Diagnostic Models Combining Clinical Information, Ultrasound and Biochemical Markers for Ovarian Cancer: Cochrane Systematic Review and Meta-Analysis.

Background: Ovarian cancer (OC) is a diagnostic challenge, with the majority diagnosed at late stages. Existing systematic reviews of diagnostic models either use inappropriate meta-analytic methods or do not conduct statistical comparisons of models or stratify test performance by menopausal status. Methods: We searched CENTRAL, MEDLINE, EMBASE, CINAHL, CDSR, DARE, Health Technology Assessment Database and SCI Science Citation Index, trials registers, conference proceedings from 1991 to June 2019. Cochrane collaboration review methods included QUADAS-2 quality assessment and meta-analysis using hierarchical modelling. RMI, ROMA or ADNEX at any test positivity threshold were investigated. Histology or clinical follow-up was the reference standard. We excluded screening studies, studies restricted to pregnancy, recurrent or metastatic OC. 2 × 2 diagnostic tables were extracted separately for pre- and post-menopausal women. Results: We included 58 studies (30,121 patients, 9061 cases of ovarian cancer). Prevalence of OC ranged from 16 to 55% in studies. For premenopausal women, ROMA at a threshold of 13.1 (+/−2) and ADNEX at a threshold of 10% demonstrated significantly higher sensitivity compared to RMI I at 200 (p < 0.0001) 77.8 (72.5, 82.4), 94.9 (92.5, 96.6), and 57.1% (50.6 to 63.4) but lower specificity (p < 0.002), 92.5 (90.0, 94.4), 84.3 (81.3, 86.8), and 78.2 (75.8, 80.4). For postmenopausal women, ROMA at a threshold of 27.7 (+/−2) and AdNEX at a threshold of 10% demonstrated significantly higher sensitivity compared to RMI I at a threshold of 200 (p < 0.001) 90.4 (87.4, 92.7), 97.6 (96.2, 98.5), and 78.7 (74.3, 82.5), specificity of ROMA was comparable, whilst ADneX was lower, 85.5 (81.3, 88.9), 81.3 (76.9, 85.0) (p = 0.155), compared to RMI 55.2 (51.2, 59.1) (p < 0.001). Conclusions: In pre-menopausal women, ROMA and ADNEX offer significantly higher sensitivity but significantly decreased specificity. In post-menopausal women, ROMA demonstrates significantly higher sensitivity and comparable specificity to RMI I, ADNEX has the highest sensitivity of all models, but with significantly reduced specificity. RMI I has poor sensitivity compared to ROMA or ADNEX. Choice between ROMA and ADNEX as a replacement test will depend on cost effectiveness and resource implications.

QUADAS-C: A Tool for Assessing Risk of Bias in Comparative Diagnostic Accuracy Studies.

Comparative diagnostic test accuracy studies assess and compare the accuracy of 2 or more tests in the same study. Although these studies have the potential to yield reliable evidence regarding comparative accuracy, shortcomings in the design, conduct, and analysis may bias their results. The currently recommended quality assessment tool for diagnostic test accuracy studies, QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2), is not designed for the assessment of test comparisons. The QUADAS-C (Quality Assessment of Diagnostic Accuracy Studies-Comparative) tool was developed as an extension of QUADAS-2 to assess the risk of bias in comparative diagnostic test accuracy studies. Through a 4-round Delphi study involving 24 international experts in test evaluation and a face-to-face consensus meeting, an initial version of the tool was developed that was revised and finalized following a pilot study among potential users. The QUADAS-C tool retains the same 4-domain structure of QUADAS-2 (Patient Selection, Index Test, Reference Standard, and Flow and Timing) and comprises additional questions to each QUADAS-2 domain. A risk-of-bias judgment for comparative accuracy requires a risk-of-bias judgment for the accuracy of each test (resulting from QUADAS-2) and additional criteria specific to test comparisons. Examples of such additional criteria include whether participants either received all index tests or were randomly assigned to index tests, and whether index tests were interpreted with blinding to the results of other index tests. The QUADAS-C tool will be useful for systematic reviews of diagnostic test accuracy addressing comparative questions. Furthermore, researchers may use this tool to identify and avoid risk of bias when designing a comparative diagnostic test accuracy study.

Dried blood spot and mini-tube blood sample collection kits for postal HIV testing services: a comparative review of successes in a real-world setting.

OBJECTIVES: This is a comparative review between using dried blood spot (DBS) and mini-tube (MT) HIV sampling kits as part of an online sexually transmitted infection (STI) postal testing service. England has recently seen increases in internet-based and postal (eHealth) STI services. Expanding accessibility and testing for patients, cost implications and narrowing the HIV undiagnosed margin are drivers for this. METHODS: In 2017, data were reviewed from an online postal STI kit requesting service at a time of transitioning from MT to DBS. We compared the STI postal kit and HIV blood sample return rates, and the successful processing/analysis rates of the DBS and MT kits. Descriptive statistics were applied to participant characteristics, with Pearson's χ2 or Fisher exact test used to demonstrate statistical differences. We also describe and calculate a 'request-to-result ratio' (RRR) for both kit types. The RRR is defined as the number of online kit requests required to produce one successfully analysed result. RESULTS: 550 STI postal kit requests from a North-West of England region were reviewed from 13 June 2017 to 22 September 2017 (275 MT, 275 DBS). Baseline characteristics between the two groups were comparable (63% woman, 90% white British and 86% heterosexual with a median age of 26 years). The successful processing rate for the DBS was 98.8% c.f. 55.7% for the MT (p<0.001). The RRR for MT was 2.96, c.f. 1.70 for DBS. There was a 5.4% false positive HIV rate in the MT c.f. none in the DBS. CONCLUSIONS: This comparative analysis suggests that in this community setting, the use of postal HIV DBS kits resulted in a significantly improved RRR compared with MT. The biggest factor was the large number of MT samples not analysed due to inadequate blood volumes. The unexpected level of false positive results in the MT samples needs confirming in larger studies.

Where and how to search for information on the effectiveness of public health interventions--a case study for prevention of cardiovascular disease.

BACKGROUND: This case study documents the experience of searching for information on the effectiveness of population-level multi-factor interventions for the prevention of cardiovascular disease (CVD) to inform guidance from NICE (National Institute for Health and Care Excellence). OBJECTIVES: To compare suitability of different databases for searches on a medical public health topic and performance of sensitive versus specific strategies. METHODS: A sensitive search strategy identified 34 CVD programmes (reference standard) and sensitivity, precision and number needed to read (NNTR) were compared across seven databases. Two alternative strategies were developed to improve precision while minimising the impact on sensitivity. RESULTS: MEDLINE alone retrieved 91% (31/34) relevant programme citations. Four databases (MEDLINE, CENTRAL, ASSIA and PsycINFO) were required to identify all 34 programmes. In the alternative strategies, greater use of MeSH rather than text and focus on terms directed at population-level interventions resulted in a more precise search on MEDLINE. CONCLUSIONS: MEDLINE alone provided a better yield than anticipated. Additional databases improved sensitivity by 9% but to the detriment of precision. Retrospective searching would provide additional insight into the performance of both databases and strategies. How the medical nature of this public health topic affected yield across databases also requires further investigation.

Quality assessment of diagnostic before-after studies: development of methodology in the context of a systematic review.

BACKGROUND: Quality assessment tools for primary studies of test accuracy are relatively well developed, although only one is validated (QUADAS), but very little work has been done to develop tools to quality-assess studies evaluating the impact of diagnostic testing on management of patients (diagnostic or therapeutic yield). The recent draft NICE Guide to the Methods of Technology Appraisal (2007) suggests QUADAS "as a useful starting point for appraising studies that evaluate the sensitivity and specificity of a test" but does not mention how to quality assess diagnostic or therapeutic yield studies, in particular diagnostic before-after studies. In the context of undertaking a rapid systematic review of structural neuroimaging in psychosis for NICE, we describe the modifications that we made to QUADAS, our experience of this in practice and in relation to published theory on diagnostic or therapeutic yield studies. METHODS: The QUADAS tool was assessed for use in the review by two systematic reviewers with in-depth knowledge of the clinical area being reviewed and the types of studies being found in the searches that could answer the clinical question. Modifications were made following discussion as considered appropriate. RESULTS: Two QUADAS questions were removed altogether and. four additional questions were developed to capture additional quality issues not addressed by QUADAS. However, the developed checklist only partially helped to discern implications of the study designs on the results given. CONCLUSION: The division between topic-specific and more generic quality items of relevance to diagnostic before-after studies is important. With more time, further work could have been done to create a better quality assessment tool, for example by incorporating some of the issues mentioned in previous work in this area. This paper is a discussion around quality assessment and is intended to offer insights into the types of issues that should be assessed. A quality assessment tool for diagnostic before-after studies that incorporates items from QUADAS and published theory needs to be further developed and validated.