Faculty of Medicine
Faculty of Medicine
UNIverse - Public Research Portal

[FG] Hemkens Lars

Projects & Collaborations

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COVID-evidence: a living database of trials on interventions for COVID-19

Research Project  | 2 Project Members

The COVID-19 pandemic is characterized by an unprecedented urgency to obtain reliable information on therapeutic options and their evaluation in clinical trials.Objective: We aim to provide a freely available and continuously updated online database of worldwide trial evidence on benefits and harms of interventions for COVID-19, including interventions for prevention, diagnosis, treatment and clinical management.Data sources include literature databases (e.g. PubMed), trial registries (e.g. ClinicalTrials.gov, WHO's International Clinical Trials Registry Platform (WHO-ICTRP) and Chinese Clinical Trial Registry (ChiCTR)) and preprint servers (medRxiv and bioRxiv).Selection criteria: We will include reports, registry entries, and manuscripts of trials testing any intervention actively allocated to humans with COVID-19. We will include a broad range of trial designs (including multi-arm but also uncontrolled trials) and interventions (including drug and non-drug treatments, vaccines, diagnostic procedures, and decision algorithms) without restrictions to language, region, or healthcare setting. Design and Methods: In close collaboration with a world-wide network of partners, we will use a multi-method approach combining peer-reviewed search strategies, continuous automated extraction of search results, automated classifications combined with crowd-based manual screening and data extraction, and quality control through expert review. We will start with a set of core variables and gradually expand the amount of information based on the needs of different stakeholders (including patients, clinicians, systematic reviewers, guideline developers and policy makers). The new website COVID-evidence.org will provide both the extracted information and links to the original data sources. The modular design of the database will allow continuous updates, addition of new data sources and content, and flexible adjustments to future projects.Relevance of the project: COVID-evidence.org will continuously monitor the clinical trial research agenda on COVID-19 and present decision-makers and researchers with the latest available trial evidence on how to prevent, diagnose, treat and manage COVID-19. Finally, by including key experts in the field and catalyzing international collaborations, we aim to foster evidence-based decisions on all levels of health policy and practice.

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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.

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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.