Comparison of Sample Size and Rejection Limits for Lot-to-Lot Verification Using Two Different Protocols: A Cross-sectional Study

Abstract

Introduction: Good laboratory practice necessitates verifying each new lot of reagents before it is put into service to ensure that the results of patient samples are consistent across different lots of reagents. Current laboratory protocols use uniform criteria such as a 10% difference, measurement uncertainty, etc., for the acceptance of Lot-to-Lot Verification (LTLV) across all parameters. Although a detailed guideline was introduced by the Clinical and Laboratory Standards Institute (CLSI), there is limited literature on laboratories using this. Aim: To compare the sample size and rejection limits for LTLV for common chemistry analytes using two different protocols. Materials and Methods: The present cross-sectional analytical study was carried out in the Department of Biochemistry, St. John’s Medical College, Bengaluru, Karnataka, India, from January 2017 to January 2019. The LTLV for reagents was done using patient and Internal Quality Control (IQC) data for common analytes such as glucose, creatinine, albumin and calcium on Siemens Dimension EXL 200 chemistry analyser. Sample size and rejection limits obtained using CLSI EP26-A guidelines were compared with one of the current protocols, which uses one sample at each concentration, usually a maximum of two at two different concentrations, and defines less than a 10% difference in value between the two lots as acceptable criteria. The quality control data was analysed, and descriptive statistics such as the coefficient of variation were used to arrive at precision. Rejection limit and sample size were directly read from the EP26-A guideline using the tables given for the same, based on the two ratios at 90% power. Results: The sample size needed was found to be the same for creatinine and albumin using both protocols, while it was higher for glucose and calcium based on EP26-A guideline. The rejection limit obtained using EP26-A guideline was different for each parameter between the two protocols. The rejection limit obtained using EP26-A was lower for all analytes as compared to the first protocol. Conclusion: Lot-to-Lot Verification (LTLV) using the CLSI guideline reinforces the fact that the sample size needed and the rejection limit for each parameter varies based on its performance and the critical difference to be detected. Hence, the practice of using a fixed sample size and fixed criteria, such as a 10% acceptable difference across all parameters, may not be appropriate.

Keywords

• accuracy
• critical difference
• internal quality control
• precision
• validation