The Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG) released a formal statement on 23 October 2025 regarding a draft concept paper from the European Medicines Agency. The source document, Stellungnahme des IQWiG zum Entwurf eines Konzeptpapiers der EMA zur Erstellung eines Reflexionspapiers über den Einsatz externer Kontrollen zur Evidenzgenerierung in der regulatorischen Entscheidungsfindung (Statement of IQWiG on the draft of an EMA concept paper for the creation of a reflection paper on the use of external controls for evidence generation in regulatory decision-making), addresses the rising use of single-arm trials in drug development.
Thomas Kaiser, Director of IQWiG, oversaw the submission. This intervention comes as the European Union implements its Joint Clinical Assessment (JCA) legislation, which seeks to harmonise the scientific evaluation of innovative treatments across member states. Previously, regulatory bodies and health technology assessment (HTA) organisations often operated under diverging evidence requirements. The new measures aim to align these processes while ensuring high standards for patient-relevant data.
The German institute highlighted that while external controls are increasingly common, basic methodological requirements are often unmet. Specifically, the statement insists that reliable adjustments for confounding variables are only possible using individual patient-level data. The authority explicitly recommended against using aggregated data for un-anchored indirect comparisons, as this often leads to unreliable results in determining a drug’s added benefit.
The implementation of these standards will influence how manufacturers design their clinical programmes for the European market. By aligning with guidance from the EU Health Technology Assessment Coordination Group, the Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen ensures that evidence generated for marketing authorisation remains robust enough for subsequent national reimbursement negotiations.
Future drug submissions will require a more systematic identification of confounding variables and a greater reliance on individual patient data. Products that fail to meet these stricter methodological thresholds risk receiving unfavourable assessments during the joint European evaluation process, which could hinder their path to market entry and funding.
Source: Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG)
Link: Statement of IQWiG on the draft of an EMA concept paper for the creation of a reflection paper on the use of external controls for evidence generation in regulatory decision-making
Date: 23 October 2025