title: Use of Salivary Diurnal Cortisol as an Outcome Measure in Randomised Controlled Trials: a Systematic Review.
abstract: BACKGROUND
  Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with diverse adverse health outcomes, making it an important therapeutic target. Measurement of the diurnal rhythm of cortisol secretion provides a window into this system. At present, no guidelines exist for the optimal use of this biomarker within randomised controlled trials (RCTs).
  
  
  OBJECTIVE
  The aim of this study is to describe the ways in which salivary diurnal cortisol has been measured within RCTs of health or behavioural interventions in adults.
  
  
  METHODS
  Six electronic databases (up to May 21, 2015) were systematically searched for RCTs which used salivary diurnal cortisol as an outcome measure to evaluate health or behavioural interventions in adults. A narrative synthesis was undertaken of the findings in relation to salivary cortisol methodology and outcomes.
  
  
  RESULTS
  From 78 studies that fulfilled the inclusion criteria, 30 included healthy participants (38.5 %), 27 included patients with physical disease (34.6 %) and 21 included patients with psychiatric disease (26.9 %). Psychological therapies were most commonly evaluated (n = 33, 42.3 %). There was substantial heterogeneity across studies in relation to saliva collection protocols and reported cortisol parameters. Only 39 studies (50 %) calculated a rhythm parameter such as the diurnal slope or the cortisol awakening response (CAR). Patterns of change in cortisol parameters were inconsistent both within and across studies and there was low agreement with clinical findings.
  
  
  CONCLUSIONS
  Salivary diurnal cortisol is measured inconsistently across RCTs, which is limiting the interpretation of findings within and across studies. This indicates a need for more validation work, along with consensus guidelines.
authors.affiliation: Palliative Care Department, Cambridge University Hospitals NHS Foundation Trust, Elsworth House, Box 63, Hill's Road, Cambridge, CB2 0QQ, UK. richella.ryan@nhs.net.|Department of Oncology, University of Cambridge, Hutchison/MRC Research Centre, Cambridge Biomedical Campus, Box 197, Cambridge, CB2 0XZ, UK. richella.ryan@nhs.net.
authors.forename: Richella
authors.initials: R
authors.lastname: Ryan
authors.affiliation: Palliative Care Department, Cambridge University Hospitals NHS Foundation Trust, Elsworth House, Box 63, Hill's Road, Cambridge, CB2 0QQ, UK.|Department of Oncology, University of Cambridge, Hutchison/MRC Research Centre, Cambridge Biomedical Campus, Box 197, Cambridge, CB2 0XZ, UK.
authors.forename: Sara
authors.initials: S
authors.lastname: Booth
authors.affiliation: Palliative Care Department, Cambridge University Hospitals NHS Foundation Trust, Elsworth House, Box 63, Hill's Road, Cambridge, CB2 0QQ, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Spathis
authors.affiliation: St. Nicholas Hospice Care, Hardwick Lane, Bury St. Edmunds, Suffolk, IP33 2QY, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Mollart
authors.affiliation: Department of Psychology, University of Westminster, 101 New Cavendish Street, London, W1W 6XH, UK.
authors.forename: Angela
authors.initials: A
authors.lastname: Clow
mesh_terms: D002940:Circadian Rhythm / Q000502:physiology*; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D017063:Outcome Assessment, Health Care; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D012463:Saliva / Q000737:chemistry*
chemical_list: D006854:Hydrocortisone
keywords: Diurnal rhythm; Intervention; Randomized controlled trial; Salivary cortisol; Systematic review