Many important variables in biomedical studies of HIV/AIDS are ordered categorical. A few examples include WHO clinical stage, level of education, frequency of douching, stage of cervical lesions, self- reported condom use, and biallelic genotypes. Although ordinal variables are common, statistical methods that account for their ordered nature are lacking, particularly when the ordinal variable is a predictor variable. Most standard methods either treat the ordinal predictor as categorical (ignoring the order information) or continuous (making linearity assumptions). This proposal develops statistical methods that account for the ordered nature of ordinal variables without making linearity assumptions. The methods address situations when a predictor variable (X) is ordered categorical;the outcome variable (Y) is continuous, discrete, counts, time-to-event, or repeated measures;and there are multiple covariates (Z). The general approach is to fit appropriate regression models of Y on Z, and X on Z, and then to test for correlation between the residuals from these two models. The methods therefore rely on a new definition of residual for ordered categorical data. Statistical properties of this residual are evaluated, as well as its use in model diagnostics. Asymptotic properties of the residual- based test statistics are computed, relationships with other methods are derived, user-friendly software that implements these methods is developed, and the advantages of the new methods are studied using simulated and real data. The methods are applied to two HIV studies: The first assesses the effect of the frequency of douching on sexually transmitted infections among a cohort of adolescent females using marginal structural models. The second data application looks for human genetic polymorphisms associated with drug plasma levels, virologic failure, and toxicities for patients initiating an efavirenz- or abacavir-based antiretroviral regimen.

Public Health Relevance

The new methods are put into computer software and applied to studies of 1) the effect of douching on sexually transmitted infections among adolescent females, and 2) which patients may be able to better respond to specific HIV-treatments based on genetic patterns.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI093234-01A1
Application #
8209824
Study Section
AIDS Clinical Studies and Epidemiology Study Section (ACE)
Program Officer
Gezmu, Misrak
Project Start
2011-05-18
Project End
2016-04-30
Budget Start
2011-05-18
Budget End
2012-04-30
Support Year
1
Fiscal Year
2011
Total Cost
$389,584
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Biostatistics & Other Math Sci
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
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Shepherd, Bryan E; Rebeiro, Peter F; Caribbean, Central and South America network for HIV epidemiology (2017) Brief Report: Assessing and Interpreting the Association Between Continuous Covariates and Outcomes in Observational Studies of HIV Using Splines. J Acquir Immune Defic Syndr 74:e60-e63
Oh, Eric J; Shepherd, Bryan E; Lumley, Thomas et al. (2017) Considerations for analysis of time-to-event outcomes measured with error: Bias and correction with SIMEX. Stat Med :
Liu, Qi; Li, Chun; Wanga, Valentine et al. (2017) Covariate-adjusted Spearman's rank correlation with probability-scale residuals. Biometrics :
Shepherd, Bryan E; Liu, Qi (2016) Discussion of 'Regularized Regression for Categorical Data'. Stat Modelling 16:238-248
Shepherd, Bryan E; Liu, Qi; Mercaldo, Nathaniel et al. (2016) Comparing results from multiple imputation and dynamic marginal structural models for estimating when to start antiretroviral therapy. Stat Med 35:4335-4351
Shepherd, Bryan E; Li, Chun; Liu, Qi (2016) Probability-scale residuals for continuous, discrete, and censored data. Can J Stat 44:463-479
Blevins, Meridith; Wehbe, Firas H; Rebeiro, Peter F et al. (2016) Interactive Data Visualization for HIV Cohorts: Leveraging Data Exchange Standards to Share and Reuse Research Tools. PLoS One 11:e0151201
Ray, Wayne A; Liu, Qi; Shepherd, Bryan E (2015) Performance of time-dependent propensity scores: a pharmacoepidemiology case study. Pharmacoepidemiol Drug Saf 24:98-106

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