RESUMO
Patient registries offer a powerful and practical means of real-world data collection system for rare diseases. Many guidelines have been released to standardize patient registries, although most of them do not address issues specific to rare disease patient registries. In November 2018, the European Medicines Agency (EMA) released a draft discussion paper on methodological and operational aspects of disease registries and made proposals on good registry practice (henceforth referred to as EMA guidance). This guidance was highly anticipated by all stakeholders with a strong interest toward governance, operationalization, and study conduct in registries. With improved clarity toward conduct of patient registries, this guidance will encourage overall registry use in regulatory decision making. TuberOus SClerosis registry to increase disease Awareness (TOSCA) was an international, multicenter patient registry to assess the manifestations, interventions, and outcomes in patients with tuberous sclerosis complex (TSC). The planning of TOSCA was initiated in 2011, patient enrolment commenced in August 2012, and final analysis database was locked in August 2017, long before the EMA guidance was released. Moreover, initial publications of TOSCA, such as first interim analysis, had also been published before the release of the EMA guidance. Extensive feedback and lessons learned from the TOSCA registry have provided insights into rare disease registry planning and operations. In this paper, we tested the recommendations from the EMA guidance on a rare disease registry, that is, the TOSCA registry. We elaborated the compliance and deviations of the TOSCA registry from the EMA guidance on a point-by-point basis. A careful observation revealed that in most aspects, TOSCA was in compliance with EMA. However, there were several practical issues identified in TOSCA, which deviated from EMA guidance. These issues demonstrate that deviations from EMA guidance, particularly in rare disease registries, do not signify compromised registry quality and can be somewhat expected in small populations. Despite multiple deviations of TOSCA from the EMA guidance, TOSCA was able to meet its objectives to enhance our understanding of TSC and its manifestations.