A new health-related quality of life (QOL) outcome measure has been developed and validated for children and adolescents with Charcot-Marie-Tooth disease (CMT) in a longitudinal study.
The patient-reported measure was deemed sensitive and may be used to assess disease burden in clinical settings and remotely, as well as to evaluate clinical trial outcomes.
“Our goal was not to merely show that QOL is impaired in CMT, but rather to systematically determine and quantify the factors that contribute to reduced QOL in children with CMT,” the researchers wrote.
The study, “Development and Validation of the Pediatric CMT Quality of Life Outcome Measure,” was published in the Annals of Neurology.
CMT is a genetic disorder characterized by muscle weakness and loss of muscle tone. Because symptoms of the disease often emerge in childhood, tools that enable clinicians and researchers to better assess CMT progression and patient-reported outcomes (PRO) in children and adolescents are of particular value.
While generic health-related QOL evaluations are often accurate measures of patient outcomes, they are not specific to CMT, making them unsuitable as clinical assessments.
Thus, a team of researchers in the U.S., the U.K., and Australia sought to develop and validate a health-related QOL patient outcome measure to assess the disease burden in CMT youth.
To identify the areas relevant to pediatric CMT, the team conducted a systematic literature review and analysis of existing pediatric and adult generic QOL measures.
A total of six areas, called domains, were identified in the literature as impacting quality of life in children with CMT; these were combined into physical and social composites. The physical composite domain included physical complaints — fatigue, weakness, pain, or tremor, among others — loss of function and ability to perform activities of daily living, and physical activities with other children and adults.
Conversely, the social domain included emotional and psychological symptoms, such as feelings of stigma, fear, depression, and stress, cognitive problems, and self-esteem and bonding with others.
The team developed 10 items per domain, for a total of 60 items. These were reviewed by a team of 21 researchers and two patient representatives, from nine countries.
The draft version of the pCMT-QOL measure — the pediatric CMT quality of life measure — was then administered in a pilot test to 31 children with the disease. Participants included 15 boys and 16 girls, ages 4-17, who were recruited from Wayne State University, in Michigan.
The content was validated by the pilot test and well-accepted by the participants. But the surveys were difficult for children under the age of 8 to complete, resulting in an adjustment of the target age for the measure to 8-18 years.
Based on patient input, response options were simplified to a uniform five-point scale, which included answer options of never, almost never, sometimes, almost always, and always. Additional clarified language also was incorporated into a working version of the measure.
To test its validity, consistency, and disease specificity, the pCMT-QOL working version was administered to 398 CMT children, ages 8-18, who were participating in an ongoing natural history study (NCT01193075). Of them, 54.8% were male and 76% had a confirmed genetic diagnosis.
Finally, the reliability of the pCMT-QOL working version was measured in a group of 13 participants from the University of Iowa. For that, the measure was administered twice over seven weeks, once in the clinic and once at home. Items with low test-retest reliability were removed from the final version of the measure.
The final pCMT-QOL PRO measure consists of six individual domain scores, corresponding well to the initial six domains, a Physical Composite Domain Score, a Mental Composite Domain Score, and a Total pCMT-QOL Score. The scores are on a 0-100 scale, with 0 indicating the best quality of life.
The researchers then compared scores on the measure across distinct genders, disease severity, and CMT subtypes. Patients with higher disease severity and girls showed worse total and physical QOL, but no differences in mental QOL was observed between the groups.
Moreover, no association was observed between QOL and disease subtypes or age, suggesting that QOL in pediatric CMT may depend on disease severity rather than disease subtype or age alone.
One-year changes in QOL were assessed over a five-year period. Of the original 358 patients, 57 were assessed in year one, with the number decreasing each year to five children in year five. The average Patient’s Global Impression of Change score each year was between “no change” and “a little better” and the Total pCMT-QOL Score was similarly consistent year-to-year.
“The disease-specific pCMT-QOL PRO measure thus has important distinctions and advantages from generic QOL outcome measures; it includes items pertinent to pediatric CMT patients, which were modified and refined by prospective pilot testing prior to undergoing longitudinal validation,” the researchers wrote.
Among the limitations of this study was the relatively young age of the participants, which may affect the QOL, and the reduced number of participants in the longitudinal analysis.
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