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Prof. Dr. med. Stefan Schaub

Department of Clinical Research
Profiles & Affiliations

Projects & Collaborations

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The Swiss Transplant Cohort Study (STCS)

Research Project  | 9 Project Members

The STCS was operationally as successful in the current funding period as in previous periods. Between May 2008 and June 2020, 6141 transplantations have been performed in 5879 patients of which 290 were pediatric patients. By end of June 2020, the size of the active cohort was 4839 patients. This important figure corresponds size of the cohort actively followed by the centers on an everyday basis. A total of 149 scientific project are completed or currently run on the data. More than 30 national or international collaborations are in place. Seventy peer-reviewed papers were published or are accepted in total. Representatives of the Swiss Personalized Health Network (SPHN) have become members of the STCS and a close collaboration with the Swiss Biobanking Platform (SBP) is established. During the current funding period, the different working groups achieved 22 of 33 previously stated milestones. The reminder could not be pursued or are yet ongoing. The Data Center is the responsible provider of the STCS data infrastructure. The main tasks include the management of the complex data structure of the STCS, to provide comprehensive public outcome reporting and to support researchers in data management and statistical analysis. In 2020, the data center took moreover the responsibility to act as the scientific IT provider after our current provider had decided to gradually discontinue its activities. Professional data services are essential for the STCS since transplantation is a highly complex medical intervention. Complex processes range from donor recruitment, organ allocation, and organ procurement, to the process of transplantation and post-transplant care. Distinct systems are interrelated and making demanding data integration processes necessary. The STCS is operating a decentralized, center-based Biobank of recipient samples. Since its creation, the STCS harvested 14'448 plasma, 14'297 viable cell samples and 5791 DNA samples in consenting patients. Fifteen percent of all nested projects (NP) used the Biobank over the past years. The genetic dataset of the STCS has been enlarged to 3000 patients with genome-wide data, making the STCS one of the largest cohorts of SOT recipients with long-term follow-up, accurate clinical-, psychosocial-, and genome-wide data. STCS data are available "open access" for research within the framework of the Scientific Committee guidelines and upon EC approval. Next funding period:The current application involves a research-oriented Data Infrastructure and Service (DIS). The described scientific aims only represent a crude summary of the working groups' aims and of the aims of the DIS. In the next period, the scientific strategy of the STCS will mainly consist on consolidating its current scientific groups and study domains, and to build upon and expand on new and timely issues that have become important in transplantation. Moreover, new research initiatives in the personalized medicine area will represent a key aim in future research. The STCS is well positioned to contribute significantly in this regard due to important structure work and networking that took place during the last years. Hence the focus of our research will be on traditional and deep learning methods. A further aim will be to assess the role of Covid-19 in immunosuppressed SOT recipients. A successfully launched SNF-supported platform trials project in collaboration with SHCS is in the set-up phase. A large update of the immunology datasets and the implementation of a new, integrated phenotyping system will add to the clinical interpretation of our transplant immunology research and the use of genetic data to predict immunologic phenotypes is planned. This shall be achieved through candidate gene studies or GWAS. The interdisciplinary Psychosocial Interest Group (PSIG) will analyze psychosocial and behavioral outcomes over the transplant continuum and invest in innovative e-health supported care models allowing personalized health approaches. The Oncology group plans association studies across various types of transplantations and evaluates the progression frequency of patients with previously known monoclonal gammopathy. In collaboration with the STCS Psychosocial Interest Group (PSIG) the oncology group plans to collect information on SOT patients subsequently developing cancer and their risk of poor quality of life and psychosocial status.The Data Center will mainly be in charge of further developing the data infrastructure and services. This includes the following core tasks and challenges: -Development of a structure for the sharing of sensitive patient data between transplant hospitals and the STCS. The SPHN/BioMedIT supported IDEAL project plays a key role in this process.-Implementation of semantic interoperability standards and FAIR principles.

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Swiss Transplant Cohort Study

Research Project  | 4 Project Members

The Swiss Transplant Cohort Study (STCS) is a prospective open multicentre cohort study of all solid organ transplant (SOT) recipients in Switzerland. The project was initiated in 2007 and started to actively enrol patients in May 2008. The project has been funded, among others, by the SNSF as the core funding agency and currently stays in its 4th funding period. The STCS has evolved into the key tool of transplantation outcome research in Switzerland and has gained rapid international recognition due to the high granularity of data and systematic sampling, resulting in a remarkable scientific output. The key strength that made the STCS a prominent research platform is that the leading national experts from various disciplines collaborate under one roof. Over the last years, the number of scientific projects conducted within the STCS network was continuously increasing, with the 100th project approved by the STCS Scientific committee in 2016. Currently, 41 publications appeared in peer-reviewed scientific journals. Transplant infectious diseases continued to be one of the key areas of interest with a particular track record of critical issues in CMV infections. New areas have emerged, such as airway microbiome assessments in lung transplant recipients, T-cell response studies of BK virus infections in renal transplant recipients or genetic host factors of various infectious diseases phenotypes. Since 2012, the STCS collects antibiotic drug resistance data and first results are expected in 2017. Also recently, the genetic dataset has been enlarged to 3000 patients with genome-wide data and 10 published genetic studies of various phenotypes. The Psychosocial Interest Group (PISG) presented novel studies on body weight evolution, the influence of drug adherence and on workability after renal transplantation. Multiple national and international partners collaborate with the STCS for knowledge- and data exchange, resulting in high-ranked publications. A new level will be achieved with the inter-cohort collaboration with the Danish Persimune cohort and the creation of a metacohort with a common research portfolio. The backbone of the STCS is the unique data structure that allows reflecting every transplant type and the monitoring of even more complicated follow-up scenarios. The data involves clinical -, organ-specific -, laboratory -, psychosocial and behavioural -, genetic and infectious disease contents prospectively collected on a long-term schedule. In parallel, bio-banking of plasma, cell and DNA samples takes place at 0 - 6 - 12 months. Moreover, the STCS is legally mandated to keep a limited-registry of non-consenting patients. By the end of 2016, the STCS centres enrolled 4023 patients with 4187 transplantations, and a total of 4392 transplanted organs. During a maximum follow-up of nearly 9 years, 545 patients died (13.5%) and only 42 patients were lost to follow-up (1%). 93% of all Swiss transplant recipients provided written informed consent to the full STCS datasets, and 99% of consenting patients contributed to the STCS bio-bank. The STCS publishes comprehensive reports for the public and key federal institutions, such as the Federal Office of Public Health, UniMedSuisse and the Swiss Highly Specialized Medicine Board. In 2017, clinical transplant experts conducted in-depth reviews of all datasets and defined the necessary adaptations for the next upgrade (STCS generation 3). Furthermore the genetic working group was created to coordinate funding of extended genotyping and regulate the further use of genetic data. By May 2017, 76 persons were working for the STCS corresponding to 23.8 full-time equivalents being financed by SNF, third party, and own funds. For the next funding period, the STCS will face a number of significant challenges. Patients will be involved more closely to specify their needs and integrate their priorities. In addition to the two randomized trials ongoing and in preparation, additional trials are planned to improve the management of infectious complications post-transplant. The immunological datasets need an update to enable high-quality immunological studies. The current data model will expend towards an interoperability platform to link hospital routine care- and lab data from the centres using the standards proposed by the Swiss Personalized Health Network (SPHN). Conclusion: At the end of four SNF funding periods, the STCS represents a transplant cohort with a patient volume largely above 4000, that experiences large international recognition and that serves a broad variety of clinical, translational, interventional, psychosocial, and health services research. The presented approach to expand the data model towards a data and interoperability platform will prepare the STCS to enter the personalized health area.

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Urine CXCL10 chemokine monitoring post-renal transplant: a randomized controlled effectiveness trial

Research Project  | 3 Project Members

Renal replacement therapy due to end-stage renal disease is common (~3700 Swiss are currently on dialysis) and costly (~100'000 CHF/patient/year). Transplantation is the therapy of choice for many patients due to improved survival, better quality of life and it has significant cost-savings after the first year post-transplant compared to dialysis (~80'000 CHF/patient/year).A major challenge in transplantation is how to optimize anti-rejection therapy to balance the risk of rejection from under-immunosuppression against the risk of infections/cancer from over-immunosuppression. The ideal regimen would provide the minimum therapy to avoid complications while being sufficient to prevent rejection, which accounts for ~50% of death-censored allograft failures. In the 1st year post-transplant, 30% patients have rejection of which 2/3 is not detected by currently used standard-of-care tests (i.e. serum creatinine, proteinuria). Accurate non-invasive tests are required so that rejection can be treated early and anti-rejection therapy optimized.We have identified new non-invasive urine tests to detect early pre-clinical rejection (i.e. CXCL10 chemokine) and to predict long-term outcomes (i.e. CXCL10 and CCL2) in kidney transplantation. We showed that urine CXCL10 detects rejection better than standard-of-care tests. The primary goal of this two-center, randomized clinical trial is to evaluate the effectiveness of urine CXCL10 monitoring to detect early pre-clinical rejection and to determine if its treatment improves important kidney transplant outcomes. Secondary goals are the characterization of urine CXCL10 kinetics in response to anti-rejection therapy, and the independent validation of urine CXCL10 and CCL2 for prediction of intermediate and long-term outcomes. This trial is the first of its kind to evaluate the impact of a monitoring by an early rejection biomarker on transplant outcomes. If successful, implementation of the biomarker for clinical practise can be envisioned. These new urine tests may be used to personalize medicine and improve patient and transplant outcomes. Finally, strategies that improve transplant outcomes may result in significant long-term health care savings.

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Swiss Transplant Cohort Study PSIG

Research Project  | 10 Project Members

The Swiss Transplant Cohort Study (STCS) is a prospective open multicentre cohort study of all solid organ transplant (SOT) recipients in Switzerland. The project was initiated in 2007 and started to actively enrol patients in May 2008. The project has been funded, among others, by the SNSF as the core funding agency and currently stays in its 4th funding period. The STCS has evolved into the key tool of transplantation outcome research in Switzerland and has gained rapid international recognition due to the high granularity of data and systematic sampling, resulting in a remarkable scientific output. The key strength that made the STCS a prominent research platform is that the leading national experts from various disciplines collaborate under one roof. Over the last years, the number of scientific projects conducted within the STCS network was continuously increasing, with the 100th project approved by the STCS Scientific committee in 2016. Currently, 41 publications appeared in peer-reviewed scientific journals. Transplant infectious diseases continued to be one of the key areas of interest with a particular track record of critical issues in CMV infections. New areas have emerged, such as airway microbiome assessments in lung transplant recipients, T-cell response studies of BK virus infections in renal transplant recipients or genetic host factors of various infectious diseases phenotypes. Since 2012, the STCS collects antibiotic drug resistance data and first results are expected in 2017. Also recently, the genetic dataset has been enlarged to 3000 patients with genome-wide data and 10 published genetic studies of various phenotypes. The Psychosocial Interest Group (PISG) presented novel studies on body weight evolution, the influence of drug adherence and on workability after renal transplantation. Multiple national and international partners collaborate with the STCS for knowledge- and data exchange, resulting in high-ranked publications. A new level will be achieved with the inter-cohort collaboration with the Danish Persimune cohort and the creation of a metacohort with a common research portfolio. The backbone of the STCS is the unique data structure that allows reflecting every transplant type and the monitoring of even more complicated follow-up scenarios. The data involves clinical -, organ-specific -, laboratory -, psychosocial and behavioural -, genetic and infectious disease contents prospectively collected on a long-term schedule. In parallel, bio-banking of plasma, cell and DNA samples takes place at 0 - 6 - 12 months. Moreover, the STCS is legally mandated to keep a limited-registry of non-consenting patients. By the end of 2016, the STCS centres enrolled 4023 patients with 4187 transplantations, and a total of 4392 transplanted organs. During a maximum follow-up of nearly 9 years, 545 patients died (13.5%) and only 42 patients were lost to follow-up (1%). 93% of all Swiss transplant recipients provided written informed consent to the full STCS datasets, and 99% of consenting patients contributed to the STCS bio-bank. The STCS publishes comprehensive reports for the public and key federal institutions, such as the Federal Office of Public Health, UniMedSuisse and the Swiss Highly Specialized Medicine Board. In 2017, clinical transplant experts conducted in-depth reviews of all datasets and defined the necessary adaptations for the next upgrade (STCS generation 3). Furthermore the genetic working group was created to coordinate funding of extended genotyping and regulate the further use of genetic data. By May 2017, 76 persons were working for the STCS corresponding to 23.8 full-time equivalents being financed by SNF, third party, and own funds. For the next funding period, the STCS will face a number of significant challenges. Patients will be involved more closely to specify their needs and integrate their priorities. In addition to the two randomized trials ongoing and in preparation, additional trials are planned to improve the management of infectious complications post-transplant. The immunological datasets need an update to enable high-quality immunological studies. The current data model will expend towards an interoperability platform to link hospital routine care- and lab data from the centres using the standards proposed by the Swiss Personalized Health Network (SPHN). Conclusion: At the end of four SNF funding periods, the STCS represents a transplant cohort with a patient volume largely above 4000, that experiences large international recognition and that serves a broad variety of clinical, translational, interventional, psychosocial, and health services research. The presented approach to expand the data model towards a data and interoperability platform will prepare the STCS to enter the personalized health area.