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Analytical Control
Systems, Inc Analytical Control Systems, Inc. |
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317-841-0458
317-841-3186
Analytical Control Systems, Inc.
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The making of a point-of-care Activated Clotting Time Control Quality Control for the Point-of-Care Activated Clotting Time Test By Pauline W. Bonderman January 1995. Recent changes in American medical practice dictate that near-patient care will play an increasing part in clinical testing. This means that the role of health-care providers will be divided between patient care and patient testing. A nurse's job will become less distinguishable from that of laboratory personnel. Until the time that fundamental training for nursing and other patient-care personnel changes, there is a greater burden on the manufacturers of quality control material to provide adequate training material. This does not exclude the primary need for reliable quality controls. One test within the complex field of coagulation, the activated clotting time (ACT) test, presents a unique example of this dual need. The most successful of ACT quality control manufacturers must provide services and materials. The controls must fit all of the requirements of high quality that make any quality control product useful, and the technical support must address the unique needs of a medical care system in flux.
A good, comprehensive quality assurance program includes teaching and support. Since near-patient care is frequently performed by nursing service personnel, a concerted effort must be made to have clear, concise test instructions; easily followed quality control procedures; stable quality control materials packaged in user-friendly, color coded containers; simple, easy-to-read graphic presentations; and complete and authoritative corrective procedures. This is true because nursing service duty has not emphasized the principles, chemistry, and methods so commonly found in the central laboratories. When these programs are available, personnel willingly adopt and employ them. This improves test results, and concomitantly, physicians' reliance on them.
To institute these kinds of successful near-service procedures, the quality control program must be carefully constructed and monitored. The role of the manufacturer is to ensure the end user of a good program designed to inspire confidence. It must be easy to use, accurate, and be accompanied by very reliable, stable, and reproducible control material.
The ideal way to address this problem is as a holistic program. For instance, control for ACT tests starts with a simple, illustrated instruction street, the purpose of which is to explain the test steps necessary to perform the quality control procedures. The verbal statement is accompanied in the text by an illustration that visually acquaints the user with that operation.
The actual quality control material is packaged so that the whole blood can be reconstituted through a septum with a syringe. Since nurses feel comfortable with syringe use, and because the clotting time recovered is insensitive to minor variations in reconstitution (results are an intrinsic property of this control's material), this yields very good field performance.
After the test is performed, the elapsed time is recorded on a simple report form. Following a specified interval, the data are available for statistical analysis. Means, standard deviation, and a Youden plot are generated by the manufacturer, and a new graphical presentation is returned to the user. If any unusual circumstance arises, the manufacturer's technical staff reviews the data, and technical support can be offered.
A further service that may be requested entails having a specialist come on-site to hold a brief training session that highlights purpose, good technique, data collection, and troubleshooting. These programs must include a supervised performance of the test using provided quality control material. Critique sessions and individual help can be offered to everyone who is to use the test until they become comfortable with the performance.
The manual provided should emphasize problem-solving. Every effort should be made to identify the cause of all problems. These can be described, and the cure for them illustrated. This may be the most useful aspect of the program, because the person who performs the test is ensured that the problem he or she may encounter has been seen before and addressed successfully.
The quality control material for point-of-care testing, on the other hand, must do its part to help ensure good quality control technique. A control targeted for the near-patient-care use must address the unique needs of a system in which attention and time are divided between the unpredictable world of patient care and interaction and the precise world of quality control procedures. The shelf-life of the control material must be long enough to make statistical analysis useful. To this end, products should be dated for at least two years from the date of manufacture. In addition, ACT controls should be stable long enough after reconstitution so that tests may be repeated if necessary. This means that the nurses need not worry unduly if emergency situations arise that prevent them from finishing the test as soon as the vial has been reconstituted. To maximize uniformity, the appropriate type of water and calcium chloride should be supplied with the set.
However, the best of programs requires reliable materials. The control must produce as precise and accurate an answer as possible. When the control yields high-quality data, the ability of the healthcare provider to monitor testing techniques and machine performance increases. In effect, the better and more appropriate the control, the better the test.
Materials: The following materials were used: ACT-Trol™ sets (patent pending) (Analytical Control Systems, Inc., Fishers, IN); Hemochron® instrument and Hemochron FTCA 510/CA 510 and P214/P215 tubes (International Technidyne Corp., Edison, NJ); HemoTec® instrument and HemoTec LR and HR cartridges (Medtronic HemoTec Inc., Englewood, CO); Quest® tester and tubes (Quest Medical, Dallas, TX); 3- and 1 -cc syringes; automatic 1 and 0.25-mL pipetting devices and plastic tips; Fibrometer instrument and Fibrometer cuvettes (Becton Dickinson Co., Rutherford, NJ); and APCT (activated plasma clotting time) reagent (patent pending) (Analytical Control Systems).
Discussion: Because some near-patient coagulation analyzers are whole blood based and are sensitive to the presence or absence of hemoglobin pigment, a basic requirement of the control developed (Analytical Control Systems) was that it mimic the patient sample as closely as possible. It is for this and for appearance reasons that the final product configuration contains hemoglobin in significant quantities.
A further consideration for the control was that it not be a possible source of human viral pathogens. To be certain of that result, animal-based coagulation material was chosen as a source of plasma and cellular components (patent pending). No human source material should be used in near-patient care controls. Since animal coagulation times vary from species to species, the desired ACTs are varied either by blending or by laboratory manipulation of the clotting factors (patent pending). In general, three target levels are prepared. These are the normal ACT times (all results are based on human times), the moderately anticoagulated times, and the strongly anticoagulated times. Because activators (such as celite, diatomaceous earth, and micronized silica) provide dissimilar results and because different instruments give varied results, values are set by using a Fibrometer and APCT reagent. Each lot is then tested using a Hemochron instrument and a HemoTec instrument.
The product is packaged in lyophilized form in a 6-mL clear vial. Each vial has a color-coded label and seal; i.e., normal time control is blue; the level II is coded yellow. A box of product contains one vial of level I (blue), one vial of level II (yellow), two vials of water (black), and two vials of calcium chloride (0.02 M) (silver). For most users, the product is supplied in a 3-mL fill size. Therefore, 3 mL of water is withdrawn from the water vial and injected into the control vial. The mixture is allowed to sit for 5 min and then swirled gently and allowed to sit for 5 min more. The calcium chloride is withdrawn from the vial and placed in the reaction tube where it wets the activator. When the operator wishes to initiate the test, the reconstituted control is withdrawn with a syringe and injected into the tube. The reaction tube must be agitated to thoroughly mix the activator with the whole-blood control. The tube and its contents are then inserted into the analyzer, and the test is promptly started. The value (the elapsed time in seconds) is recorded from the analyzer. This process is illustrated in Figure 1. In practice, this representation is colored to match the appropriate vials.
Three levels of quality control material on Hemochron and Quest instruments were tested, while two levels of material were tested on HemoTec instruments. The mean and standard deviation of data obtained on Hemochron instruments are as follows: normal level x = 129 ± 10 see with n = 20 (1 SD), and the mildly prolonged level x = 195 ± 6 see with n = 20 1 SD). In both cases, the number of assays was 20 completed. The same control gave the following results on the HemoTec: normal level x = 87 ± 3 see with n = 20 and prolonged level 190 ± 5 sec. These data reflect the total assay precision as well as control precision, with the level of precision being quite similar to that achieved on repeated patient specimens.
The greatly prolonged control accurately mimics the situation seen in patients receiving large amounts of heparin; that is, the clot is very soft and slow forming. Other commercial controls have not been successful at producing this result. However, ACT-Trol level III (greatly prolonged) uniformly clots sufficiently well to be useful. When level III controls were tested on the Hemochron, the control yielded the following data: x = 521 ± 26.8 see, n = 10 (1 SD). In every case, a clot was detected. Similar results were obtained on the Quest tester.
A necessary prerequisite for any commercial control is to achieve good reproducibility between different technicians at different skill levels. The mean of three operators' results using the same instrument and control was 1) 123 ± 7 see, 2) 129 ± 4 see, and 3) 123 ± 2 see (n = 10). Only one of these technicians routinely runs this assay (number 1).
Vial-to-vial reproducibility was estimated by assaying 10 randomly selected vials. The data for Hemochron and HemoTec instruments are tabulated in tables 1-4. In all cases, the controls give highly reproducible results.
Since Hemochron commonly employs two activators for the ACT test, celite and glass beads, the results were broken down into two tables, which also demonstrate good precision. The precision achieved using a single lot of controls is illustrated in tables 3 and 4. HemoTec uses kaolin as an activator. HemoTec's high- and low-range cartridges differ in concentration. Tables 5 and 6 illustrate the precision achieved using these tests. This study was performed using two different lots of controls; thus, the absolute times are not comparable. However, each activator level shows good reproducibility.
Instrument reproducibility studies were performed using sufficient controls, when reconstituted and mixed, to perform 10 assays. Since the control material was the same throughout the testing, instrument variation can be measured. The coefficient of variation for the instrument was similar to the overall performance for the control (as shown in Table 5). No drift of values during analysis was detected. Elapsed time stability studies were performed hourly for 5 hr, and no statistically significant change in values was observed. This stability aspect is especially useful if the analyst is interrupted during the testing procedure.
When the entire package of controls, illustrations, and instructions were implemented at a nearby hospital that uses Hemochron instruments, the program was well received. Table 5 shows the data obtained by nurses in critical-care units, cardiac catheterization laboratories, etc. Data collected on the same lot of material at a second beta test site on a HemoTee instrument are tabulated in Table 6.
Two lots of commercially available controls are now nearing their expiration date. The values being recovered on these controls after two years have not changed. This result was predicted based on intensive, accelerated heat-aging studies conducted before the product was released for either beta testing or commercial use.
Conclusion: The major problems of quality control of near-patient-care ACT testing have been identified, addressed, and solved. To achieve this end result, an education program; an illustrated instruction procedure; and a stable, reproducible control were developed. This control is designed to provide long-term continuity, allowing meaningful quality control charts and Youden graphs to be generated. The program enhances the test's utility and operator confidence. As in any successful laboratory program, the one who benefits is the patient, whose care is improved when better outcomes are achieved.
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