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Prof. Dr. Dr. Matthias Briel

Department of Clinical Research
Profiles & Affiliations

Projects & Collaborations

8 found
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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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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.

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When clinical research fails: a study of controlled trials that were discontinued

Research Project  | 1 Project Members

Clinical trials may be discontinued for different reasons, for example when it becomes apparent that a clinically relevant treatment effect will not be seen; when unanticipated adverse effects occur; or when outcomes are clearly superior in one study group. In addition, many trials are discontinued due to insufficient recruitment (slow accrual) of participants. This has ethical implications because participants consent on the premise of contributing to the advancement of medical knowledge, research ethics committees and funding agencies spend considerable resources on reviewing protocols of planned studies, and finite resources for research are wasted. Little is known about the epidemiology of discontinued trials in Switzerland. We propose to assemble a cohort of clinical trials based on protocols approved by research ethics committees in Lausanne, Basel, Lucerne, and Zurich between 2000 and 2004. We will explore other sources of trials, for example trials funded by the Swiss National Science Foundation. We will analyze this cohort to determine the risk of discontinuation of trials for different reasons. Using a case-control design, we will focus on trials that were discontinued due to insufficient recruitment. We will compare these trials with trials that were completed and thus identify characteristics of study protocols associated with discontinuation due to poor recruitment. Finally, we will examine the publication history of trials that were discontinued, and assess to what extent any lessons learned have been disseminated. We will extract relevant data from the files of the collaborating ethics committees and from published trial reports, and through a survey of trialists. The study will be based on over 1000 protocols of clinical trials, and about 150 trials that were discontinued due to poor recruitment. The proposed research is timely: recruitment of trial participants has repeatedly been identified as a serious ?bottleneck? in clinical research. The planning of effective recruitment strategies and anticipation of problems is a core task of the Clinical Trial Units (CTUs) that have been established in Switzerland with the support of SNSF. Our study will provide important insights into the problems with recruitment of participants that were encountered in randomized trials conducted in Switzerland in the recent past. It will identify modifiable barriers to successful study completion and inform future recommendations to individual trialists, research groups and units providing methodological support.

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Procalcitonin to initiate or withhold antibiotics in acute respiratory tract infections: Systematic review and individual patient data meta-analysis of randomized trials.

Research Project  | 2 Project Members

The ultimate goal for the use of biomarkers in clinical medicine is to inform decision making for the benefit of the patient. Four intervention trials enrolling more than 1250 patients from the University Hospital Basel have shown that procalcitonin-guidance reduced AB use and AB exposure in patients with acute respiratory tract infections (ARTI) by over 50%. We aim to systematically review all randomised trials comparing a strategy to initiate or withhold antibiotic therapy in patients with ARTI based on PCT cut-off ranges with a control arm without PCT measurement. Our primary objective is to summarize the effects on disease-specific failure of therapy and all-cause mortality by means of an individual patient data meta-analysis.

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Implementation of liquid biopsies during routine clinical care in patients with advanced malignancies (LIQPLAT)

Research Project  | 10 Project Members

This is a trial using routinely collected health care data from an ongoing registry (AO_2023- 00091) in cancer patients with advanced solid malignancies receiving first line systemic anti- cancer treatment for advanced disease.

This trial will assess the feasibility and implementation of routine measurement of ctDNA and its association with clinical outcomes, including quality of life and survival. All patients will receive routine diagnostics, treatment and follow-up. All patients with a new cancer diagnosis will be assessed for eligibility based on the routinely collected information available in the registry. We will then randomly decide which eligible patients are invited to participate in the trial. If patients accept the invitation and intend to get a measurement of ctDNA, they have to provide written informed consent.

The feasibility target sample size is 150 patients who accepted the invitation. We have chosen to randomly invite patients to participate, because: first, current capacities are not sufficient to offer regular ctDNA measurement to all cancer patients; second, we aim to recruit an unbiased and representative sample of patients; third, we aim to conduct comparative analyses with high internal and external validity so that our results are directly and reliably transferable to a large group of future cancer patients.