Pediatric Quality of Life Inventory Version 4.0 Generic Core Scales (PedsQL 4.0)

The original Pediatric Quality of Life Inventory (PedsQL) was developed as a health-related quality of life (HRQoL) measure that addressed the paucity of appropriately validated and reliable instruments incorporating both the child and parental experience with chronic health conditions. The PedsQL uses a modular approach and incorporates both generic and disease/symptom specific items that are appropriate for the assessment of pediatric chronic conditions.³⁸ The generic HRQoL measure was developed using pediatric cancer as the model, due to the fact that consequences of pediatric cancer (rather than specific cancer symptoms) are applicable to many other pediatric chronic health conditions.³⁸ The PedsQL 4.0 Generic Core Scales comprise 23 items under the following modules: Physical Functioning (8 items), Emotional Functioning (5 items), Social Functioning (5 items), and School Functioning (5 items).³⁹ These Generic Core Scales are comprised of both the parent proxy report and the child self-report formats that assess health perceptions. The child self-report format is specific for ages 5 years to 7 years, 8 years to 12 years, and 13 years to 18 years of age, while the corresponding parent proxy reports are specific for toddlers (ages 2 years to 4 years, for which there is no child self-assessment report), young children (ages 5 years to 7 years), children (ages 8 years to 12 years), and adolescents (ages 13 years to 18 years). The questions ask how much of a problem each item has been in the past month. A 5-point Likert response scale is used across the child reports (from ages 8 years to 18 years) and the corresponding parent report, and include the following responses with corresponding scores: 0 = never a problem; 1 = almost never a problem; 2 = sometimes a problem; 3 = often a problem; and 4 = almost always a problem. In addition, a 3-point scale is used for simplification and ease of use for children who are aged 5 years to 7 years and include 0 = not at all a problem; 2 = sometimes a problem; and 4 = a lot of a problem, with each of the response choices anchored to a happy face to sad face scale.³⁹ The scores, which are reversed scored, are transformed linearly to a 0 to 100 scale, whereby 0 = 100, 1 = 75, 2 = 50, 3 = 25, and 4 = 0, with higher scores indicative of a higher HRQoL. In order to account for missing data, the sum of the items divided by the number of items that are answered is computed in order to ascertain the scale score. If greater than 50% of the items within the scale are missing, then the scale score cannot be obtained. In order to ascertain the Psychosocial Health Summary Score (comprised of 15 items), the sum of the items is divided by the items answered in the School Functioning, Emotional, and Social Subscales.³⁹ There are currently more than 60 translations of the PedsQL 4.0 that have been validated.^40,41

In order to validate the PedsQL 4.0, a sample of chronically ill (as reported by their parents in a specialty clinic [n = 683]), acutely ill (parents reported no presence of chronic illness and attended a specialty clinic [n = 207]), and healthy children (identified at their physician’s office during regular visits or using telephone calls [n = 730]) between the ages of two years to 18 years were included.³⁹ Construct validity was ascertained using the known-groups method, whereby scale scores were compared across groups that are known to differ in the specific health constructs being examined (in this case healthy versus acute or healthy versus chronic conditions). In addition, potentially confounding factors such as age, gender, and ethnicity were also examined across health states. Hypothesizing that healthy children would have a higher HRQoL, Varni et al. noted that the PedsQL 4.0 differentiated between the different health states (healthy, acute, and chronically ill) and it also correlated with illness burden and morbidity measures.³⁹ Internal consistency reliabilities generally exceeded the standard alpha coefficients of 0.70. The total scale scores across the ages for the self-report and proxy-report were 0.88 and 0.90, respectively, thus indicating this as an appropriate primary analysis summary score. The Physical Health and Psychosocial Health Summary Scores were greater than 0.8 for the self-report and the proxy-report; hence, the authors determined they were best for secondary analyses. The Emotional, Social, and School Functioning Subscales generally obtained alpha coefficients around 0.70; therefore, the authors suggested these be used for descriptive or exploratory analyses.³⁹

Varni et al.⁴² then examined three studies in order to determine the sensitivity and responsiveness of the PedsQL 4.0 Generic Core Scales. The population included pediatric patients (age range 2 years to 18 years) with acute or chronic health conditions (n = 115 presenting to a cardiology clinic; n = 47 presenting to an orthopedic clinic; n = 127 presenting to a rheumatology clinic) and their parents. Statistically significant differences were observed between pediatric patients defined as New York Health Assessment (NYHA) Class II/IV and Classes I and II, suggesting that the PedsQL 4.0 was likely to be sensitive.⁴² Likewise, statistically significant changes between the initial and follow-up visit of patients attending the orthopedic clinic were observed (and the follow-up visit results also corresponded to that of healthy children responses), demonstrating the responsiveness of the PedsQL 4.0.⁴² In another study by Desai et al.,⁴³ patients admitted to medical or surgical units were administered the PedsQL 4.0 upon admission (64.5%; n = 4,637/7,184) and during follow-up (58.1%; n = 2,694/4,637). The responsiveness of the PedsQL 4.0 was demonstrated upon examination of the mean differences between admission and follow-up; 22.1 (standard deviation [SD] of 22.7) for the total score, 29.3 (SD of 32.4) for the physical domain, and 17.1 (SD of 21.0) for the psychosocial domain. Moderate variability in responsiveness was observed by age and minimal variability in responsiveness was observed for patients having been admitted for medical or surgical reasons.⁴³ Construct validity was further demonstrated as patients with no chronic illness (and their parents) scored higher on the total score, physical domain, and psychosocial domain when compared with patients with either complex or non-complex chronic illness.⁴³

No minimal clinically important difference (MCID) has been identified for any specific chronic or acute condition, including nephropathic cystinosis.

Short Form 36 (SF-36)

The SF-36 is a 36-item, general health status instrument that has been used extensively in clinical trials in many disease areas.⁴⁴ The SF-36 consists of eight health domains: physical functioning (PF), role physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role emotional (RE), and mental health (MH).^44–46 For each of the eight categories, a subscale score can be calculated. The SF-36 also provides two component summaries, the physical component summaries (PCS) and the mental component summary (MCS), derived from aggregating the eight domains according to a scoring algorithm. The PCS and MCS scores range from 0 to 100, with higher scores indicating better health status.^44,45 The summary scales are scored using norm-based methods, with regression weights and constants derived from the general US population. Both the PCS and MCS scales are transformed to have a mean of 50 and an SD of 10 in the general US population. Therefore, all scores above/below 50 are considered above/below average for the general US population. The SF-36 has been validated in a variety of disease conditions.^46–48

On any of the scales, an increase in score indicates improvement in health status. In general use, a change of 2 points in the SF-36 PCS and 3 points in the SF-36 MCS indicates a clinically meaningful improvement as determined by the patient.⁴⁹ Based on anchor data, the SF-36 User’s Manual also proposed the following minimal mean group differences, in terms of t score points, for SF-36v2 individual dimension scores: PF, 3; RP, 3; BP, 3; GH, 2; VT, 2; SF, 3; RE, 4; and MH, 3. It should be noted that these minimally important difference (MID) values were determined as appropriate for groups with mean t score ranges of 30 to 40. For higher t score ranges, MID values may be higher.⁴⁹ No MCID values were identified that were specific to patients with nephropathic cystinosis.

Two versions of the SF-36 exist: the original and the SF-36 version 2 (SF-36v2 was made available in 1996).⁴⁹ The SF-36v2 contains minor changes to the original survey, including changes to: instructions (reduced ambiguity), questions and answers (better layout), item-level response choices (increased), cultural/language comparability (increased), and elimination of a response option from the items in the mental health and vitality dimensions.⁴⁹

Visual Analogue Scale (VAS) for Swallowing

The manufacturer used a VAS for swallowing scale in order to assess the pain a patient with nephropathic cystinosis may experience when swallowing.¹⁸ This VAS scale contained a 0 to 10 metric with 0 = no pain with swallowing and 10 = very much pain with swallowing. No additional evidence was identified in a supplemental search with regard to the validity or reliability of this outcome measure in any type of patient. In addition, no MCID was identified in any type of patient.