterized by accuracy in planning, budget oversight, compliance, and execution. ECRI operates on the basis of close collaboration and rapid communication among stakeholders. As a non-profit organization, ECRI is solely funded by research grants provided by the medical industry which typically is not involved in the design of the studies, but without which investigator-initiated studies could not be executed via ECRI. Moreover, they may facilitate devices or drugs, if this would be part of the agreed research grant contribution.

ECRI operates within networks of clinical sites with extensive experience in clinical research who facilitate a timely patient enrolment. Being compliant to regulations at an institutional level as well as having the necessary logistics and personnel to set-up a clinical investigation, adequately consent patients, implement best practices for experimental therapies or devices, ensure timely and accurate data entry, as well as thorough follow-up of study participants, demand significant resources from participating sites and vouch for the unfaltering commitment of health care providers to improving patient care. ECRI networks goes beyond Europe and are represented globally.

The challenges of the COVID-19 pandemic have affected every industry around the world, and as many other leaders in the field, ECRI adapted through the pandemic. Given the primary focus on device and open-label pharma trials, ECRI’s completed on time studies planned to end in 2020 and 2021, without important challenges. Significant adaptions, however, took place around monitoring activities where specialized research professionals visit hospitals to review the quality of data entered in the study databases compared with data available in the patient charts. This review needs to be in-person, and in Europe it is not allowed to perform these reviews remotely. For this reason, monitoring visits had to be reprogrammed based on the two or three waves of COVID-19 peaks in different countries.

For the organization’s operations outside Europe, some countries did allow remote verification of source documents, through innovative remote review systems. Probably most interestingly, the research suggests that the impact of a COVID-19 infection is linked to several cardiac conditions, such as myocardial infarction, stroke, or thrombotic conditions, this required to immediately adapt procedures for timely reporting COVID-19 related clinical events. At ECRI, it has been essential to develop a consistent approach to classify relatedness of procedures or devices to COVID-19, in alignment with the efforts of the European Society of Cardiology, which published in Summer 2020, recommendations for assessment of the interaction between COVID-19 and cardiovascular disease.

To ensure that the organization remains at the top of its game, the scientific advisory board was entirely renewed over the last two years. Generational changes are something that the team pay great attention to, and ensure that ECRI remains at the forefront of the industry, so this turnover ensures that the organization can keep moving forward with bold ideas and new concepts at its forefront. This can clearly be seen through the projects that the team have undertaken over the years, perhaps most obviously in the changeover of 2021.

2021 actually represents a point of inflection for the team, with the end of five clinical trials and the start of three innovative projects. These new projects are focused on the high complexity treatment of coronary artery disease. The OPTIMAL trial (NCT04111770), the IVUS CHIP trial (NCT04854070), and the FAST III trial (NCT04931771) are some of the most innovative in their field, pushing ahead with new ideas and concepts that could have a major impact on clinical practice guidelines. The first two projects will generate data that would clarify the role of intravascular ultrasound imaging in the treatment of complex high risk interventions. To provide the right amount of information, the research team are aiming to enrol up to 2800 patients across both projects. These patients will come from seven different European countries.

The FAST III trial takes a slightly different tack, utilizing a novel technology to determine the severity of coronary stenosis called vessel Fractional Flow Reserve (vFFR). ECRI runs this study through research grants from two technology companies, Pie Medical Imaging in Maastricht in The Netherlands, and Siemens Healthineers AG, based in Erlangen, Germany. The scope of this impressive project showcases the best of what the team can do, acting as a collaborative effort that includes thirty-five centres in seven European countries.

The very nature of ECRI allows it to distinguish itself from other organizations. The institute, by design, focused on the specific needs of cardiologists, with an advisory board includes members who are among the most distinguished academic thought leaders in Europe. As a result, ECRI has become a one-stop-shop for investigator-initiated clinical trials, where grant-givers and investigators can rely on its strengths to manage and monitor the studies. There are very few organizations that can match its reputation for quality, for accuracy and for good solid results.

For further information, please contact Dr. Ernest Spitzer or visit www.ECRI-Trials.com