Department of Health

Eshghi A

European Organisation for Rare Diseases

Karnebeek CDM

English

Chin, Richard

Edinburgh Research Explorer

Lumpers versus Splitters: towards finding a common ground in classifying paediatric rare and progressive genetic conditions There is increasing awareness of the importance of rare diseases (RD).  Individually such diseases may be considered rare but collectively they are not. An estimated 8% of people have one of the 6000–8000 known RD(1).  In 2002, in the USA, the National Institutes of Health Office of Rare Diseases Research (ORDR) was established.  In 2008, the European Commission adopted a communication setting out an overall Community strategy to support Member States in diagnosing, treating and caring for European Union citizens with RD. 2013 saw the publication of the United Kingdom’s Strategy for Rare Diseases.  Research is a key element of the European Commission and United Kingdom strategies.  Research on RD can be hampered by the low prevalence of individual diseases. However, coordination on an international scale, can overcome this, facilitating gathering and analyzing of a large pool of individual patient cases and or groups of conditions, leading to new insights into RD with potentially far-reaching patient benefits.  Shared understanding is central to such coordination and is best achieved through an internationally agreed classification but establishing such a classification can be difficult in itself(2).  In this edition of the journal, van Karnebeek et al (REF TBC) report on their development of a novel classification system to facilitate research reporting in paediatric rare and progressive genetic conditions.  Through a 5-year prospective, longitudinal, descriptive study of the natural history of progressive paediatric genetic conditions, the authors identified 113 individual conditions and were faced with the challenge of grouping them to highlight the similarities and differences between conditions, while also providing enough definition to create meaningful categories for data reporting in the research setting. They reviewed available classification systems and concluded that they all failed to provide either a useful level of specificity or generalization for the conditions they had identified. Further, none specifically focused on rare, progressive childhood conditions due to genetic disorders.  Their approach of using a small panel of experts to draft an initial classification system and then apply a Delphi system to obtain consensus and improve on it to arrive at a final classification may not be the approach that others may have used. Indeed, others may have preferred a statistically driven cluster analysis or latent class analysis(3) but such approaches would still need clinical input to ensure there was biological plausibility/rationale for obtained categories Sceptics will no doubt also point out that some areas of the classification performed better than others and that this variability in performance lessens igeneralisability. Others may question the sample size of conditions, and the non-blinded nature of the modest number of assessors used in each round of the Delphi process.  The “splitters” may not be inherently keen on the “lumping” approach.  However, despite these drawbacks, for the reasons outlined earlier this is a well needed, logical proposed classification for rare and progressive genetic paediatric diseases. Further studies to validate the proposed classification, with larger cohorts and larger number of blinded assessors from a wider background are needed. It may not be the final system used, but the early signs are encouraging.  It has the potential of a landmark new system that could become the standard for the field.    References1.	European Organisation for Rare Diseases (EURORDIS). "Rare Diseases: Understanding This Public Health Priority". 2005. 2.	Berg AT. New classification efforts in epilepsy: Opportunities for clinical neurosciences. Epilepsy Behav. 2016;64(Pt B):304-5.3.	Eshghi AH, D.; Legrand, P.; Skaletsky, M.; Woolford, S. . Identifying Groups: A Comparison of Methodologies. Journal of Data Science. 2011;9:271-91.2.	Berg AT. New classification efforts in epilepsy: Opportunities for clinical neurosciences. Epilepsy Behav. 2016;64(Pt B):304-5.3.	Eshghi AH, D.; Legrand, P.; Skaletsky, M.; Woolford, S. . Identifying Groups: A Comparison of Methodologies. Journal of Data Science. 2011;9:271-91.

Reporting rare paediatric progressive genetic conditions: a step towards international classification

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https://www.pure.ed.ac.uk/ws/files/105264275/dev_med_commentary_1.doc

Reporting rare paediatric progressive genetic conditions: a step towards international classification

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