Comparing Marginal Structural Cox Proportional Hazards Models (MSCM) to Standard Methods for Estimating Causal Effects of ART on the Survival of HIV-Infected Patients in a Regional Referral Hospital in Western Kenya, 2011-2014

Mutai K, Burmen Burmen

Abstract


Estimating causal inferences in observational studies
with time varying covariates require methods that can address
complexities such as non-random allocation of patients’ to
treatment groups, possible censoring of, exposure variables e.g.,
time to antiretroviral therapy (ART) initiation, and outcome
variables e.g., mortality. Marginal Structural Cox Proportional
Hazard Model (MSCM) adopts inverse probability of treatment
and censoring weights to correct for non-random allocation of
treatment groups, patient attrition or administrative censoring and
confounding. We set out to evaluate the causal effects of ‘time to
ART initiation’ on the survival of human immunodeficiency
(HIV) infected patients enrolled in Jaramogi Oginga Odinga
Teaching and Referral Hospital (JOOTRH), a high HIV-burden
hospital in Western Kenya.A retrospective review of
observational data was conducted at JOOTRH for patients aged
≥15 years enrolled between May 2011 and December 2013.
Patients were categorized as ‘early initiators’ if they were
initiated on ART within 12 weeks of determination of ART
eligibility and ‘late initiators’ if they were initiated on ART
after.We compared the results from MSCM to those from
unadjusted standard Cox Proportional Hazard (Cox-PH) model
and adjusted standard Cox-PH model (adjusting for age, gender,
CD4 category, WHO stage, education level, marital status, and
weight) to assess the extent to which standard methods can bias
estimates for causal effects.Of 786 patients enrolled; 606 (77%)
were ART-eligible of whom 444 (73%) had documenteddates of
ART initiation. Among patients who were initiated on ART, 41
(9%) were late-initiators. There were3 deaths and 9.2 personyears
of
follow-up
and
31
deaths
and
115.8
person-years
of

follow-up
among
‘late-initiators’
and
‘early-initiators’

respectively.
Compared
to
‘early-initiators’,
the
hazard
of
dying

among
‘late-initiators’
computed
using
unadjusted
standard
CoxPH
model,
adjusted
standard
Cox-PH
model
and
MSCM
was1.6

(95%
CI
0.5-5.4)
and
1.9
(95%
CI
0.5-6.7)
and
3.2
(95%
CI
1.76.4)
respectively.Delays
in
ART
initiation
was
associated
with
an

increased
risk
of
mortality
only
after
employing
MSCM.
When

randomized trials are not feasible due to costs or ethical
concerns, causal inference could still be deduced from
longitudinal observational data by applying appropriate causal
models.

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