TY - JOUR
T1 - Quantifying an Adherence Path-Specific Effect of Antiretroviral Therapy in the Nigeria PEPFAR Program
AU - Miles, Caleb H.
AU - Shpitser, Ilya
AU - Kanki, Phyllis
AU - Meloni, Seema
AU - Tchetgen Tchetgen, Eric J.
N1 - Funding Information:
This work was funded, in part, by the U.S. Department of Health and Human Services, Health Resources and Services Administration (U51HA02522), and by the National Institutes of Health (R01AI104459-01A1). The contents are solely the responsibility of the authors and do not represent the official views of the funding institutions.
Publisher Copyright:
© 2017 American Statistical Association.
PY - 2017/10/2
Y1 - 2017/10/2
N2 - Since the early 2000s, evidence has accumulated for a significant differential effect of first-line antiretroviral therapy (ART) regimens on human immunodeficiency virus (HIV) viral load suppression. This finding was replicated in our data from the Harvard President’s Emergency Plan for AIDS Relief (PEPFAR) program in Nigeria. Investigators were interested in finding the source of these differences, that is, understanding the mechanisms through which one regimen outperforms another, particularly via adherence. This question can be naturally formulated via mediation analysis with adherence playing the role of a mediator. Existing mediation analysis results, however, have relied on an assumption of no exposure-induced confounding of the intermediate variable, and generally require an assumption of no unmeasured confounding for nonparametric identification. Both assumptions are violated by the presence of drug toxicity. In this article, we relax these assumptions and show that certain path-specific effects remain identified under weaker conditions. We focus on the path-specific effect solely mediated by adherence and not by toxicity and propose an estimator for this effect. We illustrate with simulations and present results from a study applying the methodology to the Harvard PEPFAR data. Supplementary materials for this article are available online.
AB - Since the early 2000s, evidence has accumulated for a significant differential effect of first-line antiretroviral therapy (ART) regimens on human immunodeficiency virus (HIV) viral load suppression. This finding was replicated in our data from the Harvard President’s Emergency Plan for AIDS Relief (PEPFAR) program in Nigeria. Investigators were interested in finding the source of these differences, that is, understanding the mechanisms through which one regimen outperforms another, particularly via adherence. This question can be naturally formulated via mediation analysis with adherence playing the role of a mediator. Existing mediation analysis results, however, have relied on an assumption of no exposure-induced confounding of the intermediate variable, and generally require an assumption of no unmeasured confounding for nonparametric identification. Both assumptions are violated by the presence of drug toxicity. In this article, we relax these assumptions and show that certain path-specific effects remain identified under weaker conditions. We focus on the path-specific effect solely mediated by adherence and not by toxicity and propose an estimator for this effect. We illustrate with simulations and present results from a study applying the methodology to the Harvard PEPFAR data. Supplementary materials for this article are available online.
KW - Human immunodeficiency virus
KW - Mediation
KW - Nonparametric identification
KW - Unobserved confounding
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U2 - 10.1080/01621459.2017.1295862
DO - 10.1080/01621459.2017.1295862
M3 - Article
AN - SCOPUS:85041138436
SN - 0162-1459
VL - 112
SP - 1443
EP - 1452
JO - Journal of the American Statistical Association
JF - Journal of the American Statistical Association
IS - 520
ER -