Fool's Gold: Why Imperfect Reference Tests Are Undermining the Evaluation of Novel Diagnostics: A Reevaluation of 5 Diagnostic Tests for Leptospirosis
| Autor: | Sharon J. Peacock, Janjira Thaipadungpanit, Lee D. Smythe, Direk Limmathurotsakul, Nicholas P. J. Day, Yupin Suputtamongkol, Ben S. Cooper, Elizabeth L. Turner, Vanaporn Wuthiekanun, Wirongrong Chierakul |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Microbiology (medical) endocrine system medicine.medical_specialty Adolescent 030231 tropical medicine Gastroenterology Lateral flow test Young Adult 03 medical and health sciences 0302 clinical medicine Leptospira Internal medicine Direct agglutination test parasitic diseases medicine Credible interval Humans Leptospirosis Blood culture Diagnostic Errors Articles and Commentaries Randomized Controlled Trials as Topic Microscopy 0303 health sciences Models Statistical medicine.diagnostic_test biology Diagnostic Tests Routine 030306 microbiology business.industry Diagnostic test Gold standard (test) Reference Standards medicine.disease biology.organism_classification 3. Good health Surgery Infectious Diseases business |
| Zdroj: | Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America |
| ISSN: | 1537-6591 1058-4838 |
| Popis: | We hypothesized that the gold standard for diagnosing leptospirosis is imperfect. We used Bayesian latent class models and random-effects meta-analysis to test this hypothesis and to determine the true accuracy of a range of alternative tests for leptospirosis diagnosis. Background. We observed that some patients with clinical leptospirosis supported by positive results of rapid tests were negative for leptospirosis on the basis of our diagnostic gold standard, which involves isolation of Leptospira species from blood culture and/or a positive result of a microscopic agglutination test (MAT). We hypothesized that our reference standard was imperfect and used statistical modeling to investigate this hypothesis. Methods. Data for 1652 patients with suspected leptospirosis recruited during three observational studies and one randomized control trial that described the application of culture, MAT, immunofluorescence assay (IFA), lateral flow (LF) and/or PCR targeting the 16S rRNA gene were reevaluated using Bayesian latent class models and random-effects meta-analysis. Results. The estimated sensitivities of culture alone, MAT alone, and culture plus MAT (for which the result was considered positive if one or both tests had a positive result) were 10.5% (95% credible interval [CrI], 2.7%–27.5%), 49.8% (95% CrI, 37.6%–60.8%), and 55.5% (95% CrI, 42.9%–67.7%), respectively. These low sensitivities were present across all 4 studies. The estimated specificity of MAT alone (and of culture plus MAT) was 98.8% (95% CrI, 92.8%–100.0%). The estimated sensitivities and specificities of PCR (52.7% [95% CrI, 45.2%–60.6%] and 97.2% [95% CrI, 92.0%–99.8%], respectively), lateral flow test (85.6% [95% CrI, 77.5%–93.2%] and 96.2% [95% CrI, 87.7%–99.8%], respectively), and immunofluorescence assay (45.5% [95% CrI, 33.3%–60.9%] and 96.8% [95% CrI, 92.8%–99.8%], respectively) were considerably different from estimates in which culture plus MAT was considered a perfect gold standard test. Conclusions. Our findings show that culture plus MAT is an imperfect gold standard against which to compare alterative tests for the diagnosis of leptospirosis. Rapid point-of-care tests for this infection would bring an important improvement in patient care, but their future evaluation will require careful consideration of the reference test(s) used and the inclusion of appropriate statistical models. |
| Databáze: | OpenAIRE |
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