title: Validation of treatment escalation as a definition of atopic eczema flares.
abstract: BACKGROUND
  Atopic eczema (AE) is a chronic disease with flares and remissions. Long-term control of AE flares has been identified as a core outcome domain for AE trials. However, it is unclear how flares should be defined and measured.
  
  
  OBJECTIVE
  To validate two concepts of AE flares based on daily reports of topical medication use: (i) escalation of treatment and (ii) days of topical anti-inflammatory medication use (topical corticosteroids and/or calcineurin inhibitors).
  
  
  METHODS
  Data from two published AE studies (studies A (n=336) and B (n=60)) were analysed separately. Validity and feasibility of flare definitions were assessed using daily global bother (scale 0 to 10) as the reference standard. Intra-class correlations were reported for continuous variables, and odds ratios and area under the receiver operator characteristic (ROC) curve for binary outcome measures.
  
  
  RESULTS
  Good agreement was found between both AE flare definitions and change in global bother: area under the ROC curve for treatment escalation of 0.70 and 0.73 in studies A and B respectively, and area under the ROC curve of 0.69 for topical anti-inflammatory medication use (Study A only). Significant positive relationships were found between validated severity scales (POEM, SASSAD, TIS) and the duration of AE flares occurring in the previous week - POEM and SASSAD rose by half a point for each unit increase in number of days in flare. Smaller increases were observed on the TIS scale. Completeness of daily diaries was 95% for Study A and 60% for Study B over 16 weeks).
  
  
  CONCLUSIONS
  Both definitions were good proxy indicators of AE flares. We found no evidence that 'escalation of treatment' was a better measure of AE flares than 'use of topical anti-inflammatory medications'. Capturing disease flares in AE trials through daily recording of medication use is feasible and appears to be a good indicator of long-term control.
  
  
  BACKGROUND
  Current Controlled Trials ISRCTN71423189 (Study A).
authors.affiliation: Centre of Evidence Based Dermatology, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Kim S
authors.initials: KS
authors.lastname: Thomas
authors.affiliation: Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
authors.forename: Beth
authors.initials: B
authors.lastname: Stuart
authors.affiliation: MRC Clinical Trials Unit, London, United Kingdom.
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: O'Leary
authors.affiliation: Centre of Evidence Based Dermatology, University of Nottingham, Nottingham, United Kingdom; Centre for Evidence-based Healthcare, Medical Faculty Carl Gustav Carus, TU Dresden, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Schmitt
authors.affiliation: INSERM 1056, Dermatology, Paul Sabatier University, Toulouse, France.
authors.forename: Carle
authors.initials: C
authors.lastname: Paul
authors.affiliation: Centre of Evidence Based Dermatology, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Hywel C
authors.initials: HC
authors.lastname: Williams
authors.affiliation: Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Sinead
authors.initials: S
authors.lastname: Langan
mesh_terms: D000279:Administration, Cutaneous; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D065095:Calcineurin Inhibitors / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003876:Dermatitis, Atopic / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D003879:Dermatologic Agents / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008499:Medical Records; D012372:ROC Curve; D012720:Severity of Illness Index; D000067251:Symptom Flare Up; D009626:Terminology as Topic; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D065095:Calcineurin Inhibitors; D003879:Dermatologic Agents