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International Paediatric Mitochondrial Disease Scale
Saskia Koene1, Jan C M Hendriks2, Ilse Dirks3
1Radboudn Center for Mitochondrial Medicine at the Department of Paediatrics, Radboudumc, Geert Grooteplein 10. 6500 HB, PO BOX 9101, Nijmegen, The Netherlands. Saskia.koene@radboudumc.nl.
Insights
The International Paediatric Mitochondrial Disease Scale (IPMDS) is a reliable tool for assessing children with mitochondrial diseases. This new scale shows good feasibility, construct validity, and reliability for clinical trials.
Area of Science:
- Pediatric Neurology
- Rare Diseases
- Clinical Outcome Measures
Background:
- Mitochondrial diseases in children lack standardized outcome measures.
- The Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) is an existing measure.
- International collaboration is needed to develop universal assessment tools.
Purpose of the Study:
- To adapt the NPMDS into the International Paediatric Mitochondrial Disease Scale (IPMDS).
- To evaluate the feasibility, construct validity, and reliability of the IPMDS in a multicenter setting.
- To establish a reliable tool for assessing pediatric mitochondrial disease progression.
Main Methods:
- A Delphi-based process involving international experts, patients, and caretakers.
- Pilot reliability study in eight pediatric patients.
- Multicenter study evaluating feasibility, construct validity, and reliability in 17 patients (aged 1.6-16 years) across five centers.
Main Results:
- The IPMDS demonstrated good feasibility with low missing item rates (4%) and positive user feedback.
- Principal component analysis revealed three factors explaining 57.9% of the variance.
- Good construct validity and high interrater reliability (median ICCagreement 0.85) were observed.
Conclusions:
- The IPMDS is recommended for assessing the natural history of pediatric mitochondrial diseases.
- Further research should explore construct validity, age limits, responsiveness, and minimal clinically important differences.
- The IPMDS can aid in sample size calculations for future clinical trials.
Objective:
There is an urgent need for reliable and universally applicable outcome measures for children with mitochondrial diseases. In this study, we aimed to adapt the currently available Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) to the International Paediatric Mitochondrial Disease Scale (IPMDS) during a Delphi-based process with input from international collaborators, patients and caretakers, as well as a pilot reliability study in eight patients. Subsequently, we aimed to test the feasibility, construct validity and reliability of the IPMDS in a multicentre study.
Methods:
A clinically, biochemically and genetically heterogeneous group of 17 patients (age 1.6-16 years) from five different expert centres from four different continents were evaluated in this study.
Results:
The feasibility of the IPMDS was good, as indicated by a low number of missing items (4 %) and the positive evaluation of patients, parents and users. Principal component analysis of our small sample identified three factors, which explained 57.9 % of the variance. Good construct validity was found using hypothesis testing. The overall interrater reliability was good [median intraclass correlation coefficient for agreement between raters (ICCagreement) 0.85; range 0.23-0.99).
Conclusion:
In conclusion, we suggest using the IPMDS for assessing natural history in children with mitochondrial diseases. These data should be used to further explore construct validity of the IPMDS and to set age limits. In parallel, responsiveness and the minimal clinically important difference should be studied to facilitate sample size calculations in future clinical trials.
