Search tips
Search criteria

Results 1-4 (4)

Clipboard (0)
Year of Publication
Document Types
1.  Associations of Non-Hodgkin Lymphoma (NHL) Risk With Autoimmune Conditions According to Putative NHL Loci 
American Journal of Epidemiology  2015;181(6):406-421.
Autoimmune conditions and immune system–related genetic variations are associated with risk of non-Hodgkin lymphoma (NHL). In a pooled analysis of 8,692 NHL cases and 9,260 controls from 14 studies (1988–2007) within the International Lymphoma Epidemiology Consortium, we evaluated the interaction between immune system genetic variants and autoimmune conditions in NHL risk. We evaluated the immunity-related single nucleotide polymorphisms rs1800629 (tumor necrosis factor gene (TNF) G308A), rs1800890 (interleukin-10 gene (IL10) T3575A), rs6457327 (human leukocyte antigen gene (HLA) class I), rs10484561 (HLA class II), and rs2647012 (HLA class II)) and categorized autoimmune conditions as primarily mediated by B-cell or T-cell responses. We constructed unconditional logistic regression models to measure associations between autoimmune conditions and NHL with stratification by genotype. Autoimmune conditions mediated by B-cell responses were associated with increased NHL risk, specifically diffuse large B-cell lymphoma (odds ratio (OR) = 3.11, 95% confidence interval (CI): 2.25, 4.30) and marginal zone lymphoma (OR = 5.80, 95% CI: 3.82, 8.80); those mediated by T-cell responses were associated with peripheral T-cell lymphoma (OR = 2.14, 95% CI: 1.35, 3.38). In the presence of the rs1800629 AG/AA genotype, B-cell-mediated autoimmune conditions increased NHL risk (OR = 3.27, 95% CI: 2.07, 5.16; P-interaction = 0.03) in comparison with the GG genotype (OR = 1.82, 95% CI: 1.31, 2.53). This interaction was consistent across major B-cell NHL subtypes, including marginal zone lymphoma (P-interaction = 0.02) and follicular lymphoma (P-interaction = 0.04).
PMCID: PMC4402340  PMID: 25713336
autoimmune conditions; environment; genetics; interaction; human leukocyte antigen; lymphoma, non-Hodgkin; tumor necrosis factor
2.  Estimating the Efficacy of Preexposure Prophylaxis for HIV Prevention Among Participants With a Threshold Level of Drug Concentration 
American Journal of Epidemiology  2013;177(3):256-263.
Assays for detecting levels of antiretroviral drugs in study participants are increasingly popular in preexposure prophylaxis (PrEP) trials, since they provide an objective measure of adherence. Current correlation analyses of drug concentration data are prone to bias. In this article, we formulate the causal estimand of prevention efficacy among drug compliers, those who would have had a threshold level of drug concentration had they been assigned to the drug arm of the trial. The identifiability of the causal estimand is facilitated by exploiting the exclusion restriction; that is, drug noncompliers do not acquire any prevention benefit. In addition, we develop an approach to sensitivity analysis that relaxes the exclusion restriction. Applications to published data from 2 PrEP trials, namely the Preexposure Prophylaxis Initiative (iPrEx) trial and the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 trial, suggest high efficacy estimates among drug compliers (in the iPrEx trial, odds ratio = 0.097 (95% confidence interval: 0.027, 0.352); in the CAPRISA 004 trial, odds ratio = 0.104 (95% confidence interval: 0.024, 0.447)). In summary, the proposed inferential method provides an unbiased assessment of PrEP efficacy among drug compliers, thus adding to the primary intention-to-treat analysis and correlation analyses of drug concentration data.
PMCID: PMC3577049  PMID: 23302152
causal inference; compliance; exclusion restriction; potential outcome; principal stratification; two-phase sampling
3.  Evaluating the Incremental Value of New Biomarkers With Integrated Discrimination Improvement 
American Journal of Epidemiology  2011;174(3):364-374.
The integrated discrimination improvement (IDI) index is a popular tool for evaluating the capacity of a marker to predict a binary outcome of interest. Recent reports have proposed that the IDI is more sensitive than other metrics for identifying useful predictive markers. In this article, the authors use simulated data sets and theoretical analysis to investigate the statistical properties of the IDI. The authors consider the common situation in which a risk model is fitted to a data set with and without the new, candidate predictor(s). Results demonstrate that the published method of estimating the standard error of an IDI estimate tends to underestimate the error. The z test proposed in the literature for IDI-based testing of a new biomarker is not valid, because the null distribution of the test statistic is not standard normal, even in large samples. If a test for the incremental value of a marker is desired, the authors recommend the test based on the model. For investigators who find the IDI to be a useful measure, bootstrap methods may offer a reasonable option for inference when evaluating new predictors, as long as the added predictive capacity is large.
PMCID: PMC3202159  PMID: 21673124
biological markers; bootstrap confidence interval; prediction; risk assessment; sampling distribution; sampling error; selection bias; type I error
4.  Longitudinal Data Analysis for Generalized Linear Models Under Participant-Driven Informative Follow-up: An Application in Maternal Health Epidemiology 
American Journal of Epidemiology  2009;171(2):189-197.
It is common in longitudinal studies for scheduled visits to be accompanied by as-needed visits due to medical events occurring between scheduled visits. If the timing of these as-needed visits is related to factors that are associated with the outcome but are not among the regression model covariates, naively including these as-needed visits in the model yields biased estimates. In this paper, the authors illustrate and discuss the key issues pertaining to inverse intensity rate ratio (IIRR)-weighted generalized estimating equations (GEE) methods in the context of a study of Kenyan mothers infected with human immunodeficiency virus type 1 (1999–2005). The authors estimated prevalences and prevalence ratios for morbid conditions affecting the women during a 1-year postpartum follow-up period. Of the 484 women under study, 62% had at least 1 as-needed visit. Use of a standard GEE model including both scheduled and unscheduled visits predicted a pneumonia prevalence of 2.9% (95% confidence interval: 2.3%, 3.5%), while use of the IIRR-weighted GEE predicted a prevalence of 1.5% (95% confidence interval: 1.2%, 1.8%). The estimate obtained using the IIRR-weighted GEE approach was compatible with estimates derived using scheduled visits only. These results highlight the importance of properly accounting for informative follow-up in these studies.
PMCID: PMC2878101  PMID: 20007201
data analysis; data interpretation, statistical; epidemiologic methods; follow-up studies; generalized estimating equation; generalized linear model; longitudinal studies; models, statistical

Results 1-4 (4)