Reference Value Advisor: a new freeware set of macroinstructions to calculate reference intervals with Microsoft...

Area of Science:

• Clinical Chemistry
• Biostatistics
• Laboratory Medicine

Background:

• International recommendations for reference interval determination have been updated, emphasizing robust methods and Box-Cox transformation, particularly for small sample groups.
• Current clinical laboratory software often lacks these updated statistical methods for reference interval calculation.
• Accurate reference intervals are crucial for diagnosing and monitoring patient health.

Purpose of the Study:

• To develop and present a user-friendly software tool, Reference Value Advisor, for calculating reference intervals using various statistical methods.
• To provide a means to compare results from different methods, including those not commonly available in standard software.
• To assist clinical laboratories, especially in veterinary medicine, in adhering to updated international recommendations for reference interval determination.

Main Methods:

• Development of macroinstructions for Microsoft Excel named Reference Value Advisor.
• Implementation of nonparametric, parametric, and robust methods for reference limit calculation.
• Inclusion of Box-Cox transformation for data normalization.
• Integration of normality testing (Anderson-Darling) and outlier detection (Tukey, Dixon-Reed).
• Generation of visual aids including dot plots, histograms, and Q-Q plots.

Main Results:

• Reference Value Advisor calculates reference limits with 90% confidence intervals using multiple methods.
• The tool facilitates the assessment and comparison of results from different calculation methods.
• It provides visual diagnostic tools for data distribution and normality.
• Guidelines based on international recommendations are incorporated.

Conclusions:

• Reference Value Advisor enables rapid assessment and comparison of reference interval calculation methods, including advanced techniques.
• The software is particularly valuable for veterinary clinical pathology dealing with small reference sample groups.
• While not a substitute for proper sample collection and handling, the tool supports accurate reference interval determination when preanalytical and analytical conditions are met.