Abstract

Objectives

Inclusion of patient-reported outcome (PRO) data in Summaries of Product Characteristics (SmPCs) and package leaflets published by the European Medicines Agency (EMA) is critical to communicate patient-reported value of new medicines. This study aimed to identify key issues in the incorporation and interpretation of PROs in clinical trials that may hinder approval of PRO-related language in SmPCs/package leaflets.

Methods

Indications of new medicines recommended for approval by the EMA between 2020 and 2023 were identified. The Public Assessment Reports, SmPCs, and package leaflets were systematically reviewed. Information pertaining to inclusion of PROs in confirmatory trial(s) and PRO-related reviewer comments were extracted and categorized.

Results

Of 167 indications examined, 58 (35%) included PRO-related statements of treatment effect in the SmPC/package leaflet. Critical comments by EMA reviewers focused on study design and PRO data robustness, concerns about statistical analysis, data quality, and PRO measure appropriateness. Such critiques did not always lead to exclusion of PROs from the SmPC, particularly when PRO endpoints were multiplicity-controlled. PRO data collected in unblinded trials—sometimes unavoidable—were often deemed acceptable if multiplicity-controlled.

Conclusions

Review findings emphasize that thoughtful selection of PRO measures, their implementation in trial protocol design, and appropriate statistical analysis planning can strengthen the credibility of PRO results in confirmatory trials, which is critical for supporting the approval of PRO-based value messaging. Insights generated may be used by marketing authorization applicants to support a favorable assessment of PRO data by the EMA.