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Methodological challenges in measuring vaccine effectiveness using population cohorts in low resource settings.

ABSTRACT: Post-licensure real world evaluation of vaccine implementation is important for establishing evidence of vaccine effectiveness (VE) and programme impact, including indirect effects. Large cohort studies offer an important epidemiological approach for evaluating VE, but have inherent methodological challenges. Since March 2012, we have conducted an open prospective cohort study in two sites in rural Malawi to evaluate the post-introduction effectiveness of 13-valent pneumococcal conjugate vaccine (PCV13) against all-cause post-neonatal infant mortality and monovalent rotavirus vaccine (RV1) against diarrhoea-related post-neonatal infant mortality. Our study sites cover a population of 500,000, with a baseline post-neonatal infant mortality of 25 per 1000 live births. We conducted a methodological review of cohort studies for vaccine effectiveness in a developing country setting, applied to our study context. Based on published literature, we outline key considerations when defining the denominator (study population), exposure (vaccination status) and outcome ascertainment (mortality and cause of death) of such studies. We assess various definitions in these three domains, in terms of their impact on power, effect size and potential biases and their direction, using our cohort study for illustration. Based on this iterative process, we discuss the pros and cons of our final per-protocol analysis plan. Since no single set of definitions or analytical approach accounts for all possible biases, we propose sensitivity analyses to interrogate our assumptions and methodological decisions. In the poorest regions of the world where routine vital birth and death surveillance are frequently unavailable and the burden of disease and death is greatest We conclude that provided the balance between definitions and their overall assumed impact on estimated VE are acknowledged, such large scale real-world cohort studies can provide crucial information to policymakers by providing robust and compelling evidence of total benefits of newly introduced vaccines on reducing child mortality.

SUBMITTER: King C

PROVIDER: S-EPMC4570930 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundMonitoring financial protection against catastrophic health expenditures is important to understand how health financing arrangements in a country protect its population against high costs associated with accessing health services. While catastrophic health expenditures are generally defined to be when household expenditures for health exceed a given threshold of household resources, there is no gold standard with several methods applied to define the threshold and household resources. These different approaches to constructing the indicator might give different pictures of a country's progress towards financial protection. In order for monitoring to effectively provide policy insight, it is critical to understand the sensitivity of measurement to these choices.MethodsThis paper examines the impact of varying two methodological choices by analysing household expenditure data from a sample of 47 countries. We assess sensitivity of cross-country comparisons to a range of thresholds by testing for restricted dominance. We further assess sensitivity of comparisons to different methods for defining household resources (i.e. total expenditure, non-food expenditure and non-subsistence expenditure) by conducting correlation tests of country rankings.ResultsWe found country rankings are robust to the choice of threshold in a tenth to a quarter of comparisons within the 5-85% threshold range and this increases to half of comparisons if the threshold is restricted to 5-40%, following those commonly used in the literature. Furthermore, correlations of country rankings using different methods to define household resources were moderate to high; thus, this choice makes less difference from a measurement perspective than from an ethical perspective as different definitions of available household resources reflect varying concerns for equity.ConclusionsInterpreting comparisons from global monitoring based on a single threshold should be done with caution as these may not provide reliable insight into relative country progress. We therefore recommend financial protection against catastrophic health expenditures be measured across a range of thresholds using a catastrophic incidence curve as shown in this paper. We further recommend evaluating financial protection in relation to a country's health financing system arrangements in order to better understand the extent of protection and better inform future policy changes.

Project description:ImportancePneumonia is the leading cause of childhood mortality worldwide. Severe pneumonia associated with hypoxemia requires oxygen therapy; however, access remains unreliable in low- and middle-income countries. Solar-powered oxygen delivery (solar-powered O2) has been shown to be a safe and effective technology for delivering medical oxygen. Examining the cost-effectiveness of this innovation is critical for guiding implementation in low-resource settings.ObjectiveTo determine the cost-effectiveness of solar-powered O2 for treating children in low-resource settings with severe pneumonia who require oxygen therapy.Design, setting, and participantsAn economic evaluation study of solar-powered O2 was conducted from January 12, 2020, to February 27, 2021, in compliance with the World Health Organization Choosing Interventions That Are Cost-Effective (WHO-CHOICE) guidelines. Using existing literature, plausible ranges for component costs of solar-powered O2 were determined in order to calculate the expected total cost of implementation. The costs of implementing solar-powered O2 at a single health facility in low- and middle-income countries was analyzed for pediatric patients younger than 5 years who required supplemental oxygen.ExposuresTreatment with solar-powered O2.Main outcomes and measuresThe incremental cost-effectiveness ratio (ICER) of solar-powered O2 was calculated as the additional cost per disability-adjusted life-year (DALY) saved. Sensitivity of the ICER to uncertainties of input parameters was assessed through univariate and probabilistic sensitivity analyses.ResultsThe ICER of solar-powered O2 was estimated to be $20 (US dollars) per DALY saved (95% CI, $2.83-$206) relative to the null case (no oxygen). Costs of solar-powered O2 were alternatively quantified as $26 per patient treated and $542 per life saved. Univariate sensitivity analysis found that the ICER was most sensitive to the volume of pediatric pneumonia admissions and the case fatality rate. The ICER was insensitive to component costs of solar-powered O2 systems. In secondary analyses, solar-powered O2 was cost-effective relative to grid-powered concentrators (ICER $140 per DALY saved) and cost-saving relative to fuel generator-powered concentrators (cost saving of $7120).Conclusions and relevanceThe results of this economic evaluation suggest that solar-powered O2 is a cost-effective solution for treating hypoxemia in young children in low- and middle-income countries, relative to no oxygen. Future implementation should prioritize sites with high rates of pediatric pneumonia admissions and mortality. This study provides economic support for expansion of solar-powered O2 and further assessment of its efficacy and mortality benefit.

Project description:BackgroundAccurate estimation of blood loss is central to prompt diagnosis and management of post-partum hemorrhage (PPH), which remains a leading cause of maternal mortality in low-resource countries. In such settings, blood loss is often estimated visually and subjectively by attending health workers, due to inconsistent availability of laboratory infrastructure. We evaluated the diagnostic accuracy of weighed blood loss (WBL) versus changes in peri-partum hemoglobin to detect PPH.MethodsData from this analysis were collected as part of a randomized controlled trial comparing oxytocin with misoprostol for PPH (NCT01866241). Blood samples for complete blood count were drawn on admission and again prior to hospital discharge or before blood transfusion. During delivery, women were placed on drapes and had pre-weighed sanitary towels placed around their perineum. Blood was then drained into a calibrated container and the sanitary towels were added to estimate WBL, where each gram of blood was estimated as a milliliter. Sensitivity, specificity, negative and positive predictive values (PPVs) were calculated at various blood volume loss and time combinations, and we fit receiver-operator curves using blood loss at 1, 2, and 24 hours compared to a reference standard of haemoglobin decrease of >10%.ResultsA total of 1,140 women were enrolled in the study, of whom 258 (22.6%) developed PPH, defined as a haemoglobin drop >10%, and 262 (23.0%) had WBL ≥500mL. WBL generally had a poor sensitivity for detection of PPH (<75% for most volume-time combinations). In contrast, the specificity of WBL was high with blood loss ≥ 500mL at 1h and ≥750mL at any time points excluding PPH in over 97% of women. As such, WBL has a high PPV (>85%) in high prevalence settings when WBL exceeds 750mL.ConclusionWBL has poor sensitivity but high specificity compared to laboratory-based methods of PPH diagnosis. These characteristics correspond to a high PPV in areas with high PPH prevalence. Although WBL is not useful for excluding PPH, this low-cost, simple and reproducible method is promising as a reasonable method to identify significant PPH in such settings where quantifiable red cell indices are unavailable.

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Methodological challenges in measuring vaccine effectiveness using population cohorts in low resource settings.

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