From authorisation to clinical practice: evolution of the use of biological medicines according to the SmPC and guidelines (2006 to 2025).

purposeAfter the marketing authorisation of biologicals, uncertainty often remains regarding their real-world effectiveness, safety, and rational use. This study investigates how frequently the recommended use of biologicals changes post-authorisation, and who funds the studies leading to these changes.

methodsBiologicals receiving a positive opinion for adult indications by the Committee for Medicinal Products for Human use (CHMP) between 2006 and 2010 were identified. For each indication, we compared the initial and current Summary of Product Characteristics (SmPC), as well as current SmPC and European clinical guidelines, to identify discrepancies in start and stop criteria, dosage, and administration frequency. We assessed whether discrepancies led to increased or decreased use of the biological and whether this was associated with the sponsor type of supporting publications.

findingsSmPC changes, driven by Marketing Authorisation Holder (MAH)-sponsored studies, were found in 47% of identified indication-biological combinations: 41% led to increased use, 29% to decreased use, and 29% were neutral. Guideline-SmPC discrepancies, mostly supported by publicly sponsored studies, were identified in 75% of cases, with most discrepancies (86%) recommending decreased use. Publications sponsored by public healthcare stakeholders were associated with decreased use, as compared to publications sponsored by the MAH (p < 0.05, OR 28·2, 95% CI 4·8-166·1).

conclusionRecommendations for the use of biologicals often evolve post-authorisation. MAH-sponsored studies tend to support increased use, whereas guideline recommendations, typically based on publicly sponsored studies, more often favor restriction. Rational use of biologicals requires timely evidence generation and should ideally lead to amendments in SmPC's.