[Roaming through methodology. XII. Pragmatic and pathophysiologic trials: a question of goal formulation]

The design of clinical trials depends on the research question. In pragmatic trials the research question is: 'How do I treat patients with this disease?' In explanatory trials this question is: 'What is the mechanism of this new treatment?' Pragmatic trials are characterised by liberal patient selection, open treatment modalities corresponding with regular care, outcome measures considered from the patient's perspective and intention-to-treat analysis. In explanatory trials patient selection is strict and treatment is double-blind and pathophysiologically pure. Often proxy outcome measures are used and emphasis is on per protocol ('on treatment') analysis.