1988 — 1993 |
Brookmeyer, Ronald S |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Statistical Methods in Aids Research @ Johns Hopkins University
The overall objective of this grant is to continue to develop and apply statistical methods in AIDS research. With over 150,000 AIDS cases reported to the Centers for Disease Control as of October 1990, the AIDS epidemic is one of the most urgent public health problems in the United States. The focus of this research is on statistical modeling of the AIDS epidemic. There are three specific objectives of this proposal. The first is to develop statistical methods for obtaining improved estimates of current HIV prevalence .and future AIDS incidence. Methods will be investigated for combining AIDS incidence data and incubation distribution estimates with direct estimates of HIV prevalence obtained from epidemiologic surveys. The second objective is to develop a statistical framework for analyzing serial HIV prevalence surveys and to determine what information can be gleaned about the incidence of HIV infection from such data. The methods will be applied to military applicant screening data in the U.S. The third objective is to carefully study the uncertainties which may effect the back-calculation methodology and how these uncertainties are propagated into the estimates of current and past HIV prevalence, and projections of future AIDS incidence. The sources of uncertainty that will be considered include the parametric mode-1 for the infection rate, the incubation period distribution, reporting delays and errors in AIDS incidence, and the efficacy and availability of treatment. This work will entail detailed sensitivity analyses and quantification of the effects of model misspecification. We will characterize the performance of back-calculation methods In a wide range of situations.
|
0.958 |
1995 — 1997 |
Brookmeyer, Ronald S |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Statistical Methods in Aids Epidemiology @ Johns Hopkins University
The overall objective of this grant is to develop and apply statistical methods in AIDS epidemiology. There are three specific objectives of this proposal. The first is to develop and compare different statistical methods and study designs for estimating current HIV incidence. One approach will be to investigate the use of diagnostic tests such as tests for p24 antigen or other markers to identify individuals in cross-sectional surveys who were recently infected. The work will entail a detailed analysis of the sources of uncertainty in estimates of HIV incidence using these approaches. These approaches for estimating HIV incidence will be compared to other approaches including cohort studies and backcalculation methods with respect to sources of uncertainty, precision of the estimates, sample size requirements and sensitivities to model assumptions. The methods will be used to estimate current HIV incidence rates in India, and in an inner city emergency department. The second objective is to develop statistical models and methods for studies of the preantibody (window) period, and in particular to estimate the duration of p24 antigenemia. New statistical methods will be developed and applied to the analysis of data from emergency department patients and plasma donors. The third objective is to generalize the method of backcalculation to account for changes in the AIDS surveillance definition, and in particular to account for the significant revision of the case definition in 1993. This work will include application of the methods to U.S. AIDS incidence data, detailed sensitivity analyses and quantification of the effects of model misspecification.
|
0.958 |
1999 — 2001 |
Brookmeyer, Ronald S |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Statistical Methods in Aids Research @ Johns Hopkins University
DESCRIPTION (The applicant's abstract) The overall objective of this grant is to develop and apply statistical methods in AIDS research. The focus is on the development of statistical methods for the analysis of longitudinal studies of HIV disease to improve scientific inferences from studies of HIV epidemiology, prevention and treatment. There are three specific aims of this proposal. The first specific aim is the development of methods for the analysis of data that are subject to informative censoring or more generally informative stochastic coarsening in longitudinal studies of HIV disease with time to event data. Right censored, interval censored and current status data are all examples of coarsened time to event data. This work will have applicability to studies of HIV prevention, treatment and epidemiology for estimation of HIV incidence rates, relative risks, vaccine and treatment efficacy. The work under specific aim 1 will be applied to a study of high risk HIV-negative individuals attending STD clinics in India, needle exchange evaluations in Baltimore, and a cohort of IV drug users in the U.S. (ALIVE). The second specific aim is the development of statistical methods for studies of maternal-infant transmission. This work will include regression models to estimate maternal-infant transmission rates that adequately account for loss to follow-up and differential infant mortality, as well as longitudinal data methods for tracking viral loads in maternal sera and breast milk and for correlating these loads with risks of maternal-infant transmission. The work under specific aim 2 will be applied to studies in Haiti and Zimbabwe. The third specific aim concerns the development of statistical methods for the analysis of recurrent events such as repeat hospitalizations and infections. The work under specific aim 3 will entail the development of one-sample and regression models for recurrent event data that address the issue of informative censoring for estimation of the occurrence rate of recurrent events over time and regression models. The methods will be applied to the ALIVE study.
|
0.958 |
2002 — 2003 |
Brookmeyer, Ronald S |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Statistical Models For Anthrax @ Johns Hopkins University
DESCRIPTION (provided by applicant): The objective of this application is to develop statistical models for anthrax outbreaks and the pathogenesis of inhalation anthrax. Because of limited laboratory and field study data on inhalation anthrax relative to other diseases, it is imperative to glean as much information as possible from the available data through development and application of state-of-the-art statistical methods and mathematical and statistical models. There are three specific aims: 1. Develop statistical models for anthrax outbreaks. These models would allow one to estimate the size of an anthrax outbreak, the impact of antimicrobial prophylaxis, the probability that an outbreak has ended, and the likely date cases were exposed to the spores. The methods will be applied to the 2001 U.S anthrax outbreak. The performance and operating characteristics of the methods will be evaluated by computer simulation. The methods will be extended to develop statistical algorithms that could be used to forecast and characterize future anthrax outbreaks. 2. Develop statistical and mathematical models for the incubation period distribution of inhalation anthrax that account for dependence on age and numbers of inhaled spores. These models will be based on reanalysis of the Sverdlovsk outbreak in 1979 as well as other published experimental and field studies. 3. Perform sensitivity analyses to underlying assumptions of the proposed models and methods, and, quantify the statistical error in the results. This work will address sensitivity of the results to the parametric form of the incubation period distribution, confidence interval procedures for parameters, and impact of phenomenon such as resuspension of spores or prolonged spore circulation in the atmosphere. This work will depend on results from specific aims 1 and 2.
|
0.958 |
2003 |
Brookmeyer, Ronald S |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Statistical Methods For Partially Controlled Studies @ Johns Hopkins University
DESCRIPTION (provided by applicant): The objective of this project is to develop new statistical designs and methods to better evaluate partially controlled studies in public health. There are three specific aims. The first aim is to develop methods to evaluate treatments in studies that: do not directly control which subjects get which treatment, or which subjects provide outcomes; but do control the location of the sites that provide the treatments. Because existing methods, including standard instrumental variables, cannot handle the coexistence of the uncontrolled factors of taking treatment and of providing outcomes, the work under aim 1 is essential for proper treatment evaluation. This work will be applied to ongoing needle exchange programs in Baltimore, for preventing HIV transmission. The second aim is to develop new methods for clinical trials where treatment received is controlled, and outcomes are measured; a post-treatment surrogate endpoint is measured; and the goal is to estimate the treatments effects on the outcome that are concurrent and not concurrent with the surrogate. The methods under aim 2 use a new type of stratification for the uncontrolled surrogates that avoid the complications of standard stratifications on post-treatment variables. This work is essential for proper evaluation of early post-treatment symptoms as measures of later treatment effect, and we will apply it to cancer and ophthalmology trials. The third aim is to develop methods for study designs where: some persons drop out of a longitudinal follow-up, and where we can find (double-sample) a representative subset of the dropouts. This work is essential for preserving generalizability of results from long follow-up studies, and we will apply it to better evaluate time to potential drug dependence in youths.
|
0.958 |
2011 — 2014 |
Brookmeyer, Ronald S Eshleman, Susan H [⬀] |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Laboratory and Statistical Development of Cross-Sectional Hiv Incidence Assays @ Johns Hopkins University
DESCRIPTION (provided by applicant): HIV incidence is the rate at which new HIV infections occur in populations. While HIV prevalence measures overall disease burden, HIV incidence tracks the leading edge of the HIV/AIDS epidemic. Accurate HIV incidence estimates are critical for monitoring the HIV/AIDS epidemic, identifying populations at high risk of HIV acquisition, targeting prevention efforts, and designing and evaluating HIV prevention trials. Current methods for cross-sectional HIV incidence determination are insufficiently accurate. Our goal is to develop and validate accurate, cost-effective methods for cross-sectional HIV incidence determination. Our hypothesis is that diverse laboratory assays and robust statistical modeling can be combined to improve the accuracy of cross-sectional HIV incidence estimates. We will focus on analysis of HIV incidence in both subtype B (the major subtype driving the HIV/AIDS epidemic in the United States) and subtype C (the major subtype driving the HIV/AIDS epidemic in sub-Saharan Africa); other subtypes prevalent in sub-Saharan Africa will also be analyzed. The Specific Aims of the project are: Aim 1: Continue to build a repository of diverse, well-characterized samples with information on the duration of HIV infection. Analyze the samples using serologic HIV incidence assays. Aim 2: Further develop and validate a novel high resolution melting (HRM) assay for HIV diversity. Determine whether HIV diversity can be used as a biomarker to differentiate between individuals with recent vs. chronic HIV infection. Aim 3: Use statistical analysis and mathematical modeling to assess the accuracy of methods for HIV incidence determination. Apply those approaches to data from Aim 1 (CD4 cell count, HIV viral load, and data from serologic assays) and Aim 2 (data from the HRM assay) to identify methods for HIV incidence determination that perform well in a wide variety of settings, and to assess their relative costs. Our repository will include samples from at least 19 completed clinical trials, cohort studies, and research projects representing key geographic, demographic, and clinically-relevant populations. Over 10,000 of the samples are already in hand. We will integrate laboratory science with statistical analysis and mathematical modeling in all phases of the project, and will evaluate a broad range of design parameters, including use of individual assays versus multi-assay algorithms, use of different assay cutoffs, and sequential ordering of assays. We believe that this comprehensive approach will lead to identification of accurate and cost-effective methods for cross-sectional HIV incidence determination. ) )
|
0.958 |