Meta-analysis of diagnostic accuracy studies in mental health

Objectives To explain methods for data synthesis of evidence from diagnostic test accuracy (DTA) studies, and to illustrate different types of analyses that may be performed in a DTA systematic review. Methods We described properties of meta-analytic methods for quantitative synthesis of evidence. We used a DTA review comparing the accuracy of three screening questionnaires for bipolar disorder to illustrate application of the methods for each type of analysis. Results The discriminatory ability of a test is commonly expressed in terms of sensitivity (proportion of those with the condition who test positive) and specificity (proportion of those without the condition who test negative). There is a trade-off between sensitivity and specificity, as an increasing threshold for defining test positivity will decrease sensitivity and increase specificity. Methods recommended for meta-analysis of DTA studies --such as the bivariate or hierarchical summary receiver operating characteristic (HSROC) model --jointly summarise sensitivity and specificity while taking into account this threshold effect, as well as allowing for between study differences in test performance beyond what would be expected by chance. The bivariate model focuses on estimation of a summary sensitivity and specificity at a common threshold while the HSROC model focuses on the estimation of a summary curve from studies that have used different thresholds. Conclusions Meta-analyses of diagnostic accuracy studies can provide answers to important clinical questions. We hope this article will provide clinicians with sufficient understanding of the terminology and methods to aid interpretation of systematic reviews and facilitate better patient care

Diagnostic accuracy of laparoscopy following computed tomography (CT) scanning for assessing the resectability with curative intent in pancreatic and periampullary cancer

BACKGROUND: Surgical resection is the only potentially curative treatment for pancreatic and periampullary cancer. A considerable proportion of patients undergo unnecessary laparotomy because of underestimation of the extent of the cancer on computed tomography (CT) scanning. Laparoscopy can detect metastases not visualised on CT scanning, enabling better assessment of the spread of cancer (staging of cancer). This is an update to a previous Cochrane Review published in 2013 evaluating the role of diagnostic laparoscopy in assessing the resectability with curative intent in people with pancreatic and periampullary cancer. OBJECTIVES: To determine the diagnostic accuracy of diagnostic laparoscopy performed as an add-on test to CT scanning in the assessment of curative resectability in pancreatic and periampullary cancer. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via PubMed, EMBASE via OvidSP (from inception to 15 May 2016), and Science Citation Index Expanded (from 1980 to 15 May 2016). SELECTION CRITERIA: We included diagnostic accuracy studies of diagnostic laparoscopy in people with potentially resectable pancreatic and periampullary cancer on CT scan, where confirmation of liver or peritoneal involvement was by histopathological examination of suspicious (liver or peritoneal) lesions obtained at diagnostic laparoscopy or laparotomy. We accepted any criteria of resectability used in the studies. We included studies irrespective of language, publication status, or study design (prospective or retrospective). We excluded case-control studies. DATA COLLECTION AND ANALYSIS: Two review authors independently performed data extraction and quality assessment using the QUADAS-2 tool. The specificity of diagnostic laparoscopy in all studies was 1 because there were no false positives since laparoscopy and the reference standard are one and the same if histological examination after diagnostic laparoscopy is positive. The sensitivities were therefore meta-analysed using a univariate random-effects logistic regression model. The probability of unresectability in people who had a negative laparoscopy (post-test probability for people with a negative test result) was calculated using the median probability of unresectability (pre-test probability) from the included studies, and the negative likelihood ratio derived from the model (specificity of 1 assumed). The difference between the pre-test and post-test probabilities gave the overall added value of diagnostic laparoscopy compared to the standard practice of CT scan staging alone. MAIN RESULTS: We included 16 studies with a total of 1146 participants in the meta-analysis. Only one study including 52 participants had a low risk of bias and low applicability concern in the patient selection domain. The median pre-test probability of unresectable disease after CT scanning across studies was 41.4% (that is 41 out of 100 participants who had resectable cancer after CT scan were found to have unresectable disease on laparotomy). The summary sensitivity of diagnostic laparoscopy was 64.4% (95% confidence interval (CI) 50.1% to 76.6%). Assuming a pre-test probability of 41.4%, the post-test probability of unresectable disease for participants with a negative test result was 0.20 (95% CI 0.15 to 0.27). This indicates that if a person is said to have resectable disease after diagnostic laparoscopy and CT scan, there is a 20% probability that their cancer will be unresectable compared to a 41% probability for those receiving CT alone.A subgroup analysis of people with pancreatic cancer gave a summary sensitivity of 67.9% (95% CI 41.1% to 86.5%). The post-test probability of unresectable disease after being considered resectable on both CT and diagnostic laparoscopy was 18% compared to 40.0% for those receiving CT alone. AUTHORS' CONCLUSIONS: Diagnostic laparoscopy may decrease the rate of unnecessary laparotomy in people with pancreatic and periampullary cancer found to have resectable disease on CT scan. On average, using diagnostic laparoscopy with biopsy and histopathological confirmation of suspicious lesions prior to laparotomy would avoid 21 unnecessary laparotomies in 100 people in whom resection of cancer with curative intent is planned

Study flow diagrams in Cochrane systematic review updates: an adapted PRISMA flow diagram.

Cochrane systematic reviews are conducted and reported according to rigorous standards. A study flow diagram must be included in a new review, and there is clear guidance from the PRISMA statement on how to do this. However, for a review update, there is currently no guidance on how study flow diagrams should be presented. To address this, a working group was formed to find a solution and produce guidance on how to use these diagrams in review updates.A number of different options were devised for how these flow diagrams could be used in review updates, and also in cases where multiple searches for a review or review update have been conducted. These options were circulated to the Cochrane information specialist community for consultation and feedback. Following the consultation period, the working group refined the guidance and made the recommendation that for review updates an adapted PRISMA flow diagram should be used, which includes an additional box with the number of previously included studies feeding into the total. Where multiple searches have been conducted, the results should be added together and treated as one set of results.There is no existing guidance for using study flow diagrams in review updates. Our adapted diagram is a simple and pragmatic solution for showing the flow of studies in review updates

Defining the role of cellular immune signatures in diagnostic evaluation of suspected tuberculosis

BACKGROUND: Diagnosis of paucibacillary tuberculosis (TB) including extrapulmonary TB is a significant challenge, particularly in high-income, low-incidence settings. Measurement of Mycobacterium tuberculosis (Mtb)-specific cellular immune signatures by flow cytometry discriminates active TB from latent TB infection (LTBI) in case-control studies; however, their diagnostic accuracy and clinical utility in routine clinical practice is unknown. METHODS: Using a nested case-control study design within a prospective multicenter cohort of patients presenting with suspected TB in England, we assessed diagnostic accuracy of signatures in 134 patients who tested interferon-gamma release assay (IGRA)-positive and had final diagnoses of TB or non-TB diseases with coincident LTBI. Cellular signatures were measured using flow cytometry. RESULTS: All signatures performed less well than previously reported. Only signatures incorporating measurement of phenotypic markers on functional Mtb-specific CD4 T cells discriminated active TB from non-TB diseases with LTBI. The signatures measuring HLA-DR+IFNγ + CD4 T cells and CD45RA-CCR7-CD127- IFNγ -IL-2-TNFα + CD4 T cells performed best with 95% positive predictive value (95% confidence interval, 90-97) in the clinically challenging subpopulation of IGRA-positive but acid-fast bacillus (AFB) smear-negative TB suspects. CONCLUSIONS: Two cellular immune signatures could improve and accelerate diagnosis in the challenging group of patients who are IGRA-positive, AFB smear-negative, and have paucibacillary TB

Accuracy of single progesterone test to predict early pregnancy outcome in women with pain or bleeding: Meta-analysis of cohort studies

Objective To determine the accuracy with which a single progesterone measurement in early pregnancy discriminates between viable and non-viable pregnancy. Design Systematic review and meta-analysis of diagnostic accuracy studies. Data sources Medline, Embase, CINAHL, Web of Science, ProQuest, Conference Proceedings Citation Index, and the Cochrane Library from inception until April 2012, plus reference lists of relevant studies. Study selection Studies were selected on the basis of participants (women with spontaneous pregnancy of less than 14 weeks of gestation); test (single serum progesterone measurement); outcome (viable intrauterine pregnancy, miscarriage, or ectopic pregnancy) diagnosed on the basis of combinations of pregnancy test, ultrasound scan, laparoscopy, and histological examination; design (cohort studies of test accuracy); and sufficient data being reported. Results 26 cohort studies, including 9436 pregnant women, were included, consisting of 7 studies in women with symptoms and inconclusive ultrasound assessment and 19 studies in women with symptoms alone. Among women with symptoms and inconclusive ultrasound assessments, the progesterone test (5 studies with 1998 participants and cut-off values from 3.2 to 6 ng/mL) predicted a non-viable pregnancy with pooled sensitivity of 74.6% (95% confidence interval 50.6% to 89.4%), specificity of 98.4% (90.9% to 99.7%), positive likelihood ratio of 45 (7.1 to 289), and negative likelihood ratio of 0.26 (0.12 to 0.57). The median prevalence of a non-viable pregnancy was 73.2%, and the probability of a non-viable pregnancy was raised to 99.2% if the progesterone was low. For women with symptoms alone, the progesterone test had a higher specificity when a threshold of 10 ng/mL was used (9 studies with 4689 participants) and predicted a non-viable pregnancy with pooled sensitivity of 66.5% (53.6% to 77.4%), specificity of 96.3% (91.1% to 98.5%), positive likelihood ratio of 18 (7.2 to 45), and negative likelihood ratio of 0.35 (0.24 to 0.50). The probability of a non-viable pregnancy was raised from 62.9% to 96.8%. Conclusion A single progesterone measurement for women in early pregnancy presenting with bleeding or pain and inconclusive ultrasound assessments can rule out a viable pregnancy.Jorine Verhaegen, Ioannis D Gallos, Norah M van Mello, Mohamed Abdel-Aziz, Yemisi Takwoingi, Hoda Harb, Jonathan J Deeks, Ben W J Mol, Arri Coomarasam

Health technology assessment of diagnostic tests: a state of the art review of methods guidance from international organizations

This is the final version. Available on open access from Cambridge University Press via the DOI in this recordOBJECTIVES: To identify which international health technology assessment (HTA) agencies are undertaking evaluations of medical tests, summarize commonalities and differences in methodological approach, and highlight examples of good practice. METHODS: A methodological review incorporating: systematic identification of HTA guidance documents mentioning evaluation of tests; identification of key contributing organizations and abstraction of approaches to all essential HTA steps; summary of similarities and differences between organizations; and identification of important emergent themes which define the current state of the art and frontiers where further development is needed. RESULTS: Seven key organizations were identified from 216 screened. The main themes were: elucidation of claims of test benefits; attitude to direct and indirect evidence of clinical effectiveness (including evidence linkage); searching; quality assessment; and health economic evaluation. With the exception of dealing with test accuracy data, approaches were largely based on general approaches to HTA with few test-specific modifications. Elucidation of test claims and attitude to direct and indirect evidence are where we identified the biggest dissimilarities in approach. CONCLUSIONS: There is consensus on some aspects of HTA of tests, such as dealing with test accuracy, and examples of good practice which HTA organizations new to test evaluation can emulate. The focus on test accuracy contrasts with universal acknowledgment that it is not a sufficient evidence base for test evaluation. There are frontiers where methodological development is urgently required, notably integrating direct and indirect evidence and standardizing approaches to evidence linkage.Medical Research Council (MRC