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Bayesian estimation of the time-varying sensitivity of a diagnostic test with application to mother-to-child transmission of HIV.

ABSTRACT: We present a Bayesian model to estimate the time-varying sensitivity of a diagnostic assay when the assay is given repeatedly over time, disease status is changing, and the gold standard is only partially observed. The model relies on parametric assumptions for the distribution of the latent time of disease onset and the time-varying sensitivity. Additionally, we illustrate the incorporation of historical data for constructing prior distributions. We apply the new methods to data collected in a study of mother-to-child transmission of HIV and include a covariate for sensitivity to assess whether two different assays have different sensitivity profiles.

SUBMITTER: Brown ER

PROVIDER: S-EPMC2940984 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Bayesian estimation of the time-varying sensitivity of a diagnostic test with application to mother-to-child transmission of HIV.

Brown Elizabeth R ER

Biometrics 20101201 4

We present a Bayesian model to estimate the time-varying sensitivity of a diagnostic assay when the assay is given repeatedly over time, disease status is changing, and the gold standard is only partially observed. The model relies on parametric assumptions for the distribution of the latent time of disease onset and the time-varying sensitivity. Additionally, we illustrate the incorporation of historical data for constructing prior distributions. We apply the new methods to data collected in a ...[more]

PMID: 20222936

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Project description:BackgroundBayesian estimation with informative priors permits updating previous findings with new data, thus generating cumulative knowledge. To reduce subjectivity in the process, the present study emphasizes how to systematically weigh and specify informative priors and highlights the use of different aggregation methods using an empirical example that examined whether observed mother-adolescent positive and negative interaction behavior mediate the associations between maternal and adolescent internalizing symptoms across early to mid-adolescence in a 3-year longitudinal multi-method design.MethodsThe sample consisted of 102 mother-adolescent dyads (39.2% girls, M age T1 = 13.0). Mothers and adolescents reported on their internalizing symptoms and their interaction behaviors were observed during a conflict task. We systematically searched for previous studies and used an expert-informed weighting system to account for their relevance. Subsequently, we aggregated the (power) priors using three methods: linear pooling, logarithmic pooling, and fitting a normal distribution to the linear pool by means of maximum likelihood estimation. We compared the impact of the three differently specified informative priors and default priors on the prior predictive distribution, shrinkage, and the posterior estimates.ResultsThe prior predictive distributions for the three informative priors were quite similar and centered around the observed data mean. The shrinkage results showed that the logarithmic pooled priors were least affected by the data. Most posterior estimates were similar across the different priors. Some previous studies contained extremely specific information, resulting in bimodal posterior distributions for the analyses with linear pooled prior distributions. The posteriors following the fitted normal priors and default priors were very similar. Overall, we found that maternal, but not adolescent, internalizing symptoms predicted subsequent mother-adolescent interaction behavior, whereas negative interaction behavior seemed to predict subsequent internalizing symptoms. Evidence regarding mediation effects remained limited.ConclusionA systematic search for previous information and an expert-built weighting system contribute to a clear specification of power priors. How information from multiple previous studies should be included in the prior depends on theoretical considerations (e.g., the prior is an updated Bayesian distribution), and may also be affected by pragmatic considerations regarding the impact of the previous results at hand (e.g., extremely specific previous results).

Project description:Mother-to-child transmission (MTCT) of Human T-cell lymphotropic virus type 1 (HTLV-1) causes lifelong infection. At least 5-10 million individuals worldwide are currently living with HTLV-1. Studies of regional variation are required to better understand the contribution of MTCT to the global burden of infection. Although most infected individuals remain asymptomatic ∼10% develop high morbidity, high mortality disease. Infection early in life is associated with a higher risk of disease development. Adult T-cell leukemia (ATL), which is caused by HTLV-1 and has a median survival of 8 months is linked to MTCT, indeed evidence of ATL following infection as an adult is sparse. Infective dermatitis also only occurs following neonatal infection. Whilst HTLV-1-associated myelopathy (HAM) follows sexual and iatrogenic infection approximately 30% of patients presenting with HAM/TSP acquired the infection through their mothers. HAM/TSP is a disabling neurodegenerative disease that greatly impact patient's quality of life. To date there is no cure for HTLV-1 infection other than bone marrow transplantation for ATL nor any measure to prevent HTLV-1 associated diseases in an infected individual. In this context, prevention of MTCT is expected to contribute disproportionately to reducing both the incidence of HTLV-1 and the burden of HTLV-1 associated diseases. In order to successfully avoid HTLV-1 MTCT, it is important to understand all the variables involved in this route of infection. Questions remain regarding frequency and risk factors for in utero peri-partum transmission whilst little is known about the efficacy of pre-labor cesarean section to reduce these infections. Understanding the contribution of peripartum infection to the burden of disease will be important to gauge the risk-benefit of interventions in this area. Few studies have examined the impact of HTLV-1 infection on fertility or pregnancy outcomes nor the susceptibility of the mother to infection during pregnancy and lactation. Whilst breast-feeding is strongly associated with transmission and avoidance of breast-feeding a proven intervention little is known about the mechanism of transmission from the breast milk to the infant and there have been no clinical trials of antiretroviral therapy (ARV) to prevent this route of transmission.

Project description:BackgroundThe Gambia has successfully reduced malaria transmission. The human reservoir of infection could further decrease if malaria-infected individuals could be identified by highly sensitive, field-based, diagnostic tools and then treated.MethodsA cross-sectional survey was done at the peak of the 2017 malaria season in 47 Gambian villages. From each village, 100 residents were randomly selected for finger-prick blood samples to detect Plasmodium falciparum infections using highly sensitive rapid diagnostic tests (HS-RDT) and PCR. The sensitivity and specificity of the HS-RDT were estimated (assuming PCR as the gold standard) across varying transmission intensities and in different age groups. A deterministic, age-structured, dynamic model of malaria transmission was used to estimate the impact of mass testing and treatment (MTAT) with HS-RDT in four different scenarios of malaria prevalence by PCR: 5, 15, 30, and 60%, and with seasonal transmission. The impact was compared both to MTAT with conventional RDT and mass drug administration (MDA).ResultsMalaria prevalence by HS-RDT was 15% (570/3798; 95% CI 13.9-16.1). The HS-RDT sensitivity and specificity were 38.4% (191/497, 95% CI 34.2-42.71) and 88.5% (2922/3301; 95% CI 87.4-89.6), respectively. Sensitivity was the highest (50.9%, 95% CI 43.3-58.5%) in high prevalence villages (20-50% by PCR). The model predicted that in very low transmission areas (≤ 5%), three monthly rounds of MTAT with HS-RDT, starting towards the end of the dry season and testing 65 or 85% of the population for 2 consecutive years, would avert 62 or 78% of malaria cases (over 2 years), respectively. The effect of the intervention would be lower in a moderate transmission setting. In all settings, MDA would be superior to MTAT with HS-RDT which would be superior to MTAT with conventional RDT.ConclusionThe HS-RDT's field sensitivity was modest and varied by transmission intensity. In low to very low transmission areas, three monthly rounds per year of MTAT with HS-RDT at 85% coverage for 2 consecutive years would reduce malaria prevalence to such low levels that additional strategies may achieve elimination. The model prediction would need to be confirmed by cluster-randomized trials.

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Bayesian estimation of the time-varying sensitivity of a diagnostic test with application to mother-to-child transmission of HIV.

Publications

Bayesian estimation of the time-varying sensitivity of a diagnostic test with application to mother-to-child transmission of HIV.

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