Materials and Methods

one, material

1. data materials: collect 2020 year 4 moon 1 Solstice 2021 year 3 moon 31 Blood routine testing of outpatient and inpatient patients in Hebei Children's Hospital WBC Total results 113 532 a, Strictly label patient data, Does not involve the use of patient personal information; Collect selected items 12 Every working day of the month 1 Comparison data of new blood samples 248 group.

2. Instruments and Reagents: Active duty in the Medical Laboratory Department of Hebei Children's Hospital 5 Taiwan Blood Cell Analyzer, respectively: Reference instrument Sysmex XN1000 1 platform (Hisense Meikang Co. , Ltd. , Japan, recorded as A1) , The reference instrument runs stably and has excellent inter room quality evaluation results; Comparing instruments 4 platform, Among them, Mindray BC5310 1 platform (Shenzhen Mindray Biomedical Electronics Co. , Ltd, recorded as A2) , Sysmex XN350 1 platform (Hisense Meikang Co. , Ltd. , Japan, recorded as A3) , Sysmex xs500i 2 platform (Hisense Meikang Co. , Ltd. , Japan, recorded as A4, A5) , The comparison instruments are running stably and are regularly compared with the reference instruments indoors to ensure they are qualified; All reagents, Calibration product, All quality control products are used in their original packaging.

3. Conventional quality control: Strictly follow ISO15189 Quality Management System Standards, All blood analyzers are replaced with reagents by authorized personnel in the department, Maintenance and calibration verification, etc, Attend the proficiency test on time, Inter room comparison and indoor comparison. daily 3 Indoor quality control at a certain level, After control, Using fresh blood 5 Consistency comparison of results between analyzers and routine sample testing.

4. PBRTQC Professional intelligent software system: Real time quality control intelligent monitoring platform for patient data (artificial intelligence moving average intelligent monitoring platform, AI-MA) (Shanghai Senxu Medical Technology Co. , Ltd) . based on AI-MA conduct PBRTQC Normal distribution test of patient data in quality control procedures, Program establishment, performance verification, Optimal method selection, Comparison and statistical analysis between instruments.

two, method

(one) PBRTQC Program establishment, Performance validation and selection

based on AI-MA Set parameters, Select quality objectives, Quality control rules, Outlier removal criteria, Truncated value range, weighting coefficient, Control limits, etc, And verify the selected time range EWMA The quality control effectiveness of the method, Evaluate quality control effectiveness indicators such as accuracy and sensitivity by screening parameters, choice WBC optimal PBRTQC method, Real time monitoring of performance changes in various instruments and comparison between instruments. EWMA Algorithm calculation model: among which, For the tht+1 Estimated value of points, For the thtEstimated value of points, For the thtActual measurement value of the point, λFor weighting coefficients, 0 'λ≤1.

(two) Comparison plan

1. Comparison of concentration and time interval selection: According to the health industry standards of the People's Republic of China WS/T 406-2012 "Quality requirements for analysis of routine items in clinical hematology testing" ^［6］Sample selection concentration requirements for comparability validation and laboratory patients WBC The distribution of data, utilize AI-MA Analyze the distribution characteristics of patient data, Choose data with a relatively concentrated distribution that basically meets clinical needs 3 A concentration range, low concentration (2. 5~4. 5) ×10⁹/L, Medium concentration (6. 0~8. 0) ×10⁹/L, high concentration (12. 0~14. 0) ×10⁹/L The concentration cutoff interval used for comparison; According to the principle of stratified sampling, choice 1 within the year 12 Month by month 1 Every Monday, Corresponding weekly, Monthly time interval used for comparison.

2. Comparison plan implementation: Import patient sample data and fresh blood comparison sample data AI-MA "Comparison of instruments in the laboratory" module. Calculate each instrument WBC of EWMA Cumulative mean, The relative deviation of each instrument compared to the reference instrument obtained by the median and two calculation methods, This is how to proceed EWMA Comparative analysis between instruments in two dimensions of different concentration ranges and time intervals using the method and median method, research EWMA Comparability between Law and Median Method; In the platform EWMA Real time comparison and analysis of data with fresh blood comparison data, research EWMA Comparability between the method of comparing fresh blood and the method of comparing fresh blood.

3. statistical method: Relative deviation of instrument comparison= (Compare instrument experimental results-Reference instrument results) /Reference instrument results×100%.

(three) criteria for judgment

1. PBRTQC Quality Control Efficiency Evaluation: EWMA method Z The alarm data in the score quality control chart matches the quality event, The distribution of patient data results is relatively stable and follows a normal distribution^［5］, Performance meets the probability of error detection' 90%And false alarm rate '5%For the best PBRTQC program.

2. Acceptable standards for inter instrument comparison: Quality objectives refer to the health industry standards of the People's Republic of China WS/T 406-2012 Quality requirements for analysis of routine items in clinical hematology testing, Sample concentration for comparability validation using a blood cell analyzer≥2. 0×10⁹/L time, The allowable relative deviation is±7. 50%^［6］.

3. Consistency evaluation of comparison between methods: 2 Compare the instrument to instrument deviations obtained by each method with the allowable range required by the industry standard, If all can pass and the trend is basically consistent, It is believed that 2 All methods have equal effectiveness in determining the consistency of results between instruments.

result

one, best EWMA Evaluation of Quality Control Efficiency of Programs

As a reference instrument A1 for example, sutra AI-MA Filter validation, Choose a pediatric laboratory WBC reference interval (5. 5~11. 0) ×10⁹/L For quality control concentration, λ=0. 03 For weighting coefficients. 2019 year 10 moon 1 day—2020 year 9 moon 30 During the daily quality control verification, a common occurrence occurred 2 Secondary warning (picture 1) ; among which 2019 year 11 moon 19 day 9 time 9 There is a positive deviation in the accuracy performance of the white blood cell test results at the beginning, Yellow warning appears on the quality control chart, 11 moon 21 Daily correction (picture 2) ; Check maintenance records 11 moon 21 The puncture needle was replaced on a daily basis, Performance changes determined to be caused by puncture needle wear; 2020 year 3 moon 15 day 10 time 36 part WBC The detection result shows a negative deviation in accuracy performance, Yellow warning appears on the quality control chart, 3 moon 17 day 9 time 18 Separate correction, Check the technical records for display 3 moon 17 The instrument underwent maintenance by flushing the waste liquid chamber, It is speculated that the waste discharge pipeline is slightly blocked. Inclusion of statistical cycles 38 313 Sample results, Number of samples indicating potential quality risks 70 a, The warning rate is 0. 183‰, The probability of error detection is 100%, The probability of false loss of control is 0, The results show EWMA Reasonable setting of quality control parameters, Good quality control efficiency.

picture 1  XN1000 Overall patient data Z Score quality control chart 12 A natural month dataset (EWMA Law and 3 A level of quality control product, 2019 year 10 moon 1 day—2020 year 9 moon 30 day)

picture 2  XN1000 Overall patient data Z Score quality control chart shows positive deviation result (EWMA Law and 3 A level of quality control product, 2019 year 11 moon 17—25 day)

two, Based on patient data EWMA Comparative analysis between instruments using the median method in terms of concentration and time dimensions

Taking high concentration as an example, 5 The analyzer collected a total of EWMA Compare data with median method 138 group (46/46/46, day/week/moon) , Daily comparison, 2 The consistency rate of the methods is 95. 65% (44/46) ; When comparing weekly and monthly, 2 The consistency rate of all methods is 100% (46/46) .

When the truncation range is daily, EWMA Display that the relative deviation between each instrument is within the allowable range for comparison, But the median method shows that 2020 year 8 moon 3 Daily instruments A5 Deviation from the reference instrument exceeds the allowable range, 2020 year 12 moon 7 day, A2 Deviation exceeds the allowable range, Compared to the median method EWMA Show significant variation (watch 1, picture 3) , After investigation, the sample size of the devices that exceeded the scope for daily testing was 4 example; The cutoff time range is weeks and months, EWMA The deviation between the devices obtained by the median method is within the allowable range of the results, And the trend is basically consistent (watch 2, 3, picture 4, 5) .

picture 3  Based on patient data EWMA Line graph of daily comparison deviation between the blood cell analysis instrument and the median method

picture 4  Based on patient data EWMA Line graph of weekly comparison deviation between the blood cell analysis instrument and the median method

picture 5  Based on patient data EWMA Line graph of monthly comparison deviation between blood cell analysis instruments using the median method

three, EWMA Comparison of instrument comparison results with daily fresh blood comparison method

with A2 for example, select 2020 year 7 Monthly patient data and fresh blood comparison data 21 group, adopt EWMA The method of comparing fresh blood with the reference instrument is used for daily comparison, Relative deviation and allowable deviation (≤±7. 50%) compare. The results show, EWMA The method displays the comparison between the instrument and the reference instrument for the current month WBC The relative deviation is within the allowable range, However, the fresh blood comparison results showed that 2020 year 7 moon 6 day, The deviation between this instrument and the reference instrument is 7. 53%, Exceeding the allowed range (watch 4) , The consistency rate of comparison is 95. 24% (20/21) .

discuss

currently, Clinical laboratories typically conduct daily indoor quality control, Participate in inter laboratory quality assessment on time and regularly compare fresh venous blood samples to ensure consistency of results between different blood cell analysis equipment in the laboratory. Indoor quality control is limited by the differences in matching quality control products of different brands and models, Only the stability of the monitoring instrument's own operation can be guaranteed, Unable to visually monitor the consistency of results between instruments; However, due to its high price, inter room quality evaluation is more expensive, Most laboratories only choose representative instruments to participate in quality evaluation and testing, Cannot simultaneously monitor the comparability of results from all instruments; The plan of regularly comparing fresh venous blood cannot continuously monitor the consistency of results between instruments in daily work, Therefore, it will increase the risk of clinical laboratory quality. Therefore, Establish a more efficient approach, economy, A convenient scheme for continuous comparison between laboratory instruments is essential.

This study takes WBC for example, based on PBRTQC In the method EWMA The algorithm has established a scheme for continuous comparison between blood cell analyzers in the laboratory. Patient big data validation results show, In the reference instrument WBC project EWMA Both the method and indoor quality control results show stable operation under control, but EWMA The method detected the wear of the sample needle, System offset caused by slight blockage of pipelines, Real time continuous monitoring of the stability of the inspection process can be achieved. This study aims to establish EWMA Selected during algorithm 2 Methods for Optimal Parameter Configuration, Filtering and validation, adopt IFCC One of the recommended methods is the manual introduction of error model, in AI-MI Perform manual error introduction model validation, Then, based on this, the obtained alarm or loss of control results will be applied, Compare and verify the error results with real-world quality events. The sources of errors in the real world are often more complex and intricate, Therefore, this verification method maximizes the avoidance of error omission or false detection, Can better ensure the quality control effectiveness of the established quality control model. From the perspective of modern laboratory construction, Indoor quality control should focus more on patient risk, Instead of solely focusing on statistical analysis^{［7,  8］}, And this result suggests PBRTQC The method can discover quality risks based on patient data, Not only is it a beneficial supplement to indoor quality control, It is a modern quality control tool that meets the requirements of comprehensive quality management in laboratories.

China's Health Industry Standards WS/T 641-2018 "Clinical laboratory quantitative determination indoor quality control" It is pointed out that the median of patient data can be used for experimental quality, comparability, Monitoring of stability and sources of variation^［9］. Xia Jun and others^［10］Reported a plan for indoor quality control using patient data mean and percentage method, Goossens wait^［4］Established a method for evaluating and monitoring the comparability and stability of clinical laboratory test indicators between laboratories using median patient data. But it has not yet been adopted EWMA Research report on the consistency and comparability of instrument detection results in the monitoring laboratory.

This study is based on patient big data, adopt EWMA Method and median method respectively calculate the deviation of instrument comparison, The results show, When the cutoff time range is weeks and months, EWMA The relative deviation results between the instruments obtained by the method and the median method are within the allowable range, And the trend is basically consistent, Good consistency of results between display instruments; Shorten the cutoff time to daily hours, The median method shows significant variation, Some comparison instruments have exceeded the allowable deviation when compared with reference instruments, This may be due to the small sample size, The median method is greatly affected by individual differences among patients, Reduced data efficiency, Therefore, more false alarms are prone to occur during the consistency of results between monitoring instruments, This is related to Goossens wait^［4］The research reports are consistent. EWMA The method introduced the influence of historical result data during its establishment, Can more comprehensively monitor the trend of changes in the process, And the introduction of weighting coefficients makes it more sensitive to detecting small changes^［11］. This study compared patient data from different time dimensions and concentrations, Result prompt EWMA Method compared to median method, In the comparability monitoring between instruments, it has the same efficiency and the trend is basically consistent, But EWMA The method can still maintain relatively stable monitoring efficiency even with a small amount of data.

EWMA The method can continuously monitor the stability of laboratory testing systems, To verify its ability to continuously monitor the consistency of test results during the day, This article chooses continuous 1 The monthly data was compared and analyzed with the results of daily fresh blood samples, The results showed that when using the fresh blood comparison scheme for instrument to instrument comparison, there were cases where the instrument to instrument deviation exceeded the allowable range, 2 The consistency rate of the results of the methods exceeds 95%. This laboratory 2016 Starting from the year, Daily quality control involves using multiple instruments to detect the same fresh venous blood sample after control, Calculate the deviation between instruments, As a supplement to indoor quality control to assist in monitoring the consistency of daily instrument results, Good application effect. Many domestic laboratories use this method for daily monitoring of the consistency of results between blood cell analyzers or as a supplement to indoor quality control^［12］, However, the daily fresh blood comparison method has certain limitations, Like daily random selection 1 Perform a single test of fresh blood on each instrument, There may be many uncontrollable factors causing random errors, As if operated manually, The impact of sample placement time, etc, Therefore, this plan needs to be combined with the comparison results of other blood cell analysis projects, Indoor quality control and regular comparison method jointly determine the stable state of the current instrument. Zheng Cuiling and others^［2］Case study of daily fresh sample comparison assisted indoor quality control reported, Turn on each tube of fresh blood on each instrument after startup, During operation and before shutdown 3 Secondary determination, This plan only selects daily options 1 Detect the concentration within a reference interval, Unable to cover the commonly used testing range in the laboratory. Moreover, Fresh blood comparison requires daily sample collection and testing, Increased labor and material costs. This result suggests EWMA Can replace daily fresh venous blood comparison, As a supplement to indoor quality control, Continuously and effectively monitor the consistency of results between different blood cell analyzers in the laboratory.

The plan established by this research institute still has shortcomings. When introducing comparison instruments, Not introducing a total detection volume less than the average daily 20 test 2 Taiwan Instruments, This may lead to a lack of comparison between instruments. But in laboratory management, If it is found that a certain instrument has been in a state of low application efficiency for a long time, The workflow should be changed in a timely manner, Improve equipment utilization, To shorten the laboratory turnover time of samples, Improve work efficiency and management effectiveness.

in short, use PBRTQC The plan's EWMA Compare blood cell analyzers between instruments in the laboratory using the method, No matrix effect, No need to add quality control products, Reagents and consumables, Human and time costs, Can continuously monitor the consistency of detection results between devices, More conducive to controlling quality risks in laboratory testing, Provide assurance for standardized quality management in laboratories; Using patient data for laboratory management, Enhance awareness of scientific and rational application of clinical laboratory data resources, It also provides new perspectives and ideas for the construction of modern intelligent laboratories.

References (omit)