@article{3172209,
    title = "Using observational data to emulate a randomized trial of dynamic
treatment-switching strategies: an application to antiretroviral therapy",
    author = "Cain, Lauren E. and Saag, Michael S. and Petersen, Maya and May, and Margaret T. and Ingle, Suzanne M. and Logan, Roger and Robins, James M. and and Abgrall, Sophie and Shepherd, Bryan E. and Deeks, Steven G. and and Gill, M. John and Touloumi, Giota and Vourli, Georgia and Dabis, and Francois and Vandenhende, Marie-Anne and Reiss, Peter and van Sighem, and Ard and Samji, Hasina and Hogg, Robert S. and Rybniker, Jan and Sabin, and Caroline A. and Jose, Sophie and del Amo, Julia and Moreno, Santiago and and Rodriguez, Benigno and Cozzi-Lepri, Alessandro and Boswell, Stephen L. and and Stephan, Christoph and Perez-Hoyos, Santiago and Jarrin, Inma and and Guest, Jodie L. and Monforte, Antonella D'Arminio and Antinori, Andrea and and Moore, Richard and Campbell, Colin N. J. and Casabona, Jordi and and Meyer, Laurence and Seng, Remonie and Phillips, Andrew N. and Bucher, and Heiner C. and Egger, Matthias and Mugavero, Michael J. and Haubrich, and Richard and Geng, Elvin H. and Olson, Ashley and Eron, Joseph J. and and Napravnik, Sonia and Kitahata, Mari M. and Van Rompaey, Stephen E. and and Teira, Ramon and Justice, Amy C. and Tate, Janet P. and Costagliola, and Dominique and Sterne, Jonathan A. C. and Hernan, Miguel A. and and Antiretroviral Therapy Cohort and Ctr Aids Res Network Integra and and HIV-CAUSAL Collaboration",
    journal = "International Journal of Epidemiology",
    year = "2016",
    volume = "45",
    number = "6",
    pages = "2038-2049",
    publisher = "Oxford University Press",
    issn = "0300-5771, 1464-3685",
    doi = "10.1093/ije/dyv295",
    keywords = "HIV; antiretroviral therapy; inverse-probability weighting;
observational studies; mortality; dynamic strategies",
    abstract = "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."
}