Validating biological reference intervals (also known as reference ranges or normal ranges) in a medical laboratory is essential to ensure that the reported test results are accurate and clinically meaningful. Here are the steps to validate biological reference intervals:
- Define the Reference Population: Determine the target population for which the reference intervals will be established. This involves selecting a healthy population that represents the specific demographic or age group for which the test is intended.
- Sample Collection: Collect a sufficient number of blood samples from individuals in the defined reference population. The sample collection should follow standardized protocols, and samples should be collected under appropriate conditions, such as fasting or non-fasting, as required for the specific test.
- Data Collection: Record relevant demographic and clinical information of individuals in the reference population, such as age, sex, and relevant medical history.
- Data Exclusion: Carefully review the collected data and exclude any samples with outliers or those that do not meet the defined criteria for a healthy reference population. Exclude individuals with any known acute or chronic medical conditions that could affect the test results.
- Statistical Analysis: Perform statistical analysis on the collected data to establish the reference intervals. Commonly used methods include the non-parametric method (e.g., 2.5th and 97.5th
- Sample Size Determination: Ensure that the sample size is sufficient to achieve statistically significant results. The sample size required for validation depends on the test and the desired level of confidence in the reference intervals.
- Subgroup Analysis (Optional): If the test is intended for different subgroups (e.g., different age ranges or sexes), consider conducting separate statistical analysis for each subgroup to establish specific reference intervals.
- Clinical Validation: Clinical validation involves comparing the established reference intervals with the clinical presentation of patients. This step helps ensure that the reference intervals align with the expected ranges for healthy individuals and can identify potential issues with the reference intervals.
- Continuous Monitoring: Reference intervals should be periodically reviewed and updated, especially if there are changes in the population demographics or if new evidence becomes available. Regular monitoring helps maintain the accuracy and relevance of the reference intervals over time.
- Documentation and Reporting: Document the validation process, including the methodology used, the reference population characteristics, and the statistical analysis performed. Clearly report the established reference intervals in laboratory reports and reference range documents for easy reference.
By following these steps, a medical laboratory can validate biological reference intervals that are representative of the target population and support accurate interpretation of test results for clinical decision-making.
About the author
Dr. Sambhu Chakraborty is a distinguished consultant in quality accreditation for laboratories and hospitals. With a leadership portfolio that includes directorial roles in two laboratory organizations and a consulting firm, as well as chairmanship in a prominent laboratory organization, Dr. Chakraborty is a respected voice in the field. For further engagement or inquiries, Dr. Chakraborty can be contacted through email at director@iaqmconsultants.com and info@sambhuchakraborty.com. Additional resourcesand contact information are available on his websites, https://www.quality-pathshala.com and https://www.sambhuchakraborty.com, or via WhatsApp at +919830051583