Indirect Reference Intervals: Harnessing the Power of Stored Laboratory Data.

Abstract

Reference intervals are relied upon by clinicians when interpreting their patients’ test results. Therefore, laboratorians directly contribute to patient care when they report accurate reference intervals. The traditional approach to establishing reference intervals is to perform a study on healthy volunteers. However, the practical aspects of the staff time and cost required to perform these studies make this approach difficult for clinical laboratories to routinely use. Indirect methods for deriving reference intervals, which utilise patient results stored in the laboratory’s database, provide an alternative approach that is quick and inexpensive to perform. Additionally, because large amounts of patient data can be used, the approach can provide more detailed reference interval information when multiple partitions are required, such as with different age-groups. However, if the indirect approach is to be used to derive accurate reference intervals, several considerations need to be addressed. The laboratorian must assess whether the assay and patient population were stable over the study period, whether data ‘clean-up’ steps should be used prior to data analysis and, often, how the distribution of values from healthy individuals should be modelled. The assumptions and potential pitfalls of the particular indirect technique chosen for data analysis also need to be considered. A comprehensive understanding of all aspects of the indirect approach to establishing reference intervals allows the laboratorian to harness the power of the data stored in their laboratory database and ensure the reference intervals they report are accurate.

The indirect method in the establishment of reference intervals for complement 3 and complement 4: A retrospective study

“…Although the direct sampling technique is deemed an a priori approach, it is particularly helpful in drawing on resources from modern laboratory databases when the establishment of RIs faces practical constraints or difficulties. 16 In addition, the LMS method and z test were used to determine the cut-off point for age. In recent years, some scholars have proposed applying the LMS method to the establishment of RIs and age partition.…”

“…Generally, researchers have noted the following advantages of the indirect method over the direct method: (1) less time-consuming and costly, (2) guaranteed sample size for each interval when partitioning, (3) reflection of routine laboratory operating conditions, and (4) ethical advantages, as, for a reference interval study, participants are not subjected solely to venesection. 16 …”

Establishment of Pediatric Reference Intervals for Routine Laboratory Tests in Korean Population: A Retrospective Multicenter Analysis

“…While the possibility of including “unhealthy” patients in the reference group cannot be completely excluded owing to the intrinsic limitation of this approach, best efforts to derive reliable, sophisticated results from data have been made by careful medical record review and discussion by the international CALIPER research team, which leads studies on the establishment of authoritative pediatric reference intervals. While we did select “presumed healthy” patients on the basis of medical record review, various statistical techniques are available to extract “healthy” population data from a mixed dataset using visualization or formulation, under the assumption that the reference values from the healthy population have a near-Gaussian distribution [ 21 ].…”

“…In accordance with CLSI EP28-A3c guidelines, to obtain data from “presumed healthy” individuals [ 2 , 21 ], patients who underwent routine preoperative laboratory evaluation for minor surgery in the departments of general surgery, orthopedics, plastic surgery, thoracic surgery, ophthalmology, otorhinolaryngology, urology, dermatology, and dental surgery were considered as the “healthy” pediatric population. Preoperative laboratory test results of these patients were collected as reference values, following the indirect sampling method [ 2 ].…”

refineR: A Novel Algorithm for Reference Interval Estimation from Real-World Data

“…In contrast, the direct method approach utilizes ‘super-healthy’ individuals, such as blood donors, to define reference intervals 9 . The indirect method also poses a faster and less expensive approach than the direct method, with fewer ethical concerns, especially in the pediatric field 6 – 8 , 10 , 11 . Additionally, due to the large number of measurements available, indirect methods can be expected to provide a substantial gain in precision of the estimated reference intervals.…”