Moving test accuracy research forward

This thesis addresses challenges in biomarker and test evaluation research, particularly focusing on non-invasive biomarkers for detecting outcomes in patients with non-alcoholic fatty liver disease (NAFLD). NAFLD is a progressive disease characterized by fat accumulation in hepatocytes, and liver biopsy is the current standard for diagnosis, but non-invasive alternatives are sought.
First, systematic reviews and meta-analyses to assess the diagnostic accuracy of cytokeratin-18 (M30 and M65 antigens) and vibration controlled transient elastography (VCTE) as potential biomarkers for NAFLD (Chapters 2 and 3) were performed. Prognostic accuracy of three established liver tests for detecting future NAFLD-related events is evaluated in Chapter 4, leading to the development of a risk of bias tool called QUAPAS to appraise prognostic accuracy studies (Chapter 5).
After the evidence synthesis phase, a comparative diagnostic accuracy study evaluates seventeen biomarkers, multi-marker scores, and VCTE for detecting NAFLD conditions (Chapter 6). This study inspires the development of diagnostic models using supervised machine learning techniques (Chapter 7). We further evaluated the role of covariates in ROC curve analysis in the context of D-dimer as a diagnostic test for venous thromboembolism (Chapter 8).
With this research, we emphasize the need to systematically consider factors that can modify test performance or introduce bias in evaluating test performance. By doing so, the thesis aims to expand our understanding of the operational characteristics of medical tests and optimize their implementation for specific purposes, settings, or patient profiles.
The work presented in the thesis aims to raise awareness of the complexities involved in test accuracy evaluation and encourages the thoughtful consideration of novel methods and technologies in future research. By addressing these challenges, researchers can contribute to the development of more effective and reliable diagnostic alternatives for NAFLD and other medical conditions.