Disease Registries and Outcomes Research in Children

Abstract

Assessing medicines specifically for use in children has been neglected in the past, with the majority of formal clinical studies being conducted in adults. Clinical trials are a pivotal part of the drug approval process; however, they are not always applicable to the diverse populations - including children - that receive the drug after approval. They may not be the most informative assessment tool, especially in rare (or orphan) disorders where there are few patients, due to a lack of existing natural history data and the challenges of designing appropriately powered statistical analyses. Disease registries, which can collect clinical information in larger, more heterogeneous populations than can be included in a clinical trial, are becoming increasingly valuable. Their use is particularly beneficial for diseases affecting very small patient populations, such as lysosomal storage disorders (LSDs), and for looking at specific populations, for example, children. Such disease registries can provide natural history data as well as enable the impact of therapy to be examined. Moreover, despite potential limitations of enrollment bias and unmonitored data, patient registries can play a valuable role in assuring pediatric health, providing longitudinal data that can be used to monitor developmental outcomes in chronic lifelong diseases, and assessing the effectiveness of treatment. This review describes the role of registries in drug development and regulatory approval, the impact of global registry programs on pediatric research, with some examples from the field of LSDs, and how registries are impacting the clinical care such children receive.

Ten years of the Hunter Outcome Survey (HOS): insights, achievements, and lessons learned from a global patient registry

“…As a result, clinical data obtained in the real-world setting over a longer period of follow-up in larger patient groups are increasingly required to complement and extend findings from clinical trials. This is particularly true for rare diseases, where the number of patients available to participate in trials is often small and the natural disease course may be poorly defined or highly variable [2]. Patient registries are valuable sources of information on disease course and treatment outcomes, and there are now more than 600 rare disease registries in Europe alone [3, 4].…”

Limitations of drug registries to evaluate orphan medicinal products for the treatment of lysosomal storage disorders

“…The European authorities therefore depend heavily on the outcomes of these registries for final authorization. The need for a post-marketing surveillance system to improve our understanding of long term effectiveness and safety of treatments for LSD's is not debated and LSD registries have proven to add meaningful data [8]. However, the EMA requires separate post-marketing registries for each drug, even when more OMP's are available for one rare disease.…”

Designing robust clinical trials for orphan drugs

“…females, children) may be answered, which normally would not be possible in the case of rare disease studies (Jones et al 2011;Hoffmann et al 2005;Hughes et al 2011;Ramaswami et al 2012). However, limitations introduced by selection bias should be kept in mind.…”