Development and validation of a questionnaire measuring quality of ...

E P ID EMIOL O GY AN D HE AL TH S ER VI CE S R ESEA RCH

BJD

British Journal of Dermatology

Development and validation of a questionnaire measuring quality of life in primary caregivers of children with atopic dermatitis (QPCAD) K. Kondo-Endo, Y. Ohashi,* H. Nakagawa, T. Katsunuma, Y. Ohya,§ K. Kamibeppu– and I. Masuko§ Department of Experimental Therapeutics, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogin, Sakyo-ku, Kyoto 606-8507, Japan *Departments of Biostatistics and –Family Nursing, University of Tokyo, Tokyo, Japan Departments of Dermatology and Pediatrics, The Jikei University School of Medicine, Tokyo, Japan §Division of Allergy, the National Center for Child Health and Development, Tokyo, Japan

Summary Correspondence Kayoko Kondo-Endo. E-mail: [email protected]

Accepted for publication 25 January 2009

Key words atopic dermatitis, caregiver, child, quality of life, statistical validation

Conﬂicts of interest None declared. DOI 10.1111/j.1365-2133.2009.09177.x

Background Disease-specific health-related quality of life (HRQoL) instruments for primary caregivers of children with atopic dermatitis are useful in evaluating the efficacy of treatment in clinical practice and study. However, no such scale has been available in Japan. Objectives To develop and validate a self-administered instrument specifically designed to measure quality of life in primary caregivers of children with atopic dermatitis (QPCAD). Methods This study consisted of three successive phases: the item generation phase, pilot test phase and validation phase. In the item generation phase, questionnaire items were derived from 33 qualitative interviews with primary caregivers. In the pilot test phase, the face and content validity of the preliminary scale were assessed (n = 33). In the validation phase, the questionnaire was finalized and assessed in terms of statistical performance (n = 416). Results The QPCAD included 19 items in the following categories: ‘exhaustion’, ‘worry about atopic dermatitis’, ‘family cooperation’ and ‘achievement’. The reliability of internal consistency was fair (Cronbach’s alpha coefficients 0Æ66–0Æ87). The QPCAD subscales and total score were significantly correlated with psychological health, physical health, anxiety, depression and severity score, with mild to moderate correlation coefficients. Test–retest reliability and responsiveness to change in severity were also satisfactory. Conclusions The QPCAD is an appropriate tool for assessing HRQoL of primary caregivers of children with atopic dermatitis in clinical practice and clinical trials.

Atopic dermatitis (AD) affects not only patients themselves, but also impacts on the life of their family and their caregivers.1–5 AD is an inflammatory skin disease with a chronically relapsing course characterized by episodes of intense pruritus, lichenification, severely dry skin and susceptibility to cutaneous infections.6,7 AD is one of the most common skin disorders seen in infants and children,3,8 and that number has gradually been increasing.8 As children cannot manage the disease by themselves, the primary caregivers of children with AD are required to perform time-consuming care on their behalf1,4 and pay excess financial cost,9,10 and they have the worry about the child’s disease.4,5 The resulting psychosocial impact on the caregivers is tremendous. Health-related quality of life (HRQoL) is a multidimensional concept incorporating all factors that impact on an individual’s

life in terms of health.11–13 HRQoL is measured subjectively with questions regarding physical, psychological and social aspects.11–13 As the emphasis has shifted from disease-oriented to patient-oriented treatment,11,13,14 HRQoL has become a much used measure of efficacy in clinical practice, research, audit and political and financial fields.11–13,15,16 Consideration of the HRQoL of caregivers is important for better management of childhood AD.17 There are several reasons for this. Firstly, decision-making in the course of treatment and daily skin care for children with AD depends on their caregiver(s),2,18 and because maintaining higher level of caregivers’ HRQoL seems to lead to better adherence with skin care and treatment, evaluation of the HRQoL of caregivers is relevant. Secondly, when measuring the HRQoL level of children with AD, there are two options: their caregiver(s) are

2009 The Authors Journal Compilation 2009 British Association of Dermatologists • British Journal of Dermatology 2009 161, pp617–625

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618 Development and validation of QPCAD, K. Kondo-Endo et al.

asked to rate the level on the child’s behalf or, alternatively, the HRQoL of the caregiver is assessed instead. A previous study found that the parents’ rating of the HRQoL of children does not agree with that of the children themselves;19 therefore evaluation of the caregivers’ HRQoL is preferable and more appropriate.5 The Dermatitis Family Impact (DFI) questionnaire2 and the Parents’ Index of Quality of Life in AD (PIQoL-AD)5 are disease-specific HRQoL instruments currently available for caregivers of children with AD. The DFI was constructed to evaluate functioning of a family raising a child with AD.2 The PIQoL-AD is a HRQoL measure that has the needs model as its theoretical basis.5 Both are well-constructed scales and have come to be used in this field. However, both have some methodological problems. Firstly, they include only items for negative aspects of psychological well-being making it impossible to measure positive aspects of the patient’s life. Inclusion of positive items, such as pleasure in life and positive outlook on life, can help measure overall HRQoL more accurately, regardless of the medical condition.11 Secondly, the PIQoL-AD adopts a dichotomous response system, because it was developed via item response theory. However, a dichotomous response seems to be less sensitive to subtle changes in HRQoL as a person’s thoughts about their life are not always clear-cut and may not be well captured by binary response options. For these reasons a multiple-point scale is more suitable for measuring degree of HRQoL.13,20 Thirdly, the DFI is still under statistical validation. These problems make it highly desirable to develop and validate a new instrument specifically designed to assess HRQoL in primary caregivers of children with AD. The purpose of this study was to develop an instrument specifically designed to measure HRQoL in primary caregivers of children with AD (QPCAD) and to validate this instrument.

Patients and methods Recent research indicates that careful steps are required to enhance reliability and validity of HRQoL questionnaires.20–22 Based on this recommendation, this study consisted of three successive phases: the item generation phase, pilot test phase and validation phase. In the item generation phase, semistructured interviews were performed to extract important aspects of life for primary caregivers of children with AD. Items were generated based on these results. In the pilot test phase, the preliminary QPCAD was administered to participants, and items were analysed to find statistical problems. Content validity was assured in this phase. In the validation phase, redundant items were eliminated to finalize the questionnaire and assessed in terms of statistical performance via correlation analysis and factor analysis. Approval of the protocol and study instruments, and informed consent documents were obtained from relevant ethics committees for each study phase. Written informed consent was obtained from all participants after assuring them of the protection of their privacy.

Participants The participants were the caregivers of children receiving outpatient treatment for AD diagnosed according to the criterion of the Japanese Society of Dermatology. Caregivers were excluded if the child or any of his ⁄her siblings had severe disease in addition to AD, or if the caregiver had a serious health problem or difficulty communicating in Japanese. Those caregivers who agreed to participate were recruited into the study after giving fully informed consent to participate. In each phase, the major reason for refusal to take part was ‘No time to participate’. The medical facilities were four general hospitals and one paediatric clinic. In all facilities, a combination treatment based on steroid ointment or tacrolimus ointment, antiallergic drugs and emollient was administered to patients. Item generation phase Semistructured interviews were conducted individually with 33 participants, according to a predetermined interview protocol, in January and March 2005. The interview protocol was devised to retrieve information such as demographic background and medical circumstances. The interviewer asked open-ended questions to invite each participant to describe freely how their life is influenced by AD. After each interview participants were given a sheet of plain paper with a stamped envelope and asked to describe additional information if applicable. A coupon valued at US $25 was given to each participant. Thirty-nine participants were invited to take part and of these 33 (85%) agreed. The average interview time was 40 ± 16Æ1 min. Each interview was recorded, transcribed verbatim and analysed via content analysis by K.K.-E. The results were reworded into closed-ended questions content by content. The original words of the interviewees were preserved as far as possible. Some questions derived from a review of recent literature1–5 were also added into the draft. An expert panel consisting of one statistician, one dermatologist, two paediatricians, one nurse and two clinical psychologists revised the draft questionnaire for the pilot test. Three newly recruited caregivers also independently checked the questionnaire for content and wording. The preliminary QPCAD consisted of 85 items grouped into seven domains. The domains were physical exhaustion, psychological aspects, future outlook, concern about the disease, family functioning, financial aspects and social relations. Pilot test phase Thirty-three participants who had not been involved in the first phase of the study were individually approached to complete the preliminary QPCAD. After completion, they were asked to comment on the applicability, understandability, relevance and comprehensiveness of the HRQoL scale. A coupon valued at US $8 was given to each participant. 2009 The Authors

Journal Compilation 2009 British Association of Dermatologists • British Journal of Dermatology 2009 161, pp617–625

Development and validation of QPCAD, K. Kondo-Endo et al. 619

The pilot test questionnaire solicited information regarding demographic details of the primary caregiver and children in addition to the preliminary QPCAD. Disease severity was also assessed using the Investigators’ Global Assessment (IGA)23,24 and the Primary caregivers’ Global Assessment (PGA). The IGA and PGA are six-point ordinal measures of AD severity based on an overall assessment of skin lesions ranging from 0 (clear, no inflammatory signs of AD) to 5 (very severe disease).23,24 The IGA is rated by a doctor and the PGA by the primary caregiver. These instruments enable prompt assessment of severity. Progression to severe flare was defined as a score over 4 (i.e. at least severe erythema and severe infiltration ⁄papulation) indicating severe AD.23,24 Of the 34 caregivers approached, 33 (97%) agreed to participate in this phase in May and August 2005. All caregivers were mothers, and their mean age was 32 years (range 20–41). The mean age of the children was 36 months. The mean ± SD of the IGA and PGA were 1Æ7 ± 1Æ2 and 2Æ1 ± 1Æ2, respectively, suggesting that severity of the population was mild to moderate. The feasibility of items was evaluated in terms of frequency, mean ± SD, skewness and kurtosis. Items which met the following criteria were eliminated from the scale: (i) percentage of missing values > 5%; (ii) extreme response tendency (floor effect ⁄ceiling effect) present; and (iii) inter-item correlation of 0Æ80 or above due to conceptual overlap. The expert panel checked the results. In total 18 items were deleted. No item met the first deletion criterion. At first, 24 items were deleted due to the floor effect and three items due to the ceiling effect and 22 pairs of items had high inter-item correlation. One pair of items that had a similar content was combined into one question. Items that most of the participants graded with the same score were also removed because these items were less informative. The panel finally decided that 10 items, which met the second elimination criterion, would nevertheless be retained in the questionnaire after consideration of the importance of the question content. The draft of the QPCAD for the validation phase consisted of 67 items in seven domains. The panel checked the items to confirm that content validity was retained. Validation phase A well-validated scale meets the requirements of reliability, validity and responsiveness.11,13,20,21 Reliability is the degree to which an instrument is free from random error.21 Internal consistency and test–retest reliability are particularly important to HRQoL instruments.21 Internal consistency is the precision of a scale based on the homogeneity of the scale’s items,20 and is frequently represented by Cronbach’s alpha coefficient.25 The range of Cronbach’s alpha coefficients is 0–1. The alpha coefficient should be in the range 0Æ6–0Æ9 as too high an alpha indicates item redundancy.20 Test–retest reliability is the ability of an instrument to yield consistent scores over time when measuring a person in a stable condition;20 therefore longitudinal data are

required to determine this. Test–retest reliability is assessed by calculating intraclass correlation coefficients and weighted kappa coefficients.20,21 The range of both coefficients is 0–1. Larger coefficients indicate better reliability.20 Validity is the degree to which the instrument measures what it purports to measure.20,21 In determining validity, the minimum requirement is to determine content and construct validity. Content validity is the extent to which an instrument measures a representative range of the attribute under study. Content validity is assured by generating items from the population experiencing the situation and careful adoption of items. Content validity was assured by the previous two phases in this study. Construct validity is the extent to which an instrument supports a proposed interpretation of scores based on theoretical implications associated with the constructs being measured. Construct validity is classically shown by evaluating if the measure is, in a theoretically reasonable way, correlated with related measures. Responsiveness is an instrument’s ability to detect change overtime,21 and is sometimes referred to as longitudinal validity or sensitivity to change.26 Scales that are used in clinical trials are required to improve as the disease becomes less severe in response to treatment. Assessment of responsiveness involves estimation of the correlation with change in clinical variables.21,26 Data collection The self-administered QPCAD was finalized based on data from two longitudinal groups and one cross-sectional group. Four hundred and fifty-five participants were asked to complete the questionnaire and of these 416 (91%) agreed to participate in November 2005 and June 2006 (Fig. 1). Of the total 416, 78 caregivers whose children attended the facility for the first time were allocated to the follow-up group. In this group, questionnaires were completed at their first attendance, followed by the second administration on their next visit which was made 2–4 weeks later. At each visit, primary doctors evaluated AD severity. Results from this group were used to assess responsiveness because both AD severity and HRQoL are expected to improve to a large degree in this group. Of the participants whose children attended the facility more than once, 198 were assigned to the postal survey group. In this group, questionnaires were filled in at the time of their first attendance and 1 week later at home. The questionnaire for response at home was given to participants during their first visit. The questionnaire used at home was returned by post to the University of Tokyo. Findings from this group were used to assess test–retest reliability because AD severity was expected to be more stable in this group. Only the questionnaire used at home asked about stressful life events27 in order to confirm no remarkable change had occurred in their daily life. The remaining 179 caregivers were assigned to the crosssectional group in which participants completed the questionnaire only once. The questionnaires were delivered to


620 Development and validation of QPCAD, K. Kondo-Endo et al. Table 1 Demographics of caregivers who were enrolled in the validation phase (n = 416)

Caregivers invited to participate.

Characteristic

N = 455

Participants N = 416 (91·4%)

Follow-up

Postal survey

group n = 78

group n = 198

group n = 179

Caregivers whose

Caregivers whose

The remaining

children attended

children attended

caregivers whose

the facility for the

the facility more

children attended

first time

than once

the facility more

Cross-sectional

than once

First visit

Visit

n = 70 (89·7%)

n = 180 (90·9%)

Second visit

Postal response

n = 68 (87·2%)

n = 161 (81·3%)

Responsiveness

Test–retest reliability

(correlation analysis)

(intra-class correlation)

Visit n = 166 (92·7%)

Combined data from all three groups at (first) visit was used to finalize the QPCAD. Basic statistics, factor analysis, SAS VERCLUS procedure, and construct validity analysis was performed.

Age (years) Relationship with the child Mother Father Grandmother Marital status Married Unmarried Educational level Junior high school Senior high school Technical school Vocational school or junior college University Graduate school Occupation Housewife Office worker Civil servant Part-time worker Self-employed Student Others Medical status Presence of atopic dermatitis Number of hospitals previously visited for atopic dermatitis treatment Presence of chronic illness

34Æ3 ± 4Æ9 399 (95Æ9) 12 (2Æ9) 2 (0Æ5) 395 (95Æ0) 21 (5Æ0) 8 (1Æ9) 98 (23Æ6) 77 (18Æ5) 95 (22Æ8) 122 (29Æ3) 12 (2Æ9) 248 (59Æ6) 50 (12Æ0) 26 (6Æ3) 54 (13Æ0) 18 (4Æ3) 4 (1Æ0) 12 (2Æ9) 84 (20Æ2) 2Æ6 ± 1Æ5 35 (8Æ4)

Data are given as mean ± SD or n (%).

Fig 1. Flowchart of participant allocation and analysis in the validation phase. Numbers in parentheses represent the response rate for each group at each point.

participants while they waited for medical examination or payment. Therefore, there was little or no additional time demand on the participants. A coupon valued at US $8 was given to each participant. Variables The questionnaire included a draft of the QPCAD, other psychological instruments and questions about the demographics of the caregivers and their children (see Tables 1 and 2 for details). It took approximately 10–15 min to complete the questionnaire. The Quality of life questionnaire for Parents of Children with Atopic Dermatitis The QPCAD is a self-report questionnaire to evaluate the quality of life in the past week of primary caregivers of a child with AD. In general, treatment recommended by the Japanese

Table 2 Characteristics of children of participants who were enrolled in the validation phase (n = 416) Characteristics Age (months) Sex Male Female Attendance at a nursery school Medical status Age when atopic dermatitis was diagnosed (months) Investigators’ global assessment Primary caregivers’ global assessment ADSIC total score ADSIC severity score ADSIC affected area score (%) Presence of comorbidity Presence of bronchial asthma Presence of food allergy

39Æ0 ± 20Æ8 258 (62Æ0) 155 (37Æ3) 224 (53Æ8) 12Æ3 ± 15Æ4 1Æ5 ± 1Æ2 1Æ7 ± 1Æ0 2Æ18 ± 2Æ15 9Æ8 ± 13Æ0 14Æ3 ± 16Æ8 117 (28Æ1) 74 (17Æ8) 24 (5Æ8)

ADSIC, atopic dermatitis severity inventory for child. Data are given as mean ± SD or n (%).


Development and validation of QPCAD, K. Kondo-Endo et al. 621

Dermatology Association improves skin symptoms substantially in about 1 week. Therefore, the time frame of the HRQoL question was set at 1 week. Response was made on a five-point scale. The scoring system employed was a simple summation as suggested by Fletcher et al.28 Sixty-seven items were included in the draft of the scale. Based on the data in this phase it was intended that the final version would consist of around 19 items. Higher scores indicate a worse health state. The QPCAD was used at all measurements. The Medical Outcome Study 8-Item Short-Form Health Survey The Medical Outcome Study 8-Item Short-Form Health Survey (SF-8) is a short version of a self-administered generic HRQoL instrument29 consisting of eight items concerning eight categories: general health, physical functioning, role – physical, bodily pain, vitality, social functioning, mental health and role – emotional. These categories are summarized in two subscales: physical component summary score and mental component summary score. These summary scores are produced in such a way that raw scores in a sample from the general Japanese population are transformed into a distribution with a mean of 50. Higher scores indicate a better physical ⁄mental health state.

total of the four signs in each body part was defined as the degree of signs in that part. Then, each area affected was assessed by the percentage of involved body surface area (BSA) in each part. Involvement was evaluated on a five-point scale that begins at 0% and increases by 25% for each point up to 100% at a score of 4. Due to the large proportion of children in the study aged £ 6 years, 20% of the body surface area was assigned to the head and neck, frontal trunk and back, and 10% for extremities. A simple sum of the degree of signs and a sum of involved area were the ADSIC symptom score and the ADSIC affected area score, respectively. Higher scores represent more severely affected individuals. The range of the severity score is 0–84 and that of affected area score 0–100%. To heighten inter-rater reliability, the authors produced a scoring manual containing photographs of skin conditions in patients with AD of different degrees of severity. One dermatologist and two paediatric allergists independently rated the photographs in the manner outlined above and reached a consensus about the scores though discussion. The Investigators’ Global Assessment and the Primary caregivers’ Global Assessment The IGA and PGA were also used in this phase.24,34

The State-Trait Anxiety Inventory – Form JYZ

Severity improvement rated by doctors/participants

The State-Trait Anxiety Inventory – Form JYZ (STAI) is a selfadministered 40-item instrument with a four-point response that measures a person’s level of both state and trait anxiety.30 The subscale for anxiety state (20 items), which is expected to change more in the short term, was used in this study. Scores range from 0 to 40, with higher scores reflecting greater anxiety. Cronbach’s alpha coefficient was 0Æ88.

Severity improvement was also evaluated by doctors and by parents on a five-point scale. Higher scores indicate that AD severity had improved relative to that at the first visit of the follow-up group.

The Center for Epidemiologic Studies Depression Scale The Center for Epidemiologic Studies Depression Scale (CES-D) is a self-administered 20-item scale with a four-point response that screens for depressive symptoms.31,32 The total score ranges from 0 to 60, with higher scores reflecting more severe depression. Traditionally, a cut-off score of 16 ⁄15 has been used to distinguish depressed from nondepressed individuals. Cronbach’s alpha coefficient was 0Æ88. The Atopic Dermatitis Severity Index for Child The Atopic Dermatitis Severity Index for Child (ADSIC) was developed for doctors to evaluate AD severity in juvenile patients.33 A doctor first evaluates the degree of dermatitis signs in each of seven body parts: head and neck, frontal trunk, back, right ⁄left upper extremities, and right ⁄left lower extremities. The severity of AD signs was assessed on erythema and ⁄or infiltration, papulation, excoriation and lichenification, each on a four-point scale of 0 (absent) to 3 (severe). The

Change of caregiving burden rated by participants Change of caregiving burden was also rated by participants on a five-point scale at the second visit. Higher scores indicate a greater decrease in caregiving demand during the study period. Statistical analysis The QPCAD was finalized by three analyses. Items that met the deletion criteria were deleted. Then, the variables were clustered using PROC VARCLUS (SAS Institute Inc., Cary, NC, U.S.A.).35,36 Items identified by the clustering procedure as having a cluster value < 0Æ5 were deleted from the model. Finally, redundant items were removed via factor analysis using maximum likelihood with promax rotation.20 The final version of the QPCAD scale was examined by the expert panel to ensure content validity. The QPCAD was also tested in terms of reliability, validity and responsiveness. Cronbach’s alpha coefficients were calculated based on the accumulated data of all three groups. Test–retest reliability was evaluated by intraclass correlation coefficients together with their 95% confidence intervals on



the subscale basis. At an item level, weighted kappa coefficients37 were calculated. Construct validity of the QPCAD was tested by correlating the QPCAD other variables. Responsiveness was assessed by correlations between changes in the QPCAD and changes in other variables.21,26 Probability < 0Æ1 was considered significant considering the relatively small sample size. Statistics were calculated using SAS version 9.1 (SAS Institute Inc.) and SPSS version 11.5 (SPSS Inc., Chicago, IL, U.S.A.).

variance was adopted as the result. The categories were ‘exhaustion’ (seven items), ‘worry about AD’ (six items), ‘family cooperation’ (three items) and ‘achievement’ (three items). Details are shown in Appendix 1. Reliability

Tables 1 and 2 show demographic and medical details of the participants and their children. The majority of participants were the mothers of an affected child, with a mean age of 34 years (range 21–66). Mean age of the children was 39 months. Mean ± SD of the IGA and PGA were 1Æ5 ± 1Æ2 and 1Æ7 ± 1Æ0, respectively, suggesting that severity of the population was mild to moderate.

Cronbach’s alpha coefficients for the QPCAD were 0Æ87 for ‘exhaustion’, 0Æ84 for ‘worry about AD’, 0Æ81 for ‘family cooperation’ and 0Æ66 for ‘achievement’. The value for ‘achievement’ was slightly low to acceptable overall. Although data were returned from 161 participants of the postal survey group, in 10 of these cases there had been a stressful life event27 in the week between measurement points and consequently these were excluded; hence data from 151 individuals were entered into the reliability analysis. Apart from the ‘family cooperation’ score of the QPCAD, scores did not significantly change between the two observations. Good levels of test–retest reliability were observed. The intraclass correlation coefficients were around 0Æ80–0Æ87. The weighted kappa coefficients were 0Æ43–0Æ72.

Completion of the QPCAD

Validity

Thirteen items of a new draft of QPCAD with 67 items, 10 of which again met deletion criteria, were removed because of the floor effect. The remaining 54 items were of normal distribution and were used for the advanced analysis. The variable clustering procedure was used on the condition that items with an own cluster value of < 0Æ5 would be deleted from the model. Of 54 items, the variable clustering procedure resulted in 28 items in 10 categories. Redundant items were further removed via factor analysis. A structure of 19 items in four categories accounting for 51% of the total

The QPCAD subscales and total score were significantly correlated with other variables with mild to moderate correlation coefficients (Table 3). Correlation was observed in an expected way. Only ‘exhaustion’ and total score were associated with physical health (r = )0Æ38 and )0Æ25, respectively). The association between ‘worry about AD’ and anxiety measured by STAI was somewhat weaker than expected (r = 0Æ27). ‘Family cooperation’ showed a borderline correlation only with change of caregiving burden rated by participants (r = 0Æ20, P = 0Æ05).

Results Participants in validation phase

Table 3 Construct validity of the QPCAD (n = 416) Exhaustion Exhaustion Worry about AD Family cooperation Achievement Total score Physical healtha Psychological healtha Anxietyb Depressionc ADSIC severity score ADSIC affected area score IGA PGA

1Æ00

)0Æ38*** )0Æ52*** 0Æ54*** 0Æ50*** 0Æ12* 0Æ10* 0Æ12* 0Æ27***

Worry about AD 0Æ40*** 1Æ00

)0Æ06 )0Æ22*** 0Æ27*** 0Æ21*** 0Æ31*** 0Æ27*** 0Æ31*** 0Æ45***

Family cooperation 0Æ05 )0Æ03 1Æ00

0Æ02 )0Æ10* 0Æ25*** 0Æ20*** 0Æ03 0Æ04 0Æ03 0Æ04

Achievement 0Æ04 0Æ07 0Æ25*** 1Æ00 )0Æ07 )0Æ12* 0Æ25*** 0Æ17*** 0Æ14** 0Æ14** 0Æ13** 0Æ10*

Total score 0Æ79*** 0Æ74*** 0Æ35*** 0Æ35*** 1Æ00 )0Æ25*** )0Æ46*** 0Æ57*** 0Æ48*** 0Æ25*** 0Æ22*** 0Æ25*** 0Æ40***

QPCAD, quality of life in primary caregivers of children with atopic dermatitis; AD, atopic dermatitis; ADSIC, atopic dermatitis severity index for child; IGA, Investigators’ Global Assessment; PGA, Primary caregivers’ Global Assessment. aMeasured by the Medical Outcome Study 8-Item Short-Form Health Survey; bmeasured by the State-Trait Anxiety Inventory-Form; cmeasured by the Center for Epidemiologic Studies Depression Scale. All entries are Pearson’s correlation coefficients. ***P < 0Æ001; **P < 0Æ01; *P < 0Æ05.


Development and validation of QPCAD, K. Kondo-Endo et al. 623 Table 4 Responsiveness of the QPCAD and other related scales (n = 68) D QPCADa

D ADSIC severity score D ADSIC affected area score D Investigators’ Global Assessment D Primary caregivers’ Global Assessment Severity improvement rated by doctors Severity improvement rated by participants Change of caregiving burden rated by participants

D D Worry D Family D D Total Exhaustion about AD cooperation Achievement score

D Physical D Psychological D healthb healthb Anxietyc

0Æ12 )0Æ01

0Æ28* 0Æ21

0Æ14 0Æ04

0Æ16 0Æ06

0Æ24 0Æ11

)0Æ08 )0Æ09

)0Æ05 0Æ10

0Æ22 0Æ06

0Æ23 0Æ15

0Æ10

0Æ27*

0Æ10

0Æ04

0Æ19

0Æ01

0Æ00

0Æ24*

0Æ21

0Æ39***

0Æ53***

0Æ14

0Æ19

0Æ49***

0Æ01

)0Æ36**

0Æ41***

0Æ34**

0Æ09

0Æ12

)0Æ01

)0Æ13

)0Æ09

0Æ19

)0Æ29*

)0Æ24

0Æ04

0Æ16

)0Æ38**

)0Æ18

)0Æ18

)0Æ17

)0Æ10

)0Æ26*

)0Æ24*

)0Æ27*

)0Æ34**

)0Æ14

)0Æ14

)0Æ33**

)0Æ45***

)0Æ29*

)0Æ20

)0Æ27*

)0Æ44***

D Depressiond

QPCAD, quality of life in primary caregivers of children with atopic dermatitis; AD, atopic dermatitis; ADSIC, atopic dermatitis severity index for child. aHigher score of family corporation, achievement and total score means a more deteriorated state; bmeasured by the Medical Outcome Study 8-Item Short-Form Health Survey; cmeasured by the State-Trait Anxiety Inventory-Form; dmeasured by the Center for Epidemiologic Studies Depression Scale. All entries are Pearson’s correlation coefficients which were calculated by correlating changes of each scale between T1 and T2. ***P < 0Æ001; **P < 0Æ01; * P < 0Æ05; P < 0Æ1.

Responsiveness As expected, in the postal survey group neither the total nor subscale score changed significantly between the two observations, whereas in the follow-up group, these changed except for ‘family cooperation’. ‘Exhaustion’ and ‘worry about AD’ showed an improvement of more than three points, and the total score increased by approximately seven points at followup. Significant correlation coefficients between the QPCAD change and change in severity variables were observed (Table 4). In particular, ‘worry about AD’ was significantly correlated to ADSIC, IGA and other severity scales (r = 0Æ21– 0Æ53). ‘Family cooperation’ level did not change and consequently was not correlated to change in AD severity. The QPCAD was superior to the other well-being instruments in detecting severity change.

Discussion The overall goal of this study was to develop and validate a HRQoL instrument for the primary caregivers of children with AD. The final version of the QPCAD contains 19 items measuring ‘exhaustion’, ‘worry about AD’, ‘family cooperation’ and ‘achievement’. The QPCAD is printed on one side of an A4 sheet, and can be completed in 1–2 min. The QPCAD showed satisfactory performance; therefore wide use in clinical trials as well as daily clinical practice is expected. One of the important characteristics of the QPCAD lies in the measurement of positive aspects of life. Although life has positive as well as negative aspects, other AD-specific HRQoL questionnaires2,5 assess only the negative impact of children’s

AD on their family and caregivers. In this measure, six items out of 19 relate to positive influences of AD, for instance, ‘achievement’ in daily care or ability to control AD. These subscales enable users to overview the respondent’s life from different angles. As for negative aspects, ‘exhaustion’ and ‘worry about AD’ in the QPCAD were both referred to in the Family Dermatology Life Quality Index,17 the DFI2 and the PIQoL-AD,5 which supports the construct validity of the scale. The QPCAD was revealed to possess satisfactory statistical performance. Each subscale and the total score were shown to be internally consistent and to have retest reliability. Data in this study also demonstrated that the QPCAD possesses satisfactory validity. Total scores had reasonable correlation with psychological ⁄physical health,29 depression31,32 and anxiety,30 which suggests good convergent validity of the QPCAD. For example, the physical component summary of the SF-829 was only correlated with ‘exhaustion’ and total score of the QPCAD (r = )0Æ38 and )0Æ25, respectively). Factor analysis also revealed a satisfactory factor loading pattern of the QPCAD because all factor loading coefficients were exclusively high in one domain. These results strongly indicate that the QPCAD is sufficiently reliable to assess the HRQoL of a caregiver of AD children in cross-sectional and ⁄or longitudinal studies. One more interesting result is that although ‘worry about AD’ and anxiety measured by the STAI30 are similar concepts, the association between them was weak. It may be that those two measures sample different aspects of anxiety. Comparing items, ‘worry about AD’ measures more profound anxiety, while the STAI30 measures general anxiety which was not totally related to the disease of the children. Therefore, as



Ohashi14 and Brenner et al.38 point out, combination use with another scale appears to be more informative. Further study to support convergent validity of the QPCAD is needed to describe more fully the characteristics of the QPCAD. It is important to note that the responsiveness analysis indicated that the QPCAD, especially the item ‘worry about AD’, is sensitive to severity improvement to a sufficient extent. Such demonstration of the responsiveness of the HRQoL scale was considered to be difficult in preceding studies.39,40 In addition, the results revealed superiority of the QPCAD over other generic scales in responding to change in disease severity, as expected.41,42 Correlation between the HRQoL measure and subjectively measured severity change is generally expected to be stronger, as both are rated by the same person and concern about his ⁄her HRQoL. However, this study further showed the responsiveness of the QPCAD with respect to objectively measured severity, which supports the stable performance of the QPCAD in clinical evaluation. Although for some pairs of variables correlation coefficients were barely significant (e.g. correlation between change of total score and change of ADSIC were 0Æ24 with probability of 0Æ050), the reason for this seems to be due to the small sample size (n = 68). Numerous publications have emphasized the importance of familial function in management of AD in childhood.9,17 We started with the assumption that caregivers of children with more severe AD receive much assistance from their family. However, the result of ‘family cooperation’ contradicted this supposition. ‘Family cooperation’ level was only barely correlated with change of caregiving burden rated by participants, which indicates that ‘family corporation’ has determinants other than disease severity. In general, the QPCAD was shown to be sensitive to change of disease severity. Additional work is required to establish whether or not the QPCAD subscales can change in response to severity improvement over a relatively long time. In particular, it is necessary to examine how ‘family cooperation’ changes and if it is correlated with improvement of severity, which was not confirmed in this study. In terms of cultural differences, items related to financial demands and leisure that were included in the PIQoL-AD and the DFI were excluded from the final version of the QPCAD. This seems to be due to cultural differences. In Japan it is often taken for granted that parents sacrifice their life for their children and consequently parents seem unwilling to complain about loss of leisure time. In addition, medical expenses are covered by national health insurance and financial aid from municipal government. This seems to be the reason that the participants in this study did not regard financial demands as a serious life problem. This study has several limitations. One is that, as data presented here were based on caregivers of outpatients whose disease severity was mild to modest, the performance of the scale with inpatients with more severe AD is not known. Secondly, participants were recruited in five hospitals that are located in Tokyo and the surrounding region. Additional data

in other areas of Japan and abroad are required to confirm the robustness of the QPCAD. In conclusion, this study developed and validated a selfadministered instrument measuring health-related quality of life in primary caregivers of children with AD. The QPCAD is shown to be of satisfactory reliability, validity and responsiveness, which indicate it for wide use for many purposes from clinical study to daily clinical practice.

Acknowledgments This study was funded by the Public Health Research Foundation. We express heartfelt thanks to Dr Mark Rogers of Monash University for commenting on the manuscript. We also appreciate the invaluable advice of Professor Andrew Finlay. We thank the associate editor and the referees for their thoughtful and constructive comments and suggestions. Particular thanks are given to the participants who gave up their time to take part, and to the participating facilities.

References 1 Lewis-Jones S. Quality of life and childhood atopic dermatitis: the misery of living with childhood eczema. Int J Clin Pract 2006; 60:984–92. 2 Lawson V, Lewis-Jones MS, Finlay AY et al. The family impact of childhood atopic dermatitis: the Dermatitis Family Impact Questionnaire. Br J Dermatol 1998; 138:107–13. 3 Balkrishnan R, Housman TS, Grummer S et al. The family impact of atopic dermatitis in children: the role of the parent caregiver. Pediatr Dermatol 2003; 20:5–10. 4 Warschburger P, Buchholz HT, Petermann F. Psychological adjustment in parents of young children with atopic dermatitis: which factors predict parental quality of life? Br J Dermatol 2004; 150:304– 11. 5 McKenna SP, Whalley D, Dewar AL et al. International development of the Parents’ Index of Quality of Life in Atopic Dermatitis (PIQoL-AD). Qual Life Res 2005; 14:231–41. 6 Williams HC. Clinical practice. Atopic dermatitis. N Engl J Med 2005; 352:2314–24. 7 Ruzicka T, Bieber T, Schopf E et al. A short-term trial of tacrolimus ointment for atopic dermatitis. European Tacrolimus Multicenter Atopic Dermatitis Study Group. N Engl J Med 1997; 337:816–21. 8 The International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee. Worldwide variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema: ISAAC. Lancet 1998; 351:1225–32. 9 Su JC, Kemp AS, Varigos GA et al. Atopic eczema: its impact on the family and financial cost. Arch Dis Child 1997; 76:159–62. 10 Emerson RM, Williams HC, Allen BR. What is the cost of atopic dermatitis in preschool children? Br J Dermatol 2001; 144:514–22. 11 Fayers PM, Machin D. Quality of Life: Assessment, Analysis and Interpretation. Chichester: John Wiley & Sons, 2000. 12 Fayers PM, Sprangers MA. Understanding self-rated health. Lancet 2002; 359:187–8. 13 Spilker B. Quality of Life and Pharmacoeconomics in Clinical Trials, 2nd edn. New York: Lippincott Williams & Wilkins, 1996. 14 Ohashi Y. Feasibility and significance of measuring patients’ QOL in cancer treatment. Saishinigaku 2001; 56:696–704.


Development and validation of QPCAD, K. Kondo-Endo et al. 625 15 Finlay AY, Khan GK. Dermatology life quality index (DLQI) – simple practical measure for routine clinical use. Clin Exp Dermatol 1994; 19:210–16. 16 Staab D, Kaufmann R, Brautigam M et al. Treatment of infants with atopic eczema with pimecrolimus cream 1% improves parents’ quality of life: a multicenter, randomized trial. Pediatr Allergy Immunol 2005; 16:527–33. 17 Basra MK, Sue-Ho R, Finlay AY. The family dermatology life quality index: measuring the secondary impact of skin disease. Br J Dermatol 2007; 156:528–38. 18 O’Connell EJ. The burden of atopy and asthma in children. Allergy 2004; 59 (Suppl. 78):7–11. 19 Eiser C, Morse R. Can parents rate their child’s health-related quality of life? Results of a systematic review Qual Life Res 2001; 10:347–57. 20 Ohashi Y, Morita S. QOL no toukeigakuteki hyouka. In: Rinsho no tameno QOL hyouka handbook (Ikegami N, Shimozuma K, Fukuhara S, Ikeda S, eds). Tokyo: Igaku-shoin Ltd, 2001; 21–31. 21 Anonymous. Assessing health status and quality-of-life instruments: attributes and review criteria. Qual Life Res 2002; 11:193–205. 22 Fayers PM. Quality-of-life measurement in clinical trials – the impact of causal variables. J Biopharm Stat 2004; 14:155–76. 23 Kapp A, Papp K, Bingham A et al. Long-term management of atopic dermatitis in infants with topical pimecrolimus, a nonsteroid antiinflammatory drug. J Allergy Clin Immunol 2002; 110:277–84. 24 Papp KA, Werfel T, Folster-Holst R et al. Long-term control of atopic dermatitis with pimecrolimus cream 1% in infants and young children: a two-year study. J Am Acad Dermatol 2005; 52:240–6. 25 Cronbach L. Coefficient alpha and the internal structure of tests. Psychometrika 1951; 16:297–334. 26 Terwee CB, Dekker FW, Wiersinga WM et al. On assessing responsiveness of health-related quality of life instruments: guidelines for instrument evaluation. Qual Life Res 2003; 12:349–62. 27 Holmes TH, Rahe RH. The Social Readjustment Rating Scale. J Psychosom Res 1967; 11:213–18. 28 Fletcher A, Gore S, Jones D et al. Quality of life measures in health care. II: design, analysis, and interpretation. BMJ 1992; 305:1145– 8. 29 Fukuhara S, Suzukamo Y. Manual of the SF-8 Japanese Version. Kyoto: Institute for Health Outcome & Process Evaluation Research, 2004. 30 Iwata N, Mishima N, Shimizu T et al. Positive and negative affect in the factor structure of the State-Trait Anxiety Inventory for Japanese workers. Psychol Rep 1998; 82:651–6. 31 Radloff LS. The CES-D scale: a self-report depression scale for research in the general population. Appl Psychol Meas 1977; 11:385– 401. 32 Iwata N, Roberts RE. Age differences among Japanese on the Center for Epidemiologic Studies Depression Scale: an ethnocultural perspective on somatization. Soc Sci Med 1996; 43:967–74. 33 Study Group of Neoral Treatment of Atopic Dermatitis. Dose– response relationship of cyclosporin MEPC (Neoral) in patients with severe atopic dermatitis: multicenter, randomized, open-label, phase II clinical trial [in Japanese]. Nishi Nihon Hifuka 2008; 70:541–52. 34 Jones G, Jenkinson C, Kennedy S. Development of the short form endometriosis health profile questionnaire: the EHP-5. Qual Life Res 2004; 13:695–704. 35 Kishimoto J. Clustering variables – unveiling PROC VARCLUS. In: Nippon SAS Yuzakai Ronbunshu 1996; 199–212 [In Japanese].

36 Mathias SD, Warren EH, Colwell HH et al. A new treatment satisfaction measure for asthmatics: a validation study. Qual Life Res 2000; 9:873–82. 37 Cohen J. Multiple regression as a general data-analytic system. Psychol Bull 1968; 70:426–43. 38 Brenner MH, Curbow B, Legro MW. The proximal-distal continuum of multiple health outcome measures: the case of cataract surgery. Med Care 1995; 33:AS236–44. 39 Whalley D, Huels J, McKenna SP et al. The benefit of pimecrolimus (Elidel, SDZ ASM 981) on parents’ quality of life in the treatment of pediatric atopic dermatitis. Pediatrics 2002; 110:1133–6. 40 Finlay AY. Measurement of disease activity and outcome in atopic dermatitis. Br J Dermatol 1996; 135:509–15. 41 Wiebe S, Guyatt G, Weaver B et al. Comparative responsiveness of generic and specific quality-of-life instruments. J Clin Epidemiol 2003; 56:52–60. 42 Guyatt GH, Bombardier C, Tugwell PX. Measuring disease-specific quality of life in clinical trials. Can Med Assoc J 1986; 134:889–95.

Appendix 1 The final 19 items of the QPCAD. Considering your feelings over the past week with respect to your child’s atopic dermatitis (AD), to what extent do you agree with each of the statements below? Please circle one number for each question. 1 I feel tired. 2 I suffer disturbances such as cold, change in body weight, indigestion or headache. 3 I would like to have more time to rest. 4 I feel irritated. 5 I have little time to spare for the other members of my family after caring for my child with AD. 6 I need to change plans because of my child’s AD. 7 My life revolves around my child with AD. 8 I am anxious about my child’s AD. 9 I am concerned whether AD will be cured in the future. 10 I worry about whether AD influences a child’s development. 11 I am concerned about how my child will look as an adult. 12 It is hard for me to see my child scratching. 13 I worry about the possible adverse effects of my child’s treatment for AD. 14 My family is interested in caring for my child. 15 I think that the family has cooperated well in my child’s care. 16 My family and I discuss my child’s problems together. 17 I think that my child’s disease has led to positive personal development in me. 18 I am proud of myself for learning how to manage AD. 19 I think that I control my child’s AD well. The QPCAD must not be reproduced or used without permission. Anyone wishing to use the scale should contact Dr Hidemi Nakagawa at the Jikei University ([email protected]).
