Qual Life Res (2015) 24:363–378 DOI 10.1007/s11136-014-0781-x

PedsQLTM Gastrointestinal Symptoms Scales and Gastrointestinal Worry Scales in pediatric patients with functional and organic gastrointestinal diseases in comparison to healthy controls James W. Varni • Cristiane B. Bendo • Jolanda Denham • Robert J. Shulman Mariella M. Self • Deborah A. Neigut • Samuel Nurko • Ashish S. Patel • James P. Franciosi • Miguel Saps • Alyson Yeckes • Annette Langseder • Shehzad Saeed • John F. Pohl

•

Accepted: 8 August 2014 / Published online: 23 August 2014 Ó Springer International Publishing Switzerland 2014

Abstract Objective The primary objective was to compare the gastrointestinal (GI) symptoms and worry of pediatric patients with functional GI disorders (FGIDs) and organic GI diseases to healthy controls utilizing the Pediatric Quality of Life InventoryTM (PedsQLTM) Gastrointestinal Symptoms and Worry Scales for patient self-reports ages 5–18 years and parent proxy-reports for ages 2–18 years. The secondary objective was to compare FGIDs and organic GI diseases to each other. Methods The PedsQLTM Gastrointestinal Symptoms and Worry Scales were completed in a 9-site study by 587 pediatric patients with GI disorders and 685 parents of patients. Patients had physician-diagnosed GI disorders (chronic constipation, functional abdominal pain, irritable

For the Pediatric Quality of Life InventoryTM Gastrointestinal Symptoms Module Testing Study Consortium. A list of the Pediatric Quality of Life InventoryTM Gastrointestinal Symptoms Module Testing Study Consortium sites is contained in the ‘‘Appendix’’. Drs. Franciosi and Denham are now at the Division of Gastroenterology, Hepatology and Nutrition, Nemours Children’s Hospital, Orlando, FL. J. W. Varni Department of Pediatrics, College of Medicine, Texas A&M University, College Station, TX, USA J. W. Varni (&) Department of Landscape Architecture and Urban Planning, College of Architecture, Texas A&M University, 3137 TAMU, College Station, TX 77843-3137, USA e-mail: [email protected] URL: http://www.pedsql.org

bowel syndrome, functional dyspepsia, Crohn’s disease, ulcerative colitis, and gastroesophageal reflux disease). Ten Gastrointestinal Symptoms Scales measuring Stomach Pain, Stomach Discomfort When Eating, Food and Drink Limits, Trouble Swallowing, Heartburn and Reflux, Nausea and Vomiting, Gas and Bloating, Constipation, Blood, and Diarrhea were administered along with two Gastrointestinal Worry Scales. Five hundred and thirteen healthy children and 337 parents of healthy children completed the PedsQLTM Gastrointestinal Scales in an Internet panel survey. Results The PedsQLTM Gastrointestinal Symptoms and Worry Scales distinguished between pediatric patients with FGIDs and organic GI diseases in comparison with healthy controls, supporting known-groups validity. Patients with FGIDs reported more GI symptoms and worry than patients with organic GI diseases. Conclusions The PedsQLTM Gastrointestinal Symptoms and Worry Scales may be utilized as common metrics across pediatric patient groups with FGIDs and organic GI diseases and healthy samples to measure GI-specific symptoms in clinical research and practice. C. B. Bendo Department of Pediatric Dentistry and Orthodontics, Faculty of Dentistry, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil J. Denham Division of Pediatric Gastroenterology, Nationwide Children’s Hospital, Ohio State University School of Medicine, Columbus, OH, USA R. J. Shulman Department of Pediatrics, Baylor College of Medicine, Children’s Nutrition Research Center, Texas Children’s Hospital, Houston, TX, USA

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Keywords PedsQL
Gastrointestinal
Gastroenterology
Symptoms
Pediatrics
Patient-reported outcomes
Health-related quality of life

Qual Life Res (2015) 24:363–378

Generic health-related quality of life (HRQOL) measurement instruments are increasingly utilized to assess the impact of pediatric diseases and treatments from the perspective of pediatric patients and their parents [1–4], including pediatric patients with functional gastrointestinal (GI) disorders (FGIDs) and organic GI diseases (hereafter referred to as ‘‘GI disorders’’ when discussed as a combined group of patients with FGIDs and organic GI diseases) [5–17]. Well-validated generic HRQOL measures provide a common metric on which to compare interventions both within and across patient groups, and represent important patient-reported outcome (PRO) measures for the evaluation of treatments targeting pediatric disorders [18]. Generic HRQOL is a multidimensional construct, consisting at the minimum of the physical, psychological (including emotional and cognitive), and social health dimensions delineated by the World Health Organization [19, 20]. Although a generic HRQOL measurement instrument enables comparisons across pediatric

populations and facilitates benchmarking with healthy population norms [21], a multidimensional GI symptomspecific instrument is essential to understanding the particular health issues most germane for pediatric patients across multiple FGIDs and organic GI diseases from the patient’s and parent’s perspective [22, 23]. Based on existing theoretical models [21, 24], a GI symptom-specific instrument would be hypothesized to be more sensitive in measuring the impact of disease modifying therapies and detecting change in health status over time within a population of children with GI disorders. To our knowledge, there was not previously available an empirically derived generic pediatric multidimensional GI symptom-specific instrument that measured GI symptoms across multiple FGIDs and organic GI diseases from the patient and parent perspectives utilizing patient self-reports for ages 5–18 years and parent proxy-reports for ages 2–18 years. To address this significant gap in the literature, we developed the generic multidimensional Pediatric Quality of Life InventoryTM (PedsQLTM) Gastrointestinal Symptoms Module [22]. The PedsQLTM Gastrointestinal Symptoms Module includes 74 items incorporated into 14 individual scales [25]. The PedsQLTM Gastrointestinal Symptoms Module consists of ten Gastrointestinal Symptoms Scales, two Gastrointestinal Worry Scales, a Medicines Scale, and a Communication Scale. Figure 1 illustrates the conceptual framework for the PedsQLTM Gastrointestinal Symptoms Module. The ten PedsQLTM Gastrointestinal Symptoms Scales and the two PedsQLTM Gastrointestinal Worry Scales from the PedsQLTM Gastrointestinal Symptoms Module were designed as generic GI symptom-specific scales to measure GI symptoms and worry across pediatric populations [25]. Previously, the PedsQLTM Gastrointestinal Symptoms Scales and Gastrointestinal Worry Scales demonstrated good to excellent reliability and validity in pediatric patients across seven pediatric FGIDs and organic GI diseases as part of the

M. M. Self Departments of Psychiatry and Pediatrics, Baylor College of Medicine, Texas Children’s Hospital, Houston, TX, USA

J. P. Franciosi
S. Saeed Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

D. A. Neigut
A. Yeckes Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital Colorado, Aurora, CO, USA

M. Saps Division of Gastroenterology, Hepatology and Nutrition, Lurie Children’s Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

Abbreviations PedsQLTM Pediatric Quality of Life InventoryTM FDA Food and Drug Administration HRQOL Health-related quality of life GI Gastrointestinal FGIDs Functional gastrointestinal disorders PRO Patient-reported outcome

Introduction

S. Nurko Center for Motility and Functional Gastrointestinal Disorders, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA A. S. Patel Division of Pediatric Gastroenterology, Children’s Medical Center of Dallas, University of Texas Southwestern Medical School, Dallas, TX, USA

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A. Langseder Division of Pediatric Gastroenterology, Hepatology and Nutrition, Goryeb Children’s Hospital, Morristown Medical Center, Morristown, NJ, USA J. F. Pohl Department of Pediatric Gastroenterology, Primary Children’s Hospital, University of Utah, Salt Lake City, UT, USA

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Fig. 1 Conceptual framework for the PedsQLTM Gastrointestinal Symptoms Module. All 14 individual scales comprise the PedsQLTM Gastrointestinal Symptoms Module Total Score (74 items). Ten Gastrointestinal Symptoms Scales comprise the PedsQLTM Gastrointestinal Symptoms Scales Total Score (58 items)

PedsQLTM Gastrointestinal Symptoms Module field test study [25]. Based on the conceptualization of diseasespecific symptoms as causal indicators of generic HRQOL [26], the PedsQLTM Gastrointestinal Symptoms and Worry Scales demonstrated significant correlations with generic HRQOL (greater GI symptoms and worry associated with lower generic HRQOL as measured by the PedsQLTM 4.0 Generic Core Scales), supporting initial construct validity [25]. However, there has been no prior investigation comparing GI symptoms and worry in pediatric FGIDs and organic GI diseases individually and as a group with a healthy population utilizing the PedsQLTM Gastrointestinal Symptoms and Worry Scales. Further, there has been no prior investigation comparing patients with FGIDs as a group to patients with organic GI diseases as a group with these new GI symptoms and worry scales. Consequently, the primary objective of the present study was to compare GI symptoms and worry in pediatric patients with GI disorders as a combined group of FGIDs and organic GI diseases to a matched sample of healthy controls utilizing the PedsQLTM Gastrointestinal Symptoms Scales and Gastrointestinal Worry Scales from the PedsQLTM Gastrointestinal Symptoms Module [25]. We hypothesized that the ten PedsQLTM Gastrointestinal Symptoms Scales and the two Gastrointestinal Worry Scales would distinguish between pediatric patients with GI disorders as a group in comparison with healthy children based on previous PedsQLTM generic symptom-

specific scales measuring multidimensional fatigue [27– 31], supporting construct validity utilizing the knowngroups method [32]. Only the PedsQLTM Gastrointestinal Symptoms and Worry Scales from the PedsQLTM Gastrointestinal Symptoms Module field test study were included in the current analyses since the two remaining scales (Medicines Scale and Communication Scale) contain items that are not relevant to a healthy population. The secondary objective was to compare the PedsQLTM Gastrointestinal Symptoms and Worry Scales scores between pediatric patients with FGIDs as a group and organic GI diseases as a group to each other and to the healthy controls. We hypothesized that patients with FGIDs as a group and organic GI diseases as a group would be significantly different from the healthy controls on the PedsQLTM Gastrointestinal Symptoms and Worry Scales. However, given the heterogeneity of the diagnostic subgroups within the FGIDs and organic GI diseases groups and the lack of definitive literature comparing these groups on the constructs measured, directional hypotheses were not considered warranted in the comparison of the two groups of patients. We further conducted exploratory analyses of the individual PedsQLTM Gastrointestinal Symptoms and Worry Scales scores across seven diagnostic groups of patients with FGIDs and organic GI diseases to the healthy controls, expecting greater GI symptoms and worry in individual patient groups in comparison with the healthy controls

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generally consistent with the disease characteristics of the individual GI disorders.

Methods Pediatric patients and settings Pediatric patients ages 5–18 years and parents of pediatric patients ages 2–18 years with physician-diagnosed GI disorders utilizing ICD-9-CM Diagnosis Codes and/or Rome III criteria for FGIDs for seven GI diagnostic groups including both functional (chronic constipation, functional abdominal pain, irritable bowel syndrome, and functional dyspepsia) and organic diseases (Crohn’s disease, ulcerative colitis, and gastroesophageal reflux disease) were recruited from nine pediatric tertiary care GI clinical sites across the United States for the PedsQLTM Gastrointestinal Symptoms Module field test study [25]. Only patients with a single primary diagnosis were included. Although these seven GI disorders were targeted, we also included a small number of patients with other GI disorders (indeterminate colitis and eosinophilic esophagitis) given that the intent of the PedsQLTM Gastrointestinal Symptoms Module is utilization across the full spectrum of pediatric GI disorders [25]. Data collection for the PedsQLTM Gastrointestinal Symptoms Module field test study took place between March 2011 and November 2013 [25]. Written parental informed consent and child assent (when age appropriate) were obtained for these data during the field test study [25]. The research protocol for the field test study was approved by the Institutional Review Board at each participating institution. Healthy control sample The PedsQLTM Gastrointestinal Symptoms Scales and Gastrointestinal Worry Scales healthy controls comparison sample was derived from data collected by the Scientific Research group at YouGovÒ (see www.yougov.com), an Internet polling firm based in Palo Alto, CA, which had been utilized by a number of National Institutes of Health funded Patient-Reported Outcomes Measurement System (PROMISÒ) investigators [33–35]. YouGovÒ maintains a large panel of respondents who have agreed to participate in online surveys. YouGovÒ was contracted to select participants from among their panel that age, gender, and race/ ethnicity matched the age, gender, and race/ethnicity of the GI sample. Data collection for the Internet panel survey took place between July 2013 and September 2013, and thus, the majority of the GI sample had already been accrued by the time the Internet panel survey was conducted.

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In addition to completing the PedsQLTM Gastrointestinal Symptoms Scales and Gastrointestinal Worry Scales, parents completed the PedsQLTM Family Information Form, which included a question on whether their child had a chronic health condition [36]. Specifically, parents answered a question on the presence of a chronic health condition (‘‘In the past 6 months, has your child had a chronic health condition?’’) defined as a physical or mental health condition that had lasted or was expected to last at least 6 months and interfered with the child’s activities as previously utilized in PedsQLTM studies [36–38]. Families in which parents self-reported that their child had a chronic health condition were not included in the matched healthy sample, consistent with previous PedsQLTM studies [39, 40]. From the total sample of 792 families who participated in the Internet survey, an age, gender, and race/ethnicity sample of 552 families with healthy children were derived to match the age, gender, and race/ethnicity of the final GI sample [25]. Parental informed consent and child assent (when age appropriate) were obtained through the panel survey protocol. The research protocol for the healthy sample Internet panel survey was approved by the Institutional Review Board at Texas A&M University. Measures PedsQLTM Gastrointestinal Symptoms Module development The PedsQLTM Gastrointestinal Symptoms Module items and scales were developed through a literature review of the relevant research, national consultation with pediatric gastroenterologists, as well as focus interviews, cognitive interviews, and pretesting protocols with pediatric patients and their parents [22]. Development of the items for the PedsQLTM Gastrointestinal Symptoms Module began in 2008. The PedsQLTM Gastrointestinal Symptoms Module includes 74 items incorporated into 14 individual scales [25]. The PedsQLTM Gastrointestinal Symptoms Module consists of ten Gastrointestinal Symptoms Scales, two Gastrointestinal Worry Scales, a Medicines Scale, and a Communication Scale (see Fig. 1 for the conceptual framework). Only the PedsQLTM Gastrointestinal Symptoms Scales and Gastrointestinal Worry Scales from the PedsQLTM Gastrointestinal Symptoms Module are included in the present study since the Medicines and Communication Scales are not relevant to healthy populations. PedsQLTM Gastrointestinal Symptoms Scales The PedsQLTM Gastrointestinal Symptoms Scales encompass ten individual scales: (1) Stomach Pain and Hurt Scale (6 items), (2) Stomach Discomfort When Eating Scale (5

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items), (3) Food and Drink Limits Scale (6 items), (4) Trouble Swallowing Scale (3 items), (5) Heartburn and Reflux Scale (4 items), (6) Nausea and Vomiting Scale (4 items), (7) Gas and Bloating Scale (7 items), (8) Constipation Scale (14 items), (9) Blood in Poop Scale (2 items), and (10) Diarrhea Scale (7 items). The format, instructions, Likert response scale, and scoring method for the PedsQLTM Gastrointestinal Symptoms Scales are identical to the PedsQLTM 4.0 Generic Core Scales [36], with higher scores indicating better HRQOL and hence lower symptoms [25]. The scales are comprised of parallel child self-report and parent proxy-report formats for children ages 5–18 years and a parent proxy-report format for children ages 2–4 years. Child self-report forms are specific for ages 5–7, 8–12, and 13–18 years. Parent proxy-report forms are specific for children ages 2–4 (toddler), 5–7 (young child), 8–12 (child), and 13–18 (adolescent) and assess parents’ perceptions of their child’s GI-specific symptoms. The items for each of the forms are essentially identical, differing in developmentally appropriate language, or first or third person tense. The instructions ask how much of a problem each item has been during the past 1 month. The grammar and syntax of the items are structurally equivalent to those in the existing PedsQLTM item bank. Instructions and response scales were created to be consistent with the instructions and response scales of the PedsQLTM 4.0 Generic Core Scales for ages 2–18 years and other PedsQLTM Disease-Specific Modules [17, 29, 36, 41–43]. A 5-point response scale is utilized across child and adolescent self-report for ages 8–18 and parent proxy-report (0 = never a problem; 1 = almost never a problem; 2 = sometimes a problem; 3 = often a problem; and 4 = almost always a problem). To further increase the ease of use for the young child self-report (ages 5–7), the response scale is reworded and simplified to a 3-point scale (0 = not at all a problem; 2 = sometimes a problem; and 4 = a lot of a problem). Items are reverse-scored and linearly transformed to a 0–100 scale (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0), so that lower scores demonstrate more GI symptoms and hence lower GI-specific HRQOL. Scale Scores are computed as the sum of the items divided by the number of items answered (this accounts for missing data). If more than 50 % of the items in the scale are missing, the Scale Score is not computed [44]. This accounts for the differences in sample sizes for scales reported in the tables. Although there are other strategies for imputing missing values, this computation is consistent with the previous PedsQLTM peer-reviewed publications as well as other well-established HRQOL measures [1]. To create the PedsQLTM Gastrointestinal Symptoms Scales Total Score (58 items), the mean is computed as the sum of the items divided by the number of items answered in the ten PedsQLTM Gastrointestinal Symptoms Scales

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(Stomach Pain and Hurt, Stomach Discomfort When Eating, Food and Drink Limits, Trouble Swallowing, Heartburn and Reflux, Nausea and Vomiting, Gas and Bloating, Constipation, Blood in Poop, and Diarrhea Scales). PedsQLTM Gastrointestinal Worry Scales The PedsQLTM Gastrointestinal Worry Scales encompass two individual scales: (1) Worry About Going Poop Scale (5 items) and (2) Worry About Stomach Aches Scale (2 items). The format, instructions, Likert response scale, and scoring method for the PedsQLTM Gastrointestinal Worry Scales are identical to the PedsQLTM 4.0 Generic Core Scales [36], with higher scores indicating better HRQOL and hence lower worry [25]. PedsQLTM Family Information Form Parents completed the PedsQLTM Family Information Form that contains demographic information including the child’s date of birth, gender, race/ethnicity, presence of a chronic health condition, and parental education information [36]. Statistical analysis Feasibility was determined from the percentage of missing values [45]. Missing B2 % of data in applied research settings is considered acceptable [46]. Cronbach’s coefficient alpha was utilized to determine scale internal consistency reliability [47]. Scales with internal consistency reliabilities of 0.70 or greater are recommended for comparing patient groups, while an internal consistency reliability criterion of 0.90 is recommended for analyzing individual patient scores [48]. Construct validity was determined utilizing the knowngroups method [32]. The known-groups validity method compares scale scores across groups known to differ in the health construct being investigated [49, 50]. In this study, PedsQLTM Gastrointestinal Symptoms Scales and Gastrointestinal Worry Scales scores in groups differing in known health condition (healthy participants and participants known to have a GI disorder) were computed [45, 51], using independent samples t tests (Bonferroni’s family-wise correction for multiple comparisons = 0.05/13 for child selfreport and parent proxy-report, respectively). In order to determine the magnitude of the anticipated differences, effect sizes were calculated [52]. Effect size as used in these analyses was calculated by taking the difference between the healthy sample means and the GI sample means, divided by the pooled standard deviation. Effect sizes for differences in means are designated as small (0.20), medium (0.50), and large (0.80) in magnitude [52].

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In order to explore potential differences between patients with FGIDs as a group and organic GI diseases as a group to each other and to the healthy controls, we utilized Welch’s analysis of variance (ANOVA) with Games–Howell post hoc tests since the homogeneity of variances assumption was not supported by the Levene’s test. The Games–Howell post hoc tests were only utilized when there was a significant omnibus Welch’s ANOVA F test [53], indicating that there were significant differences among the groups for a particular scale. The Games–Howell post hoc tests were used to determine which GI groups differed from the healthy controls for each scale, as well as whether the two GI groups differed from each other. Since these were exploratory analyses, we did not control for the number of statistical tests conducted. In order to explore an evaluation of the known-groups validity of the individual PedsQLTM Gastrointestinal Symptoms Scales and Gastrointestinal Worry Scales across the seven individual FGIDs and organic GI diseases in comparison with the healthy controls, we utilized Welch’s ANOVA with Games–Howell post hoc tests since the homogeneity of variances assumption was not supported by the Levene’s test. The Games–Howell post hoc tests were only utilized when there was a significant omnibus Welch’s ANOVA F test [53], indicating that there were significant differences among the groups for a particular scale. The Games–Howell post hoc tests were used to determine which GI groups differed from the healthy controls for each scale. Given that this study included a heterogeneous sample of patients with GI disorders, we were interested in exploring the pattern of the ten individual Symptoms Scales and the two Worry Scales across the seven GI disorders to the healthy controls, and whether the pattern of findings was generally consistent with the disease characteristics of the seven GI disorders included in the present investigation. Since these were exploratory analyses with small sample sizes for some of the subgroups, we did not control for the number of statistical tests conducted. Statistical analyses were conducted using SPSS for Windows [54].

Qual Life Res (2015) 24:363–378 Table 1 Characteristics of pediatric patients with gastrointestinal disorders and healthy controls Characteristics

Patient families n (%) or Mean (SD)

Healthy families n (%) or Mean (SD)

Total number

689

552

11.43 (4.58)

11.43 (4.33)

1.00

Male

318 (46.2 %)

255 (46.2 %)

1.00

Female

371 (53.8 %)

297 (53.8 %)

517 (75.0 %)

415 (75.2 %)

Age

a

Genderb

Race/ethnicityb White nonHispanic Hispanic

68 (9.9 %)

55 (10.0 %)

Black nonHispanic

63 (9.1 %)

50 (9.1 %)

Asian/Pacific Islander

13 (1.9 %)

10 (1.8 %)

Native American

1 (0.1 %)

1 (0.2 %)

Other

27 (3.9 %)

21 (3.8 %)

Less than high school graduate

40 (5.8 %)

42 (7.6 %)

High school graduate

88 (12.8 %)

85 (15.4 %)

Some college or certification course

180 (26.1 %)

124 (22.5 %)

College graduate

228 (33.1 %)

193 (35.0 %)

Graduate or professional degree

122 (17.7 %)

108 (19.6 %)

Missing

31 (4.5 %)

0 (0 %)

Less than high school graduate

59 (8.6 %)

42 (7.6 %)

High school graduate

111 (16.1 %)

99 (17.9 %)

Some college or certification course

141 (20.5 %)

134 (24.3 %)

Results

College graduate

170 (24.7 %)

164 (29.7 %)

Patient characteristics

Graduate or professional degree

118 (17.1 %)

113 (20.5 %)

Missing

90 (13.1 %)

0 (0 %)

Table 1 contains the demographic characteristics of the patient sample. A total of 689 families (587 children ages 5–18 years and 685 parents of children ages 2–18 years) participated and completed the PedsQLTM scales.

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p value

1.00

Parent education mothersb 0.30

Parent education fathersb

a b

Independent samples t tests Chi-square test

0.73

Qual Life Res (2015) 24:363–378 Table 2 PedsQLTM Gastrointestinal Symptoms Scales and Worry Scales scores comparisons between pediatric patients with gastrointestinal disorders and healthy controls for child self-report and parent proxy-report

369

Gastrointestinal Symptoms Scales and Worry Scales

Items

Child self-report

a

a

Mean

SD

58

0.96

72.5

Mean

Differences*** (95 % CI)

Effect size

16.1 (14.3–17.9)

1.07

SD

N = 513 17.0

0.98

88.6

12.9

Stomach Pain and Hurt

6

0.92

54.6

26.4

0.90

79.2

19.1

24.6 (21.8–27.4)

1.07

Stomach Discomfort When Eating

5

0.90

74.0

25.7

0.90

89.6

16.2

15.6 (13.0–18.2)

0.73

Food and Drink Limits

6

0.90

68.6

27.0

0.91

89.7

17.0

21.1 (18.3–23.9)

0.94

Trouble Swallowing

3

0.81

91.1

16.1

0.88

95.6

10.9

4.5 (2.9–6.1)

0.33

Heartburn and Reflux

4

0.72

78.8

20.0

0.78

90.6

14.3

11.8 (9.7–13.9)

0.68

Nausea and Vomiting

4

0.85

79.7

22.5

0.88

91.6

14.7

11.9 (9.7–14.1)

0.63

Gas and Bloating

7

0.90

64.3

24.6

0.93

83.3

20.1

19.0 (16.4–21.6)

0.85

14

0.94

71.1

23.5

0.96

86.9

17.6

15.8 (13.3–18.3)

0.76

Constipation

Lower scores demonstrate more gastrointestinal symptoms and hence lower gastrointestinalspecific HRQOL

Healthy controls

N = 587

Symptoms Total Scorea

Effect sizes are designated as small (0.20), medium (0.50), and large (0.80)

Gastrointestinal disordersb

Blood in Poop

2

0.89

85.9

23.6

0.87

96.3

12.0

10.4 (8.1–12.7)

0.55

Diarrhea

7

0.89

78.5

22.7

0.91

94.3

11.5

15.8 (13.7–17.9)

0.88

Worry About Going Poop

5

0.86

78.1

25.4

0.85

94.2

12.4

16.1 (13.8–18.4)

0.81

Worry About Stomach Aches

2

0.84

60.5

32.8

0.77

91.2

16.4

30.7 (27.6–33.8)

1.18

1.33

Parent proxy-report

N = 685

N = 337

a

58

0.97

70.0

17.1

0.98

90.0

12.7

20.0 (17.9–22.1)

Stomach Pain and Hurt

6

0.95

51.3

26.5

0.94

79.1

20.3

27.8 (24.6–31.0)

1.18

Stomach Discomfort When Eating

5

0.93

66.0

26.8

0.94

88.6

17.7

22.6 (19.4–25.8)

1.00

Food and Drink Limits

6

0.95

68.2

29.5

0.92

91.0

15.6

22.8 (19.4–26.2)

0.97

Trouble Swallowing

3

0.89

92.2

15.3

0.93

96.5

11.3

4.3 (2.4–6.2)

0.32

*** All values are statistically significant at p \ 0.001 based on independent samples t tests (Bonferroni’s family-wise correction for multiple comparisons, p = 0.0038)

Heartburn and Reflux Nausea and Vomiting

4 4

0.81 0.93

80.8 78.3

20.8 24.9

0.80 0.92

93.3 92.1

13.0 15.2

12.5 (10.0–15.0) 13.8 (10.9–16.7)

0.72 0.67

Gas and Bloating

7

0.93

62.9

25.3

0.94

86.9

18.9

24.0 (21.0–27.0)

1.08

14

0.95

66.5

26.0

0.96

89.3

16.0

22.8 (19.7–25.9)

1.06

Blood in Poop

2

0.94

84.5

24.8

0.92

96.3

12.7

11.8 (9.0–14.6)

0.60

a

Diarrhea

7

0.90

77.4

22.6

0.92

94.8

11.3

17.4 (14.9–19.9)

0.97

Worry About Going Poop

5

0.90

75.7

26.0

0.90

95.4

11.9

19.7 (16.8–22.6)

0.97

Worry About Stomach Aches

2

0.86

60.0

32.0

0.79

92.8

16.1

32.8 (29.1–36.5)

1.29

a Cronbach’s alpha internal consistency reliability, SD standard deviation, CI confidence interval

Summary Score of the ten Gastrointestinal Symptoms Scales scores

b

Data for gastrointestinal disorders derived from Varni [25]

Symptoms Total Score

Constipation

Healthy controls characteristics Table 1 contains the demographic characteristics of the healthy controls. A total of 552 families (513 children ages 5–18 years and 337 parents of children ages 2–18 years) participated and completed the PedsQLTM scales. Feasibility: missing item responses For the GI disorders, the percentage of missing item responses on the 58 items of the PedsQLTM Gastrointestinal Symptoms Scales was 1.56 and 1.89 % for child self-

reports and parent proxy-reports, respectively. For the healthy controls, the percentage of missing item responses on the PedsQLTM Gastrointestinal Symptoms Scales was 0.16 and 0.09 % for child self-reports and parent proxyreports, respectively. For the GI disorders groups, the percentage of missing item responses on the seven items of the PedsQLTM Gastrointestinal Worry Scales was 1.24 and 1.92 % for child self-reports and parent proxy-reports, respectively. For the healthy controls, the percentage of missing item responses on the PedsQLTM Gastrointestinal Worry Scales was 0.22 and 0.00 % for child self-reports and parent proxy-reports, respectively.

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65.1 (29.3)

87.4 (19.5)

74.3 (22.5)

73.1 (23.9)

60.4 (26.8)

65.4 (25.5)

89.3 (22.3)

75.2 (23.3)

72.7 (28.5)

51.7 (34.2)

Food and Drink Limits

Trouble Swallowing

Heartburn and Reflux

Nausea and Vomiting

Gas and Bloating

Constipation

Blood in Poop

Diarrhea

Worry About Going Poop

Worry About Stomach Aches

66.3 (16.6)

44.1 (25.6)

Symptoms Total Scorea

Stomach Pain and Hurt

N = 363

66.8 (28.5)

Stomach Discomfort When Eating

Parent proxy-report

44.3 (26.7)

67.5 (17.8)

Stomach Pain and Hurt

Symptoms Total Score

N = 282

Child self-report

a

Functional gastrointestinal disordersa Mean (SD)

Gastrointestinal Symptoms Scales and Worry Scales

59.4 (25.1)

79.1 (20.3)

90.0 (12.7)

N = 337

N = 312 74.4 (16.8)

91.2 (16.4)

94.2 (12.4)

94.3 (11.5)

96.3 (12.0)

86.9 (17.6)

83.3 (20.1)

91.6 (14.7)

90.6 (14.3)

95.6 (10.9)

89.7 (17.0)

89.6 (16.2)

79.2 (19.1)

88.6 (12.9)

N = 513

Mean (SD)

Healthy controlsc

68.5 (29.1)

83.0 (21.1)

81.3 (21.8)

82.6 (24.5)

76.4 (20.2)

68.0 (21.7)

85.6 (19.2)

82.9 (16.4)

94.6 (11.1)

72.1 (24.1)

80.7 (20.9)

64.0 (22.3)

77.2 (14.7)

N = 299

Organic gastrointestinal diseasesb Mean (SD)

19.7*** (15.4 to 24.0)

35.0***

(12.9 to 18.3) (30.9 to 39.1)

15.6***

23.7*** (21.1 to 26.3)

22.7*** (18.4 to 27.0)

(8.1 to 14.3)

(17.4 to 25.6) 39.5*** (34.4 to 44.6)

11.2***

(9.8 to 16.2)

(15.6 to 22.6) 21.5***

13.0***

(10.1 to 17.3)

19.1***

13.7***

7.0***

(7.1 to 13.9)

(3.5 to 10.5)

10.5***

21.5***

(11.7 to 18.9)

(17.4 to 25.6)

15.3***

22.9***

(3.0 to 9.0)

(14.8 to 22.2) (18.6 to 27.2)

6.0***

(5.0 to 10.4)

(12.8 to 19.8) 18.5***

7.7***

16.3***

1.0 (-0.9 to 2.9)

(13.9 to 21.3)

(20.1 to 29.1) 8.2*** (5.3 to 11.1)

17.6***

(5.7 to 12.1)

(18.5 to 27.1) 24.6***

8.9***

(11.5 to 18.9)

22.8***

15.2***

34.9***

(9.0 to 13.8)

(30.6 to 39.2)

11.4***

21.1***

Differencesb b versus c (95 % CI)

(18.3 to 23.9)

Differencesb a versus c (95 % CI)

(10.7 to 19.9)

15.3***

(5.1 to 11.1)

8.1***

16.8*** (10.5 to 23.1)

(5.4 to 15.2)

10.3***

(1.7 to 10.5)

6.1***

(2.1 to 11.3)

6.7***

(6.5 to 15.5)

11.0***

(2.8 to 12.4)

7.6***

(8.3 to 16.7)

12.5***

(4.7 to 12.5)

8.6***

7.2 (4.1 to 10.3)

(1.7 to 12.3)

7.0***

(9.0 to 18.8)

13.9***

(14.9 to 24.5)

19.7***

(6.5 to 12.9)

9.7***

Differencesb a versus b (95 % CI)

1.51

1.60

1.47

0.98

1.04

0.39

0.98

0.97

0.93

0.86

0.52

1.03

0.98

1.54

1.36

Effect size a versus c

0.86

1.05

0.85

0.65

0.75

0.71

0.55

0.73

0.35

0.50

0.10

0.84

0.48

0.73

0.82

Effect size b versus c

0.60

0.49

0.53

0.41

0.27

0.29

0.48

0.31

0.58

0.44

0.45

0.26

0.56

0.80

0.59

Effect size a versus b

Table 3 PedsQLTM Gastrointestinal Symptoms Scales and Worry Scales Scores comparisons between pediatric patients with functional gastrointestinal disorders, organic gastrointestinal diseases, and healthy controls

370 Qual Life Res (2015) 24:363–378

68.3 (30.3)

91.0 (16.9)

80.0 (22.1)

76.0 (26.1)

58.5 (25.2)

58.3 (26.9)

88.9 (22.4)

76.7 (22.5)

71.8 (27.8)

54.1 (33.5)

Food and Drink Limits

Trouble Swallowing

Heartburn and Reflux

Nausea and Vomiting

Gas and Bloating

Constipation

Blood in Poop

Diarrhea

Worry About Going Poop

Worry About Stomach Aches

66.6 (28.7)

80.2 (23.0)

78.2 (22.8)

79.6 (26.3)

76.1 (21.2)

67.8 (24.4)

80.8 (23.1)

81.8 (19.2)

93.5 (13.3)

68.4 (28.4)

70.8 (26.0)

Organic gastrointestinal diseasesb Mean (SD)

92.8 (16.1)

95.4 (11.9)

94.8 (11.3)

96.3 (12.7)

89.3 (16.0)

86.9 (18.9)

92.1 (15.2)

93.3 (13.0)

96.5 (11.3)

91.0 (15.6)

88.6 (17.7)

Mean (SD)

Healthy controlsc

26.2*** (21.8 to 30.6)

(11.8 to 18.6)

38.7*** (34.1 to 43.3)

15.2***

23.6***

(13.3 to 19.9)

(19.9 to 27.3)

16.6***

18.1***

(12.8 to 20.6)

(15.0 to 21.2)

16.7***

7.4***

(9.7 to 16.7)

(27.1 to 34.9) (4.2 to 10.6)

13.2***

(15.1 to 23.1)

(24.5 to 32.3) 31.0***

19.1***

(7.7 to 14.9)

28.4***

11.3***

(8.5 to 14.5)

(10.1 to 16.5) 16.1***

(0.7 to –5.3) 11.5***

(12.4 to 19.8)

3.0**

5.5***

(18.3 to 26.9)

(3.0 to 8.0) 13.3***

22.6***

22.7***

(13.7 to 21.9)

(18.4 to 27.0)

17.8***

26.7***

Differencesb b versus c (95 % CI)

(22.7 to 30.7)

Differencesb a versus c (95 % CI)

b

a

12.5*** (6.9 to 18.1)

(3.8 to 13.0)

8.4***

(-2.6 to 5.6)

1.5

(4.9 to 13.7)

9.3***

(13.4 to 22.2)

17.8***

(4.9 to 13.7)

9.3***

(0.3 to 9.3)

4.8*

(-1.9 to 5.5)

(-0.3 to 5.3) 1.8

2.5

(-5.2 to 5.4)

0.1

(4.1 to 13.7)

8.9***

Differencesb a versus b (95 % CI)

* p \ 0.05, ** p \ 0.01, *** p \ 0.001 based on Games–Howell post hoc tests after Welch’s one-way analysis of variance (ANOVA)

Summary score of the 10 Gastrointestinal Symptoms Scales scores

a Cronbach’s alpha internal consistency reliability, SD standard deviation, CI confidence interval

Lower scores demonstrate more gastrointestinal symptoms and hence lower gastrointestinal-specific HRQOL

Effect sizes are designated as small (0.20), medium (0.50), and large (0.80)

61.9 (26.9)

Functional gastrointestinal disordersa Mean (SD)

Stomach Discomfort When Eating

Gastrointestinal Symptoms Scales and Worry Scales

Table 3 continued

1.47

1.10

1.02

0.41

1.40

1.28

0.75

0.73

0.38

0.94

1.17

Effect size a versus c

1.13

0.83

0.92

0.81

0.70

0.88

0.58

0.70

0.24

0.99

0.81

Effect size b versus c

0.40

0.33

0.07

0.38

0.73

0.37

0.16

0.09

0.16

0.00

0.34

Effect size a versus b

Qual Life Res (2015) 24:363–378 371

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Table 4 PedsQLTM Gastrointestinal Symptoms Scales and Worry Scales means (SD) across individual diagnostic groups in comparison with healthy controls Gastrointestinal Symptoms Scales and Worry Scales

Healthy n = 513

Diagnostic groupsa,

b

CC n = 116

FAP n = 115

FD n = 14

IBS n = 38

CD n = 191

UC n = 65

GERD n = 43

88.6 (12.9)

68.7*** (19.1)

67.6*** (16.9)

70.2* (16.4)

61.9*** (16.6)

76.4*** (15.1)

79.6*** (14.8)

76.9*** (12.8) 52.2***

Child self-report Symptoms Total Scorec Stomach Pain and Hurt

79.2

58.0***

34.9***

39.6***

33.6***

64.9***

69.3*

(19.1)

(27.1)

(21.9)

(21.3)

(22.6)

(21.6)

(22.1)

(21.9)

Stomach Discomfort When Eating

89.6

76.3***

61.0***

67.2

55.7***

80.4***

84.7

76.2*

(16.2)

(25.7)

(27.2)

(29.0)

(32.2)

(20.9)

(17.9)

(24.1)

Food and Drink Limits

89.7

71.6***

62.1***

59.8*

56.6***

70.4***

74.6***

75.4*

(17.0)

(27.6)

(27.5)

(29.3)

(36.0)

(24.4)

(22.3)

(25.5)

Trouble Swallowing

95.6

89.9*

83.0***

84.5

94.0

95.1

96.5

89.3

(10.9)

(17.6)

(22.9)

(18.2)

(10.1)

(10.2)

(8.4)

(16.0)

Heartburn and Reflux

90.6

77.7***

71.8***

68.8

73.6**

84.0***

86.5

72.8***

(14.3)

(22.1)

(22.2)

(28.0)

(21.8)

(15.6)

(14.7)

(18.8)

91.6

79.4***

69.0***

58.9*

71.5**

86.8*

90.4

73.3**

(14.7)

(22.7)

(22.1)

(30.7)

(25.7)

(17.8)

(14.8)

(25.5)

Gas and Bloating

83.3

61.1***

62.3***

67.3

50.1***

66.8***

72.5**

66.6**

(20.1)

(29.1)

(24.6)

(24.6)

(25.0)

(21.2)

(21.4)

(24.0)

Constipation

86.9 (17.6)

59.6*** (26.9)

72.0*** (23.9)

74.8 (21.5)

59.6*** (21.7)

74.3*** (21.0)

79.3 (18.8)

81.9 (17.2)

Blood in Poop

96.2

87.3**

91.5

92.0

88.2

82.5***

76.4***

91.9

(12.0)

(24.9)

(20.2)

(18.1)

(21.5)

(23.3)

(30.2)

(16.8)

Diarrhea

94.3

68.6***

80.6***

89.5

73.8***

80.2***

78.4***

90.7

(11.5)

(24.5)

(20.8)

(10.4)

(24.6)

(22.4)

(23.1)

(13.8)

Worry About Going Poop

94.2

59.5***

82.4***

90.4

76.5**

81.4***

82.7**

90.6

(12.4)

(30.3)

(23.5)

(10.1)

(25.0)

(21.2)

(24.2)

(13.0)

Worry About Stomach Aches

91.2

60.2***

46.6***

58.9*

39.1***

67.5***

74.2***

64.0***

(16.4)

(34.7)

(32.3)

(33.0)

(33.2)

(29.8)

(26.5)

(29.2)

Healthy n = 337

CC n = 187

FAP n = 118

FD n = 17

IBS n = 43

CD n = 192

UC n = 67

GERD n = 54

Symptoms Total Scorec

90.0

66.9***

66.7***

69.6***

60.9***

74.4***

78.3***

69.3***

(12.7)

(17.0)

(16.1)

(13.5)

(16.3)

(16.7)

(15.3)

(17.9)

Stomach Pain and Hurt

79.1

53.6***

33.9***

38.2***

32.1***

61.1***

63.9***

47.8***

(20.3)

(25.3)

(21.8)

(21.6)

(22.6)

(25.2)

(22.5)

(24.7)

Stomach Discomfort When Eating

88.6

69.1***

55.3***

56.0**

50.2***

71.4***

76.7**

61.3***

(17.7)

(25.6)

(25.7)

(26.5)

(28.1)

(25.0)

(23.7)

(30.2)

Food and Drink Limits

91.0

75.0***

62.7***

62.5*

56.3***

69.1***

72.7***

60.6***

Trouble Swallowing

(15.6) 96.5

(27.4) 93.2

(31.8) 87.4***

(30.0) 87.7

(32.3) 92.4

(27.4) 94.7

(27.5) 97.8

(31.8) 84.3**

(11.6)

(15.0)

(20.2)

(16.7)

(13.0)

(11.5)

(6.6)

(19.9)

Heartburn and Reflux

93.3

87.1**

71.5***

66.2**

78.3**

84.5***

88.7

63.2***

(13.0)

(19.1)

(22.7)

(22.0)

(21.7)

(17.6)

(13.1)

(20.0)

92.1

83.9**

67.2***

59.9**

72.4**

82.8***

88.4

63.9***

(15.2)

(23.4)

(25.2)

(27.6)

(28.6)

(21.1)

(17.1)

(28.1)

Nausea and Vomiting

Parent proxy-report

Nausea and Vomiting

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373

Table 4 continued Healthy n = 337

CC n = 187

FAP n = 118

FD n = 17

IBS n = 43

CD n = 192

UC n = 67

GERD n = 54

86.9

58.5***

60.4***

61.1*

52.3***

66.9***

75.1**

62.5***

(18.9)

(25.1)

(24.9)

(28.9)

(25.5)

(22.4)

(23.4)

(30.1)

Constipation

89.3

48.4***

71.2***

79.3

58.5***

74.9***

80.5**

74.5**

(16.0)

(26.4)

(22.8)

(18.6)

(22.5)

(20.8)

(18.0)

(25.8)

Blood in Poop

96.3

85.6***

91.8

94.9

93.5

79.6***

72.0***

89.1

(12.7)

(26.0)

(17.7)

(13.3)

(16.8)

(25.8)

(31.1)

(17.9)

Diarrhea

94.8

75.2***

80.4***

89.3

68.0***

76.5***

75.2***

87.9

(11.3)

(23.6)

(18.8)

(12.9)

(25.9)

(23.2)

(23.8)

(17.4)

Worry About Going Poop

95.4

63.7***

81.2***

87.6

74.4***

79.0***

78.6***

86.4

(11.9)

(30.0)

(22.8)

(14.4)

(22.7)

(23.5)

(22.9)

(21.1)

92.8

64.3***

42.4***

47.8**

44.8***

66.6***

68.8***

63.7***

(16.1)

(32.9)

(30.1)

(37.0)

(30.5)

(28.5)

(29.5)

(28.8)

Gas and Bloating

Worry About Stomach Aches

Lower scores demonstrate more gastrointestinal symptoms and hence lower gastrointestinal-specific HRQOL Healthy healthy controls, CC chronic constipation, FAP functional abdominal pain, FD functional dyspepsia, IBS irritable bowel syndrome, CD Crohn’s disease, UC ulcerative colitis, GERD gastroesophageal reflux disease, SD standard deviation * p \ 0.05, ** p \ 0.01, *** p \ 0.001 based on Games–Howell post hoc tests after Welch’s one-way analysis of variance (ANOVA) a

Data for gastrointestinal disorders derived from Varni [25]

b

Differences between healthy controls and individual gastrointestinal diagnostic groups

c

Summary Score of the ten Gastrointestinal Symptoms Scales scores

Internal consistency reliability Cronbach’s alpha internal consistency reliability coefficients for the PedsQLTM Gastrointestinal Symptoms Scales and Gastrointestinal Worry Scales are shown in Table 2. All child self-reports and parent proxy-reports exceeded the minimum reliability standard of 0.70 required for group comparisons for both healthy controls and pediatric patients with GI disorders. The Gastrointestinal Symptoms Scales Total Score for both child self-reports and parent proxy-reports exceeded the reliability criterion of 0.90 recommended for analyzing individual patient scores, as did a number of the individual scales. Known-groups validity Table 2 demonstrates comparisons between pediatric patients with GI disorders as a group in comparison with the healthy controls. For each PedsQLTM Gastrointestinal Symptoms and Gastrointestinal Worry Scales scores, pediatric patients with GI disorders demonstrated significantly greater symptoms and worry (lower scale scores) than the healthy controls (Bonferroni’s family-wise correction for multiple comparisons, p = 0.0038). Most effect sizes were in the large effect size range. Table 3 presents the findings for the Games–Howell post hoc tests of the ten individual PedsQLTM Gastrointestinal Symptoms Scales and the two Gastrointestinal

Worry Scales between pediatric patients with FGIDs as a group and patients with organic GI diseases as a group to the healthy controls and to each other. The omnibus Welch’s ANOVA F tests for all ten Symptoms Scales and the two Gastrointestinal Worry Scales for both child selfreports and parent proxy-reports were significant at p B 0.001. The findings demonstrate that pediatric patients with FGIDs as a group and pediatric patients with organic diseases as a group demonstrated significantly greater symptoms and worry (lower scale scores) than the healthy controls, with most effect sizes in the large effect size range supporting known-groups validity. The findings in Table 3 also show that pediatric patients with FGIDs as a group manifested greater symptoms and worry than pediatric patients with organic GI diseases. Table 4 presents the findings for the Games–Howell post hoc tests of the ten individual PedsQLTM Gastrointestinal Symptoms Scales and the two Gastrointestinal Worry Scales across the seven GI disorders in comparison with the healthy controls. The omnibus Welch’s ANOVA F tests for all ten Symptoms Scales and the two Gastrointestinal Worry Scales for both child self-reports and parent proxy-reports were significant at p B 0.001. The findings demonstrate that the individual scales across the seven GI disorders demonstrated known-groups validity in comparison with the healthy controls, generally consistent with the individual disease characteristics of the GI disorders.

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Discussion The findings support the feasibility, internal consistency reliability, and known-groups validity of the PedsQLTM Gastrointestinal Symptoms Scales and Gastrointestinal Worry Scales when compared to healthy controls. Previously, we demonstrated the content validation of the PedsQLTM Gastrointestinal Symptoms Module, which includes the PedsQLTM Gastrointestinal Symptoms Scales and Gastrointestinal Worry Scales, utilizing qualitative methods in which pediatric patients with various GI disorders and their parents fully participated in the item generation process and were instrumental in developing items that reflect the patient perspective [22]. Taken together, the current findings on feasibility, reliability, and known-groups validity in comparison with healthy controls, along with the prior analyses supporting construct validity utilizing intercorrelations between the PedsQLTM Gastrointestinal Symptoms and Worry Scales with generic HRQOL [25], further support the measurement properties of these new scales. The PedsQLTM Gastrointestinal Symptoms Scales and Gastrointestinal Worry Scales make a significant contribution to the empirical literature by creating generic multidimensional GI-specific symptoms and worry scales that can be utilized across different pediatric FGIDs and organic GI diseases, as well as healthy populations. The PedsQLTM Gastrointestinal Symptoms Scales and Worry Scales had minimal missing responses, supporting feasibility, suggesting that pediatric patients and healthy children and their parents were willing and able to provide good quality data regarding the child’s gastrointestinal symptoms. The PedsQLTM Gastrointestinal Symptoms Scales and Worry Scales internal consistency reliabilities exceeded the recommended minimum alpha coefficient standard of 0.70 for group comparisons, while the Gastrointestinal Symptoms Scales Total Scores and a number of the individual scales exceeded the reliability criterion of 0.90 recommended for analyzing individual patient scores. The individual PedsQLTM Gastrointestinal Symptoms Scales may be utilized to examine specific domains of GI symptoms given the requirements of a particular clinical trial or practice need, as well as subgroup differences across scales. Each of the individual PedsQLTM Gastrointestinal Symptoms Scales and PedsQLTM Gastrointestinal Worry Scales can be used as standalone symptoms scales targeting the particular symptoms profile for a particular pediatric FGID or organic GI disease. This use of individual PedsQLTM Scales has precedence from other PedsQLTM Modules. For example, the PedsQLTM Asthma Symptoms Scale from the PedsQLTM Asthma Module has been utilized as a standalone scale in treatment research [55], as has the PedsQLTM Cognitive Functioning Scale from the

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PedsQLTM Multidimensional Fatigue Scale [18]. We anticipate that the PedsQLTM Gastrointestinal Symptoms and Worry Scales, in combination with the PedsQLTM 4.0 Generic Core Scales (physical, emotional, social, and school functioning) [36], and when indicated the PedsQLTM Multidimensional Fatigue Scale [6], will provide a more comprehensive understanding of the health and well-being of children with different FGIDs and organic GI diseases. We also expect that the PedsQLTM Gastrointestinal Symptoms Scales will be a valuable contribution to the empirical literature in measuring changes in GI symptoms over time in these pediatric patients, as well as providing insight into new areas for future interventions to enhance GI-specific symptom management for these patients. Although the primary focus of the current study was to demonstrate the known-groups validity of the PedsQLTM Gastrointestinal Symptoms and Worry Scales in patients with GI disorders as a group in comparison with a matched healthy sample, we also explored potential differences between patients with FGIDs as a group and organic GI diseases as a group to each other and to the healthy controls. The results demonstrated that pediatric patients with FGIDs as a group and pediatric patients with organic diseases as a group manifested significantly greater symptoms and worry (lower scale scores) than the healthy controls. The results also showed that pediatric patients with FGIDs as a group manifested greater symptoms and worry than pediatric patients with organic GI diseases. We further explored evidence of known-groups validity across the individual GI diagnostic groups. The majority of the individual scales across most of the seven GI disorders demonstrated known-groups validity in comparison with the healthy controls, generally consistent with the individual disease characteristics of the seven FGIDs and organic GI diseases. Since gastrointestinal symptoms are relatively ubiquitous in pediatric populations [56–58], future research should investigate whether these new scales have potential application not only in disease-specific groups, but also at the population health level in identifying children and adolescents with persistent gastrointestinal symptoms that may warrant further evaluation and intervention. Given the prevalence of gastrointestinal symptoms in the general pediatric population [56–58], it was deemed essential to demonstrate known-groups validity of the PedsQLTM Gastrointestinal Symptoms and Worry Scales between pediatric patients with FGIDs and organic GI diseases in comparison to a matched healthy sample. The present study has several strengths, including the relatively large overall sample size for both the GI patients and matched healthy samples, the broad age range of participants, and the nationwide representation of the participants (nine clinical sites from across the country).

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Limitations include the lack of information on families who chose not to participate in the study, and the small sample sizes for some of the exploratory analyses. Although only patients with a single primary diagnosis were included based on the predominant symptom of each patient, there could have been some patients in which a major symptom was accompanied by the coexistence of other symptoms. Thus, even though patients with multiple diagnoses were not intentionally included, there is the possibility that concurrent symptoms associated with secondary diagnoses were present in some patients in the study. Nevertheless, the diagnosis of a FGID or an organic GI disease was made by each of the site investigators, who were board certified pediatric gastroenterologists. Diagnoses were based on current diagnostic criteria for FGIDs (Rome III) and organic GI diseases [North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and/or European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) guidelines/consensus statements/reports]. Feasibility in the present study was assessed solely by the percentage of missing values. It is possible that greater attention was given to completeness in this research study than would be given in a routine clinical setting. Future investigations should also evaluate the feasibility of these measures with regard to completion time and non-response rate in routine clinical practice. Further, we were not able to include all possible GI disorders (e.g., celiac disease) and certain patient groups contained relatively small numbers of participants (e.g., functional dyspepsia), which reduced the statistical power to detect group differences for some GI disorders in the known-groups validity analyses. For the Trouble Swallowing Scale, only the chronic constipation and functional abdominal pain groups were significantly different from the healthy controls for child selfreport. There may be several explanations for this finding. One explanation may be that this 3-item scale is not very discriminating, and may need additional items to more fully discriminate across known groups. In our previous field test study [25], this scale demonstrated significant ceiling effects, indicating that as a group, the patients in this study did not manifest significant problems in swallowing as measured by this scale. Even in patients with gastroesophageal reflux disease (GERD), trouble swallowing is nonspecific and is usually not identified as a primary symptom by children with GERD, which describe the symptoms related to the retrograde passage of the gastric contents, and not a problem during the swallowing event. Other scales have not included problem swallowing as one of the markers of GERD in pediatric patients [59, 60]. This also applies for functional dyspepsia, where trouble swallowing is not typically a primary symptom [61]. In fact, the Trouble Swallowing Scale may be best

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suited for patient groups in which trouble swallowing is a primary or major symptom, such as patients with eosinophilic esophagitis [17]. In the PedsQLTM Eosinophilic Esophagitis Module field test study, we found that patients with eosinophilic esophagitis manifested a score of 70.9 with no ceiling effects on the 4-item Symptoms II Scale, which includes items on trouble swallowing similar in content to the Trouble Swallowing Scale [17]. Thus, future research with the Trouble Swallowing Scale should include a trial in patients with eosinophilic esophagitis to more fully determine the measurement properties of this scale in known-groups analyses. Nevertheless, this does not explain the significant findings on the patients with chronic constipation and functional abdominal pain in comparison with healthy controls. Perhaps in these patient groups, similar to other patients with FGIDs, there is a general pattern of greater symptom reporting across a myriad of symptoms beyond the primary symptom [62]. Even though there were differences in comparison with the healthy controls score of 95.6, the chronic constipation and functional abdominal pain groups’ scores of 89.9 and 83.0, respectively, are within the ‘‘never’’ to ‘‘almost never’’ a problem range on the PedsQLTM response scale. Future research comparing these FGIDs with patients groups such as patients with eosinophilic esophagitis will be needed to further determine the known-groups validity of the Trouble Swallowing Scale. Future research will also need to determine the value of the PedsQLTM Gastrointestinal Symptoms Scales Total Score. Since this Total Score combines multiple gastrointestinal symptoms domains, it will be informative in future research to test whether the Total Score measures greater disease burden, that is, whether those pediatric patients with higher PedsQLTM Gastrointestinal Symptoms Scales Total Scores have lower overall functioning and other indicators of disease burden. Finally, the recall period for the PedsQLTM Gastrointestinal Symptoms Scales and Gastrointestinal Worry Scales utilized in the present study was the PedsQLTM standard ‘‘past 1 month’’ recall version. Although there are PedsQLTM Modules that also offer the acute ‘‘past 7 days’’ recall period option, we have found that the data from both recall periods are quite similar [29]. Nevertheless, future research studies should explore utilizing the PedsQLTM acute 7-day recall period with these scales to compare the acute and standard recall period versions, including responsiveness analyses and test–retest reliability. The development of the PedsQLTM Gastrointestinal Symptoms Scales and Gastrointestinal Worry Scales should help clinicians and researchers identify patient groups with different GI symptom profiles. The PedsQLTM Gastrointestinal Symptoms and Worry Scales can also assist in evaluating patient-reported outcomes in targeted interventions and identifying emerging symptoms and

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response to therapy over time for patient groups utilizing a common metric for both FGIDs and organic GI diseases. Acknowledgments No funding was specifically designated for the PedsQLTM Gastrointestinal Symptoms Module field test study data collection effort or manuscript preparation. Item development for the PedsQLTM Gastrointestinal Symptoms Module was previously supported by Takeda Pharmaceuticals North America, Inc. Data collection for the healthy controls sample was supported by intramural funding from the Texas A&M University Foundation. Conflict of interest Dr. Varni holds the copyright and the trademark for the PedsQLTM and receives financial compensation from the Mapi Research Trust, which is a nonprofit research institute that charges distribution fees to for-profit companies that use the Pediatric Quality of Life InventoryTM. Dr. Varni received investigator-initiated funding from Takeda Pharmaceuticals North America, Inc. (Deerfield, Illinois) for the previous item generation qualitative methods study. Dr. Pohl received investigator-initiated funding from Takeda Pharmaceuticals North America, Inc. (Deerfield, Illinois) for the previous item generation qualitative methods study. Drs. Varni and Pohl did not receive funding from Takeda Pharmaceuticals North America, Inc., for the current quantitative methods field test study. Dr. Pohl has received the following funding: INSPPIRE to Study Acute Recurrent and Chronic Pancreatitis is Children, Grant # 10987759, National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Nurko is supported by NIH Grant K24DK082792A. Dr. Shulman is supported by NIH Grants R01 NR013497, R34 AT006986, and T32 DK007664. These grants are not related to the current study. The other authors report no competing interests related to this study.

Appendix The Pediatric Quality of Life InventoryTM Gastrointestinal Symptoms Module Testing Study Consortium sites include a Network and Statistical Center at the Center for Health Systems and Design, Colleges of Architecture and Medicine, Texas A&M University, College Station, TX (PI: James W. Varni, Ph.D.), and nine primary research data collection sites: Division of Pediatric Gastroenterology, Nationwide Children’s Hospital, Ohio State University School of Medicine, Columbus, OH (PI: Jolanda Denham, MD); Department of Pediatrics, Baylor College of Medicine, Children’s Nutrition Research Center, Texas Children’s Hospital, Houston, TX (PIs: Robert J. Shulman, MD and Mariella M. Self, Ph.D.); Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital Colorado, Aurora, CO (PI: Deborah A. Neigut, MD); Center for Motility and Functional Gastrointestinal Disorders, Boston Children’s Hospital, Harvard Medical School, Boston, MA (PI: Samuel Nurko, MD); Division of Pediatric Gastroenterology, Children’s Medical Center of Dallas, University of Texas Southwestern Medical School, Dallas, TX (PI: Ashish S. Patel, MD); Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH (PIs: James P. Franciosi,

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MD, Shehzad Saeed, MD, and George M. Zacur, MD); Division of Gastroenterology, Hepatology and Nutrition, Lurie Children’s Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL (PI: Miguel Saps, MD); Division of Pediatric Gastroenterology, Hepatology and Nutrition, Goryeb Children’s Hospital, Morristown Medical Center, Morristown, NJ (PI: Barbara Verga, MD); Department of Pediatric Gastroenterology, Primary Children’s Hospital, University of Utah, Salt Lake City, UT (PI: John F. Pohl, MD).

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