TY - JOUR
TI - Using observational data to emulate a randomized trial of dynamic
treatment-switching strategies: an application to antiretroviral therapy
AU - Cain, Lauren E.
AU - Saag, Michael S.
AU - Petersen, Maya
AU - May,
AU - Margaret T.
AU - Ingle, Suzanne M.
AU - Logan, Roger
AU - Robins, James M.
AU - and Abgrall, Sophie
AU - Shepherd, Bryan E.
AU - Deeks, Steven G. and
AU - Gill, M. John
AU - Touloumi, Giota
AU - Vourli, Georgia
AU - Dabis,
AU - Francois
AU - Vandenhende, Marie-Anne
AU - Reiss, Peter
AU - van Sighem,
AU - Ard
AU - Samji, Hasina
AU - Hogg, Robert S.
AU - Rybniker, Jan
AU - Sabin,
AU - Caroline A.
AU - Jose, Sophie
AU - del Amo, Julia
AU - Moreno, Santiago and
AU - Rodriguez, Benigno
AU - Cozzi-Lepri, Alessandro
AU - Boswell, Stephen L.
AU - and Stephan, Christoph
AU - Perez-Hoyos, Santiago
AU - Jarrin, Inma and
AU - Guest, Jodie L.
AU - Monforte, Antonella D'Arminio
AU - Antinori, Andrea
AU - and Moore, Richard
AU - Campbell, Colin N. J.
AU - Casabona, Jordi and
AU - Meyer, Laurence
AU - Seng, Remonie
AU - Phillips, Andrew N.
AU - Bucher,
AU - Heiner C.
AU - Egger, Matthias
AU - Mugavero, Michael J.
AU - Haubrich,
AU - Richard
AU - Geng, Elvin H.
AU - Olson, Ashley
AU - Eron, Joseph J. and
AU - Napravnik, Sonia
AU - Kitahata, Mari M.
AU - Van Rompaey, Stephen E. and
AU - Teira, Ramon
AU - Justice, Amy C.
AU - Tate, Janet P.
AU - Costagliola,
AU - Dominique
AU - Sterne, Jonathan A. C.
AU - Hernan, Miguel A. and
AU - Antiretroviral Therapy Cohort
AU - Ctr Aids Res Network Integra and
AU - HIV-CAUSAL Collaboration
JO - International Journal of Epidemiology
PY - 2016
VL - 45
TODO - 6
SP - 2038-2049
PB - Oxford University Press
SN - 0300-5771, 1464-3685
TODO - 10.1093/ije/dyv295
TODO - HIV; antiretroviral therapy; inverse-probability weighting;
observational studies; mortality; dynamic strategies
TODO - Background: When a clinical treatment fails or shows suboptimal results,
the question of when to switch to another treatment arises. Treatment
switching strategies are often dynamic because the time of switching
depends on the evolution of an individual’s time-varying covariates.
Dynamic strategies can be directly compared in randomized trials. For
example, HIV-infected individuals receiving antiretroviral therapy could
be randomized to switching therapy within 90 days of HIV-1 RNA crossing
above a threshold of either 400 copies/ml (tight-control strategy) or
1000 copies/ml (loose-control strategy).
Methods: We review an approach to emulate a randomized trial of dynamic
switching strategies using observational data from the Antiretroviral
Therapy Cohort Collaboration, the Centers for AIDS Research Network of
Integrated Clinical Systems and the HIV-CAUSAL Collaboration. We
estimated the comparative effect of tight-control vs. loose-control
strategies on death and AIDS or death via inverse-probability weighting.
Results: Of 43 803 individuals who initiated an eligible antiretroviral
therapy regimen in 2002 or later, 2001 met the baseline inclusion
criteria for the mortality analysis and 1641 for the AIDS or death
analysis. There were 21 deaths and 33 AIDS or death events in the
tight-control group, and 28 deaths and 41 AIDS or death events in the
loose-control group. Compared with tight control, the adjusted hazard
ratios (95% confidence interval) for loose control were 1.10 (0.73,
1.66) for death, and 1.04 (0.86, 1.27) for AIDS or death.
Conclusions: Although our effective sample sizes were small and our
estimates imprecise, the described methodological approach can serve as
an example for future analyses.
ER -