Περίληψη:
Decisions about when to start or switch a therapy often depend on the
frequency with which individuals are monitored or tested. For example,
the optimal time to switch antiretroviral therapy depends on the
frequency with which HIV-positive individuals have HIV RNA measured.
This paper describes an approach to use observational data for the
comparison of joint monitoring and treatment strategies and applies the
method to a clinically relevant question in HIV research: when can
monitoring frequency be decreased and when should individuals switch
from a first-line treatment regimen to a new regimen? We outline the
target trial that would compare the dynamic strategies of interest and
then describe how to emulate it using data from HIV-positive individuals
included in the HIV-CAUSAL Collaboration and the Centers for AIDS
Research Network of Integrated Clinical Systems. When, as in our
example, few individuals follow the dynamic strategies of interest over
long periods of follow-up, we describe how to leverage an additional
assumption: no direct effect of monitoring on the outcome of interest.
We compare our results with and without the “no direct effect”
assumption. We found little differences on survival and AIDS-free
survival between strategies where monitoring frequency was decreased at
a CD4 threshold of 350 cells/mu l compared with 500 cells/mu l and where
treatment was switched at an HIV-RNA threshold of 1000 copies/ml
compared with 200 copies/ml. The “no direct effect” assumption
resulted in efficiency improvements for the risk difference estimates
ranging from an 7- to 53-fold increase in the effective sample size.
Συγγραφείς:
Caniglia, Ellen C.
Robins, James M.
Cain, Lauren E.
Sabin,
Caroline
Logan, Roger
Abgrall, Sophie
Mugavero, Michael J.
and Hernandez-Diaz, Sonia
Meyer, Laurence
Seng, Remonie and
Drozd, Daniel R.
Seage, III, George R.
Bonnet, Fabrice
Le
Marec, Fabien
Moore, Richard D.
Reiss, Peter
van Sighem, Ard
and Mathews, William C.
Jarrin, Inma
Alejos, Belen
Deeks,
Steven G.
Muga, Roberto
Boswell, Stephen L.
Ferrer, Elena
and Eron, Joseph J.
Gill, John
Pacheco, Antonio
Grinsztejn,
Beatriz
Napravnik, Sonia
Jose, Sophie
Phillips, Andrew and
Justice, Amy
Tate, Janet
Bucher, Heiner C.
Egger, Matthias
and Furrer, Hansjakob
Miro, Jose M.
Casabona, Jordi
Porter,
Kholoud
Touloumi, Giota
Crane, Heidi
Costagliola, Dominique
and Saag, Michael
Hernan, Miguel A.
