R37AI131771

Statistical methods and designs for correlated outcome and covariate errors in studies of HIV/AIDS - Project Summary/Abstract

Electronic Health Record (EHR) and other routinely collected data are often used as cost-effective data sources for HIV/AIDS research. These data sources, however, are known to be prone to errors, typically across multiple variables, which can lead to biased study results and misleading conclusions.

In addition, EHR data sources often lack gold-standard measurements that are needed to clearly define the presence or absence of co-morbidities (e.g., liver fibrosis). To address limitations of EHR data sources, researchers can validate or collect additional data on a subsample of their patient records.

By combining the rich, but error-prone EHR data on all study subjects with the gold-standard/validated data collected on a subsample of subjects, researchers can improve study estimates. Specifically, researchers can eliminate the bias of estimates had they only used the EHR data, and they can improve the precision (e.g., narrower confidence intervals) of study estimates had they only used the subsample with gold-standard/validated data.

In earlier research, we developed statistical methods and software to combine EHR data with validated subsamples of data. We developed optimal, multi-wave designs for targeting records for data validation. Importantly, we applied these methods to multiple HIV studies using retrospective observational data from the International Epidemiology Databases to Evaluate AIDS (IEDEA).

However, in our applications, we have encountered additional challenges that have not yet been addressed. In particular, there is great potential in combining expensive, prospectively collected, gold-standard data that are sparsely measured (e.g., once per year) on a subsample of patients with EHR data that are collected much more frequently on a larger number of patients.

We will develop methods to handle this setting, and we will develop statistical designs to better select which participants should be approached for prospective data collection and which patient records should be validated. We will also develop statistical methods to address other challenges encountered with using EHR data, including how to incorporate validation data into studies when inclusion in the study is error-prone, and methods to address more complex types of data (e.g., interval censored data), for which there are a lack of techniques to handle error-prone data.

Our methods and designs will focus on extensions of multiple imputation, maximum likelihood, and generalized raking techniques. Open source tools and tutorials will be developed to help researchers implement these novel methods and study designs.

The methods and designs will be applied to data from the IEDEA network to estimate the incidence of and risk factors for liver fibrosis/steatosis and frailty among people living with HIV in East Africa and Latin America.

Vanderbilt University Medical Center

TO ASSIST PUBLIC AND PRIVATE NONPROFIT INSTITUTIONS AND INDIVIDUALS TO ESTABLISH, EXPAND AND IMPROVE BIOMEDICAL RESEARCH AND RESEARCH TRAINING IN INFECTIOUS DISEASES AND RELATED AREAS, TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS. TO ASSIST PUBLIC, PRIVATE AND COMMERCIAL INSTITUTIONS TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS, TO PROVIDE RESEARCH SERVICES AS REQUIRED BY THE AGENCY FOR PROGRAMS IN INFECTIOUS DISEASES, AND CONTROLLING DISEASE CAUSED BY INFECTIOUS OR PARASITIC AGENTS, ALLERGIC AND IMMUNOLOGIC DISEASES AND RELATED AREAS. PROJECTS RANGE FROM STUDIES OF MICROBIAL PHYSIOLOGY AND ANTIGENIC STRUCTURE TO COLLABORATIVE TRIALS OF EXPERIMENTAL DRUGS AND VACCINES, MECHANISMS OF RESISTANCE TO ANTIBIOTICS AS WELL AS RESEARCH DEALING WITH EPIDEMIOLOGICAL OBSERVATIONS IN HOSPITALIZED PATIENTS OR COMMUNITY POPULATIONS AND PROGRESS IN ALLERGIC AND IMMUNOLOGIC DISEASES. BECAUSE OF THIS DUAL FOCUS, THE PROGRAM ENCOMPASSES BOTH BASIC RESEARCH AND CLINICAL RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM EXPANDS AND IMPROVES PRIVATE SECTOR PARTICIPATION IN BIOMEDICAL RESEARCH. THE SBIR PROGRAM INTENDS TO INCREASE AND FACILITATE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATES AND FOSTERS SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. RESEARCH CAREER DEVELOPMENT AWARDS SUPPORT THE DEVELOPMENT OF SCIENTISTS DURING THE FORMATIVE STAGES OF THEIR CAREERS. INDIVIDUAL NATIONAL RESEARCH SERVICE AWARDS (NRSAS) ARE MADE DIRECTLY TO APPROVE APPLICANTS FOR RESEARCH TRAINING IN SPECIFIED BIOMEDICAL SHORTAGE AREAS. IN ADDITION, INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDS ARE MADE TO ENABLE INSTITUTIONS TO SELECT AND MAKE AWARDS TO INDIVIDUALS TO RECEIVE TRAINING UNDER THE AEGIS OF THEIR INSTITUTIONAL PROGRAM.

93.855 - Allergy and Infectious Diseases Research

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Nashville, Tennessee 37203 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 279% from $893,452 to $3,384,785.