title: Biomarkers predicting treatment outcome in depression: what is clinically significant?
abstract: OBJECTIVE
  To extend to biomarker studies the consensus clinical significance criterion of a three-point difference in Hamilton Rating Scale for Depression.
  
  
  METHODS
  We simulated datasets modeled on large clinical trials.
  
  
  RESULTS
  In a typical clinical trial comparing active treatment and placebo, a difference of three Hamilton Rating Scale for Depression (HRSD) points at the end of treatment corresponds to 6.3% of variance in outcome explained. To achieve a similar explanatory power, genotypes with minor allele frequencies of 5, 10, 20, 30 and 50% need to attain a per allele difference of 4.7, 3.6, 2.8, 2.4 and 2.2 HRSD points, respectively. A normally distributed continuous biomarker will need an effect size of 1.5 HRSD points per standard deviation. A number needed to assess of three suggests that with this effect size, a biomarker will significantly improve the prediction of outcome in one out of every three patients assessed.
  
  
  CONCLUSIONS
  This report provides guidance on assessing clinical significance of biomarkers predictive of outcome in depression treatment.
authors.affiliation: Institute of Psychiatry, King's College London, 16 De Crespigny Park, SE5 8AF, London, UK. rudolf.uher@kcl.ac.uk
authors.forename: Rudolf
authors.initials: R
authors.lastname: Uher
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Tansey
authors.forename: Karim
authors.initials: K
authors.lastname: Malki
authors.forename: Roy H
authors.initials: RH
authors.lastname: Perlis
mesh_terms: D000928:Antidepressive Agents / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological; D002986:Clinical Trials as Topic; D003198:Computer Simulation; D003362:Cost-Benefit Analysis; D003863:Depression / Q000188:drug therapy*; D005838:Genotype; D006801:Humans; D012015:Reference Standards; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D054316:Biomarkers, Pharmacological