TOMAS-R: A template to identify and plan analysis for clinically important variation and multiplicity in diagnostic test accuracy systematic reviews

Abstract

The Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy (DTA) provides guidance on important aspects of conducting a test accuracy systematic review. In this paper we present TOMAS-R (Template of Multiplicity and Analysis in Systematic Reviews), a structured template to use in conjunction with current Cochrane DTA guidance, to help identify complexities in the review question and to assist planning of data extraction and analysis when clinically important variation and multiplicity is present. Examples of clinically important variation and multiplicity could include differences in participants, index tests and test methods, target conditions and reference standards used to define them, study design and methodological quality. Our TOMAS-R template goes beyond the broad topic headings in current guidance that are sources of potential variation and multiplicity, by providing prompts for common sources of heterogeneity encountered from our experience of authoring over 100 reviews. We provide examples from two reviews to assist users. The TOMAS-R template adds value by supplementing available guidance for DTA reviews by providing a tool to facilitate discussions between methodologists, clinicians, statisticians and patient/public team members to identify the full breadth of review question complexities early in the process. The use of a structured set of prompting questions at the important stage of writing the protocol ensures clinical relevance as a main focus of the review, while allowing identification of key clinical components for data extraction and later analysis thereby facilitating a more efficient review process.

Keywords: Diagnostic test accuracy; Heterogeneity; Meta-analysis; Methodology; Multiplicity; SROC; Systematic review; Template; forest.

Fig. 1

Flowchart of planned analyses: Typhoid review. Different components of variation leading to complexity in review of typhoid rapid tests. Coloured boxes indicate the TOMAS-R domain where complexity identified: pink boxes review topic; light blue boxes participant domain; dark blue boxes index test domain; light green boxes target condition domain; dark green boxes study design and quality domain. Dotted lines separate complexity and allow alignment to the diagnostic accuracy that the analysis would address. Each bullet point follows the question “What is the diagnostic accuracy...” so for example if all rapid test results are combined the first bullet point is used so the analysis will answer the question “What is the diagnostic accuracy averaged over all tests and test thresholds?” Yellow stars indicate key complexities identified as requiring separate analyses for the review to have clinical relevance

Fig. 2

Flowchart of planned analyses: Ovarian cancer serum biomarker review. Different components of variation leading to complexity in review of serum biomarkers in ovarian cancer. Coloured boxes indicate the TOMAS-R domain where complexity identified: pink boxes review topic; light blue boxes participant domain; dark blue boxes index test domain; light green boxes target condition domain. Dotted lines separate complexity and allow alignment to the diagnostic accuracy that the analysis would address. Each bullet point follows the question “What is the diagnostic accuracy...” so for example if test results are separated by the menopausal status of the women, the second bullet point is used so the analysis will answer the question “What is the diagnostic accuracy averaged separately for each menopausal group?” Yellow stars indicate key complexities identified as requiring separate analyses for the review to have clinical relevance