Differential Distributions: A refined methodology to indirect reference interval estimation by including Patient's health status according to associated ICD-10 codes.

Background: Traditional methods for estimating reference intervals (RIs) using patient's blood test results from the clinical routine, typically remove outliers without considering the nuanced health statuses of patients. This removes a vast majority of test results for reference interval estimation without considering the actual health status of the patient. Methods: We introduce the Differential Distribution Method (DDM) which uses laboratory routine data coded with ICD-10 to approximate an underlying non-diseased age and sex stratified population from mixed clinical data. By removing test results that stem from subpopulations significantly different from the general population, reference intervals can be generated stratified by sex and age, taking into account the associated health conditions of the patients as derived by the ICD-10 coding system. Results: Applying the DDM to blood plasma potassium levels demonstrated its ability to adjust RIs dynamically across different patient groups. The method effectively differentiated RIs in a decade-based stratification, showing significant variability and tighter confidence intervals, particularly in older (above 60 years old) adults. The RIs were slightly wider with advancing age in both males and females, while their standard deviation was reduced by removing large portions of test results differing significantly, grouped by either their individual ICD-10 code or clusters of ICD-10 codes. Conclusions: This DDM data mining approach offers a robust framework for RI inference by generating adjusted RIs that incorporate clinical nuances reflected in ICD-10 codes. This approach not only enhances the accuracy of patient diagnostics but also facilitates the identification of potential multimorbidities affecting laboratory results.