Jauregui et al. Health and Quality of Life Outcomes (2019) 17:23 https://doi.org/10.1186/s12955-019-1087-z RESEARCH Open Access Psychometric properties of the Spanish version of the once-daily Urticaria Activity Score (UAS) in patients with chronic spontaneous urticaria managed in clinical practice (the EVALUAS study) Ignacio Jauregui1, Ana Gimenez-Arnau2, Joan Bartra3,4, Moises Labrador-Horrillo5, Javier Ortiz de Frutos6, Juan Francisco Silvestre7, Joaquin Sastre8, Manuel Velasco9, Marta Ferrer10, Cristina Ballesteros11 and Antonio Valero3,4,12* Abstract Background: The daily diary Urticaria Activity Score (UAS) and its weekly score (UAS7) are widely used to assess signs and symptoms in patients with chronic spontaneous urticaria (CSU). The objective of this study was to assess the psychometric properties of a Spanish version of the once-daily UAS. Methods: Observational study in patients ≥18 years old receiving usual care for CSU (daily or almost daily occurrence of generalized hives or angioedema for ≥6 weeks). Patients were included consecutively and completed the UAS, EQ- 5D, and the Chronic Urticaria Quality of Life scale (CU-Q2oL) at two study visits 6 weeks apart. On each occasion, the UAS was completed once-daily for 7 consecutive days to be able to calculate the UAS7 score. Psychometric properties of reliability, construct validity, and responsiveness were assessed. The Minimal Important Difference (MID) was estimated for the UAS7 using anchor- and distribution-based approaches. Results: Data from 166 patients was available for analysis (mean age 49 years, 65.7% female). Floor (5.4% of patients with the lowest possible score) and ceiling (1.2%) effects were low; 15% of patients had missing values. Internal consistency and test-retest reliability were good (Cronbach’s alpha of 0.83 and an ICC of 0.84, respectively). Convergent validity was demonstrated through the pattern of correlations with the EQ-5D and CU-Q2oL and known groups’ validity was demonstrated by the instrument’s ability to discriminate between patients with different overall levels of urticaria severity, with between-group effect-sizes (ES) ranging from 0.36 to 1.19. The UAS7 proved responsive to change with effect sizes ranging from 0.3 to 1.52 in patients reporting improvement or deterioration in overall urticaria status. The MID for the UAS7 score was estimated at 7–8 points, on a scale of 0–42. Conclusions: The Spanish version of the UAS score has demonstrated a robust psychometric performance in patients with CSU managed in conditions of usual care. It can therefore be considered a suitable instrument to assess disease activity in clinical practice in Spanish-speaking patients. The Spanish version’s reliability and validity are similar to those reported for other language versions of the once- and twice-daily variants of the UAS. Keywords: Chronic urticaria, Questionnaire, Psychometric, Reliability, Validity, Spanish * Correspondence: Valero@clinic.ub.es 3 Allergy Unit, Pneumology Department, Hospital Clinic, University of Barcelona, Barcelona, Spain 4 Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain Full list of author information is available at the end of the article © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Jauregui et al. Health and Quality of Life Outcomes (2019) 17:23 Page 2 of 9 Background properties of linguistically adapted versions of a question- Chronic urticaria (CU) is a mast-cell-driven disease naire to guarantee that the new version shows adequate characterized by the development of hives, angioedema, reliability, validity and responsiveness. The objective of or both. The chronic form of the disease is differentiated this study was therefore to evaluate the psychometric from the more acute form by duration, with CU typically properties of a Spanish version of the once-daily UAS and characterized by the development of repeated episodes the corresponding UAS7 in patients with CSU managed of hives for more than six weeks [1]. Chronic urticaria according to usual clinical practice and to provide an can be classified as spontaneous (or idiopathic) or as in- estimate of a MID for that version. We hypothesised that ducible and several sub-types of urticaria exist and may the Spanish version of the UAS and UAS7 would show in- co-present. Prevalence of CU in the Spanish population ternal consistency and test-retest reliability coefficients has been calculated at approximately 0.6% with a signifi- over 0.70 wich is a good indicator of reliability, good con- cantly higher prevalence in women than in men [2]. vergent validity with other disease-specific and generic Approximately 9% of cases were found to last from one measures of HRQOL, ability to discriminate between to 5 years and 11.3%, for more than 5 years [2]. groups defined by patient self-ratings of overall urticaria Several studies have shown that urticaria can have a severity and clinician ratings of the disease, and that it significant negative impact on patients’ health-related would be responsive to self- and clinician-perceived quality of life (HRQOL), with patients reporting prob- change in disease activity. lems attributable to their skin condition in many areas of everyday life, including personal care, recreation and Methods social interaction, mobility, sleep, and work [3–5]. In Study design and patient population comparison with reference groups from the general This was an observational, prospective, multicentre population, patients with CU scored worse on all do- study conducted in the dermatology and allergy depart- mains of the SF-36 instrument as well as having poorer ments of several Spanish hospitals under conditions of scores on several domains than patients with respiratory usual clinical practice. Data collection was performed allergy. Their scores on a life satisfaction scale were also between October 2013 and May 2014. Patients were in- affected [6]. cluded consecutively in the study if they were ≥ 18 years The Urticaria Activity Score (UAS) is a commonly used of age with a diagnosis of CSU, defined as the daily or patient reported outcome (PRO) measure that assesses almost daily occurrence of generalized hives or angio- the symptoms (itch) and signs (hives) of CSU. The UAS7 edema for at least 6 weeks prior to inclusion. Patients score is calculated as the sum over 7 days of the daily in- were excluded from the study if they had acute urticaria, tensity of itch (itch severity score) and number of hives urticaria vasculitis or other forms of urticaria not associ- score (range: 0–42), with higher scores denoting greater ated with the chronic form of the disease, any form of disease activity [7, 8]. The UAS7 has been recommended inducible CU that was not associated with CSU, angio- by the guidelines for use in clinical practice to determine edema without the presence of hives, pruritus related to disease activity and response to treatment [7]. Currently, dermatitis or other skin disease, any systemic disease or the UAS7 score can be computed using the twice-daily or other conditions which might hinder data collection or the once-daily UAS questionnaires. The once-daily UAS interpretation. All patients included in the study gave was validated in German patients in an observational their written informed consent to participate. Patients study [9] while the twice-daily UAS patient assessment were followed up for a period of 6 weeks from inclusion has been accepted by the United States’ Federal Drug in the study and were managed according to the criteria Administration (FDA) as a PRO supporting a label claim of the attending physician following their usual practice. for drugs in CSU and validated as per FDA guidelines for PRO instruments using data from several clinical trials Patient-reported outcomes measures (PROM) [10, 11]. As part of the validation study of the twice daily The once-daily UAS measures urticaria activity in terms of version of the UAS, the Minimal Important Difference itch severity and number of hives over the past 24 h. Re- (MID) was calculated in patients with chronic spontan- sponse options for itch severity are 0 = None, 1 = Mild eous urticaria (CSU) treated with omalizumab or placebo (present but not annoying or troublesome), 2 = Moderate in a randomized, double-blind, placebo-controlled trial (troublesome but does not interfere with normal daily activ- [11] and confirmed in a later study [12]. ity or sleep), 3 = Intense (severe itching, which is sufficiently To date, the UAS once-daily version and corresponding troublesome to interfere with normal daily activity or sleep). UAS7 has not been adapted and validated for use specifi- Response options for hives are 0 = None, 1 = Mild (< 20 cally in a Spanish-speaking population and no MID has hives/24 h), 2 = Moderate (20–50 hives/24 h), 3 = Intense been estimated for that version in conditions of usual cli- (> 50 hives/24 h or large confluent areas of hives). Scores nical practice. It is important to test the psychometric on these two items are summed to create a total daily UAS Jauregui et al. Health and Quality of Life Outcomes (2019) 17:23 Page 3 of 9 score (range: 0–6 points). A Spanish version of the instru- visit, a categorical scale (Global Index of Change, or ment was produced for use in the present study following GIC) was completed by physicians and patients to obtain standard procedures of translation and cultural adaptation their opinion of the evolution of the CSU over the study of patient reported outcome (PRO) measures [13]. The period. The GIC consisted of 13 response options ran- version is shown in Appendix. ging from ‘Very much worse’ to ‘Very much improved’. Patients completed the UAS over 7 days following the Patient opinions on the ease of completion and rele- first visit and in the week prior to the second visit. vance of the scale for assessing their urticaria were also Patients were asked to complete the questionnaire just evaluated using a 5-point Likert scale. before going to bed in the evening. Summing daily Additional study variables collected included age, sex, non-missing values UAS scores over the seven-day weight and height, ethnicity, educational level, presence period provides the UAS7 score, with a score range from of chronic spontaneous urticaria (CSU), presence of 0 (no activity) to 42 (most intense activity). other types of urticaria associated with CSU, years since Other PROs included in the study were the Chronic Urti- onset of symptoms, years from diagnosis, number of caria Quality of Life scale (CU-Q2oL) and EQ-5D-3 L. The episodes in the previous year, presence of angiodema, CU-Q2oL is a disease-specific HRQOL questionnaire for number of exacerbations in the previous year, whether use in patients with chronic urticaria [14]. It consists of 23 receiving treatment or not, presence of co-morbidities items assessing HRQOL in 6 dimensions: itching (2 associated with CSU, history of other atopic diseases, ex- questions), swelling (2 questions), impact on daily activities acerbation of CSU through NSAIDs, thyroid pathology, (6 questions), sleep problems (5 questions), limitations (3 and associated autoimmune conditions. questions) and aesthetic problems (5 questions). Questions are answered on a 5-point Likert scale and scores are trans- Sample size formed to a 0 to 100 scale, with higher scores indicating Sample size was calculated to be able to detect a change poorer quality of life. The questionnaire generates both an equivalent to 0.5 standard deviations in the overall score overall score and scores by dimension and has been vali- of UAS7 (score range 0–42) between the two study visits dated in Spanish [15]. with the aim of being able to test the instrument’s re- The EQ-5D-3 L is a widely used generic question- sponsiveness. It was estimated that a minimum of 128 naire designed to assess health status in a wide range patients would be required for validation of the Spanish of conditions in adult populations [16]. It consists of version of UAS7. A further 20% was added to take ac- 5 dimensions (mobility, personal care, daily activities, count of possible loss to follow-up and non-usable data pain/discomfort, and anxiety/depression) with three to give a total sample of approximately 150 patients. possible levels of response in each dimension (absence of problems, moderate problems, extreme problems) Statistical analysis to assess self-perceived health status on the day of Descriptive analysis of all variables was performed using completion. Utility indices based on the preferences absolute numbers and frequencies in the case of catego- of the general population for each of the 243 states rical variables and means or medians together with defined by the descriptive system provide a summary standard deviations or interquartile ranges in the case of score of self-rated health on the 5 dimensions and continuous quantitative variables. The chi-square test are available for various countries. They provide was used to study the relationship between qualitative values on a scale anchored at 0 (death) to 1 (full health) variables. Parametric (Student t test or ANOVA) or and the Spanish value set was used to calculate the utility non-parametric (U-Mann Whitney or Kruskal Wallis) score in the present study [17]. Patients also assess their tests were used to study the relationship between con- overall health on a vertical visual analogue scale (EQ-VAS) tinuous variables, depending on whether distribution from 0 to 100 where 0 represents the worst imaginable was normal or non-normal. A statistical significance health state and 100 represents the best imaginable health level of p < 0.05 was used in all analysis. Statistical ana- state. The validated Spanish version of EQ-5D was used in lyses were carried out on the study population with valid the present study [18]. data, without any type of imputation of missing data. The Physician’s In-Clinic UAS, which provides a rating The feasibility and psychometric properties (reliability, of the patient’s itching and hives (measured on a 0–6 validity, and responsiveness) of the UAS were analysed scale), was also completed by the attending clinician, using a variety of approaches. with input from the patient, at both study visits. Further- Feasibility was assessed by analysing the proportion of more, a 5 item Likert scale with responses of ‘Very mild’, missing or unusable responses per item at each visit as ‘Mild’, ‘Moderate’, ‘Severe’, and ‘Very severe’ was used to well as the proportion of patients with at least one miss- obtain the clinician and patient’s opinion on the overall ing or unusable response. We also calculated floor and severity of their CSU in both study visits. In the final ceiling effects, i.e. patients scoring the minimum (0) and Jauregui et al. Health and Quality of Life Outcomes (2019) 17:23 Page 4 of 9 maximum scores for the UAS and UAS7 (6 and 42, re- moderate (ES of 0.50) or large (0.80 or more) [22]. In spectively) scores at each visit. Floor and ceiling effects addition, scores were calculated for the UAS7 according under 15% are usually considered acceptable [19]. to the clinician rating on the In-Clinic UAS at the first The reliability of the questionnaire was assessed by es- visit using the categorization proposed by Mathias et al. timating internal consistency (i.e., the degree of homo- of < 4, 4, 5, 6 points [11]. geneity of the 2 items forming the scale) and by Responsiveness was investigated by analysing the magni- assessing test-retest reliability (i.e., the degree of stability tude of the change in the UAS7 score corresponding to of the score when there are no changes in health status) different levels of patient- and clinician-reported improve- [20]. The internal consistency of the scale was evaluated ment on the global urticaria rating scale. The global index by calculating the Cronbach’s alpha for the overall in- of change was also used for this analysis. strument score. Test-retest reliability was assessed by Finally, the MID for the UAS7 score was estimated in calculating the intraclass correlation coefficient (ICC) several ways, using both anchor- and distribution-based for patients who, in the second study visit, declared that approaches [23]. For the anchor-based approach, clin- their urticaria symptoms had not changed from baseline ician and patient ratings of the overall severity of CSU using the global change item. For both Cronbach’s alpha were used as the reference and a linear regression model and the ICC, a value of 0.7 or more was considered to was constructed to estimate the score change on the indicate an acceptable level of reliability [21]. UAS and UAS7 corresponding to a one category shift on Construct validity, i.e. the degree to which the instru- the scale between the two visits. Patient ratings on the ment performs as expected in meeting a series of GIC were also used as an anchor in an alternative pre-defined hypotheses, was assessed by evaluating its model. Distribution-based MIDs were estimated based convergent and discriminant validity, as well as its on the standard error of measurement (SEM) and stan- known groups’ validity. dardised effect size (SES) using values of 1 SEM and 0.5 Convergent and discriminant validity refer to whether SES, as recommended [23]. the instruments shows expected patterns of correlations with instruments measuring similar (convergent) and Results dissimilar (discriminant) constructs. They were assessed Data from a total of 166 patients meeting inclusion here by analysing the correlations of UAS7 scores with criteria were available for analysis. All patients were re- scores on the EQ-5D-3 L and CU-Q2oL at baseline. We cruited consecutively as specified in the study protocol. also analysed the correlations between individual items Table 1 shows the demographic and clinical character- (itch and number of hives) on the UAS and dimension istics of the study population at baseline: 65.7% were fe- scores on the CU-Q2oL. A series of hypotheses were de- male and mean (SD) age was 48.8 (14.3) yearsPatients veloped regarding the expected pattern of correlations had a median of > 2 years with symptoms of CSU and between the different instruments. The UAS7 score was 96% was being treated for CSU at the time of the visit. expected to show lower correlations (r between 0.2 and 0.5) with the EQ-5D-3 L Index and VAS than with the Score distributions, feasibility, and reliability CU-Q2oL global score, as the latter is a Table 2 shows the data relating to the instrument’s feasi- condition-specific measure. Higher correlations were ex- bility and reliability, as well as the mean scores and score pected between the UAS7 score and the EQ-5D-3 L di- distributions at baseline. Mean (SD) for the UAS7 at mensions of usual activities, pain/discomfort, and baseline was 16.4 (10.5) and there were 15% of patients anxiety/depression than with the dimensions of mobility with missing values. Ninety-one percent of patients and self-care, as the former were considered more likely found the UAS-7 ‘easy’ or ‘very easy’ to complete while to be affected by CSU. On the CU-Q2oL, we expected 71% considered it ‘appropriate’ or ‘very appropriate’ to moderate to high correlations (r = 0.5–0.8) between the measure their health status in relation to their urticaria. UAS7 score and all dimensions of the CU-Q2oL, but we Floor and ceiling effects were 5.4 and 1.2%, respectively. expected particularly high correlations between the itch Cronbach’s alpha for the UAS7 score was 0.83 and the items on the two questionnaires. intra-class correlation coefficient in the test-retest Known groups’ validity was assessed by determining sample was 0.84. the extent to which the instrument discriminated between patients according to their self-rating on the Convergent and discriminant validity global CSU severity scale. The comparison was per- The pattern of correlations between the UAS and EQ-5D formed using ANOVA and between group effect sizes, and CU-Q2oL at baseline was generally as expected which were calculated as the difference between group (Table 3). Convergence with the generic instrument was means divided by the pooled standard deviation. Effect somewhat weaker than with the disease-specific measure. sizes were classified as small (ES of approximately 0.20), Almost all of the correlations with the CU-Q2oL were Jauregui et al. Health and Quality of Life Outcomes (2019) 17:23 Page 5 of 9 Table 1 Study population baseline demographic and clinical Table 3 Convergent validity of the UAS7 score. Pearson characteristics correlation coefficients with EQ-5D and CU-Q2oL summary Baseline scores and dimensions at baseline (statistically significant (n = 166) correlations at p < 0.05 in bold) Sex, female, n (%) 109 (65.7%) UAS7 Age (years), mean (SD) 48.8 (14.3) Hives Itch Overall Body mass index, mean (SD) 26.6 (4.6) EQ-5D-3L Education, n (%): Mobility -0.030 0.037 0.005 No formal education 5 (3.2%) Self-care 0.066 0.025 0.055 Primary 56 (35.4%) Usual activities 0.147 0.287 0.243 Secondary 59 (37.3%) Pain/discomfort 0.143 0.251 0.218 Higher 38 (24.1%) Anxiety/depression 0.076 0.238 0.162 Urticaria associated with CSU 65 (39.6%) EQ VAS -0.111 –0.299 –0.222 Symptomatic Dermographism 49 (75.4%) EQ Índex -0.148 –0.301 –0.247 Delayed pressure 19 (29.2%) CU-Q2oL Heat 7 (10.8%) Itch 0.606 0.574 0.628 Cholinergic urticaria 10 (15.4%) Swelling 0.289 0.360 0.334 Years since first appearance of symptoms, mean (SD) 2.2 (0.1-51.3) Impact on life activities 0.366 0.474 0.450 Years since diagnosis of urticaria, mean (SD) 1.1 (0-24.2) Sleep Problems 0.286 0.422 0.383 Nº of episodes in the prior year, median (range) 2 (0-36) Limits 0.260 0.395 0.343 Angioedema during any episode, n (%) 77 (47.0%) Looks 0.168 0.341 0.265 Receiving treatment for CSU, n (%) 153 (96.2%) Overall score 0.379 0.510 0.471 Patients with comorbidities associated with CSU, n (%) 85 (51.5%) SD standard deviation, CSU chronic spontaneous urticari statistically significant both between summary scores and at the level of individual dimensions, and correlation coef- ficients tended to be higher than those with the EQ-5D. Table 2 Score distributions, feasibility, and reliability of the The strongest correlations between the CU-Q2oL and the UAS7 score UAS were seen between the UAS itching item and the Hives Itching UAS7 CU-Q2oL itching item (as expected) and summary score Baseline scores and distributions (0.574 and 0.628, respectively). On EQ-5D, as expected, the highest correlations were with the dimensions of pain Mean (SD) 7.2 9.3 16.4 (5.8) (5.6) (10.5) / discomfort, usual activities, and anxiety / depression, but Median (range) 7 8 15 only the UAS itch item and overall score showed statisti- (0-21) (0-21) (0-42) cally significant correlations with the EQ-5D. Missing values; floor and ceiling effects, n (%) Known groups’ validity Missing 21 21 25 (12.7%) (12.7%) (15.1%) Known groups’ validity was demonstrated through the Minimum score (floor) 22 9 9 instrument’s capacity to discriminate between groups (13.3%) (5.4%) (5.4%) classified according to patient- and clinician-perceived Maximum score (ceiling) 4 6 2 overall urticaria severity. UAS7 scores increased with in- (2.4%) (3.6%) (1.2%) creasing severity of urticaria and with a statistically sig- Reliability nificant linear trend (p < 0.0001 for between-group Internal consistency assessed 0.83 differences in both cases) and moderate to large using Cronbach’s alpha (95% CI)a (0.721 – 0.895) between-group effect sizes (Table 4). A similar trend was Test-retest reliability, asessed 0.84 seen when patients were categorised according to the using ICC (95% CI) (0.735 – 0.906) clinician rating on the UAS at the first visit as < 4, 4, 5, SD standard deviation, Min minimum, Max maximum, ICC Intraclass correlation 6, with corresponding mean (SD) UAS7 scores of 13.3 coefficient. 95% CI 95% confidence interval. Missing values defined as number (9.3) for < 4 vs 21.6 (9.6), 19.2 (8.8), and 22.5 (14.6) for and proportion of patients with at least one missing response. aTest-retest reliability analysis performed in patients reporting no or minimal change in the 4, 5, and 6 categories, respectively; p = 0.0047 for lin- urticaria status at visit 2 ear trend (data not shown). Jauregui et al. Health and Quality of Life Outcomes (2019) 17:23 Page 6 of 9 Table 4 Known groups’ validity for the UAS7 score: mean one category (e.g. from ‘moderate’ to ‘mild’) on the rat- scores for different patient-rated categories of overall CSU ing scale (mean [SD] change of 1.7 [7.0] points). severity and corresponding between-group effect sizes Hives Itch Global Between group Minimal important difference effect size Distribution-based approaches to estimating a MID for the Very mild (n = 20) 2.10 (2.90) 4.26 (4.42) 6.47 (6.69) UAS7 score suggested a range for the MID between 4.4 Mild (n = 32) 4.81 (5.45) 7.48 (4.43) 12.40 (8.43) 0.76 (based on the SEM) and 5.3 (based on half of one SES). A Moderate (n = 58) 7.74 (4.37) 9.93 (5.0) 17.62 (8.30) 0.63 more conservative estimate using the anchor-based ap- proach indicates that the MID might be approximately 7–8 Severe/intense 9.61 (5.83) 11.52 (5.88) 21.04 (11.36) 0.36 (n = 28) points based on the change in UAS7 score corresponding to a two category shift on the Global Impression of Severity Very severe /intense 17.71 (3.35) 16.63 (5.32) 33.86 (7.84) 1.19 (n = 7) scale, as shown in Table 5, and as derived from linear re- p < 0.0001 for between group differences gression modelling, which indicated that a two category shift on the GIS would correspond to a change of 6.4 points on the UAS7. Using the same criteria, on the Itching and Responsiveness Hives sub-scales, the MID could be considered to be in the The results of analysing responsiveness are shown in range of 3.5–4 points. Table 5 and are based on changes in patient ratings of their overall urticaria severity between the two study visits. Effect sizes were generally larger the greater the Discussion magnitude of change. For example, a three-level change The UAS is widely used to assess CSU activity. To date, in the global rating scale corresponded to an effect size however, there is no published information relating to of 1.28 on the UAS7, which would represent a large ef- the psychometric performance of a Spanish version of fect size. This compares to an effect size of approxi- the once-daily version of the instrument. This study mately 0.2 (a small effect size) on UAS7 for those remedies that and has shown that the Spanish version of indicating no change or a one-level change in their con- the UAS has very good reliability, construct validity, and dition overall. There was essentially no difference in the responsiveness. Given the international nature of many size of the change on the UAS7 score between patients clinical trials and epidemiological studies today, it is of reporting identical levels of overall severity at the two considerable importance to test and demonstrate the visits (mean [SD] change of 1.9 [8.9] points) and those psychometric properties of other language versions of who reported an improvement equivalent to a change of PROs such as the UAS and to compare results with those for other language versions. The fact that the UAS is a relatively simple instrument Table 5 Responsiveness of the UAS7 score: mean score may facilitate its adaptation and use in other languages changes and effect sizes based on change in patient ratings of as well as tending to produce relatively robust psy- overall urticaria severity chometric characteristics. In the present study, 91% of Difference between visits Hives Itch Global patients found the instrument ‘easy’ or ‘very easy’ to in patient rating of overall urticaria severity complete, attesting to the simple nature of the question- – 3 category change (n = 4) –7.6 (5.6) –7.2 (6.3) –15.0 (11.8) naire. On the other hand, while 71% considered it “ap- propriate” or “very appropriate” to measure their health ES: 1.39 ES: 1.14 ES: 1.28 status and disease activity in relation to their urticaria, – 2 category change (n = 16)a –3.7 (5.3) –4.3 (6.3) –8.3 (11.2) 30% rated the questionnaire as being of only ‘intermedi- ES: 0.69 ES: 0.68 ES: 0.74 ate’ relevance or less. This suggests that patients might – 1 category change (n = 47) –1.1 (4.2) –0.7 (5.2) –1.9 (8.9) prefer other aspects of their condition to be included. ES: 0.26 ES: 0.13 ES: 0.21 In terms of reliability, the Spanish version of the No change (n = 59) –0.7 (3.9) –0.9 (4.0) –1.7 (7.0) once-daily UAS shows good levels of internal consistency and test-retest reliability which exceeded the ES: 0.18 ES: 0.23 ES: 0.25 value of 0.70 which is typically considered an acceptable + 1 category change (n = 13) 2.3 (2.6) -0.5 (4.6) 2.3 (4.6) threshold [21]. Earlier testing of the once-daily version ES: 0.90 ES: 0.12 ES: 0.51 did not include evaluation of its reliability [9] and reli- + 2 category change (n = 2) –1.5 (4.9) 1.5 (3.5) –3.0 (8.5) ability testing of the twice-daily version showed similar ES: 0.30 ES:0.42 ES: 0.35 results to those reported here for internal consistency a For example, a two category change would mean moving from ‘moderate’ to but somewhat poorer results for test-reliability, with an ‘very mild’, or ‘Very severe’ to ‘Moderate’ ICC for the global UAS7 score of 0.66 [11]. Jauregui et al. Health and Quality of Life Outcomes (2019) 17:23 Page 7 of 9 The Spanish version of the UAS also demonstrated ac- Other limitations of the present study include the fact ceptable convergent validity, as our a priori hypotheses that responsiveness was not assessed using a before and regarding the pattern of correlations between them and after, interventional design. Nevertheless, based on pa- the EQ-5D and CU-Q2oL were generally satisfied. As tients’ global ratings of the severity of their condition predicted, correlations were higher between the UAS and of change in their condition, we found evidence that and the disease-specific CU-Q2oL than with the generic the instrument is able to detect changes in patients’ HRQOL measure EQ-5D. The UAS itch severity urticaria status. Another limitation is that no external or sub-scale was found to be more often statistically signifi- objective measure of disease severity was available to cantly correlated with EQ-5D dimensions and summary provide a reference for testing of known groups’ validity, scores than the scale measuring number of hives, sug- which meant we had to rely on patient and investigator gesting that itch is likely to have a greater impact on ratings of overall disease severity using a single item overall quality of life, as assessed by EQ-5D. The UAS categorical scale. itch severity item also showed the highest correlation with the EQ-5D pain/discomfort dimension, as would be expected. The moderate correlations observed here be- Conclusion tween the UAS7 and the CU-Q2oL also confirm Koti et The Spanish version of the UAS score has demonstrated al’s contention that disease activity only moderately cor- a robust psychometric performance in patients with relates with QOL impairment in patients with CSU [24]. CSU managed in conditions of usual care. It can there- Interestingly, the Looks dimension of the CU-Q2oL fore be considered a suitable instrument to assess dis- showed the weakest correlation with disease activity ease activity in Spanish-speaking patients in clinical though this may be connected to the location of the practice. The Spanish version’s reliability and validity are hives, which is something we did not investigate in the similar to those reported for other language versions of present study. the once-daily and twice-daily variants of the UAS. This study also provides evidence of the Spanish ver- sion’s responsiveness, with effect sizes for UAS7 scores Appendix increasing as patients indicated larger degrees of change Spanish version of the Urticaria Activity Score (UAS) in overall urticaria severity. The effect sizes observed in Instrucciones this study were somewhat smaller than those reported  Conteste a cada pregunta lo mejor que pueda. by Mathias et al. [11] for the twice-daily version of the  No hay respuestas correctas ni incorrectas. UAS using data from a clinical trial. They reported SES  En cada pregunta, escoja la respuesta que mejor se ranging from 0.78 to 1.12 in the placebo arm and from ajuste a su experiencia. 1.28 to 2.88 in the treatment arms. This compares with,  Al responder a las preguntas, piense en las últimas for example, an effect size of 0.74 in our study for pa- 24 horas. Marque solo una respuesta. tients reporting a two-level improvement in their global rating of disease severity. Given that our study included a range of patients many of whom were already on treat- ment when they entered the study, it is perhaps to be 1. ¿Cuántos habones ha tenido en las últimas 24 expected that effect sizes would be smaller. horas? Our suggested MID of 7–8 points for the UAS7 score is slightly lower than the estimates of 9.5 to 10.5 0 No he tenido ningún habón o roncha provided by Mathias et al. based on data from several 1 He tenido menos de 20 habones o ronchas clinical trials [11, 12]. This may be due to differences in study design and to the anchors used to estimate 2 He tenido entre 20 y 50 habones o ronchas MIDs. For example, Mathias et al. used changes on 3 He tenido más de 50 habones o bien extensas zonas con habones confluentes o que se juntan entre ellos the P-UAS, Dermatology Quality of Life Index and EQ-5D as anchors, whereas we focused on overall changes in urticaria severity as perceived by patients. Habones o ronchas son manchas rojas que pican, que They also used data from clinical trials while our data se hinchan y que desaparecen rápidamente (en horas) en was collected from patients treated in usual clinical una zona del cuerpo para aparecer en otra zona del practice. Our sample size was smaller and the number cuerpo en los sucesivos minutos u horas. Cuente cada of patients in the responsiveness analysis showing a habón por separado aunque tenga varios agrupados. two-category change was low (n = 16). Additional work on a MID for the UAS7 in clinical practice would 2. Valore entre 0 y 3 la intensidad del picor o prurito therefore be advisable. que ha tenido durante las últimas 24 horas Jauregui et al. Health and Quality of Life Outcomes (2019) 17:23 Page 8 of 9 0 No he tenido picor o prurito Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in 1 Leve (presente pero que no molesta) published maps and institutional affiliations. 2 Moderado (molesta pero no interfiere con la actividad diaria y con el sueño) Author details 1 Allergy Department, Hospital Universitario Basurto, Bilbao, Spain. 3 Intenso (picor o prurito grave que es capaz de interferir con la 2 Dermatology Department, Hospital del Mar, Parc de Salut Mar, Universitat actividad diaria y con el sueño) Autonoma Barcelona, Barcelona, Spain. 3Allergy Unit, Pneumology Department, Hospital Clinic, University of Barcelona, Barcelona, Spain. 4 Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. 5Allergy Section, Department of Internal Medicine, Hospital Acknowledgements Vall d’Hebron, Universitat Autonoma de Barcelona, Barcelona, Spain. 6 We thank Michael Herdman, of Insight Consulting & Research (funded by Dermatology Department, Hospital Universitario 12 de Octubre, Madrid, Novartis Pharmaceuticals, Spain), for providing medical editorial assistance Spain. 7Dermatology Department, Hospital General Universitario de Alicante, with this manuscript. The authors would also like to acknowledge the Alicante, Spain. 8Allergy Department, Fundacion Jimenez Diaz, Madrid, Spain. 9 contribution of Marco Pavesi (European Foundation for the Study of Chronic Dermatology Department, Hospital Arnau de Vilanova, Valencia, Spain. 10 Liver Failure), who performed the statistical analysis for the study, as well as Department of Allergy and Clinical Immunology, Clınica Universidad de the patients and health care staff who contributed their time and energy Navarra, Pamplona, Spain. 11Novartis Farmacéutica, Barcelona, S.A, Spain. 12 and without whom the study would not have been possible. Servicio de Alergia, Hospital Clínic de Barcelona, Carrer de Villarroel 170, 08036 Barcelona, Spain. Funding Funding for the EVALUAS Study was provided by Novartis Pharmaceuticals, Received: 16 February 2018 Accepted: 9 January 2019 Spain. Availability of data and materials References The dataset generated and/or analysed during the current study is the 1. 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Allergy. payment from Novartis, Spain for his work on this study. Dr. Bartra has served 2008;63:777–80. as consultant to Novartis, Faes Farma, and Hal Allergy, and has received lec- 10. Mathias SD, Dreskin SC, Kaplan A, Saini SS, Spector S, Rosén KE. ture fees from Novartis, Stallergenes, UCB, Thermofisher, Menarini, and Chiesi. Development of a daily diary for patients with chronic idiopathic urticaria. Dr. Labrador-Hornillo has acted as a paid consultant for Novartis and Shire, Ann Allergy Asthma Immunol. 2010;105:142–8. has received speaking honorarium from Novartis and Shire and received 11. Mathias SD, Crosby RD, Zazzali JL, Maurer M, Saini SS. Evaluating the grant support from Thermofisher. Dr. Ortiz de Frutos has acted as a paid con- minimally important difference of the urticaria activity score and other sultant for Novartis and has received research grants from Astellas and Leo measures of disease activity in patients with chronic idiopathic urticaria. Pharmaceuticals. 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