Data processing: measuring – calibrating – or testing – Measurement system – Performance or efficiency evaluation
Reexamination Certificate
1999-11-05
2003-09-30
Hoff, Marc S. (Department: 2857)
Data processing: measuring, calibrating, or testing
Measurement system
Performance or efficiency evaluation
C073S073000, C374S102000
Reexamination Certificate
active
06629057
ABSTRACT:
BACKGROUND OF THE INVENTION
Monitoring of blood samples for clinical indicators, such as glucose levels, cholesterol levels and coagulation times, is medically imperative to properly treat patients undergoing drug therapy and to safeguard the health of patients with chronic conditions. For example, such monitoring is used with oral anticoagulant therapy. Oral anticoagulants are used to treat patients with a trial fibrillation, deep vein thrombosis (DVT), artificial heart valves, post-myocardial infarction and other cardiovascular disorders. These medications prevent blood clots which can cause thromboembolic events, such as stroke, recurrent myocardial infarction and pulmonary embolism. However, oral anticoagulant drug actions are highly variable requiring individualized management of each patient's treatment. The most common method of managing such treatment is by using a prothrombin time test. Here, a blood sample is taken and is subject to a reagent, thromboplastin, which initiates the clotting cascade. The time in which the blood takes to clot is measured by an analytical machine.
Traditionally, such testing was undertaken in centralized laboratories, where typically one or more full time medical technologists administered to various types of automated analytical machines. However, as technology has advanced, it has become both feasible and medically necessary to take certain tests out of the centralized clinical laboratory and into the hands of patients and physicians. Some tests, such as blood glucose, must be performed so frequently (several times a day) as to make centralized testing impractical for most diabetics. Other tests, such as the prothrombin time testing, must also be performed at a high frequency (optimally weekly) and utilize samples that tend to deteriorate rapidly, over several hours and thus are less suited for centralized laboratories.
Therefore, simple, reliable, point-of-care tests have been developed. A blood sample is taken, often obtained by finger stick methods, and placed on a disposable test element (test strip) containing the test reagents, usually stored in a dry form on the test element. The test element is then analyzed by a small, portable electronic analyzer device (meter) which outputs the testing result. To ensure that the testing result is accurate, the analyzer system (meter plus reagent) must undergo routine quality control (QC) testing. Erroneous testing results may be due to reagent degradation, instrument failure, mechanical or electrical malfunction or operator misuse.
In centralized laboratories, such QC testing is typically undertaken on a daily basis by using “liquid controls”. These controls consist of samples of one or more analytes with known values. If the analytical machine or the reagents malfunction, for whatever reason, the liquid controls will have an unexpected value. This result will inform the manufacturer or operator that there is a problem, however it will not reveal the underlying failure mode for the system.
Although daily liquid QC testing is quite appropriate for full time professionals in labs that test many patients, it can triple the cost and time per test in the point-of-care environment. This can raise the barrier of such testing so high that the tests are not used, even when they are needed. In addition, many point-of-care systems use disposable, one-time-use test elements containing dry reagents. Because such dry-reagent tests are unitized, daily liquid QC tells the user only that the disposable unit just tested was good. It does not guarantee that the next unitized test will be good.
Due to the limitations in QC testing, patient use of monitoring systems has been significantly impeded. Home prothrombin time tests, such as the Roche-Boehringer Coaguchek, became available for use in America in 1997. However, the adoption of such tests was slowed because of the requirement that each patient perform two levels of liquid QC testing each time the test was used, compounding the time and cost of each test. But the highest cost is to the health of the patient. Patients denied access to prothrombin time tests, due to burdensome liquid QC requirements, may not receive proper anticoagulation treatment. For example, a recent US government patient outcomes research (PORT) study estimated that for a trial fibrillation alone, 40,000 excess strokes per year occurred due to sub-optimal anticoagulation treatment. Patients suffering from a trial fibrillation have a 4.3% chance of having a stroke each year. Warfarin, an oral anticoagulant, can reduce the incidence of stroke in these patients by 83%. However, numerous studies have shown that warfarin has a narrow therapeutic range. Too little warfarin is ineffective and too much can cause bleeding. Thus, monitoring by frequent prothrombin time tests is imperative. And, the results of such monitoring must be accurate. Thus, there is a need for improved methods of quality assurance testing.
SUMMARY OF THE INVENTION
The present invention provides improved systems and methods for verifying accurate test performance of monitoring systems, particularly for point-of-care service. Such monitoring systems typically include a test element containing the test reagent(s), and an electronic analyzer device. A blood or other patient sample is applied to the test element, which is introduced to the analyzer. As the reaction proceeds, the analyzer stores the data and outputs the testing result. Accuracy in the result is dependent upon proper functioning of both the test element and the analyzer. The systems of the present invention provide indicators to evaluate the integrity of the test elements and a verification device to evaluate the performance of the analyzer. Such systems may be provided as kits with instructions for use.
The method of the present invention tests both for proper status and functioning of the test element and of the electronic system without destruction or consumption of any of the system components or reagents. Most disposable, test elements are comprised of dry reagents. Such dry reagent test elements are usually made in the factory in high volumes, and are subjected to a high degree of statistical quality control. The test elements are developed to have a known shelf life and are individually unit packed in sealed foil containers. Assuming that the test elements are competently manufactured, which is addressed by normal medical GMP regulations and systems, the predominant failure modes of the test elements are exposure to environmental degradation factors during shipping and storing. Specifically, the reagents comprising the test elements may suffer degradation by exposure to excess humidity or temperature leading to testing malfunction. To confirm that environmental degradation has not occurred, indicators are provided. Such indicators include, but are not limited to, a moisture indicator and/or a time-temperature indicator.
Each testing element may be packaged with its own drying agent packet which serves as a moisture indicator. Typically, the drying agent is a desiccant which changes color when it has reached capacity. The desiccant may be blue in its initial state. An increase in humidity causes the desiccant to absorb the extra moisture. At which point the desiccant is replete, the hue changes to another color, such as pink. Such a color change indicates that the testing element has been exposed to excess humidity and the dry reagent(s) may not function properly. Such use of indicating desiccants is fairly common in the diagnostics industry.
The testing elements may be further packaged with a time-temperature indicator (TTI). The characteristics of the TTI are designed to match the time-temperature stability characteristics of the degradable material, in this case the test element, as closely as possible within a conservative margin. The TTI progressively changes state over time as a function of temperature. Thus, the TTI will reveal if the package has been exposed to extreme temperature conditions during shipping and storage. A variety of different TT
Downey Thomas D.
Meyer Benjamin G.
Spink Benjamin J.
Zweig Stephen E.
Baran Mary Catherine
Beckman Coulter Inc.
Hill D. David
Hoff Marc S.
May William H.
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