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Clinical Chemistry 50: 530-536, 2004. First published January 12, 2004; 10.1373/clinchem.2003.019786
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Right arrow Evidence Based Laboratory Medicine and Test Utilization
(Clinical Chemistry. 2004;50:530-536.)
© 2004 American Association for Clinical Chemistry, Inc.

Evidence-based Laboratory Medicine and Test Utilization

Methodology in Diagnostic Laboratory Test Research in Clinical Chemistry and Clinical Chemistry and Laboratory Medicine

Blanca Lumbreras-Lacarra1, José Manuel Ramos-Rincón2 and Ildefonso Hernández-Aguado3,a

1 Department of Clinic Analysis, General University Hospital of Alicante, Alicante, Spain. 2 Department of Internal Medicine, General University Hospital of Elche, Elche, Spain. 3 Department of Public Health, University of Miguel Hernández, San Juan de Alicante, Spain.

aAddress correspondence to this author at: Department of Public Health, Facultad de Medicina, University of Miguel Hernández, Carretera de Valencia Km. 8.7, 03550 San Juan de Alicante, Spain. Fax 34-96-5919551; e-mail ihernandez{at}umh.es.


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Background: The application of epidemiologic principles to clinical diagnosis has been less developed than in other clinical areas. Knowledge of the main flaws affecting diagnostic laboratory test research is the first step for improving its quality. We assessed the methodologic aspects of articles on laboratory tests.

Methods: We included articles that estimated indexes of diagnostic accuracy (sensitivity and specificity) and were published in Clinical Chemistry or Clinical Chemistry and Laboratory Medicine in 1996, 2001, and 2002. Clinical Chemistry has paid special attention to this field of research since 1996 by publishing recommendations, checklists, and reviews. Articles were identified through electronic searches in Medline. The strategy combined the Mesh term "sensitivity and specificity" (exploded) with the text words "specificity", "false negative", and "accuracy". We examined adherence to seven methodologic criteria used in the study by Reid et al. (JAMA1995;274:645–51) of papers published in general medical journals. Three observers evaluated each article independently.

Results: Seventy-nine articles fulfilled the inclusion criteria. The percentage of studies that satisfied each criterion improved from 1996 to 2002. Substantial improvement was observed in reporting of the statistical uncertainty of indices of diagnostic accuracy, in criteria based on clinical information from the study population (spectrum composition), and in avoidance of workup bias. Analytical reproducibility was reported frequently (68%), whereas information about indeterminate results was rarely provided. The mean number of methodologic criteria satisfied showed a statistically significant increase over the 3 years in Clinical Chemistry but not in Clinical Chemistry and Laboratory Medicine.

Conclusions: The methodologic quality of the articles on diagnostic test research published in Clinical Chemistry and Clinical Chemistry and Laboratory Medicine is comparable to the quality observed in the best general medical journals. The methodologic aspects that most need improvement are those linked to the clinical information of the populations studied. Editorial actions aimed to increase the quality of reporting of diagnostic studies could have a relevant positive effect, as shown by the improvement observed in Clinical Chemistry.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
The recently published STARD initiative concerning the publication of studies on diagnostic accuracy is an important step forward in improving the quality of diagnostic investigation. Its relevance is even greater if we consider the many challenges of research on diagnostic tests and that application of epidemiologic principles to the field of clinical diagnosis has been less developed than other clinical areas, or perhaps less effective (1)(2).

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, JAMA, Lancet, and New England Journal of Medicine). 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, Clinical Biochemistry, Clinical Chemistry and Laboratory Medicine, JAMA, Journal of Clinical Microbiology, 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 (Clinical Chemistry and Clinical Chemistry and Laboratory Medicine), and applied the criteria proposed by Reid et al. (3).


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
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 Devillé 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 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 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.


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
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)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62)(63) and 27 from Clinical Chemistry and Laboratory Medicine (7 published in 1996, 10 in 2001, and 10 in 2002) (64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85)(86)(87)(88)(89)(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.


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  		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.

We compared our results in 1996 with those observed by Reid et al. (3) in the subsample of articles published between 1990 and 1993 from a group of relevant clinical journals (Table 1Up ). 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.


   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
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 sociodemographic 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) (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.


   Acknowledgments
 
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.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  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.[Abstract/Free Full Text]
  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.[Abstract/Free Full Text]
  3. Reid MC, Lachs MS, Feinstein AR. Use of methodological standards in diagnostic test research. JAMA 1995;274:645-651.[Abstract/Free Full Text]
  4. Bogardus ST, Jr, Concato J, Feinstein AR. Clinical epidemiological quality in molecular genetic research. The need for methodological standards. JAMA 1999;281:1919-1926.[Abstract/Free Full Text]
  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. JAMA 1999;282:1061-1066.[Abstract/Free Full Text]
  6. Bruns DE. The clinical chemist. Clin Chem 1997;43:2211-2212.[Free Full Text]
  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;46:893-895.[Abstract/Free Full Text]
  8. Price CP. Evidence-based laboratory medicine. Supporting decision making. Clin Chem 2000;46:1041-1050.[Abstract/Free Full Text]
  9. McQueen MJ. Overview of evidence based medicine challenges for evidence based laboratory medicine. Clin Chem 2001;47:1536-1546.[Abstract/Free Full Text]
  10. Bruns DE. The STARD initiative and the reporting of studies of diagnostic accuracy. Clin Chem 2003;49:19-20.[Free Full Text]
  11. Deville WL, Bezemer PD, Bouter LM. Publications on diagnostic test evaluations in family medicine journals: an optimal search strategy. J Clin Epidemiol 2000;53:65-69.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  12. Schellenberg F, Martin M, Caces E, Benard JY, Weill J. Nephelometric determination of carbohydrate deficient transferrin. Clin Chem 1996;42:551-557.[Abstract/Free Full Text]
  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;42:1796-1804.[Abstract/Free Full Text]
  14. Gerard B, Peponnet C, Brunie G, Cave H, Denamur E, d’Auriol L, et al. Fluorometric detection of HIV-I genome through use of an internal control, inosine-substituted primers, and microtiter plate format. Clin Chem 1996;42:696-703.[Abstract/Free Full Text]
  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 for diagnosing acute myocardial infarction. Clin Chem 1996;42:1454-1459.[Abstract/Free Full Text]
  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 for differentiating tuberculous and non tuberculous pleural effusion. Clin Chem 1996;42:218-221.[Abstract/Free Full Text]
  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;42:1838-1842.[Abstract/Free Full Text]
  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;42:1861-1868.[Abstract/Free Full Text]
  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;42:1843-1846.[Abstract/Free Full Text]
  20. Marquet PY, Daver A, Sapin R, Bridgi B, Muratet JP, Hartmann DJ, et al. Highly sensitive immunoradiometric assay for serum thyroglobulin with minimal interference from autoantibodies. Clin Chem 1996;42:258-262.[Abstract/Free Full Text]
  21. Helander A, Beck O, Jones AW. Laboratory testing for recent alcohol consumption: comparison of ethanol, methanol, and 5-hydroxytryptophol. Clin Chem 1996;42:618-624.[Abstract/Free Full Text]
  22. Guéchot J, Laudat A, Loria A, Serfaty L, Poupon R, Giboudeau J. Diagnostic accuracy of hyaluronan and type III procollagen amino-terminal peptide serum assays as markers of liver fibrosis in chronic viral hepatitis C evaluated by ROC curve analysis. Clin Chem 1996;42:558-563.[Abstract/Free Full Text]
  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;47:1089-1093.[Abstract/Free Full Text]
  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;47:1649-1659.[Abstract/Free Full Text]
  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;47:821-828.[Abstract/Free Full Text]
  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 patients: a multicenter study. Clin Chem 2001;47:464-470.[Abstract/Free Full Text]
  27. Turpeinen U, Methuen T, Alfthan H, Laitinen K, Salaspuro M, Stenman UH. Comparison of HPLC and small column (CDTect) methods for disialotransferrin. Clin Chem 2001;47:1782-1787.[Abstract/Free Full Text]
  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;47:1378-1383.[Abstract/Free Full Text]
  29. Cassinat B, Darsin D, Guardiola P, Toubert ME, Rain JD, Gluckman E, et al. Intermethod discordance for {alpha}-fetoprotein measurements in Fanconi anemia. Clin Chem 2001;47:1405-1409.[Abstract/Free Full Text]
  30. Bijwaard KE, Aguilera NS, Monczak Y, Trudel M, Taubenberger JK, Lichy JH. Quantitative real-time reverse transcription PCR assay for cyclin D1 expression: utility in the diagnosis of mantle cell lymphoma. Clin Chem 2001;47:195-201.[Abstract/Free Full Text]
  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 and islet antigen-2 in insulin-dependent diabetes mellitus. Clin Chem 2001;47:926-934.[Abstract/Free Full Text]
  32. Jensen UG, Brandt NJ, Christensen E, Skovby F, Norgaard-Pedersen B, Simonsen H. Neonatal screening for galactosemia by quantitative analysis of hexose monophosphates using tandem mass spectrometry: a retrospective study. Clin Chem 2001;47:1364-1372.[Abstract/Free Full Text]
  33. Lempinen M, Kylänpää-Bäck 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;47:2103-2107.[Abstract/Free Full Text]
  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 Lys145–Lys146. Clin Chem 2001;47:1415-1423.[Abstract/Free Full Text]
  35. Sillanaukee P, Olsson U. Improved diagnostic classification of alcohol abusers by combining carbohydrate-deficient transferrin and {gamma}-glutamyltransferase. Clin Chem 2001;47:681-685.[Abstract/Free Full Text]
  36. Mourad M, Malaise J, Chaib Eddour D, De Meyer M, König 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;47:1241-1248.[Abstract/Free Full Text]
  37. Anton RF, Dominic KC, Bigelow M, Westby C, . CDTect Research Group. Comparison of Bio-Rad %CDT TIA and CDTect as laboratory markers of heavy alcohol use and their relationships with {gamma}-glutamyltransferase. Clin Chem 2001;47:1769-1775.[Abstract/Free Full Text]
  38. Jonsson M, Carlson J, Jeppsson JO, Simonsson P. Computer-supported detection of M-components and evaluation of immunoglobulins after capillary electrophoresis. Clin Chem 2001;47:110-117.[Abstract/Free Full Text]
  39. Andersen JM, Hedström J, Kemppainen E, Finne P, Poulakkainen P, Stenman UH. The ratio of trypsin-2-{alpha}1-antitrypsin to trypsinogen-1 discriminates biliary and alcohol-induced acute pancreatitis. Clin Chem 2001;47:231-236.[Abstract/Free Full Text]
  40. Richard S, Miossec V, Moreau JF, Taupin JL. Detection of oligoclonal immunoglobulins in cerebrospinal fluid by an immunofixation-peroxidase method. Clin Chem 2002;48:167-173.[Abstract/Free Full Text]
  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;48:261-268.[Abstract/Free Full Text]
  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 of mycophenolic acid in pediatric renal-transplant recipients on mycophenolate mofetil therapy. Clin Chem 2002;48:517-525.[Abstract/Free Full Text]
  43. Filler G, Priem F, Lepage N, Sinha P, Vollmer I, Clark H, et al. ß-Trace protein, cystatin C, ß2-microglobulin, and creatinine compared for detecting impaired glomerular filtration rates in children. Clin Chem 2002;48:729-736.[Abstract/Free Full Text]
  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. Clin Chem 2002;48:761-765.[Abstract/Free Full Text]
  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;48:850-858.[Abstract/Free Full Text]
  46. Wasmuth JC, Oliver y Minarro D, Homrighausen A, Leifeld L, Rockstroh JK, Sauerbruch T, et al. Phospholipid autoantibodies and the antiphospholipid antibody syndrome: diagnostic accuracy of 23 methods studied by variation in ROC curves with number of clinical manifestations. Clin Chem 2002;48:1004-1010.[Abstract/Free Full Text]
  47. Xu SQ, He M, Yu HP, Wang XY, Tan XL, Lu B, et al. Bioluminescent method for detecting telomerase activity. Clin Chem 2002;48:1016-1020.[Abstract/Free Full Text]
  48. Poon TC, Mok TS, Chan AT, Chan CM, Leong V, Tsui SH, et al. Quantification and utility of monosialylated {alpha}-fetoprotein in the diagnosis of hepatocellular carcinoma with nondiagnostic serum total {alpha}-fetoprotein. Clin Chem 2002;48:1021-1027.[Abstract/Free Full Text]
  49. Martinez M, Espana F, Royo M, Alapont JM, Navarro S, Estelles A, et al. The proportion of prostate-specific antigen (PSA) complexed to {alpha}1-antichymotrypsin improves the discrimination between prostate cancer and benign prostatic hyperplasia in men with a total PSA of 10 to 30 µg/L. Clin Chem 2002;48:1251-1256.[Abstract/Free Full Text]
  50. Stephan C, Cammann H, Semjonow A, Diamandis EP, Wymenga LF, Lein M, et al. Multicenter evaluation of an artificial neural network to increase the prostate cancer detection rate and reduce unnecessary biopsies. Clin Chem 2002;48:1279-1287.[Abstract/Free Full Text]
  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;48:1296-1304.[Abstract/Free Full Text]
  52. Krauss T, Emons G, Kuhn W, Augustin HG. Predictive value of routine circulating soluble endothelial cell adhesion molecule measurements during pregnancy. Clin Chem 2002;48:1418-1425.[Abstract/Free Full Text]
  53. Panteghini M, Cuccia C, Bonetti G, Giubbini R, Pagani F, Bonini E. Single-point cardiac troponin T at coronary care unit discharge after myocardial infarction correlates with infarct size and ejection fraction. Clin Chem 2002;48:1432-1436.[Abstract/Free Full Text]
  54. Oda H, Shiina Y, Seiki K, Sato N, Eguchi N, Urade Y. Development and evaluation of a practical ELISA for human urinary lipocalin-type prostaglandin D synthase. Clin Chem 2002;48:1445-1453.[Abstract/Free Full Text]
  55. Carroccio A, Vitale G, Di Prima L, Chifari N, Napoli S, La Russa C, et al. Comparison of anti-transglutaminase ELISAs and an anti-endomysial antibody assay in the diagnosis of celiac disease: a prospective study. Clin Chem 2002;48:1546-1550.[Abstract/Free Full Text]
  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 mass spectral serum profiles discriminates prostate cancer from noncancer patients. Clin Chem 2002;48:1835-1843.[Abstract/Free Full Text]
  57. Kauppinen R, von und zu Fraunberg M. Molecular and biochemical studies of acute intermittent porphyria in 196 patients and their families. Clin Chem 2002;48:1891-1900.[Abstract/Free Full Text]
  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;48:1919-1923.[Abstract/Free Full Text]
  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;48:1924-1930.[Abstract/Free Full Text]
  60. Kulpa J, Wojcik E, Reinfuss M, Kolodziejski L. Carcinoembryonic antigen, squamous cell carcinoma antigen, CYFRA 21-1, and neuron-specific enolase in squamous cell lung cancer patients. Clin Chem 2002;48:1931-1937.[Abstract/Free Full Text]
  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;48:2177-2186.[Abstract/Free Full Text]
  62. Ryden I, Pahlsson P, Lindgren S. Diagnostic accuracy of {alpha}1-acid glycoprotein fucosylation for liver cirrhosis in patients undergoing hepatic biopsy. Clin Chem 2002;48:2195-2201.[Abstract/Free Full Text]
  63. Penders J, Fiers T, Delanghe JR. Quantitative evaluation of urinalysis test strips. Clin Chem 2002;48:2236-2241.[Abstract/Free Full Text]
  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;34:377-384.[Web of Science][Medline] [Order article via Infotrieve]
  65. Bacigalupo MA, Bazzini P, Farina L, Ius A. Evaluation of three immunoassays for detection of toxoplasma-specific immunoglobulin G and M. Eur J Clin Chem Clin Biochem 1996;34:503-505.[Web of Science][Medline] [Order article via Infotrieve]
  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 System. Eur J Clin Chem Clin Biochem 1996;34:829-835.[Web of Science][Medline] [Order article via Infotrieve]
  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 radioimmunoassays for neuron-specific enolase. Eur J Clin Chem Clin Biochem 1996;34:679-682.[Web of Science][Medline] [Order article via Infotrieve]
  68. Conejo JR, Benedito JE, Jiménez A, Menchén M, Cano J, Granizo V, et al. Diagnostic value of three tumour markers determined in pleural effusions. Eur J Clin Chem Clin Biochem 1996;34:139-142.[Web of Science][Medline] [Order article via Infotrieve]
  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;34:579-584.[Web of Science][Medline] [Order article via Infotrieve]
  70. Collinson P, Gerhardt W, Katus HA, Müller-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;34:591-598.[Web of Science][Medline] [Order article via Infotrieve]
  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;39:374-379.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  72. von Eyben FE, Blaabjerg O, Hyltoft-Petersen P, Madsen EL, Amato R, Liu F, et al. Serum lactate dehydrogenase isoenzyme 1 and prediction of death in patients with metastatic testicular germ cell tumors. Clin Chem Lab Med 2001;39:38-44.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  73. Shaarawy M, Salem ME. Clinical value of microtransferrinuria and microalbuminuria in the prediction of preeclampsia. Clin Chem Lab Med 2001;39:29-34.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  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.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  75. Tello FL, Prats CH, González MD. Free and complexed prostate-specific antigen (PSA) in the early detection of prostate cancer. Clin Chem Lab Med 2001;39:116-120.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  76. Glojnaric I, Casl MT, Simic D, Lukac J. Serum amyloid A protein (SAA) in colorectal carcinoma. Clin Chem Lab Med 2001;39:129-133.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  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;39:801-805.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  78. Schellenberg F, Mennetrey L, Bacq Y, Pages JC. Carbohydrate-deficient transferrin (CDT)determination by nephelometry using a commercial kit. Analytical and diagnostic aspects. Clin Chem Lab Med 2001;39:866-871.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  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;39:223-228.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  80. Siekmeier R, Bierlich A, Jaross W. The white blood cell differential: three methods compared. Clin Chem Lab Med 2001;39:432-445.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  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.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  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;40:351-355.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  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;40:480-484.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  84. Kocna P, Vanícková Z, Peruicová J, Dvorák M. Tissue transglutaminase—serology markers for coeliac disease. Clin Chem Lab Med 2002;40:485-492.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  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;40:817-823.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  86. Iinuma 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 antigen. Clin Chem Lab Med 2002;40:832-836.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  87. Al-Daghistani HI, Abdel-Dayem M. Diagnostic value of various urine tests in the Jordanian population with urinary tract infection. Clin Chem Lab Med 2002;40:1048-1051.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  88. Hernando M, Gonzalez C, Sanchez A, Guevara P, Navajo JA, Papisch W, et al. Clinical evaluation of a new automated anti-dsDNA fluorescent immunoassay. Clin Chem Lab Med 2002;40:1056-1060.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  89. Burkhardt H, Bojarsky G, Gladisch R. Diagnostic efficiency of cystatin C and serum creatinine as markers of reduced glomerular filtration rate in the elderly. Clin Chem Lab Med 2002;40:1135-1138.[CrossRef][Medline] [Order article via Infotrieve]
  90. Zago L, Dupraz H, Sarchi M, Río 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;40:1301-1307.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  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 trial. A comparative before-and-after evaluation. JAMA 2001;285:1912-1915.
  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;134:663-694.[Abstract/Free Full Text]
  93. Knottnerus JS. The evidence based of clinical diagnosis 2002:237 BMJ Books London. .
  94. Feinstein AR. Misguided efforts and future challenges for research on "diagnostic tests". J Epidemiol Community Health 2002;56:330-332.[Abstract/Free Full Text]
  95. Hernández Aguado I. The winding road towards evidence based diagnoses. J Epidemiol Community Health 2002;56:323-325.[Free Full Text]



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