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Prof. Dr. Dr. Matthias Briel

Department of Clinical Research
Profiles & Affiliations

Projects & Collaborations

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RETUNE

Research Project  | 7 Project Members

Reduce Tobacco Use in People Living with HIV in Switzerland (RETUNE)


Tobacco smoking represents a leading health burden in the aging population of people living with HIV in Switzerland. New tools for smoking cessation like electronic cigarettes or nicotine pouches are promising to reduce the harm caused by tobacco smoking. However, high quality evidence of their effectiveness among people living with HIV and outside of explanatory randomized trials is missing. 


RETUNE is a highly pragmatic randomized trial, fully embedded in the Swiss HIV Cohort Study (SHCS), using the “Trials within Cohorts” (TwiCs) design. 

In the TwiCs design, participants are recruited within a prospective cohort study and can consent not only to regular data collection at cohort visits, but also to be randomized in future low-risk pragmatic trials (“randomization consent”). Participants are informed that only participants randomized to the intervention arm are approached and may then accept or decline the offered intervention. Participants in the intervention who accept the intervention, are asked to sign an “intervention consent”, that only covers additional data collection in this group and the safety/side-effects of the intervention – similar to a routine clinical consent (e.g. consent for a lumbar puncture in clinical care). 


RETUNE aims to assess the effectiveness of the offer of a menu including different tobacco cigarettes substitutional products (e-cigarettes, nicotine pouches, nicotine patches) to quit smoking. People with HIV in the SHCS who smoke tobacco cigarettes and who signed the randomization consent will be randomized in a 1:1 ratio to the offer of the menu or to usual care. People are included regardless of their willingness to quit smoking. The primary endpoint is tobacco abstinence after 6 months. RETUNE is a multicenter trial which will include centers in Basel, Bern, Geneva, Lausanne, St. Gallen, and Zurich. 


RETUNE is funded by the Tobacco Prevention Fund, the Novartis foundation for medical-biological research, and the Swiss National Science Foundation.



Involved partner:

Swiss HIV Cohort Study

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MARTA: Making clinical trials more affordable - systematic investigation of trial costs and tool development

Research Project  | 1 Project Members

Randomized clinical trials (RCTs) are an essential method of evaluating health care interventions and a cornerstone for evidence-based health care. Their conduct, in particular for investigator-initiated RCTs, has long involved many practical challenges, challenges that have become increasingly complex and costly. Efforts to render RCTs more cost-effective are, therefore, urgently needed. Identifying lever-points for cost reductions requires knowledge of cost structures and cost drivers (e.g. recruitment duration, sample size, therapeutic area, number of trial sites). The medical literature, however, currently lacks detailed empirical data addressing costs and resource use of investigator-initiated RCTs as well as information about current practices of budget planning and cost monitoring, attitudes, needs, and preferences of trial investigators, trial support organizations (e.g. Clinical Trial Units), and funding agencies. Academic investigators usually depend on scarce financial resources; user-friendly and reliable tools to effectively limit costs of RCTs through optimized budget planning and cost monitoring during the conduct of an RCT are currently unavailable and sorely needed. We therefore propose three complementary projects using mixed-methods to render investigator-initiated RCTs more affordable and efficient through evidence-based budget planning, stakeholder consensus regarding relevant budget items, and the development of suitable tools. In Project A we will gather empirical resource use and cost data from 180 investigator-initiated RCTs in Switzerland, Germany, Canada, and the United Kingdom to investigate cost patterns, empirically identify major cost drivers and lever-points for cost savings, examine planned versus actual RCT costs, and explore heterogeneity of costs across medical fields and countries. Project B will consist of semi-structured interviews to explore current practices, attitudes, needs, and preferences of trial investigators, trial funders, and trial support organizations with respect to budget planning, funding acquisition for RCTs, managing costs during RCT conduct, and supporting tools in Switzerland. In Project C we will develop reliable and user-friendly budget calculation and cost monitoring tools for RCTs with stakeholder consensus based on systematically collected evidence from the literature/internet and informed by user needs and preferences (as elicited in Project B). We will formally user-test and evaluate the reliability and accuracy of developed tools using the generated database of empirical RCT cost data from Project A. The results of the proposed mixed-methods work will have immediate impact on the research practice of trial investigators, trial support organizations, and funders of RCTs in Switzerland and abroad. Given the increasing costs and complexity of RCTs, our project is timely and should shift the discussion from "rough guesses" to "analysing transparent and valid data" so that costs of clinical trials can be assessed, cost drivers identified, and costs effectively limited so that RCTs, critical to advancing clinical science, become more affordable.

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Functional Aging in Health and Disease - the COmPLETE Project

Research Project  | 5 Project Members

The increasing prevalence of chronic non-communicable diseases and associated risk factors contribute to earlier disability and frailty onset over the course of life in industrialized western countries. This process applies also to diseases of the cardiovascular system, including heart failure, which is a widespread syndrome in middle-aged and older people. Although life expectancy has steadily increased in past decades, the traditional curative way of thinking in medicine is unlikely to compress the disease phase to the final stage of life and thus increase the health span, which is defined as a period of relatively disease-free aging followed by a period of age-related diseases and disabilities. In the period of healthy aging, the function of the organs, including the cardiovascular system, is already deteriorating. To counteract this process and to increase the health span, the preservation or improvement of components of physical fitness (endurance capacity, muscle strength, and neuromuscular function) is thought to be an essential element. The proven, independently predictive value of the single physical fitness components for total and cardiovascular mortality confirms this assumption. However, comprehensive data regarding individual physical fitness characteristics over the course of life are not yet available. Such data is necessary for any targeted prevention program with physical activity and exercise training as crucial pillars. Furthermore, healthy reference values could be used to estimate the adaptive capacity in healthy individuals compared to patients. Therefore, the aims of the COmPLETE project are:1.To determine the trajectories of physical fitness components of healthy aging by measurement of endurance capacity, muscular strength and neuromuscular coordination in a healthy population sample between 20 and 100 years (COmPLETE-Health) and 2.To determine the health distance between healthy individuals (COmPLETE-Health) and heart failure patients (COmPLETE-Heart) on the basis of different physical fitness components (endurance capacity, muscular strength and neuromuscular coordination). We anticipate that, for the first time, a basis for targeted prevention programs will be created through better and comprehensive knowledge of the individual physical fitness to improve the health span. In addition, we are convinced that by calculating the health distance between healthy and heart failure patients, we are laying the foundation for more individual exercise therapy. The COmPLETE project could be the starting point for strengthening the in-depth diagnostics of physical fitness as a component of preventative health care.

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INSPIRE: Einführung eines gemeindebasierten Versorgungsprogramms für ältere Menschen im Kanton Basel-Landschaft (Implementation of a Community-based Care Program for Senior Citizens in Canton BL)

Research Project  | 14 Project Members

In der Schweiz steigt die Lebenserwartung. Somit wird auch der Anteil von älteren Menschen mit Unterstützungsbedarf grösser. Die Unterstützung wird dabei von verschiedenen Anbietern zur Verfügung gestellt. Ältere Menschen brauchen oft eine Kombination von Dienstleistungen, diese sind jedoch weder zentralisiert noch koordiniert, so dass ältere Menschen dem Risiko einer fragmentierten Versorgung ausgesetzt sind. Negative Folgen sind die Mehrfachnutzung von Diensten, Lücken in der Informationsbereitstellung, unpassende oder widersprüchliche Empfehlungen und Medikationsfehler. Dies führt zu Unsicherheit, Stress und Belastung bei älteren Personen und ihren Angehörigen. Dazu kommen höhere Pflegekosten durch unnötige Spitalaufenthalte, das Aufsuchen von Notfallabteilungen und andere unnötige Inanspruchnahme von Dienstleistungen. Solche unerwünschten Prozesse und Auswirkungen können durch Investitionen in integrierte Versorgungsmodelle verhindert werden. INSPIRE geht diesen drängenden Fragen nach und zeigt, wie neue Versorgungsmodelle in der Praxis mit hoher Nachhaltigkeit umgesetzt werden können. Angesichts der demografischen Entwicklung der Bevölkerung im Kanton Basel-Landschaft (BL) und des bevorstehenden Mangels an Hausärzten und Betreuungspersonen wurde die Organisation der Gesundheitsversorgung für ältere Personen im Kanton überdacht. Am 16. Nov. 2017 wurde im Landrat das neue Altersbetreuungs- und Pflegegesetz (APG) verabschiedet. Dieses schreibt eine Reorganisation des Kantons BL in Versorgungsregionen vor, was eine Zusammenarbeit auf Gemeindeebene erfordert. In den Versorgungsregionen werden Informations- und Beratungsstellen zu Fragen der Betreuung und Pflege im Alter eingerichtet. Diese stellen den Bewohnerinnen und Bewohnern einer Versorgungsregion Informationen zum Thema Alter(n) und Altersfragen zur Verfügung, und ermöglichen Beratung und Bedarfsabklärung durch eine Pflegefachperson, insbesondere vor dem Eintritt in ein Pflegeheim. Eine zentrale Aufgabe der Versorgungsregionen ist es, ein Versorgungskonzept zu erstellen, um eine angemessene ambulante, intermediäre und stationäre Versorgung sicherzustellen. Das Ziel von INSPIRE besteht darin, ein effizientes und nachhaltiges gemeindebasiertes Versorgungskonzept für ältere Menschen mit neuen Methoden der Public Health- und Implementierungsforschung im Kanton BL zu entwickeln und umzusetzen. Das Projekt wird in folgenden Schritten durchgeführt: Organisation einer kantonalen Steuergruppe und eines lokalen Stakeholder-Gremiums, die sich aktiv für die Entwicklung und Umsetzung des gemeindebasierten Versorgungsmodelles einsetzen. Ermittlung bestehender gemeindebasierter Versorgungsprogramme, und Analyse der Wirksamkeit und Nachhaltigkeit (Literaturrecherche, gute Praxisbeispiele in der Schweiz inklusiv lokalen Beispielen im Kanton BL). Kontextanalyse: Erfassung der aktuellen gemeindebasierten Gesundheitsversorgung im Kanton BL. Evidenzbasierte Entwicklung eines gemeindebasierten Versorgungsmodells, das dem Gesundheitswesen von BL entspricht und aus der Sicht der Stakeholder passt und umsetzbar ist. Entwicklung eines Monitoring-Systems, das die Umsetzung und Auswirkungen des gemeindebasierten Programmes auf ältere Menschen, Anbieter und Gesundheitssystem laufend evaluiert. Als Resultat der oben beschriebenen Arbeitspakete liegt ein auf die lokalen Gegebenheiten von BL angepasstes Versorgungsmodell mit geplantem Monitoring-System vor. Dies wird in einem weiteren Schritt in einer Versorgungsregion von BL umgesetzt und evaluiert.

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Effect of the Swiss human research legislation on the costs associated with randomized clinical trials in Switzerland

Research Project  | 3 Project Members

In any medical and health related field there is often uncertainty from which of two or more available treatment options a patient would profit most. Allocating groups of patients randomly to different treatment options in the context of so-called randomised controlled trials (RCTs) provides the most reliable comparisons and evidence for decision making in clinical practice. However, the conduct of RCTs is costly, administratively burdensome and highly regulated to protect study participants. The conduct of an RCT does not only consist of patient enrolment, treatment and follow-up, but also of a comprehensive preparation phase, during which multiple tasks have to be accomplished. For example, a study protocol and a number of other documents need to be created, approval from research ethics committees (RECs) and in some cases from the Swiss Agency for Therapeutic Products ( Swissmedic ) has to be obtained. To create favourable research conditions in Switzerland, the new law on research with human beings (Human Research Act) and its ordinances, jointly abbreviated in this report as Swiss Legislation on Human Research (LHR), was enacted in January 2014. The main aim of this study was to assess if the new LHR had an impact on the administrative burden and costs to plan and prepare an RCT. To find out about required working efforts and costs to plan and prepare an RCT, we contacted investigators from RCTs which were approved by Swiss RECs in 2012 and 2016 (before and after the implementation of the LHR). Investigators received a comprehensive excel sheet in which all possible preparation steps for an RCT were listed. They were asked to retrospectively estimate the working efforts for all involved staff members and to give information about fixed costs. Based on this information, we aimed to calculate the working efforts and the costs to plan and prepare an RCT. Furthermore, we assessed approval times (i.e. times from submission of study documents until final approval) by RECs and Swissmedic. We received complete resource use and cost data for the preparation phase of 18 RCTs which were approved in 2012 and of 35 RCTs which were approved in 2016. The median working time to plan and prepare an RCT was 113 days (25 th to 75 th percentile range [IQR]: 51-190 days) in 2012 and 133 days (IQR: 79-239 days) in 2016. The median costs to plan and prepare these RCTs were estimated to be CHF 81'100 (IQR: CHF 69'500-123'100) in 2012 and CHF 73'800 (IQR: CHF 43'500-176'700) in 2016. Given the small number of RCTs for which we received data and a strong possibility of selection effects, it was not possible to draw firm conclusions on a cost impact of the LHR. Approval times from RECs were available for a total of 183 RCTs approved in 2012 and 217 RCTs approved in 2016. The median time from application to approval was 72 days (IQR: 41-72 days) in 2012 and 109 days (IQR: 79-154 days) in 2016. Further data provided by Swissmedic indicated that Swissmedic approval times for clinical trials (not only RCTs) were also longer in 2016 (median: 27.0 days; IQR: 19.0-50.5 days) than in 2012 (median: 49.0 days; IQR: 36.0-67.0 days). Gathering actual resource use and cost data for RCTs was difficult, because such information was not systematically documented and it required active collaboration of RCT investigators to comprehensively capture spent resources. Due to the sparseness of the available data, we could not draw firm conclusions regarding changes in the working efforts and costs for the preparation phases of RCTs. Approval times by RECs and Swissmedic were higher in 2016 compared to 2012. However, it is difficult to differentiate whether these differences were due to the LHR or due to other reasons.

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Learning from failure - Understanding the mechanisms of trial discontinuation

Research Project  | 6 Project Members

One out of four randomized controlled trials (RCTs) is discontinued; insufficient recruitment of participants is the most frequent reason, in particular in investigator-initiated RCTs. Trials initiated by commercial sponsors are less likely to be discontinued suggesting that professional planning and conduct as well as sufficient funding of RCTs help complete recruitment as planned. Currently, the mechanisms and specific root causes of trial discontinuation remain unclear. Evidence-based guidance for trialists and other stakeholders on how to plan and assess recruitment in RCTs is lacking. In most cases, participants and research ethics committees (RECs) are not informed about discontinuation or publication of trial results. Accounts of the work done so far are not disseminated to the scientific community in up to 60% of discontinued RCTs. This entails ethical problems: The patients' and the public's trust in clinical research is undermined, and finite research resources are wasted. It is unknown to what extent trialists are aware of the ethical implications with trial discontinuation and what their attitudes and views are. We propose three complementary projects that will use both qualitative and quantitative methods to better understand the mechanisms that lead to RCT discontinuation, find ways to meet the associated ethical challenges, and develop guiding principles for involved stakeholders. In Project A we will conduct semi-structured interviews with principal investigators of RCTs discontinued for insufficient recruitment and with key stakeholders of clinical research in Switzerland representing Clinical Trial Units, RECs, the Swiss National Science Foundation (SNSF), the pharmaceutical industry, and Swissmedic. Project B will empirically examine all health-care RCTs funded by the SNSF to explore whether a rigorous selection of trials for funding and monitoring decreases the risk of trial discontinuation including potential effects of full versus partial funding. In Project C we will perform a comprehensive analysis of recruitment patterns from about 500 completed and discontinued RCTs conducted in different countries and settings. It will explore whether insufficient recruitment can reliably be identified at an early stage and determine optimal time points and criteria for the assessment of recruitment progress in RCTs. Using a mixed methods approach, this study will further our understanding of the complex mechanisms leading to failure in trial recruitment and identify potential lever points for targeted interventions. Following on the successfully completed DISCO study it will continue a line of methodological research that is of high relevance to clinical researchers and trial participants in Switzerland and abroad. At a time in which the legal framework of research involving humans is being revised, the study will provide a most needed empirical base for the elaboration of guidance documents to be used by trialists and other stakeholders.