Implementation of the HOME core outcome set for clinical trials of atopic eczema-barriers and opportunities: the HOME IX meeting report.

The Harmonising Outcome Measures for Eczema (HOME) initiative established a core outcome set (COS) for atopic eczema (AE) clinical trials in 2019. This set encompasses four core outcome domains and corresponding measurement instruments: clinical signs (EASI), patient-reported symptoms (POEM and NRS 11 point for worst itch over the last 24 h), quality of life (DLQI/CDLQI/IDQoLI), and long-term control (Recap or ADCT). Following its roadmap, the HOME initiative is now focused on supporting implementation of the COS. To identify barriers and facilitators to implementation of the COS, and to guide the effort to promote COS uptake, a virtual consensus meeting was held over 2 days (September 25-26, 2021) attended by 55 participants (26 healthcare professionals, 16 methodologists, 5 patients, 4 industry representatives, and 4 students). Implementation themes were identified by a pre-meeting survey distributed to HOME members, presentations, and whole-group discussion. Participants were divided into five multi-professional small groups which ranked their top 3 most important themes, followed by whole-group discussion and anonymous consensus voting (consensus criteria: < 30% disagreement). Three most important implementation themes were identified and agreed upon: (1) awareness and stakeholder engagement, (2) universal applicability of the COS, and (3) ensuring minimum administrative burden. Working groups to address these issues are now a priority for the HOME initiative. The results from this meeting will inform the development of a HOME Implementation Roadmap in an effort to support other COS groups planning for effective implementation of their core sets.

Refinement and validation of the ItchyQoL using classical test theory and item response theory resulted in a reduction of the response categories from a 5-point to a 3-point scale.

BACKGROUND: The ItchyQoL is an itch-specific patient-reported outcome measure used to assess quality of life in patients with chronic pruritus (CP). OBJECTIVES: We aimed to assess and extend the psychometric properties of the ItchyQoL using classical test theory (CTT) and item response theory (IRT). METHODS: Item characteristic curves were analysed to investigate whether the response categories were functioning optimally. Confirmatory factor analyses were carried out on the ItchyQoL prior to and after rescoring of the response categories. We conducted a Rasch analysis for the ItchyQoL with revised response options and assessed the mean fit residuals in addition to the assumptions of unidimensionality and local independence. RESULTS: In total, 551 patients with CP from nine European countries completed the 22 items of the ItchyQoL. IRT analysis supported the revision of response options from five points to three. This revision was supported by excellent structural validity using CTT. The overall fit to the Rasch model was adequate. Unidimensionality was supported by the ItchyQoL overall scale and by the single subscales; however, local independence was violated in eight cases. CONCLUSIONS: We suggest a revision of the response categories of the ItchyQoL from a 5-point to a 3-point scale. When this revision was applied, the ItchyQoL showed excellent structural validity according to CTT and IRT/Rasch. The calculation of an overall ItchyQoL sum score is allowed.

Piloting an ICU follow-up clinic to improve health-related quality of life in ICU survivors after a prolonged intensive care stay (PINA): study protocol for a pilot randomised controlled trial.

BACKGROUND: Intensive care unit (ICU) survivors often suffer from cognitive, physical and mental impairments, known as post-intensive care syndrome (PICS). ICU follow-up clinics may improve aftercare of these patients. There is a lack of evidence whether or which concept of an ICU follow-up clinic is effective. Within the PINA study, a concept for an ICU follow-up clinic was developed and will be tested in a pilot randomised controlled trial (RCT), primarily to evaluate the feasibility and additionally the potential efficacy. METHODS/DESIGN: Design: Pilot RCT with intervention and control (usual care) arms plus mixed-methods process evaluation. PARTICIPANTS: 100 ICU patients (50 per arm) of three ICUs in a university hospital (Regensburg, Germany), ≥ 18 years with an ICU stay of > 5 days, a sequential organ failure assessment (SOFA) score > 5 during the ICU stay and a life expectancy of more than 6 months. INTERVENTION: The intervention will contain three components: information, consultation and networking. Information will be available in form of an intensive care guide for patients and next of kin at the ICU and phone support during follow-up. For consultation, patients will visit the ICU follow-up clinic at least once during the first 6 months after discharge from ICU. During these visits, patients will be screened for symptoms of PICS and, if required, referred to specialists for further treatment. The networking part (e.g. special referral letter from the ICU follow-up clinic) aims to provide a network of outpatient care providers for former ICU patients. Feasibility Outcomes: Qualitative and quantitative evaluation will be used to explore reasons for non-participation and the intervention´s acceptability to patients and caregivers. Efficacy Outcomes: Health-related quality of life (HRQOL) will be assessed as primary outcome by the physical component score (PCS) of the Short-Form 12 Questionnaire (SF-12). Secondary outcomes encompass further patient-reported outcomes. All outcomes are assessed at 6 months after discharge from ICU. DISCUSSION: The PINA study will determine feasibility and potential efficacy of a complex intervention in a pilot RCT to enhance follow-up care of ICU survivors. The pilot study is an important step for further studies in the field of ICU aftercare and especially for the implementation of a pragmatic multi-centre RCT. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04186468 . Submitted 2 December 2019.

Development of a validated short-form of the Childhood Atopic Dermatitis Impact Scale, the CADIS-SF15.

BACKGROUND: The Childhood Atopic Dermatitis Impact Scale (CADIS) with 45 items may be burdensome to complete. We therefore aimed to develop a CADIS short-form. METHODS: Parents of 300 children completed the prototype CADIS. Exploratory factor analysis was conducted on the 45-item CADIS version. The most representative items were chosen. Confirmatory factor analysis was used to confirm the a priori factor structure. Content validity was assessed in a focus group of patients, parents, clinicians, methodologists and industry delegates. Internal consistency, 48-h test-retest reliability, construct validity and responsiveness of the newly developed short-form were assessed. RESULTS: A total of 270 families provided data at baseline, 34 after 48 h and 228 after 4 weeks. Fourteen items of three different factors fulfilled the proposed eligibility criteria and were included in the draft short-form. After the content validity rating, one item relating to the child's sleep was added to further improve content validity. The confirmatory factor analyses showed good model fit, and a 15-item short-form was initiated, the CADIS-SF15. The total scale and the three domains showed good internal consistency and test-retest reliability. The correlation between SCORAD and other subjective measures was consistent with our hypotheses. Differences in scores between mild, moderate and severe AD patients were significant, and the CADIS-SF15 was able to detect changes in 'improving' patients over time. CONCLUSION: The CADIS-SF15 with 15 items in three domains is an internally consistent, reliable, valid, responsive and brief measure of QoL in children affected with AD and their parents. Further evaluation of clinical applicability is required.

Evaluation of responsiveness and estimation of smallest detectable change and minimal important change scores for the Childhood Atopic Dermatitis Impact Scale.

BACKGROUND: The Childhood Atopic Dermatitis Impact Scale (CADIS) is an instrument to measure quality of life in young children affected by atopic dermatitis, and their parents. OBJECTIVES: To evaluate the responsiveness (sensitivity to change), smallest detectable change (SDC) and minimal important change (MIC) of the CADIS. METHODS: Parents and primary caregivers of 300 young children completed the CADIS and a global rating of their child's skin condition at baseline and a 4-week follow-up. Kruskal-Wallis tests, Wilcoxon tests and effect sizes were used to assess responsiveness. The SDC can be seen as a change beyond measurement error. Anchor-based and distribution-based methods, and an integration of both methods were used to estimate the MIC. RESULTS: In total, 270 families provided data at baseline and 228 at follow-up. The CADIS total change score and most of the domain scores had moderate-to-strong correlations with the skin change score. Patients were grouped according to the skin change score, which served as an anchor. Children whose parents noted an improvement of the skin showed lower CADIS scores at follow-up (P < 0·001). For the SDC we obtained score changes of 1·34 points on the total score and < 1·0 points on each domain score. All detected MIC values passed the SDC cut-off. CONCLUSIONS: The CADIS is sensitive to change towards improvement of quality of life. A change > 12% on the total score or each domain score very likely represents a clinically important change. What's already known about this topic? Atopic dermatitis reduces the quality of life of affected children and their parents. The Childhood Atopic Dermatitis Impact Scale (CADIS) has been evaluated and translated into two further languages. What does this study add? Further validation of the responsiveness of the CADIS, and whether it is sensitive to change in patients whose condition had changed. Calculation of the smallest detectable change. What are the clinical implications of this work? Estimation of the minimal important change in CADIS provides benchmarks for clinical practice.

TREatment of ATopic eczema (TREAT) Registry Taskforce: protocol for a European safety study of dupilumab and other systemic therapies in patients with atopic eczema.

BACKGROUND: A long-term prospective observational safety study is essential to characterize fully the safety profile of systemic immunomodulating therapies for patients with atopic eczema. The TREatment of ATopic eczema (TREAT) Registry Taskforce offers a large platform to conduct such research using national registries that collect the same data using a predefined core dataset. OBJECTIVES: To present a protocol for a safety study comparing dupilumab with other systemic immunomodulating therapies in children and adults with moderate-to-severe atopic eczema, to assess the long-term safety risk of these therapies in a routine clinical care setting. METHODS: We describe a registry-embedded international observational prospective cohort study. Adult and paediatric patients who start treatment with dupilumab or another systemic immunomodulating agent for their atopic eczema will be included. The primary end point is the incidence of malignancies (excluding nonmelanoma skin cancer) compared between the treatment groups. Secondary end points include other serious adverse events and adverse events of special interest, such as eye disorders and eosinophilia. CONCLUSIONS: This protocol delineates a safety study for dupilumab in adult and paediatric patients with atopic eczema, using a standardized methodological approach across several national registries. The protocol could also be used for other novel systemic immunomodulating therapies, and could provide licensing and reimbursement authorities, pharmaceutical companies and clinicians with safety evidence from a routine clinical care setting. What's already known about this topic? There is a need for long-term data on the safety of systemic immunomodulating therapies in patients with atopic eczema. Regulatory bodies, such as the European Medicines Agency, increasingly stipulate the collection of such data as part of the licensing agreement for new treatments, to assess the new agent's long-term safety profile against established therapies. Large numbers of patients with a long duration of follow-up are necessary in order to detect rare events like malignancies. What does this study add? The TREAT Registry Taskforce offers a platform to conduct such research with a network of multiple national atopic eczema research registries. We present a protocol for an investigator-initiated multicentre safety study comparing dupilumab with other systemic immunomodulating therapies in adults and subsequently adolescents and children with moderate-to-severe atopic eczema. This protocol can be used as a framework for similar studies for other novel systemic immunomodulating therapies across both adult and paediatric populations.

The Patient-Oriented Eczema Measure: estimating the minimal important change in an outpatient clinic cohort.

BACKGROUND: Patient-Oriented Eczema Measure (POEM) measures patient-reported symptoms in atopic dermatitis (AD). It is the recommended core outcome instrument to capture the symptoms domain in AD clinical trials. Understanding the minimal important change (MIC) in the POEM score is therefore important in both trial and clinical care settings. Previous studies have mainly evaluated MIC estimates among children in trial settings. The MIC estimate for POEM in a clinical setting is often lacking. OBJECTIVES: We aim to estimate the MIC of the POEM using both distribution-based and anchor-based methods in a clinical cohort of adult eczema patients. METHODS: Both distribution-based and anchor-based methods were used to calculate the MIC of the POEM in a clinical cohort of Asian adult patients attending the eczema clinic at a tertiary dermatology centre in Singapore. Scoring AD (SCORAD) was used as the disease severity anchor for the anchor-based methods. The smallest detectable change (SDC) for POEM was also calculated as the threshold for any measurement error. RESULTS: There were a total of 85 adult AD patients in the cohort that contributed a total of 114 paired measurements of both POEM and SCORAD. The SDC in our study was 1.68. The MIC estimates were 3.64 and 1.46 based on 0.5 standard deviation (SD) and 0.2 SD distribution-based methods. Anchor-based methods such as the receiver operating curve and predictive modelling methods yielded MIC values of 0.50 and 1.05, respectively. CONCLUSIONS: Minimal important change for POEM varied according to the methods and approaches used. Only a change of two points or more in POEM could be considered beyond any measurement errors and clinically important. This finding is consistent even in a clinical setting of Asian adults with eczema.

Suicidality and risk of suicidality in psoriasis: a critical appraisal of two systematic reviews and meta-analyses.

AIM: Chi et al.1 and Singh et al.2 each conducted a systematic review and meta-analysis of observational studies examining the relationship between suicidality and psoriasis. SETTING AND DESIGN: Chi et al. included only cohort studies while Singh et al. included cohort, cross-sectional and case-control studies. PRIMARY EXPOSURE AND OUTCOME: The primary outcome, suicidality, was assessed in people with psoriasis (exposure) and people without psoriasis. Analyses were separated for suicidal ideation and behaviour. RESULTS: Chi et al. included five population-based cohort studies that were considered to be of high quality according to the Newcastle-Ottawa Scale (NOS). They found no significant increase in the risk of suicide [risk ratio (RR) 1·13, 95% confidence interval (CI) 0·87-1·46], suicide attempt (RR 1·25, 95% CI 0·89-1·75) or suicidality (RR 1·26, 95% CI 0·97-1·64) among people with psoriasis. Singh et al. included 18 studies that were rated to be of medium quality to high quality according to the NOS. They found a pooled odds ratio (OR) of 2·05 (95% CI 1·54-2·74) for suicidal ideation among patients with psoriasis. For suicidal behaviours (combined attempted and completed suicides) a pooled OR of 1·26 (95% CI 1·13-1·40) was obtained, suggesting a higher risk of these behaviours in people with psoriasis. Subgroup analysis showed that patients with psoriasis were more likely to attempt suicide (OR 1·32, 95% CI 1·14-1·54) and complete suicide (OR 1·20, 95% CI 1·04-1·39) than those without psoriasis. CONCLUSIONS: Singh et al. concluded that patients with psoriasis have a significantly higher risk of suicidal ideation, suicide attempts and completed suicides, while Chi et al. concluded that the available, limited, very low-quality evidence does not support the notion of an association between psoriasis on the one hand, and suicide, suicidal ideation and suicide attempts on the other.

TREatment of ATopic eczema (TREAT) Registry Taskforce: consensus on how and when to measure the core dataset for atopic eczema treatment research registries.

BACKGROUND: Comparative, real-life and long-term evidence on the effectiveness and safety of phototherapy and systemic therapy in moderate-to-severe atopic eczema (AE) is limited. Such data must come from well-designed prospective patient registries. Standardization of data collection is needed for direct comparisons and data pooling. OBJECTIVES: To reach a consensus on how and when to measure the previously defined domain items of the TREatment of ATopic eczema (TREAT) Registry Taskforce core dataset for research registries for paediatric and adult patients with AE. METHODS: Proposals for the measurement instruments were based on recommendations of the Harmonising Outcome Measures for Eczema (HOME) initiative, the existing AE database of TREATgermany, systematic reviews of the literature and expert opinions. The proposals were discussed at three face-to-face consensus meetings, one teleconference and via e-mail. The frequency of follow-up visits was determined by an expert survey. RESULTS: A total of 16 experts from seven countries participated in the 'how to measure' consensus process and 12 external experts were consulted. A consensus was reached for all domain items on how they should be measured by assigning measurement instruments. A minimum follow-up frequency of initially 4 weeks after commencing treatment, then every 3 months while on treatment and every 6 months while off treatment was defined. CONCLUSIONS: This core dataset for national AE research registries will aid in the comparability and pooling of data across centres and country borders, and enables international collaboration to assess the long-term effectiveness and safety of phototherapy and systemic therapy used in patients with AE. What's already known about this topic? Comparable, real-life and long-term data on the effectiveness and safety of phototherapy and systemic therapy in patients with atopic eczema (AE) are needed. There is a high diversity of outcomes and instruments used in AE research, which require harmonization to enhance comparability and allow data pooling. What does this study add? Our taskforce has reached international consensus on how and when to measure core domain items for national AE research registries. This core dataset is now available for use by researchers worldwide and will aid in the collection of unified data. What are the clinical implications of this work? The data collected through this core dataset will help to gain better insights into the long-term effectiveness and safety of phototherapy and systemic therapy in AE and will provide important information for clinical practice. Standardization of such data collection at the national level will also allow direct data comparisons and pooling across country borders (e.g. in the analysis of treatment-related adverse events that require large patient numbers).

TREatment of ATopic eczema (TREAT) Registry Taskforce: an international Delphi exercise to identify a core set of domains and domain items for national atopic eczema photo- and systemic therapy registries.

BACKGROUND: Evidence of immunomodulatory therapies to guide clinical management of atopic eczema (AE) is scarce, despite frequent and often off-label use. Patient registries provide valuable evidence for the effects of treatments under real-world conditions that can inform treatment guidelines, give the opportunity for health economic evaluation and the evaluation of quality of care, as well as pharmacogenetic and dynamic research, which cannot be adequately addressed in clinical trials. OBJECTIVES: The TREatment of ATopic eczema (TREAT) Registry Taskforce aims to seek international consensus on a core set of domains and items ('what to measure') for AE research registries, using a Delphi approach. METHODS: Participants from six stakeholder groups were included: doctors, nurses, nonclinical researchers, patients, industry and regulatory body representatives. The eDelphi comprised three sequential online rounds, requesting participants to rate the importance of each proposed domain item. Participants could add domain items to the proposed list in round 1. A final consensus meeting was held to ratify the core set. RESULTS: Participants (n = 479) from 36 countries accessed the eDelphi platform, of whom 86%, 79% and 74% completed rounds 1, 2 and 3, respectively. At the face-to-face consensus meeting attended by 42 participants the final core set was established containing 19 domains with 69 domain items (49 baseline and 20 follow-up items). CONCLUSIONS: This core set of domains and items to be captured by national AE systemic therapy registries will standardize data collection and thereby allow direct comparability across registries and facilitate data pooling between countries. Ultimately, it will provide greater insight into the effectiveness, safety and cost-effectiveness of photo- and systemic immunomodulatory therapies.

Overview of systematic reviews in allergy epidemiology.

BACKGROUND: There is a substantial body of evidence on the epidemiology of allergic conditions, which has advanced the understanding of these conditions. We aimed to systematically identify systematic reviews and meta-analyses on the epidemiology of allergic diseases to assess what has been studied comprehensively and what areas might benefit from further research. METHODS: We searched PubMed and EMBASE up to 12/2014 for systematic reviews on epidemiological research on allergic diseases. We indexed diseases and topics covered and extracted data on the search characteristics of each systematic review. RESULTS: The search resulted in 3991 entries after removing duplicates, plus 20 other items found via references and conference abstracts; 421 systematic reviews were relevant and included in this overview. The majority contained some evidence on asthma (72.9%). Allergic rhinitis, atopic eczema and food hypersensitivity were covered in 15.7%, 24.5% and 9.0%, respectively. Commonly studied risk factors for atopic eczema included dietary and microbial factors, while for asthma, pollution and genetic factors were often investigated in systematic reviews. There was some indication of differing search characteristics across topics. CONCLUSION: We present a comprehensive overview with an indexed database of published systematic reviews in allergy epidemiology. We believe that this clarifies where most research interest has focussed and which areas could benefit from further research. We propose that this effort is updated every few years to include the most recently published evidence and to extend the search to an even broader list of hypersensitivity/allergic disorders.

Evaluation of the measurement properties of symptom measurement instruments for atopic eczema: a systematic review.

BACKGROUND: Symptoms have been identified as a core outcome domain for atopic eczema (AE) trials. Various instruments exist to measure symptoms in AE, but they vary in quality and there is a lack of standardization between clinical trials. Our objective was to systematically evaluate the quality of the evidence on the measurement properties of AE symptom instruments, thereby informing consensus discussions within the Harmonising Outcome Measures for Eczema (HOME) initiative regarding the most appropriate instruments for the core outcome domain symptoms. METHODS: Using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist and predefined criteria for good measurement properties on identified development and validation studies of AE symptom instruments, a best evidence synthesis was performed to draw an overall conclusion on quality of the instruments and to provide recommendations. RESULTS: Eighteen instruments were identified and evaluated. When the quality and results of the studies were considered, only five of these instruments had sufficient validation data to consider them for the core outcome set for the core outcome domain symptoms. These were the paediatric Itch Severity Scale (ISS), Patient-Oriented Eczema Measure (POEM), Patient-Oriented SCOring Atopic Dermatitis (PO-SCORAD), Self-Administered Eczema Area and Severity Index (SA-EASI) and adapted SA-EASI. CONCLUSIONS: ISS (paediatric version), POEM, PO-SCORAD, SA-EASI and adapted SA-EASI are currently the most appropriate instruments and therefore have the potential to be recommended as core symptom instrument in future clinical trials. These findings will be utilized for the development of a core outcome set for AE.

Patient-Oriented Eczema Measure (POEM), a core instrument to measure symptoms in clinical trials: a Harmonising Outcome Measures for Eczema (HOME) statement.

BACKGROUND: The Harmonising Outcome Measures for Eczema (HOME) initiative has defined four core outcome domains for a core outcome set (COS) to be measured in all atopic eczema (AE) trials to ensure cross-trial comparison: clinical signs, symptoms, quality of life and long-term control. OBJECTIVES: The aim of this paper is to report on the consensus process that was used to select the core instrument to consistently assess symptoms in all future AE trials. METHODS: Following the HOME roadmap, two systematic reviews were performed which identified three instruments that had sufficient evidence of validity, reliability and feasibility to be considered for the final COS. RESULTS: At the fourth international HOME meeting, there was broad consensus among all stakeholders that the Patient-Oriented Eczema Measure (POEM) should be used as the core instrument (87·5% agreed, 9·4% unsure, 3·1% disagreed). CONCLUSIONS: All relevant stakeholders are encouraged to use POEM as the chosen instrument to measure the core domain of symptoms in all future AE clinical trials. Other instruments of interest can be used in addition to POEM.

Report from the fourth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative).

This article is a report of the fourth meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in Malmö, Sweden on 23-24 April 2015 (HOME IV). The aim of the meeting was to achieve consensus over the preferred outcome instruments for measuring patient-reported symptoms and quality of life for the HOME core outcome set for atopic eczema (AE). Following presentations, which included data from systematic reviews, consensus discussions were held in a mixture of whole group and small group discussions. Small groups were allocated a priori to ensure representation of different stakeholders and countries. Decisions were voted on using electronic keypads. For the patient-reported symptoms, the group agreed by vote that itch, sleep loss, dryness, redness/inflamed skin and irritated skin were all considered essential aspects of AE symptoms. Many instruments for capturing patient-reported symptoms were discussed [including the Patient-Oriented SCOring Atopic Dermatitis index, Patient-Oriented Eczema Measure (POEM), Self-Administered Eczema Area and Severity Index, Itch Severity Scale, Atopic Dermatitis Quickscore and the Nottingham Eczema Severity Score] and, by consensus, POEM was selected as the preferred instrument to measure patient-reported symptoms. Further work is needed to determine the reliability and measurement error of POEM. Further work is also required to establish the importance of pain/soreness and the importance of collecting information regarding the intensity of symptoms in addition to their frequency. Much of the discussion on quality of life concerned the Dermatology Life Quality Index and Quality of Life Index for Atopic Dermatitis; however, consensus on a preferred instrument for measuring this domain could not be reached. In summary, POEM is recommended as the HOME core outcome instrument for measuring AE symptoms.