Clinical Investigation and Performance Evaluation Requirements
Investigations and performance studies are the evidence route used where a manufacturer cannot rely on literature or equivalence. The exam tests the regulatory mechanics and the difference between MDR investigations and IVDR performance studies.
MDR: Articles 62 to 80 and Annex XV
A clinical investigation requires a written clinical investigation plan, an ethics committee opinion and, where national law requires it, authorisation from the Member State. Annex XV specifies the content of the application dossier and the plan, including objectives, design, endpoints, statistical analysis and risk-benefit assessment. Conduct follows ISO 14155:2020 in practice. Serious adverse events must be recorded and reported: the investigator notifies the sponsor within very short, calendar-day deadlines (shorter for death or serious injury), and the sponsor forwards them to the Member State through EUDAMED. Substantial modifications require prior authorisation.
IVDR: performance evaluation and performance studies
Article 56 and Annex XIII require a performance evaluation comprising scientific validity, analytical performance and clinical performance, each documented in its own report. A performance study under Articles 57 to 77 requires a performance study plan, ethics approval and a Member State application; Class D devices additionally involve an EU reference laboratory.
Worked example
A manufacturer of a Class C IVD submits only an analytical performance report and argues that clinical performance is covered by the CE-marked comparator. The file fails Article 56: all three parts are required, and clinical performance must be demonstrated for the claimed intended use unless a performance evaluation based on equivalence is properly justified with access to the comparator's data.
Traps
Confusing the clinical investigation plan with the clinical evaluation plan; assuming ethics approval replaces Member State authorisation; omitting the scientific validity report for an IVD; and submitting a study protocol written only to ISO 14155 without the legislative references compliance requires.