Methodology in diagnostic laboratory test research in Clinical Chemistry and Clinical Chemistry and Laboratory Medicine.
In 1996, Reid et al. (3) pointed out serious methodologic limitations of research on diagnostic tests published in the most prestigious international scientific clinical journals. More recently, serious methodologic limitations have been brought to light in reports on genetic testing (4,5).
Clinical Chemistry has been paying special attention to this field of research. From 1996, Clinical Chemistry has included in the instructions for authors the seven criteria used by Reid et al. (3) in their study of the methodologic quality of studies of diagnostic accuracy studies published in general medical journals (Annals of Internal Medicine Annals of Internal Medicine (Ann Intern Med) is an academic medical journal published by the American College of Physicians (ACP). It publishes research articles and reviews in the area of internal medicine. Its current editor is Harold C. Sox. , JAMA, Lancet, and New England Journal of Medicine The New England Journal of Medicine (New Engl J Med or NEJM) is an English-language peer-reviewed medical journal published by the Massachusetts Medical Society. It is one of the most popular and widely-read peer-reviewed general medical journals in the world. ). In 1997 and 2000, Clinical Chemistry published drafts of a checklist for reporting of studies of diagnostic accuracy (6, 7), and in 2001, a 28-item checklist became part of the Information for Authors. Furthermore, Clinical Chemistry has published methodologic reviews on diagnostic research and evidence-based laboratory medicine (8, 9). In 2003, Clinical Chemistry published the STARD Initiative for reporting studies of diagnostic accuracy (1, 2,10), a guideline that was also published or promoted in several other journals, including Academic Radiology, American Journal of Clinical Pathology, Annals of Internal Medicine, British Medical Journal The British Medical Journal, or BMJ, is one of the most popular and widely-read peer-reviewed general medical journals in the world. It is published by the BMJ Publishing Group Ltd (owned by the British Medical Association), whose other , Clinical Biochemistry, Clinical Chemistry and Laboratory Medicine, JAMA, Journal of Clinical Microbiology The Journal of Clinical Microbiology is an academic journal published by the American Society for Microbiology. The title is commonly abbreviated JCM and the ISSN is 0095-1137 for the print version, and 1098-660X for the electronic version. , Lancet, and Radiology.
Despite outstanding efforts to improve the quality of methodologic aspects of diagnostic investigations, there is a lack of specific information concerning the quality of the investigation of tests carried out in the laboratory. Knowledge of particular weaknesses in this research field could guide progress toward evidence-based laboratory diagnosis.
The objective of our study was to analyze the reporting and methodologic quality of published studies of diagnostic accuracy of laboratory tests. We considered diagnostic studies published in two journals dealing with clinical chemistry, included in the journal Citation Reports Journal Citation Reports (JCR) is an annual publication by the Institute of Scientific Information, a division of Thomson Scientific. It provides information about academic journals in the sciences and social sciences. (Clinical Chemistry and Clinical Chemistry and Laboratory Medicine), and applied the criteria proposed by Reid et al. (3).
Materials and Methods
Clinical Chemistry and Clinical Chemistry and Laboratory Medicine (previously called European Journal of Clinical Chemistry and Clinical Biochemistry) are journals specializing in clinical laboratory studies that, in addition to having a major impact, frequently publish articles on the evaluation of diagnostic tests in the clinical chemistry laboratory. We reviewed the articles on diagnostic tests published in the two journals in 1996, 2001, and 2002. To select the articles we carried out a search in PubMed, using the most accurate strategy described by Deville et al. (11). The strategy combined the Mesh term "sensitivity and specificity" (exploded) with the text words "specificity", "false negative", and "accuracy". To improve sensitivity we expanded the search including the Mesh term "area under the curve" and the text words "diagnostic odds ratio" and "likelihood ratios".
Articles were accepted for further review if they fulfilled the inclusion criteria described by Reid et al. (3): humans were tested, the test was intended for clinical use, and indexes of accuracy were provided with both sensitivity and specificity or with the counterpart likelihood ratio. Additionally, we reviewed papers that provided ROC curves. Only original articles showing an abstract in Medline were finally reviewed. Two authors checked the abstracts for eligibility criteria, and in case of doubt the full article was reviewed.
APPLICATION OF METHODOLOGIC CHECKLIST
We applied the seven methodologic criteria recommended by Reid et al. (3), which we reproduce below literally:
(1) Spectrum composition: This standard was met if at least three of the following four descriptors were provided: sex distribution, age distribution, summary of presenting clinical symptoms and/or disease stage, and eligibility criteria for study subjects.
(2) Analysis of pertinent subgroups: This standard was fulfilled when results for indexes of accuracy were cited for any pertinent demographic or clinical subgroup of the investigated population.
(3) Avoidance of workup work·up
n. Abbr. w/u
A thorough medical examination for diagnostic purposes. bias: For cohort studies, this standard was met if all subjects were assigned to receive both diagnostic testing and gold standard verification, either by direct procedure or by suitable clinical follow-up. In case-control studies, credit depends on whether the diagnostic test preceded or followed the gold standard procedure. If the diagnostic test preceded, credit was given if disease verification was obtained for a consecutive series of study subjects regardless of their diagnostic test result. If the diagnostic test followed, credit was given if the results were stratified stratified /strat·i·fied/ (strat´i-fid) formed or arranged in layers.
Arranged in the form of layers or strata. according to the clinical factor that evoked the gold standard procedure.
(4) Avoidance of review bias: For prospective cohort studies in which patients always receive the diagnostic test first, credit was given if the gold standard procedures were evaluated independently. A statement about independence in interpreting both the test and the gold standard procedure was required for prospective studies in which the gold standard procedure was sometimes done before the diagnostic test and for case-control studies in which the test preceded the gold standard procedure. In case-control studies in which the diagnostic test followed disease verification, a statement was required to indicate an independent evaluation of the diagnostic test.
(5) Precision of results for test accuracy: This standard was met if standard error or confidence intervals, regardless of magnitude, were reported for test sensitivity and specificity or likelihood ratios.
(6) Presentation of indeterminate test results: To meet this standard, a study had to report all of the appropriate positive, negative, and indeterminate results generated during evaluation of the diagnostic test and whether indeterminate results had been included or excluded when indexes of accuracy were calculated.
(7) Test reproducibility: For test requiring observer interpretation, at least some of the tests subjects should have been evaluated for a summary measure of observer variability. For tests performed without observer interpretation, credit was given for a summary measure of instrument variability.
Each article was evaluated independently by at least two observers. The observer agreement in this phase was 87%. In a second step, all disagreements were evaluated by the third author and solved by consensus. Data analyses were carried out with Epiinfo 2000.
Clinical Chemistry published 440 articles in 1996, 436 in 2001, and 417 in 2002. Clinical Chemistry and Laboratory Medicine published 162 articles in 1996, 210 in 2001, and 232 in 2002. Of the 1897 articles published in both journals, PubMed searches identified 460 on test evaluation. Of those 460 articles, only 358 were original reports. Finally, 79 papers fulfilled the eligibility criteria: 52 were from the journal Clinical Chemistry (11 were published in 1996, 17 in 2001, and 24 in 2002) (12-63) and 27 from Clinical Chemistry and Laboratory Medicine (7 published in 1996, 10 in 2001, and 10 in 2002) (64-90).
Regarding the diagnostic procedures evaluated in these studies, biochemistry was the field most frequently referred to (55%), followed by immunology (22%), microbiology (8%), hormones (9%), genetics (4%), and hematology (2%). The mean number of patients/ samples included in the studies was 331 (range, 10-2971 patients/ samples).
The mean number of methodologic criteria satisfied was 2.3 in 1996, 2.7 in 2001, and 3.4 in 2002 (P = 0.047). For Clinical Chemistry, the means were 2.0 in 1996, 2.9 in 2001, and 4.0 in 2002 (P = 0.001). For Clinical Chemistry and Laboratory Medicine, the means were 2.7 in 1996, 2.4 in 2001, and 1.9 in 2002 (P = 0.66).
Fulfillment of individual methodologic criteria ranged from 0% to 83% for studies published in 1996, from 15% to 81% for studies published in 2001, and from 6% to 82% for studies published in 2002 (Table 1). Articles published in 2002 showed better fulfillment than those published in 1996 or 2001 in all but two criteria. Presentation of data for test reproducibility was met by most studies in 1996 (83%); this value did not change in 2001 (81%), but in 2002 changed to 68%. Forty-four percent of the studies in 1996, 26% in 2001, and 38% in 2002 satisfied the second standard, estimation of accuracy in pertinent subgroups. Among the criteria that appeared to have improved in 2002, the statistical uncertainty of test indexes changed from 22% in articles published in 1996 to 44% in 2001 and to 65% in 2002. The spectrum composition, from 22% in articles published in 1996 to 37% in 2001 and 71% in 2002. Unexpectedly, the incidence and handling of indeterminate test results were hardly discussed.
We compared our results in 1996 with those observed by Reid et al. (3) in the subsample sub·sam·ple
A sample drawn from a larger sample.
tr.v. sub·sam·pled, sub·sam·pling, sub·sam·ples
To take a subsample from (a larger sample). of articles published between 1990 and 1993 from a group of relevant clinical journals (Table 1). In spite of the reduced sample sizes, some statistically significant differences were observed. The articles published in 1996 in Clinical Chemistry more frequently met the second (accuracy in subgroups) and seventh standards (reproducibility). The articles studied by Reid et al. (3) did better in the presentation of indeterminate results.
Judging by the articles published in Clinical Chemistry and Clinical Chemistry and Laboratory Medicine, both with a high impact factor, the quality of the methodology used in research on diagnostic laboratory tests is comparable to the most important international clinical journals. In certain aspects of the methodology, specifically the reproducibility of test results, the articles published in laboratory journals appear to be of higher quality. On the other hand, there are some methodologic flaws that would be easy to correct and would substantially improve the clinical applicability of the results of the investigations. On average the quality of the articles published in laboratory journals is high, but very few articles comply with all or almost all of the methodologic standards.
It is difficult to evaluate whether our analysis was more or less strict than that performed by Reid et al. (3). Although the criteria for application of some of the methodologic standards were not clearly specified by Reid et al., we did not observe any great interobserver variation in the results of the evaluation, and this gives us a certain degree of confidence in our findings.
One of the main discrepancies with the results obtained by Reid et al. (3) is the frequency with which the authors described the reproducibility of the results of the diagnostic test they were evaluating. Our results show that the laboratory studies report this characteristic much more frequently [83% in 1996, 81% in 2001, and 68% in 2002 vs 32% in Reid et al. (3)]. This result may have been expected because the experts in diagnostic laboratory tests usually pay more attention to analytical imprecision than do others.
A key shortcoming of the diagnostic studies done until 2001 in the laboratory is the lack of a full description of the spectrum of patients or samples studied (22% in 1996, 37% in 2001, and 71% in 2002). The improvement observed in 2002, particularly in Clinical Chemistry, has two important positive consequences. On the one hand, readers can better judge whether the population studied is comparable to other populations, which favors the applicability of results. On the other hand, the description of the clinical spectrum allows the presentation of findings by strata so that the reader can judge whether the accuracy of the test evaluated may change depending on the clinical or socio-demographic characteristics of the patients studied. Not only do we believe that authors should describe the spectrum of patients or samples studied and present the analysis by strata, but also that the STARD criteria (1, 2) should be applied, and it should be necessary to provide a more detailed explanation of the scope of the study, the way of presenting the patients, and the type of sampling. This would be a decisive step forward in improving the applicability of the results.
Regarding the presence of workup and review biases, it seems that in our series they have been prevented to an extent similar to that in the series studied by Reid et al. (3). However, it has to be pointed out that many of the publications evaluated appeared to be free of those biases such that potential for them might be said not to exist. The lack of explicit information, however, makes it impossible to guarantee that the study was indeed free of such biases.
Few articles took indeterminate results into account when evaluating the diagnostic test (none in 1996, 15% in 2001, and 6% in 2002) compared with 38% in the study by Reid et al. (3). It is possible that many of the articles analyzed in our study did not have any indeterminate results, but even so, they do not comply with the criterion because they do not say so explicitly, as required by the criteria of Reid et al.
Undoubtedly, the recommendations of the STARD initiative published in Clinical Chemistry (1, 2) include more exhaustive requirements than those proposed by Reid et al. (3). Use of the latter enabled us to compare the papers from clinical laboratory journals with those described in the most important international clinical journals. In addition, it allowed us to analyze the trend. For example, we studied the articles published a year before the appearance in Clinical Chemistry of the first article dealing with the importance of methodology in evaluation of diagnostic tests (1996) (5) and 5-6 years later (2001-2002). This enabled us to study the change produced in the literature and, therefore, the effect of publication in the journal Clinical Chemistry of the recommendations to be followed in the study of laboratory tests.
In 1996, the journal Clinical Chemistry included criteria similar to those of Reid et al. (3) in its instructions to authors, and in 1997 and in 2000 it published preliminary versions of a 28-item checklist, whereas Clinical Chemistry and Laboratory Medicine began to advocate the use of the STARD criteria in 2003 only. It therefore seems logical that Clinical Chemistry improved between 1996, 2001, and 2002, whereas Clinical Chemistry and Laboratory Medicine did not. Similar results were observed by Moher et al. (91) and Altman et al. (92), who demonstrated that the quality of reports in journals that promoted the Consolidated Standards of Reporting Trials CONSORT Statement
CONSORT stands for Consolidated Standards Of Reporting Trials. It encompasses various initiatives developed by the CONSORT Group to alleviate the problems arising from inadequate reporting of randomized controlled trials. (CONSORT) (British Medical Journal, JAMA, and Lancet) showed greater improvement than in a journal that did not advocate its use (New England Journal of Medicine). The results presented in these two reports, as well as ours, support the conclusion that editors and reviewers, in adopting criteria such as STARD or CONSORT, can play a key role in improving the quality of published reports of studies of this sort.
Both the STARD initiative and the appearance of the first-ever publication dedicated specifically to diagnostic investigation (93) may lead to future improvement of the quality of this type of investigation. Indeed, in the case of Clinical Chemistry, this is already evident. In the future, improvement in the quality of the methodology should be monitored to confirm the possible beneficial effects. Furthermore, there are other aspects of diagnostic investigation, with objectives other than accuracy, that will require development and new standards (94, 95). These objectives include both the use of clinical trials of diagnostic tests and investigation of the undesirable effects on health of unwanted information given by these tests.
We thank Judith Williams help in preparing the manuscript; we also thank the two anonymous reviewers and Dr. Joseph Watine for their useful comments during the peer reviewing of the manuscript.
(1.) Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig LM, et al. Standards for Reporting of Diagnostic Accuracy. Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD statement. Clin Chem 2003;49:1-6.
(2.) Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig LM, et al. Standards for Reporting of Diagnostic Accuracy. The STARD statement for reporting studies of diagnostic accuracy: explanation and elaboration. Clin Chem 2003;49:7-18.
(3.) Reid MC, Lachs MS, Feinstein AR. Use of methodological standards in diagnostic test research. DAMA 1995;274:645-51.
(4.) Bogardus ST Jr, Concato J, Feinstein AR. Clinical epidemiological quality in molecular genetic research. The need for methodological standards. DAMA 1999;281:1919-26.
(5.) Lijmer JG, Mol BW, Heisterkamp S, Bonsel GJ, Prins MH, van der Meulen JH, et al. Empirical evidence of design-related bias in studies of diagnostic tests. DAMA 1999;282:1061-6.
(6.) Bruns DE. The clinical chemist. Clin Chem 1997;43:2211-2.
(7.) Bruns DE, Huth EJ, Magid E, Young DS. Towards a checklist for reporting of studies of diagnostic accuracy of medical tests. Clin Chem 2000;46:893-5.
(8.) Price CP. Evidence-based laboratory medicine. Supporting decision making. Clin Chem 2000;46:1041-50.
(9.) McQueen MJ. Overview of evidence based medicine challenges for evidence based laboratory medicine. Clin Chem 2001;47:1536-46.
(10.) Bruns DE. The STARD initiative and the reporting of studies of diagnostic accuracy. Clin Chem 2003;49:19-20.
(11.) Deville WL, Bezemer PD, Bouter LM. Publications on diagnostic test evaluations in family medicine journals: an optimal search strategy. J Clin Epidemiol 2000;53:65-9.
(12.) Schellenberg F, Martin M, Caces E, Benard JY, Weill J. Nephelometric determination of carbohydrate deficient transferrin Carbohydrate-deficient transferrin (CDT) is a laboratory test used to help detect heavy ethanol consumption.
Transferrin is a plasma protein that carries iron through the bloodstream to the bone marrow, where red blood cells are manufactured, as well as to the liver . Clin Chem 1996;42:551-7.
(13.) Woitge HW, Seibel MJ, Ziegler R. Comparison of total and bone-specific alkaline phosphatase inpatients with non skeletal disorders or metabolic bone diseases. Clin Chem 1996;42: 1796-804.
(14.) Gerard B, Peponnet C, Brunie G, Cave H, Denamur E, d'Auriol L, et al. Fluorometric detection of HIV-1 genome through use of an internal control, inosine-substituted primers, and microtiter plate format. Clin Chem 1996;42:696-703.
(15.) Laurino JP, Bender EW, Kessimian N, Chang J, Pelletier T, Usategui M. Comparative sensitivities and specificities of the mass measurements of CK-MB2, CK-MB, and myoglobin myoglobin (mī'əglō`bĭn), protein molecule isolated from the cells of vertebrate skeletal muscle that is both a structural and functional relative of hemoglobin, the oxygen-transport protein of the blood of higher animals. for diagnosing acute myocardial infarction acute myocardial infarction (·kyōōtˑ mī·ō·karˑ·dē· . Clin Chem 1996;42: 1454-9.
(16.) Villena V, Navarro-Gonzalvez JA, Garcia-Benayas C, Manzanos JA, Echave J, Lopez-Encuentra A, et al. Rapid automated determination of adenosine deaminase and lysozyme lysozyme: see immunity.
An enyme that was first identified and named by Alexander Fleming, who recognized its bacteriolytic properties. for differentiating tuberculous tuberculous /tu·ber·cu·lous/ (too-ber´ku-lus) pertaining to or affected with tuberculosis; caused by Mycobacterium tuberculosis.
1. and non tuberculous pleural effusion. Clin Chem 1996;42:218-21.
(17.) Sacchetti L, Ferrajolo A, Salerno G, Esposito P, Lofrano MM, Oriani G, et al. Diagnostic value of various serum antibodies detected by diverse methods in childhood celiac disease. Clin Chem 1996; 42:1838-42.
(18.) Rohlfs EM, Chaing SH, Chapman JF. Analytical and clinical evaluation of refractive index-matched anomalous diffraction (RIMAD) for assessment of fetal lung maturation. Clin Chem 1996;42: 1861-8.
(19.) Castaldo G, Intrieri M, Calcagno G, Cimino L, Budillon G, Sacchetti L, et al. Ascitic pseudiuridine discriminates between hepatocarcinoma-derived ascites and cirrhotic ascites. Clin Chem 1996;42: 1843-6.
(20.) Marquet PY, Daver A, Sapin R, Bridgi B, Muratet JP, Hartmann DJ, et al. Highly sensitive immunoradiometric assay for serum thyroglobulin thyroglobulin /thy·ro·glob·u·lin/ (thi?ro-glob´u-lin) an iodine-containing glycoprotein of high molecular weight, occurring in the colloid of the follicles of the thyroid gland; the iodinated tyrosine moieties of thyroglobulin form the with minimal interference from autoantibodies. Clin Chem 1996;42:258-62.
(21.) Helander A, Beck O, Jones AW. Laboratory testing for recent alcohol consumption: comparison of ethanol, methanol, and 5-hydroxytryptophol. Clin Chem 1996;42:618-24.
(22.) Guechot J, Laudat A, Loria A, Serfaty L, Poupon R, Giboudeau J. Diagnostic accuracy of hyaluronan and type III procollagen aminoterminal peptide serum assays as markers of liver fibrosis in chronic viral hepatitis C evaluated by ROC curve analysis. Clin Chem 1996;42:558-63.
(23.) Bizzaro N, Mazzanti G, Tonutti E, Villalta D, Tozzoli R. Diagnostic accuracy of the anti-citrulline antibody assay for rheumatoid arthritis. Clin Chem 2001;47:1089-93.
(24.) Hayashi N, Kawamoto T, Mukai M, Morinobu A, Koshiba M, Kondo S, et al. Detection of antinuclear antibodies by use of an enzyme immunoassay with nuclear Hep-2 cell extract and recombinant antigens: comparison with immunofluorescence assay in 307 patients. Clin Chem 2001;47:1649-59.
(25.) Norberg T, Klaar S, Lindqvist L, Lindahl T, Ahlgren J, Bergh J. Enzymatic mutation detection method evaluated for detection of p53 mutations in cDNA from breast cancers. Clin Chem 2001;47: 821-8.
(26.) Christenson RH, Duh SH, Sanhai WR, Wu AH, Holtman V, Painter P, et al. Characteristics of an albumin cobalt binding test for assessment of acute coronary syndrome acute coronary syndrome
A sudden, severe coronary event that mimics a heart attack, such as unstable angina.
acute coronary syndrome patients: a multicenter study. Clin Chem 2001;47:464-70.
(27.) Turpeinen U, Methuen T, Alfthan H, Laitinen K, Salaspuro M, Stenman UH. Comparison of HPLC HPLC high-performance liquid chromatography.
high performance liquid chromatography.
HPLC High-performance liquid chromatography Lab instrumentation A highly sensitive analytic method in which analytes are placed and small column (CDTect) methods for disialotransferrin. Clin Chem 2001;47:1782-7.
(28.) Umapathysivam K, Hopwood JJ, Meikle PJ. Determination of acid [alpha]-glucosidase activity in bloodspots as a diagnostic test for Pompe disease. Clin Chem 2001;47:1378-83.
(29.) Cassinat B, Darsin D, Guardiola P, Toubert ME, Rain JD, Gluckman E, et al. Intermethod discordance discordance /dis·cor·dance/ (dis-kord´ans) the occurrence of a given trait in only one member of a twin pair.discor´dant
n. for a-fetoprotein measurements in Fanconi anemia. Clin Chem 2001;47:1405-9.
(30.) Bijwaard KE, Aguilera NS, Monczak Y, Trudel M, Taubenberger J K, Lichy JH. Quantitative real-time reverse transcription PCR PCR polymerase chain reaction.
polymerase chain reaction
Polymerase chain reaction (PCR) assay for cyclin D1 expression: utility in the diagnosis of mantle cell lymphoma Mantle cell lymphoma (MCL) is one of the rarer of the non-Hodgkin's lymphomas, comprising about 6% of NHL cases. There are only about 15,000 patients presently in the U.S. (The incidence seems to be somewhat higher in Europe. . Clin Chem 2001;47:195-201.
(31.) Rickert M, Seissler J, Dangel W, Lorenz H, Richter W. Fusion protein for combined analysis of autoantibodies to the 65-kDa isoform of glutamic acid decarboxylase decarboxylase /de·car·box·y·lase/ (de?kahr-bok´si-las) any enzyme of the lyase class that catalyzes the removal of a carbon dioxide molecule from carboxylic acids.
n. and islet islet /is·let/ (-lit) an island.
islets of Langerhans irregular microscopic structures scattered throughout the pancreas and comprising its endocrine portion. antigen-2 in insulin-dependent diabetes mellitus insulin-dependent diabetes mellitus
Abbr. IDDM See diabetes mellitus. . Clin Chem 2001;47:926-34.
(32.) Jensen UG, Brandt NJ, Christensen E, Skovby F, Norgaard-Pedersen B, Simonsen H. Neonatal screening for galactosemia galactosemia (gəlăk'təsē`mēə), inherited metabolic disorder caused by an enzyme deficiency and transmitted as a recessive trait; it results in the accumulation of the sugar galactose in the body. by quantitative analysis of hexose hexose /hex·ose/ (hek´sos) a monosaccharide containing six carbon atoms in a molecule.
n. monophosphates using tandem mass spectrometry Tandem mass spectrometry, also known as MS/MS, involves multiple steps of mass spectrometry selection, with some form of fragmentation occurring in between the stages. : a retrospective study. Clin Chem 2001;47: 1364-72.
(33.) Lempinen M, Kylanpaa-Back ML, Stenman UH, Puolakkainen P, Haapiainen R, Finne P, et al. Predicting the severity of acute pancreatitis by rapid measurement of trypsinogen-2 in urine. Clin Chem 2001;47:2103-7.
(34.) Nurmikko P, Pettersson K, Piironen T, Hugosson J, Lilja H. Discrimination of prostate cancer from benign disease by plasma measurement of intact, free prostate-specific antigen lacking an internal cleavage site at [Lys.sup.145]-[Lys.sup.146]. Clin Chem 2001;47: 1415-23.
(35.) Sillanaukee P, Olsson U. Improved diagnostic classification of alcohol abusers by combining carbohydrate-deficient transferrin and [gamma]-glutamyltransferase. Clin Chem 2001;47:681-5.
(36.) Mourad M, Malaise J, Chaib Eddour D, De Meyer M, Konig J, Schepers R, et al. Pharmacokinetic basis for the efficient and safe use of low-dose mycophenolate mofetil in combination with tacrolimus in kidney transplantation. Clin Chem 2001;47:1241-8.
(37.) Anton RF, Dominic KC, Bigelow M, Westby C, CDTect Research Group. Comparison of Bio-Rad %CDT CDT
Central Daylight Time
CDT Central Daylight Time
CDT n abbr (US) (= Central Daylight Time) → hora de verano del centro;
(BRIT TIA (1) (Telecommunications Industry Association, Arlington, VA, www.tiaonline.org) A membership organization founded in 1988 that sets telecommunications standards worldwide. It was originally an EIA working group that was spun off and merged with the U.S. and CDTect as laboratory markers of heavy alcohol use and their relationships with [gamma]-glutamyltransferase. Clin Chem 2001;47:1769-75.
(38.) Jonsson M, Carlson J, Jeppsson JO, Simonsson P. Computersupported detection of M-components and evaluation of immunoglobulins after capillary electrophoresis. Clin Chem 2001;47: 110-7.
(39.) Andersen JM, Hedstrom J, Kemppainen E, Finne P, Poulakkainen P, Stenman UH. The ratio of trypsin-2-al-antitrypsin to trypsinogen-1 discriminates biliary and alcohol-induced acute pancreatitis. Clin Chem 2001;47:231-6.
(40.) Richard S, Miossec V, Moreau JF, Taupin JL. Detection of oligoclonal immunoglobulins in cerebrospinal fluid by an immunofixation-peroxidase method. Clin Chem 2002;48:167-73.
(41.) Ferre N, Camps J, Prats E, Vilella E, Paul A, Figuera L, et al. Serum paraoxonase activity: a new additional test for the improved evaluation of chronic liver damage. Clin Chem 2002;48:261-8.
(42.) Weber LT, Shipkova M, Armstrong VW, Wagner N, Schutz E, Mehls O, et al. Comparison of the Emit immunoassay with HPLC for therapeutic drug monitoring therapeutic drug monitoring Clinical pharmacology The regular measurement of serum levels of drugs requiring close 'titration' of doses in order to ensure that there are sufficient levels in the blood to be therapeutically effective, while avoiding potentially of mycophenolic acid in pediatric pediatric /pe·di·at·ric/ (pe?de-at´rik) pertaining to the health of children.
Of or relating to pediatrics. renal-transplant recipients on mycophenolate mofetil therapy. Clin Chem 2002;48:517-25.
(43.) Filler G, Priem F, Lepage N, Sinha P, Vollmer I, Clark H, et al. R-Trace protein, cystatin C, Rrmicroglobulin, and creatinine compared for detecting impaired glomerular glomerular /glo·mer·u·lar/ (glo-mer´u-ler) pertaining to or of the nature of a glomerulus, especially a renal glomerulus.
adj. filtration rates in children. Clin Chem 2002;48:729-36.
(44.) Fantz CR, Powell C, Karon B, Parvin CA, Hankins K, Dayal M, et al. Assessment of the diagnostic accuracy of the TDx-FLM II to predict fetal lung maturity fetal lung maturity Obstetrics A parameter that determines the likelihood a neonate will develop RDS; infants delivered at 40 ± 2 wks have 0% incidence of RDS; at 36 wks 0-2%, at 34 wks 8-34%–depending on birthweight . Clin Chem 2002;48:761-5.
(45.) Orlando R, Mussap M, Plebani M, Piccoli P, De Martin S, Floreani M, et al. Diagnostic value of plasma cystatin C as a glomerular filtration marker in decompensated liver cirrhosis. Clin Chem 2002;48:850-8.
(46.) Wasmuth JC, Oliver y Minarro D, Homrighausen A, Leifeld L, Rockstroh JK, Sauerbruch T, et al. Phospholipid phospholipid (fŏs'fōlĭp`ĭd), lipid that in its simplest form is composed of glycerol bonded to two fatty acids and a phosphate group. autoantibodies and the anti phospholipid antibody syndrome: diagnostic accuracy of 23 methods studied by variation in ROC curves with number of clinical manifestations. Clin Chem 2002;48:1004-10.
(47.) Xu SQ, He M, Yu HP, Wang XY, Tan XL, Lu B, et al. Bioluminescent bi·o·lu·mi·nes·cence
Emission of visible light by living organisms such as the firefly and various fish, fungi, and bacteria.
bi method for detecting telomerase activity. Clin Chem 2002;48: 1016-20.
(48.) Poon TC, Mok TS, Chan AT, Chan CM, Leong V, Tsui SH, et al. Quantification and utility of monosialylated a-fetoprotein in the diagnosis of hepatocellular carcinoma with nondiagnostic serum total a-fetoprotein. Clin Chem 2002;48:1021-7.
(49.) Martinez M, Espana F, Royo M, Alapont JM, Navarro S, Estelles A, et al. The proportion of prostate-specific antigen (PSA (Professional Services Automation) An information system designed to organize, track and manage all opportunities, work, resources, costs, revenues and invoices to improve the productivity and efficiency of the workforce. ) complexed to [[alpha].sub.1]-antichymotrypsin improves the discrimination between prostate cancer and benign prostatic hyperplasia benign prostatic hyperplasia
n. Abbr. BPH
A nonmalignant enlargement of the prostate gland commonly occurring in men after the age of 50, and sometimes leading to compression of the urethra and obstruction of the flow of urine. in men with a total PSA of 10 to 30 [micro]g/L. Clin Chem 2002;48:1251-6.
(50.) Stephan C, Cammann H, Semjonow A, Diamandis EP, Wymenga LF, Lein M, et al. Multicenter evaluation of an artificial neural network (artificial intelligence) artificial neural network - (ANN, commonly just "neural network" or "neural net") A network of many very simple processors ("units" or "neurons"), each possibly having a (small amount of) local memory. to increase the prostate cancer detection rate and reduce unnecessary biopsies. Clin Chem 2002;48:1279-87.
(51.) Li J, Zhang Z, Rosenzweig J, Wang YY, Chan DW. Proteomics and bioinformatics approaches for identification of serum biomarkers to detect breast cancer. Clin Chem 2002;48:1296-304.
(52.) Krauss T, Emons G, Kuhn W, Augustin HG. Predictive value of routine circulating soluble endothelial cell adhesion molecule Cell Adhesion Molecules (CAMs) are proteins located on the cell surface involved with the binding with other cells or with the extracellular matrix (ECM) in the process called cell adhesion. measurements during pregnancy. Clin Chem 2002;48:1418-25.
(53.) Panteghini M, Cuccia C, Bonetti G, Giubbini R, Pagani F, Bonini E. Single-point cardiac troponin T at coronary care unit coronary care unit
Abbr. CCU A hospital unit that is specially equipped to treat and monitor patients with serious heart conditions, such as coronary thrombosis. discharge after myocardial infarction correlates with infarct infarct /in·farct/ (in´fahrkt) a localized area of ischemic necrosis produced by occlusion of the arterial supply or the venous drainage of the part. size and ejection fraction. Clin Chem 2002;48:1432-6.
(54.) Oda H, Shiina Y, Seiki K, Sato N, Eguchi N, Urade Y. Development and evaluation of a practical ELISA ELISA (e-li´sah) Enzyme-Linked Immuno-Sorbent Assay; any enzyme immunoassay using an enzyme-labeled immunoreactant and an immunosorbent.
n. for human urinary lipocalin-type prostaglandin D synthase. Clin Chem 2002;48:1445-53.
(55.) Carroccio A, Vitale G, Di Prima L, Chifari N, Napoli S, La Russa C, et al. Comparison of anti-transglutaminase ELISAs and an antiendomysial antibody assay in the diagnosis of celiac disease: a prospective study. Clin Chem 2002;48:1546-50.
(56.) Qu Y, Adam BL, Yasui Y, Ward MD, Cazares LH, Schellhammer PF, et al. Boosted decision tree analysis of surface-enhanced laser desorption/ionization Surface-enhanced laser desorption/ionization (SELDI) is an ionization method in mass spectrometry that is used for the analysis of protein mixtures. SELDI is typically used with time-of-flight mass spectrometers and is used to detect proteins in tissue samples, blood, mass spectral serum profiles discriminates prostate cancer from noncancer patients. Clin Chem 2002;48: 1835-43.
(57.) Kauppinen R, von and zu Fraunberg M. Molecular and biochemical studies of acute intermittent porphyria acute intermittent porphyria
See intermittent acute porphyria.
Acute intermittent porphyria
An inherited disease affecting the liver and bone marrow. in 196 patients and their families. Clin Chem 2002;48:1891-900.
(58.) Schwartz GL, Chapman AB, Boerwinkle E, Kisabeth RM, Turner ST. Screening for primary aldosteronism: implications of an increased plasma aldosterone/renin ratio. Clin Chem 2002;48:1919-23.
(59.) Derhaschnig U, Laggner AN, Roggla M, Hirschl MM, Kapiotis S, Marsik C, et al. Evaluation of coagulation markers for early diagnosis of acute coronary syndromes in the emergency room. Clin Chem 2002;48:1924-30.
(60.) Kulpa J, Wojcik E, Reinfuss M, Kolodziejski L. Carcinoembryonic antigen, squamous cell carcinoma squamous cell carcinoma
A carcinoma that arises from squamous epithelium and is the most common form of skin cancer. Also called cancroid, epidermoid carcinoma. antigen, CYFRA 21-1, and neuron-specific enolase enolase /eno·lase/ (e´no-las) an enzyme that catalyzes the dehydration of 2-phosphoglycerate to form phospho, a step in the pathway of glucose metabolism. in squamous cell lung cancer patients. Clin Chem 2002;48:1931-7.
(61.) Legros FJ, Nuyens V, Minet E, Emonts P, Boudjeltia KZ, Courbe A, et al. Carbohydrate-deficient transferrin isoforms measured by capillary zone electrophoresis for detection of alcohol abuse. Clin Chem 2002;48:2177-86.
(62.) Ryden I, Pahlsson P, Lindgren S. Diagnostic accuracy of ai acid glycoprotein fucosylation for liver cirrhosis in patients undergoing hepatic biopsy. Clin Chem 2002;48:2195-201.
(63.) Penders J, Fiers T, Delanghe JR. Quantitative evaluation of urinalysis test strips. Clin Chem 2002;48:2236-41.
(64.) van Dalen A, Kessler AC. A multicentre evaluation of tumour marker determinations using the automatic Enzymum-test systems ES 300 and ES 600/700. Eur J Clin Chem Clin Biochem 1996;34:377-84.
(65.) Bacigalupo MA, Bazzini P, Farina L, lus A. Evaluation of three immunoassays for detection of toxoplasma-specific immunoglobulin G and M. Eur J Clin Chem Clin Biochem 1996;34:503-5.
(66.) Matsushita H, Xu J, Kuroki M, Kondo A, Inoue E, Teramura Y, et al. Establishment and evaluation of a new chemiluminescent enzyme immunoassay for carcinoembryonic antigen adapted to the fully automated ACCES ACCES Army Command & Control Evaluation System
ACCES Army Civilian Career Evaluation System
ACCES Accessible Community Counselling and Employment Services (Toronto, Canada)
ACCES Automated Command & Control Evaluation System System. Eur J Clin Chem Clin Biochem 1996; 34:829-35.
(67.) Schmitt UM, Stieber P, Hasholzner U, Pahl H, Hofmann K, Fateh-Moghadam A. Methodological and clinical evaluation of two automated enzymatic immunoassays as compared with a radio immunoassays for neuron-specific enolase. Eur J Clin Chem Clin Biochem 1996;34:679-82.
(68.) Conejo JR, Benedito JE, Jimenez A, Menchen M, Cano J, Granizo V, et al. Diagnostic value of three tumour markers determined in pleural Pleural
Pleural refers to the pleura or membrane that enfolds the lungs.
Mentioned in: Pneumothorax
emanating from or pertaining to the pleura. effusions. Eur J Clin Chem Clin Biochem 1996;34:139-42.
(69.) Plebani M, Borghesan F, Bernardi D, Faggian D. Clinical evaluation of a new quantitative method for specific IgE antibodies. Eur J Clin Chem Clin Biochem 1996;34:579-84.
(70.) Collinson P, Gerhardt W, Katus HA, Muller-Bardorff M, Braun S, Schricke U, et al. Multicentre evaluation of an immunological rapid test for the detection of troponin T in whole blood samples. Eur J Clin Chem Clin Biochem 1996;34:591-8.
(71.) Mroczko B, Szmitkowski M, Niklinski J. Granulocyte-colony stimulating factor and macrophage-colony stimulating factor in patients with non-small cell lung cancer. Clin Chem Lab Med 2001;39: 374-9.
(72.) von Eyben FE, Blaabjerg O, Hyltoft-Petersen P, Madsen EL, Amato R, Liu F, et al. Serum lactate dehydrogenase isoenzyme isoenzyme /iso·en·zyme/ (-en´zim) isozyme.
i 1 and prediction of death in patients with metastatic testicular germ cell tumors. Clin Chem Lab Med 2001;39:38-44.
(73.) Shaarawy M, Salem ME. Clinical value of microtransferrinuria and microalbuminuria in the prediction of preeclampsia preeclampsia /pre·eclamp·sia/ (pre?e-klamp´se-ah) a toxemia of late pregnancy, characterized by hypertension, proteinuria, and edema.
n. . Clin Chem Lab Med 2001;39:29-34.
(74.) Genser B, Truschnig-Wilders M, Stunzner D, Landini MP, Halwachs-Baumann G. Evaluation of five commercial enzyme immunoassays for the detection of human cytomegalovirus-specific IgM antibodies in the absence of a commercially available gold standard. Clin Chem Lab Med 2001;39:62-70.
(75.) Tello FL, Prats CH, Gonzalez MD. Free and complexed prostatespecific antigen (PSA) in the early detection of prostate cancer. Clin Chem Lab Med 2001;39:116-20.
(76.) Glojnaric I, Casl MT, Simic D, Lukac J. Serum amyloid A Serum amyloid A (SAA) proteins are a family of apolipoproteins associated with high-density lipoprotein (HDL) in plasma. Different isoforms of SAA are expressed constitutively (constitutive SAAs) at different levels or in response to inflammatory stimuli (acute phase SAAs). protein (SAA (Systems Application Architecture) A set of interfaces designed to cross all IBM platforms from PC to mainframe. Introduced by IBM in 1987, SAA includes the Common User Access (CUA), the Common Programming Interface for Communications (CPI-C) and Common Communications ) in colorectal carcinoma. Clin Chem Lab Med 2001;39:129-33.
(77.) Mello G, Parretti E, Ognibene A, Mecacci F, Cioni R, Scarselli G, et al. Prediction of the development of pregnancy induced hypertensive disorders in high risk pregnant women by artificial neural networks. Clin Chem Lab Med 2001;39:801-5.
(78.) Schellenberg F, Mennetrey L, Bacq Y, Pages JC. Carbohydrate-deficient transferrin (CDT)determination by nephelometry nephelometry
measurement of the concentration of a suspension by means of a nephelometer. using a commercial kit. Analytical and diagnostic aspects. Clin Chem Lab Med 2001;39:866-71.
(79.) Sarno M, Sarno L, Baylink D, Drinkwater B, Farley S, Kleerekoper M, et al. Excretion of sweat and urine pyridinoline crosslinks in healthy controls and subjects with established metabolic bone disease. Clin Chem Lab Med 2001;39:223-8.
(80.) Siekmeier R, Bierlich A, Jaross W. The white blood cell differential: three methods compared. Clin Chem Lab Med 2001;39:432-45.
(81.) Giovanella L, Ceriani L, Giardina G, Bardelli D, Tanzi F, Garancini S. Serum cytokeratin fragment 21.1 (CYFRA 21.1) as tumour marker for breast cancer: comparison with carbohydrate antigen 15.3 (CA 15.3) and carcinoembryonic antigen (CEA). Clin Chem Lab Med 2002;40:298-303.
(82.) Mroczko B, Szmitkowski M, Okulczyk B. Granulocyte-colony stimulating factor (G-CSF) and macrophage-colony stimulating factor (M-CSF) in colorectal cancer patients. Clin Chem Lab Med 2002; 40:351-5.
(83.) Giovanella L, Ceriani L. High-sensitivity human thyroglobulin (hTG) immunoradiometric assay in the follow-up of patients with differentiated thyroid cancer. Clin Chem Lab Med 2002;40:480-4.
(84.) Kocna P, Vanickova Z, Perusicova J, Dvorak M. Tissue transglutaminase-serology markers for coeliac disease. Clin Chem Lab Med 2002;40:485-92.
(85.) Barlandas-Rendon E, Muller MM, Garcia-Latorre E, Heinschink A. Comparison of urine cell characteristics by flow cytometry and cytology in patients suspected of having bladder cancer. Clin Chem Lab Med 2002;40:817-23.
(86.) linuma Y, Senda K, Takakura S, Ichiyama S, Tano M, Abe T, et al. Evaluation of a commercially available serologic assay for antibodies against tuberculosis-associated glycolipid Glycolipid
One of a class of compounds having solubility properties of a lipid and containing one or more molecules of a covalently attached sugar. antigen. Clin Chem Lab Med 2002;40:832-6.
(87.) AI-Daghistani HI, Abdel-Dayem M. Diagnostic value of various urine tests in the Jordanian population with urinary tract infection urinary tract infection (UTI),
n infection in one or more of the structures that make up the urinary system. Occurs more often in women and is most commonly caused by bacteria. . Clin Chem Lab Med 2002;40:1048-51.
(88.) Hernando M, Gonzalez C, Sanchez A, Guevara P, Navajo JA, Papisch W, et al. Clinical evaluation of a new automated antids-DNA fluorescent immunoassay. Clin Chem Lab Med 2002;40: 1056-60.
(89.) Burkhardt H, Bojarsky G, Gladisch R. Diagnostic efficiency of cystatin C and serum creatinine as markers of reduced glomerular filtration rate glomerular filtration rate
n. Abbr. GFR
The volume of water filtered out of the plasma through glomerular capillary walls into Bowman's capsules per unit of time. in the elderly. Clin Chem Lab Med 2002;40:1135-8.
(90.) Zago L, Dupraz H, Sarchi M, Rio M. The molar ratio of retinol-binding protein to transthyretin in the assessment of vitamin A status in adults. Proposal of a cut-off point. Clin Chem Lab Med 2002;40:1301-7.
(91.) Moher D, Jones A, Lepage L. CONSORT Group (Consolidated Standards for Reporting of Trials). Use of the CONSORT statement and quality of reports of randomised Adj. 1. randomised - set up or distributed in a deliberately random way
irregular - contrary to rule or accepted order or general practice; "irregular hiring practices" trial. A comparative before-and-after evaluation. JAMA 2001;285:1912-5.
(92.) Altman DG, Schulz KF, Moher D, Egger M, Davidoff F, Elbourne D, et al. The revised CONSORT statement for reporting randomised trials: explanation and elaboration. Ann Intern Med 2001;134: 663-94.
(93.) Knottnerus JS. The evidence based of clinical diagnosis. London: BMJ BMJ n abbr (= British Medical Journal) → vom BMA herausgegebene Zeitschrift Books, 2002:237pp.
(94.) Feinstein AR. Misguided efforts and future challenges for research on "diagnostic tests". J Epidemiol Community Health 2002;56: 330-2.
(95.) Hernandez Aguado I. The winding road towards evidence based diagnoses. J Epidemiol Community Health 2002;56:323-5.
BLANCA LUMBRERAS-LACARRA,  JOSE MANUEL RAMOS-RINCON,  and ILDEFONSO HERNANDEZ-AGUAD0  *
 Department of Clinic Analysis, General University Hospital of Alicante, Alicante, Spain.
 Department of Internal Medicine, General University Hospital of Elche, Elche, Spain.
 Department of Public Health, University of Miguel Hernandez, San Juan de Alicante, Spain.
* Address correspondence to this author at: Department of Public Health, Facultad de Medicina, University of Miguel Hernandez, Carretera de Valencia Km. 8.7, 03550 San Juan de Alicante, Spain. Fax 34-96-5919551; e-mail email@example.com.
Received April 4, 2003; accepted December 12, 2003.
Previously published online at DOI: 10.1373/clinchem.2003.019786
Table 1. Fulfillment of the methodologic criteria used by Reid et al. (3) in the articles published in 1996, 2001, and 2002 in Clinical Chemistry and Clinical Chemistry and Laboratory Medicine and in articles published in general medical journals and reviewed by Reid et al. Number (%) of articles Year 19968 Year 2001 Year 2002 (n = 18) (n=27) (n=34) Spectrum composition 4 (22) 10 (37) 24 (71) Age distribution 9 (50) 18 (67) 28 (82) Sex distribution 9 (50) 19 (70) 26 (76) Clinical symptoms and/or disease stage 6 (33) 11 (41) 12 (35) Study eligibility criteria 4 (22) 10 (37) 18 (53) Accuracy in subgroups 8 (44) 7 (26) 13 (38) Avoidance of workup bias 6 (33) 13 (48) 24 (71) Avoidance of review bias 4 (22) 10 (37) 15 (44) Test accuracy precision 4 (22) 12 (44) 22 (65) Indeterminate tests results 0 4 (15) 2 (6) Test reproducibility 15 (83) 22 (81) 21 (68) Number (%) of articles Reid et al. (1990-1993) (b) (n=34) Spectrum composition 11(32) Age distribution Sex distribution Clinical symptoms and/or disease stage Study eligibility criteria Accuracy in subgroups 4 (12) (c) Avoidance of workup bias 21 (62) Avoidance of review bias 16 (47) Test accuracy precision 8 (24) Indeterminate tests results 13 (38) (c) Test reproducibility 11 (32) (c) (a) Differences between 1996 and 2001 were not statistically significant. (b) Articles from Reid et al. (3) were restricted to those published in 1990-1993, the closest dates to 1996. (c) P <0.05 in Epiinfo Fisher exact test comparing proportions between 1996 and articles reviewed by Reid et al. (3).
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|Title Annotation:||Evidence-based Laboratory Medicine and Test Utilization|
|Author:||Lumbreras-Lacarra, Blanca; Ramos-Rincon, Jose Manuel; Hernandez-Aguado, Ildefonso|
|Date:||Mar 1, 2004|
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