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

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.


Funding sources
Funding for the consensus meeting was received from the Swedish Asthma and Allergy Association, LEO Foundation and the Region of Sk ane (county), Sweden.

Conflicts of interest
H.C.W. was involved with the development and validation of POEM. C.J.A., E.S., P.I.S., K.S.T., J.S. and H.C.W. are members of the executive committee of the HOME initiative. L.A.A.G., J.R.C., C.A.C.P. and L.B.v.K. are members of the HOME initiative. J.A.S. is a member of the executive of OMERACT, an organization that develops outcome measures in rheumatology and receives arms-length funding from 36 companies. The

Summary
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 (87Á5% agreed, 9Á4% unsure, 3Á1% 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.

What's already known about this topic?
• There is insufficient high-quality evidence for many of the treatments of atopic eczema (AE), which is partly due to the heterogeneity in outcomes used in clinical trials.
• The Harmonising Outcome Measures for Eczema initiative defined 'symptoms' as one of the core outcome domains that should be measured in AE clinical trials.
What does this study add?
• Consensus was reached on the Patient-Oriented Eczema Measure (POEM) as the core instrument to measure symptoms. There is insufficient high-quality evidence for many of the treatments of atopic eczema (AE) (synonym atopic dermatitis), which is partly due to the high clinical and methodological heterogeneity in AE studies. 1 Results cannot be compared and pooled properly in systematic reviews due to heterogeneity in outcomes used, hampering evidence-based clinical decision-making. The international Harmonising Outcome Measures for Eczema (HOME) initiative, founded in 2010, standardizes outcome measurement in AE clinical trials by developing a core outcome set (COS) for AE clinical trials. [2][3][4][5] A COS is defined as an agreed standardized set of outcomes that should be measured and reported, as a minimum, in all clinical trials of a specific disease or trial population. 6 The use of a COS does not preclude the use of additional outcome measurement instruments (further referred to as 'instruments') of interest for a particular trial nor does a COS specify which instrument should be used as a primary outcome.
To guide the development of a COS, HOME has developed a roadmap, 7 which includes the Outcome Measures in Rheumatology (OMERACT) filter of 'truth, discrimination and feasibility' in order to recommend core instruments 8 and the methodology of the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist (cosmin.nl). It was agreed within HOME that there should be an instrument per domain, rather than a composite instrument covering more than one domain.
Previously, HOME defined physician-assessed clinical signs, patient-reported symptoms, health-related quality of life and long-term control as core outcome domains for AE clinical trials (HOME II meeting Amsterdam 2011). 4 During the HOME III meeting (San Diego, 2013), consensus was reached that the Eczema Area and Severity Index (EASI) should be used as the core instrument to measure clinical signs. 5,9,10 The objective of this current consensus study (HOME IV, Malm€ o, April 2015) was to establish an agreement statement on the core instrument to measure the domain of patientreported symptoms in AE clinical trials.
Harmonising Outcome Measures for Eczema (HOME) roadmap steps and results of the HOME IV meeting To identify and recommend an adequate instrument to measure symptoms of AE in clinical trials, a predefined process was followed as detailed in the HOME roadmap ( Fig. 1). This figure summarizes the process adopted to develop consensus in a graphical way. 7 To adequately assess symptoms of AE, the following definition of AE symptoms was employed: 11 'a departure from normal function, appearance or feeling which is noticed by a patient, indicating the presence of disease or abnormality'. A symptom is subjective and can be measured only by patients themselves.

Stage 1: Identify instruments used to measure symptoms in atopic eczema treatment trials
A systematic review of all AE trials published since 2000 showed that most (78%, 295/378) randomized controlled trials (RCTs) of AE treatments reported symptoms of AE with itch and sleep loss the most frequently measured. 12 However, symptoms were assessed by only 37% of RCTs by a standalone symptom measurement (visual analogue scale or numeric rating scale). Sixty-three per cent reported symptoms as part of a composite measure [such as the SCORing Atopic Dermatitis (SCORAD) index, a composite instrument of clinician-rated signs and patient-reported symptoms] rather than a stand-alone outcome. A total of 30 composite instruments that included symptoms were identified, of which SCORAD was the most commonly used. Only 23% of RCTs reported the SCORAD symptom score separately.

Stage 2: Establish the extent and quality of testing of the identified instruments
A subsequent systematic review of published validation studies of instruments to measure symptoms of AE was performed according to COSMIN methodology. 13 This review provided evidence of how well the instruments performed for measuring the symptoms of AE and the methodological quality of the validation studies. The methods and detailed results of this systematic review are published separately. 14,15 Preliminary results included 26 eligible papers evaluating 15 different instruments for assessing symptoms of AE with varying degrees of validation (Table 1).
Only three instruments had the potential to be recommended for the COS based on validation studies: the Itch Severity Scale (ISS), Patient-Oriented Eczema Measure (POEM) and Self-Administered EASI (SA-EASI). The most extensively validated instrument was POEM, with adequate internal Step 3: Develop core set of outcome measurement instruments Identification and recommendation of adequate measurement instrument(s) for each core outcome domain by a five-stage process Step 1: Define scope and applicability Population (condition) Setting (e.g. trial, registry, clinical practice) Geographical /regional scope a Stakeholders Step  15 All conflicts of interest were disclosed to the meeting prior to discussions and voting.
In line with previous HOME consensus meetings, 4,5 consensus was achieved if less than 30% of the voters disagreed. This means that consensus was reached when ≥ 70% voted 'agree' or 'unsure'. Full details of the meeting and attendees can be found in the published meeting report. 15 The consensus process began by agreeing which patientreported symptoms were considered essential. The long-list of symptoms and discussions that led to this consensus were based on previously published studies, 14,20 the results of a large international survey of patients 21 and input from patients' discussions at the pre-meeting patient session and the main meeting. It was agreed that itch, sleep loss, dryness, red skin and irritation should be ideally included in the core instrument ( Table 2).
The results of the systematic reviews (Stages 1 and 2) were then considered alongside this agreed short-list of essential symptoms to determine which instruments were of sufficient quality and relevance to be considered further (Table 1). Despite performing well in validation studies, the Itch Severity Scale (ISS) was excluded because it measures only itch and itch-related aspects and therefore does not reflect the multiplicity of symptoms associated with AE. The Nottingham Eczema Severity Score (NESS) was also excluded as it is primarily an epidemiological tool. Atopic Dermatitis Quickscore (ADQ), web-based Characteristics of Itch Questionnaire (CoIQ), Method 4 and Skin Detective Questionnaire (SDQ) lack sufficient validation studies to enable any meaningful assessment to be made. 14,22 Instruments that demonstrated  low quality in at least one criterion in validation studies were not considered further.
POEM, Patient-Oriented SCORAD (PO-SCORAD) and Selfadministered EASI (SA-EASI) were considered in detail for their suitability. The PO-SCORAD was included in these further discussions and voting despite a lack of validation studies because it was felt important by some participants. After lengthy small and large group discussions, a vote was held to establish whether any of the instruments that had been considered in detail could be recommended as the core outcome instrument.
After lengthy discussions and consideration of the evidence presented, consensus was achieved (87Á5% agreed, 9Á4% unsure) in the voting that POEM is the most appropriate instrument to measure symptoms and was therefore recommended for inclusion in the COS to measure AE symptoms in clinical trials.
The PO-SCORAD and SA-EASI were not favoured, largely because it was argued that these instruments ask patients to perform an assessment of clinical signs ratings rather than being a true measurement of patient-reported symptoms. POEM (http://nottingham.ac.uk/research/groups/cebd/ resources/poem.aspx) is free to use and typically takes less than 2 min to complete. It asks about the frequency of seven symptoms (itch, sleep disturbance, dryness, flaking, weeping or oozing, bleeding and cracking) in the past 7 days. However, the agreed essential symptom of redness is not included in POEM. In the development of this instrument, redness was deliberately excluded because of the difficulties in detecting it in people with darker skin types. 16 Additionally, POEM captures only the frequency of symptoms but does not measure the intensity; the relative importance of intensity of symptoms requires further investigation.
POEM generally meets the OMERACT filter of truth, discrimination and feasibility, but some validation gaps remain including structural validity and cross-cultural validity, which is particularly important for global use of the instrument. These validation gaps will be addressed as per the HOME roadmap (Stage 4). If POEM does not perform well in these additional validation studies, its inclusion in the core set will be reassessed. All COSs should evolve over time in response to new data. These validation studies are now ongoing and the results will be discussed at a future HOME consensus meeting.

Consensus recommendation
POEM is recommended as the core outcome instrument to measure symptoms of AE in all future clinical trials. We encourage all stakeholders, including clinicians, researchers, pharmaceutical industries, regulatory agencies, journal editors and insurance companies to acknowledge this recommendation and include POEM in all future trials in AE.

Strengths and limitations
The inclusion of core outcome instruments in all future trials will reduce selective outcome reporting bias and facilitate comparison and pooling of study data allowing clinicians and patients to make better evidence-based decisions in clinical practice.
The HOME consensus process is an evidence-based approach with participants from several continents providing an international perspective at the meeting and in the wider HOME initiative. The inclusion of different stakeholder groups, all of whom participate on a voluntary basis, ensures that recommendations are widely applicable and support widespread dissemination and implementation. The systematic reviews investigating which instruments were used and the quality of these instruments provided a good evidence base and allowed the discussions to focus on the instruments with good measurement properties.
The inclusion of patients is a key element of the HOME consensus process. Patients' views are actively sought and have equal weight. The international survey by von Kobyletzki et al. provided the opinion of a large number of patients with different skin types and ethnicities from several continents regarding what symptoms are important. 21 Also, POEM was explicitly developed with patients using focus groups. 16 Taken together with discussions from the pre-meeting patient session and active participation of patients during the main meeting, we hope the results of this consensus process are a good reflection of what is important to patients with regard to the symptoms of AE.
Although the interdisciplinary, multi-stakeholder HOME group agreed a list of essential symptoms, it was clear that there is no available instrument that measures all of these. The most relevant stakeholderssuch as patient representatives, clinicians, and researchers and industry representatives planning, performing and interpreting AE trialsagreed to use POEM as the core instrument to assess AE symptoms. However, there were no representatives from regulatory agencies or government funders of research at the HOME IV meeting, so greater efforts to engage with these stakeholder groups is required to ensure awareness and support for this core outcome instrument recommendation.