EMA develops a Concept Paper on the development of guidance concerning use of external controls for evidence generation in regulatory decision making

The European Medicines Agency (EMA) has published a Concept Paper on the Development of a Reflection Paper on the Use of External Controls for Evidence Generation in Regulatory Decision Making (Concept paper). The Concept Paper recalls the current lack of specific regulatory guidance concerning the use of external controls to support regulatory decision making in the EU. It outlines general principles for assessing when external controls could be appropriate for regulatory decision making. These will be included in the Reflection Paper to be prepared.

The principles include definition of external controls, appropriate clinical and regulatory setting and minimal requirements for external controls, operational and feasibility aspects, planning, design, conduct, analysis and reporting of studies for which external controls are used, error control, sample size and data quality. The Reflection Paper will not address issues such as use of historical data for contextualisation, external control data used to augment randomised controlled trials, and indirect comparisons using a network meta-analysis. Adoption of the Reflection Paper by the EMA’s Committee on Human Medicinal Products (CHMP) is expected by Q2 2027.