From 1949, the College of American Pathologists (CAP for short) first began to study the clinical laboratory indoor quality control (abbreviated as quality control). American scholars Levery and Jenning published the first article on laboratory indoor quality using quality control charts in 1950. Control, the indoor quality control work of the clinical testing laboratory officially kicked off. By the 1970s, laboratory quality control had entered a new stage—total quality management and the implementation of Good Laboratory Parctice (abbreviated as GLP). In the late 1980s, the unified standard of GLP came into being and developed to the management stage of "certified laboratory". The purpose of total quality management is to prevent errors. The purpose of statistical quality control in quality control charts is to detect errors. Statistical laboratory quality control is an important part of total quality management. This chapter mainly introduces the statistical laboratory quality control method of immunology test. Because ELISA is the most commonly used immunological test method in clinical practice, ELISA test is used as an example to introduce related issues. The immunological quality control room of the Clinical Laboratory Center of the Ministry of Health has been conducting quality evaluation activities for hepatitis B marker testing nationwide since 1988. It has been using this set of quality evaluation methods and has continued to practice, improve and improve in practice. I hope to find To develop an effective quality management path that suits China's national conditions. 5.1 Basic concepts 5.1.1 Quality control (Quaility Control, QC) Quality control is a management process that monitors the entire process, eliminates errors, prevents changes, and maintains the current status of standardization. This process is carried out through a feedback loop. 1) Determine the object of control; 2) Specify the standard (expected value) of the controlled object; 3) Formulate or select control methods and means; 3) Measuring actual data; 4) Compare or compare the difference between the actual data and the expected value, and explain the reason for this difference. If the predetermined error range is exceeded, the alarm system sends a signal and the feedback channel is interrupted. 5) Take action to resolve differences. The means of restoring the original state (original standard state) come into play. Quality control is mainly carried out using quality control charts. A quality control chart is a chart that compares the performance data of a certain test with the calculated expected "control limits". This performance data is selected in chronological order when it is carried out normally according to the regulations. Its purpose is to detect the "traceable" cause of the variation in the inspection process. The "reversible" error causes refer to other causes than random errors. The "control limit" is calculated statistically, and we will introduce it in detail later (see 5.3. Indoor quality control procedures). 5.1.2 Errors Experimental errors are divided into three types: systematic errors, random errors and negligent errors. Systematic error refers to a series of errors with the same tendency as the true value or target value, with obvious regularity, which can be repeated under certain conditions and can be prevented and corrected by quality control. Random error, also known as accidental error, is an accidental and unpredictable error that is difficult to avoid and correct. The distribution of random errors in the inspection work conforms to the law of normal distribution. Negligence error is a human responsibility error. It can be avoided by strengthening laboratory management and carrying out quality control. 5.1.3 Normal distribution and standard deviation In the ELISA test, when the same sample is tested more than 20 times, you will find that this set of data (referred to as the absorbance of the measurement result) is distributed on both sides of the mean, most of which are concentrated around the mean. If the measured value is plotted on the abscissa and the frequency of occurrence on the ordinate, a bell-shaped curve can be drawn. As shown in Figure 5-1, the mean is at the top of the bell, and the other values ​​are symmetrically distributed with the mean at the center. This is the normal distribution. The area under the normal curve is called probability, which is usually expressed by the mean (X) and standard deviation (SD) of the sample. The calculation method is as follows: The relationship between mean, standard deviation and probability is as follows: X ± 1SD, probability 0.68 X ± 2SD, probability 0.95 X ± 3SD, probability 0.99 In other words, a set of data obtained when ELSIA detects the same sample for a certain number of times, which is close to the mean (X ) Data within the range of ± 1SD, accounting for 68% of the data in the group, data distributed within the range of X ± 2SD accounted for 95% of the population, and data distributed within the range of X ± 3SD accounted for 99% of the population. When we require the test result to be qualified within the range of X ± 2SD, 95% of the data may be qualified. 5.1.4 True value The value measured by the exact and ideal decisive method is called the true value. The truth value is generally undetectable. The value measured by a reliable decisive method is called the target value, and the target value is usually used to represent the magnitude of the true value. 5.1.5 Accuracy refers to the degree to which the measurement result is close to the true value (or target value). Accuracy cannot be expressed in numbers, and is often measured by inaccuracy. The degree of deviation between the measurement result and the target value is called deviation, which indicates the inaccuracy of the test. Absolute deviation = mean value of test-true value (or target value) Relative deviation = absolute value of true deviation ÷ (or target value) × 100% 5.1.6 Precision (Precision) refers to the repeated measurement of the same sample, each measurement The closeness of the result to the average, that is, the degree of agreement between the repeated measurements. 5.1.7 Standard products 1. The international standard products are calibrated by WHO or corresponding organizations, and are determined materials by affirmative, recognized and accurate physical or chemical methods. 2. The international biological activity standard is the material of the international activity unit calibrated by WHO or corresponding organizations according to the biological reaction. 3. Reference Standards The legal materials produced by the National Standardization Organization according to international standardization. It can be used to identify the accuracy of instruments and methods. 5.1.8 Clinical decision leuel When the concentration of a certain test substance reaches a certain level, the clinician must adopt medical measures. This concentration of the test substance is called the clinically decisive level. 5.2 Quality Control Serum Quality control serum is the serum with the target value. Add one or several parts to each routine test to understand the status of the test by the results obtained. If the result of the quality control serum test can control the error within a certain range, it means that the test has not allowed no error. If there is an abnormal result that exceeds the allowable error range, it indicates that the inspection is unqualified, and the cause should be found. After correction, the specimen to be tested should be re-examined. Therefore, quality control serum plays an important role in quality control. 5.2.1 Use of quality control serum The serum of hepatitis B marker substance prepared by the Clinical Inspection Center of the Ministry of Health can be kept constant at -20 ℃ for half a year. When melting in a frozen state, it should be mixed first, and the unused part can be stored at 4 ℃ for 5 days. It is not advisable to repeatedly melt ice or distribute it by yourself. The quality control serum required for the indoor quality control work of a certain test is generally prepared according to the dosage of 3-6 months. For the self-made variable quality control serum, before the batch of quality control serum will be used up, the next batch of quality control serum needs to be prepared. The quality control serum requires stable performance, the potency remains unchanged for a long period of time, and its physical and chemical properties should be similar to the patient samples, so as to effectively play a monitoring role. 5.2.2 Critical value quality control Serum quality control serum is divided into two kinds of fixed value and undetermined value. If only one set of quality control serum is used, it is generally set at the boundary between normal and abnormal values. It is at a weak positive level during qualitative determination, which is called the critical value. The establishment of the threshold value of hepatitis B markers should provide a unified standard for judging weak positives according to clinical requirements. The cut-off quality control serum can be used as the third control in addition to the positive control and negative control in the kit. It can sensitively reflect the detection level of the kit to ensure that samples with weak positive reactions are not missed. 5.2.3 Preparation of quality control serum Each laboratory can choose the quality control serum provided by the clinical center according to its own conditions, or prepare the quality control serum used in this laboratory by itself (taking hepatitis B quality control serum as an example). 1) Collect fresh positive serum without hemolysis, jaundice, or bacterial contamination. 2) Live at 56 ℃ for 10 hours. 3) Centrifuge or filter to remove the precipitate. 4) Dilute the collected serum with 10% calf serum or normal human serum (PBS buffer) to the desired concentration. If it can be diluted with normal human serum, its composition is closer to the test specimen. 5) Suction and filter sterilization. Dispense small ampoules according to the amount of one-time use, seal, and store at 20 ℃ for future use. Do not freeze and thaw repeatedly. The level of the test substance required to be detected is often regarded as the level that should be selected for the quality control serum. If there are other requirements for this test, the quality control substance at the required concentration should be added. 6) Calibration content. 20-30 times of measurement results delete the average value of> ± 2SD data as the target value, and compare it with the known fixed value serum. 5.3 The test results of the clinical inspection of the indoor quality control procedures cannot be free of errors every time or every day. To determine the allowable error range, the quality control range shall be determined through the following steps based on clinical misdiagnosis and missed diagnosis. 1) Measurement error under optimal conditions. 2) The error of the serum with known value under the routine test conditions. 3) The error of serum of unknown value under routine test conditions. 4) Requirements for clinical application. For any test, an allowable error range should be determined. The previous question is to meet the clinical requirements. If the allowable error is set too small, there is no clinical significance, but in order to comply with the regulations, it takes a lot of manpower, material resources and time. On the contrary, if the allowable error is set too large, the monitoring system will not notice the clinically required error and lose the meaning of quality control. 5.3.1 Determination of known values ​​of optimal conditions variance (OCV) under the best conditions The quality control serum is tested 20-30 times under the best conditions of the laboratory (including operators, reagents, instruments, etc.) , Calculate the measured results, find the mean and standard deviation (SD) of the set of data to indicate the best work quality of the laboratory. Here is an example to illustrate the determination of OCV during HBsAg ELISA detection. The quality control serum used was the critical serum, and the HBsAg concentration was 5 ng / ml. In this laboratory, select the best quality and most skilled technicians to carry out careful and specific measurements, select the best kits, before testing, carefully calibrate, adjust, adjust and debug the constant box, sampler, etc. The sampling tips, etc., are tested under the best and most ideal conditions. In addition to the quality control serum, the negative control and positive control were measured simultaneously. And make a double determination, get two absorbance values ​​(A value), find X. Do 20 times in a row, find 20 X, namely X1 ... X20. From these 20 data, find X and SD of OCV. 5.3.2 Determination of routine conditions variance-known value (RCVK) under known conditions. The technicians who conduct routine inspections will place the quality control serum in the routine test samples under the conditions of routine inspections and conduct 20 inspections. The calculation results are the same as the OCV method. It is generally accepted that the SD of RCV is acceptable within twice the SD of OCV. If it is too large, the cause should be found to bring it closer to the SD value of OCV. After improving laboratory conditions (such as correcting the sampler, correcting the plate washing operation, adjusting the incubation temperature, etc.), re-measure the RVCK. If the SD value of RCVK is smaller, it means that OCV is not measured under the best conditions, and OCV should be measured again. Under normal conditions, RCVK must be larger than OCV. Through quality control to control various conditions, make the RCVK data as close as possible to the OCV value. RCVK's data reflect the quality of the laboratory's daily work and are used for quality control drawings to control the results of indoor inspections. The results of daily inspections can be issued. 5.3.3 Under normal conditions, the measurement of unknown conditions (variant conditions variancl-unknown value referred to as RCVU) sometimes in order to avoid subjectivity, and then RCVU determination. The measurement procedure is the same as that of RCVK, but the operator of the test does not know the value of the quality control serum, or conduct routine inspections under the condition that the operator does not know which part is the quality control blood Wang Qing to exclude the operator's subjectivity. No more examples are given here. 5.3.4 Quality control chart Through the above three steps, you can start to make indoor quality control chart, according to RCVK and SD for quality control block diagram. The quality control chart can be used to monitor the results of each test. When there is no replacement of another batch of reagent kit and another batch of quality control serum, the quality control chart can be continued. The S / CO value of the quality control serum is below the range of -2SD, which is an "alarm". You should find the reason and record the detected reason on the quality control chart. In the ELISA test, the tolerance range of various inspection items has to be concluded in practice. The above is only an example to illustrate the quality control method, not a conclusion. 2SD is the generally accepted tolerance limit. When a batch of quality control serum is placed in each batch of measurements, one time exceeding 2SD shall be regarded as an "alarm", and a second exceeding 2SD shall be regarded as "out of control". When out of control occurs during the quality control process, the cause should be found, usually caused by the failure of the kit or the quality control serum. Replace the kit or replace the quality control serum, find out the cause and correct it, and then re-examine. If the inspection result still fails to meet the requirements or the cause cannot be found, the OCV inspection should be repeated. If the result of the OCV test is still good, it indicates that there is a problem with routine operations. It is generally believed that: ①exceeds 3SD for one time; ② exceeds 2SD for two consecutive times; ③ is within 2SD of one side for 3-5 consecutive times; In cases ③ and ④, relying solely on records is often difficult to detect, but this kind of runaway can be clearly found on the quality control chart. 5.3.5 Statistical calculation method-"Immediate" quality control The quality control method described above is basically the same as the quality control method for clinical chemistry determination, but ELISA has its particularity, and the most suitable quality control method has yet to be established . Some laboratories do not test ELISA items every day, and ELSIA kits have a short validity period, and it is difficult to use a batch of kits for 20 consecutive tests. Using the "immediate method" quality control statistical method, you only need to measure 3 times in a row to perform quality control on the third inspection result. The specific calculation method of the "immediate method" is as follows: 1) First arrange the measured values ​​from small to large 2) Calculate X and SD. 3) Calculate the upper limit of SDI and the lower limit of SDI. 4) Compare the SDI upper limit and SDI lower limit value with the numbers in the SDI value. When the upper limit value of SDI and the lower limit value of SDI are n2SD, it means that the value is outside the range of 3SD, which is "out of control". The values ​​in the "alarm" and "out of control" states should be discarded, and the quality control serum and patient samples should be re-determined. Only the value out of control this time is discarded, and other measured values ​​can still be used. Immediate property control statistical method, suitable for quality control of ELISA determination. When the detected value exceeds 20 times, there is no need to use the "immediate method" quality control statistical calculation, you can transfer to the conventional quality control chart quality control. Use the sum of the values ​​obtained from the previous 20 times and SD as the quality control framework, and click the 21st value in sequence. 5.4 External quality assessment (external quality assessment, referred to as EQA) Inter-room quality assessment, referred to as inter-room quality assessment, is a series of methods used by the quality control center to continuously and objectively evaluate the test results of various laboratories and find indoor quality Control inaccuracies that are not easy to find, understand the differences in results between laboratories, and help corrections to make them comparable. The test results of each laboratory are reported to the quality control center, and after statistical analysis, the results of comparison with each other are obtained. This kind of evaluation can not control the inspection report issued by each laboratory every day, but a retrospective evaluation. The indoor quality control mainly monitors the precision of the test results, while the inter-room quality control mainly controls the accuracy of the test results and cannot be replaced by each other. The laboratories participating in the quality assessment should first perform indoor quality control. 5.4.1 Methods of inter-room quality assessment 1. Investigation of quality control materials This is a common form of inter-room quality assessment at home and abroad. The interim laboratory quality assessment of the Ministry of Clinical Examination Center for ELISA testing of hepatitis B markers regularly issues quality control materials to the laboratories. Each laboratory conducts the inspection on the specified date and reports the test results to the Ministry of Clinical Examination Center. The Ministry of Clinical Examination Center sent the evaluation results to the laboratories after statistical analysis. Through evaluation, each laboratory understands the work quality of the laboratory, finds gaps, and seeks to improve to continuously improve the quality of inspection. This evaluation method has certain shortcomings, that is, each laboratory often treats the quality control materials specially. Special kits are selected during the inspection, and special technicians are selected for inspection. Some laboratories and each other modify the results. This makes the results of EQA unable to reflect the daily working level of the laboratory. 2. Send observers to the laboratory for reagent investigations. Such investigations are not notified in advance. Temporarily send observers to the laboratory, designate a conventional method to test a set of specimens for evaluation. This kind of investigation method is easy to find the actual problems in the laboratory, and you can directly give guidance and help to solve the problems and improve the inspection quality. 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