Disease Severity in Sickle Cell Disease: Understanding Impairment in Health-Related Quality of Life.
Authors: Panepinto Julie A. , Foerster Lisa M. 
Published: October 2019

Abstract
Recently it has been suggested that investigators should present health-related quality of life (HRQL) data in a more clinically interpretable way. The objective of this study was to determine the validity and reliability of the PedsQL questionnaire in children with sickle cell disease and to utilize proportions and a dichotomous outcome to demonstrate the impaired HRQL of children with sickle cell disease. A cross sectional study was conducted. Parents of children (ages 2 to 18 years) with sickle cell disease who presented to the clinic for a routine visit completed the PedsQL questionnaire. The PedsQL 4.0 generic questionnaire consists of 23 items that measure the child’s well being. The primary outcome measured was HRQL. Children were classified as severe sickle cell disease if they had a history of 1 or more major complications of sickle cell disease (overt stroke, acute chest syndrome, or priapism) or 3 or more hospitalizations for pain in the prior 3 years. All other children were considered mild. To determine validity, a two-sample t-test was used to compare HRQL scores between those with mild and severe disease with adjustment made for multiple comparisons. To determine internal reliability, a Cronbach’s alpha coefficient was calculated. To make the HRQL differences more clinically meaningful, the proportion of children who have problems walking a block or participating in sports or exercise (based on dichotomized Likert scale responses of “often/almost always” versus “sometimes/almost never/never”) was plotted against the mean physical summary score from the PedsQL. A total of 96 parents of children with sickle cell disease completed the PedsQL. Children with mild sickle cell disease had significantly better HRQL, as evidenced by a higher total (74.9), physical (75.2), and psychosocial (74.9) mean HRQL summary score, than those with severe disease (total score 60.3, physical summary score 58.9, psychosocial summary score 61.1; all p<0.01). All scales of the PedsQL had an acceptable alpha coefficient of greater than 0.7. Figure 1 shows the proportion of children with sickle cell disease, given their mean physical summary score on the PedsQL, who have problems walking a block or participating in sports or exercise. One out of 10 (10%) children with a mean score of 58.9 (mean score for severe disease) have problems walking around the block while 1 out of 6 (17%) have problems exercising or playing sports. In contrast, no children with a mean score of 75.2 (mean score for mild disease) report having problems with walking a block while just 1 out of 41 (2%) children report problems exercising or playing sports. In conclusion, the PedsQL 4.0 generic core scales demonstrated both validity, by differentiating between children with severe and mild sickle cell disease, and reliability in children with sickle cell disease. While the meaning of a 16 point difference in quality of life may not be readily apparent, a 10–15% decrease in the ability to walk a block or play sports certainly is easily understandable. Further work to broaden the HRQL field in sickle cell disease by developing a companion PedsQL sickle cell disease specific module and to promote presentation of HRQL results in an interpretable fashion is needed.
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