Study On The Performance Evaluation Method Of Reagents For Quantitative Detection Based On The Biological Variation In Adults

Objectives: Laboratory test index play an indispensable role in the secondary prevention of disease,and the clinical use of a large number of un-routine test items provides more options for early diagnosis and treatment of the diseases.However,the lack of corresponding industry standards and performance specifications for un-routine test items make it difficult to guarantee the quality,performance verification cannot be carried out,and performance specifications are often dependent on biological variation data.According to the internationally recognized experimental design,the research on biological variation was carried out to obtain the data of within-subject biological variation(CVBw)and between-subject biological variation(CVBb)for the test items with no or little reported biological variation data at home and abroad.Export "optimal","moderate" and "minimum" three level.Performance verification and performance evaluation work are carried out on the performance specifications of the above un-routine test items,including precision,accuracy,linear range,reportable range and evaluation of reagent lot-lot variation.Methods: 1.Biological Variation Research: This study first screened clinical and commonly used items,compared with the Westgard website summary database and the latest literature reports,selected items that had never been reported and only one document support project as screened items,recruited eligible volunteers,the experiment lasted for 6 months,each volunteer took blood once a month,according to Cotlove and Costongs experimental design,the long-term CVBw and CVBb are obtained.According to Klee’s viewpoint,the allowable imprecision,allowable offset and allowable total error of the three levels of "best","appropriate" and "lowest" are calculated by formula.2.Performance validation,performance validation and evaluation of inter-batch variation of reagents: selection of samples,elimination of outliers,number of batches and days of detection,statistical analysis,etc.are carried out in strict accordance with China’s health industry standards and the document scheme issued by the Clinical and Laboratory Standards Institute(CLSI).To validate the accuracy,accuracy,linear range and reportable range of these projects,and to evaluate the inter-batch variation of reagents.Results: 1.Biological Variation Research: The PREA,ADA,beta 2M and HBDH projects in 7 projects supported by only one document have no difference with the foreign research results,the intra-individual variation coefficient of A-Tpo and A-Tg is larger than the existing data,and the inter-individual variation data is smaller than the existing data,while the CVBw and CVBb of TG project are smaller than the existing data.Other 12 international and domestic non-biological variation data items Apo E,TBA,MAO,m AST,AFU,GPDA,IVC,LAP,CA-724,HE4,NSE,Pro GRP were used to obtain biological variation data,and the corresponding performance specifications were calculated based on CVBw and CVBb.2.Performance validation,performance confirmation and evaluation of inter-batch variation of reagents: In terms of precision research,GPDA,IVC,LAP and ADA are all domestic reagents.The inaccuracy performance characteristics declared by the manufacturer are greater than the minimum allowable inaccuracy derived from the biological variation in this study.At the same time,the reagents conforming to the best performance specifications derived from the biological variation in this study are all imported manufacturers.83% of the reagents conforming to the appropriate performance specifications are imported manufacturers,and the reagents conforming to the most.80% of the reagent suppliers with low performance specifications are domestic manufacturers.Correctness verification all projects had passed.In terms of linear range validation,APOE,PREA and A-Tpo conform to statistical standard linearity,that is,first-order linearity,all other items are clinically acceptable nonlinearity.In terms of validation and validation of reportable scope,nine project manufacturers declared the validated dilution ratios,all of which passed the validation,the dilution multiples of PREA,HBDH,beta 2M,CA-724,NSE,HE4 and Pro GRP are larger than the performance characteristics of the manufacturer’s statement.Ten projects manufacturers have not given the corresponding performance characteristics.This study confirms the dilution ratio and reporting range of all projects.In the evaluation of inter-batch variability of reagents,based on the results of precision verification data of this study,and combined with the "appropriate" allowable total error derived from this study,the number and rejection limit of samples needed for evaluation can meet all items and concentrations,and the evaluation effect is consistent with that of the original inter-batch evaluation scheme of reagents in our laboratory.Conclusions: 1.The long-term random biological variation data of Chinese adults in 19 projects such as apolipoprotein were obtained.Nine of them were first reported at home and abroad,and seven were first reported at home.At the same time,the "best","appropriate" and "minimum" performance criteria were derived from intra-individual and inter-individual biological variation data.2.Combined with the performance specifications derived above,the performance verification and inter-batch variation evaluation of the above 19 projects were carried out strictly according to industry standards for the first time.GPDA,IVC,LAP and ADA were all domestic reagents,the inaccuracy performance characteristics declared by the manufacturer are greater than the minimum allowable inaccuracy derived from the biological variation in this study.These four items do not meet the requirements of national standard documents.At the same time,most of the certified imprecisions of domestic reagents only conform to the minimum performance specifications derived from biological variations.It is suggested that domestic reagent manufacturers should pay enough attention to the performance confirmation work in strict accordance with domestic and international industry standards on the premise of guaranteeing the quality of reagents.According to the results of linear range validation,samples approaching the high and low values of linear range are recommended to be diluted or concentrated and then re-tested.PREA,HBDH,beta 2M,CA-724,NSE,HE4,Pro GRP can be reported more than the dilution multiple prescribed by the manufacturer,and have excellent performance.It is the first time to confirm the reporting range of 10 testing items.For the first time,the evaluation of inter-batch variation of reagents was carried out in 19 projects.The results showed that the laboratory’s own imprecision combined with biological variation data,and the rejection limit and sample number of the evaluation of inter-batch variation of reagents most suitable for laboratory were derived.