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<title>Statistical Communications in Infectious Diseases</title>
<copyright>Copyright (c) 2011 Berkeley Electronic Press All rights reserved.</copyright>
<link>http://www.bepress.com/scid</link>
<description>Recent documents in Statistical Communications in Infectious Diseases</description>
<language>en-us</language>
<lastBuildDate>Tue, 08 Nov 2011 02:10:35 PST</lastBuildDate>
<ttl>3600</ttl>


	
		
	







<item>
<title>Statistical Considerations in Determining HIV Incidence from Changes in HIV Prevalence</title>
<link>http://www.bepress.com/scid/vol3/iss1/art9</link>
<guid isPermaLink="true">http://www.bepress.com/scid/vol3/iss1/art9</guid>
<pubDate>Sun, 06 Nov 2011 05:51:36 PST</pubDate>
<description>
	<![CDATA[
	<p>The development of methods for estimating HIV incidence is critical for tracking the epidemic and for designing, targeting and evaluating HIV prevention efforts. One method for estimating incidence is based on changes in HIV prevalence. That method is attracting increased attention because national population-based HIV prevalence surveys, such as Demographic and Health Surveys, are being conducted throughout the world. Here, we consider some statistical issues associated with estimating HIV incidence from two population-based HIV prevalence surveys conducted at two different points in time. We show that the incidence estimator depends on the relative survival rate. We evaluate the sensitivity of estimates to incorrect assumptions about the relative survival rate, and show that small errors in the relative survival can, in some situations, create large biases in HIV incidence. We determine sample sizes of prevalence surveys to estimate incidence with precision and show how the sample sizes depend on baseline prevalence, the relative survival rate, and the population HIV incidence rate. We find that even if the relative survival rate were known exactly, there are situations where prohibitively large prevalence surveys would be required to produce reliable incidence estimates. These situations can occur either when the baseline prevalence is large, the relative survival rate is near 1, or the population incidence is small. Because information on the relative survival rate may be limited or not specific to the population under study, we suggest an approach to empirically estimate this critical parameter by augmenting population-based prevalence surveys with a mortality follow-up sub-study. We determine sample sizes of the prevalence surveys and mortality sub-studies for this augmented design and provide the necessary R code (version 2.13.0) for sample size determinations. We conclude that caution should be exercised when solely relying on changes in prevalence as the method for determining HIV incidence because of the method's sensitivity to mortality assumptions and the very large sample size requirements in some settings.</p>

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</description>

<author>Ron Brookmeyer et al.</author>


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<title>Sample Size for a Binomial Proportion with Autocorrelation</title>
<link>http://www.bepress.com/scid/vol3/iss1/art8</link>
<guid isPermaLink="true">http://www.bepress.com/scid/vol3/iss1/art8</guid>
<pubDate>Mon, 24 Oct 2011 13:11:38 PDT</pubDate>
<description>
	<![CDATA[
	<p>A flexible sample size computation is desired for a binomial outcome consisting of repeated binary measures with autocorrelation over time.  This type of outcome is common in viral shedding studies, in which each individual's outcome is a proportion:  the number of samples on which virus is detected out of number of samples assessed.  Autocorrelation between proximal samples occurs in some conditions such as herpes infection, in which reactivation is episodic.  We determine a sample size computation that accounts for: (1) participant-level differences in outcome frequency, (2) autocorrelation in time between samples, and (3) varying number of samples per participant.  In addition, we develop a computation appropriate for crossover designs that accounts for the dependence of the investigational treatment effect on the pre-treatment detection frequency.  The computations are validated through comparison with real and simulated data, and sensitivity to misspecification of parameter values is examined graphically.</p>

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</description>

<author>Amalia S. Magaret et al.</author>


<category>virology</category>

<category>infectious diseases</category>

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<item>
<title>Nonparametric and Semiparametric Analysis of Current Status Data Subject to Outcome Misclassification</title>
<link>http://www.bepress.com/scid/vol3/iss1/art7</link>
<guid isPermaLink="true">http://www.bepress.com/scid/vol3/iss1/art7</guid>
<pubDate>Fri, 21 Oct 2011 11:31:11 PDT</pubDate>
<description>
	<![CDATA[
	<p>In this article, we present nonparametric and semiparametric methods to analyze current status data subject to outcome misclassification. Our methods use nonparametric maximum likelihood estimation (NPMLE) to estimate the distribution function of the failure time when sensitivity and specificity are known and may vary among subgroups. A nonparametric test is proposed for the two sample hypothesis testing. In regression analysis, we apply the Cox proportional hazard model and likelihood ratio based confidence intervals for the regression coefficients are proposed. Our methods are motivated and demonstrated by data collected from an infectious disease study in Seattle, WA.</p>

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</description>

<author>Victor G. Sal y Rosas et al.</author>


<category>Analysis of failure time data</category>

<category>outcome misclassification</category>

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<item>
<title>Using HIV Diagnostic Data to Estimate HIV Incidence: Method and Simulation</title>
<link>http://www.bepress.com/scid/vol3/iss1/art6</link>
<guid isPermaLink="true">http://www.bepress.com/scid/vol3/iss1/art6</guid>
<pubDate>Tue, 11 Oct 2011 14:38:17 PDT</pubDate>
<description>
	<![CDATA[
	<p>We propose a new approach to estimate the number of new infections with the human immunodeficiency virus (HIV), by integrating the back-calculation method based on HIV diagnostic data with proportions of recent infections among newly diagnosed individuals. This is done by establishing an explicit link between the distribution of time-since-infection given being tested and the distribution of time-to-testing given being infected. The trend in the proportions of recent infections identifies the time-to-testing distribution, which would have not been identifiable based on HIV surveillance data alone, and makes back-calculation possible. The integration of the proportions of recent infections among newly diagnosed HIV into the model allows a probabilistic interpretation of the estimated proportions of recent infections based on the results of laboratory tests, in terms of the estimated distribution of the time-since-infection given being tested.</p>

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</description>

<author>Ping Yan et al.</author>


<category>Physical Sciences and Mathematics: Statistics and Probability: Biostatistics</category>

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<title>Prediction of an Epidemic Curve: A Supervised Classification Approach</title>
<link>http://www.bepress.com/scid/vol3/iss1/art5</link>
<guid isPermaLink="true">http://www.bepress.com/scid/vol3/iss1/art5</guid>
<pubDate>Tue, 04 Oct 2011 09:35:04 PDT</pubDate>
<description>
	<![CDATA[
	<p>Classification methods are widely used for identifying underlying groupings within datasets and predicting the class for new data objects given a trained classifier. This study introduces a project aimed at using a combination of simulations and classification techniques to predict epidemic curves and infer underlying disease parameters for an ongoing outbreak.</p>
<p>Six supervised classification methods (random forest, support vector machines, nearest neighbor with three decision rules, linear and flexible discriminant analysis) were used in identifying partial epidemic curves from six agent-based stochastic simulations of influenza epidemics. The accuracy of the methods was compared using a performance metric based on the McNemar test.</p>
<p>The findings showed that: (1) assumptions made by the methods regarding the structure of an epidemic curve influences their performance i.e. methods with fewer assumptions perform best, (2) the performance of most  methods is consistent across different individual-based networks for Seattle, Los Angeles and New York and (3) combining classifiers using a weighting approach does not guarantee better prediction.</p>

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</description>

<author>Elaine O. Nsoesie et al.</author>


<category>Statistics and Epidemiology</category>

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<title>A Sequential Phase 2b Trial Design for Evaluating Vaccine Efficacy and Immune Correlates for Multiple HIV Vaccine Regimens</title>
<link>http://www.bepress.com/scid/vol3/iss1/art4</link>
<guid isPermaLink="true">http://www.bepress.com/scid/vol3/iss1/art4</guid>
<pubDate>Tue, 04 Oct 2011 09:34:57 PDT</pubDate>
<description>
	<![CDATA[
	<p>Five preventative HIV vaccine efficacy trials have been conducted over the last 12 years, all of which evaluated vaccine efficacy (VE) to prevent HIV infection for a single vaccine regimen versus placebo.  Now that one of these trials has supported partial VE of a prime-boost vaccine regimen, there is interest in conducting efficacy trials that simultaneously evaluate multiple prime-boost vaccine regimens against a shared placebo group in the same geographic region, for accelerating the pace of vaccine development.  This article proposes such a design, which has main objectives (1) to evaluate VE of each regimen versus placebo against HIV exposures occurring near the time of the immunizations; (2) to evaluate durability of VE for each vaccine regimen showing reliable evidence for positive VE; (3) to expeditiously evaluate the immune correlates of protection if any vaccine regimen shows reliable evidence for positive VE; and (4) to compare VE among the vaccine regimens.  The design uses sequential monitoring for the events of vaccine harm, non-efficacy, and high efficacy, selected to weed out poor vaccines as rapidly as possible while guarding against prematurely weeding out a vaccine that does not confer efficacy until most of the immunizations are received.  The evaluation of the design shows that testing multiple vaccine regimens is important for providing a well-powered assessment of the correlation of vaccine-induced immune responses with HIV infection, and is critically important for providing a reasonably powered assessment of the value of identified correlates as surrogate endpoints for HIV infection.</p>

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</description>

<author>Peter B. Gilbert et al.</author>


<category>HIV vaccine clinical trials</category>

<category>immunology</category>

<category>surrogate endpoint evaluation</category>

<category>group sequential monitoring</category>

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<item>
<title>Joint Modeling of HCV and HIV Co-Infection among Injecting Drug Users in Italy and Spain Using Individual Cross-Sectional Data</title>
<link>http://www.bepress.com/scid/vol3/iss1/art3</link>
<guid isPermaLink="true">http://www.bepress.com/scid/vol3/iss1/art3</guid>
<pubDate>Tue, 05 Jul 2011 15:06:51 PDT</pubDate>
<description>
	<![CDATA[
	<p>The aim of the analysis presented in this paper is to study co-infection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) in injecting drug users (IDUs) using a joint modeling approach that makes use of multivariate statistical methods for current status data.</p>
<p>Using marginal models, we estimate association measures between HCV and HIV infections at individual level, i.e., odds ratios and correlation coefficients, and we regress them against some risk factors, e.g., the length of the injecting career, the age at first injection, the ever sharing of syringes, and the frequency of current injecting. In addition, we fit random-effects models that take into account the individual heterogeneity in the acquisition of the infections. For our analysis, we use cross-sectional data from two independent serological surveys, one carried out in Italy (IT) in 2005 on 856 subjects, and the other in three Spanish (ES) cities, between 2001 and 2003, on 589 subjects.</p>
<p>We found that the infections are positively associated within individuals, e.g., OR<sub>IT</sub>=2.56 with 95% confidence interval (CI) (1.43, 6.68) and OR<sub>ES</sub>= 2.42, with 95% CI (1.41, 4.30). We found that the odds ratio and the correlation between HCV and HIV infections increase positively with the length of the injecting career. Moreover, they are found to be significantly positive in case IDUs have never shared syringes or report low injecting frequencies. The variance of the individual random effects is positive, e.g., σ<sub>b</sub><sup>2</sup>=0.34 (0.14, 0.62), indicating that there is significant individual heterogeneity in the acquisition of the infections.</p>
<p>Our results show that a significant association between HCV and HIV infections within IDUs is related to significant individual heterogeneity in the acquisition of the infections. Indeed, the association between these infections in IDUs who report ever sharing syringes is not significant, which can be explained by a higher homogeneity in their behaviors and, therefore, in their acquisition of the infections.</p>

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</description>

<author>Emanuele Del Fava et al.</author>


<category>Categorical Data Analysis</category>

<category>Disease Modeling</category>

<category>Multivariate Analysis</category>

<category>Statistical Models</category>

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<title>Using Approximate Bayesian Computation to Estimate Transmission Rates of Nosocomial Pathogens</title>
<link>http://www.bepress.com/scid/vol3/iss1/art2</link>
<guid isPermaLink="true">http://www.bepress.com/scid/vol3/iss1/art2</guid>
<pubDate>Wed, 22 Jun 2011 09:49:29 PDT</pubDate>
<description>
	<![CDATA[
	<p>In this paper, we apply a simulation based approach for estimating transmission rates of nosocomial pathogens.  In particular, the objective is to infer the transmission rate between colonised health-care practitioners and uncolonised patients (and vice versa) solely from routinely collected incidence data.   The method, using approximate Bayesian computation, is substantially less computer intensive and easier to implement than likelihood-based approaches we refer to here.  We find through replacing the likelihood with a comparison of an efficient summary statistic between observed and simulated data that little is lost in the precision of estimated transmission rates.  Furthermore, we investigate the impact of incorporating uncertainty in previously fixed parameters on the precision of the estimated transmission rates.</p>

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</description>

<author>Christopher C. Drovandi et al.</author>


<category>Statistics</category>

<category>Pathogen Transmission</category>

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<item>
<title>Joint Modeling of HCV and HIV Infections among Injecting Drug Users in Italy Using Repeated Cross-Sectional Prevalence Data</title>
<link>http://www.bepress.com/scid/vol3/iss1/art1</link>
<guid isPermaLink="true">http://www.bepress.com/scid/vol3/iss1/art1</guid>
<pubDate>Tue, 24 May 2011 13:26:51 PDT</pubDate>
<description>
	<![CDATA[
	<p>During their injecting career, injecting drug users (IDUs) are exposed to some infections, like hepatitis C virus (HCV) infection and human immunodeficiency virus (HIV) infection, due to their injecting behavioral risk factors, such as sharing syringes or other paraphernalia containing infected blood, or sexual behavior risk factors. If we consider that these IDUs might belong to a social network of people where these behavioral risk factors are spread, then HCV and HIV infections might be associated at both the individual and the population level. In this paper, we study the association between HCV and HIV infection at the population level using aggregate data. Our aim is to define a hierarchy of structured models with which the association between HCV and HIV infection at population level and the time trend of prevalence can be investigated. The data analyzed in the paper are “diagnostic testing data,” which consist of repeated cross-sectional prevalence measurements from 1998 to 2006 for HCV and HIV infection, obtained from a sample of 515 drug treatment centers spread among the 20 regions in Italy, where subjects went for a serum diagnostic test. Since we do not have any individual data, it is not possible to relate these prevalence data to socio-demographic or behavioral risk data. Each region defines a cluster with repeated prevalence data for HCV and HIV infection over time. Several modeling approaches, such as generalized linear mixed models (GLMMs) and hierarchical Bayesian models are applied to the data. First, we test different covariance structures for the region-specific random effects in the GLMM context; second, a hierarchical Bayesian model is used to refit the best GLMM in order to obtain the posterior distribution for the parameters of primary interest. We found that the correlation at population level between HCV and HIV is approximately 0.68 and the prevalence of the two infections generally decreased over the years, compared to the situation in 1998.</p>

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</description>

<author>Emanuele Del Fava et al.</author>


<category>Multivariate Analysis</category>

<category>Categorical Data Analysis</category>

<category>Bayesian modeling</category>

</item>






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<title>An Imputation Method for Interval Censored Time-to-Event with Auxiliary Information: Analysis of the Timing of Mother-to-Child Transmission of HIV</title>
<link>http://www.bepress.com/scid/vol2/iss1/art8</link>
<guid isPermaLink="true">http://www.bepress.com/scid/vol2/iss1/art8</guid>
<pubDate>Tue, 21 Dec 2010 15:13:42 PST</pubDate>
<description>
	<![CDATA[
	<p>The timing of mother-to-child transmission (MTCT) of HIV is critical in understanding the dynamics of MTCT. It has a great implication to developing any effective treatment or prevention strategies for such transmissions. In this paper, we develop an imputation method to analyze the censored MTCT timing in presence of auxiliary information. Specifically, we first propose a statistical model based on the hazard functions of the MTCT timing to reflect three MTCT modes: in utero, during delivery and via breastfeeding, with different shapes of the baseline hazard that vary between infants. This model also allows that the majority of infants may be immuned from the MTCT of HIV. Then, the model is fitted by MCMC to explore marginal inferences via multiple imputation. Moreover, we propose a simple and straightforward approach to take into account the imperfect sensitivity in imputation step, and study appropriate censoring techniques to account for weaning. Our method is assessed by simulations and applied to a large trial designed to assess the use of antibiotics in preventing MTCT of HIV.</p>

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</description>

<author>Elizabeth R. Brown et al.</author>


<category>HIV/AIDS</category>

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<title>The Effect of Misspecifying Latent and Infectious Periods in Space-Time Epidemic Models</title>
<link>http://www.bepress.com/scid/vol2/iss1/art7</link>
<guid isPermaLink="true">http://www.bepress.com/scid/vol2/iss1/art7</guid>
<pubDate>Mon, 06 Dec 2010 13:37:05 PST</pubDate>
<description>
	<![CDATA[
	<p>Individual level models (ILMs) are a class of models that can be applied to epidemic data to help in the understanding of the spatio-temporal dynamics of infectious diseases. Typically, these models are analyzed in a Bayesian framework using Markov chain Monte Carlo (MCMC) methodology. Here, we test the effect of misspecifying the latent and infectious period in such a model. We do this by simulating data from a simple spatial ILM, and then fitting various misspecified models to the simulated data. The fitted models serve as a basis for investigating the effect of the misspecification of latent and infectious periods on model parameter estimates, as well as estimates of the basic reproduction number.</p>
<p>Additionally, we analyze how a given preventative control strategy, optimized via simulation from a fitted model with assumed latent and infectious periods, is affected by such misspecification. We observe bias in the estimation of model parameters as latent and infectious periods become more misspecified, as well as a significant deviation in estimates of the basic reproduction number from those observed under the true model. Where the misspecification results in a higher basic reproduction number estimate, we also find that a more stringent control policy is required to achieve a given policy goal.</p>

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</description>

<author>Babak Habibzadeh et al.</author>


<category>epidemic modelling</category>

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<title>Probabilistic Record Linkage of Infection Records and Death Registrations: A Tool to Strengthen Surveillance</title>
<link>http://www.bepress.com/scid/vol2/iss1/art6</link>
<guid isPermaLink="true">http://www.bepress.com/scid/vol2/iss1/art6</guid>
<pubDate>Thu, 02 Dec 2010 08:21:02 PST</pubDate>
<description>
	<![CDATA[
	<p>An important element for many infectious disease surveillance programmes is their capacity to monitor not only the incidence of infection, but also the associated mortality.  The ability to monitor post-infection mortality is dependent on outcome information being collected through the surveillance reports, or on infections being precisely specified on death certificates.  For many infectious diseases, neither of these sources provides a reliable source of this information, so a method for linking infection and death registration data is needed.  Given that surveillance data often lacks a unique patient identifier, a probabilistic record linkage method was developed to reliably bring together large-scale data sources to identify deaths following infection.  The method was developed using <em>Streptococcus pneumonia</em> infection records but with wider applicability to other infectious disease surveillance programmes.  Evaluation of the mechanism was undertaken by tracing patients through a central health service database.  Results of the evaluation showed a positive predictive value of 97.7-99.8% for correctly identifying deaths following infection, and a negative predictive value of 90.2-98.0%.  The successful application of probabilistic matching to link infections and death registrations paves the way for a new era in infectious disease surveillance in the UK, with its potential application to augment a wide array of ongoing surveillance programmes with information on patient outcome.</p>

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</description>

<author>Nicola Potz et al.</author>


<category>infectious disease surveillance</category>

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<title>Optimal Dynamic Policies for Influenza Management</title>
<link>http://www.bepress.com/scid/vol2/iss1/art5</link>
<guid isPermaLink="true">http://www.bepress.com/scid/vol2/iss1/art5</guid>
<pubDate>Tue, 12 Oct 2010 13:41:11 PDT</pubDate>
<description>
	<![CDATA[
	<p>Management policies for influenza outbreaks balance the expected morbidity and mortality costs versus the cost of intervention policies. We present a methodology for dynamic determination of optimal policies in a completely observed stochastic compartmental model with parameter uncertainty. Our approach is simulation-based and searches the full set of sequential control strategies. For each time point, it generates a policy map describing the optimal intervention to implement as a function of outbreak state and Bayesian parameter posteriors. As a running example, we study a stochastic SIR model with isolation and vaccination as two possible interventions. Numerical simulations based on a classic influenza outbreak are used to explore the impact of various cost structures on management policies. Comparisons demonstrate the realized cost savings of choosing interventions based on the computed dynamic policy over simpler decision rules.</p>

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</description>

<author>Michael Ludkovski et al.</author>


<category>Statistics and Probability</category>

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<title>Who Will Benefit from a Wide-Scale Introduction of Vaginal Microbicides in Developing Countries?</title>
<link>http://www.bepress.com/scid/vol2/iss1/art4</link>
<guid isPermaLink="true">http://www.bepress.com/scid/vol2/iss1/art4</guid>
<pubDate>Wed, 07 Jul 2010 14:02:00 PDT</pubDate>
<description>
	<![CDATA[
	<p>Vaginal microbicides (VMB) are currently among the few biomedical interventions designed to help women reduce their risk of acquiring HIV infection. However, the microbicide containing antiretroviral (ARV-VMB) may lead to the development of antiretroviral resistance and could paradoxically become more beneficial to men at the population level.</p>
<p>We developed a mathematical model to study the impact of a wide-scale population usage of VMB in a heterosexual population. Gender ratios of prevented infections and prevalence reduction are evaluated in 63 different intervention schedules including continuous and interrupted ARV-VMB use by HIV-positive women. The influence of different factors on population-level benefits is also studied through Monte Carlo simulations using parameters sampled from primary ranges representative of developing countries.</p>
<p>Our analysis indicates that women are more likely than men to benefit from ARV-VMB use since 78-80% of the total 63,000 simulations investigated (under different parameter sets) showed a female advantage  whether benefit is measured as cumulative number of infections prevented, the percentage of cumulative infections prevented, or the expected reduction in prevalence. Stratified analysis by scenarios indicates that the likelihood of a male advantage with respect to the fractions of prevented infections varies from 6% to 49% among the scenarios. It is substantial only if the risk of systemic absorption and development of resistance to ARV-VMB is high and the HIV-positive women use VMB indefinitely without interruption. Therefore, the use of ARV-VMB, with successful control measures restricting usage by HIV-positive women, is still very much a female prevention tool.</p>

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</description>

<author>Dobromir T. Dimitrov et al.</author>


<category>Epidemic modeling and simulation</category>

</item>






<item>
<title>Is There an Association between Levels of Bovine Tuberculosis in Cattle Herds and Badgers?</title>
<link>http://www.bepress.com/scid/vol2/iss1/art3</link>
<guid isPermaLink="true">http://www.bepress.com/scid/vol2/iss1/art3</guid>
<pubDate>Tue, 30 Mar 2010 01:06:31 PDT</pubDate>
<description>
	<![CDATA[
	<p>Wildlife diseases can have undesirable effects on wildlife, on livestock and people. Bovine tuberculosis (TB) is such a disease. This study derives and then evaluates relationships between the proportion of cattle herds with newly detected TB infection in a year and data on badgers, in parts of Britain.</p>
<p>The relationships are examined using data from 10 sites which were randomly selected to be proactive culling sites in the UK Randomized Badger Culling Trial. The badger data are from the initial cull only and the cattle incidence data pre-date the initial badger cull.</p>
<p>The analysis of the proportion of cattle herds with newly detected TB infection in a year, showed strong support for the model including significant frequency-dependent transmission between cattle herds and significant badger-to-herd transmission proportional to the proportion of <em>M. bovis</em>-infected badgers. Based on the model best fitting all the data, 3.4% of herds (95% CI: 0 – 6.7%) would be expected to have TB infection newly detected (i.e. to experience a TB herd breakdown) in a year, in the absence of transmission from badgers. Thus, the null hypothesis that at equilibrium herd-to-herd transmission is not sufficient to sustain TB in the cattle population, in the absence of transmission from badgers cannot be rejected (p=0.18). Omitting data from three sites in which badger carcase storage may have affected data quality; the estimate dropped to 1.3% of herds (95% CI: 0 – 6.5%) with p=0.76.</p>
<p>The results demonstrate close positive relationships between bovine TB in cattle herds and badgers infectious with <em>M. bovis</em>. The results indicate that TB in cattle herds could be substantially reduced, possibly even eliminated, in the absence of transmission from badgers to cattle. The results are based on observational data and a small data set to provide weaker inference than from a large experimental study.</p>

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</description>

<author>Christl A. Donnelly et al.</author>


<category>transmission of bovine tuberculosis</category>

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<item>
<title>The Impact of Secondary Condom Interventions on the Interpretation of Results from HIV Prevention Trials</title>
<link>http://www.bepress.com/scid/vol2/iss1/art2</link>
<guid isPermaLink="true">http://www.bepress.com/scid/vol2/iss1/art2</guid>
<pubDate>Fri, 12 Feb 2010 10:49:24 PST</pubDate>
<description>
	<![CDATA[
	<p>Given the recent failure of a number of randomized trials to demonstrate effectiveness of proposed methods for prevention of sexual transmission of HIV, novel approaches to study design and analysis that address adherence and other post-randomization behaviors are of increasing interest. The inclusion of a mandatory condom use intervention in all randomized groups in such trials can significantly impact interpretation of study results, especially when levels of use observed in the study may differ from real world levels.</p>
<p>We use quantitative examples and simulations to investigate this issue, focusing on effectiveness estimated by the standard intention to treat analysis approach. We also assess the application of recently developed methods for estimating the causal effect of treatment assignment, accounting for observed levels of condom use.</p>
<p>Results show that observed levels of condom use may have substantial impacts on the conclusions drawn from standard analyses of prevention trials, with the most serious effects observed in studies with unblinded control groups. Causal estimation methods accounting for post-randomization behaviors can help clarify these impacts by focusing attention on effectiveness for controlled levels of condom use.</p>
<p>Supplemental causal analyses that account for post-randomization condom use may provide useful information about possible efficacy that complement standard analyses. However, interpretation of results may be limited by the quality of available data on adherence behavior, and limited statistical power.</p>

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</description>

<author>Stephen Shiboski et al.</author>


<category>HIV prevention</category>

<category>clinical trials</category>

<category>causal methods</category>

</item>






<item>
<title>Increasing the Efficiency of Prevention Trials by Incorporating Baseline Covariates</title>
<link>http://www.bepress.com/scid/vol2/iss1/art1</link>
<guid isPermaLink="true">http://www.bepress.com/scid/vol2/iss1/art1</guid>
<pubDate>Thu, 04 Feb 2010 08:31:10 PST</pubDate>
<description>
	<![CDATA[
	<p>Most randomized efficacy trials of interventions to prevent HIV or other infectious diseases have assessed intervention efficacy by a method that either does not incorporate baseline covariates, or that incorporates them in a non-robust or inefficient way.  Yet, it has long been known that randomized treatment effects can be assessed with greater efficiency by incorporating baseline covariates that predict the response variable.  Tsiatis et al. (2007) and Zhang et al. (2008) advocated a semiparametric efficient approach, based on the theory of Robins et al. (1994), for consistently estimating randomized treatment effects that optimally incorporates predictive baseline covariates, without any parametric assumptions. They stressed the objectivity of the approach, which is achieved by separating the modeling of baseline predictors from the estimation of the treatment effect.  While their work adequately justifies implementation of the method for large Phase 3 trials (because its optimality is in terms of asymptotic properties), its performance for intermediate-sized screening Phase 2b efficacy trials, which are increasing in frequency, is unknown. Furthermore, the past work did not consider a right-censored time-to-event endpoint, which is the usual primary endpoint for a prevention trial.  For Phase 2b HIV vaccine efficacy trials, we study finite-sample performance of Zhang et al.'s (2008) method for a dichotomous endpoint, and develop and study an adaptation of this method to a discrete right-censored time-to-event endpoint. We show that, given the predictive capacity of baseline covariates collected in real HIV prevention trials, the methods achieve 5-15% gains in efficiency compared to methods in current use.  We apply the methods to the first HIV vaccine efficacy trial. This work supports implementation of the discrete failure time method for prevention trials.</p>

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</description>

<author>Min Zhang et al.</author>


<category>Clinical Trial</category>

</item>






<item>
<title>Infectious Disease Modeling:  Creating a Community to Respond to Biological Threats</title>
<link>http://www.bepress.com/scid/vol1/iss1/art1</link>
<guid isPermaLink="true">http://www.bepress.com/scid/vol1/iss1/art1</guid>
<pubDate>Thu, 06 Aug 2009 14:25:48 PDT</pubDate>
<description>
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	<p>The rise of global economies in the 21<sup>st</sup> century, the rapid national and international movement of people, and the increased reliance of developed countries on global trade, all greatly increase the potential and possible magnitude of a worldwide pandemic. New epidemics may be the result of global climate change, vector-borne diseases, food-borne illness, new naturally occurring pathogens, or bio-terrorist attacks. The threat is most severe for highly communicable diseases. When rapidly spreading microparasitic infections coincide with the rapid transportation, propagation, and dissemination of the pathogens and vectors for infection, the risks associated with emerging infectious disease increase. We discuss the use of publicly-available technologies in assisting public health officials and scientists in protecting populations from emerging disease or in implementing improved response measures. We illustrate possibilities using the SpatioTemporal Epidemiological Modeler (STEM) that was developed to run on the Open Health Framework (OHF) created by the Eclipse Foundation in 2004. An illustration regarding the spread of the influenza H1N1 virus from Mexico to the United States via air travel in Spring 2009 is briefly discussed.</p>

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<author>James Kaufman et al.</author>


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