Clinical research methods

Clinical research methods

The research area ‘Clinical research methods’ focuses on improving existing and developing innovative methodology for the design, conduct, analysis and reporting of clinical epidemiologic research in the cardiovascular domain. This includes methods for research on the clinical value and cost-effectiveness of diagnostic and prognostic tests and (bio)markers, and of therapeutic and preventive interventions.

Our research uitklapper, klik om te openen

The methodology developed and addressed in the theme ‘clinical research methods’ has a direct relationship with all the patient groups within circulatory health, as in these patient group themes all above discussed types of research are conducted. Emphasis, however, is on stroke, peripheral artery, heart failure, coronary heart disease, and diabetes.

On the one hand the work in this research area includes pure innovative methodological research, thus aiming to develop new methods for clinical cardiovascular research. On the other hand, it involves applied or empirical cardiovascular studies related to a specific disease, therapy, test, marker, risk factor, in which these methodological innovations are directly applied and tested.

There is substantial expertise in the methodology of diagnostic and prognostic studies with a clear focus on the development, validation, and implementation of clinical prediction models or decision  tools, as well as on the methodology of randomized trials, meta-epidemiological (meta-analytical) and cost-effectiveness studies. The expertise regarding ethical issues of modern clinical research is internationally unique. In this research area, several lines of research can be identified:

1. Predicting disease occurrence

Developing novel methods to properly estimate the predictive accuracy and clinical value of the latest biomarkers and, e.g. imaging, tests, in order to attain as good as possible prognostic and diagnostic tools for predicting disease development and presence, respectively.

2. Improved design and analysis for randomised  trials

Developing, testing and applying new epidemiological and statistical approaches to enhance the validity and generalizability of randomised trial results, including the use of Bayesian approaches in design and analysis, sequential and enriched designs, and novel methods to address loss to follow-up in such studies.

3. (Early) health technology assessments (HTA) of medical interventions

Developing methods for estimating the long term cost-effectiveness of medical interventions, i.e. therapeutic, diagnostic, prognostic, screening or monitoring interventions, preferably as early as possible in the life cycle of such interventions.

4. Research ethics

Research and consultancy on the conditions under which a responsible innovation in drug or medical device development will be possible, mainly concerning informed consent and responsible use of patient data.

5. Causal inference

Testing new methods for design and analysis to enhance the validity and causal inference of non-randomised studies on risk factors of cardiovascular diseases, as well as of non-randomised studies on the intended and unintended (side) effects of medical interventions.

6. Meta-epidemiology (systematic reviews and meta-analysis)

Developing novel methods for systematic reviews and meta-analytical studies using either aggregate data or individual participant data or a combination of both. The focus is on meta-analyses of diagnostic and prognostic test/marker studies, but also includes therapeutic and preventive intervention studies.

Key publications uitklapper, klik om te openen

• A systematic review, analyzing the methodological soundness of prediction studies published in high impact journals, which showed that the majority of prediction studies in high impact journals do not follow current methodological recommendations, limiting their reliability and applicability. This work was published in Plos Medicine (see reference).
• Ethical research on adaptive trials in therapeutic  research, which was published in JAMA.
• Bouwmeester W, Zuithoff NPA, Mallett S, Geerlings MI, Vergouwe Y, Steyerberg EW, Altman DG, Moons KGM. Reporting and methods in clinical prediction research: a systematic review. Plos Medicine 2012; 9: 1-13

Recent highlights, showing the diversity of the work, and published in high-impact journals are:

• The finding that extremely low-coverage sequencing in genome-wide association studies captures almost as much of the common and low-frequency variation across the genome as SNP arrays. This makes it a much more efficient method given the reductions in sample preparation and sequencing costs. The work was published in Nature Genetics.
• A simulation study to explore how to deal with missing outcome data in randomized trials and observational studies, which is an important problem and difficult to address in the analyses. This work was published in the American Journal of Epidemiology.

Principal investigators uitklapper, klik om te openen

Coordinator

Prof. dr. Carl Moons

PIs

Algra, Biessels, Greving, Kappelle, Klijn, Koffijberg, Moons, Reitsma, Rinkel, Fauser, van der Graaf, van Herwaarden, Moons, Bots, Fischer, Franx, Nathoe, Cramer, Rutten F, Hoes, Vos, Eijkemans, Roes, van de Tweel, van Delden, Kalkman, Algra, Greving, van Hout, de Wit