EMA: Scientific guideline: Reflection paper on the need for active control in therapeutic areas where use of placebo is deemed ethical and one or more established medicines are available, draft:
This paper describes regulatory considerations, and expectations of applicants, in discussing the importance of a direct comparison to active control for a properly informed decision on benefit-risk. The scope of the paper is limited to those therapeutic areas where placebo is deemed ethical and one or more established medicines are available. The principles outlined are applicable to pivotal trials to establish efficacy and safety, for ‘add-on’ trials as well as trials without background treatment. CHMP has previously provided Position Statements on issues related to this topic (EMEA/17424/01 and EMEA/119319/04). This paper supplements these documents. The paper should be read in conjunction with relevant therapeutic area and methodological guidance documents.