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Using observational data to emulate a randomized trial of dynamic treatment-switching strategies: an application to antiretroviral therapy.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Cain Lauren E, Saag Michael S, Petersen Maya, May Margaret T, Ingle Suzanne M, Logan Roger, Robins James M, Abgrall Sophie, Shepherd Bryan E, Deeks Steven G, Gill M John, Touloumi Giota, Vourli Georgia, Dabis François, Vandenhende Marie-Anne, Reiss Peter, van Sighem Ard, Samji Hasina, Hogg Robert S, Rybniker Jan, Sabin Caroline A, Jose Sophie, Del Amo Julia, Moreno Santiago, Rodríguez Benigno,
Project Swiss HIV Cohort Study (SHCS)
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Original article (peer-reviewed)

Journal International journal of epidemiology
Page(s) 000 - 000
Title of proceedings International journal of epidemiology
DOI 10.1093/ije/dyv295


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). 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. 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. Although our effective sample sizes were small and our estimates imprecise, the described methodological approach can serve as an example for future analyses.