| dc.description.abstract | Abstract
Background: Advanced Therapy Medicinal Products (ATMPs) are novel medicines that often offer new opportunities to treat conditions with a high unmet medical need. To allow for early authorisation and aiming for early patient access marketing authorisation applications for ATMPs are often granted whilst the evidence is still immature, with data often having limited follow-up and small patient populations. Assessing these medicines has therefore posed challenges for both regulators and Health Technology Assessment (HTA) decision makers. Despite having been mentioned in the literature, there is little empirical evidence of similarities and differences as well as the impact on patient access.
Aim: To provide empirical insight in the similarities and differences of the evidence base used for the benefit-risk assessments by the EMA versus the relative effectiveness assessments by HTA agencies of ATMPs, and to analyse the institutions’ perceived shortcomings of the evidence base.
Methods: We performed a retrospective cohort study of the evidence packages used for the assessments of ATMPs that were performed by the European Medicine Agency (EMA) as well at least one of the following HTA institutions: the Federal Joint Committee (G-BA), the French National Authority for Health (HAS), the National institute for Healthcare and Excellence (NICE), and the National Health Care Institute (ZIN). Characteristics like the number of studies in the evidence package, the number of included studies, the pivotal trials, the main efficacy endpoints, uncertainties and assessment outcomes were extracted from the reports and analysed. The results were compared to investigate similarities and differences in the evidence provided as well as the institutions’ perceived unresolved uncertainties that were key to the benefit risk.
Results: Of the 22 ATMPs that had been approved during their medicine lifecycle, a total of 18 ATMPs had been assessed by the EMA as well as one of the before mentioned HTA institutions. This study included 68 assessment reports. Although results showed that the number of studies in the evidence base and the follow-up was largely similar when comparing reports of the institutions, differences between them emerged upon their assessment of the evidence. HTA institutions, G-BA and ZIN in particular, showed greater preference for overall survival data than the EMA when assessing oncology products. For non-oncology products, the same endpoints were generally accepted by all institutions. Differences were also seen in the types of unresolved uncertainties that were identified, with HTA agencies generally identifying more uncertainties related to efficacy (45%) than the EMA (35%). Other notable results were that G-BA had identified more uncertainties (59%) regarding the quality of evidence than other agencies and that the EMA had a greater focus on safety (33%) as compared to other institutions (15%).
Conclusion: The results of the study seem to indicate that the evidence packages used for the assessment of ATMPs is similar for various institutions. Differences emerge upon the assessment of the evidence packages, with G-BA standing out in particular. Heterogeneity in evidence needs could perhaps negatively affect patient access. Therefore, these results highlight the importance of early discussion of expectations and stimulating collaboration efforts between manufacturers, regulators, and HTA institutions during the early stage of clinical development of ATMPs. | |
