Faculty of Medicine
Faculty of Medicine
UNIverse - Public Research Portal

[FG] Briel Matthias

Projects & Collaborations

14 found
Show per page
Project cover

Pharmacological antiemetic prophylaxis and treatment for opioid induced nausea and vomiting (OINV) in patients treated for cancer pain: Cochrane systematic review

Research Project  | 6 Project Members

Background:

In cancer patients with incurable disease pain is one of the most debilitating symptoms with a prevalence of about 70% (1). Many of these patients need opioids, which are the mainstay in managing cancer pain. Initiation of opioid therapy is frequently hindered by opioid induced nausea and vomiting (OINV) in up to 40% of patients (2). Nausea is highly distressing symptom that may occur with or without vomiting and can affect overall outcome and quality of life (3). To avoid discontinuation of the opioid therapy 50-80% of doctors prescribe prophylactic or on-demand antiemetics to reduce OINV (4), although evidence for this practice is scarce or not supported by randomised controlled trials (RCTs) (5). However, the medications used to prevent OINV, e.g. dopamine antagonists can trigger adverse events in the central nervous system (headaches, drowsiness) or even parkinsonism-like symptoms.

 Aims / Methods:

To better inform physicians, guidelines and patients, we propose a Cochrane systematic review and meta-analysis of RCTs concerning the benefits and harms of antiemetic drug therapy for the prevention and treatment of OINV in patients treated with opioids for cancer pain therapy.

Benefit for patients and / or public

The numbers of affected patients are expected to increase during the decades to come due to the medical progress in oncology and the demographic change (9,10).


Project cover

Increasing value of health research: development of a new methodological decision support system to assist researchers in study design, conduct, and analysis

Research Project  | 1 Project Members

Methods applied in health research are often uninformed and inappropriate. One important reason is that methodological guidance has limitations regarding access, presentation, and veracity. AIM: We propose to develop a new online methodological decision support system that provides health researchers with access to up-to-date, trustworthy, and user-friendly methodological recommendations. If feasible, the new system could become the key reference for those seeking methodological guidance. METHODS: We have formulated an overall development plan in which we identified key features and processes. To inform the feasibility of the overall initiative, we will start with pilot studies addressing key features of the proposed system: We will explore existing approaches for systematically reviewing and monitoring the methodological literature for a specific methodological question. We will test candidate approaches by applying them to a specific topic (e.g. adaptive designs for randomized trials). Based on the test results, we will draft a standard process for reviewing a methodological topic. In addition, we will explore ways to develop methodological recommendations together with experts. Specifically, we are interested in the extent to which we can adapt guideline processes from the medical context (e.g. the GRADE approach). We will draft processes for transparently selecting, evaluating, and integrating methodological evidence (i.e. results of research on research and simulation studies) in methodological practice recommendations.

Project cover

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.

Project cover

Generalizability, applicability and pragmatism of clinical trials and their impact on treatment effect estimates: a meta-epidemiological study

Research Project  | 2 Project Members

It is often claimed that results from some randomized clinical trials (RCT) are difficult to transfer into real life situations. Pragmatic RCTs provide decision-oriented, real world evidence that is perceived as highly applicable and generalizable to routine care. Conversely, explanatory RCTs conducted in highly controlled research settings are often considered little or not applicable and generalizable. Pragmatic and explanatory RCTs are the extremes of a continuum measurable using the PRECIS-2 tool, which is increasingly being used to design and assess clinical trials. It is widely assumed that treatment effects provided by more pragmatic trials differ from those given by more explanatory trials. However, it is unknown how they differ and which features determine pragmatism, generalizability and applicability. Our goal is to provide empirical evidence on the strengths, weaknesses and the impact on treatment effect estimates of pragmatism, applicability and generalizability beyond the theoretical expectations of their value in the decision-making process of patient care.Objectives: (1) To set up the PragMeta database, which will include trials investigating the same clinical questions but having different aspects of generalizability, applicability and pragmatism; (2) to descriptively characterize those aspects using the PRECIS-2 score and specific trial population- and setting-related determinants of generalizability (for example strict or broad eligibility criteria) and applicability (for example highly controlled environment versus routine care); and (3) to determine their impact on the treatment effect estimatesDesign and Methods: This is a meta-epidemiological study of published trials. We will work in a large international research collaboration, with key experts in the field, to incorporate and share in the PragMeta database large already available datasets of pragmatic trials, supplemented by specific systematic searches of pragmatic and explanatory trials on the same clinical questions. Standard methods of systematic reviewing, meta-analysis and meta-epidemiology will be used. We will compare treatment effects from pragmatic versus explanatory trials and from trials with versus without specific determinants of pragmatism, generalizability, and applicability using meta- regressions and the ratio of odds ratio method. We plan to include over 2000 trials that will be representative of the pragmatic-explanatory continuum.Relevance of the project: The cornerstone of real world evidence is that treatment effects under real world conditions in routine care may differ from that in highly controlled research settings, such as in drug approval trials. The PragMeta project aims to provide a better understanding of the pragmatic-explanatory continuum, and the generation and interpretation of real world evidence. It will give practical guidance for clinicians, researchers, regulators, health insurers and health-care policy makers, developers of reporting guidelines, and other stakeholders who develop, fund, conduct, assess or otherwise use clinical trials. Ultimately it may help to generate, report and use evidence that is more relevant for patients, clinicians and other key health care decision-makers.

Project cover

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.

Project cover

GET ON: GETting tOwards Ninety

Research Project  | 4 Project Members

Improving the HIV care cascade in Lesotho: Towards 90-90-90 - A research collaboration with the Ministry of Health

Background: Despite enormous progress in the last decade, HIV/AIDS remains the most important cause of morbidity and mortality in most countries of Southern Africa and a central contributor to economic underdevelopment and poverty in many societies. The 2014 UNAIDS "90-90-90" targets for 2020 represent an important step towards an AIDS-free generation by 2030. The targets emphasize the importance of antiretroviral therapy (ART) to prolong the life of people living with HIV and as the most effective preventative measure for reducing the spread of new infections through better virus control. The three key targets of "90-90-90" are: - 90% of all people living with HIV will know their HIV status. - 90% of all people with diagnosed HIV infection receive treatment. - 90% of all people receiving therapy will have their virus suppressed.

This project represents a collaboration between the Research Coordination Unit (RCU) of the Ministry of Health (MoH) of Lesotho, the District Health Management Team (DHMT) of Butha-Buthe, SolidarMed (Lesotho-based Swiss organization for health in Africa), the Swiss Tropical and Public Health Institute (SwissTPH) and the Molecular Virology unit at the Department of Biomedicine (DBM) of the University of Basel. The project combines epidemiological, operational and clinical research to address key questions related to reaching 90-90-90 targets in rural Lesotho, a country with the second-highest HIV prevalence in the world, high transmission rates and low ART coverage.

Methods: The proposed project is planned in Butha-Buthe district, Northern Lesotho, involving 2 hospitals and 10 health centers. As a crucial first step, the project has established the technical basis for the intended studies. As part of Lesotho's national viral load (VL) roll-out plan, the country's first decentralized VL monitoring platform was installed in the district laboratory of Butha-Buthe by the end of October 2015. Two randomized controlled trials (RCTs) and additional observational studies are planned within the proposed project.

RCT-1 (CASCADE-trial; NCT02692027, www.visibleimpact.org/projects/1197-cascade-trial) addresses the care-cascade from HIV-test to linkage to care to retention in care and achievement of viral suppression in the era of test-and-treat. Individuals who are newly tested HIV-positive during home-based HIV testing and counseling (HTC) are randomized into 2 groups. The control group provides standard of care with post-test counseling and a referral letter for enrolment in pre-ART care at the nearest facility. In the intervention-group, baseline laboratory testing and adherence counseling is provided after a positive HIV test at the participant's home with the option to start ART on the same day. The first primary endpoint is linkage to care at the facility within 3 months. The secondary endpoint is retention in care and viral suppression 12 months after HIV diagnosis. This trial has two nested observational studies. The first examines HTC-coverage achieved through home-based HTC while recruiting trial-participants. The second examines glucose- and lipid-profiles pre-ART and after ART initiation.

RCT-2 (SAVIR-trial): A culturally adapted, short, standardized adherence intervention for patients on ART with unsuppressed VL will be rolled out to the facilities in the district using a step-wedged design with the primary endpoint of VL re-suppression at follow-up determination. Establishing routine viral load monitoring will be linked to a database, a plasma-bank and introduction of genotypic sequencing in the district. This will allow observational studies on roll-out of viral load monitoring, treatment failure, switch to second-line ART and HIV resistance. Based on these observational data, a protocol for a third RCT will be elaborated by end of 2016. This RCT will address challenges identified in the field of treatment failure and switch to second-line ART.


Also see: the Cascade Trial at Visible Impact

Project cover

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.