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      Limitations to current methods to estimate cause of death: a validation study of a verbal autopsy model

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          Abstract

          Background: Accurate information on causes of death (CoD) is essential to estimate burden of disease, track global progress, prioritize cost-effective interventions, and inform policies to reduce mortality. In low-income settings, where a significant proportion of deaths take place at home or in poorly-resourced peripheral health facilities, data on CoD often relies on verbal autopsies (VAs). Validations of VAs have been performed against clinical diagnosis, but never before against an acceptable gold standard: the complete diagnostic autopsy (CDA).

          Methods: We have validated a computer-coded verbal autopsy method –the InterVA- using individual and population metrics to determine CoD against the CDA, in 316 deceased patients of different age groups who died in a tertiary-level hospital in Maputo, Mozambique between 2013 and 2015.  

          Results: We found a low agreement of the model across all age groups at the individual (kappa statistic ranging from -0.030 to 0.232, lowest in stillbirths and highest in adults) and population levels (chance-corrected cause-specific mortality fraction accuracy ranging from -1.00 to 0.62, lowest in stillbirths, highest in children). The sensitivity in identifying infectious diseases was low (0% for tuberculosis, diarrhea, and disseminated infections, 32% for HIV-related infections, 33% for malaria and 36% for pneumonia). Of maternal deaths, 26 were assigned to eclampsia but only four patients actually died of eclampsia.

          Conclusions: These findings do not lead to building confidence in current estimates of CoD. They also call to the need to implement autopsy methods where they may be feasible, and to improve the quality and performance of current VA techniques.

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          Most cited references28

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          Changes in rates of autopsy-detected diagnostic errors over time: a systematic review.

          Substantial discrepanies exist between clinical diagnoses and findings at autopsy. Autopsy may be used as a tool for quality management to analyze diagnostic discrepanies. To determine the rate at which autopsies detect important, clinically missed diagnoses, and the extent to which this rate has changed over time. A systematic literature search for English-language articles available on MEDLINE from 1966 to April 2002, using the search terms autopsy, postmortem changes, post-mortem, postmortem, necropsy, and posthumous, identified 45 studies reporting 53 distinct autopsy series meeting prospectively defined criteria. Reference lists were reviewed to identify additional studies, and the final bibliography was distributed to experts in the field to identify missing or unpublished studies. Included studies reported clinically missed diagnoses involving a primary cause of death (major errors), with the most serious being those likely to have affected patient outcome (class I errors). Logistic regression was performed using data from 53 distinct autopsy series over a 40-year period and adjusting for the effects of changes in autopsy rates, country, case mix (general autopsies; adult medical; adult intensive care; adult or pediatric surgery; general pediatrics or pediatric inpatients; neonatal or pediatric intensive care; and other autopsy), and important methodological features of the primary studies. Of 53 autopsy series identified, 42 reported major errors and 37 reported class I errors. Twenty-six autopsy series reported both major and class I error rates. The median error rate was 23.5% (range, 4.1%-49.8%) for major errors and 9.0% (range, 0%-20.7%) for class I errors. Analyses of diagnostic error rates adjusting for the effects of case mix, country, and autopsy rate yielded relative decreases per decade of 19.4% (95% confidence interval [CI], 1.8%-33.8%) for major errors and 33.4% (95% [CI], 8.4%-51.6%) for class I errors. Despite these decreases, we estimated that a contemporary US institution (based on autopsy rates ranging from 100% [the extrapolated extreme at which clinical selection is eliminated] to 5% [roughly the national average]), could observe a major error rate from 8.4% to 24.4% and a class I error rate from 4.1% to 6.7%. The possibility that a given autopsy will reveal important unsuspected diagnoses has decreased over time, but remains sufficiently high that encouraging ongoing use of the autopsy appears warranted.
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            A global assessment of civil registration and vital statistics systems: monitoring data quality and progress.

            Increasing demand for better quality data and more investment to strengthen civil registration and vital statistics (CRVS) systems will require increased emphasis on objective, comparable, cost-effective monitoring and assessment methods to measure progress. We apply a composite index (the vital statistics performance index [VSPI]) to assess the performance of CRVS systems in 148 countries or territories during 1980-2012 and classify them into five distinct performance categories, ranging from rudimentary (with scores close to zero) to satisfactory (with scores close to one), with a mean VSPI score since 2005 of 0·61 (SD 0·31). As expected, the best performing systems were mostly in the European region, the Americas, and Australasia, with only two countries from east Asia and Latin America. Most low-scoring countries were in the African or Asian regions. Globally, only modest progress has been made since 2000, with the percentage of deaths registered increasing from 36% to 38%, and the percentage of children aged under 5 years whose birth has been registered increasing from 58% to 65%. However, several individual countries have made substantial improvements to their CRVS systems in the past 30 years by capturing more deaths and improving accuracy of cause-of-death information. Future monitoring of the effects of CRVS strengthening will greatly benefit from application of a metric like the VSPI, which is objective, costless to compute, and able to identify components of the system that make the largest contributions to good or poor performance.
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              Verbal autopsy: methods in transition.

              Understanding of global health and changing morbidity and mortality is limited by inadequate measurement of population health. With fewer than one-third of deaths worldwide being assigned a cause, this long-standing dearth of information, almost exclusively in the world's poorest countries, hinders understanding of population health and limits opportunities for planning, monitoring, and evaluating interventions. In the absence of routine death registration, verbal autopsy (VA) methods are used to derive probable causes of death. Much effort has been put into refining the approach for specific purposes; however, there has been a lack of harmony regarding such efforts. Subsequently, a variety of methods and principles have been developed, often focusing on a single aspect of VA, and the resulting literature provides an inconsistent picture. By reviewing methodological and conceptual issues in VA, it is evident that VA cannot be reduced to a single one-size-fits-all tool. VA must be contextualized; given the lack of "gold standards," methodological developments should not be considered in terms of absolute validity but rather in terms of consistency, comparability, and adequacy for the intended purpose. There is an urgent need for clarified thinking about the overall objectives of population-level cause-of-death measurement and harmonized efforts in empirical methodological research.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Funding AcquisitionRole: InvestigationRole: Project AdministrationRole: SupervisionRole: ValidationRole: Writing – Original Draft PreparationRole: Writing – Review & Editing
                Role: ConceptualizationRole: Data CurationRole: Formal AnalysisRole: MethodologyRole: SoftwareRole: VisualizationRole: Writing – Original Draft PreparationRole: Writing – Review & Editing
                Role: Data CurationRole: InvestigationRole: MethodologyRole: ValidationRole: Writing – Review & Editing
                Role: InvestigationRole: Writing – Review & Editing
                Role: InvestigationRole: Writing – Review & Editing
                Role: InvestigationRole: Writing – Review & Editing
                Role: InvestigationRole: Writing – Review & Editing
                Role: Data CurationRole: InvestigationRole: MethodologyRole: ValidationRole: Writing – Review & Editing
                Role: Data CurationRole: InvestigationRole: MethodologyRole: ValidationRole: Writing – Review & Editing
                Role: InvestigationRole: Writing – Review & Editing
                Role: InvestigationRole: Writing – Review & Editing
                Role: ConceptualizationRole: Writing – Review & Editing
                Role: ConceptualizationRole: Writing – Review & Editing
                Role: Data CurationRole: InvestigationRole: MethodologyRole: ValidationRole: Writing – Review & Editing
                Role: ConceptualizationRole: Funding AcquisitionRole: InvestigationRole: MethodologyRole: Project AdministrationRole: SupervisionRole: ValidationRole: Writing – Review & Editing
                Role: ConceptualizationRole: Writing – Original Draft PreparationRole: Writing – Review & Editing
                Role: ConceptualizationRole: Data CurationRole: Funding AcquisitionRole: InvestigationRole: MethodologyRole: Project AdministrationRole: SupervisionRole: ValidationRole: Writing – Review & Editing
                Journal
                Gates Open Res
                Gates Open Res
                Gates Open Res
                Gates Open Research
                F1000 Research Limited (London, UK )
                2572-4754
                28 May 2020
                2020
                : 4
                : 55
                Affiliations
                [1 ]Barcelona Institute for Global Health (ISGlobal), Hospital Clinic of Barcelona, Universitat de Barcelona, Barcelona, Spain
                [2 ]Centro de Investigação em Saúde de Manhiça, Maputo, Mozambique
                [3 ]Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
                [4 ]Pathology, Hospital Clinic of Barcelona, Universitat de Barcelona, Barcelona, Spain
                [5 ]Pathology, Maputo Central Hospital, Maputo, Mozambique
                [6 ]Faculty of Medicine, Eduardo Mondlane University, Maputo, Mozambique
                [7 ]Microbiology, Hospital Clinic of Barcelona, Universitat de Barcelona, Barcelona, Spain
                [8 ]ICREA, Catalan Institution for Research and Advanced Studies, Barcelona, Spain
                [9 ]Global Malaria Programme, World Health Organisation, Geneva, Switzerland
                [1 ]The Aurum Institute, Johannesburg, South Africa
                [1 ]Department of Population Health, London School of Hygiene & Tropical Medicine, London, UK
                [1 ]Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
                [2 ]Center for Reproductive Health, Universitas Gadjah Mada, Yogyakarta, Indonesia
                Author notes

                No competing interests were disclosed.

                Competing interests: No competing interests were disclosed.

                Competing interests: No competing interests were disclosed.

                Competing interests: No competing interests were disclosed.

                Author information
                https://orcid.org/0000-0002-2641-6907
                https://orcid.org/0000-0001-9992-6951
                https://orcid.org/0000-0002-9284-8601
                Article
                10.12688/gatesopenres.13132.1
                7590499
                33145479
                b6793ace-7c62-4190-92dc-2f32483da52d
                Copyright: © 2020 Menéndez C et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 19 May 2020
                Funding
                Funded by: Generalitat de Catalunya
                Funded by: Instituto de Salud Carlos III
                Award ID: PI12/00757
                Funded by: Bill and Melinda Gates Foundation
                Award ID: OPP1128001
                Award ID: OPP1067522
                This work was supported by the Bill & Melinda Gates Foundation [OPP1067522 and OPP1128001]. This work is also supported by the Spanish Instituto de Salud Carlos III [FIS, PI12/00757; CM, Acciones CIBER]. ISGlobal is included in the CERCA Programme /Generalitat de Catalunya.
                The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Articles

                validation,verbal autopsy,cause of death,complete diagnostic autopsy,mozambique

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