Introduction to Clinical Diagnosis

  • Giuseppe Biondi-ZoccaiEmail author
  • Mariangela Peruzzi
  • Simona Mastrangeli
  • Giacomo Frati


Clinical practice is based on decision-making, with choices stemming from a coherent yet pragmatic modeling process of the actual clinical scenario, and diagnosis a key preamble of any decision. Briefly, diagnosis is the process of identifying the actual cause(s) of a complex maze of pathological signs and symptoms from beginning to late consequences. Diagnosis is however an elusive concept in real-world medical practice, as physicians continue to face uncertainty with pragmatism. Accordingly, different diagnostic levels can be envisioned even for the simplest conditions, such as the common cold or anemia. More specifically, medical diagnosis in a living being requires almost always some approximation and reliance on a reference standard (improperly also called gold standard). Whenever a formal comparison is made between the index test being used and the expected or actual findings from the reference test, a study on the diagnostic accuracy of such index test is generated, relying on the comparative accuracy of the index versus reference test. Yet, in the current era of plural and connected medical practice and research, no single study can be considered final, in terms of perfect and enduring internal and external validity. Facing a plethora of similar studies on the diagnostic test accuracy of a medical test can be very challenging. The only acceptable and constructive approach to such challenge is to compile a qualitative and quantitative collection of such studies and to generate a comprehensive summary. This is exactly the goal of systematic reviews and meta-analyses of diagnostic test accuracy studies.


Accuracy Diagnosis Meta-analysis Systematic review 





  1. 1.
    Ackerknecht EH, Rosenberg CE, Hausshofer L. A short history of medicine. Baltimore, MD: Johns Hopkins University Press; 2016.Google Scholar
  2. 2.
    Adeleye GG, Acquah-Dadzie K, Dadzie KA, Sienkewicz TJ, McDonough JT. World dictionary of foreign expressions: a resource for readers and writers. Mundelein, IL: Bolchazy-Carducci; 1999.Google Scholar
  3. 3.
    Popper K. The logic of scientific discovery. London, UK: Routledge; 2002.Google Scholar
  4. 4.
    Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C, Budaj A, Bugiardini R, Crea F, Cuisset T, Di Mario C, Ferreira JR, Gersh BJ, Gitt AK, Hulot JS, Marx N, Opie LH, Pfisterer M, Prescott E, Ruschitzka F, Sabaté M, Senior R, Taggart DP, van der Wall EE, Vrints CJ. 2013 ESC guidelines on the management of stable coronary artery disease: the task force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J. 2013;34:2949–3003.CrossRefPubMedGoogle Scholar
  5. 5.
    Smith SC Jr, Allen J, Blair SN, Bonow RO, Brass LM, Fonarow GC, Grundy SM, Hiratzka L, Jones D, Krumholz HM, Mosca L, Pearson T, Pfeffer MA, Taubert KA, AHA; ACC; National Heart, Lung, and Blood Institute. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update endorsed by the National Heart, Lung, and Blood Institute. J Am Coll Cardiol. 2006;47(10):2130–9.CrossRefPubMedGoogle Scholar
  6. 6.
    Cochrane collaboration: handbook for diagnostic test accuracy reviews. Accessed 27 June 2018.
  7. 7.
  8. 8.
    Bossuyt PM, Irwig L, Craig J, Glasziou P. Comparative accuracy: assessing new tests against existing diagnostic pathways. BMJ. 2006;332:1089–92.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Nudi F, Iskandrian AE, Schillaci O, Peruzzi M, Frati G, Biondi-Zoccai G. Diagnostic accuracy of myocardial perfusion imaging with CZT technology: systemic review and meta-analysis of comparison with invasive coronary angiography. JACC Cardiovasc Imaging. 2017;10:787–94.CrossRefPubMedGoogle Scholar
  10. 10.
    Pucci S, Bonanno E, Sesti F, Mazzarelli P, Mauriello A, Ricci F, Zoccai GB, Rulli F, Galatà G, Spagnoli LG. Clusterin in stool: a new biomarker for colon cancer screening? Am J Gastroenterol. 2009;104:2807–15.CrossRefPubMedGoogle Scholar
  11. 11.
    D’Ascenzo F, Barbero U, Cerrato E, Lipinski MJ, Omedè P, Montefusco A, Taha S, Naganuma T, Reith S, Voros S, Latib A, Gonzalo N, Quadri G, Colombo A, Biondi-Zoccai G, Escaned J, Moretti C, Gaita F. Accuracy of intravascular ultrasound and optical coherence tomography in identifying functionally significant coronary stenosis according to vessel diameter: a meta-analysis of 2,581 patients and 2,807 lesions. Am Heart J. 2015;169:663–73.CrossRefPubMedGoogle Scholar
  12. 12.
    Deeks JJ, Macaskill P, Irwig L. The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. J Clin Epidemiol. 2005;58:882–93.CrossRefPubMedGoogle Scholar
  13. 13.
    Dinnes J, Deeks J, Kirby J, Roderick P. A methodological review of how heterogeneity has been examined in systematic reviews of diagnostic test accuracy. Health Technol Assess. 2005;9:1–113.CrossRefPubMedGoogle Scholar
  14. 14.
    Irwig L, Tosteson AN, Gatsonis C, Lau J, Colditz G, Chalmers TC, Mosteller F. Guidelines for meta-analyses evaluating diagnostic tests. Ann Intern Med. 1994;120:667–76.CrossRefPubMedGoogle Scholar
  15. 15.
    Garrone P, Biondi-Zoccai G, Salvetti I, Sina N, Sheiban I, Stella PR, Agostoni P. Quantitative coronary angiography in the current era: principles and applications. J Interv Cardiol. 2009;22:527–36.CrossRefPubMedGoogle Scholar
  16. 16.
    Novara M, D'Ascenzo F, Gonella A, Bollati M, Biondi-Zoccai G, Moretti C, Omedè P, Sciuto F, Sheiban I, Gaita F. Changing of SYNTAX score performing fractional flow reserve in multivessel coronary artery disease. J Cardiovasc Med (Hagerstown). 2012;13:368–75.CrossRefGoogle Scholar
  17. 17.
    Biondi-Zoccai G, editor. Network meta-analysis: evidence synthesis with mixed treatment comparison. Hauppauge, NY: Nova Science Publishers; 2014.Google Scholar
  18. 18.
    Biondi-Zoccai G. Umbrella reviews. Evidence synthesis with overviews of reviews and meta-epidemiologic studies. Springer International: Cham, Switzerland; 2016.Google Scholar
  19. 19.
    Nudi F, Lotrionte M, Biasucci LM, Peruzzi M, Marullo AG, Frati G, Valenti V, Giordano A, Biondi-Zoccai G. Comparative safety and effectiveness of coronary computed tomography: systematic review and meta-analysis including 11 randomized controlled trials and 19,957 patients. Int J Cardiol. 2016;222:352–8.CrossRefPubMedGoogle Scholar
  20. 20.
    Siontis KC, Siontis GC, Contopoulos-Ioannidis DG, Ioannidis JP. Diagnostic tests often fail to lead to changes in patient outcomes. J Clin Epidemiol. 2014;67:612–21.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Giuseppe Biondi-Zoccai
    • 1
    • 2
    Email author
  • Mariangela Peruzzi
    • 1
  • Simona Mastrangeli
    • 3
  • Giacomo Frati
    • 1
    • 2
  1. 1.Department of Medico-Surgical Sciences and BiotechnologiesSapienza University of RomeLatinaItaly
  2. 2.Department of AngioCardioNeurologyIRCCS NeuromedPozzilliItaly
  3. 3.Superior School of Advanced StudiesSapienza University of RomeRomeItaly

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