These analyses demonstrate the feasibility, reliability and validity of the PedsQL™ as a multidimensional pediatric patient-reported outcome instrument for fibromyalgia consistent with the OMERACT Fibromyalgia Syndrome Workshop recommendations . These PedsQL™ Scales measure the OMERACT prioritized domains that should be consistently measured in FM clinical trials, specifically, pain, generic HRQOL, fatigue, sleep quality, and physical function . In addition, in adult patients with FM, recent evidence suggests the importance of measuring cognitive difficulties ("fibrofog"), frequently reported by adult patients with FM as memory and attention problems . The PedsQL™ Cognitive Fatigue Scale measures the construct of cognitive problems as delineated in the adult FM literature, and to our knowledge, represents the first measurement presentation of this construct in pediatric patients with FM.
Items on the PedsQL™ Scales had minimal missing responses, suggesting that pediatric patients with FM and their parents are willing and able to provide good quality data regarding the patient's HRQOL. The PedsQL™ self-report and proxy-report internal consistency reliabilities generally exceeded the recommended minimum alpha coefficient standard of 0.70 for group comparisons. The PedsQL™ Generic Core Scales Total Score and Multidimensional Fatigue Scale Total Score for pediatric patient self-report and parent proxy-report approached or exceeded an alpha of 0.90, recommended for individual patient analysis , making the Generic Core Scales Total Scale Score suitable as a summary score for the primary analysis of HRQOL outcome in clinical trial analyses for pediatric patients with FM, with the PedsQL™ Psychosocial Health Summary Score, the Multidimensional Fatigue Scale Total Score, and individual scales suitable alternatively as either the primary or secondary outcome score depending on the intent of a particular clinical trial.
As hypothesized, pediatric patients with FM self-reported significantly lower PedsQL™ scores on dimensions of physical and psychosocial health and fatigue in comparison to healthy children. These findings are consistent with findings in adult patients with FM using the SF-36 [13–15]. We believe the consistency of the present findings in which differences between healthy children and pediatric patients with FM for both child self-report and parent proxy-report support the magnitude of the reported impairment in these pediatric patients with FM. This illustrates the benefits of the PedsQL™ Measurement Model in which both child self-report and parent proxy-report are measured .
The comparisons between pediatric patients with FM with pediatric cancer patients receiving cancer treatment and those pediatric patients with other rheumatologic diseases are useful in understanding the relative clinical impact of fibromyalgia on HRQOL. The extant literature on the adaptation of children with chronic physical health conditions demonstrates that children with chronic physical health conditions are reported to not only experience lower physical functioning, but also manifest lower emotional, social, and school functioning in comparison to healthy children . The findings that pediatric patients with FM report physical and psychosocial health generally lower than children receiving chemotherapy and radiation for the treatment of pediatric cancer provide further insight into the comparative negative impact of this chronic health condition on HRQOL in comparison to other serious pediatric chronic conditions. The findings that pediatric patients with FM, whose examinations and laboratory tests are generally normal, demonstrated significantly lower overall HRQOL and more severe pain and fatigue than pediatric patients with other rheumatologic conditions, whose examinations and tests are generally abnormal, further emphasizes the importance of measuring HRQOL outcomes in these children and adolescents.
These findings with the PedsQL™ Scales have potential clinical implications for the healthcare needs of children with FM. Given the degree of reported impairment in their HRQOL, the urgent need for efficacious treatments is quite evident. The immediate and long-term consequences of untreated or under-treated FM appears quite severe for these children, their families, and society as a whole [7, 64]. The challenge for health care is to identify and enroll pediatric patients with FM in high quality evidence-based comprehensive healthcare services in order to mitigate the potential long-term negative consequences on patient HRQOL. For chronic health conditions such as fibromyalgia, HRQOL and symptom scales completed by patients may be the only indicators of disease activity and treatment effect [21–23]. In such patient populations, PROs are often indicated as the primary end-points for drug approval [21–23]. Given that pharmaceutical and nonpharmaceutical treatment regimens for adults with FM are emerging [65–68], trials which evaluate the impact of similar regimens on the patient-reported health outcomes of pediatric patients with FM are urgently needed [7, 64, 69].
Finally, while self-report is considered the standard for measuring perceived HRQOL, it is typically parents' perceptions of their children's HRQOL that influences healthcare utilization [37–39]. Thus, the imperfect agreement observed between child self-report and parent proxy-report supports the need to measure the perspectives of both the child and parent in evaluating pediatric HRQOL since these perspectives may be independently related to healthcare utilization and risk factors. The availability of a validated parent proxy-report measure in FM provides the opportunity to estimate child HRQOL when the child is either unable or unwilling to complete the HRQOL measure. Although the intercorrelations between child and parent report across the physical, psychosocial, fatigue and pain domains might be expected to follow the conceptualization that more observable domains (i.e., physical functioning) would yield higher intercorrelations, this has not necessarily been the case in either PedsQL™ publications across various pediatric chronic health conditions, or in the published literature with other HRQOL instruments. In a comprehensive review, Eiser  found mixed results in terms of higher intercorrelations between self and proxy report of physical functioning across pediatric HRQOL instruments, with most studies demonstrating this effect, while some others did not. In a condition such as FM that is highly associated with significant pain, fatigue, and emotional distress, parents may be more acutely attuned to these symptoms, and consequently their perception of their child's HRQOL on these domains may more closely align with their child's perceptions.
The present findings have several potential limitations. Given that the comparative analyses were with an exiting database, we were only able to match the FM sample to the pediatric cancer and rheumatology samples by age, not gender, given the small sample sizes for these chronic health conditions. Other sociodemographic differences of these existing databases may have further influenced the comparative findings with healthy children, and pediatric patients with cancer and other rheumatologic conditions; however, our findings are consistent with the literature on adult patients with FM. Further, the PedsQL™ Multidimensional Fatigue Scale was not administered initially in our FM recruitment efforts, and thus we report a smaller sample size for analyses here. Additionally, sensitivity and responsiveness data were not available for these analyses; however, previous PedsQL™ research with patients with rheumatologic and other chronic health conditions have demonstrated the sensitivity and responsiveness of the PedsQL™ Scales [17, 20, 45, 71–73]. Finally, we have no information on nonparticipants given the requirements of the local IRB.