scholarly journals On estimating a constrained bivariate random effects model for meta-analysis of test accuracy studies

2022 ◽  
pp. 096228022110651
Author(s):  
Mohammed Baragilly ◽  
Brian Harvey Willis

Tailored meta-analysis uses setting-specific knowledge for the test positive rate and disease prevalence to constrain the possible values for a test's sensitivity and specificity. The constrained region is used to select those studies relevant to the setting for meta-analysis using an unconstrained bivariate random effects model (BRM). However, sometimes there may be no studies to aggregate, or the summary estimate may lie outside the plausible or “applicable” region. Potentially these shortcomings may be overcome by incorporating the constraints in the BRM to produce a constrained model. Using a penalised likelihood approach we developed an optimisation algorithm based on co-ordinate ascent and Newton-Raphson iteration to fit a constrained bivariate random effects model (CBRM) for meta-analysis. Using numerical examples based on simulation studies and real datasets we compared its performance with the BRM in terms of bias, mean squared error and coverage probability. We also determined the ‘closeness’ of the estimates to their true values using the Euclidian and Mahalanobis distances. The CBRM produced estimates which in the majority of cases had lower absolute mean bias and greater coverage probability than the BRM. The estimated sensitivities and specificity for the CBRM were, in general, closer to the true values than the BRM. For the two real datasets, the CBRM produced estimates which were in the applicable region in contrast to the BRM. When combining setting-specific data with test accuracy meta-analysis, a constrained model is more likely to yield a plausible estimate for the sensitivity and specificity in the practice setting than an unconstrained model.

2010 ◽  
Vol 49 (01) ◽  
pp. 54-64 ◽  
Author(s):  
J. Menke

Summary Objectives: Meta-analysis allows to summarize pooled sensitivities and specificities from several primary diagnostic test accuracy studies. Often these pooled estimates are indirectly obtained from a hierarchical summary receiver operating characteristics (HSROC) analysis. This article presents a generalized linear random-effects model with the new SAS PROC GLIMMIX that obtains the pooled estimates for sensitivity and specificity directly. Methods: Firstly, the formula of the bivariate random-effects model is presented in context with the literature. Then its implementation with the new SAS PROC GLIMMIX is empirically evaluated in comparison to the indirect HSROC approach, utilizing the published 2 x 2 count data of 50 meta-analyses. Results: According to the empirical evaluation the meta-analytic results from the bivariate GLIMMIX approach are nearly identical to the results from the indirect HSROC approach. Conclusions: A generalized linear mixed model with PROC GLIMMIX offers a straightforward method for bivariate random-effects meta-analysis of sensitivity and specificity.


2020 ◽  
Vol 29 (11) ◽  
pp. 3308-3325
Author(s):  
Zelalem F Negeri ◽  
Joseph Beyene

Due to the inevitable inter-study correlation between test sensitivity (Se) and test specificity (Sp), mostly because of threshold variability, hierarchical or bivariate random-effects models are widely used to perform a meta-analysis of diagnostic test accuracy studies. Conventionally, these models assume that the random-effects follow the bivariate normal distribution. However, the inference made using the well-established bivariate random-effects models, when outlying and influential studies are present, may lead to misleading conclusions, since outlying or influential studies can extremely influence parameter estimates due to their disproportional weight. Therefore, we developed a new robust bivariate random-effects model that accommodates outlying and influential observations and gives robust statistical inference by down-weighting the effect of outlying and influential studies. The marginal model and the Monte Carlo expectation-maximization algorithm for our proposed model have been derived. A simulation study has been carried out to validate the proposed method and compare it against the standard methods. Regardless of the parameters varied in our simulations, the proposed model produced robust point estimates of Se and Sp compared to the standard models. Moreover, our proposed model resulted in precise estimates as it yielded the narrowest confidence intervals. The proposed model also generated a similar point and interval estimates of Se and Sp as the standard models when there are no outlying and influential studies. Two published meta-analyses have also been used to illustrate the methods.


2017 ◽  
Vol 28 (1) ◽  
pp. 263-274 ◽  
Author(s):  
Lie Li ◽  
Xinlei Wang

Meta-analysis has been widely used to synthesize information from related studies to achieve reliable findings. However, in studies of rare events, the event counts are often low or even zero, and so standard meta-analysis methods such as fixed-effect models with continuity correction may cause substantial bias in estimation. Recently, Bhaumik et al. developed a simple average estimator for the overall treatment effect based on a random effects model. They proved that the simple average method with the continuity correction factor 0.5 (SA_0.5) is the least biased for large samples and showed via simulation that it has superior performance when compared with other commonly used estimators. However, the random effects models used in previous work are restrictive because they all assume that the variability in the treatment group is equal to or always greater than that in the control group. Under a general framework that explicitly allows treatment groups with unequal variability but assumes no direction, we prove that SA_0.5 is still the least biased for large samples. Meanwhile, to account for a trade-off between the bias and variance in estimation, we consider the mean squared error to assess estimation efficiency and show that SA_0.5 fails to minimize the mean squared error. Under a new random effects model that accommodates groups with unequal variability, we thoroughly compare the performance of various methods for both large and small samples via simulation and draw conclusions about when to use which method in terms of bias, mean squared error, type I error, and confidence interval coverage. A data example of rosiglitazone meta-analysis is used to provide further comparison.


2021 ◽  
Vol 178 (2) ◽  
pp. 313-339
Author(s):  
Michael L. Begnaud ◽  
Dale N. Anderson ◽  
Stephen C. Myers ◽  
Brian Young ◽  
James R. Hipp ◽  
...  

AbstractThe regional seismic travel time (RSTT) model and software were developed to improve travel-time prediction accuracy by accounting for three-dimensional crust and upper mantle structure. Travel-time uncertainty estimates are used in the process of associating seismic phases to events and to accurately calculate location uncertainty bounds (i.e. event location error ellipses). We improve on the current distance-dependent uncertainty parameterization for RSTT using a random effects model to estimate slowness (inverse velocity) uncertainty as a mean squared error for each model parameter. The random effects model separates the error between observed slowness and model predicted slowness into bias and random components. The path-specific travel-time uncertainty is calculated by integrating these mean squared errors along a seismic-phase ray path. We demonstrate that event location error ellipses computed for a 90% coverage ellipse metric (used by the Comprehensive Nuclear-Test-Ban Treaty Organization International Data Centre (IDC)), and using the path-specific travel-time uncertainty approach, are more representative (median 82.5% ellipse percentage) of true location error than error ellipses computed using distance-dependent travel-time uncertainties (median 70.1%). We also demonstrate measurable improvement in location uncertainties using the RSTT method compared to the current station correction approach used at the IDC (median 74.3% coverage ellipse).


2021 ◽  
pp. 219256822110308
Author(s):  
Andrew Platt ◽  
Mostafa H. El Dafrawy ◽  
Michael J. Lee ◽  
Martin H. Herman ◽  
Edwin Ramos

Study Design: Systematic review and meta-analysis. Objectives: Indications for surgical decompression of gunshot wounds to the lumbosacral spine are controversial and based on limited data. Methods: A systematic review of literature was conducted to identify studies that directly compare neurologic outcomes following operative and non-operative management of gunshot wounds to the lumbosacral spine. Studies were evaluated for degree of neurologic improvement, complications, and antibiotic usage. An odds ratio and 95% confidence interval were calculated for dichotomous outcomes which were then pooled by random-effects model meta-analysis. Results: Five studies were included that met inclusion criteria. The total rate of neurologic improvement was 72.3% following surgical intervention and 61.7% following non-operative intervention. A random-effects model meta-analysis was carried out which failed to show a statistically significant difference in the rate of neurologic improvement between surgical and non-operative intervention (OR 1.07; 95% CI 0.45, 2.53; P = 0.88). In civilian only studies, a random-effects model meta-analysis failed to show a statistically significant difference in the rate of neurologic improvement between surgical and non-operative intervention (OR 0.75; 95% CI 0.21, 2.72; P = 0.66). Meta-analysis further failed to show a statistically significant difference in the rate of neurologic improvement between patients with either complete (OR 4.13; 95% CI 0.55, 30.80; P = 0.17) or incomplete (OR 0.38; 95% CI 0.10, 1.52; P = 0.17) neurologic injuries who underwent surgical and non-operative intervention. There were no significant differences in the number of infections and other complications between patients who underwent surgical and non-operative intervention. Conclusions: There were no statistically significant differences in the rate of neurologic improvement between those who underwent surgical or non-operative intervention. Further research is necessary to determine if surgical intervention for gunshot wounds to the lumbosacral spine, including in the case of retained bullet within the spinal canal, is efficacious.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
P Ioannidou ◽  
J Bosdou ◽  
D Papanikolaou ◽  
D Goulis ◽  
A Lambropoulos ◽  
...  

Abstract Study question Does oral antioxidant supplementation improve sperm quality in infertile men with varicocele who have not undergone surgical repair? Summary answer Oral antioxidant supplementation improves sperm concentration and motility in infertile men with varicocele who have not undergone surgical repair. What is known already: Benefit from oral antioxidant supplementation has been shown in infertile men with varicocele following surgical repair. Similarly, oral antioxidant supplementation has been suggested in infertile men with varicocele who have not undergone surgical repair. However, its effect currently remains controversial. Study design, size, duration A literature search was performed until January 2021 aiming to identify prospective studies evaluating the use of oral antioxidant supplementation alone or in combination in men with varicocele who have not undergone surgical repair. Participants/materials, setting, methods Seven prospective studies were identified, published between 1987 and 2018, including 278 infertile men with varicocele who had not undergone surgical repair. The number of patients included ranged from 20 to 65. Sperm analysis, evaluating sperm concentration, motility and morphology was performed in these studies before and after oral antioxidant supplementation. Meta-analysis of weighted data was performed using random effects model. Results are reported as weighted mean difference (WMD) with 95% confidence interval (CI). Main results and the role of chance Seven studies were included in the systematic review. Oral antioxidant supplementation was performed by a combination of pentoxifylline, zinc and folic acid (single study), a combination of l-carnitine, fumarate, acetyl-l-carnitine, fructose, CoQ, vitamin C, zinc, folic acid and vitamin B12 (single study), a combination of L-Carnitine, vitamin C, coenzyme Q10, vitamin E, vitamin B9, vitamin B12, zinc , and selenium, l-carnitine (single study), or sole treatment with acetyl-l-carnitine (single study), L-Carnitine (single study), Coenzyme Q10 (single study) or zinc sulfate (single study). For the purpose of meta-analysis, the effect of oral antioxidant supplementation was evaluated after three months of treatment. Oral antioxidant supplementation significantly increased sperm concentration (WMD +5.65x106/ml 95% CI: +1.11 to + 10.12 p = 0.01, random effects model) and motility (WMD +4.30%, 95% CI: +0.86 to + 7.74 p = 0.01, random effects model) in infertile men with varicocele who had not undergone surgical repair. On the other hand, no significance difference was observed in sperm morphology (WMD +3.9%, 95% CI: –0.16 to + 8.04 p = 0.06, random effects model) and volume (WMD +0.53ml, 95% CI: 0.0 to + 1.0 p = 0.052, random effects model). Limitations, reasons for caution The number of relevant trials and that of patients included is small to allow for solid conclusions to be drawn. Moreover, although different oral antioxidants have been administered in infertile who had not undergone surgical repair, subgroup analysis was not feasible. Wider implications of the findings: Currently, limited evidence supports the use of oral antioxidants in the treatment of men with varicocele, who have not undergone surgical repair. Although the benefit in sperm concentration and motility appears to be modest, it might be important regarding achievement of pregnancy in these men. Trial registration number Not applicable


Cephalalgia ◽  
2014 ◽  
Vol 35 (1) ◽  
pp. 63-72 ◽  
Author(s):  
Amy A Gelfand ◽  
Peter J Goadsby ◽  
I Elaine Allen

Context Infant colic is a common and distressing disorder of early infancy. Its etiology is unknown, making treatment challenging. Several articles have suggested a link to migraine. Objective The objective of this article was to perform a systematic review and, if appropriate, a meta-analysis of the studies on the relationship between infant colic and migraine. Data sources Studies were identified by searching PubMed and ScienceDirect and by hand-searching references and conference proceedings. Study selection For the primary analysis, studies specifically designed to measure the association between colic and migraine were included. For the secondary analysis, studies that collected data on colic and migraine but were designed for another primary research question were also included. Data extraction Data were abstracted from the original studies, through communication with study authors, or both. Two authors independently abstracted data. Main outcomes and measures The main outcome measure was the association between infant colic and migraine using both a fixed-effects model and a more conservative random-effects model. Results Three studies were included in the primary analysis; the odds ratio for the association between migraine and infant colic was 6.5 (4.6–8.9, p < 0.001) for the fixed-effects model and 5.6 (3.3–9.5, p = 0.004) for the random-effects model. In a sensitivity analysis wherein the study with the largest effect size was removed, the odds ratio was 3.6 (95% CI 1.7–7.6, p = 0.001) for both the fixed-effects model and random-effects model. Conclusions In this meta-analysis, infant colic was associated with increased odds of migraine. If infant colic is a migrainous disorder, this would have important implications for treatment. The main limitation of this meta-analysis was the relatively small number of studies included.


Diagnostics ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1665
Author(s):  
Dong Hwan Kim ◽  
Sang Hyun Choi ◽  
Ju Hyun Shim ◽  
So Yeon Kim ◽  
Seung Soo Lee ◽  
...  

Our meta-analysis aimed to evaluate the diagnostic performance of surveillance magnetic resonance imaging (sMRI) for detecting hepatocellular carcinoma (HCC), and to compare the diagnostic performance of sMRI between different protocols. Original articles about the diagnostic accuracy of sMRI for detecting HCC were found in major databases. The meta-analytic pooled sensitivity and specificity of sMRI for detecting HCC were determined using a bivariate random effects model. The pooled sensitivity and specificity of full MRI and abbreviated MRI protocols were compared using bivariate meta-regression. In the total seven included studies (1830 patients), the pooled sensitivity of sMRI for any-stage HCC and very early-stage HCC were 85% (95% confidence interval, 79–90%; I2 = 0%) and 77% (66–85%; I2 = 32%), respectively. The pooled specificity for any-stage HCC and very early-stage HCC were 94% (90–97%; I2 = 94%) and 94% (88–97%; I2 = 96%), respectively. The pooled sensitivity and specificity of abbreviated MRI protocols were 87% (80–94%) and 94% (90–98%), values that were comparable with those of full MRI protocols (84% [76–91%] and 94% [89–99%]; p = 0.83). In conclusion, sMRI had good sensitivity for detecting HCC, particularly very early-stage HCC. Abbreviated MRI protocols for HCC surveillance had comparable diagnostic performance to full MRI protocols.


2020 ◽  
Vol 4 (18) ◽  
pp. 4296-4311
Author(s):  
Parth Patel ◽  
Payal Patel ◽  
Meha Bhatt ◽  
Cody Braun ◽  
Housne Begum ◽  
...  

Abstract Pulmonary embolism (PE) is a common, potentially life-threatening yet treatable condition. Prompt diagnosis and expeditious therapeutic intervention is of paramount importance for optimal patient management. Our objective was to systematically review the accuracy of D-dimer assay, compression ultrasonography (CUS), computed tomography pulmonary angiography (CTPA), and ventilation-perfusion (V/Q) scanning for the diagnosis of suspected first and recurrent PE. We searched Cochrane Central, MEDLINE, and EMBASE for eligible studies, reference lists of relevant reviews, registered trials, and relevant conference proceedings. 2 investigators screened and abstracted data. Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. We pooled estimates of sensitivity and specificity. The review included 61 studies. The pooled estimates for D-dimer sensitivity and specificity were 0.97 (95% confidence interval [CI], 0.96-0.98) and 0.41 (95% CI, 0.36-0.46) respectively, whereas CTPA sensitivity and specificity were 0.94 (95% CI, 0.89-0.97) and 0.98 (95% CI, 0.97-0.99), respectively, and CUS sensitivity and specificity were 0.49 (95% CI, 0.31-0.66) and 0.96 (95% CI, 0.95-0.98), respectively. Three variations of pooled estimates for sensitivity and specificity of V/Q scan were carried out, based on interpretation of test results. D-dimer had the highest sensitivity when compared with imaging. CTPA and V/Q scans (high probability scan as a positive and low/non-diagnostic/normal scan as negative) both had the highest specificity. This systematic review was registered on PROSPERO as CRD42018084669.


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