Clinical Chemistry Link to Randox Laboratories Web Site
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 QUICK SEARCH:   [advanced]


     


Clinical Chemistry 48: 42-54, 2002;
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit an electronic Letter to
the Editor about this paper
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (6)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Takemura, Y.
Right arrow Articles by Beck, J. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Takemura, Y.
Right arrow Articles by Beck, J. R.
Related Collections
Right arrow Evidence Based Laboratory Medicine and Test Utilization
(Clinical Chemistry. 2002;48:42-54.)
© 2002 American Association for Clinical Chemistry, Inc.

Yield and Cost of Individual Common Diagnostic Tests in New Primary Care Outpatients in Japan

Yuzuru Takemura1a, Haku Ishida2, Yuji Inoue3 and J. Robert Beck4

1 Department of Laboratory Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan

2 Department of Clinical Pathology, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan

3 Department of Medical Informatics and Decision Sciences, Yamaguchi University School of Medicine, Ube, Yamaguchi 755-8505, Japan

4 Pathology/Information Technology Program, Baylor College of Medicine, Houston, TX 77030-3498

aAuthor for correspondence. Fax 81-42-995-0633; e-mail yutakemu{at}interlink.or.jp.


   Abstract
Top
Abstract
Introduction
Patients and Methods
Results
Discussion
References
 
Background:Appropriate diagnostic testing involves considerations of cost-effectiveness. We examined the cost-effectiveness of individual tests in a panel of tests defined by the Japan Society of Clinical Pathology.

Methods: We studied 540 new, symptomatic primary care outpatients with a set of 30 common diagnostic tests [the Essential Laboratory Tests (2); ELT(2) panel] for clinical evaluation and identification of occult disease. A useful result (UR) of testing was defined as a finding that contributed to a change in a physician’s diagnosis or decision-making relating to a "tentative initial diagnosis" obtained from history and physical examination alone.

Results: The ELT(2) panel testing yielded 398 URs and uncovered 261 occult diseases among 540 patients. In total, 1592 tests contributed to either UR-generation or discovery of occult disease. The cost per effective test (cost required per test that contributed to either definition of effectiveness) ranged from ¥108 (~US$0.92) for total cholesterol to ¥6200 (~$52.50) for chest x-ray. Contribution rates and the cost per effective test varied among disease categories. We restructured panel components considering the effectiveness of each test. Subsets of the ELT(2) would have improved cost-effectiveness and achieved cost savings in five of eight disease categories.

Conclusions: Assembly of tests based on cost-effectiveness can improve clinical efficiency and decrease total cost of panel testing for selected patient groups.


   Introduction
Top
Abstract
Introduction
Patients and Methods
Results
Discussion
References
 
In our previous studies, we analyzed the clinical effectiveness and economic efficiency of common diagnostic test panels, which are advocated by the Japan Society of Clinical Pathology (JSCP)5 1 (1)(2). The test packages, designated the Essential Laboratory Tests (ELT) panels, are composed of the ELT(1) basic test panel and the ELT(2) extensive test panel. The JSCP intends for the ELT(1) panel to be universally ordered irrespective of a patient’s presenting symptoms for evaluation of the patient’s physical condition and for estimation of the presence or absence of a clinically significant disease, whereas the ELT(2) panel test items, including basic tests in the ELT(1) and some optional tests such as chest and abdominal plain x-rays and electrocardiogram (ECG), should be selected in addition to the ELT(1) tests if a primary care physician needs more tests to focus the initial clinical diagnosis at the first clinical visit (3). When a new outpatient is diagnosed as having a significant disease based on the results of the ELT panel testing, the patient is tested with organ- or disease-specific test panels, which include more sophisticated tests to obtain a detailed or definite diagnosis. This step-by-step approach to a final diagnosis is the basic concept of the JSCP.

We have applied the ELT(2) panel to 540 new, symptomatic outpatients in primary care settings for the purpose of clinical evaluation. We developed a relevant measure for the assessment of effectiveness of the ELT panels in the previous study (1). A useful result (UR), a unit of clinical usefulness of testing, was assigned by determining the impact of test results on a physician’s diagnosis or decision-making. Three physicians participated in the determination of URs. If a test result contributed to diagnosis or decision-making, it was deemed useful. The ELT(2) panel yielded 398 URs for 540 patients. In the following study, we further analyzed the efficiency of the ELT panels for identification of occult disease (case finding) 2 because panel testing can lead to opportunistic discovery of occult disease. The ELT(2) panel testing uncovered 276 occult diseases and conditions among 540 patients (2). However, the cost-effectiveness found in these studies did not support universal use of the full ELT(2) panel for either clinical evaluation of a disease or case finding. Consequently, we concluded that (a) selective test combinations should be used for the clinical evaluation of selected patients, and (b) only a few test components can contribute to occult disease identification with an acceptable cost-effectiveness.

Our results did not match the JSCP recommendation for the routine use of the ELT panels for all new patients, although tests are limited to the most common ones in the ELT(1) basic panel. Indeed, in the current movement to avoid unnecessary testing in the United States and other countries, panel testing is discouraged and efforts are made to use more carefully selected individual tests or small groups of tests (4)(5)(6). However, few studies have demonstrated the optimal combinations of common diagnostic tests on the basis of the cost-effectiveness of each test because of difficulties in obtaining suitable cost-effectiveness measures in primary care settings. In the present study, we attempted to further analyze the yield and cost of each ELT(2) panel component. Generation of separate cost-effectiveness data for individual tests will contribute to establishing the most efficacious combinations of common diagnostic tests for selected patient groups, differing from the "empirical" ELT system. Although we demonstrate the cost and effectiveness data in a limited patient population in Japan, the evidence that we present here can be generalized to common tests in most primary care practice settings.


   Patients and Methods
Top
Abstract
Introduction
Patients and Methods
Results
Discussion
References
 
patients
Among all new outpatients who visited the Comprehensive Medicine Clinics, National Defense Medical College, Tokorozawa, Japan and its affiliated hospital from June 1991 to March 1997, 540 patients (250 males and 290 females; age range, 9–83 years), who were seen by three specified primary care physicians, were entered in this study. Two of three physicians participating in the clinical evaluation were certified by the Japanese Boards of Internal Medicine and Clinical Pathology. Any patients presenting with symptoms and seen by these three physicians were included irrespective of the specific symptom or disease category, without any selection process. Those referred from physicians in other medical facilities with test results and/or tentative clinical diagnoses were excluded in advance from the study or not evaluated in the analyses.

As described in our previous studies (1)(2), each patient was given a diagnostic test package corresponding to the ELT(2) panel (see Table 1 ) after the history was taken and a physical examination was performed. The diagnostic sensitivity, specificity, and positive predictive value of each panel component were analyzed in our preliminary study (7). Chest and abdominal plain x-rays, ECGs, and fecal occult blood tests were optional choices. Diagnoses were classified by tentative initial diagnosis (TID), which was made by the primary care physician based on the history and physical examination alone, and the "initial clinical diagnosis", which was established after integrating the results of diagnostic tests. A diagnosis related to a patient’s chief complaint was characterized as the "primary diagnosis or disease", whereas abnormal test results unexpectedly elicited by the ELT(2) panel and not related directly to a patient’s illness led to "additional diagnoses or occult diseases".


View this table:
[in this window]
[in a new window]
 
Table 1. Costs1 for individual common diagnostic tests analyzed in the present study.

ur determination
Clinical usefulness of the ELT panel testing was determined by assessing its impact on a physician’s diagnosis or decision-making. A UR, which is the unit of usefulness of the ELT panel testing, was assigned objectively according to criteria described in our previous study (1). When test result(s) contributed to a change in a physician’s diagnosis or decision-making between the TID obtained from the history and physical examination alone and the initial clinical diagnosis, one UR was assigned for each TID. Briefly, when test results contributed to the establishment of the initial clinical diagnosis relating to a patient’s chief complaint in those with undetermined TIDs, to the negation and/or correction of a TID, or confirmation of a TID clinically suspected, a UR was assigned. In addition, when test results contributed to the evaluation of the nature or severity of a disease and were followed by a change in the physician’s decision-making for the treatment or management of the patient, by additional ordering of organ- or disease-specific tests, by reference to a specialist, or by transfer of the patient to a specific clinic, one UR was also given. A patient may have had more than one UR.

For determination of URs, patients’ medical records were reviewed closely to find any changes or modifications in the clinical diagnosis of, treatment for, or management of a patient before and after interpretation of test results. Additional ordering of organ- or disease-specific diagnostic tests and reference to a specialist after interpretation of the ELT(2) test results were also counted as URs. Three physicians participated in the determination of URs. One of these physicians was a participant in the initial clinical evaluation of the patients. The diagnosis and decision-making of that physician or other physicians were strictly reviewed by the other two examining the assigned URs.

We analyzed test items that contributed to UR-generation and case finding for the establishment of cost-effectiveness of individual common diagnostic tests used in this study. Abnormalities of tests with similar function [e.g., C-reactive protein (CRP) and white blood cell count] usually yielded a single UR unless they contributed to different categories of UR-generation.

assay methods
Assay methods for the common diagnostic tests performed have been described in detail elsewhere (1)(2). Briefly, chemistry tests [total protein, albumin, total cholesterol, triglycerides, glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LD), alkaline phosphatase (ALP), {gamma}-glutamyltransferase (GGT), cholinesterase, serum urea nitrogen, creatinine, uric acid], CRP, and sialic acid were measured simultaneously on an automated multichannel analyzer (Model 736; Hitachi). Because sialic acid is considered a delayed responder to inflammation and shows a movement in the inflammation process different from that of CRP, this test is also adopted in the ELT(2) panel. The complete blood count (CBC) and leukocyte differential count (LDC) were analyzed by an automated blood cell counter (Model E-5000; Sysmex). Serum protein fraction profiles (protein fractions) were analyzed on a Model CTE1200 automated analyzer (Johkoh). Dipstick urinalysis (protein, glucose, occult blood, urobilinogen, bilirubin, ketones, pH, and specific gravity) was performed with Ames reagent strips (Multistix SGL; Miles-Sankyo Co., Ltd.). The standard Westergren method was used for measurement of the erythrocyte sedimentation rate (ESR). Chest and abdominal plain x-rays, ECGs, and fecal occult blood tests were ordered optionally if necessary. Microscopic examination of peripheral blood smears was performed on samples with any values of CBC outside the reference intervals or qualitative abnormalities detected by the analyzer.

Diagnoses were established taking into account the reference values that were adopted in the hospitals in which this study was carried out. However in this study, not only test values outside of reference intervals but also those within the intervals that indicated negative results against a TID could contribute to UR-generation because the latter may have URs for negation and/or correction of the TID.

New outpatients visited the hospital in a postprandial condition. The clinical evaluation for these patients was usually done during the morning and early afternoon. Some patients may have consumed alcoholic beverages the night before the visit, which increased triglyceride values. Although our previous study demonstrated the diagnostic value of serum glucose for diabetes mellitus in our patients if it was >7.77 mmol/L (>140 mg/dL) even postprandially (7), the triglyceride values fluctuated widely with ingestion of food or alcohol, frequently leading to a misdiagnosis of hyperlipidemia. Therefore, triglycerides were not analyzed for clinical evaluation of a patient’s illness or for identification of occult disease in this study.

costs and cost-effectiveness of individual diagnostic tests
Because of a lack of availability of cost data at the National Defense Medical College, costs 3 were calculated by considering all expenditures required to obtain test results at the Kawasaki Medical School Hospital (Kurashiki, Japan). These included costs for test reagents, consumptive materials required for operation of analyzers, computers and printers, disposables needed for specimen collection and sample analysis, equipment amortization, and personnel expenses for medical technologists. Indirect costs, which cover the laboratory facility and electricity (overhead or fixed costs), were excluded. Our cost data consisted of two portions: the test-specific cost (cost of reagents and consumptive materials specific to each test), and the common baseline cost, the latter being required for analyzer operation, including equipment amortization and personnel expenses, and being shared with all tests simultaneously performed.

The unit cost of a test measured by the automated multichannel analyzer (14 chemistry test items, CBC, CRP, and sialic acid) was calculated by adding the test-specific cost to the baseline cost divided by the number of tests measured simultaneously. In most cases in this study, we simultaneously measured 16 tests on the Hitachi automated multichannel analyzer, so that 1/16 of the common baseline cost (¥331.5/16) was allocated to each unit cost of these tests. Because the albumin/globulin ratio (A/G) was actually obtained from the total protein and albumin values, the unit cost for the A/G was defined as the sum of those of both tests. Unit costs for the individual tests are shown in Table 1Up .

The contribution rate of a test to UR-generation or identification of occult disease is expressed as the number of tests that either yield a UR or contribute to case finding per total tests performed. In other words, this is the fraction of the tests that produced either effectiveness. The cost per effective test (or cost-effectiveness of a test) is defined as the cost required per effective test, which produces either effectiveness. It is valid to calculate the cost per effective test by dividing the costs for total tests by the total number of effective tests. The incremental cost-effectiveness ratio is defined as the incremental cost for new panel testing per additional effective test gained against the ELT(1) baseline panel ({Delta}cost/{Delta}effective test). In this study, we assumed that the two categories of effectiveness that a test can produce have the same weight.

The contribution rate of each test and the cost per effective test were also calculated in each disease category. Because a UR was assigned against each TID in our previous study (1), a finding of occult disease was concordantly reanalyzed in each TID in the present study. Thus, 601 tests contributed to the detection of 323 occult diseases among 633 TIDs, allowing the overlap of 146 effective tests for 62 occult conditions in multiple disease categories.

redesign of test combinations on the basis of effectiveness and cost-effectiveness of new test panels
To pursue a test combination that provids maximal effectiveness at a minimal cost increment in each disease category, we reconstructed panel component tests, considering contribution rates of the individual tests to either effectiveness. Costs for redesigned panel testing were calculated basically by totaling the costs of each panel component in Table 1Up . For test items simultaneously measured on the automated multichannel analyzer, the total cost of such tests was calculated by adding each test-specific cost to a single common baseline cost required for their testing. For example, when a panel included three chemistry tests, the test-specific costs of these three items were added to a common baseline cost (¥331.5 in Table 1Up ). Because the automated blood cell counter used in this study automatically outputs the results of all CBC items, selection of only one item of the CBC required that the costs for all effective tests produced by the aggregate CBC be included. Cost-effectiveness parameters of the redesigned panels {overall contribution rates (total number of effective tests/total number of tests performed for patients in each disease category), cost per effective test values, and incremental cost-effectiveness ratios of new panels against the JSCP baseline panel [ELT(1)]} were calculated based on the actual patient data in this study.


   Results
Top
Abstract
Introduction
Patients and Methods
Results
Discussion
References
 
contribution rates of individual tests and cost per effective test
As shown in our previous studies (1)(2), 1137 tests in the ELT(2) panel yielded 398 URs, and 511 tests uncovered 276 occult diseases among 540 new outpatients. Because 23 patients who had tentative diagnoses made by other medical facilities were incorporated in the latter study (2), we excluded these cases for analyses of both categories of effectiveness in the present study. Thus, 455 tests contributed to the identification of 261 occult diseases among patients. Accordingly, there were 1592 total effective tests, which either yielded a UR or contributed to case finding, among 12 646 tests performed for all patients in the present study.

Because test abnormalities would increase with the age of the patients, the ELT(2) panel testing uncovered more occult diseases in patients >=60 years of age (0.71 occult diseases/patient) than in those <60 years (0.47 occult diseases/patient). However, for UR-generation by tests, this relationship was less obvious: the ELT(2) panel yielded URs at a rate of 0.85 URs/patient in the older age group compared with 0.71 URs/patient in the younger group.

Table 2 shows the contribution rates of the individual tests to either category of effectiveness and their cost per effective test values in the patients. Contribution rates of the respective tests to UR-generation ranged from 0.252 for CRP to 0.006 for uric acid, and the contributions to case finding ranged from 0.184 for total cholesterol to 0.004 for serum urea nitrogen and creatinine when optional test items were excluded. The cost per test that yielded a UR varied greatly, from ¥116 (~US $0.98) for CRP to ¥7731 (~$65.50)/effective test for urine sediment. The cost per test that contributed to case finding ranged from ¥153 (total cholesterol) to ¥12 739 per effective test for case finding (sialic acid). The optional tests contributed little to case finding. When we integrated both types of effectiveness of tests, total cholesterol produced the best cost per effective test (¥108), followed by CRP (¥113), and ALT (¥154/effective test). Dipstick urinalysis, urine sediment examination, and creatinine were the least "cost-effective" tests in the aggregate.


View this table:
[in this window]
[in a new window]
 
Table 2. Yield and cost of individual common diagnostic tests performed for the clinical evaluation of patient’s illness and the case finding among 540 new, symptomatic primary care outpatients.

The cost-effectiveness of fecal occult blood tests, chest and abdominal x-rays, and ECGs was very poor despite being selectively ordered by physicians because of the higher testing costs for and the lower prevalence of the occult diseases detected by these tests.

contribution rates of individual tests to ur-generation or case finding in each disease category
Fig. 1 illustrates the contribution rates of individual tests to UR-generation and identification of occult disease in eight major disease categories. Because there were very few URs in the neurologic, miscellaneous (others), and diagnosis-undetermined disease groups (1), the contribution rates in these disease categories are not shown in Fig. 1 . There were large differences in contribution rates of the individual tests to UR-generation in different disease categories. In general, the ELT(2)-specific test items contributed more frequently to identification of occult disease compared with the basic tests in the ELT(1) panel. Tests that yielded a UR were fewer than those contributing to case finding in the gastrointestinal, neurologic, cardiovascular, and miscellaneous (other) disease groups and in patients with undetermined diagnoses. In particular, tests that detected an occult disease were much more frequent than tests generating a UR in patients with cardiovascular TIDs (90 vs 35 tests, respectively).




View larger version (81K):
[in this window]
[in a new window]
 
Figure 1. Contribution rates of the ELT(1) and ELT(2) items to either UR-generation (checked columns) or identification of occult disease (filled columns) in eight major disease categories.

(A), infectious or inflammatory diseases; 626 tests contributed to 179 URs and 132 tests to find 75 occult diseases in patients with 177 TIDs. (B), gastrointestinal diseases; 69 tests for 31 URs and 81 tests for 40 occult diseases in 84 TIDs. (C), cardiovascular diseases; 35 tests for 27 URs and 90 tests for 48 occult diseases in 60 TIDs. (D), metabolic/endocrine diseases; 45 tests for 17 URs and 20 tests for 12 occult diseases in 25 TIDs. (E), liver/pancreatobiliary diseases; 125 tests for 43 URs and 24 tests for 13 occult diseases in 33 TIDs. (F), hematologic diseases; 68 tests for 38 URs and 19 tests for 9 occult diseases in 23 TIDs. (G), renal/urinary tract diseases; 41 tests for 13 URs and 19 tests for 9 occult diseases in 9 TIDs. (H), respiratory diseases; 29 tests for 9 URs and 13 tests for 6 occult diseases in 7 TIDs. BUN, serum urea nitrogen; RBC, red blood cell; WBC, white blood cell count. The top 9 tests along each vertical axis are the components of the ELT(1) panel; the next 20 tests are ELT(2)-specific test items, including 4 optional tests (fecal occult blood test, chest and abdominal x-rays, and ECGs; shown at the bottom).

To illustrate the best combination of tests for selected patient groups, the sum of both contribution rates of a test is shown in Fig. 1Up . Total cholesterol frequently contributed to UR-generation and case finding in most patient groups, whereas contribution rates of other tests were highly dependent on the patient groups.

cost per effective test in different patient groups
The cost per effective test in each disease group is shown in Table 3 . The cost per effective test differed depending on the TID categories. The difference was minimal in total cholesterol testing, which ranged from ¥49 to ¥157 per effective test, as anticipated from the contribution rates shown in Fig. 1Up . Dipstick urinalysis and urine sediment examination showed an acceptable cost-effectiveness only in the renal/urinary tract diseases (¥410 and ¥371/effec-tive test, respectively). A similar result was observed with glucose, which produced the best cost-effectiveness in the metabolic/endocrine disease group (¥96/effective test). Among the inflammation indicators included in the ELT(2) panel, CRP revealed the best cost-effectiveness in the infectious or inflammatory disease group (¥57/effective test), followed by the white blood cell count, sialic acid, ESR, and protein fractionation. CRP was ~30-fold more cost-effective when applied to patients with infectious or inflammatory diseases than to those with cardiovascular diseases. The LDC also demonstrated good cost-effectiveness in patients with infection or inflammation (¥94/effective test). ALT and cholinesterase produced considerably better cost-effectiveness values not only in the liver/pancreatobiliary diseases, but also in other disease groups because these two tests could contribute to identifying asymptomatic patients with liver dysfunction.


View this table:
[in this window]
[in a new window]
 
Table 3. Cost per test that either yielded a UR or contributed to case finding in each disease category.

Cost per test that either yielded a UR or contributed to case finding1

In the case of the optional tests, the cost-effectiveness values were poor even in the cardiovascular disease group, in which chest x-ray and ECG yielded URs at their highest frequencies (0.29 and 0.38/test performed, respectively; Fig. 1Up ).

reconstruction of test panels on the basis of effectiveness of individual common diagnostic tests
Considering contribution rates of individual tests to UR-generation and identification of occult disease in each disease category (Fig. 1Up ), we redesigned the test panels to have an acceptable effectiveness in the aggregate for the respective patient groups (Table 4 ). The reconstructed test combinations demonstrated overall contribution rates ranging from 0.346 for the renal/urinary tract disease and respiratory disease groups to 0.106 for the gastrointestinal disease group. All test combinations for the gastrointestinal disease group failed to show satisfactory contribution rates because of the small number of tests that yielded a UR in this group. There were very few effective tests in patients with the neurologic TIDs, so it was difficult to analyze the best test combination with clinical significance for this disease group. Otherwise, new panels substantially improved the overall contribution rates compared with the ELT(1) panel testing.


View this table:
[in this window]
[in a new window]
 
Table 4. Test combinations redesigned based on contribution rates of individual common diagnostic tests to UR-generation and case finding.

The cost-effectiveness parameters of the redesigned panels are shown separately in Table 5 compared with those of the ELT(1) baseline panel. Although the addition of the automated multichannel analyzer-based tests did not yield large cost increments, x-rays and ECGs substantially increased costs [compare the total costs required for testing of the redesigned panels for cardiovascular and respiratory disease groups with that for the ELT(1) panel, which does not include the optional tests]. Thus, the incremental cost-effectiveness ratios of these new panels against the ELT(1) baseline panel were high (¥1249 and ¥493 per additional effective test gained for the cardiovascular and respiratory panel, respectively), whereas other redesigned panels could achieve cost savings compared with the ELT(1) baseline panel. The exception was the renal/urinary tract disease panel, which was cost-effective but did not cost-saving.


View this table:
[in this window]
[in a new window]
 
Table 5. Cost-effectiveness parameters of redesigned panels for the respective patient groups compared to those of the ELT(1) baseline panel.


   Discussion
Top
Abstract
Introduction
Patients and Methods
Results
Discussion
References
 
In our previous studies (1)(2), we focused on evaluating the cost-effectiveness of the ELT panel testing system. We considered the JSCP ELT(1) panel as the basic test package to be used for clinical evaluation of new patients. Nevertheless, a question arose regarding the effectiveness of the ELT(1) panel. Although, according to the JSCP, the ELT(1) panel is the test package to be performed for all new outpatients irrespective of disease categories, we demonstrated a wide difference in effectiveness among patients with different TIDs (1). In addition, the ELT(1) panel scarcely contributed to identification of occult disease (2). We wondered whether the ELT(1) panel should be used routinely for every new outpatient to obtain minimally essential information for a disease or a patient’s physical condition. The question prompted us to analyze the cost and effectiveness of the individual diagnostic tests not only in the extensive ELT(2) panel, but also in the basic panel. We further extended the present study to build new test combinations that were not based on the ELT(1) panel but had definite evidence to justify their utilization, for the respective patient groups, with step-by-step analyses.

We assumed the costs of tests simultaneously measured on an automated multichannel analyzer. Our cost data were composed of two portions: the test-specific cost (the cost of reagents required for testing) and the common baseline cost, the latter being shared for all tests performed simultaneously and including costs for analyzer operation, equipment amortization, and for personnel labor involved in the testing process. The unit costs of the automated multichannel analyzer-based chemistry test items, CBC, CRP, and sialic acid were calculated by adding the test-specific cost to the baseline cost divided by the number of tests that were analyzed simultaneously. The lower costs of these tests resulted from the economy of simultaneous measurements on such multichannel analyzers. For example, when we calculated costs in a different way, in which the cost of a test was a simple sum of both portions ("a la carte" testing, i.e., assuming that each test is measured separately by the same analyzer), the cost-effectiveness of these tests became strikingly worse. Indeed, profile testing produced a big cost saving compared with a la carte test ordering (8). Medicare billing regulations allow some small panel testing based on the automated multichannel analyzers because of their apparent economy (9). In most cases in this study, we simultaneously performed 16 tests, including chemistry tests, CRP, and sialic acid, on an automated multichannel analyzer; thus, the a la carte testing cost does not reflect the actual cost for our patients. However, it should be noted that testing costs, which were calculated by the former method that we adopted in this study, vary depending on the number of tests measured simultaneously, increasing the unit costs when analyzed with fewer test items. In this context, our cost data in this study cannot be generalized to other primary care settings where different numbers of tests may be combined.

The effectiveness and costs of the most common tests in the ELT(1) panel differed widely among patients with different TIDs (Fig. 1Up and Table 3Up ). For example, dipstick urinalysis showed an acceptable cost-effectiveness only for patients with renal/urinary tract diseases [¥410 (~US$3.80)/effective test], although urinalysis has long been considered an important screening test in adults and children. Screening urinalysis seldom yields important and unexpected findings in either outpatient (10)(11) or hospital settings (12)(13). Thus, routine screening of all adults with dipstick urinalysis is not recommended in the United States at present because of the low incidence of significant disease (14).

For disease screening with urinalysis, aggregate costs were disproportionately high and outweighed their clinical effectiveness (15). In addition, routine urinalysis frequently provides nonspecific abnormal results, which do not lead to a change in a physician’s diagnosis and decision-making but, conversely, sometimes lead to unnecessary, additional testing. Our results support the common diagnostic test utilization guideline approved by the American College of Physicians (ACP), which states that there is little value of urinalysis in the diagnoses of various systemic diseases (16). Similarly, there were >10-fold disparities in the cost per effective test of other ELT(1) tests between the patient groups in which tests yielded the highest and the lowest effectiveness. Our results demonstrate that there was little effectiveness produced by these common tests in the gastrointestinal, neurologic, and cardiovascular disease groups (Fig. 1Up ). Thus, our results clearly indicate a need to redesign the common diagnostic test packages, assembling only tests with a distinct cost-effectiveness for respective patient groups.

The goal of this and our previous studies (1)(2)(7)(17) was to establish the best combinations of common diagnostic tests for specific patient groups. Considering the contribution rates of the individual tests to UR-generation and identification of occult disease in each disease category (Fig. 1Up ), we built new, smaller panels for respective patient groups in primary care practice (Table 4Up ) and analyzed their cost-effectiveness parameters (Table 5Up ). Each new panel demonstrated an improved effectiveness (overall contribution rate). Cost-effectiveness parameters for new panel testing revealed cost savings in five of eight disease categories (except for the cardiovascular, respiratory, and renal/urinary tract disease groups) against the ELT(1) panel. Higher costs for optional tests (chest x-ray and ECG) incorporated into new panels for the cardiovascular and respiratory disease groups increased the incremental costs. These optional tests were critically important for some patients, but not for all in these disease groups. Thus, more careful selection of patients for ordering these tests will be required to improve the cost-effectiveness of the cardiovascular and respiratory panels.

The new panels include plural tests with similar functions. For example, CRP and white blood cell count, which should increase in the early phase of inflammation, were incorporated into the infection/inflammation panel. Although CRP and/or white blood cell count yielded URs in 106 of 177 patients with infection/inflammation TIDs, only 54% of the patients showed parallel results for both inflammation indicators, and the remainder had only one positive result (32% for CRP alone and 14% for white blood cell count alone). In addition, dissociated movement of these inflammation indicators led to UR-generation in some patients in estimating the nature of the infection (e.g., viral origin). Thus, we could not select one but omit the other unless one showed extremely low cost-effectiveness. Moreover, duplication of tests that assess somewhat different physiologic functions (e.g., cholinesterase and GGT) might be allowable. Among 91 patients in whom cholinesterase and/or GGT contributed to either UR-generation or case finding, both results were positive in only 23% of patients, whereas 51% showed positive cholinesterase alone and 25% showed positive GGT alone. Sialic acid may be substituted for ESR, which sometimes shows a nonspecific acceleration without clinical significance. Because these two tests are considered to reflect a later phase of inflammation than does CRP (18), it is clinically valid to add either ESR or sialic acid to the panel as well as CRP. Sialic acid is less popular than ESR, but it can be measured on an automated multichannel analyzer with other chemistry tests.

ALT and cholinesterase produced considerably favorable cost-effectiveness values (Table 2Up ). In fact, our earlier study demonstrated a higher prevalence of chronic viral hepatitis, which subsequently progresses to liver cirrhosis and hepatocellular carcinoma, in Japan than in Western countries (19), prompting the need to find asymptomatic patients with chronic liver diseases. In this context, cholinesterase was helpful in distinguishing possible fatty changes of the liver from hepatitis virus-related chronic liver diseases in patients with increased transaminases. On the other hand, the lower prevalence of diabetes mellitus in Japan produced an unfavorable cost-effectiveness values for serum glucose in patients with a TID other than the metabolic/endocrine diseases, despite the ACP guideline that recommends serum glucose for screening diabetes mellitus in asymptomatic adults (20). In the case of cholesterol screening, our results entirely support the clinical guidelines issued by the ACP (21)(22) or the National Cholesterol Education Program (23), which state that all adults older than 20 years with hypercholesterolemia be identified, educated, and treated. Thus, total cholesterol should be incorporated into all test combinations reconstructed.

We should clarify the limitations of this study for future extensive prospective studies to verify our results presenting here. The first limitation is that this study analyzed the yield and costs of common tests only during the early diagnostic process; thus, no long-term cost or effectiveness data were included. Ideally, a cost-effectiveness analysis should be linked not only to the testing itself, but also to the costs and benefits of patient care and treatment after a diagnosis is established, although these long-term effects of testing will not be easily obtained in the settings of primary care practice. Although the prevalence of colorectal cancer is low in the general population, identifying this disease early may be of much greater benefit to patients than identifying common diseases. This will be evidenced only with analyses of the long-term effects of testing. The second limitation is that we did not analyze the negative effects of testing, e.g., incremental costs and disadvantages resulting from a misdiagnosis. Similarly, abnormalities unexpectedly uncovered by tests but with little clinical significance may lead to the ordering of additional unnecessary, sophisticated (and sometimes harmful) tests, increasing medical expenditures. The third limitation is that the patient population in this study was not large and was insufficient to address conclusively certain groups of patients, such as those with renal/urinary tract and respiratory diseases. In addition, the numbers of physicians participating in the clinical evaluation and analyses were also small. Studies involving more patients in multiple institutions will be necessary for more extended analysis.

In conclusion, analyses of the effectiveness and costs of individual common diagnostic tests led to the establishment of new test panels, which differ from the ELT panel system and give maximal effectiveness at an acceptable cost, for selected patient groups. Although cost data will not be identical in different primary care settings with different numbers of tests combined, evidence elicited from this study can guide the optimal usage of common diagnostic tests on the basis of cost-effectiveness.


   Acknowledgments
 
This study was supported in part by grants from the Clinical Pathology Research Foundation of Japan, from the Pfizer Health Research Foundation, and from the Kurozumi Medical Foundation. We are grateful to Drs. Yasumasa Kajihara, Reishi Izumi, Katsunori Koguchi, Mitsugi Okura, and Kuniki Takamatsu (Kawasaki Medical School, Kurashiki, Japan) for providing cost data for x-rays and laboratory tests. We also thank Drs. Nobuo Kugai, Hiroyuki Kobayashi, and Hirokazu Matsuta (National Defense Medical College, Tokorozawa, Japan) for assistance in collecting clinical data.


   Footnotes
 
1 Nonstandard abbreviations: JSCP, Japan Society of Clinical Pathology; ELT, Essential Laboratory Tests; ECG, electrocardiogram; UR, useful result; TID, tentative initial diagnosis; CRP, C-reactive protein; AST, aspartate aminotransferase; ALT, alanine aminotransferase; LD, lactate dehydrogenase; ALP, alkaline phosphatase; GGT, {gamma}-glutamyltransferase; CBC, complete blood count; LDC, leukocyte differential count; ESR, erythrocyte sedimentation rate; A/G, albumin/globulin ratio; and ACP, American College of Physicians.

2 Definitions for descriptions used specifically: case finding, efforts to detect disease in patients seen for unrelated symptoms or diseases; contribution rate of a test, the fraction of tests that yield either a UR or contribute to identification of occult disease, divided by the total number of tests performed in each disease category; cost per effective test (or cost-effectiveness of a test), cost required per test that yields either a UR or contributes to identification of occult disease; incremental cost-effectiveness ratio, incremental cost for new panel testing per additional effective test gained against the baseline panel ({Delta}cost/{Delta}effective test).

3 Cost (¥) can be converted to US dollars at a rate of US$1.00 = ¥118.00 on February 1, 2001.


   References
Top
Abstract
Introduction
Patients and Methods
Results
Discussion
References
 

  1. Takemura Y, Ishida H, Inoue Y, Beck JR. Common diagnostic test panels for clinical evaluation of new primary care outpatients in Japan: a cost-effectiveness evaluation. Clin Chem 1999;45:1752-1761.[Abstract/Free Full Text]
  2. Takemura Y, Ishida H, Inoue Y, Kobayashi H, Beck JR. Opportunistic discovery of occult disease by use of test panels in new, symptomatic primary care outpatients: yield and cost of case finding. Clin Chem 2000;46:1091-1098.[Abstract/Free Full Text]
  3. Hashimoto N. Essential laboratory tests: a proposal. Subcommittee of the Uses of Clinical Laboratory Tests in Daily Primary Medical Care, the Japan Society of Clinical Pathology eds. The uses of clinical laboratory tests in daily primary medical care 1st ed. 1989:1-16 The Japan Society of Clinical Pathology Tokyo. .
  4. Takemura Y, Beck JR. Laboratory testing under the managed care dominance in the United States. J Clin Pathol 2001;54:89-95.[Abstract/Free Full Text]
  5. Kricka LJ, Parsons D, Coolen RB. Healthcare in the United States and the practice of laboratory medicine. Clin Chim Acta 1997;267:5-32.[ISI][Medline] [Order article via Infotrieve]
  6. Robinson A. Rationale for cost-effective laboratory medicine. Clin Microbiol Rev 1994;7:185-199.[Abstract/Free Full Text]
  7. Takemura Y, Kobayashi H, Kugai N, Sekiguchi S. The results of the "Essential Laboratory Tests" applied to new outpatients—re-evaluation of diagnostic efficiencies of the test items. Jpn J Clin Pathol 1996;44:555-563.
  8. Lehmann C, Leiken A. Cost of laboratory ordering strategies. Lab Med 1985;15:759-760.
  9. Root CB. Medicare coding and reimbursement for clinical laboratory services. Clin Chem 1998;44:1713-1727.[Abstract/Free Full Text]
  10. Fraser CG, Smith BC, Peake MJ. Effectiveness of an outpatient urine screening program. Clin Chem 1977;23:2216-2218.[Abstract/Free Full Text]
  11. Froom P, Ribak J, Benbassat J. Significance of microhematuria in young adults. BMJ 1984;288:20-22.
  12. Akin BV, Hubbell FA, Frye EB, Rucker L, Friis R. Efficacy of the routine admission urinalysis. Am J Med 1987;82:719-722.[ISI][Medline] [Order article via Infotrieve]
  13. Lawrence VA, Kroenke K. The unproven utility of the preoperative urinalysis: clinical use. Arch Intern Med 1988;148:1370-1373.[Abstract]
  14. Thaller TR, Wang LP. Evaluation of asymptomatic microscopic hematuria in adults. Am Fam Physician 1999;60:1143-1152.[ISI][Medline] [Order article via Infotrieve]
  15. Lawrence VA, Gafni A, Gross M. The unproven utility of the preoperative urinalysis: economic evaluation. J Clin Epidemiol 1989;42:1185-1192.[ISI][Medline] [Order article via Infotrieve]
  16. Komaroff AL. Urinalysis and urine culture in women with dysuria. Sox HC, Jr eds. Common diagnostic tests: use and interpretation 2nd ed. 1990:286-301 American College of Physicians Philadelphia. .
  17. Takemura Y, Ishida H, Inoue Y, Beck JR. A cost-effectiveness analysis of a pre-visit testing system for new outpatients in primary care medicine [in Japanese with English abstract]. Jpn J Clin Pathol 2000;48:269-275.
  18. Takemura Y, Matsuta H, Kugai N, Sekiguchi S. Application of inflammation markers in the "Essential Laboratory Tests" to new outpatients and analysis for the efficacious selection of these items [in Japanese with English abstract]. Jpn J Clin Pathol 1994;42:1055-1061.
  19. Takemura Y, Kobayashi H, Kamachi M, Sekiguchi S, Shioikari M, Tamura M. Pathogenesis-screening tests for liver dysfunction in the asymptomatic patients with increased ALT values and their diagnostic efficiencies in primary care medicine [in Japanese with English abstract]. Jpn J Clin Pathol 1996;44:261-266.
  20. Cebul RD, Beck JR. Biochemical profiles: applications in ambulatory screening and preadmission testing of adults. Sox HC, Jr eds. Common diagnostic tests: use and interpretation 2nd ed. 1990:344-366 American College of Physicians Philadelphia. .
  21. . American College of Physicians. Clinical guideline, part 1: guidelines for using serum cholesterol, high-density lipoprotein cholesterol, and triglyceride levels as screening tests for preventing coronary heart disease in adults. Ann Intern Med 1996;124:515-517.[Abstract/Free Full Text]
  22. Garber AM, Browner WS, Hulley SB. Clinical guideline, part 2: cholesterol screening in asymptomatic adults, revised. Ann Intern Med 1996;124:518-531.[Abstract/Free Full Text]
  23. . National Cholesterol Education Program. Second report of the expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel II). Circulation 1994;89:1333-1345.[Medline] [Order article via Infotrieve]



The following articles in journals at HighWire Press have cited this article:


Home page
J. Clin. Pathol.Home page
Y Takemura, K Ebisawa, H Kakoi, H Saitoh, H Kure, H Ishida, and M Kure
Antibiotic selection patterns in acutely febrile new outpatients with or without immediate testing for C reactive protein and leucocyte count
J. Clin. Pathol., July 1, 2005; 58(7): 729 - 733.
[Abstract] [Full Text] [PDF]


Home page
Clin. Chem.Home page
Y. Takemura, H. Kakoi, H. Ishida, H. Kure, Y. Tatsuguchi-Harada, M. Sugawara, Y. Inoue, K. Ebisawa, and M. Kure
Immediate Availability of C-Reactive Protein and Leukocyte Count Data Influenced Physicians' Decisions to Prescribe Antimicrobial Drugs for New Outpatients with Acute Infections
Clin. Chem., January 1, 2004; 50(1): 241 - 244.
[Full Text] [PDF]


This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit an electronic Letter to
the Editor about this paper
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (6)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Takemura, Y.
Right arrow Articles by Beck, J. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Takemura, Y.
Right arrow Articles by Beck, J. R.
Related Collections
Right arrow Evidence Based Laboratory Medicine and Test Utilization


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS