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Bayesian hierarchical regression on clearance rates in the presence of "lag" and "tail" phases with an application to malaria parasites.

ABSTRACT: We present a principled technique for estimating the effect of covariates on malaria parasite clearance rates in the presence of "lag" and "tail" phases through the use of a Bayesian hierarchical linear model. The hierarchical approach enables us to appropriately incorporate the uncertainty in both estimating clearance rates in patients and assessing the potential impact of covariates on these rates into the posterior intervals generated for the parameters associated with each covariate. Furthermore, it permits us to incorporate information about individuals for whom there exists only one observation time before censoring, which alleviates a systematic bias affecting inference when these individuals are excluded. We use a changepoint model to account for both lag and tail phases, and hence base our estimation of the parasite clearance rate only on observations within the decay phase. The Bayesian approach allows us to treat the delineation between lag, decay, and tail phases within an individual's clearance profile as themselves being random variables, thus taking into account the additional uncertainty of boundaries between phases. We compare our method to existing methodology used in the antimalarial research community through a simulation study and show that it possesses desirable frequentist properties for conducting inference. We use our methodology to measure the impact of several covariates on Plasmodium falciparum clearance rate data collected in 2009 and 2010. Though our method was developed with this application in mind, it can be easily applied to any biological system exhibiting these hindrances to estimation.

SUBMITTER: Fogarty CB

PROVIDER: S-EPMC4575239 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Bayesian hierarchical regression on clearance rates in the presence of "lag" and "tail" phases with an application to malaria parasites.

Fogarty Colin B CB Fay Michael P MP Flegg Jennifer A JA Stepniewska Kasia K Fairhurst Rick M RM Small Dylan S DS

Biometrics 20150407 3

We present a principled technique for estimating the effect of covariates on malaria parasite clearance rates in the presence of "lag" and "tail" phases through the use of a Bayesian hierarchical linear model. The hierarchical approach enables us to appropriately incorporate the uncertainty in both estimating clearance rates in patients and assessing the potential impact of covariates on these rates into the posterior intervals generated for the parameters associated with each covariate. Further ...[more]

PMID: 25851174

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Project description:BACKGROUND:Emerging resistance to anti-malarial drugs has led malaria researchers to investigate what covariates (parasite and host factors) are associated with resistance. In this regard, investigation of how covariates impact malaria parasites clearance is often performed using a two-stage approach in which the WWARN Parasite Clearance Estimator or PCE is used to estimate parasite clearance rates and then the estimated parasite clearance is regressed on the covariates. However, the recently developed Bayesian Clearance Estimator instead leads to more accurate results for hierarchial regression modelling which motivated the authors to implement the method as an R package, called "bhrcr". METHODS:Given malaria parasite clearance profiles of a set of patients, the "bhrcr" package performs Bayesian hierarchical regression to estimate malaria parasite clearance rates along with the effect of covariates on them in the presence of "lag" and "tail" phases. In particular, the model performs a linear regression of the log clearance rates on covariates to estimate the effects within a Bayesian hierarchical framework. All posterior inferences are obtained by a "Markov Chain Monte Carlo" based sampling scheme which forms the core of the package. RESULTS:The "bhrcr" package can be utilized to study malaria parasite clearance data, and specifically, how covariates affect parasite clearance rates. In addition to estimating the clearance rates and the impact of covariates on them, the "bhrcr" package provides tools to calculate the WWARN PCE estimates of the parasite clearance rates as well. The fitted Bayesian model to the clearance profile of each individual, as well as the WWARN PCE estimates, can also be plotted by this package. CONCLUSIONS:This paper explains the Bayesian Clearance Estimator for malaria researchers including describing the freely available software, thus making these methods accessible and practical for modelling covariates' effects on parasite clearance rates.

Project description:BackgroundThere is increasing interest in the role played by maternal depression in mediating the effects of adversity during pregnancy and poor infant outcomes. There is also increasing evidence from multilevel regression studies for an association of area-level economic deprivation and poor individual mental health. The purpose of the study reported here is to explore the spatial distribution of postnatal depressive symptoms in South Western Sydney, Australia, and to identify covariate associations that could inform subsequent multilevel studies.MethodsMothers (n?=?15,389) delivering in 2002 and 2003 were assessed at 2-3 weeks after delivery for risk factors for depressive symptoms. The individual-level binary outcome variables were Edinburgh Depression Scale (EDS) >9 and >12. The association between social, demographic and ecological factors and aggregated outcome variables were investigated using exploratory factor analysis and multivariate hierarchical Bayesian spatial regression. Relative risks from the final EDS?>12 regression model were mapped to visualise the contribution from explanatory covariates and residual components.ResultsThe exploratory factor analysis identified six factors: neighbourhood adversity, social cohesion, health behaviours, housing quality, social services, and support networks. Variables associated with neighbourhood adversity, social cohesion, social networks, and ethnic diversity were consistently associated with aggregated depressive symptoms. Measures of social disadvantage, lack of social cohesion and lack of social capital were associated with increased depressive symptoms. The association with social disadvantage was not significant when controlling for ethnic diversity and social capital.ConclusionsThe findings support the theoretical proposition that neighbourhood adversity causes maternal psychological distress and depression within the context of social buffers including social networks, social cohesion, and social services. The finding have implications for the distribution of health services including early nurse home visiting which has recently been confirmed to be effective in preventing postnatal depression.

Dataset Information

Bayesian hierarchical regression on clearance rates in the presence of "lag" and "tail" phases with an application to malaria parasites.

Publications

Bayesian hierarchical regression on clearance rates in the presence of "lag" and "tail" phases with an application to malaria parasites.

Similar Datasets

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