Abstract
ObjectiveThere 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.MethodsA 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.ResultsThe 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).ConclusionIn 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s10545-016-9948-7) contains supplementary material, which is available to authorized users.
Highlights
Mitochondrial diseases (MD) are the most prevalent inherited metabolic diseases, with an incidence of ∼1:5000 live births (Schaefer et al 2004)
There is no cure for MD, but there are some promising results of pharmacological interventions in cells and animals, and the prospects for randomised clinical trials of novel and repurposed pharmaceuticals are increasing (Koene and Smeitink 2009; Wenz 2009; Viscomi et al 2011, 2015; Koopman et al 2012; Blanchet et al 2015; Peng et al 2015)
Outcome measures that are valid, reliable, sensitive and clinically relevant are critical to the success of such trials, but the heterogeneity and multisystemic nature of MD pose significant challenges in choosing an appropriate, universally applicable outcome measure (Koene et al 2013a)
Summary
Mitochondrial diseases (MD) are the most prevalent inherited metabolic diseases, with an incidence of ∼1:5000 live births (Schaefer et al 2004). The most commonly affected organs and tissues include the brain, eye, heart, and skeletal muscle (Koopman et al 2012). Whereas some children with MD thrive in mainstream school and live well into adult life, others follow a more rapidly progressive course and die in the neonatal period or function at a low level, barely interacting with their environment. There is no cure for MD, but there are some promising results of pharmacological interventions in cells and animals, and the prospects for randomised clinical trials of novel and repurposed pharmaceuticals are increasing (Koene and Smeitink 2009; Wenz 2009; Viscomi et al 2011, 2015; Koopman et al 2012; Blanchet et al 2015; Peng et al 2015). To be able to measure disease severity and progression within the full range of the phenotypic spectrum, a combination of objective, subjective, functional and biochemical end points will probably be necessary
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