title: Reference interval computation: which method (not) to choose?
abstract: BACKGROUND
  When different methods are applied to reference interval (RI) calculation the results can sometimes be substantially different, especially for small reference groups. If there are no reliable RI data available, there is no way to confirm which method generates results closest to the true RI.
  
  
  METHODS
  We randomly drawn samples obtained from a public database for 33 markers. For each sample, RIs were calculated by bootstrapping, parametric, and Box-Cox transformed parametric methods. Results were compared to the values of the population RI.
  
  
  RESULTS
  For approximately half of the 33 markers, results of all 3 methods were within 3% of the true reference value. For other markers, parametric results were either unavailable or deviated considerably from the true values. The transformed parametric method was more accurate than bootstrapping for sample size of 60, very close to bootstrapping for sample size 120, but in some cases unavailable.
  
  
  CONCLUSIONS
  We recommend against using parametric calculations to determine RIs. The transformed parametric method utilizing Box-Cox transformation would be preferable way of RI calculation, if it satisfies normality test. If not, the bootstrapping is always available, and is almost as accurate and precise as the transformed parametric method.
authors.affiliation: ARUP Institute for Clinical and Experimental Pathology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah 84108, USA. igor.pavlov@aruplab.com
authors.forename: Igor Y
authors.initials: IY
authors.lastname: Pavlov
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Wilson
authors.forename: Julio C
authors.initials: JC
authors.lastname: Delgado
mesh_terms: D000328:Adult; D015415:Biomarkers; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D016208:Databases, Factual; D006801:Humans; D008875:Middle Aged; D011897:Random Allocation; D012016:Reference Values; D055815:Young Adult
chemical_list: D015415:Biomarkers