Evaluating Multiple Diagnostic Tests: An Application to Cervical Intraepithelial Neoplasia

Authors: Areti Angeliki Veroniki, Sofia Tsokani, Evangelos Paraskevaidis, Dimitris Mavridis

Abstract:

The plethora of diagnostic test accuracy (DTA) studies has led to the increased use of systematic reviews and meta-analysis of DTA studies. Clinicians and healthcare professionals often consult DTA meta-analyses to make informed decisions regarding the optimum test to choose and use for a given setting. For example, the human papilloma virus (HPV) DNA, mRNA, and cytology can be used for the cervical intraepithelial neoplasia grade 2+ (CIN2+) diagnosis. But which test is the most accurate? Studies directly comparing test accuracy are not always available, and comparisons between multiple tests create a network of DTA studies that can be synthesized through a network meta-analysis of diagnostic tests (DTA-NMA). The aim is to summarize the DTA-NMA methods for at least three index tests presented in the methodological literature. We illustrate the application of the methods using a real data set for the comparative accuracy of HPV DNA, HPV mRNA, and cytology tests for cervical cancer. A search was conducted in PubMed, Web of Science, and Scopus from inception until the end of July 2019 to identify full-text research articles that describe a DTA-NMA method for three or more index tests. Since the joint classification of the results from one index against the results of another index test amongst those with the target condition and amongst those without the target condition are rarely reported in DTA studies, only methods requiring the 2x2 tables of the results of each index test against the reference standard were included. Studies of any design published in English were eligible for inclusion. Relevant unpublished material was also included. Ten relevant studies were finally included to evaluate their methodology. DTA-NMA methods that have been presented in the literature together with their advantages and disadvantages are described. In addition, using 37 studies for cervical cancer obtained from a published Cochrane review as a case study, an application of the identified DTA-NMA methods to determine the most promising test (in terms of sensitivity and specificity) for use as the best screening test to detect CIN2+ is presented. As a conclusion, different approaches for the comparative DTA meta-analysis of multiple tests may conclude to different results and hence may influence decision-making. Acknowledgment: This research is co-financed by Greece and the European Union (European Social Fund- ESF) through the Operational Programme «Human Resources Development, Education and Lifelong Learning 2014-2020» in the context of the project “Extension of Network Meta-Analysis for the Comparison of Diagnostic Tests ” (MIS 5047640).

Keywords: colposcopy, diagnostic test, HPV, network meta-analysis