Nicole Probst-Hensch, Co-Authors
Switzerland has launched the Swiss Personalized Health Network (SPHN) to ensure that Swiss research is a competitive global player in precision health. In the US, for example, of the US$ 215 million invested in the Precision Medicine Initiative, US$ 130 million are allocated to building a national research participant group, the 1 million citizen All of Us cohort, with an associated biobank . This underscores the importance of complementing routinely collected health data, including e-health data, with population-based data and a biobank. One reason for this is that the health status of an individual is governed by long-term exposure to multiple factors that are not adequately and prospectively captured via encounters in the routine healthcare setting.
In our view a question of utmost importance for our country is: What relevant research and health problems can only be addressed by a sufficiently large Swiss citizen study comparable to All of Us or other equivalent initiatives in Europe and across the globe?1. UNDERSTANDING CAUSAL AND MODIFIABLE DISEASE RISKS, PROTECTIVE FACTORS AND MECHANISMS
To improve understanding of diseases and aging from observational associations towards better mechanistic and causal understanding through refined exposure assessment and interrogation of biology such as
- Do novel brain imaging patterns allow to predict the risk of mental disorders (e.g., Alzheimer’s disease) ?
- Is the gut microbiome composition a causal risk factor for specific infections or noncommunicable diseases and what is the role of diet ?
- Why does higher cardiorespiratory fitness has such a strong impact on mortality ?
- Can we identify aging biomarkers by comparing patients with accelerated aging such as spinal cord injury or human immunodeficiency virus infection (HIV) (participants in patient cohorts) with healthy citizens (participants in citizen cohorts) ?
- What are the mechanisms leading to specific multimorbidities [10, 11]?
To derive evidence-based personalised risk prediction algorithms for identifying citizens at risk
- Which combinations of endogenous and exogenous factors predict risk of diseases and multimorbidities (e.g., cardiovascular disease and depression) in the Swiss population best ?
To evaluate long-term disease risk patterns from a socio-economic perspective
- What is the long-term effect of diseases and their risks on the labour market and economic outcomes ?
- What is the long-term cost-effectiveness of specific preventive interventions ?
To design evidence-based health-in-all policies
- What air quality standards protect the health of the most susceptible population groups ?
- What urban design aspects promote health ?
- What chemical and occupational exposures need regulation and with what standard (e.g., pesticide mixtures) ?
- What are stress- and suicide-prevention strategies at the workplace ?
Prospectively obtained biosamples and images stored in high-quality biobanks can serve personalised health research into both target discovery and target testing for clinical and public health utility. Assessing the clinical utility of various biomarkers (e.g., genomic markers; brain magnetic resonance imaging; stool/skin/lung microbiome) is essential in order to address the following questions:
- Do novel biomarkers help to predict or early detect diseases beyond current state-of-the-art strategies ?
- What are reference ranges and diagnostic or prognostic cut off levels of novel biomarkers [20, 21]?
- Does knowledge of an elevated personal/genetic disease risk motivate individuals to make evidence-based sustainable behavioural changes (e.g., lifestyle, screening, chemoprevention) ?
- Trials within cohorts for (genetically) targeted interventions and therapies 
- Family studies for understanding the penetrance of genetic variants, gene-environment interactions, and the transgenerational inheritance of epigenetic markers 
- A birth cohort of children born into the citizen cohort, by obtaining the earliest possible indication of pregnancy from citizen cohort participants [25, 26]
- One Health research, working out synergistic benefits from a closer collaboration between physicians and veterinarians (e.g., integrated human and animal disease surveillance and response systems) 
- Infectious disease and antibiotic resistance research in humans and the human-animal interface .
Active disease monitoring in the context of longitudinal studies makes it possible to measure underdiagnosis of diseases and its consequences:
- What is the percentage of persons with type 2 diabetes or hypertension who remain undetected ?
- What is the impact of a delayed diagnosis of familial hypercholesterolemia on morbidity and mortality ?
- What is the proportion and long-term health state of nutrient- or vitamin-deficient citizens ?
- What is the level of under-ascertainment of infections occurring at community level and under-diagnosing and -reporting of infections at health care level ?
Patients in citizen cohorts obtain health services in diverse geographical locations and health system settings. Aspects of relevance to the Swiss healthcare system can be evaluated.
- Are health interventions implemented according to recommendations (e.g., pharmacogenetics testing, clinical risk prediction rules for prevention of atherosclerotic cardiovascular diseases) ?
- Is there social equity in access to healthcare, including personalised health interventions ?
- What is the extent of health literacy related to health in general, and genetics and personalised health in particular ?
- What is the long-term cost-effectiveness of (personalised) health interventions ?
- Can patient counselling be individualised, based on studies of the effects of interaction between medical treatment, behaviour/environment and genetics on the disease course ?
Us-Too research - a rationale for a cohort in Switzerland
Us-Too, in the sense of contributing to an internationally harmonised data platform to become an equally respected partner, is a priority – Swissness is a priority in the conduct of innovative research in various domains with the help of this platform
Over the past decade, genome-wide association studies have demonstrated the scientific value of cohort collaborations with sufficient statistical power to decipher the biological mechanisms underlying human diseases and behaviours [38, 39]. Genetic variation is neither sufficient to explain disease risk, nor modifiable for the purpose of prevention. Large sample size, prospectively sampled biospecimens and harmonisation of study protocols across regions and countries are particularly important in personalised health research into the complex interactions between genetic and nongenetic modifiable disease risks . This is the justification for research infrastructures such as All of Us , the UK Biobank , or the German National Cohort , and also applies to Switzerland.SWITZERLAND NEEDS ITS OWN, BUT INTERNATIONALLY HARMONISED, COHORT FOR SEVERAL REASONS
- For Swiss citizens to benefit directly from high-quality research that captures their specific chronic exposures to beneficial and/or potentially toxic substances and their impact on health and well-being, while taking into account individual-specific factors, (genetic, social, environmental, cultural, etc.)
- For the Swiss healthcare system to benefit from population-based long-term information
- To have access to internationally harmonised high-quality longitudinal data and biospecimens on a large scale, Swiss researchers need to match this access by contributing own data and biosamples
- The Swiss cultural and health systems context allows the assembly of a high-quality, albeit smaller, Swiss cohort that facilitates competitive research. Interesting aspects are: cultural diversity including food diversity; geographical diversity including altitude and gradient; diversity of healthcare system across regions and cantons; high quality of clinical research to advance the phenotyping of citizens; internationally outstanding basic research offering the potential to the embed translational substudies into cohort studies.
- For decades, the Swiss National Science Foundation (SNSF) has been supporting disease-specific cohort studies (e.g., in HIV, hepatitis C, inflammatory bowel disease, acute coronary syndromes). Comparison of these data with a general-population based cohort facilitates validation of biomarkers and allows Mendelian randomisation studies to evaluate causality of risk factors and disease traits including biomarkers. The existing SNSF-funded citizen cohorts and archived biobanks (SAPALDIA, CoLaus) combined with deep phenotyping for specific diseases still serve to assess long-term effects.
- Comparative settings form an important basis for elucidating disease risk patterns. By broadening the genetic, exposure and interaction range, novel insight into disease processes will be gained.
- Longitudinal data and biospecimens of large scale support the development of academic careers in various research domains.
- An instrument to effectively investigate and respond to novel technological trends, medical innovations, as well as new environmental or pathogenic health threats
- Large citizen biobanks offer ample opportunity for public-private partnerships including SME and large capitalised companies in life sciences and life science technology
- Participants contributing their data and biosamples, and patients’ organizations could be directly active in promoting citizen science while confirming that research conducted with the cohort and beyond responds to the needs of the population.
The cost for building and maintaining a long-term study and biobank with at least 100,000 participants will surpass CHF 100 million in the long term. Such investment is expected to provide the necessary critical mass for numerous highly complex processes, while ensuring optimal privacy protection, semantic interoperability and ethical standards. It allows a high number of samples and data points of comparable quality, handled according to the same protocol and stored in a secured way. It increases with the number of research projects and partnerships that can benefit from the resource. The US All of Us research programme is, therefore, committed to engaging multiple sectors and forging strong partnerships with academic and other nonprofit researchers, as well as patient groups and the private sector to capitalise on work already underway. Partners for building and using data from a Swiss Citizen Cohort and Biobank range from basic research (e.g., genomics) to clinical research (all domains including rare disease / medical genetics; radiology, neurology), epidemiology and public health, health economics, toxicology and the social sciences. In addition to academic partners, various political bodies (e.g., FOPH, FOEN, FSVO, BASPO, SECO) rely on a Swiss-specific evidence base for policy setting. The SPHN initiative has documented in its basic report the mid-term need for a citizen reference. The SPHN patient infrastructure currently being established will greatly facilitate the identification of diagnosis incidence in a citizen cohort. Setting up a citizen reference in the next funding period is essential for the success of SPHN investments to date.CITIZEN ENGAGEMENT
Active exchange with participants in longitudinal studies assures optimal participation in the cohort [42, 43]. It enables understanding and acceptance of the expectations and needs of healthy persons and specific patient groups. This is an advantage of cohorts that are run in partnership with participants and with experts in social sciences, ethics and law, as well as communication and social marketing. By empowering study participants with data and information to improve and promote their own health through evidence-based decision-making from a sufficiently powered cohort has the potential to make a significant contribution to improving citizen health and informing public health policies. Cohorts paralleled by professional communication strategies in the context of effective information channels help educate citizens, patients, and health professionals about novel findings and technologies.OPTIONS FOR DESIGN AND STRUCTURE
The cohort design has to maximise the scientific use of the platform. It must cover the whole life-course and therefore span the range from unborn to old age. Children and patient cohorts, as well as family studies, can be nested longitudinally into large citizen cohorts (fig. 1). Identification of pregnancies at a very early stage and recruitment of children into a birth cohort is a unique setting for research into very early life effects. The integration of family studies facilitates genetic, epigenetic and rare disease research. The population-based patient cohorts evolving are fundamental for evaluating the performance of the healthcare system in various domains.
Figure 1: The potential for patient cohorts, family studies and a birth cohort evolving from a large citizen cohort.
No financial support and no other potential conflict of interest relevant to this article was reported.
Nicole Probst-Hensch: Head, Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Socinstrasse 57, CH-4051 Basel
CO-AUTHORS: Jürg H. Beer, Kantonsspital Baden, on behalf of BUGS (Beratung und Umsetzung im Gesundheitswesen: Andreas Cerny, Thomas Cerny, Stefan Krähenbühl, Raoul Blindenbacher); Georg Bauer, UniZH; Martine Bourqui, BAG; Matthias Briel, UniBas; Bettina Bringolf-Isler, Swiss TPH; Heiner Bucher, UniBas; Philippe C. Cattin, UniBas; Paco Cerletti, Swiss TPH; Francois Chappuis, UniGE; Luca Crivelli, SUPSI; Christine Currat-Zweifel, Swiss Biobanking Platform; Bogdan Draganski, CHUV-UniL; Julia Dratva, ZAHW; Holger Dressel, UniZH; Bernice Elger, UniBas; Sabina de Geest, UniBas; Jan Fehr, UniZH; Günther Fink, Swiss TPH; Antoine Flahaut, UniGE; Oscar H. Franco, UniBE; Anja Frei, UniZH; Sébastien Gagneux, Swiss TPH; Andreas Gerber-Grothe, ZAHW; Semira Gonseth Nusslé, UniL; Idris Guessous, UniGE; Matthias Gugger, UniBE; Medea Imboden, Swiss TPH; Laurent Kaiser, UniGE; Bengt Kayser, UniL; Nino Künzli, Swiss TPH & SSPH+; Regina Kunz, UniBas; Carlo Largiadèr, UniBE; Joachim Marti, UniL; Daniel Mäusezahl, Swiss TPH; Vincent Mooser, UniL; Réjane Morand, BAG; Andreas Papassotiropoulos, UniBas; Daniel Paris, Swiss TPH; Isabelle Peytremann-Bridevaux, UniL; Valérie Pittet, UniL; Martin Preisig, UniL; Milo Puhan, UniZH; Carlos Quinto, Swiss TPH; Sabine Rohrmann, UniZH; Martin Röösli, Swiss TPH; Arno Schmidt-Trucksäss, UniBas; Matthias Schwenkglenks, UniBas; Paola M. Soccal, UniGE; Dominique Sprumont, UniNE/designated chairman Research Ethics Committee VD; Daiana Stolz, UniBas; Bram Stieltjes, UniBas; Jivko Stoyanov, Swiss Paraplegic Research; Silvia Stringhini, UniL; Suzanne Suggs, USI; Thomas Szucs, UniBas; Jürg Utzinger, Swiss TPH; Thomas Vermes, Swiss TPH; Peter Vollenweider, UniL; Arnold von Eckardstein, UniZH; Viktor Vonwyl, UniZH; Penelope Vounatsou, Swiss TPH; Josias Wacker, CSEM; Kaspar Wyss, Swiss TPH; Andreas Zeller, UniBas; Jakob Zinsstag, Swiss TPH; Marcel Zwahlen, UniBE; Murielle Bochud UniL
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