We are at an important inflection point in our identification and understanding of genetically based diseases, particularly rarer paediatric-onset disorders that impact neurodevelopment. Concurrent with this movement forward in our knowledge and capacity for diagnosis is a demand for increased treatment, ideally at earlier stages of development. While early diagnosis of some conditions (e.g., Autism Spectrum Disorders) has led to enhanced referral, subsequent intervention at younger ages, and better outcomes, many rarer genetically based paediatric diseases remain without such early treatment. This is particularly the case with medications and genetic interventions, which require significant time for development within the laboratory and then multiphase clinical trials to assess efficacy. The ability to engage disparately affected communities has also proven challenging. A shared commitment by both the disease support communities and drug regulatory agencies has encouraged greater efforts for increased diverse participation in clinical trials. This article reviews where we stand regarding the involvement of diverse affected communities and identifying where specific emphases can be placed, to better allow for enhanced recruitment, assessment of change, and improved outcomes.
We are in the midst of a significant revolution in our identification and understanding of genetically based diseases, particularly regarding the range of paediatric-onset disorders that impact neurodevelopment and contribute to significant morbidity and mortality. Concurrent with this substantial leap in our knowledge and resulting capacity for diagnosis is a demand for increased treatment, ideally at an earlier stage of development, to maximise outcomes and opportunities for affected individuals. Early diagnosis in such conditions as Autism Spectrum Disorders has led to enhanced referral and engagement in intervention at a younger age, and hence, better outcomes given this earlier opportunity for significant support and change. However, many of the rarer genetically based paediatric diseases, including several lysosomal storage disorders, remain elusive to early treatment. This is particularly the case regarding medications and genetically based interventions, which require significant time for development within the laboratory, followed by multiphase clinical trials, to assess their validity and efficacy. There have, however, been important improvements in identifying and developing pharmacological interventions over the past decade, specifically for diseases like the mucopolysaccharidoses (MPS), Gaucher, and Rett. And these interventions have opened promising avenues for developmental improvement.
One significant challenge has been the difficulty with more effectively connecting and engaging the diverse communities that are affected by these diseases into clinical trials, particularly at phase II and III levels. This has been identified most recently as a significant need – in recognition that many of these diseases are more readily present in diverse groups and settings where opportunity for intervention is limited. The emphasis on this particularly important challenge has led to a shared commitment by both the disease support communities, often through patient advocacy efforts, the United States Food and Drug Administration (FDA), and the European Medicines Agency (EMA), to engage greater efforts for such increased participation. With a clear emphasis on expanding treatment development in tandem with enhanced community involvement and breadth of patient engagement, it is hoped that better options for effective interventions and stronger outcomes will alter the current landscape dramatically.
This article reviews where we presently stand with regard to the involvement of the broad diversity of communities, both in the Western countries where much research takes place, but also more directly worldwide. Furthermore, we will identify and discuss where specific emphases can be placed to better allow for enhanced recruitment, assessment of change, and for improved outcomes that are seen as efficacious and valid across the range of communities these diseases affect.
