Preface

Patrick M. Bossuyt, Jonathan J. Deeks, Mariska M. Leeflang, Yemisi Takwoingi and Ella Flemyng

Medical tests are an indispensable element of modern‐day health care. Clinicians rely on medical tests to find the likely cause of a patient’s signs and symptoms, to evaluate the extent of disease, to predict the future course of the condition, to screen for asymptomatic disease and in many other situations.

Like any other intervention in health care, a medical test should be properly evaluated before its use can be recommended. Tests must make little error in measuring chemical, biological or physical quantities, or in detecting features, whether a clinical doctor assessing symptoms, a pathologist seeing a biopsy or a radiologist identifying an image. However, as well as being accurate, tests must also provide the right information to guide clinical actions. For this reason, a medical test must be evaluated for its clinical performance.

For diagnostic tests, this clinical performance is referred to as diagnostic accuracy: the ability of a test to correctly identify people who have or do not have the target condition. A diagnostic accuracy study assesses the results of an index test (test of interest) against a reference standard and provides estimates of the test’s performance. Such evaluations of clinical performance should be done in a real‐world setting within the context of a clinical pathway taking into account the intended use and target population.

For many tests a range of diagnostic accuracy studies have been reported in the medical literature. As in other areas of science, systematic reviews of such studies can provide informative syntheses of the available evidence. A systematic review can provide decision makers and other stakeholders with an overview of the currently available evidence about a test’s diagnostic accuracy. We expect such reviews to include a well‐defined review question, systematic searches of all relevant studies, evaluations of the risk of bias and applicability of identified studies and, if possible, meta‐analyses that statistically combine the results of multiple studies.

The methods for systematic reviews of diagnostic accuracy studies were slow to develop, compared to methods for systematic reviews of randomized controlled trials of interventions. This difference parallels a difference in rigour in the primary studies and an understanding of sources of bias. Other explanations can be found as well: the wide differences in study objectives and designs of test accuracy studies, ranging from biomarker discovery studies to large‐scale clinical applications in the intended use setting. This variation and complexity of study designs can lead to results that are either not relevant or not valid for answering a test accuracy review question. This is further compounded by the fact that measures of test accuracy are not automatically transferable across different populations and settings. Unlike randomized controlled trials, test accuracy studies typically provide paired proportions to indicate how well the test performs in those who have and those who do not have the target condition, i.e. the test’s sensitivity and specificity. This poses specific challenges for meta‐analysis. Furthermore, sensitivity and specificity vary considerably more across studies than estimates of relative risk from clinical trials because they are proportions, not relative or absolute differences.

“Another challenge is in addressing clinically important comparative questions when there are competing tests that can be used at the same point in the clinical pathway. Systematic reviews of test accuracy can evaluate and compare the accuracy of two or more tests. While many studies evaluate the accuracy of a single index test, far fewer compare the accuracy of two or more index tests. Such comparative test accuracy studies, which can provide robust evidence to inform test selection, deserve greater appreciation from clinical investigators, researchers, grant‐awarding organizations funding test research, and those developing test use recommendations.”

“Evidence on how the results of primary studies differ according to methodological features may be provided by meta‐epidemiological studies. These meta‐epidemiological studies often use data collected from systematic reviews. For example, the earliest meta‐epidemiological studies based on Cochrane reviews strengthened the importance of allocation concealment in randomised trials. Similar empirical studies using systematic reviews of diagnostic accuracy have confirmed essential elements of valid test accuracy studies, from avoiding the unnecessary inclusion of healthy controls to the need for appropriate statistical methods.”

“This Handbook is informed by currently available empirical evidence and theoretical understanding of primary diagnostic accurarcy studies, review methods, and techniques for meta‐analysis. The ongoing creation of Cochrane reviews will provide data for future studies that will shape our knowledge of how primary test accuracy studies and systematic reviews could be better performed.”

This Handbook has a long history. Its development started around 2002, when a number of us felt that the methodology for systematic reviews of test accuracy studies had sufficiently advanced to guide researchers. Since then, an incredible number of colleagues have contributed to its gestation. Many of these have become authors of chapters in this Handbook. Others are explicitly acknowledged in various chapters for their contribution. Yet many more have contributed, through various discussions in methods groups sessions, conferences and other meetings. While we worked on this Handbook progress did not halt and in several steps of the review process more methodological advances were made, while best practices emerged in other areas.

Considerable progress has been made in searching, in evaluating risk of bias and applicability and in meta‐analysis. The continuing development of software programs and user‐written macros has made meta‐analysis methods more accessible. A challenging area remains the communication of findings from reviews to decision makers and other stakeholders. Systematic reviews typically reveal substantial variability across studies and this variability makes it challenging to appreciate the true diagnostic accuracy of medical tests.

The authors of this Handbook have aimed to develop guidance based on the best current knowledge. We expect that several of the methods and practices will be advanced even further in the coming years, necessitating an update of this Handbook in the future. We are confident that the guidance in this Handbook will enable researchers in Cochrane and beyond to prepare informative reviews of the available literature to benefit patients and clinicians. In short: to all of us.

About Cochrane

Cochrane is an international network of health practitioners, researchers, methodologists, patients and carers, and others, with a vision of a world of better health for all people where decisions about health and care are informed by high‐quality evidence (www.cochrane.org). Founded as The Cochrane Collaboration in 1993, it is a not‐for‐profit organization whose members aim to produce credible, accessible health information that is free from commercial sponsorship and other conflicts of interest.

Cochrane works collaboratively with health professionals, policy makers and international organizations, such as the World Health Organization (WHO), to support the development of evidence‐informed guidelines and policy. WHO guidelines on critical public health issues such as the consolidated guidelines on systematic screening for tuberculosis disease (2021) and rapid diagnostics for tuberculosis detection (2021), and the WHO Essential Diagnostics List (2021), are underpinned by Cochrane Reviews.

There are examples of the impact of Cochrane Reviews on health and health care. Globally in 2020, a WHO‐recommended rapid molecular test was used as the initial diagnostic test for 1.9 million (33%) of the 5.8 million people newly diagnosed with tuberculosis in 2020 (Global Tuberculosis Report 2021). Several rapid diagnostic tests (RDTs) for tuberculosis have been endorsed by the WHO since 2010 based on evidence from many Cochrane Reviews. A Cochrane Special Collection on diagnosing tuberculosis, first published in 2019 and last updated in March 2022 to celebrate World Tuberculosis Day (www.cochranelibrary.com/collections/doi/SC000034/full), highlighted the influential Cochrane reviews that have informed the two WHO consolidated guidelines on systematic screening and rapid diagnostics for tuberculosis. The use of RDTs for tuberculosis has contributed to the decentralization of testing and allowed patients to be diagnosed quickly with earlier initiation of appropriate treatment in many low‐ and middle‐income countries. Rapid and reliable testing has also facilitated earlier detection of drug resistance and reduced mortality from tuberculosis among persons living with HIV.

Cochrane Reviews are published in full online in the Cochrane Database of Systematic Reviews, which is a core component of the Cochrane Library (www.cochranelibrary.com). The Cochrane Library was first published in 1996, and is now an online collection of multiple databases. The first Cochrane Review of diagnostic test accuracy was published in 2008.

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