The PedsQL™ in pediatric patients with Spinal Muscular Atrophy: Feasibility, reliability, and validity of the Pediatric Quality of Life Inventory™ Generic Core Scales and Neuromuscular Module☆
Introduction
Spinal Muscular Atrophy (SMA) is a genetic disease of the anterior horn cell with a frequency of 8 per 100,000 live births [1], [2]. In 1995, the disease gene SMN1 was identified with a disease modifying gene, SMN2 [3]. This discovery has brought about some understanding of disease mechanism and several hypotheses for treatment strategies [4]. Pilot studies as well as Phase I and II clinical trials were undertaken on the basis of these hypotheses. Although no effective treatment has been found to date, much has been learned in terms of conducting clinical trials in the SMA pediatric population [5].
For Phase II and III clinical trials, reliable and valid outcome measures are necessary [6]. In 2000, the American Spinal Muscular Atrophy Randomized Trials (AmSMART) group was formed in order to develop clinical outcome measures for children with SMA. AmSMART established reliability and validity for measures of strength, lung function, and motor function in the population from age 2 years to 18 years [7], [8], [9], [10]. Biological markers of disease progression are currently under investigation.
Health-related quality of life measurement has been increasingly acknowledged as an essential health outcome measure in clinical trials involving children with neuromuscular disorders [7], [8], [9], [10], [11], [12]. The Food and Drug Administration (FDA) has strongly recommended the inclusion of health-related quality of life (HRQOL) assessment as an endpoint in clinical trials regardless of the age of the patient. A sensitive and specific HRQOL instrument must address factors unique to a particular disease and age group. Although generic HRQOL instruments have been developed for use in pediatric populations, there are few disease-specific measures available.
HRQOL is a multidimensional construct, consisting at the minimum of physical, psychological (including emotional and cognitive), and social health dimensions delineated by the World Health Organization [13], [14]. HRQOL has emerged as the most appropriate term for quality of life dimensions that represent a patient’s perceptions of the impact of an illness and its treatment on their own functioning and well-being and which are within the scope of healthcare services and medical products [14], [15]. Generic HRQOL measurement instruments enable comparisons across pediatric populations and facilitate benchmarking with healthy population norms, while disease-specific measures enhance measurement sensitivity for health domains germane to a particular chronic health condition. There is an emerging perspective that for pediatric chronic health conditions, both generic and disease-specific HRQOL measures should be administered in order to gain a comprehensive evaluation of the patient’s HRQOL [16], [17].
The PedsQL™ (Pediatric Quality of Life Inventory™) Measurement Model was designed to integrate the relative merits of a generic core instrument with disease-specific modules [18], [19], [20], [21], [22], [23]. It has been an explicit goal of the PedsQL™ Measurement Model to develop and test brief measures for the broadest age group empirically feasible, specifically including child self-report for the youngest children possible [24]. The PedsQL™ 4.0 Generic Core Scales was specifically designed for application in both healthy and patient populations [25] and has been utilized with over 35,000 healthy children and children with numerous pediatric chronic health conditions internationally [26], including children with neuromuscular disorders [12]. Findings have been reported in over 350 peer-reviewed journal articles since 2001 (A full listing of the updated peer-reviewed journal publications is available at www.pedsql.org). The PedsQL™ 4.0 Generic Core Scales, however, is not a disease-specific instrument and cannot provide detailed information on the specific factors that influence HRQOL in pediatric patients with neuromuscular disorders. Consequently, during the past decade we have developed the PedsQL™ 3.0 Neuromuscular Module to measure HRQOL dimensions specific to children ages 2–18 years with neuromuscular disorders, in particular, SMA. The aim of the current study was to investigate the feasibility, reliability, and validity of the PedsQL™ 3.0 Neuromuscular Module and the PedsQL™ 4.0 Generic Core Scales in children with SMA.
Section snippets
Spinal Muscular Atrophy sample
A total of 176 children with SMA were accrued overall for the field test of the PedsQL™ 3.0 Neuromuscular Module. Table 1 provides information for the 13 centers from which participants were recruited. Participants were approached during routinely scheduled clinic visits. SMA diagnosis was confirmed by mutation analysis for all children. The average age of the 76 boys (43.2%) and 91 girls (51.7%; Missing Gender = 9, 5.1%) was 8.53 years (SD = 4.75). With respect to ethnicity, the sample contained 19
Feasibility: missing item responses
For child self-report and parent proxy-report on the PedsQL™ 3.0 Neuromuscular Module, the percentage of missing item responses was 0.8% and 1.0%, respectively, for all scales. For child self-report and parent proxy-report on the PedsQL™ 4.0 Generic Core Scales, the percentage of missing item responses was 1.3% and 1.3%, respectively, for all scales. On the PedsQL™ Neuromuscular Module, 46.7% of the items across all forms had no missing responses; the highest percentage of missing responses for
Discussion
These data support the feasibility, reliability, and validity of the PedsQL™ 3.0 Neuromuscular Module and the PedsQL™ 4.0 Generic Core Scales in pediatric patients with SMA. The Generic Core Scales distinguished HRQOL between children with SMA and a matched sample of healthy children, with most effect sizes in the large range. Consistent with previous findings with children with neuromuscular disorders [12], the greatest deficits on the PedsQL™ 4.0 Generic Core Scales were seen in physical
Acknowledgement
This research was supported by National Institutes of Health RO1 NS 39327 (Principal Investigator: STI).
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2022, Pediatrics and NeonatologyCitation Excerpt :Home ventilator use and inability to attend school were also independently associated with lower total HRQoL scores (p = 0.030 and p = 0.032, respectively). The PedsQL™ total score in our study is consistent with those reported from other countries,10 and an inverse correlation between disease severity and quality of life has been well demonstrated. In the present study and in other reports, the psychosocial health domain score is consistently higher than physical health scores.10
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Competing interests: Dr. Varni holds the copyright and the trademark for the PedsQL™ and receives financial compensation from the Mapi Research Trust, which is a non-profit research institute that charges distribution fees to for-profit companies that use the Pediatric Quality of Life Inventory™.
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AmSMART members: Mariam Andersen, Dallas, TX; Brenda Wong, MD, and Paula Morehart, Cincinnati, OH; Barry Russman, MD, and Kirsten Zilke, Portland, OR; Robert Leshner, MD, Barbara Grillo, and Angela Zimmerman, Richmond, VA and Washington, DC; Stephen Smith, MD, John Day, MD, and Heather Wendorf, St. Paul, MN; Kathy Swoboda, MD, and Sandra Reyna, Salt Lake City, UT; Richard Finkel, MD, and Kim Schadt, Philadelphia, PA; JiriVajsar, MD, and Lynn MacMillan, Toronto, CA; Anne Connolly, MD, and Charlie Wulf, St. Louis, MO; Nancy Kuntz, MD, and Wendy Korn-Peterson, Rochester, MN; Petra Kaufmann, MD, and Jessica O’Hagen, New York, NY; Basil Darras, MD, and Erica Sanborn, Boston, MA.