COSMIN database

Towards the harmonization of outcome measures in children with mitochondrial disorders

Koene, S., Jansen, M., Verhaak, C. M., De Vrueh, R. L., De Groot, I. J., and Smeitink, J. A.
AIM: A clinical trial is only as reliable as its outcomes, therefore the careful and systematic selection of outcome measures is extremely important. Currently, the selection of outcome measures for clinical trials designed to evaluate new drugs in patients with mitochondrial disorders is inefficient and has not been addressed systematically. Given that meaningful data can be obtained only from trials in which outcomes are assessed using valid instruments, one should first focus on the validation of a set of selected instruments in the target population. The aim of this review is to systematically select a 'toolbox' of robust outcome measures that are relevant to all patients.

METHOD: Using an extensive search of published literature, we systematically compiled a toolbox with outcome measures based on a primary search for possible instruments Subsequently, we reduced this toolbox using strict criteria that were adapted from the United States Food and Drug Administration.

RESULTS: A toolbox with clinically relevant and psychometrically robust instruments for performing clinical research in children with mitochondrial disorders was compiled.

INTERPRETATION: In coming years, more experience using these outcome measures in children with various mitochondrial disease phenotypes must be obtained before reliable conclusions regarding the validity of these instruments can be drawn.
Dev Med Child Neurol
1469-8749 (Electronic)
Publication year:
Symptom status:
Cognitive/mental state
Physical state
Functional status:
Physical functioning
Role functioning
Social functioning
General health perceptions / HRQoL:
Health-related quality of life
Overall quality of life:
Overall quality of life
Children (0-18)
Congenital malformations, deformations and chromosomal abnormalities and related symptoms
Diseases of and symptoms related to the nervous system
Endocrine, nutritional and metabolic diseases and related symptoms
PRO / non-PRO:
Non-patient Reported Outcome
Patient Reported Outcome
Type of measurement instrument:
1 - Questionnaires
4 - Performance-based tests
7 - Observations
8 - Imaging tests
9 - Laboratory tests
2D/3DSTE - Three dimensional strain echocardiography
6MWT - 6-Minute Walk Test    |  | also see:
A6MCT - Assisted 6-min cycling test for arms and legs
Accelerometry [alias: accelerometer]
ACTIVLIM (self-reported scale of activity limitations)
AIMS - Alberta Infant Motor Scale     | 
AS - Ashworth scale
BADS - Barry Albright Dystonia Scale
BASC - Behavior Assessment Scale for Children (versions: First edition; Second edition; Third edition; BASC‐SRP - BASC-Self‐Report of Personality; BASC-TRS = BASC-Teacher Rating Scale)
BDI-II - Beck Depression Inventory-II   
BSID-II - Bayley Scales of Infant Development II
Burke-Fahn-Marsden Rating
CAPE/PAC - Children's Assessment of Participation and Enjoyment / Preferences for Activities of Children   
CBCL - Child Behavior Checklist    | 
CDI - Children's Depression Inventory
CDRS-R - Children’s Depression Rating Scale–Revised
CELF - Clinical Evaluation of Language Fundamentals
CHAQ - Childhood Health Assessment Questionnaire
CHQ - Child Health Questionnaire
CIS - Checklist Individual Strength   
ECBI - Eyberg Child Behaviour Inventory
Fibroblast growth factor 21
FSQ - Family Strain Questionnaire
FVC - Forced Vital Capacity
GMFM - Gross Motor Function Measure (Also: GMFM-88 - 88-item version and GMFM-66 - 66-item version)   
Graded and timed function tests
Growth charts
HMAS - Hammersmith Motor Ability Score
ITQoL - Infant Toddler Quality of Life Questionnaire (versions: ITQOL-SF47 - 47-item short form ITQOL)
JTHFT - Jebsen Taylor Hand Function Test [alias: JTT]   
K-ABC - Kaufman Assessment Battery for Children (CHC module)
KIDSCREEN - 52 items - Health Related Quality of Life Questionnaire for Children and Young People and their Parents-52 items
MAS - Modified Ashworth Scale   
MDCRS - Movement Disorder Childhood Rating Scale
MET - Maximal Exercise Test
MFM - Motor Function Measure (AND MFM-20 - 20 item version)
MRC Scale - Medical Research Council Scale   
MRI - Magnetic Resonance Imaging (versions: 2D MRI; 3D MRI)
MRS - Magnetic Resonance Spectroscopy
MUUL - Melbourne Assessment of Unilateral Upper Limb Function
MVIC - maximal voluntary isometric contraction
NPMDS - Newcastle Paediatric Mitochondrial Disease Scale
OMNI - OMNI scale
OXPHOS enzyme complex activities
PAQ-A - Physical Activity Questionnaire for Adolescents
PDMS-2 - Peabody Developmental Motor Scales-2
PEDI - Pediatric Evaluation of Disability Inventory   
PedsQL 3.0 NMM -Pediatric Quality of Life Inventory 3.0 Neuromuscular Module
PedsQL 4.0 Generic Core Scales - Pediatric Quality of Life Inventory Generic Core Scales (versions: PedsQL 4.0 Generic Short Form; PedsQL Generic Core Scales version 4.0 TODDLER; PedsQL Generic Core Scales version 4.0 YOUNG CHILD; PedsQL Generic Core Scales version 4.0 CHILD; PedsQL Generic Core Scales version 4.0 TEENAGER)
PedsQL-MFS - Pediatric Quality of Life Inventory-Multidimensional Fatigue Scale
Pimax - Maximal inspiratory pressure
PODCI - Pediatric Outcomes Data Collection Instrument
QUEST - Quality of Upper Extremity Skills Test
RDLS (-III) - Reynell Developmental Language Scales (-III)
SARA - Scale for Assessment and Rating of Ataxia
SEMG - surface electromyography
SNIP - Sniff Nasal Inspiratory Tests
Speckle tracking MRI or 2D/3D strain imaging
TECEL - Test of Early Communication and Emerging Language
TS (also MTS) - Tardieu Scale (also: Modified)
UDRS - Unified Dystonia Rating Scale
WeeFIM - Functional Independence Measure for Children [alias: PFIM - Pediatric Functional Independence Measure]
WISC-R - Wechsler Intelligence Scale for Children-Revised