GRADE guidance 37: rating imprecision in a body of evidence on test accuracy.

Objectives: To provide guidance on rating imprecision in a body of evidence assessing the accuracy of a single test. This guide will clarify when Grading of Recommendations Assessment, Development and Evaluation (GRADE) users should consider rating down the certainty of evidence by one or more levels for imprecision in test accuracy.

Study Design And Setting: A project group within the GRADE working group conducted iterative discussions and presentations at GRADE working group meetings to produce this guidance.

Xpert MTB/RIF Ultra assay for tuberculosis disease and rifampicin resistance in children.

Background: Every year, an estimated one million children and young adolescents become ill with tuberculosis, and around 226,000 of those children die. Xpert MTB/RIF Ultra (Xpert Ultra) is a molecular World Health Organization (WHO)-recommended rapid diagnostic test that simultaneously detects Mycobacterium tuberculosis complex and rifampicin resistance. We previously published a Cochrane Review 'Xpert MTB/RIF and Xpert MTB/RIF Ultra assays for tuberculosis disease and rifampicin resistance in children'.

Rapid molecular tests for tuberculosis and tuberculosis drug resistance: a qualitative evidence synthesis of recipient and provider views.

Background: Programmes that introduce rapid molecular tests for tuberculosis and tuberculosis drug resistance aim to bring tests closer to the community, and thereby cut delay in diagnosis, ensure early treatment, and improve health outcomes, as well as overcome problems with poor laboratory infrastructure and inadequately trained personnel. Yet, diagnostic technologies only have an impact if they are put to use in a correct and timely manner. Views of the intended beneficiaries are important in uptake of diagnostics, and their effective use also depends on those implementing testing programmes, including providers, laboratory professionals, and staff in health ministries.

Screening tests for active pulmonary tuberculosis in children.

Background: Globally, children under 15 years represent approximately 12% of new tuberculosis cases, but 16% of the estimated 1.4 million deaths. This higher share of mortality highlights the urgent need to develop strategies to improve case detection in this age group and identify children without tuberculosis disease who should be considered for tuberculosis preventive treatment.

Xpert MTB/RIF and Xpert Ultra assays for screening for pulmonary tuberculosis and rifampicin resistance in adults, irrespective of signs or symptoms.

Background: Tuberculosis is a leading cause of infectious disease-related death and is one of the top 10 causes of death worldwide. The World Health Organization (WHO) recommends the use of specific rapid molecular tests, including Xpert MTB/RIF or Xpert Ultra, as initial diagnostic tests for the detection of tuberculosis and rifampicin resistance in people with signs and symptoms of tuberculosis. However, the WHO estimates that nearly one-third of all active tuberculosis cases go undiagnosed and unreported.

Xpert MTB/RIF Ultra and Xpert MTB/RIF assays for extrapulmonary tuberculosis and rifampicin resistance in adults.

Background: Xpert MTB/RIF Ultra (Xpert Ultra) and Xpert MTB/RIF are World Health Organization (WHO)-recommended rapid nucleic acid amplification tests (NAATs) widely used for simultaneous detection of Mycobacterium tuberculosis complex and rifampicin resistance in sputum. To extend our previous review on extrapulmonary tuberculosis (Kohli 2018), we performed this update to inform updated WHO policy (WHO Consolidated Guidelines (Module 3) 2020).

Objectives: To estimate diagnostic accuracy of Xpert Ultra and Xpert MTB/RIF for extrapulmonary tuberculosis and rifampicin resistance in adults with presumptive extrapulmonary tuberculosis.

Variation in the observed effect of Xpert MTB/RIF testing for tuberculosis on mortality: A systematic review and analysis of trial design considerations.

Most studies evaluating the effect of Xpert MTB/RIF testing for tuberculosis (TB) concluded that it did not reduce overall mortality compared to usual care. We conducted a systematic review to assess whether key study design and execution features contributed to earlier identification of patients with TB and decreased pre-treatment loss to follow-up, thereby reducing the potential impact of Xpert MTB/RIF testing. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Scopus for literature published from 1 January 2009 to February 2019.

Xpert MTB/RIF and Xpert MTB/RIF Ultra assays for active tuberculosis and rifampicin resistance in children.

Background: Every year, at least one million children become ill with tuberculosis and around 200,000 children die. Xpert MTB/RIF and Xpert Ultra are World Health Organization (WHO)-recommended rapid molecular tests that simultaneously detect tuberculosis and rifampicin resistance in adults and children with signs and symptoms of tuberculosis, at lower health system levels. To inform updated WHO guidelines on molecular assays, we performed a systematic review on the diagnostic accuracy of these tests in children presumed to have active tuberculosis.

Current methods for development of rapid reviews about diagnostic tests: an international survey.

Background: Rapid reviews (RRs) have emerged as an efficient alternative to time-consuming systematic reviews-they can help meet the demand for accelerated evidence synthesis to inform decision-making in healthcare. The synthesis of diagnostic evidence has important methodological challenges. Here, we performed an international survey to identify the current practice of producing RRs for diagnostic tests.

Improving the design of studies evaluating the impact of diagnostic tests for tuberculosis on health outcomes: a qualitative study of perspectives of diverse stakeholders.

Studies evaluating the impact of Xpert MTB/RIF testing for tuberculosis (TB) have demonstrated varied effects on health outcomes with many studies showing inconclusive results. We explored perceptions among diverse stakeholders about studies evaluating the impact of TB diagnostic tests, and identified suggestions for improving these studies. We used purposive sampling with consideration for differing expertise and geographical balance and conducted in depth semi-structured interviews.

GRADE guidelines: 21 part 1. Study design, risk of bias, and indirectness in rating the certainty across a body of evidence for test accuracy.

Objectives: This article provides updated GRADE guidance about how authors of systematic reviews and health technology assessments and guideline developers can assess the results and the certainty of evidence (also known as quality of the evidence or confidence in the estimates) of a body of evidence addressing test accuracy (TA).

Study Design And Setting: We present an overview of the GRADE approach and guidance for rating certainty in TA in clinical and public health and review the presentation of results of a body of evidence regarding tests. Part 1 of the two parts in this 21st guidance article about how to apply GRADE focuses on understanding study design issues in test accuracy, provide an overview of the domains, and describe risk of bias and indirectness specifically.

GRADE guidelines: 21 part 2. Test accuracy: inconsistency, imprecision, publication bias, and other domains for rating the certainty of evidence and presenting it in evidence profiles and summary of findings tables.

Objectives: This article provides updated GRADE guidance about how authors of systematic reviews and health technology assessments and guideline developers can rate the certainty of evidence (also known as quality of the evidence or confidence in the estimates) of a body of evidence addressing test accuracy (TA) on the domains imprecision, inconsistency, publication bias, and other domains. It also provides guidance for how to present synthesized information in evidence profiles and summary of findings tables.

Study Design And Setting: We present guidance for rating certainty in TA in clinical and public health and review the presentation of results of a body of evidence regarding tests.

Lateral flow urine lipoarabinomannan assay for detecting active tuberculosis in people living with HIV.

Background: The lateral flow urine lipoarabinomannan (LF-LAM) assay Alere Determine™ TB LAM Ag is recommended by the World Health Organization (WHO) to help detect active tuberculosis in HIV-positive people with severe HIV disease. This review update asks the question, "does new evidence justify the use of LF-LAM in a broader group of people?", and is part of the WHO process for updating guidance on the use of LF-LAM.

Objectives: To assess the accuracy of LF-LAM for the diagnosis of active tuberculosis among HIV-positive adults with signs and symptoms of tuberculosis (symptomatic participants) and among HIV-positive adults irrespective of signs and symptoms of tuberculosis (unselected participants not assessed for tuberculosis signs and symptoms).

Guidance for Studies Evaluating the Accuracy of Sputum-Based Tests to Diagnose Tuberculosis.

Tests that can replace sputum smear microscopy have been identified as a top priority diagnostic need for tuberculosis by the World Health Organization. High-quality evidence on diagnostic accuracy for tests that may meet this need is an essential requirement to inform decisions about policy and scale-up. However, test accuracy studies are often of low and inconsistent quality and poorly reported, leading to uncertainty about true test performance.

Guidance for the Evaluation of Tuberculosis Diagnostics That Meet the World Health Organization (WHO) Target Product Profiles: An Introduction to WHO Process and Study Design Principles.

Existing high-priority target product profiles (TPPs) of the World Health Organization (WHO) establish important needs for tuberculosis (TB) diagnostic development. Building on this earlier work, this guidance series aims to provide study guidance for performing accuracy studies of novel diagnostic products that may meet the 4 high-priority WHO TPPs and thus enable adequate evidence generation to inform a WHO evidence review process. Diagnostic accuracy studies represent a fundamental step in the validation of all tests.

Rapid reviews of medical tests used many similar methods to systematic reviews but key items were rarely reported: a scoping review.

Background And Objectives: Rapid reviews provide an efficient alternative to standard systematic reviews in response to a high priority or urgent need. Although rapid reviews of interventions have been extensively evaluated, little is known about the characteristics of rapid reviews of diagnostic evidence.

Study Design And Setting: We performed a scoping review for rapid reviews of medical tests published from 2013 to 2018.

Xpert MTB/RIF and Xpert MTB/RIF Ultra for pulmonary tuberculosis and rifampicin resistance in adults.

Background: Xpert MTB/RIF (Xpert MTB/RIF) and Xpert MTB/RIF Ultra (Xpert Ultra), the newest version, are the only World Health Organization (WHO)-recommended rapid tests that simultaneously detect tuberculosis and rifampicin resistance in persons with signs and symptoms of tuberculosis, at lower health system levels. A previous Cochrane Review found Xpert MTB/RIF sensitive and specific for tuberculosis (Steingart 2014). Since the previous review, new studies have been published.

Defining ranges for certainty ratings of diagnostic accuracy: a GRADE concept paper.

Objective: The objective of the study was to clarify how the Grading of Recommendations Assessment, Development and Evaluation (GRADE) concept of certainty of evidence applies to certainty ratings of test accuracy.

Study Design And Setting: After initial brainstorming with GRADE Working Group members, we iteratively refined and clarified the approaches for defining ranges when assessing the certainty of evidence for test accuracy within a systematic review, health technology assessment, or guideline.

Results: Ranges can be defined both for single test accuracy and for comparative accuracy of multiple tests.

Challenges of rapid reviews for diagnostic test accuracy questions: a protocol for an international survey and expert consultation.

Background: Assessment of diagnostic tests, broadly defined as any element that aids in the collection of additional information for further clarification of a patient's health status, has increasingly become a critical issue in health policy and decision-making. Diagnostic evidence, including the accuracy of a medical test for a target condition, is commonly appraised using standard systematic review methodology. Owing to the considerable time and resources required to conduct these, rapid reviews have emerged as a pragmatic alternative by tailoring methods according to the decision maker's circumstances.

GRADE guidelines: 22. The GRADE approach for tests and strategies-from test accuracy to patient-important outcomes and recommendations.

Objectives: This article describes the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group's framework of moving from test accuracy to patient or population-important outcomes. We focus on the common scenario when studies directly evaluating the effect of diagnostic and other tests or strategies on health outcomes are not available or are not providing the best available evidence.

Study Design And Setting: Using practical examples, we explored how guideline developers and other decision makers can use information from test accuracy to develop a recommendation by linking evidence that addresses downstream consequences.