Per-protocol analysis (PP analysis, also known as efficacy analysis or valid-case analysis) is a secondary or supplementary analysis strategy in clinical trials in which only those participants who fully and correctly complied with the study protocol are evaluated. This generally includes: receipt of the intended treatment (at least a defined compliance threshold), no serious protocol violations, and complete collection of the primary endpoint.
The PP analysis estimates the efficacy of a treatment under optimal conditions (efficacy), whereas the Intention-to-Treat analysis (ITT) measures effectiveness under real-world conditions. In superiority trials, the ITT analysis is primary; the PP analysis serves as a sensitivity analysis. In equivalence and non-inferiority trials, the PP analysis is equally weighted or primary, since protocol violations here can systematically lead to a convergence of the groups (conservative bias in favour of the null hypothesis).
The definition of the PP population must be established in the Statistical Analysis Plan (SAP) before database lock, in order to avoid post-hoc selection bias. For CROs, careful documentation of protocol violations (protocol deviations) is a prerequisite for a valid PP analysis. Regulatory reference: ICH E9, CPMP/EWP/908/99 (Non-Inferiority Studies).