The Experts below are selected from a list of 62250 Experts worldwide ranked by ideXlab platform
T. Christopher Mast - One of the best experts on this subject based on the ideXlab platform.
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Heterogeneity of Rotavirus Vaccine Efficacy Among Infants in Developing Countries.
The Pediatric infectious disease journal, 2017Co-Authors: Joann F. Gruber, Darcy A. Hille, G. Frank Liu, Susan S. Kaplan, Micki Nelson, Michelle G. Goveia, T. Christopher MastAbstract:Background:Rotavirus is the leading cause of severe diarrhea worldwide in young children. Although rotavirus Vaccine Efficacy is high in developed countries, Efficacy is lower in developing countries. Here, we investigated heterogeneity of rotavirus Vaccine Efficacy by infant characteristics in deve
Peter B Gilbert - One of the best experts on this subject based on the ideXlab platform.
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Partial Bridging of Vaccine Efficacy to New Populations
arXiv: Methodology, 2017Co-Authors: Alexander R. Luedtke, Peter B GilbertAbstract:Suppose one has data from one or more completed Vaccine Efficacy trials and wishes to estimate the Efficacy in a new setting. Often logistical or ethical considerations make running another Efficacy trial impossible. Fortunately, if there is a biomarker that is the primary modifier of Efficacy, then the biomarker-conditional Efficacy may be identical in the completed trials and the new setting, or at least informative enough to meaningfully bound this quantity. Given a sample of this biomarker from the new population, we might hope we can bridge the results of the completed trials to estimate the Vaccine Efficacy in this new population. Unfortunately, even knowing the true conditional Efficacy in the new population fails to identify the marginal Efficacy due to the unknown conditional unvaccinated risk. We define a curve that partially identifies (lower bounds) the marginal Efficacy in the new population as a function of the population's marginal unvaccinated risk, under the assumption that one can identify bounds on the conditional unvaccinated risk in the new population. Interpreting the curve only requires identifying plausible regions of the marginal unvaccinated risk in the new population. We present a nonparametric estimator of this curve and develop valid lower confidence bounds that concentrate at a parametric rate. We use Vaccine terminology throughout, but the results apply to general binary interventions and bounded outcomes.
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Predicting Overall Vaccine Efficacy in a New Setting by Re-Calibrating Baseline Covariate and Intermediate Response Endpoint Effect Modifiers of Type-Specific Vaccine Efficacy.
Epidemiologic methods, 2016Co-Authors: Peter B Gilbert, Ying HuangAbstract:We develop a transport formula for predicting overall cumulative Vaccine Efficacy through time t (VE(t)) to prevent clinically significant infection with a genetically diverse pathogen (e.g., HIV infection) in a new setting for which a Phase III preventive Vaccine Efficacy trial that would directly estimate VE(t) has not yet been conducted. The formula integrates data from (1) a previous Phase III trial, (2) a Phase I/II immune response biomarker endpoint trial in the new setting where a follow-up Phase III trial is planned, (3) epidemiological data on background HIV infection incidence in the new setting; and (4) genomic epidemiological data on HIV sequence distributions in the previous and new settings. For (1), the randomized Vaccine versus placebo Phase III trial yields estimates of Vaccine Efficacy to prevent particular genotypes of HIV in participant subgroups defined by baseline covariates X and immune responses to vaccination S(1) measured at a fixed time point τ (potential outcomes if assigned Vaccine); often one or more immune responses to vaccination are available that modify genotype-specific Vaccine Efficacy. The formula focuses on subgroups defined by X and S(1) and being at-risk for HIV infection at τ under both the Vaccine and placebo treatment assignments. For (2), the Phase I/II trial tests the same Vaccine in a new setting, or a refined new Vaccine in the same or new setting, and measures the same baseline covariates and immune responses as the original Phase III trial. For (3), epidemiological data in the new setting are used to project overall background HIV infection rates in the baseline covariate subgroups in the planned Phase III trial, hence re-calibrating for HIV incidence differences in the two settings; whereas for (4), data bases of HIV sequences measured from HIV infected individuals are used to re-calibrate for differences in the distributions of the circulating HIV genotypes in the two settings. The transport formula incorporates a user-specified bridging assumption function that measures differences in HIV genotype-specific conditional biological-susceptibility Vaccine efficacies in the two settings, facilitating a sensitivity analysis. We illustrate the transport formula with application to HIV Vaccine Trials Network (HVTN) research. One application of the transport formula is to use predicted VE(t) as a rational criterion for ranking a set of candidate Vaccines being studied in Phase I/II trials for their priority for down-selection into the follow-up Phase III trial.
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mark specific hazard ratio model with multivariate continuous marks an application to Vaccine Efficacy
Biometrics, 2013Co-Authors: Michal Juraska, Peter B GilbertAbstract:In randomized placebo-controlled preventive HIV Vaccine Efficacy trials, an objective is to evaluate the relationship between Vaccine Efficacy to prevent infection and genetic distances of the exposing HIV strains to the multiple HIV sequences included in the Vaccine construct, where the set of genetic distances is considered as the continuous multivariate ‘mark’ observed in infected subjects only. This research develops a multivariate mark-specific hazard ratio model in the competing risks failure time analysis framework for the assessment of mark-specific Vaccine Efficacy. It allows improved efficiency of estimation by employing the semiparametric method of maximum profile likelihood estimation in the Vaccine-to-placebo mark density ratio model. The model also enables the use of a more efficient estimation method for the overall log hazard ratio in the Cox model. Additionally, we propose testing procedures to evaluate two relevant hypotheses concerning mark-specific Vaccine Efficacy. The asymptotic properties and finite-sample performance of the inferential procedures are investigated. Finally, we apply the proposed methods to data collected in the Thai RV144 HIV Vaccine Efficacy trial.
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Mark‐Specific Hazard Ratio Model with Multivariate Continuous Marks: An Application to Vaccine Efficacy
Biometrics, 2013Co-Authors: Michal Juraska, Peter B GilbertAbstract:In randomized placebo-controlled preventive HIV Vaccine Efficacy trials, an objective is to evaluate the relationship between Vaccine Efficacy to prevent infection and genetic distances of the exposing HIV strains to the multiple HIV sequences included in the Vaccine construct, where the set of genetic distances is considered as the continuous multivariate ‘mark’ observed in infected subjects only. This research develops a multivariate mark-specific hazard ratio model in the competing risks failure time analysis framework for the assessment of mark-specific Vaccine Efficacy. It allows improved efficiency of estimation by employing the semiparametric method of maximum profile likelihood estimation in the Vaccine-to-placebo mark density ratio model. The model also enables the use of a more efficient estimation method for the overall log hazard ratio in the Cox model. Additionally, we propose testing procedures to evaluate two relevant hypotheses concerning mark-specific Vaccine Efficacy. The asymptotic properties and finite-sample performance of the inferential procedures are investigated. Finally, we apply the proposed methods to data collected in the Thai RV144 HIV Vaccine Efficacy trial.
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Sieve analysis in HIV-1 Vaccine Efficacy trials.
Current opinion in HIV and AIDS, 2013Co-Authors: Paul T. Edlefsen, Peter B Gilbert, Morgane RollandAbstract:Purpose of review The genetic characterization of HIV-1 breakthrough infections in Vaccine and placebo recipients offers new ways to assess Vaccine Efficacy trials. Statistical and sequence analysis methods provide opportunities to mine the mechanisms behind the effect of an HIV Vaccine. Recent findings The release of results from two HIV-1 Vaccine Efficacy trials, Step/HVTN-502 (HIV Vaccine Trials Network-502) and RV144, led to numerous studies in the last 5 years, including efforts to sequence HIV-1 breakthrough infections and compare viral characteristics between the Vaccine and placebo groups. Novel genetic and statistical analysis methods uncovered features that distinguished founder viruses isolated from Vaccinees from those isolated from placebo recipients, and identified HIV-1 genetic targets of Vaccine-induced immune responses. Summary Studies of HIV-1 breakthrough infections in Vaccine Efficacy trials can provide an independent confirmation to correlates of risk studies, as they take advantage of Vaccine/placebo comparisons, whereas correlates of risk analyses are limited to Vaccine recipients. Through the identification of viral determinants impacted by Vaccine-mediated host immune responses, sieve analyses can shed light on potential mechanisms of Vaccine protection.
Ira M Longini - One of the best experts on this subject based on the ideXlab platform.
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Estimating influenza Vaccine Efficacy from challenge and community-based study data
American journal of epidemiology, 2008Co-Authors: Nicole E. Basta, M. Elizabeth Halloran, Laura Matrajt, Ira M LonginiAbstract:In this paper, the authors provide estimates of 4 measures of Vaccine Efficacy for live, attenuated and inactivated influenza Vaccine based on secondary analysis of 5 experimental influenza challenge studies in seronegative adults and community-based Vaccine trials. The 4 Vaccine Efficacy measures are for susceptibility (VES), symptomatic illness given infection (VEP), infection and illness (VESP), and infectiousness (VEI). The authors also propose a combined (VEC) measure of the reduction in transmission in the entire population based on all of the above Efficacy measures. Live influenza Vaccine and inactivated Vaccine provided similar protection against laboratory-confirmed infection (for live Vaccine: VES ¼ 41%, 95% confidence interval (CI): 15, 66; for inactivated Vaccine: VES ¼ 43%, 95% CI: 8, 79). Live Vaccine had a higher Efficacy for illness given infection (VEP ¼ 67%, 95% CI: 24, 100) than inactivated Vaccine (VEP ¼ 29%, 95% CI: � 19, 76), although the difference was not statistically significant. VESP for the live Vaccine was higher than for the inactivated Vaccine. VEI estimates were particularly low for these influenza Vaccines. VESP and VEC can remain high for both Vaccines, even when VEI is relatively low, as long as the other 2 measures of Vaccine Efficacy are relatively high.
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A Bayesian framework for estimating Vaccine Efficacy per infectious contact
The annals of applied statistics, 2008Co-Authors: Yang Yang, Peter B Gilbert, Ira M Longini, M. Elizabeth HalloranAbstract:In Vaccine studies for infectious diseases such as human immunodeficiency virus (HIV), the frequency and type of contacts between study participants and infectious sources are among the most informative risk factors, but are often not adequately adjusted for in standard analyses. Such adjustment can improve the assessment of Vaccine Efficacy as well as the assessment of risk factors. It can be attained by modeling transmission per contact with infectious sources. However, information about contacts that rely on self-reporting by study participants are subject to nontrivial measurement error in many studies. We develop a Bayesian hierarchical model fitted using Markov chain Monte Carlo (MCMC) sampling to estimate the Vaccine Efficacy controlled for exposure to infection, while adjusting for measurement error in contact-related factors. Our method is used to re-analyze two recent HIV Vaccine studies, and the results are compared with the published primary analyses that used standard methods. The proposed method could also be used for other Vaccines where contact information is collected, such as human papilloma virus Vaccines.
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efficiency of estimating Vaccine Efficacy for susceptibility and infectiousness randomization by individual versus household
Biometrics, 1999Co-Authors: Susmita Datta, Elizabeth M Halloran, Ira M LonginiAbstract:In designing Vaccine Efficacy studies based on the secondary attack rate (SAR) or transmission probability in which both Vaccine Efficacy for susceptibility, VE(S), and Vaccine Efficacy for infectiousness, VE(I), are estimated, the allocation of Vaccine and placebo within transmission units has an important influence on the efficiency of the study. We compared the following randomization schemes that result in different allocations of Vaccine and placebo within two-member households: (1) randomization by individual for a mixed allocation, (2) randomization by transmission unit for concordant allocation, and (3) randomization of only one individual in each transmission unit to either Vaccine or placebo. There is a complex interaction among the VE(S), VE(I), and the SAR that determines which allocation of Vaccine and placebo within households provides the most information. In general, individual randomization with a mixed allocation of Vaccine and placebo is better for estimating both VE(S) and VE(I) than is randomizing by household. However, for estimation of VE(I), at very low SARs and low VE(S), randomization by household is slightly more efficient than randomization by individual.
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optimal Vaccine trial design when estimating Vaccine Efficacy for susceptibility and infectiousness from multiple populations
Statistics in Medicine, 1998Co-Authors: Ira M Longini, Karen Sagatelian, Wasima Rida, Elizabeth M HalloranAbstract:Vaccination can have important indirect effects on the spread of an infectious agent by reducing the level of infectiousness of Vaccinees who become infected. To estimate the effect of vaccination on infectiousness, one typically requires data on the contacts between susceptible and infected vaccinated and unvaccinated people. As an alternative, we propose a trial design that involves multiple independent and interchangeable populations. By varying the fraction of susceptible people vaccinated across populations, we obtain an estimate of the reduction infectiousness that depends only on incidence data from the Vaccine and control groups of the multiple populations. One can also obtain from these data an estimate of the reduction of susceptibility to infection. We propose a vaccination strategy that is a trade-off between optimal estimation of Vaccine Efficacy for susceptibility and of Vaccine Efficacy for infectiousness. We show that the optimal choice depends on the anticipated Efficacy of the Vaccine as well as the basic reproduction number of the underlying infectious disease process. Smaller vaccination fractions appear desirable when Vaccine Efficacy is likely high and the basic reproduction number is not large. This strategy avoids the potential for too few infections to occur to estimate Vaccine Efficacy parameters reliably.
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The Effect of Disease Prior to an Outbreak on Estimates of Vaccine Efficacy Following the Outbreak
American journal of epidemiology, 1995Co-Authors: Michael Haber, M. Elizabeth Halloran, Walter A. Orenstein, Ira M LonginiAbstract:A common source of bias in evaluating Vaccine Efficacy following a disease outbreak is the presence of persons who had the disease prior to the outbreak. This paper examines the effects of including and excluding pre-outbreak disease cases from the calculation of Vaccine Efficacy based on the cumulative incidence at the end of an outbreak. Using a five-stage model, the effects of the following factors on the bias of Vaccine Efficacy estimates are examined: the true protective Efficacy of the Vaccine, the prevaccination infection rate, differences in Vaccine uptake among the previously diseased and nondiseased, differences in pre-outbreak exposure to infection between Vaccinees and nonVaccinees, and differences in exposure during the outbreak between Vaccinees and nonVaccinees. Numerical calculations of the bias are performed for a hypothetical outbreak of measles in a developing country. Exclusion of pre-outbreak disease cases requires accurate data on disease rates prior to the outbreak, and such data are often unreliable or nonexistent. Inclusion of pre-outbreak cases contributes to the bias of the estimated Vaccine Efficacy, especially when there is a high prevaccination infection rate and Vaccine uptake among the previously diseased is considerably lower than that among the nondiseased. In most practical cases, however, this bias is not very large.
Joann F. Gruber - One of the best experts on this subject based on the ideXlab platform.
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Heterogeneity of Rotavirus Vaccine Efficacy Among Infants in Developing Countries.
The Pediatric infectious disease journal, 2017Co-Authors: Joann F. Gruber, Darcy A. Hille, G. Frank Liu, Susan S. Kaplan, Micki Nelson, Michelle G. Goveia, T. Christopher MastAbstract:Background:Rotavirus is the leading cause of severe diarrhea worldwide in young children. Although rotavirus Vaccine Efficacy is high in developed countries, Efficacy is lower in developing countries. Here, we investigated heterogeneity of rotavirus Vaccine Efficacy by infant characteristics in deve
Michael W. Deem - One of the best experts on this subject based on the ideXlab platform.
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The epitope regions of H1-subtype influenza A, with application to Vaccine Efficacy
Protein engineering design & selection : PEDS, 2009Co-Authors: Michael W. Deem, Keyao PanAbstract:The recent emergence of H1N1 (swine flu) illustrates the ability of the influenza virus to create antigens new to the human immune system, even within a given hemagglutinin and neuraminidase subtype. This new H1N1 strain is sufficiently distinct, for example, from the A/Brisbane/59/2007 (H1N1)-like virus strain of influenza in the 2008/09 Northern hemisphere Vaccine that protection is not expected to be substantial. The human immune system responds primarily to the five epitope regions of the hemagglutinin protein. By determining the fraction of amino acids that differ between a Vaccine strain and a viral challenge strain in the dominant epitope regions, a measure of antigenic distance that correlates with epidemiological studies of H3 influenza A Vaccine Efficacy in humans with R2 = 0.81 is derived. This measure of antigenic distance is called pepitope. The relation between Vaccine Efficacy and pepitope is given by E = 0.47 – 2.47 × pepitope. We here identify the epitope regions of H1 hemagglutinin, so that Vaccine Efficacy may be reliably estimated for H1N1 influenza A.
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Quantifying influenza Vaccine Efficacy and antigenic distance.
Vaccine, 2006Co-Authors: Vishal Gupta, David J. Earl, Michael W. DeemAbstract:We introduce a new measure of antigenic distance between influenza A Vaccine and circulating strains. The measure correlates well with efficacies of the H3N2 influenza A component of the annual Vaccine between 1971 and 2004, as do results of a theory of the immune response to influenza following vaccination. This new measure of antigenic distance is correlated with Vaccine Efficacy to a greater degree than are current state of the art phylogenetic sequence analyses or ferret antisera inhibition assays. We suggest that this new measure of antigenic distance be used in the design of the annual influenza Vaccine and in the interpretation of Vaccine Efficacy monitoring.
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Short communication Quantifying influenza Vaccine Efficacy and antigenic distance
2006Co-Authors: Vishal Gupta, David J. Earl, Michael W. DeemAbstract:We introduce a new measure of antigenic distance between influenza A Vaccine and circulating strains. The measure correlates well with efficacies of the H3N2 influenza A component of the annual Vaccine between 1971 and 2004, as do results of a theory of the immune response to influenza following vaccination. This new measure of antigenic distance is correlated with Vaccine Efficacy to a greater degree than are current state of the art phylogenetic sequence analyses or ferret antisera inhibition assays. We suggest that this new measure of antigenic distance be used in the design of the annual influenza Vaccine and in the interpretation of Vaccine Efficacy monitoring.