Control Ranges in Laboratory Testing
When developing control ranges for laboratory testing, the standard is to use values within ± 2 standard deviations (SD) of the mean. This approach is the most widely accepted method for establishing reference intervals in clinical laboratory settings.
Statistical Basis for Control Ranges
The use of ± 2 SD from the mean has strong statistical foundations:
- For normally distributed data, the interval of mean ± 1.96 SD (often rounded to 2 SD) encompasses approximately 95% of the reference population 1
- This approach provides an optimal balance between sensitivity and specificity for detecting abnormal values
- Values falling outside this range are considered statistically significant deviations that warrant further investigation
Evidence Supporting the ± 2 SD Approach
The European Association of Cardiovascular Imaging expert consensus paper explicitly states that "using the statistical method, the normal range is defined as ±2 SD from the mean" 1. This approach is considered standard practice for establishing reference intervals in medical diagnostics.
Similarly, a manifesto for cardiovascular imaging published in the European Heart Journal notes that when using a statistical approach, "it would make sense to analyse a large random sample of the whole population including subjects with disease to define cut points corresponding to values more than, say, 2 SDs beyond the mean (Z score >2 or <2)" 1.
Alternative Approaches and Their Limitations
While other approaches exist, they have specific limitations:
- ± 1 SD (option C): Too restrictive, capturing only about 68% of normal values, leading to excessive false positives
- Between 1 and 2 SD (option B): Creates an unusual "donut" distribution that excludes the central tendency, which is counterintuitive for control ranges
- ± 3 SD (option D): Overly inclusive, capturing 99.7% of values, which may miss clinically significant deviations
Special Considerations
- For asymmetrically distributed data, percentile-based approaches may be more appropriate, typically using the 2.5th and 97.5th percentiles 1
- When establishing control ranges for clinical laboratories, the quality of the reference sample is critical
- Multiple measurements may improve the reliability of control ranges 2
Clinical Implications
Using the ± 2 SD approach has important clinical implications:
- It ensures that approximately 5% of healthy individuals will have values outside the reference range (2.5% on each end)
- This approach balances the need to identify truly abnormal results while minimizing false positives
- Values falling outside this range warrant further investigation to determine if they represent true pathology 1
By using the ± 2 SD approach, laboratories can establish control ranges that effectively distinguish between normal variation and clinically significant deviations, supporting accurate diagnosis and monitoring of patients.