Tyler J VanderWeele

Harvard University, Cambridge, Massachusetts, United States

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Publications (216)934.71 Total impact

  • Cande V. Ananth · Jessica A. Lavery · Tyler J. VanderWeele

    No preview · Article · Jan 2016 · American Journal of Obstetrics and Gynecology
  • Charles Poole · Ian Shrier · Peng Ding · Tyler VanderWeele

    No preview · Article · Jan 2016 · Epidemiology
  • Peng Ding · Tyler J. VanderWeele
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    ABSTRACT: It is often of interest to decompose a total effect of an exposure into the component that acts on the outcome through some mediator and the component that acts independently through other pathways. Said another way, we are interested in the direct and indirect effects of the exposure on the outcome. Even if the exposure is randomly assigned, it is often infeasible to randomize the mediator, leaving the mediator-outcome confounding not fully controlled. We develop a sensitivity analysis technique that can bound the direct and indirect effects without parametric assumptions about the unmeasured mediator-outcome confounding.
    No preview · Article · Jan 2016
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    ABSTRACT: Background Direct access to genomic information has the potential to transform cancer risk counseling. We measured the impact of direct-to-consumer genomic risk information on changes to perceived risk (ΔPR) of breast, prostate, colorectal and lung cancer among personal genomic testing (PGT) customers. We hypothesized that ΔPR would reflect directionality of risk estimates, attenuate with time, and be modified by participant characteristics. Methods Pathway Genomics and 23andMe customers were surveyed prior to receiving PGT results, and 2 weeks and 6 months post-results. For each cancer, PR was measured on a 5-point ordinal scale from “much lower than average” to “much higher than average.” PGT results, based on genotyping of common genetic variants, were dichotomized as elevated or average risk. The relationship between risk estimate and ΔPR was evaluated with linear regression; generalized estimating equations modeled this relationship over time. Results With the exception of lung cancer (for which ΔPR was positive regardless of result), elevated risk results were significantly associated with positive ΔPR, and average risk results with negative ΔPR (e.g., prostate cancer, 2 weeks: least squares-adjusted ΔPR = 0.77 for elevated risk versus −0.21 for average risk; p-valuedifference < 0.0001) among 1154 participants. Large changes were rare: for each cancer, <4 % of participants overall reported a ΔPR of ±3 or more units. Effect modification by age, cancer family history, and baseline interest was observed for breast, colorectal, and lung cancer, respectively. A pattern of decreasing impact on ΔPR over time was consistently observed, but this trend was significant only in the case of colorectal cancer. Conclusions We have quantified the effect on consumer risk perception of returning genetic-based cancer risk information directly to consumers without clinician mediation. Provided via PGT, this information has a measurable but modest effect on perceived cancer risk, and one that is in some cases modified by consumers’ non-genetic risk context. Our observations of modest marginal effect sizes, infrequent extreme changes in perceived risk, and a pattern of diminishing impact with time, suggest that the ability of PGT to effect changes to cancer screening and prevention behaviors may be limited by relatively small changes to perceived risk.
    Full-text · Article · Dec 2015 · BMC Medical Genomics
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    Peng Ding · Tyler J. VanderWeele
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    ABSTRACT: If an effect measure is more homogeneous than others, then its value is more likely to be stable across different subgroups or subpopulations. Therefore, it is of great importance to find a more homogeneous effect measure that allows for transportability of research results. For a binary outcome, applied researchers often claim that the risk difference is more heterogeneous than the risk ratio or odds ratio, because they find, based on evidence from surveys of meta-analyses, that the null hypotheses of homogeneity are rejected more often for the risk difference than for the risk ratio and odds ratio. However, the evidence for these claims are far from satisfactory, because of different statistical powers of the homogeneity tests under different effect scales. For binary treatment, covariate and outcome, we theoretically quantify the homogeneity of different effect scales. Because the four outcome probabilities lie in a three dimensional space of the four dimensional space when homogeneity holds for any effect scale, we compute the volumes of these three dimensional spaces to compare the relative homogeneity of the risk difference, risk ratio, and odds ratio. We demonstrate that the homogeneity space for the risk difference has the smallest volume, and the homogeneity space for the odds ratio has the largest volume, providing further evidence for the previous claim that the risk difference is more heterogeneous than the risk ratio and odds ratio.
    Preview · Article · Oct 2015
  • L. Valeri · J. T. Chen · X. Garcia-Albeniz · N. Krieger · T. J. VanderWeele · B. A. Coull
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    ABSTRACT: Background: To date, a counterfactual framework has not been used to study determinants of social inequalities in cancer. Considering the case of colorectal cancer, for which racial/ethnic differences in stage at diagnosis and survival are well documented, we quantify the extent to which black versus white survival disparities would be reduced had disparities in stage at diagnosis been eliminated in a large patient population. Methods: We obtained data on colorectal cancer patients (diagnosed between 1992 and 2005 and followed until 2010) from US-SEER (Surveillance, Epidemiology, and End Results) cancer registries. We employed a counterfactual approach to estimate the mean survival time up to the 60th month since diagnosis for black colorectal cancer patients had black-white disparities in stage at diagnosis been eliminated. Results: Black patients survive approximately 4.0 [confidence interval (CI), 4.6-3.2] months less than white patients within five years since diagnosis. Had disparities in stage at diagnosis been eliminated, survival disparities decrease to 2.6 (CI, 3.4-1.7) months, an approximately 35% reduction. For patients diagnosed after the age of 65 years, disparities would be halved, while reduction of approximately 30% is estimated for younger patients. Survival disparities would be reduced by approximately 44% for women and approximately 26% for men. Conclusions: Employing a counterfactual approach and allowing for heterogeneities in black-white disparities across patients' characteristics, we give robust evidence that elimination of disparities in stage at diagnosis contributes to a substantial reduction in survival disparities in colorectal cancer. Impact: We provide the first evidence in the SEER population that elimination of inequities in stage at diagnosis might lead to larger reductions in survival disparities among elderly and women.
    No preview · Article · Oct 2015 · Cancer Epidemiology Biomarkers & Prevention
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    ABSTRACT: A number of epidemiologic studies have described what appear to be paradoxical associations, where an incongruous relationship is observed between a certain well-established risk factor for disease incidence and favorable clinical outcome among patients with that disease. For example, the "obesity paradox" represents the association between obesity and better survival among patients with a certain disease such as coronary heart disease. Paradoxical observations cause vexing clinical and public health problems as they raise questions on causal relationships and hinder the development of effective interventions. Compelling evidence indicates that pathogenic processes encompass molecular alterations within cells and the microenvironment, influenced by various exogenous and endogenous exposures, and that interpersonal heterogeneity in molecular pathology and pathophysiology exists among patients with any given disease. In this article, we introduce methods of the emerging integrative interdisciplinary field of molecular pathological epidemiology (MPE), which is founded on the unique disease principle and disease continuum theory. We analyze and decipher apparent paradoxical findings, utilizing the MPE approach and available literature data on tumor somatic genetic and epigenetic characteristics. Through our analyses in colorectal cancer, renal cell carcinoma, and glioblastoma (malignant brain tumor), we can readily explain paradoxical associations between disease risk factors and better prognosis among disease patients. The MPE paradigm and approach can be applied to not only neoplasms but also various non-neoplastic diseases where there exists indisputable ubiquitous heterogeneity of pathogenesis and molecular pathology. The MPE paradigm including consideration of disease heterogeneity plays an essential role in advancements of precision medicine and public health.
    Full-text · Article · Oct 2015 · European Journal of Epidemiology
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    M Arfan Ikram · Tyler J VanderWeele
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    ABSTRACT: Understanding of causal pathways in epidemiology involves the concepts of direct and indirect effects. Recently, causal mediation analysis has been formalized to quantify these direct and indirect effects in the presence of exposure-mediator interaction and even allows for four-way decomposition of the total effect: controlled direct effect, reference interaction, mediated interaction, pure indirect effect. Whereas the other three effects can be intuitively conceptualized, mediated interaction is often considered a nuisance in statistical analysis. In this paper, we focus on mediated interaction and contrast it against pure mediation. We also propose a clinical and biological interpretation of mediated interaction using three hypothetical examples. With these examples we aim to make researchers aware that mediated interaction can actually provide important clinical and biological information.
    Preview · Article · Oct 2015 · European Journal of Epidemiology
  • M-A C Bind · T J Vanderweele · B A Coull · J D Schwartz
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    ABSTRACT: Mediation analysis is a valuable approach to examine pathways in epidemiological research. Prospective cohort studies are often conducted to study biological mechanisms and often collect longitudinal measurements on each participant. Mediation formulae for longitudinal data have been developed. Here, we formalize the natural direct and indirect effects using a causal framework with potential outcomes that allows for an interaction between the exposure and the mediator. To allow different types of longitudinal measures of the mediator and outcome, we assume two generalized mixed-effects models for both the mediator and the outcome. The model for the mediator has subject-specific random intercepts and random exposure slopes for each cluster, and the outcome model has random intercepts and random slopes for the exposure, the mediator, and their interaction. We also expand our approach to settings with multiple mediators and derive the mediated effects, jointly through all mediators. Our method requires the absence of time-varying confounding with respect to the exposure and the mediator. This assumption is achieved in settings with exogenous exposure and mediator, especially when exposure and mediator are not affected by variables measured at earlier time points. We apply the methodology to data from the Normative Aging Study and estimate the direct and indirect effects, via DNA methylation, of air pollution, and temperature on intercellular adhesion molecule 1 (ICAM-1) protein levels. Our results suggest that air pollution and temperature have a direct effect on ICAM-1 protein levels (i.e. not through a change in ICAM-1 DNA methylation) and that temperature has an indirect effect via a change in ICAM-1 DNA methylation. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
    No preview · Article · Aug 2015 · Biostatistics
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    ABSTRACT: Background: Low birth weight and unhealthy lifestyles in adulthood have been independently associated with an elevated risk of hypertension. However, no study has examined the joint effects of these factors on incidence of hypertension. Methods: We followed 52,114 women from the Nurses' Health Study II without hypercholesterolemia, diabetes, cardiovascular disease, cancer, prehypertension, and hypertension at baseline (1991-2011). Women born preterm, of a multiple pregnancy, or who were missing birth weight data were excluded. Unhealthy adulthood lifestyle was defined by compiling status scores of body mass index, physical activity, alcohol consumption, the Dietary Approaches to Stop Hypertension diet, and the use of non-narcotic analgesics. Results: We documented 12,588 incident cases of hypertension during 20 years of follow-up. The risk of hypertension associated with a combination of low birth weight at term and unhealthy lifestyle factors (RR, 1.95; 95 % CI, 1.83-2.07) was more than the addition of the risk associated with each individual factor, indicating a significant interaction on an additive scale (P interaction <0.001). The proportions of the association attributable to lower term birth weight alone, unhealthy lifestyle alone, and their joint effect were 23.9 % (95 % CI, 16.6-31.2), 63.7 % (95 % CI, 60.4-66.9), and 12.5 % (95 % CI, 9.87-15.0), respectively. The population-attributable-risk for the combined adulthood unhealthy lifestyle and low birth weight at term was 66.3 % (95 % CI, 56.9-74.0). Conclusion: The majority of cases of hypertension could be prevented by the adoption of a healthier lifestyle, though some cases may depend on simultaneous improvement of both prenatal and postnatal factors.
    Preview · Article · Jul 2015 · BMC Medicine
  • Charlie Poole · Ian Shrier · Tyler J VanderWeele
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    ABSTRACT: There are claims in the literature that the risk difference is a more heterogeneous measure than the odds ratio or risk ratio. These claims are based on surveys of meta-analyses showing that tests reject the null hypothesis of homogeneity more often for the risk difference than for the ratio measures. Discussions of this point have neglected the fact that homogeneity tests can have different levels of statistical power (i.e., different probabilities of rejecting the null when it is false) across different scales. We give hypothetical examples in which there is arguably equal heterogeneity across risk difference and odds ratio measures but in which the risk difference homogeneity test rejects more often, and therefore has higher power, than the odds ratio homogeneity test. These examples suggest that current empirical evidence for the claim that the risk difference is more heterogeneous is not at present satisfactory. Further research could consider other approaches to empirical comparisons of the heterogeneity of the three measures.
    No preview · Article · Jul 2015 · Epidemiology (Cambridge, Mass.)
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    Peng Ding · Tyler VanderWeele
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    ABSTRACT: Unmeasured confounding may undermine the validity of causal inference with observational studies. Sensitivity analysis provides an attractive way to partially circumvent this issue by assessing the potential influence of unmeasured confounding on the causal conclusions. However, previous sensitivity analysis approaches often make strong and untestable assumptions such as having a confounder that is binary, or having no interaction between the effects of the exposure and the confounder on the outcome, or having only one confounder. Without imposing any assumptions on the confounder or confounders, we derive a bounding factor and a sharp inequality such that the sensitivity analysis parameters must satisfy the inequality if an unmeasured confounder is to explain away the observed effect estimate or reduce it to a particular level. Our approach is easy to implement and involves only two sensitivity parameters. Surprisingly, our bounding factor, which makes no simplifying assumptions, is no more conservative than a number of previous sensitivity analysis techniques that do make assumptions. Our new bounding factor implies not only the traditional Cornfield conditions that both the relative risk of the exposure on the confounder and that of the confounder on the outcome must satisfy, but also a high threshold that the maximum of these relative risks must satisfy. Furthermore, this new bounding factor can be viewed as a measure of the strength of confounding between the exposure and the outcome induced by a confounder.
    Preview · Article · Jul 2015 · Epidemiology (Cambridge, Mass.)
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    ABSTRACT: Objectives To prospectively assess the joint association of birth weight and established lifestyle risk factors in adulthood with incident type 2 diabetes and to quantitatively decompose the attributing effects to birth weight only, to adulthood lifestyle only, and to their interaction. Design Prospective cohort study. Setting Health Professionals Follow-up Study (1986-2010), Nurses’ Health Study (1980-2010), and Nurses’ Health Study II (1991-2011). Participants 149 794 men and women without diabetes, cardiovascular disease, or cancer at baseline. Main outcome measure Incident cases of type 2 diabetes, identified through self report and validated by a supplementary questionnaire. Unhealthy lifestyle was defined on the basis of body mass index, smoking, physical activity, alcohol consumption, and the alternate healthy eating index. Results During 20-30 years of follow-up, 11 709 new cases of type 2 diabetes were documented. The multivariate adjusted relative risk of type 2 diabetes was 1.45 (95% confidence interval 1.32 to 1.59) per kg lower birth weight and 2.10 (1.71 to 2.58) per unhealthy lifestyle factor. The relative risk of type 2 diabetes associated with a combination of per kg lower birth weight and per unhealthy lifestyle factor was 2.86 (2.26 to 3.63), which was more than the addition of the risk associated with each individual factor, indicating a significant interaction on an additive scale (P for interaction<0.001). The attributable proportions of joint effect were 22% (95% confidence interval 18.3% to 26.4%) to lower birth weight alone, 59% (57.1% to 61.5%) to unhealthy lifestyle alone, and 18% (13.9% to 21.3%) to their interaction. Conclusion Most cases of type 2 diabetes could be prevented by the adoption of a healthier lifestyle, but simultaneous improvement of both prenatal and postnatal factors could further prevent additional cases.
    No preview · Article · Jul 2015 · BMJ: British medical journal
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    ABSTRACT: War-affected youth often suffer from multiple co-occurring mental health problems. These youth often live in low-resource settings where it may be infeasible to provide mental health services that simultaneously address all of these co-occurring mental health issues. It is therefore important to identify the areas where targeted interventions would do the most good. This analysis uses observational data from 3 waves of a longitudinal study on mental health in a sample of 529 war-affected youth (24.2% female; ages 10-17 at T1, 2002) in Sierra Leone. We regressed 4 mental health outcomes at T3 (2008) on internalizing (depression/anxiety) and externalizing (hostility/aggression) problems and prosocial attitudes/behaviors and community variables at T2 (2004) controlling for demographics, war exposures, and previous mental health scores at T1, allowing us to assess the relative impact of potential mental health intervention targets in shaping mental health outcomes over time. Controlling for baseline covariates at T1 and all other exposures/potential intervention targets at T2, we observed a significant association between internalizing problems at T2 and 3 of the 4 outcomes at T3: internalizing (β = 0.27, 95% confidence interval [CI]: 0.11-0.42), prosocial attitudes (β = -0.20, 95% CI: -0.33 to -0.07) and posttraumatic stress symptoms (β = 0.22, 95% CI: 0.02-0.43). No other potential intervention target had similar substantial effects. Reductions in internalizing may have multiple benefits for other mental health outcomes at a later point in time, even after controlling for confounding variables. Copyright © 2015 by the American Academy of Pediatrics.
    No preview · Article · Jun 2015 · Pediatrics
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    ABSTRACT: Observational studies of older adults showed higher mortality for first-generation antipsychotics than their second--generation counterparts, which led to US Food and Drug Administration warnings, but the actual mechanisms involved remain unclear. A cohort of 9,060 initiators of first-generation antipsychotics and 17,137 of second-generation antipsychotics enrolled in New Jersey and Pennsylvania Medicare were followed for 180 days. Medical events were assessed using diagnostic and procedure codes on inpatient billing claims. For the individual and joint set of medical events (mediators), we estimated the total, direct, and indirect effects of antipsychotic type (first versus second generation) on mortality on the risk ratio scale and the proportion mediated on the risk difference scale, obtaining 95% confidence intervals through bootstrapping. We performed bias analyses for false-negative mediator misclassification in claims data, with sensitivity ranging from 0.25 to 0.75. There were 3,199 deaths (outcomes), 862 cardiovascular events, 675 infectious events, and 491 hip fractures (potential mediators). Mortality was higher for first- than second-generation antipsychotic initiators (adjusted risk ratio: 1.14; 95% confidence interval: 1.06, 1.22). In naïve analyses, that ignored potential misclassification, less than 4% of this difference was explained by any particular medical event. In bias analyses, the proportion mediated ranged from 6% to 16% for stroke, 3% to 9% for ventricular arrhythmia, 3% to 11% for myocardial infarction, 0% venous thromboembolism, 3% to 9% for pneumonia, 0% to 1% for other bacterial infection, and 1% to 3% for hip fracture. Acute cardiovascular events and pneumonia may explain part of the mortality difference between first- and second-generation antipsychotic initiators in this analysis.
    No preview · Article · May 2015 · Epidemiology (Cambridge, Mass.)
  • Zhichao Jiang · Tyler J VanderWeele
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    ABSTRACT: Assessment of indirect effects is useful for epidemiologists interested in understanding the mechanisms of exposure-outcome relationships. A traditional way of estimating indirect effects is to use the "difference method," which is based on regression analysis in which one adds a possible mediator to the regression model and examines whether the coefficient for the exposure changes. The difference method has been criticized for lacking a causal interpretation when it is used with logistic regression. In this article, we use the counterfactual framework to define the natural indirect effect (NIE) and assess the relationship between the NIE and the difference method. We show that under appropriate assumptions, the difference method consistently estimates the NIE for continuous outcomes and is always conservative for binary outcomes. Thus, the difference method can be used to provide evidence for the presence of mediation but not for the absence of mediation. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
    No preview · Article · May 2015 · American journal of epidemiology
  • Zhichao Jiang · Tyler J VanderWeele

    No preview · Article · May 2015 · American journal of epidemiology
  • T. J. VanderWeele · Tchetgen E. J. Tchetgen

    No preview · Article · May 2015 · Epidemiology
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    ABSTRACT: Health care providers' lack of education on spiritual care is a significant barrier to the integration of spiritual care into health care services. The study objective was to describe the training program, Clinical Pastoral Education for Healthcare Providers (CPE-HP) and evaluate its impact on providers' spiritual care skills. Fifty CPE-HP participants completed self-report surveys at baseline and posttraining measuring frequency of and confidence in providing religious/spiritual (R/S) care. Four domains were assessed: (1) ability and (2) frequency of R/S care provision; (3) comfort using religious language; and (4) confidence in providing R/S care. At baseline, participants rated their ability to provide R/S care and comfort with religious language as "fair." In the previous two weeks, they reported approximately two R/S patient conversations, initiated R/S conversations less than twice, and prayed with patients less than once. Posttraining participants' reported ability to provide spiritual care increased by 33% (p<0.001). Their comfort using religious language improved by 29% (p<0.001), and frequency of R/S care increased 75% (p<0.001). Participants reported having 61% more (p<0.001) R/S conversations and more frequent prayer with patients (95% increase; p<0.001). Confidence in providing spiritual care improved by 36% overall, by 20% (p<0.001) with religiously concordant patients, and by 43% (p<0.001) with religiously discordant patients. This study suggests that CPE-HP is an effective approach for training health care providers in spiritual care. Dissemination of this training may improve integration of spiritual care into health care, thereby strengthening comprehensive patient-centered care.
    Full-text · Article · Apr 2015 · Journal of palliative medicine
  • L. Valeri · T.J. Vanderweele

    No preview · Article · Mar 2015

Publication Stats

4k Citations
934.71 Total Impact Points

Institutions

  • 2009-2016
    • Harvard University
      Cambridge, Massachusetts, United States
    • University of Illinois at Chicago
      Chicago, Illinois, United States
  • 2006-2015
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2011
    • Boston Medical Center
      Boston, Massachusetts, United States
    • Massachusetts Department of Public Health
      Boston, Massachusetts, United States
  • 2006-2009
    • University of Chicago
      • Department of Health Studies
      Chicago, Illinois, United States