Edition of 15 September 2023

A new article has been published in Clinical Therapeutics, investigating how societal preferences for non-health outcomes can influence decisions on resource allocation in healthcare.

In a study conducted in Australia, participants were asked to choose between health gains from the treatment of modern conditions and non-health gains in families with a child affected by a rare disease. Researchers found that participants were willing to trade-off adult health gains with the familial non-health benefits of genomic testing.

Traditional models of economic evaluation for health services focus primarily on health outcomes, and rarely take non-health effects into account. However, the findings of this study demonstrate that, in the case of genomic testing for rare diseases, services would be undervalued by this methodology. As a result, the authors call for a more systematic inclusion of non-health effects in economic evaluation processes.

A scoping review has been published in the Journal of Global Health which investigates the impact of primary health care (PHC) on people living with rare diseases, particularly in low- and middle-income countries (LMIC).

The study draws on evidence from 80 publications, representing data from almost 80,000 individual patients and over 4,000 health care providers. Overall, it was found that PHC services were a highly valuable resource for providing rare disease patients with timely diagnosis and quality, coordinated care. However, several publications also highlighted that current medical curricula are rarely adequate at preparing health care providers to recognise signs of an undiagnosed rare disease.

The authors also highlight the potential of PHC for improving access and health-related outcomes in LMIC, and discuss the implications this could have for addressing the unmet medical needs of the rare disease community in such regions.

An article has been published in PLoS One which examines the psychosocial impact of receiving a rare disease diagnosis, and how it is related to diagnostic delay. Drawing on survey responses from individuals registered in the Spanish Rare Diseases Patient Registry, researchers were able to elaborate the relationships between diagnostic delay, psychosocial impact, social determinants, and personal consequences.

The study found that individuals who experienced a diagnostic delay of over a year experienced greater psychosocial impact, and were more likely to be in need of psychological care while searching for a diagnosis. They also experienced exacerbated social effects, such as having more difficulty explaining symptoms to friends and family, and lost more independence.

Overall, this study demonstrated the importance of timely diagnosis for people living with a rare disease. It also points to the need for providing adequate psychological support for patients currently experiencing diagnostic delay.

Recently, an article was published in the Orphanet Journal of Rare Diseases describing how a new type of statistical methodology which allows for composite endpoints can be adapted to rare diseases. This article was written in the context of the European Joint Programme on Rare Diseases (EJP RD) series on innovative methodologies for rare diseases clinical trials, and draws on participant responses to a webinar on composite endpoints in rare diseases.

Because of the complexity of rare diseases, a single endpoint is often not sufficient to fully understand the efficacy of a new treatment in a clinical trial setting. However, there are challenges to using composite, or combined, endpoints due to limitations when conducting statistical analyses. Generalised pairwise comparisons are emerging as a statistical methodology for evaluating studies using composite endpoints which overcomes a number of these limitations. This approach shows particular promise for rare diseases, as it performs well with small sample size, and allows for outcomes to be prioritised according to clinical severity.

The potential of generalised pairwise comparisons for rare diseases was further demonstrated by the authors, through a post-hoc analysis of a small-sample trial in epidermolysis bullosa.

PLoS One recently published a study in which researchers leveraged clinical terminologies such as the Orphanet Rare Disease Ontology (ORDO) and the ICD-11 to create a classification system for inherited retinal diseases (IRD).

To develop the terminology, a list of IRDs was annotated based on a thorough literature review. The final classification was based on this list, along with concepts observed in other codification systems. In total, 158 concepts were classified into 6 categories, with genetic subtypes added to the concepts as needed. By developing a classification system specific to IRD, the authors were able to optimise it for this group of diseases and cover concepts not included in other terminologies.

Based on their findings, the authors suggest that their classification system could be used in situations such as clinical documentation, or informing future updates to other standard terminologies. The specificity of their terminology also suggests that other groups of rare diseases might benefit from work towards disease-specific systems. However, this may pose challenges related to data interoperability.