Validation of the HAPPI Kids Continuous Age-Specific Pediatric Reference Intervals

Introduction: To facilitate best possible patient care, reference intervals (RIs) adopted by a laboratory must be appropriate for the population demographics and, where applicable, the analytical principle and/or the analytical instrument used. While guidelines from the Clinical and Laboratory Standard Institute (CLSI) recommend a validation process for discrete RIs, there are no current recommendations for the validation process for continuous RIs. This study aimed to validate recently published, HAPPI Kids continuous RIs, in a routine laboratory. Methods: Initially, the difference in test results between the primary study laboratory that contributed to previous RIs development and a routine laboratory was assessed using specimens from 77 children tested in both laboratories using the Siemens ADVIA 1800 or Centaur/XP/XPT. Later, validation of the HAPPI Kids RIs was undertaken using 279 pediatric samples tested on the same analyzer type in the routine laboratory. The previously published RIs were validated if more than 90% of results in the routine laboratory were within the RIs. Results: There was minimal evidence of clinically significant differences in test results between the primary and routine laboratories. The continuous RIs were validated after initial analysis for 16 of the 18 biochemistry analytes tested, and after secondary analysis for the remaining 2 analytes. Conclusion: This study validates the HAPPI Kids RIs in a routine laboratory, satisfying the laboratory accreditation requirements for evaluation, implementation, and sourcing of RIs. In addition, this study presents a modification of the current CLSI method for validation of continuous RIs that will benefit routine laboratories in general.