Diagnostic tests are performed for various reasons. Testing has both positive and negative effects on patient outcome. The main effects are indirect, mediated through treatment decisions and their... Show moreDiagnostic tests are performed for various reasons. Testing has both positive and negative effects on patient outcome. The main effects are indirect, mediated through treatment decisions and their impact on patient outcome. To base test decisions on expected net benefit, it is important to estimate or measure those effects in a structured manner. Positive and negative effects vary over the different stakeholders in test decisions: the healthcare provider, patient and society. While testing in a situation with low pre-test probability for a certain condition can be highly valued by patients, the associated costs of testing, with limited effect on patient outcome, diverts resources from societal areas with higher benefit. In this thesis we quantified the benefit of testing across different aspects of value of diagnostic information using a pediatric example, and provided argumentation and guidance for structured evaluation of existing screening programs. We explored practice variation in pediatric testing and interviewed pediatricians to elucidate their considerations in test decisions. The general discussion provides guidance on how to increase the efficiency and thus quality of testing through both system-level interventions and interventions directed at individual providers and patients. We argue that limiting testing in diagnostic situations with a (very) low pre-test probability is equally important as a structured evaluation of test consequences for efficient use of public resources. Show less
Women with breast cancer often wonder whether they should have their other breast removed as well, to prevent a potential tumor from developing there. The exact risks vary significantly per person.... Show moreWomen with breast cancer often wonder whether they should have their other breast removed as well, to prevent a potential tumor from developing there. The exact risks vary significantly per person. We used information about patients, breast cancer characteristics and treatments, and rare and common genetic variant correlated with a higher or lower risk of developing breast cancer in the other breast in large datasets to develop and validate statistical models to predict each patient’s risk of developing a tumor. We investigated whether and how these models might be clinically useful to better inform patients and physicians to tailor clinical decision making about potential strategies to prevent or early detect a tumor in the opposite breast. We discussed statistical aspects about model development and validation, and we provided frameworks about how to develop and assess prediction performance of risk prediction models using motivating examples in breast cancer. Show less
A significant proportion of the in-hospital antimicrobial consumption is used in the empiric setting, making empiric therapy an important target of stewardship interventions.Empiric antimicrobial... Show moreA significant proportion of the in-hospital antimicrobial consumption is used in the empiric setting, making empiric therapy an important target of stewardship interventions.Empiric antimicrobial therapy is the antimicrobial regimen that is started when the definite clinical diagnosis, causative agent and/or resistance pattern are yet unknown. Empiric therapy is accompanied by a varying level of uncertainty. In daily clinical practice, this uncertainty about the source, pathogen and susceptibility pattern are often managed by prescribing relatively broad-spectrum antimicrobial therapy. This has potential negative effects, such as toxicity and selective pressure resulting in antimicrobial resistance. Balancing the potential benefits and drawbacks of more broad-spectrum therapy is a substantial challenge, in particular when the level of uncertainty is high.This thesis aims to address the uncertainties most relevant in daily clinical practice in empiric antimicrobial therapy, to determine how they affect daily decision making, and to explore how this can be translated in antimicrobial policy making and antimicrobial stewardship. Show less
