Measurement properties of the EQ-5D-Y administered through a smartphone app in children with asthma: a longitudinal questionnaire study

Mayoraletal. Health and Quality of Life Outcomes (2022) 20:51 https://doi.org/10.1186/s12955-022-01955-5 RESEARCH Measurement properties oftheEQ-5D-Y administered throughasmartphone app inchildren withasthma: alongitudinal questionnaire study Karina Mayoral1,2,3, Olatz Garin1,3,4, Catalina Lizano‑Barrantes1,5,4, Angels Pont1,3, Araceli M. Caballero‑Rabasco6,2, Manuel Praena‑Crespo7,8, Laura Valdesoiro‑Navarrete9, María Teresa Guerra10,8, José Antonio Castillo11,8, Inés de Mir12, Eva Tato13, Jordi Alonso1,3,4, Vicky Serra‑Sutton14,3, Yolanda Pardo3,1,15, Montse Ferrer1,3,4* and ARCA Group Abstract Background: Asthma impacts children’s physical, emotional, and psychosocial Health‑Related Quality of Life (HRQL). The EQ‑5D‑Y is a generic econometric instrument developed to measure HRQL in children. Objective: Evaluation of feasibility, validity, reliability, and responsiveness of EQ‑5D‑Y descriptive system and util‑ ity index to allow the assessment of HRQL in children with asthma, aged 8–11 years (self‑response version) or under 8 years old (proxy‑response version). Methods: We used data from baseline to 10 months of follow‑up of an observational, prospective study of children with persistent asthma recruited by pediatricians in Spain (2018–2020). HRQL instruments were administered through a smartphone application: ARCA app. The EQ‑5D‑Y is composed of a 5‑dimension descriptive system, a utility index ranging from 1 to − 0.5392, and a general health visual analogue scale (EQ‑VAS). The Pediatric Asthma Impact Scale (PROMIS‑PAIS) includes 8 items, providing a raw score. Construct validity hypotheses were stated a priori, and evalu‑ ated following two approaches, multitrait–multimethod matrix and known groups’ comparisons. Reliability and responsiveness subsamples were defined by stability or change in EQ‑VAS and the Asthma Control Questionnaire (ACQ), to estimate the intraclass correlation coefficient (ICC) and the magnitude of change over time. Results: The EQ‑5D‑Y was completed at baseline for 119 children (81 self‑responded and 38 through proxy response), with a mean age of 9.1 (1.7) years. Mean (SD) of the EQ‑5D‑Y utility index was 0.93 (0.11), with ceiling and floor effects of 60.3% and 0%, respectively. Multitrait–multimethod matrix confirmed the associations previously hypothesized for the EQ‑5D‑Y utility index [moderate with PROMIS‑PAIS (0.38) and weak with ACQ (0.28)], and for the EQ‑5D‑Y dimension “problems doing usual activities” [moderate with the ACQ item (0.35) and weak with the PROMIS‑ PAIS item (0.17)]. Statistically significant differences were found in the EQ‑5D‑Y between groups defined by asthma control, reliever inhalers use, and second‑hand smoke exposure, with mostly moderate effect sizes (0.45–0.75). The © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco mmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Open Access *Correspondence: mf[email protected] 1 Health Service Research Group, IMIM (Hospital del Mar Medical Research Institute), Barcelona Biomedical Research Park, office 144. Doctor Aiguader, 88, 08003 Barcelona, Spain Full list of author information is available at the end of the article Page 2 of 16 Mayoraletal. Health and Quality of Life Outcomes (2022) 20:51 Introduction Asthma is a chronic condition that affects more than 300 million people worldwide [1], and it is the most common chronic disease during childhood, affecting around 14% of children globally [2]. Patient-reported outcome measures (PROMS), such as symptom control or Health- Related Quality of Life (HRQL), have been shown to be useful for clinical management, in combination with clinical measures, providing relevant information to understand the impact of the disease on patients’ functional status and well-being [3–5]. Given its heterogeneous nature and symptoms burden, asthma has physical, emotional, and psychosocial impact on children’s lives, as has been shown through diverse generic HRQL instruments [6–10]. The most affected dimensions of asthmaspecific HRQL instruments are peer relationships, feeling of dependence on medication, shortness of breath, and activity limitations [11–13]. There is consistent evidence that HRQL and asthma control are independent predictors of future exacerbation [14–17]. Furthermore, a systematic review [18] found that asthma severity was significantly related to the child’s HRQL in most of the studies. International guidelines [19–22] have emphasized that treatment goals should focus on improving the day-to-day symptoms of the patient, preventing exacerbations, and improving patients’ HRQL. HRQL instruments are generic or specific according to their target population, and they can in turn be classified as psychometric profiles or econometric indexes according to their measurement model [23]. Psychometric instruments generate scores on different dimensions in order to describe them (profiles). Econometric measures provide a single global score (index) which incorporates societal preferences for health states (utilities) that can be used to calculate quality-adjusted life years for use in economic evaluations [24]. The EQ-5D has probably been the most widely used econometric instrument in adults, and the EuroQol Group developed in 2010 the EQ-5D-Y to enable young individuals from 8years onwards to selfreport their health [25–28]. An EQ-5D-Y proxy version was also developed [29] for children under 8years old. There are few other econometric questionnaires for children, such as the Health Utility Index (HUI) and the Child Health Utility 9D (CHU-9D). The HUI [30] has a self-administered version and a proxy version (children 5–12years old), but its administration burden is substantially greater than for the EQ-5D-Y. The interviewer-administered EQ-5D-Y showed high feasibility and agreement with the CHU-9D among 6–7years old children [31], and several studies supported the acceptability [32], feasibility [32, 33], reliability [33], validity [33, 34], and responsiveness [35] of the EQ-5D-Y selfadministered version in children and adolescents from the general population aged 8–18 years. Furthermore, the psychometric properties of the EQ-5D-Y have already been tested in several pathologies, such as chronic kidney disease [36], cystic fibrosis [37], juvenile idiopathic arthritis [38], type 1 diabetes mellitus [39], idiopathic scoliosis [40], and chronic or acute conditions [41]. As far as we know, there is only one study centered on the psychometric properties of the EQ-5D-Y in patients with asthma [42], supporting its feasibility and its convergent validity with the Pediatric Asthma Quality of Life Questionnaire. Other studies in heterogeneous samples that included children and adolescents with asthma [43, 44] also supported the EQ-5D-Y’s feasibility, reliability, and construct validity. There is extensive evidence on the reliability [45], construct validity [45, 46] and responsiveness [47] of EQ-5D in adults, both for the descriptive system and the utility index. However, all previous studies on EQ-5D-Y in children evaluated only the dimensions of the descriptive system, or an equally weighted summary score. None of them evaluated the EQ-5D-Y utility index, because the value set for children has just been published [48]: first for the Slovenian [49] and then for the Spanish [50] population. To the best of our knowledge, this is the first study evaluating the psychometric properties of the EQ-5D-Y utility index, and also the first one assessing the psychometric properties of the EQ-5D-Y proxy version for children with asthma < 8years of age. We have found only two studies supporting the reliability and construct validity of the EQ-5D-Y proxy version, both performed in the general population [29, 51]. Our aim was to evaluate the feasibility, validity, reliability, and responsiveness of the EQ-5D-Y descriptive system and utility index to allow the assessment of ICC of the EQ‑5D‑Y utility index in the stable subsamples was high (0.81 and 0.79); and responsiveness subsamples presented a moderate to large magnitude of change (0.68 and 0.78), though without statistical significance. Conclusions: These results support the use of the EQ‑5D‑Y as a feasible, valid, and reliable instrument for evaluating HRQL in children with persistent asthma. Further studies are needed on the responsiveness of the EQ‑5D‑Y in this population. Keywords: Health‑Related Quality of Life, Asthma, EQ‑5D‑Y, Validity, Reliability, Responsiveness, Smartphone app Page 3 of 16 Mayoraletal. Health and Quality of Life Outcomes (2022) 20:51 Health-Related Quality of Life in children with asthma aged 8–11 years old (self-response version) or under 8years old (proxy-response version). Methods Participants andstudy design The Asthma Research in Children and Adolescents (ARCA) is a longitudinal prospective multicenter observational study (NCT04480242), designed to provide evidence about the evolution of young patients with persistent asthma through a regular follow-up. Patients were recruited in 3 outpatient pediatric pulmonology hospital units and 8 primary care pediatric centers in Spain, from January 2018 to July 2020. Families were informed about the project and asked to participate if their children fulfilled the following inclusion criteria: aged 6–14, with clinical diagnosis of asthma, undergoing treatment with inhaled corticosteroids (alone or combined with long-acting beta-agonists) for more than 6months in the previous year, and with access to a smartphone (their own, or their parents’). Exclusion criteria were: chronic obstructive pulmonary disease,cystic fibrosis, pulmonary fibrosis, bronchiectasis, active tuberculosis, or/and immunodeficiency associated with alpha 1 antitrypsin deficiency, ciliary diseases. Study variables The ARCA study collects information through different sources: medical records, computer-assisted telephone interviews performed by trained interviewers, and the ARCA smartphone application [52]. The EQ-5D-Y and the Patient-Reported Outcomes Measurement Information System-Pediatric Asthma Impact Scale (PROMISPAIS) were administered through the ARCA app, while all the variables to define known groups for validity assessment were collected through telephone interviews, and clinical characteristics came from medical records. The ARCA app development has been described elsewhere [52]. Briefly, HRQL questionnaires are administered every 6 months: the EQ-5D-Y at baseline and month 6 of follow-up, and the PROMIS-PAIS at months 4 and 10. The ARCA app is available in 3 age versions (6–7, 8–11, and ≥ 12years old) following the EQ-5D age cut-off points. The version for the younger age group was designed to be answered by parents or guardians (proxy response), and the other two versions for children’s and adolescents’ self-response. For the evaluation of the EQ- 5D-Y, 12–14years old adolescents were excluded because the EQ-5D-5L is administered in this age version. The EQ-5D-Y was developed to measure HRQL in children [25]. It includes a descriptive system [26] of 5 dimensions and a visual analogue scale (EQ-VAS) of general health. The dimensions measure “mobility”, “looking after myself”, “doing usual activities”, “having pain or discomfort” and “feeling worried, sad or unhappy” with 3-level Likert response scales (no problems, moderate problems, and serious problems). The EQ-VAS ranges from 0, worst health possible, to 100, best health possible. The time frame for both the dimensions and the EQ-VAS is “today”. The EQ-5D-Y proxy version 1, which asked proxies to rate the child’s HRQL in their own opinion, has the same characteristics as the self-reported version. Evidence on the Spanish EQ-5D-Y’s validity, feasibility, and reliability has been reported [33]. From the three digital versions of the EQ-5D-Y, laptop/ desktop, tablets, and PDA/smartphone, we administered the latter through a smartphone app [52] with its original generic content, without including any expression for asthma-specific attribution. The preference value set to generate the EQ-5D-Y utility index for Spain [48] was obtained from adults thinking as a hypothetical 10-year- old child, as recommended in the international protocol. A single preference-based index was calculated ranging from 1 (the best health state) to negative values (health states valued by society as worse than death), where 0 is equal to death. The Patient-Reported Outcomes Measurement Information System (PROMIS) developed a disease-specific item bank to measure the HRQL of children with asthma [53]: the Pediatric Asthma Impact Scale (PROMISPAIS). The short form 8a version of the PROMIS-PAIS (v2.0) contains the item set that provides the maximum test information with the least items [52]. It has demonstrated a higher precision [53] than other asthmaspecific instruments [54, 55], while presenting a lower administration burden. Each item of the PROMIS-PAIS is attributed to asthma with the expression “because of my asthma”, except for the last one which states “My asthma bothered me”. The items [56] ask about the past seven days in a 5-level Likert response scale (1–5) with the options: never, almost never, sometimes, often, andalmost always. It is available for self-response in ages 8–17, and for proxy response in children starting at age 5. The total raw score is calculated by adding the values of the response to each question, the lowest possible score is 8 and the highest is 40. Missing items were imputed by a simple allocation method from the mean of those items that were available in each dimension of the questionnaire [57]. The information collected through telephone interviews included, among other, the Asthma Control Questionnaire (ACQ), exacerbations occurring in the previous 6months, treatments for asthma, and secondhand smoke exposure. Two versions of telephone interviews were developed, one designed to be answered by parents or Page 4 of 16 Mayoraletal. Health and Quality of Life Outcomes (2022) 20:51 guardians of children under 8years old (proxy response) and the other for self-response (participants aged 8 and older). The Asthma Control Questionnaire ACQ-symptoms only [58] assesses the frequency of 5 asthma symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, and wheeze) during the previous week on a 7-level Likert scale from 0 (no impairment) to 6 (maximum impairment). The overall score, calculated as the mean of item responses, ranges from 0 to 6. Cut-off points of 1.5 and 0.75 are established to define not well- and well-controlled asthma, respectively [59]. Results generated by this short version have shown to be very similar to those of the complete ACQ, as were its measurement properties (reliability, responsiveness, internal consistency, construct validity, and interpretability) [58]. The ACQ has been validated [60] using self-administration in children 11years and older and interviewer-administration in 6- to 10-year-olds. Asthmatic exacerbations during the last 6months were assessed through three questions constructed applying the definitions by the American Thoracic Society and the European Respiratory Society [61]: Did you visit or phone your family doctor or outpatient emergency department because your asthma got worse? Did you call an ambulance or go to the hospital because of your asthma? Did you take steroids tablets or syrup (such as Prednisolone or Deltacortril) for at least 2days because of your asthma? If the participant answers “yes” to at least one of the three questions, an asthma exacerbation is confirmed. To measure the frequency of Short-Acting Beta-Ago- nists (SABA) inhaler use during the previous 4weeks, the following question was asked to patients with SABA therapy prescription: How often have you usually taken your “reliever medication” (brand name) in the past 4weeks? (Every day; almost every day; once or twice every week; less than once a week; or I don’t know). Secondhand smoke exposure was measured through a single question taken from the High School Risk Factors Survey [62]: How many people out of those who stay in your house regularly smoke indoors? (No one smokes indoors; 1 person; 2; 3; 4; 5 people and more than 5 people). Ethics considerations The study was approved by the ethics committee of participant centers in accordance with national and international guidelines (code of ethics, Helsinki Declaration) as well as legislation on data confidentiality (Spanish Organic Law 3/2018 of December 5 on the Protection of Personal Data and the Guarantee of Digital Rights). The collection and transfer of data was carried out according to strict security and data encryption. Written informed consent was required from the parents or legally authorized representatives of all participants, and additionally oral consent was obtained from children. Analytical strategy Considering the ARCA sample of 119 patients, a statistical power of 80% (using a two-side test with a type I error of 5%) was calculated to detect moderate differences (0.5 SD) in the EQ-5D-Y utility index between two equally distributed known groups, or to detect moderate to large differences (0.65 SD) between two known groups unequally distributed into 85% and 15% of the sample [63]. Characteristics of the sample were described by calculating percentages, or means and standard deviations, according to the type of variable. To evaluate the feasibility of the EQ-5D-Y, we calculated the completion rate, the distribution of the response options, and the proportion of missing values. Distribution of the EQ-5D-Y utility index, EQ-VAS, and the PROMIS-PAIS raw score were examined by calculating the observed range, the floor and ceiling effects (proportion of participants with the worst and best possible score, respectively), and statistics of central tendency and dispersion. Construct validity of the EQ-5D-Y was assessed by applying two different approaches: multitrait-multi- method matrix, and comparison of known groups. The multitrait-multimethod matrix between the EQ-5D-Y, the PROMIS-PAIS, and the ACQ was constructed with Spearman correlations due to the scores’ distribution. Besides their scores, the dimension or item on activities was also included in the matrix, since it was covered by all three questionnaires. The strength of the correlations was defined [64] as weak (≤ 0.30), moderate (0.31–0.60), or strong (0.61–0.90). The relationships between instruments can be categorized as convergent (different instruments measuring a similar concept) or discriminant (different instruments measuring different traits or constructs). For convergent validity, we hypothesized a moderate correlation between the PROMIS-PAIS raw score and the EQ-5D-Y utility index, since both instruments intend to measure HRQL though from different perspectives (generic and asthmaspecific). Also, we expect moderate correlations between the EQ-5D-Y dimension “problems doing usual activities”, and the ACQ item “how limited were you in your activities because of your asthma?”. On the other hand, for divergent validity, we expected a weak correlation between the EQ-5D-Y utility index and the ACQ, since they differ on the construct being measured (HRQL and disease control). A weak correlation was also expected between the EQ-5D-Y dimension “problems doing usual activities” and the PROMIS-PAIS item “it was hard for Page 5 of 16 Mayoraletal. Health and Quality of Life Outcomes (2022) 20:51 me to play sports or exercise because of my asthma”, due to differences in the type of activities considered. Known groups were defined according to the ACQ (well-controlled, intermediate, and not well-controlled asthma) [59], asthmatic exacerbation during the last 6months (yes or no), frequency of SABA inhaler use during the previous 4weeks (less than once vs once or more per week), and secondhand smoke exposure (exposed or not). The hypotheses raised a priori, based on available evidence, were that patients with worse control of asthma [65], asthmatic exacerbations [66], higher frequency of SABA use [65], and second-hand smoke exposure [67] present worse HRQL. In particular, we expected the EQ- 5D-Y to present worse discriminant capacity than the disease-specific PROMIS-PAIS because of its generic nature. To assess differences among groups we used Chisquare test for proportions of participants with problems, and U-Mann Witney or Kruskall-Wallis nonparametric test for the HRQL scores. The magnitude of the differences between groups was assessed by the Cohen effect size (difference of mean/pooled SD) [68]. General guidelines define an effect size of 0.2 as small, 0.5 as moderate, and 0.8 as large [69]. To assess reliability and responsiveness, patients were divided into three subsamples defined according to stability, worsening or improvement between the two administrations of the EQ-VAS and the ACQ. On one hand, patients who changed in EQ-VAS ± 0.3 SD or less (small magnitude) were included in the stable subsample, and those with a change larger than 0.3 SD (moderate or large magnitude) in the negative and positive direction were considered for the worsening and improvement subsamples respectively. The cut-off point of 0.3 SD [69] was selected following the established interpretation of the magnitude of change. On the other hand, according to the ACQ, patients that remained in the same asthma control category were included in the stable subsample, while those which moved to a worse or better category were included in the worsening or improvement subsample. Since our hypothesis was that a stable EQ-VAS or ACQ indicates health stability over time, test–retest reproducibility of the EQ-5D-Y and PROMIS-PAIS was assessed in the stable subsamples by measuring the agreement between the two administrations with the Intra-class Correlation Coefficient (ICC). Regarding responsiveness, our hypothesis was that the EQ-5D-Y is able to detect change over time, though with a lower sensitivity than the asthma-specific instrument PROMIS-PAIS. Responsiveness was evaluated in the worsening and improvement subsamples by testing differences between the two administrations in the EQ-5D-Y or PROMIS-PAIS with the Wilcoxon paired test. The magnitude of change was measured by the effect size coefficient (mean of change/ SD of change) for the worsening and improvement subsamples analyzed together. IBM SPSS Statistics software, version 22, was used to analyze the data. Results Of the 189 participants recruited (see Fig.1), 55 patients aged 12–14 years were excluded because they were administered the EQ-5D-5L, 15 did not download the ARCA app, and 119 in total were included in the study: 81 were 8–11 years old children who completed the self-response version, and 38 were 6–7years old children whose parents or guardians completed the proxy response version of the EQ-5D-Y. Table1 shows the characteristics of the sample at baseline. Around 60% of the participants were boys and had well-controlled asthma. Differences between age groups were only found for asthmatic exacerbation, which was more frequent among 6 to 7-year-olds. Very few patients reported problems in the EQ-5D-Y dimensions (Table 2), especially for “mobility” (5.1%) and “looking after myself” (2.6%). The dimension showing the highest percentage of participants with problems was “doing usual activities” (28.8%) where there was 1 participant reporting “a lot of” problems. Very few missing values were observed in some EQ-5D-Y dimension (“mobility”, “looking after myself”, and “doing usual activities”). At month 4 after recruitment (when the PROMISPAIS was administered through the app), 44 participants were lost to follow-up, and 75 answered the PROMISPAIS. Table3 shows the results of the participants who answered the PROMIS-PAIS (self-response n = 59; proxy response n = 16). Patients reported more frequently “my asthma bothered me” and “it was hard to play sports or exercise because of asthma”. The PROMIS-PAIS was completed entirely by the responders, with no missing values for any of the items. As shown in Table4, the mean (SD) of the EQ-5D-Y utility index in the total sample was 0.93 (SD = 0.11). This high mean is explained by the accumulation of patients in 1, the highest score (best HRQL). This ceiling effect of 60.3% is caused by the high number of participants reporting “no problems” in all dimensions. Despite this accumulation in the highest score, the observed range (1–0.5095) indicates a high variance. The EQ-VAS mean (SD) was 84.3 (17.1) among the whole sample. There were three patients with a missing value in the EQ-5D-Y utility index, while the EQ-VAS was completed by all responders. The PROMIS-PAIS raw score mean (SD) was 11.9 (4.9), and its ceiling effect was 32%. Table 5 presents the multitrait-multimethod matrix between EQ-5D-Y, PROMIS-PAIS, and ACQ. For the Page 6 of 16 Mayoraletal. Health and Quality of Life Outcomes (2022) 20:51 two correlations previously hypothesized as moderate (convergent validity) we obtained a coefficient of 0.38 between the PROMIS-PAIS’ raw score and the EQ-5D-Y utility index, and of 0.35 between the EQ-5D-Y dimension “problems doing usual activities” and the ACQ item “how limited were you in your activities because of your asthma?”. Regarding discriminant validity, the two relationships hypothesized as weak obtained a correlation of 0.28 between the ACQ and the EQ-5D-Y utility index, and 0.17 between the EQ-5D-Y dimension “problems doing usual activities” and the PROMIS-PAIS item “it was hard for me to play sports or exercise because of my asthma”. The correlation of the EQ-VAS with the other two asthma-specific instruments was lower than that obtained with the EQ-5D-Y utility index. Table 6 shows statistically significant differences in some dimensions of the EQ-5D-Y, the utility index, and the EQ-VAS, among known groups defined by their asthma control with the ACQ, frequency of SABA use in the last 4weeks, and second-hand smoke exposure. The effect size of almost all these differences in both the EQ- 5D-Y utility index and the EQ-VAS was ≥ 0.5, indicating moderate magnitude. The largest magnitude of the 189 patients recruited App: 119 answered the EQ-5D-Y Telephone interviews: 119 completed App: 75 answered the PROMIS-PAIS 44 lost to follow up Baseline Month4 Month6 Month10 App: 62 answered the EQ-5D-Y 5 answered the EQ-5D-5L 52 lost to follow up Telephone interviews: 116 completed Telephone interviews: 3 not completed App: 67 answered the PROMIS-PAIS 52 lost to follow up 55 were 12–14 years old (EQ-5D-5L) 41 were 6–7 years old (EQ-5D-Y proxy version) 93 were 8–11 years old (EQ-5D-Y self-response) 15 did not download the ARCA app Fig. 1 Flow chart of the study from recruitment to month 10 Page 7 of 16 Mayoraletal. Health and Quality of Life Outcomes (2022) 20:51 difference with the PROMIS-PAIS raw score was 1.11 among asthma control groups (p = 0.02). Table 7 shows test–retest reproducibility results for the subsamples of stable patients and responsiveness results for the subsamples of patients with worsening and improvement, defined according to the changes on the EQ-VAS or the ACQ. Of the 62 participants who answered the EQ-5D-Y twice, after excluding three for missing values, 59 were finally distributed into the subsamples (24 stable, 17 worsened and 18 improved). Only 46 participants answered both the PROMIS-PAIS and the EQ-5D-Y twice. The subsamples defined according Table 1 Demographic and clinical characteristics of participants at baseline a ACQ: Asthma Control Questionnaire b SABA: Short-Acting β-Agonists All (n = 119) EQ-5D-Y Self response (n = 81) EQ-5D-Y Proxy response (n = 38) P value Age, mean (SD) 9.1 (1.7) 10.1 (1.1) 7.0 (0.6) < .001 6–7 38 (31.9%) 0 (0.0%) 38 (100.0%) < .001 8–11 81 (68.1%) 81 (100.0%) 0 (0.0%) Sex Girls 48 (40.3%) 29 (35.8%) 19 (50.0%) .14 Boys 71 (59.7%) 52 (64.2%) 19 (50.0%) Asthma control .99 ACQa, mean (SD) 0.81 (0.93) 0.81 (0.88) 0.81 (1.06) Well controlled (< 0.75) 68 (58.6%) 43 (54.4%) 25 (67.6%) .37 Intermediate (0.75–1.5) 23 (19.8%) 18 (22.8%) 5 (13.5%) Not well controlled (> 1.5) 25 (21.6%) 18 (22.8%) 7 (18.9%) Asthmatic exacerbations (last 6 months) Yes 53 (44.5%) 27 (33.3%) 26 (68.4%) < .001 No 66 (55.5%) 54 (66.7%) 12 (31.6%) Number of prescribed SABAb 0 9 (7.8%) 6 (7.6%) 3 (8.1%) .72 1 103 (88.8%) 71 (89.9%) 32 (86.5%) 2 4 (3.4%) 2 (2.5%) 2 (5.4%) Frequency of SABA inhaler use (previous 4 weeks) No use 9 (7.8%) 6 (7.6%) 3 (8.1%) .99 Less than once per week 62 (53.4%) 43 (54.4%) 19 (51.4%) Once or twice per week 29 (25.0%) 19 (24.1%) 10 (27.0%) Almost every day/Every day 16 (13.8%) 11 (13.9%) 5 (13.5%) Secondhand smoke exposure Not exposed 81 (83.5%) 55 (84.6%) 26 (81.3%) .92 Exposed 16 (16.5%) 10 (15.4%) 6 (18.7%) Missing 22 16 6 Table 2 Distribution of EQ‑5D‑Y dimensions in the entire sample at baseline EQ-5D-Y dimensions No problems Some problems A lot of problems Missing values n (%) n (%) n (%) n (%) Mobility 111 (94.9%) 6 (5.1%) 0 (0.0%) 2 (1.7%) Looking after myself 114 (97.4%) 3 (2.6%) 0 (0.0%) 2 (1.7%) Doing usual activities 84 (71.2%) 33 (28%) 1 (0.8%) 1 (0.8%) Having pain or discomfort 98 (82.4%) 21 (17.6%) 0 (0.0%) 0 (0.0%) Feeling worried, sad or unhappy 110 (92.4%) 9 (7.6%) 0 (0.0%) 0 (0.0%) Page 8 of 16 Mayoraletal. Health and Quality of Life Outcomes (2022) 20:51 to the ACQ were smaller, since we excluded nine patients whose telephone interview was more than 90days apart from their app response. For the stable EQ-VAS subsample, the mean change was of 0.01 in the EQ-5D-Y utility index and -0.5 in the PROMIS-PAIS raw score with ICCs of 0.81 and 0.89 respectively, indicating high agreement between both evaluations (reproducibility). Regarding responsiveness, though change of means was not statistically significant, the effect size was of moderate and large magnitude for the EQ-5D-Y utility index and PROMISPAIS raw score (0.68 and 1.08 respectively) among patients in the worsening or improvement subsamples, analyzed together. The agreement (reproducibility) in the stable subsample defined according to ACQ for the EQ-5D-Y utility index, EQ-VAS and the PROMIS-PAIS raw score measured with the ICC was 0.79, 0.70 and 0.68, respectively; and regarding responsiveness, the effect size of change was large (0.78, 1.15 and 1.28) among patients from the worsening or improvement subsamples, analyzed together. Discussion We found the EQ-5D-Y to be feasible and easy to administer via a smartphone application, but with a high ceiling effect (60.3% of participants reported no problem in any dimension). This generic preference-based instrument showed good validity, considering the moderate correlation between the EQ-5D-Y utility index and the PROMIS-PAIS raw score, and the discrimination among known groups based on the ACQ, frequency of Short- Acting Beta-Agonists (SABAs), and second-hand smoke exposure. Test–retest reproducibility among the stable subsamples indicated high reliability; and the magnitude of change observed between the first and second evaluation in the worsening or improvement subsamples may suggest its responsiveness, but the differences were not statistically significant. Feasibility of the EQ-5D-Y was indicated by its high response rate at baseline (97.5%): of the 119 participants who downloaded the app, 116 responded the EQ-5D-Y entirely. These results are similar to the 96% response rate reported in the abovementioned cross-sectional Swedish study on children and adolescents with asthma [42]. The flexibility of the administration through the app benefits our completion results, especially for the EQ-VAS with a completion rate of almost 100%, compared with 91% and 86.2% reported in studies where the EQ-5D-Y was administered in paper format to children with chronic conditions [43] and schoolchildren [44], respectively. The losses to follow-up (44 participants who downloaded the app but did not follow until month 6) are likely related to major misunderstandings regarding the app, such us patients thinking that it only had to be answered once and then deleted [52]. On the other hand, 8 patients who continued using the app did not answer the EQ-5D-Y at month 6, which is a response rate of 88.5%. This high level of completion in both administrations could be explained by its low response burden: response times have been estimated on 1.25 min for EQ-5D-Y web Table 3 Distribution of the Pediatric Asthma Impact Scale (PROMIS‑PAIS) items’ responses at month 4 after recruitment a PROMIS-PAIS: Patient-Reported Outcomes Measurement Information System-Pediatric Asthma Impact Scale PROMIS-PAISa items Never Almost never Sometimes Often Almost always n (%) n (%) n (%) n (%) n (%) I felt scared that I might have trouble breathing because of my asthma 60 (80.0%) 8 (10.7%) 6 (8.0%) 1 (1.3%) 0 (0.0%) My chest felt tight because of my asthma 53 (70.7%) 13 (17.3%) 7 (9.3%) 1 (1.3%) 1 (1.3%) I felt wheezy because of my asthma 52 (69.3%) 8 (10.7%) 14 (18.7%) 1 (1.3%) 0 (0.0%) I had trouble breathing because of my asthma 52 (69.3%) 12 (16.0%) 9 (12.0%) 2 (2.7%) 0 (0.0%) I had trouble sleeping at night because of my asthma 56 (74.7%) 9 (12.0%) 10 (13.3%) 0 (0.0%) 0 (0.0%) It was hard for me to play sports or exercise because of my asthma 48 (64.0%) 12 (16.0%) 9 (12.0%) 5 (6.7%) 1 (1.3%) It was hard to take a deep breath because of my asthma 52 (69.3%) 13 (17.3%) 8 (10.7%) 2 (2.7%) 0 (0.0%) My asthma bothered me 46 (61.3%) 14 (18.7%) 13 (17.3%) 2 (2.7%) 0 (0.0%) Table 4 Distribution of Health‑Related Quality of Life (HRQL) scores a EQ-VAS: EuroQol-Visual Analogue Scale b PROMIS-PAIS: Patient-Reported Outcomes Measurement Information System- Pediatric Asthma Impact Scale Distribution of scores EQ-5D-Y Utility Index EQ-VASaPROMIS- PAISb Raw score Sample 119 119 75 Theoretical Range + 1, − 0.5392 100, 0 8, 40 Best–worst Best–worst Best–worst Observed Range + 1, + 0.5095 100, 25 8, 29 Floor effect 0.0% 0.0% 0.0% Ceiling effect 60.3% 23.5% 32.0% Mean (SD) 0.93 (0.11) 84.3 (17.1) 11.9 (4.9) Missing 3 (2.5%) 0 (0.0%) 0 (0.0%) Page 9 of 16 Mayoraletal. Health and Quality of Life Outcomes (2022) 20:51 version [34]. These results support the feasibility of the EQ-5D-Y when it is administered through a smartphone application. Regarding the distribution of EQ-5D-Y results, the ceiling effect in the sample was high for the utility index (60.3%) and for three out of its five dimensions, which exceeded 90% of participants reporting no problem (“mobility”, “looking after myself”, and “feeling worried/ sad/unhappy”). This high ceiling effect in our sample could be partly explained by the considerable proportion of participants with well-controlled symptoms of asthma (58.6%). Furthermore, a similar ceiling effect, above 80%, has been also reported for the “mobility” and “looking after myself” dimensions in other studies with children or adolescents with asthma [42] and other chronic conditions [43, 44]. These ceiling effects are very high considering the established recommendation of 15% for HRQL scores [70]. However, this is a general standard, as there are none specifically for children. A higher ceiling effect could be expected in children, taking into account their capacity of adaptation to chronic diseases and treatment routines, known as the well-being paradox or response shift effect [71, 72]. The prevalence of problems reported in the dimensions of “doing usual activities” (29.6%) and “having pain or discomfort” (18.1%) are consistent with previous studies [42, 44, 73] where the EQ-5D-Y has been used to describe the impact of asthma on children and adolescents. Studies using the Pediatric Asthma Quality of Life Questionnaire (PAQLQ) [42, 74] or the Child Health Questionnaire (CHQ-CF87) [8] also highlighted the physical activity limitation, while another study measuring HRQL with the PedsQL™ [10] concludes that asthma has an impact on physical, emotional, and school performance. In our study, participants reported a low percentage of problems in the dimension of “Feeling worried, sad or unhappy” (7.6%). Construct validity of the EQ-5D-Y was evaluated by exploring its relationships as a generic measure with the asthma-specific PROMIS-PAIS, as there is no gold standard for HRQL assessment in pediatric asthma. The correlation between the EQ-5D-Y utility index and the PROMIS-PAIS raw score is moderate in our study, showing that both instruments are capturing the HRQL impact of asthma although not similarly, mainly due to differences between generic and asthma-specific approaches, and to a lesser extent due to differences between the psychometric and econometric development. In our study, these questionnaires were administered at different Table 5 Multitrait‑multimethod matrix between the EQ‑5D‑Y, the Pediatric Asthma Impact Scale and the Asthma Control Questionnaire Correlation coefficients are presented without a sign, since it only reflects that instruments’ scores are in the same or in the opposite direction a Correlation hypothesized asmoderate (0.31–0.60) b Correlation hypothesized as weak (≤ 0.30) c EQ-VAS: EuroQol-Visual Analogue Scale d ACQ: Asthma Control Questionnaire e PROMIS-PAIS: Patient-Reported Outcomes Measurement Information System-Pediatric Asthma Impact Scale EQ-5D-Y Utility index EQ-VASc Visual Analogue Scale EQ-5D-Y Dimension (Problems doing usual activities) ACQd Global Score ACQ Item (Limited in activities because of asthma) PROMIS‑PAIS Global Score 0.38a n = 74 (p = .001) CI [0.56 to 0.16] 0.16 n = 75 (p = .158) CI [0.38 to 0.06] 0.33 n = 75 (p = .003) CI [0.12 to 0.52] 0.37 n = 73 (p = .001) CI [0.15 to 0.55] 0.29 n = 73 (p = .014) CI [0.06 to 0.48] PROMIS‑PAISe Item (Hard to play sports or exercise because of asthma) 0.25 n = 74 (p = .033) CI [0.45 to 0.02] 0.16 n = 75 (p = .158) CI [0.38 to 0.06] 0.17b n = 75 (p = .151) CI [ 0.06 to 0.38] 0.31 n = 73 (p = .008) CI [0.08 to 0.50] 0.30 n = 73 (p = .011) CI [0.07 to 0.49] ACQ Global Score 0.28b n = 113 (p = .002) CI [0.44 to 0.10] 0.26 n = 116 (p = .004) CI [0.43 to 0.09] 0.30 n = 115 (p = .001) CI [0.12 to 0.46] 1 0.79 n = 116 (p = .000) CI [0.71 to 0.85] ACQ Item (Limited in activities because of asthma) 0.36 n = 113 (p = .000) CI [0.51 to 0.18] 0.26 n = 116 (p = .005) CI [0.42 to 0.08] 0.35a n = 115 (p = .000) CI [0.18 to 0.50] 0.79 n = 116 (p = .000) CI [0.71 to 0.85] 1 Page 16 of 16 Mayoraletal. 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