Projects

AMIS Plus: National Registry of Acute Myocardial Infarction in SwitzerlandThe AMIS Plus national registry collects and analyzes data on patients with acute myocardial infarction in Switzerland in the pre-admission, hospital and follow-up phases. Emphasis is placed on the evaluation of risk factors, diagnostics, urgent therapy strategies and treatment. AMIS Plus data are important for quality assurance, assessing guidelines, improving compliance with guidelines in clinical practice, verifying whether results of randomized clinical trials are translatable into everyday clinical practice, investigating patient groups not extensively studied in large randomized trials and improving therapeutic strategies.

Project lead: Dragana Radovanovic

Specifically, our interdisciplinary work focuses on novel Variants of Concern (VOC) of SARS-CoV-2

Our five main objectives are:

1. Identifying emerging new VOCs through genomic surveillance in different cohorts;
2. Deciphering the risk and protective factors to infection in different risk, gender and age groups;
3. Evaluating the impact of VOCs on the effectiveness of vaccines induced humoral and cellular responses in various populations and regions in the EU and South Africa;
4. Identifying immune correlates of protection against VOC through the development of algorithms predicting the impact of emerging VOC on the efficacy of vaccines; and
5. Informing the future vaccination strategy and design of next generation of vaccines.

For more information please see the project page: https://covicis.eu 
Further Research on SARS-CoV-2:Link

Project lead: Milo Puhan
Funding: EU Horizon Europe program

Over the past two decades, digital innovation has transformed all aspects of life. In recent years, academia, as well as the industry, have been exploring the potential of digital tools to improve human health, such as through the use of big data and artificial intelligence. The impact of that digital transformation is promising, but still attached to much uncertainty. Will healthcare become less expensive? Will digital innovation benefit all equally? What does Switzerland need to benefit from these processes? This project aims answer these questions by identifying Switzerland's needs and potential, as well as by creating a national policy roadmap for digital health innovation. The project’s methods include both established tools and more innovative approaches, drawing on the experience and knowledge of key players across Switzerland.

The EBPI will oversee and conduct two literature reviews that will contribute to this project: One review on the use of imaging-based machine learning for the diagnostic and prognostic purposes of major chronic diseases and a second review on the use of electronic cohorts in epidemiology and public health.

Project lead: Milo Puhan & Effy Vayena (ETHZ)
Funding: Swiss National Science Foundation

With an estimated 3'200 deaths yearly, lung cancer is the leading cause of cancer-related death in Switzerland. Every year about 4'300 new lung cancer cases are diagnosed (4’363 in 2015, 4’252 in 2014, 4’293 in 2013). The major risk factor for lung cancer is smoking: incidence and mortality closely follow smoking trends with a time-lag of around 20 – 30 years.
This explains why death rates in Switzerland are declining in men, but increasing in women. Given that lung cancer has a detectable, yet frequently asymptomatic pre-clinical phase with an effective treatment option (i.e. surgery), the effectiveness of early screening methods has been extensively investigated over the last 20 years.
Low-dose computed tomography (LDCT) is a sensitive imaging technique allowing detection of early stage lung cancer. Importantly, an appropriate diagnostic and treatment strategy achieves a reduction in lung cancer-specific and all-cause mortality. The results of the US National Lung Screening Trial (NLST) showed that lung cancer screening significantly reduced lung cancer mortality by 20%.The results of another landmark study, the Dutch-Belgian Lung Cancer Screening Trial NELSON, presented for the first time in September 2018 at the 19^th World Conference on Lung Cancer, demonstrated a 26% reduction in lung cancer deaths. In a smaller subset of women, LDCT screening even reduced mortality by as much as 50%. The NELSON trial is also of key importance since the volume-based approach to assess lung nodules substantially reduced false positive results and associated harms. These developments unambiguously confirm that lung cancer screening has the potential to save lives and our recent micro-simulation study indicated that this is likely to be a cost-effective intervention (around 30’000 Swiss Francs per life year saved). To date, the USA, UK, and Poland are still the only countries where lung cancer screening with LDCT has been or is being implemented following recommendations of various international associations.
In Europe, most countries including Switzerland still await publication of the NELSON study and an updated health technology assessment on which the decision for or against implementation of a lung cancer screening program would be based on. Much of the hesitation arises from the high false positive rate in the NLST trial and potential harms from diagnostic follow-up (e.g. repeated CT scans, as well as CT-guided, bronchoscopic, and surgical biopsies) or treatment.

In addition, although LDCT screening is likely to be cost-effective (which is a relative term), the cost impact (i.e. the absolute cost) of LDCT screening is substantial: Assuming a participation rate of 10% of all eligible persons, the additional annual cost is estimated around 16 Mio Swiss Francs. This project will address this area of unmet need in Switzerland by exploring the following aims:
(1) To assess the feasibility and financing of a high-quality LDCT lung cancer screening program with quality assurance in Switzerland from the multi-stakeholder perspective of persons eligible for lung cancer screening, health care providers, and the health care system.
(2) If aim (1) is deemed feasible and affordable, to establish standard operating procedures (SOPs) and a quality assurance program for the implementation of a LDCT lung cancer screening program in close collaboration with involved Swiss national stakeholders.
Download: Schweizer Screening-Programm für Lungenkrebs, Initial Lay Summary (PDF, 547 KB)

Project lead: Milo Puhan & Thomas Frauenfelder
Funding: Swiss Lung Association

Harnessing the vast amounts of observational data available today requires a nuanced approach beyond mere application of machine learning techniques. Effectively decoding such multidimensional problems demands an understanding of not just patterns, but also causality and the processes underlying the data. Traditional reductionist approaches, however, often stumble in the face of high-dimensional complexity. Our aim is to marry these two methodologies, navigating the complexity while anchoring our exploration in robust scientific principles. One such multifaceted issue is Multimorbidity (i.e., the presence of multiple chronic conditions within an individual patient) is one of the great societal health challenges of our time. The global burden is enormous and multimorbidity is the biggest driver of health care cost. High-quality, actionable research is urgently needed to inform effective, safe and patient-centered care in multimorbid patients. Our project will develop and implement a much-needed, novel research paradigm bringing together subject knowledge, methods expertise from conventional medical research, Machine Learning (ML) and Mathematics. We seek to deliver innovative, actionable methods to transform the paltry evidence-base while appropriately handling the high degree of complexity in the treatment of patients with multiple chronic conditions. Our consortium consists of leading scientists from Epidemiology (Milo Puhan, Viktor von Wyl, Miquel Serra Burriel), Particle Physics (Nicola Serra), Pharmacoepidemiology (Andrea Burden) and Mathematics (Alessio Figalli, Ashkan Nikeghbali) as well as Medicine (Cynthia Boyd, Oliver Senn, Gregory Lucas), Health Economy (Simon Wieser) and Computer Science (Andrey Ustyuzhanin). The project is hosted the University of Zurich and the Federal Institute of Technology.
PhD position in Epidemiology:
The focus of this position will be on the development methods and applications for causal inference and benefit harm balance modelling in the area of treatments for patients with chronic conditions. Candidates should have a MSc degree in epidemiology, biostatistics, econometrics or another field that brings together data science and subject knowledge. A strong interest for quantitative methods and collaborating across fields is required.

Project lead: Milo Puhan, Nico Serra, Andrea Burden (ETH), Alessio Figalli (ETH)
Funding: SNF SINERGIA

We perform Health Technology Assessments (HTAs) for the Swiss Medical Board, in cooperation with units at the Universities of Basel and Geneva. Our contributions focus on the health economic characteristics (cost-effectiveness, budget impact) of medical strategies. Another part of the project is the development of HTA methodology approrpriate for Switzerland.
For more information and to participate please visit the project page

Project lead: Milo Puhan
Funding: Swiss Medical Board

The primary objective of this project is to design a triage intervention at the point of primary care to provide palliative care support to COPD patients and their families depending on their COPD-related burden of suffering. Specifically, we aim to identify patients’ disease awareness, unmet patients’ needs, lack of relatives’ involvement and misconceptions about palliative care in order to triage patients and relatives into 3 groups based on care needs: 1) continue care as it is, 2) integrate palliative care, for example, with Living well with COPD, or 3) integrate or provide a referral to specialized palliative care. The secondary objective of the proposed project is to assess the feasibility, acceptability and usability of the triage intervention in clinical practice within an exploratory study. This will provide unique evidence about appropriate key components for a full-scale randomized controlled trial. To our knowledge no comparable triage intervention exists. Our intervention allows us to consider patients and relatives as the unit of care and strengthen the patients' autonomy and self-determination. This will shift COPD management away from diseases and health settings to a new paradigm of managing the whole spectrum of needs of patients and relatives.

Project lead: Milo Puhan
Funding: LUNGE Zürich

Hintergrund
Für Menschen mit der Lungenerkrankung COPD ist regelmässiges Krafttraining zur Erhaltung und Stärkung der Muskulatur besonders wichtig. Jedoch nehmen aktuell nur wenige Betroffene an einem regelmässigen Trainingsprogramm teil. Manchmal ist der Weg in das Fitnesscenter oder zum Physiotherapeuten zu beschwerlich, oder die erlernten Übungen können zu Hause nicht ins tägliche Leben integriert werden. Um COPD-betroffene Personen besser unterstützen zu können, entwickelten wir am Institut für Epidemiologie, Biostatistik und Prävention (EBPI) der Universität Zürich das HOMEX Trainingsprogramm (Kurzform von «Home Exercise», = Heimtraining), das ohne zusätzliche Geräte optimal zu Hause durchführbar ist.
Das HOMEX-Trainingsprogramm
Kurze aber regelmässige Trainingseinheiten
Für das HOMEX-Trainingsprogramm braucht es lediglich einen Stuhl und Trainingsbänder (Theraband), die zur Verfügung gestellt werden. Insgesamt gibt es 38 Übungen zur Kräftigung und Dehnung von Armen, Beinen und Rumpf, die in verschiedenen Schwierigkeitsgraden und mit unterschiedlicher Anzahl an Wiederholungen absolviert werden können. Jede Übung ist auf einer Trainingskarte illustriert. Ziel ist es, dass die Teilnehmenden an sechs Tagen pro Woche während 15 – 20 Minuten ausgewählte Übungen zu Hause absolvieren. Das Programm ist sowohl für Trainingsanfänger als auch für aktivere Menschen geeignet.
Persönlicher Betreuer
Teilnehmer und Teilnehmerinnen der Trainingsgruppe werden während eines Jahres durch einen persönlichen Betreuer begleitet und unterstützt. Zu Beginn besucht der Betreuer die Teilnehmenden drei Mal zu Hause, um sie in die Übungen einzuführen und die konkrete Durchführung zu planen. Für eine zusätzliche Unterstützung finden während eines Jahres begleitende Telefongespräche statt. Somit ist ein individuelles Training möglich und es kann gewährleistet werden, dass die Übungen richtig ausgeführt und allfällige Motivationsschwierigkeiten gemeinsam mit dem Betreuer überwunden werden können. Die mitgelieferte Trainingsagenda gibt vor, wann welche Körperpartie trainiert wird, sodass das Training möglichst effektiv und einfach durchführbar ist. Darin werden auch die Trainingsverläufe, die kurz- und langfristigen Ziele sowie die Erfolge oder eventuelle Rückschläge dokumentiert, die dann regelmässig mit dem persönlichen Betreuer besprochen werden können.
Wissenschaftliche Studie – Studienteilnehmende gesucht
Um die Effekte von „HOMEX-Daheim turnen“ auf die Lebensqualität, Atemnot und körperliche Leistungsfähigkeit bei Personen mit COPD überprüfen zu können, führen wir zum HOMEX-Trainingsprogramm eine begleitende Studie durch.
Dafür suchen wir Teilnehmende, die:

•    von der Lungenkrankheit COPD betroffen sind
•    mindestens 40 Jahre alt sind
•    in den vergangenen 12 Monaten an KEINER ambulanten
     oder stationären Lungenrehabilitation teilgenommen haben
•    bereit sind, ein Jahr an einer wissenschaftlichen Studie teilzunehmen

Studienteilnehmende werden zufällig (Chance 50:50) in zwei verschiedene Gruppen eingeteilt: In die Trainingsgruppe, welche während eines Jahres das HOMEX-Programm absolviert, und in die Kontrollgruppe, welche kein Trainingsprogramm durchführt, nach Abschluss der Studie aber die Trainingskarten und –bänder ebenfalls erhält. Wir laden alle Teilnehmenden zu Studienbeginn und nach einem Jahr zu uns ans Institut (Nähe Zürich Hauptbahnhof) ein. Dort finden Studien-Messungen zu ihrem Gesundheitszustand statt (Reisespesen werden vergütet).  Erlebnisbericht einer Teilnehmerin von HOMEX 1: Lunge Zürich

Project lead: Anja Frei
Funding:
HOMEX 1: Research Fund of the Swiss Lung Association Berne and Research, Fund of Klinik Barmelweid
HOMEX 2: Research Fund of Lunge Zürich

Obesity (adipositas) is a global health problem and a major risk factor for developing multiple chronic diseases, including type 2 diabetes, fatty liver, and high blood pressure which may contribute to a premature death. Cortisol is a stress related hormone, which if produced or used at high amounts results in health issues similar to those of obese individuals. Cortisol may play an important role in the development of obesity related co‐morbidities and offers a target for personalized treatment strategies. LOOBesity seeks to understand what makes obesity so risky for some patients, but not for others. This knowledge will be used for personalizing therapies according to individual molecular and imaging characteristics, the best available evidence from treatment trials, and patient preferences. We will use a prospective randomized clinical trial to determine whether a personalized treatment strategy that modulates cortisol action can help patients enjoy the maximum benefits and minimal harms of treatments for obesity. Our research team is in a unique position to combine molecular and imaging methods and advanced machine learning to extract detailed measurements of fat distribution and function. This will offer the possibility to introduce fast and less expensive MRI protocols and novel molecular methods as a future routine screening tool for obese patients and provide a firm basis for personalized approaches for obese patients with far reaching prospects for clinical practice.

Project lead: Milo Puhan & Felix Beschlein (USZ)
Funding: The Loop Zurich

Mobility – how well we walk – is an important marker of health; a slow walking speed is associated with greater mortality, morbidity, cognitive decline, dementia, and fall risk. As the population ages, the number of people experiencing mobility challenges is expected to rise. However, accurately assessing people’s mobility, especially in the real daily life world, is far from easy. The European Innovative Medicines Initiatives funded Mobilise-D project will develop a comprehensive system to monitor and evaluate people’s gait based on digital technologies, including sensors worn on the body. The project focuses on conditions which often affect mobility, namely chronic obstructive pulmonary disease (COPD), Parkinson’s disease, multiple sclerosis, hip fracture recovery, and congestive heart failure. The Mobilise-D results will help to improve the accurate assessment of daily life mobility in clinical trials and patient treatment, thereby contributing to improved and more personalized care. Within the framework of Mobilise-D, the University of Zurich leads the conduct of the review work, is responsible for the establishment of the clinical COPD cohort from Switzerland and contributes to statistical analysis, evaluation of results and data availability.
For more information or to participate please visit the project page.

Project lead: Milo Puhan & Patrick Brun, Berner Reha Zentrum, Heiligenschwendi, Marc Spielmanns, Zürcher RehaZentren, Klinik Wald & Thomas Sigrist, Klinik Barmelweid
Funding: Innovative Medicines Initiative (IMI)

Peri-Operative Outcome Research In 2008, the World Health Organization (WHO) has recognized that surgical complications account for a large proportion of preventable medical injuries and deaths globally and deemed it a global public health issue. Over 200 million operations are conducted worldwide every year. Up to 16% suffer from post-surgery complications. In Switzerland, there are over one million patients hospitalized every year and almost half of them are treated with surgery or another at least minimally invasive medical intervention. Postoperative complications can cause severe reduction in quality of life for patients and are also a major driver for healthcare costs. Measuring healthcare outcomes in and after surgery, however, is challenging. To compare different postoperative treatment paths or new surgical techniques, or to define the required minimum case volume for a hospital, researchers and clinicians lack convincing and standardized endpoints as well as sufficient research funding. As safety of surgery has improved dramatically over the last decades the postoperative mortality is very low. The focus has shifted to the still substantial postoperative burden from complications, that may, depending on the type of procedure, occur up to two years after surgery. Complications have become a key indicator of surgical quality and early recognition of complications are highly predictive for the entire postoperative burden and may be used for timely preventive interventions. They present a huge burden for the patient, the doctor and are also directly connected to raising health care costs.
At the EBPI, we have a research focus on perioperative and more long-term outcomes of surgery. We develop instruments to measures postoperative outcomes and means to reduce surgical complications together with our colleagues from surgery and perioperative medicine. We currently work on the following projects: Instruments to measure postoperative outcomes We developed a new index with the inclusion of the Clavien-Dindo classification, which now summarizes all postoperative complications in a single continuous number, the Comprehensive Complication Index (CCI®). The CCI addressed the need to capture the entire postoperative burden and not just single complications. The CCI® is based on the complication grading by the Clavien-Dindo Classification and captures every complication that occurred after an intervention. The overall morbidity is returned on a scale from 0 (no complication) to 100 (death) and reflects the gravity of this overall complication burden on the patient. The CCI® was developed together with patients to ensure the patients’ perspective is represented in the scale. In order to be able to calculate the CCI® easily and quickly in clinical practice, the team has set up a website with an online CCI calculatorwww.assessurgery.com. We currently have projects to further develop the CCI and implement it in surgical practice.

Benchmarking in surgery “Benchmarking"
Means comparing one's own business processes and key performance indicators with the best practices of other companies. The dimensions typically measured are quality, time and costs. Applied to surgery, this involves defining the best possible outcomes, for example in major liver surgeries or liver transplants. The introduction of standardized benchmarks for complex procedures can lead to improved patient outcomes or surgical performance and ultimately reduce costs. We currently have projects to apply and further develop the approach to benchmarking in surgery. PubMed Link to publications on surgical outcome assessment and benchmarking: Link to website:here

Outcome4Medicine Consensus Conference (June 2022)
With the OUTCOME4MEDICINE initiative, we brought together evidence and expertise from around the world and let a jury of citizen non-experts find a consensus on how outcomes after medical interventions should be assessed, interpreted, and communicated to the public to further improve patient-centered surgical care.. We followed a proven format involving evidence reports from experts, conducted by 9 panels representing different perspectives. At the OUTCOME4MEDICINE conference, the experts presented their findings in individual sessions and answered questions from the jury and audience creating the basis for an interactive dialogue between scientists and the attending public. This created a truly innovative way to build bridges between healthcare providers, patients, and policy makers for a more fruitful and open communication. The non-expert citizen jury members for OUTCOME4MEDICINE were selected in regard to their various and complementary profiles but without direct background in outcome research for developing final and unbiased recommendations. The main publication of the conference will be published in 2023. Link to website: here

Swiss-AF is a prospective cohort study of Swiss atrial fibrillation patients, coordinated by the University of Basel and funded by the Swiss National Foundation. The cohort aims to generate new insights into the interrelationships between atrial fibrillatiobn, structural brain alterations and cognitive decline, in a long-term perspective. This will help to define new solutions for this crucial public health issue. We are responsible for prospective health economic data collection alongside the clinical part. While data are maturing, cost-of-illness studies, cost-effectiveness analyses and research on other topics are being planned.

Project lead:  Yuki Tomonaga
Fundung: Swiss National Science Foundation

SARS-CoV-2 vaccines, along with other public health measures, have been highly efficacious in reducing infections and mortality worldwide. However, with the emergence of several variants of concern with increased transmissibility and immune-evasive properties, the SARS-CoV-2 pandemic continues to be a threat to public health. Further understanding of the development of vaccine-induced immunity, in the presence of booster and additional vaccinations and breakthrough infections, remains necessary.
The Zurich SARS-CoV-2 Vaccine Cohort study was conceived shortly after the roll-out of the first SARS-CoV-2 vaccines in the Canton of Zurich. It is an ongoing population-based longitudinal cohort study of 575 randomly selected individuals presenting for primary SARS-CoV-2 vaccination at the University of Zurich vaccination center, the reference center for the Canton of Zurich. Individuals are assessed in regular intervals up to 3 years after vaccination aiming to evaluate antibody and T cell immune responses, potential breakthrough infections, and health outcomes over time. The objectives of the study are the following:

Primary objectives:

1. Characterize the presence, dynamics and persistence of antibodies produced in response to the different SARS-CoV-2 vaccines over time.
2. Assess the presence and durability of SARS-CoV-2 specific T cell responses, as well as antigen specificity and phenotype in response to the different SARS-CoV-2 vaccines over time.

Secondary objectives:

1. Assess the relationship between antibody and T cell immune responses against SARS-CoV-2 induced by different SARS-CoV-2 vaccines.
2. Assess the occurrence of new SARS-CoV-2 infection (breakthrough infection) after vaccination and determine its association with SARS-CoV-2 binding and neutralizing antibodies and T cell responses
3. Evaluate the occurrence and severity of adverse effects among individuals  who received a SARS-CoV-2 vaccine.
4. Compare the humoral and cellular immune response between individuals with SARS-CoV-2 infection and those who received a SARS-COV-2 vaccine.
5. Compare the humoral and cellular immune response to different SARS CoV-2 vaccines with immune responses to other common vaccines.

For further information, please contact the study team via e-mail: zhcorona-impfstudie AT ebpi.uzh.ch.
Corona Immunitas
ISRCTN Registry

Project lead: Milo Puhan
Funding: Uniscientia Foundation and Swiss School of Public Health (in the frame of Corona Immunitas)

Geographic variation in the utilisation of healthcare services for chronic diseases
may indicate over- or underuse. Positive and negative clinical recommendations (e.g. within clinical guidelines, HTA reports or Choosing Wisely lists) and other factors may influence the degree of variation.
We will use health insurance claims data to describe geographic variation in the
use of healthcare interventions for chronic diseases in Switzerland. Associations with recommendation status and other factors will be assessed, e.g. using multilevel (linear mixed) regression modelling. Summary indicators of appropriateness of utilisation per geographic unit will be developed. Relationships with healthcare expenditure will be assessed; the applicability and usefulness of novel methods of analysis (trajectory analysis; 'counterfactual distributions') will be studied in this context. The status, quality and management of recommendations in Switzerland will be thoroughly assessed for eligible interventions (e.g. using the AGREE instrument).
Project results will have multifold implications for Swiss health policy makers and players in the healthcare system. To support dissemination, findings will be made publicly available on the internet. This and additional routes of dissemination will be pursued in cooperation with, at a minimum, physisican organisations, health insurance representatives and the Swiss cantons. The development of internet content will also involve patient organisations.

Project lead: Matthias Schwenklenks
Funding: Swiss National Science Foundation, as part of NRP 74 'Smarter Healthcare'. It is performed in cooperation with a large provider of health insurance (Helsana), the Swiss Academy for Quality in Medicine / FMH, and other partners.