title: Towards the Grade of Recommendations, Assessment, Development and Evaluation system: methods and results of budesonide/formoterol maintenance and reliever therapy research.
abstract: OBJECTIVE
  Guidelines for clinical practice are expected to gather evidence-based recommendations to support optimal medical behaviours. The aim of the current review is to explore how currently available research regarding the strategy of using budesonide/formoterol (BUD/FORM) as maintenance and reliever therapy (Symbicort SMART) covers the items considered by the Grade of Recommendations, Assessment, Development and Evaluation (GRADE) system, through a comparative analysis of methodological approaches, clinical outcomes, patient-reported outcomes and costs, in order to highlight uncovered areas.
  
  
  RESULTS
  Thirteen trials providing data on 21 095 analysed patients were available. No serious limits in methodological study features were found. Evaluation of the clinical outcome was consistent with the efficacy of BUD/FORM maintenance and reliever therapy. As the time to first exacerbation was the primary outcome in most of the studies, conclusive indications cannot be drawn regarding other clinical outcomes or patient-reported outcomes, which were investigated as secondary outcomes. A comprehensive systematic review exploring all critical and important outcomes is desirable, but further research concerning the safety issues of Long Acting β2 Agonists (LABA) and patients' reported outcomes about the SMART in respect to alternative strategies is likely to affect a clear recommendation in the near future.
  
  
  CONCLUSIONS
  The efficacy of BUD/FORM maintenance and reliever therapy in extending the time to first exacerbation appears consistent between studies. Further studies exploring all patients' important outcomes are needed. Clinical and economic assessments are worthy of being investigated to verify the directness of the evidence in respect to real life patients and different geographical realities.
authors.affiliation: Allergy and Respiratory Diseases, Department of Internal Medicine, University of Genova, Genova, Italy. fulvio.braido@unige.it
authors.forename: Fulvio
authors.initials: F
authors.lastname: Braido
authors.forename: Ilaria
authors.initials: I
authors.lastname: Baiardini
authors.forename: Enrico
authors.initials: E
authors.lastname: Compalati
authors.forename: Alberto
authors.initials: A
authors.lastname: Bordo
authors.forename: Giorgio W
authors.initials: GW
authors.lastname: Canonica
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use*; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D015982:Bias; D019819:Budesonide / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D000069502:Budesonide, Formoterol Fumarate Drug Combination; D002648:Child; D003365:Costs and Cost Analysis; D003625:Data Collection; D018450:Disease Progression; D004311:Double-Blind Method; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D005060:Europe; D019317:Evidence-Based Medicine / Q000379:methods / Q000592:standards*; D000068298:Fluticasone; D000068759:Formoterol Fumarate; D006801:Humans; D015337:Multicenter Studies as Topic / Q000379:methods / Q000592:standards* / Q000706:statistics & numerical data; D017060:Patient Satisfaction; D017410:Practice Guidelines as Topic; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic / Q000379:methods / Q000592:standards* / Q000706:statistics & numerical data; D012107:Research Design / Q000592:standards*; D013147:Spirometry; D013997:Time Factors; D016896:Treatment Outcome; D014944:World Health Organization
chemical_list: D000305:Adrenal Cortex Hormones; D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D000069502:Budesonide, Formoterol Fumarate Drug Combination; D004338:Drug Combinations; D004983:Ethanolamines; D019819:Budesonide; D000068298:Fluticasone; D000068759:Formoterol Fumarate