End stage kidney disease ranks among the most severe chronic non-communicable diseases with an unmet medical need, given the high (between 10 and 15%) and stable annual mortality rates. Kidney replacement therapy is necessary when kidney function is below 10% of the normal value. Much effort is put into developing strategies to prevent chronic kidney disease progression. Regenerative medicine still is in the experimental phase and kidney transplantation is only available for a small number of patients. Indeed, the everyday reality is the growing number of dialysis patients. Haemodialysis treatment is the current standard of care for the vast majority of patients with end stage kidney disease. It is a substantial burden to the patient and for society. Haemodialysis treatment is associated with high risks for fatal and non-fatal cardiovascular disease, for infections, hospitalisation and low quality of life. Improvement in the currently available standard is urgently needed. Over the past decade an alternative for haemodialysis became available, i.e. haemodiafiltration. Both are accepted by regulatory authorities. Haemodiafiltration removes waste products that are accumulated due to kidney failure, more effecticvely than standard hemodialysis. Present evidence supports the idea of superiority of haemodialfiltration compared to standard haemodialysis. However, definite proof is lacking and as a consequence haemodiafiltration is not yet widely applied. This consortium aims to determine the best possible dialysis treatment by comparing the conventional guideline based haemodialysis treatment versus high-dose haemodiafiltration by carrying out a prospective randomized controlled clinical trial addressing clinical endpoints, quality of life and a cost-utility analysis. The study will deliver an answer on the question which intervention gives the best value for money. Therefore, it will be considered a “land mark” study, allowing to publish an “end of discussion” paper

In this project, we will evaluate the use and performance of a CE-marked device (wearable), which uses sensors to measure breathing rate, pulse rate, skin temperature, and heart rate variability for the purpose of early detection and monitoring of COVID-19 in general and high-risk populations. At the same time, a mobile application will be used to track participant-reported symptoms. A prospective, observational study will follow 13,000 individuals from the general population and 7,000 high-risk individuals wearing the device and responding to participant self-report parameters via a purpose-designed app. Based on this data, an algorithm will indicate which individuals likely require general practitioner (GP) care (for COVID-19 diagnostic testing, further vital signs assessment, and/or treatment) and/or hospital care. To evaluate algorithm performance, the cohort will be tested for COVID-19 antibodies at the end of follow-up. COVID-19 seropositivity in the intervention cohort will be compared seropositivity in a control population of 20,000 individuals drawn from the same populations using the application only. Thus, this project will deliver a large body of information on COVID-19 PCR testing and antibodies that can be used to develop additional diagnostics and therapeutics in addition to validating remote vital signs and self-reported symptoms monitoring systems.

In our HIT-CF project, we aim to bring personalised disease modifying therapies to cystic fibrosis (CF) patients with ultra-rare CFTR mutations, who could otherwise never get access to such treatment. Once we have proven our unique concept, the CF community can easily extend our state-of-the-art methodology to all CF patients such that HIT-CF will impact the entire CF field. We will achieve our goals by means of a randomised, double-blind, placebo-controlled, repeated-crossover, three-armed platform trial with prospectively defined meta-analysis to evaluate efficacy at group and individual level. HIT-CF is designed to enable access to the most relevant global drug products, and each trial arm will test a drug product candidate (a single compound or a compound combination) from one of our pharmaceutical consortium partners. The patients will be assigned to the specific trial based on the effect of the drug product candidates on cultured intestinal miniature organs (termed organoids) grown from rectal biopsies, instead of based on typical genotyping only. In parallel with this H2020 project, our pharmaceutical partners will obtain market approval of their drug product candidates for common (F508del or gating) mutations in the CFTR gene. Ultimately, our project will enable ‘managed’ off-label access to these therapies towards patient groups or individuals who show response to the therapy in a prospective intestinal organoid test. One of the major impacts of this project will be the innovative methodologies to acquire reimbursement for current and future off-label treatments of people with CFTR mutations. This will represent a real paradigm shift in CF treatment as it implements a new type of personalized medicine paradigm based on organoids, by shifting therapeutic trials from patients to the laboratory.

With over 12 million cancer survivors relying on supportive care across the EU, it is essential to provide them with (cost-)effective interventions tailored to their specific needs. Many survivors suffer from long-term side effects that can lower their quality of life (QoL), functioning, and productivity. Exercise interventions have proven to be uniquely beneficial in managing both physical and psychological complaints. However, their effects are strongest when tailored to a patient's specific burden, e.g. fatigue, low physical fitness, anxiety and depressive symptoms or chemotherapy-induced peripheral neuropathy. Moreover, the use of exercise interventions in supportive cancer care is still limited due to a lack of availability, a lack of accessibility caused by time and travel constraints and low awareness. To tackle these hurdles, the PREFERABLE-II consortium sets out to design and demonstrate the (cost-)effectiveness of a novel exercise intervention that: 1) will be tailored to the side effect that bothers the survivor the most, by use of a modular design, 2) can be implemented at home, with live-remote supervision from a national broadcast centre, 3) is available to all cancer survivors, and 4) incorporates improved patient-centred communication and shared decision making. Results of our RCT, enrolling 350 cancer survivors, will be translated into guideline recommendations for exercise-oncology. Extensive ethical, legal and social impact components of the project will reveal barriers and facilitators of live-remote supervised exercise and provide policy recommendations to further support implementation. Finally, we will create communication standards and an education module for healthcare professionals to train the future workforce. As such, PREFERABLE-II contributes to improving the QoL of cancer survivors by lowering the burden of side effects, while also improving availability, access and awareness off exercise-based supportive care interventions.

Despite the tremendous improvement in early diagnosis and treatment of breast cancer, a large proportion (up to 40%) of patients with breast cancer will eventually develop metastases. Patients with metastatic breast cancer (MBC) have a median overall survival of 2-3 years, and a relative 5-year survival of 34%. Current advances in therapy have extended the life of those patients with MBC, however these patients still suffer (for longer periods) from deleterious side-effects (either related to the disease itself or to the treatment) such as fatigue, pain, nausea and vomiting, insomnia, dyspnoea, emotional, social and cognitive dysfunction. Among all these side-effects, fatigue is the most common and distressing treatment-related side-effect, as up to 90% of patients with MBC experience fatigue over the course of treatment. All these symptoms negatively affect patients’ QoL and thus an urgent solution is needed to help those with advanced breast cancer to “live well” for as long as possible. PREFERABLE’