As in other medical fields, the shift toward scientific-based clinical practice in both diagnostics and treatment is ongoing in child and adolescent psychiatry [9]. However, numerous characteristics more or less specific for our field impede the generation of evidence and therefore in the end the implementation of evidence-based guidelines. Three examples serve to illustrate this impediment. (1) The low level of introspection of young subjects reduces diagnostic accuracy. (2) The high rates of comorbidity limit specificity and generalization of findings. (3) The requirement of caregivers' consent for study participation hampers recruitment efforts. Such issues entail the frequently posed question: ''How large is the impact and cost-benefit ratio of the different sampling methodologies, i.e., comparing register-based versus clinically selected versus single case studies [8] ? '' Interestingly, in the current issue of European Child and Adolescent Psychiatry there is only one randomized controlled trial (RCT). Van den Hoofdakker et al. [12] explored the influence of paternal variables on the outcome of behavioral parent training (BPT) in n = 83 children with attention-deficit/hyperactivity disorder (ADHD) by comparing a group receiving BPT plus ongoing routine clinical care (RCC) versus an RCC alone group. This is all the more noteworthy as across the medical sciences RCTs are often considered as the most important source of evidence. But RCTs face important ethical and logistical constraints, particularly in children and adolescents with the consequence of, e.g., smaller sample sizes and shorter observation periods. In addition, RCTs have been criticized for focusing on highly selected populations and outcomes.All the other findings in the current issue are based on much larger sample sizes. Four studies used questionnaires in large samples of children and adolescents [1,2,5,7]. One population-based study rendered possible via linkage of records of three health data sets compared disordered (ADHD; n = 11,902) and non-disordered children (healthy controls; n = 27,304) under 18 years [11]. Two reviews, one on studies which reported white matter/gray matter changes in pediatric and adolescent bipolar disorder/unipolar depression, as detected by diffusion tensor imaging and voxel-based analysis [10], and the other providing an overview of ASD screening studies and ongoing programs across Europe [4], also report findings on large cumulated total samples of clinically diagnosed patients.But do studies with larger sample sizes result regularly in findings of higher quality or relevance?First, the advantages of a large sample size include a more precise estimate of the effect size and an easier assessment of the representativeness of the sample and the generalizability of the achieved results. However, a small effect size may not prove to be of clinical relevance. In addition, both selection bias and the negative impact of confounders need to be considered with care. The reduced number of variables and/or quality of ...