Edition of 07 July 2023

A team from the US Food and Drug Administration (FDA) has published a study of the different rare diseases and conditions targeted by orphan drug designations since the passage of the Orphan Drug Act.

In 1983, Congress passed the US Orphan Drug Act to incentivise the development of treatments for rare diseases which were otherwise not financially viable. In the forty years since, a total of 6,340 orphan designations have been granted, for treatments targeting 1,079 rare diseases. In total, the authors found that in the United States, approximately 5% of rare diseases have an FDA-approved drug. Additionally, there is at least one drug that has been developed and shown promise in the treatment, diagnosis or prevention of as many as 15% of RD.

Despite the improvements in available treatments which have been observed over the past four decades, there remains a need for further funding of basic and translational science to continue fulfilling the unmet medical needs of the rare disease community.

A new article in the European Journal of Human Genetics seeks to understand the service experiences and needs of parents undergoing genetic testing for rare diseases. To this end, a literature review was performed of studies conducted between 2000-2009 to identify parents’ unmet genomic services needs.

As the clinical and economic utility of exome and genome sequencing becomes better understood, there is an increasing demand for such testing that genetic services are currently unable to meet. It is important to understand the perspectives and needs of stakeholders, such as parents, in order to begin fulfilling this need by effectively integrating genetic services into mainstream clinical practice.

A number of common values were identified which were important to many parents. These included feeling “cared for”; continuous relationships with clinicians; empathic communication; provision of informational and psychosocial resources following results disclosure; and more. The study also uncovered challenges reported by parents when accessing genomic services, such as finding it difficult to absorb information during appointments, and long waiting times for test results.

Overall, the authors found that parents’ opinions of what constituted ‘good’ care in genetics was similar to what is considered ‘good’ healthcare more generally. Furthermore, the challenges identified in the study point to opportunities for how integrating genetic testing into paediatrics can be used to improve parents’ experiences, for example through more robust emotional and/or informational support. Despite these opportunities, however, there is a need for further evidence to investigate which specific interventions would be effective at fulfilling unmet parental need in genetic testing for rare diseases.

A study was recently published in the Annali dell’Istituto Superiore di Sanità which draws on data from family caregivers (FCs) for ten different rare diseases to analyse gender-specific differences of burden and quality of life.

Results from previous studies have indicated that female FCs (typically mothers) have significantly larger impairments to their QoL and mental health when compared to their male counterparts (typically fathers). However, there is a lack of such research specific to rare diseases. It is therefore unclear whether or not the rarity of such conditions may exacerbate these disparities.

In response to this uncertainty, the authors analysed data from a cross-sectional study coordinated by the Italian National Center for Rare Diseases in the framework of the BURQoL-RD project, which was funded by the European Commission. They found that there was a significant difference in the number of hours women devoted to care each week as compared to men, indicating that they are in turn at a higher risk for burden. A higher level of burden is in turn indicated with a poorer FC QoL. An association was also found between burden and the severity of the child’s disease.

Overall, there is a clear need for a gender-conscious approach in rare disease policy. The findings with this study on gender differences, as well as the identification of specific diseases which are associated with higher levels of FC burden/lower FC QoL, can be used in the future to help improve accuracy and equity in public health interventions.

A recent article in BMC Medical Research Methodology proposes a new method which uses frequency-based rare diagnoses (FB-RDx) to identify rare disease patients in large medical datasets. This method shows potential for capturing rare disease data more comprehensively than other existing approaches.

Currently, the 10^th revision of the International Classification of Diseases (ICD-10) is the most commonly used disease classification system for health data. However, there are significant limitations for its use in coding RD. The Orphanet nomenclature system is much more appropriate for RD, but not all countries have yet successfully implemented ORPHAcodes into their routine coding practice. When this is the case, ICD-10 is typically still used, making it difficult to identify RD patients in such datasets for research purposes.

As a solution to this challenge, the authors propose the use of FB-RDx when working with large datasets coded with ICD-10. In this approach, the frequency of all diagnoses in the dataset is used to determine whether or not a diagnosis is rare.

The authors tested this approach on data provided by the Swiss Federal Statistical Office, and analysed outcomes such as in-hospital death and admission to ICU for the 10% of patients with the least frequent diagnoses compared to more common diagnoses. They found that FB-RDx was an appropriate surrogate for rare diseases in this and similarly large datasets. It was also found that FB-RDx may support more comprehensive identification of rare diseases.

Despite these findings, further research is needed before this method can be broadly recommended. Future work should explore the question of which percentile of rare FB-RDx is a suitable surrogate for RD; there is also a need to test the approach on other types of patient populations, as this study was limited to only data on inpatients.