This is the introductory paper in a series of eight papers. In this series, we integrate the theoretical design options with the practice of conducting pragmatic trials. For most new market-approved treatments, the clinical evidence is insufficient to fully guide physicians and policy makers in choosing the optimal treatment for their patients. Pragmatic trials can fill this gap, by providing evidence on the relative effectiveness of a treatment strategy in routine clinical practice, already in an early phase of development, while maintaining the strength of randomized controlled trials. Selecting the setting, study population, mode of intervention, comparator, and outcome are crucial in designing pragmatic trials. In combination with monitoring and data collection that does not change routine care, this will enable appropriate generalization to the target patient group in clinical practice. To benefit from the full potential of pragmatic trials, there is a need for guidance and tools in designing these studies while ensuring operational feasibility. This paper introduces the concept of pragmatic trial design. The complex interplay between pragmatic design options, feasibility, stakeholder acceptability, validity, precision, and generalizability will be clarified. In this way, balanced design choices can be made in pragmatic trials with an optimal chance of success in practice.

The aim of this position paper is to de®ne quality control and acceptance criteria for measuring passive respiratory mechanics in infants using the occlusion techniques to ensure that valid results are obtained. These guidelines cover numerous aspects including: 1) terminology and de®nitions; 2) equipment; 3) data acquisition; 4) data handling and analysis; 5) reporting of results. Adherence to these guidelines should ensure that measurement of passive respiratory mechanics in infants in different lung function laboratories could be performed with an acceptable degree of safety, precision, and reproducibility. This will facilitate multi-centre collection of data and performance of clinical investigations.

EMBLEM is to our knowledge the largest prospective observational study assessing patients during and after an acute episode of mania. Work impairment is significant in the year prior to an acute episode of mania.

Dual mania represents a distinct and not infrequent subgroup of patients with mania. The exclusion of patients with comorbid substance problems from clinical trials creates a gap in our knowledge on treatment effectiveness.

Several factors either predictive of or associated with overall response to antidepressant treatment have been identified. Inclusion of factors predictive of response in the design of future trials may help tailor treatments to depression patients presenting to the average clinical practice, resulting in improved outcomes.