Outcome measures for children with mitochondrial disease: consensus recommendations for future studies from a Delphi‐based international workshop

Abstract

Although there are no effective disease-modifying therapies for mitochondrial diseases, an increasing number of trials are being conducted in this rare disease group. The use of sensitive and valid endpoints is essential to test the effectiveness of potential treatments. There is no consensus on which outcome measures to use in children with mitochondrial disease. The aims of this two-day Delphi-based workshop were to (i) define the protocol for an international, multi-centre natural history study in children with mitochondrial myopathy and (ii) to select appropriate outcome measures for a validation study in children with mitochondrial encephalopathy. We suggest two sets of outcome measures for a natural history study in children with mitochondrial myopathy and for a proposed validation study in children with mitochondrial encephalopathy.

Mitochondrial Diseases: Hope for the Future

“…This previous lack of clinical trial data for mitochondrial therapeutics is, in part, due to the rare nature of primary mitochondrial disorders, which impacts successful clinical trial conduct, design, and funding (Augustine, Adams and Mink, 2013). The historical scarcity of scientific evidence about the natural history (disease symptoms, heterogeneity, and progression) and the underlying disease mechanisms, in addition to the lack of clinically and regulatorily meaningful, standardized measures to assess outcomes, have collectively been recognized as critical disadvantages in informing clinical trial design in the field (Newman et al, 2015;Koene et al, 2018;Parikh et al, 2019).…”

Mitochondrial disorders and drugs: what every physician should know

“…The use of sensitive and valid endpoints is essential to test the effectiveness of potential treatments 131. A set of recommended outcome measures to be implemented in clinical studies has been identified 132.…”

Movement Disorders in Children with a Mitochondrial Disease: A Cross-Sectional Survey from the Nationwide Italian Collaborative Network of Mitochondrial Diseases

“…In order to evaluate the course of movement disorder over time, we set the online questionnaire to collect information on the motor skills of patients and their level of dependence in activities of daily living, assessed both at the onset and at the last follow-up. We also collected data on standardized rating scales used to measure the severity of movement disorder [ 25 ] if available, and reported the evolution over time and whether the course of the movement disorder was stable, or fluctuations were seen. We also asked centers (all experts in evaluating and treating patients with movement disorders) to cite drugs used in their patients and to report dichotomously their expert global impression of change since last assessment (using a “yes” or “no” response to specific treatment).…”