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https://www.arca.fiocruz.br/handle/icict/35578
EMULATING A TRIAL OF JOINT DYNAMIC STRATEGIES: AN APPLICATION TO MONITORING AND TREATMENT OF HIV-POSITIVE INDIVIDUALS
Dynamic regime
Joint treatment strategies
Marginal structural model
No direct effect
Author
Caniglia, Ellen C.
Robins, James M.
Cain, Lauren E.
Sabin, Caroline
Logan, Roger
Abgrall, Sophie
Mugavero, Michael J.
Hernández-Díaz, Sonia
Meyer, Laurence
Seng, Remonie
Drozd, Daniel R.
Seage Iii, George R.
Bonnet, Fabrice
Le Marec, Fabien
Moore, Richard D.
Reiss, Peter
van Sighem, Ard
Mathews, William C.
Jarrín, Inma
Alejos, Belén
Deeks, Steven G.
Muga, Roberto
Boswell, Stephen L.
Ferrer, Elena
Eron, Joseph J.
Gill, John
Pacheco, Antonio
Grinsztejn, Beatriz
Napravnik, Sonia
Jose, Sophie
Phillips, Andrew
Justice, Amy
Tate, Janet
Bucher, Heiner C.
Egger, Matthias
Furrer, Hansjakob
Miro, Jose M.
Casabona, Jordi
Porter, Kholoud
Touloumi, Giota
Crane, Heidi
Costagliola, Dominique
Saag, Michael
Hernán, Miguel A.
Robins, James M.
Cain, Lauren E.
Sabin, Caroline
Logan, Roger
Abgrall, Sophie
Mugavero, Michael J.
Hernández-Díaz, Sonia
Meyer, Laurence
Seng, Remonie
Drozd, Daniel R.
Seage Iii, George R.
Bonnet, Fabrice
Le Marec, Fabien
Moore, Richard D.
Reiss, Peter
van Sighem, Ard
Mathews, William C.
Jarrín, Inma
Alejos, Belén
Deeks, Steven G.
Muga, Roberto
Boswell, Stephen L.
Ferrer, Elena
Eron, Joseph J.
Gill, John
Pacheco, Antonio
Grinsztejn, Beatriz
Napravnik, Sonia
Jose, Sophie
Phillips, Andrew
Justice, Amy
Tate, Janet
Bucher, Heiner C.
Egger, Matthias
Furrer, Hansjakob
Miro, Jose M.
Casabona, Jordi
Porter, Kholoud
Touloumi, Giota
Crane, Heidi
Costagliola, Dominique
Saag, Michael
Hernán, Miguel A.
Affilliation
Harvard T. H. Chan School of Public Health. Department of Epidemiology. Boston, Massachusetts, USA / New York University. School of Medicine. Department of Population Health. New York, USA.
Harvard T. H. Chan School of Public Health. Department of Epidemiology. Boston, Massachusetts, USA / Harvard T.H. Chan School of Public Health. Department of Biostatistics. Boston, Massachusetts, USA.
Harvard T. H. Chan School of Public Health. Department of Epidemiology. Boston, Massachusetts, USA.
University College London. London, UK.
Harvard T. H. Chan School of Public Health. Department of Epidemiology. Boston, Massachusetts, USA.
APHP Hôpital Avicenne. Bobigny, France.
University of Alabama at Birmingham. School of Medicine. Birmingham, Alabama, USA..
Harvard T. H. Chan School of Public Health. Department of Epidemiology. Boston, Massachusetts, USA.
Inserm, Université Paris Sud. Orsay, France.
Inserm, Université Paris Sud. Orsay, France.
University of Washington. Seattle, Washington, USA.
Harvard T. H. Chan School of Public Health. Department of Epidemiology. Boston, Massachusetts, USA.
Centre Hospitalier Universitaire de Bordeaux. Bordeaux, France.
Centre Hospitalier Universitaire de Bordeaux. Bordeaux, France.
The Johns Hopkins University. School of Medicine. Baltimore, Maryland, USA.
Academisch Medisch Centrum Geneeskunde. Amsterdam, The Netherlands.
Academisch Medisch Centrum Geneeskunde. Amsterdam, The Netherlands.
University of California San Diego Health. Department of Medicine. San Diego, California, USA.
Instituto de Salud Carlos III. National Center of Epidemiology. Madrid, Spain.
Instituto de Salud Carlos III. National Center of Epidemiology. Madrid, Spain.
University of California. School of Medicine. San Francisco, California, USA.
Germans Trias Hospital. Barcelona, Spain.
Fenway Health. Boston, Massachusetts, USA.
Hospital Universitari de Bellvitge. Barcelona, Spain.
University of North Carolina at Chapel Hill. School of Medicine. Department of Medicine. Chapel Hill, North Carolina, USA..
Southern Alberta HIV Program. Calgary, Canada.
Fundação Oswaldo Cruz. Presidência. Programa de Computação Científica. Rio de Janeiro, RJ, Brazil.
Fundação Oswaldo Cruz. Presidência. Programa de Computação Científica. Rio de Janeiro, RJ, Brazil.
University of North Carolina at Chapel Hill. School of Medicine. Department of Medicine. Chapel Hill, North Carolina, USA.
University College London. London, UK.
University College London. London, UK.
Yale University. School of Public Health. New Haven, Connecticut, USA.
Yale University. School of Public Health. New Haven, Connecticut, USA.
Universitätsspital Basel. Basel, Switzerland.
University of Bern. Institute of Social and Preventive Medicine. Bern, Switzerland.
University of Bern. Bern University Hospital. Division of Infectious Diseases. Bern, Switzerland.
University of Barcelona. Barcelona, Spain.
Institut Català d'Oncologia. Barcelona, Spain.
University College London. London, UK.
Athens University Medical School. Department of Hygiene, Epidemiology and Medical Statistics. Athens, Greece.
University of Washington. Seattle, Washington, USA.
University Pierre and Marie Curie. Paris, France.
University of Alabama at Birmingham. Birmingham, Alabama, USA.
Harvard T. H. Chan School of Public Health. Department of Epidemiology. Boston, Massachusetts, USA / Harvard T.H. Chan School of Public Health. Department of Biostatistics. Boston, Massachusetts, USA / Harvard-MIT Division of Health Sciences and Technology. Boston, Massachusetts, USA.
Harvard T. H. Chan School of Public Health. Department of Epidemiology. Boston, Massachusetts, USA / Harvard T.H. Chan School of Public Health. Department of Biostatistics. Boston, Massachusetts, USA.
Harvard T. H. Chan School of Public Health. Department of Epidemiology. Boston, Massachusetts, USA.
University College London. London, UK.
Harvard T. H. Chan School of Public Health. Department of Epidemiology. Boston, Massachusetts, USA.
APHP Hôpital Avicenne. Bobigny, France.
University of Alabama at Birmingham. School of Medicine. Birmingham, Alabama, USA..
Harvard T. H. Chan School of Public Health. Department of Epidemiology. Boston, Massachusetts, USA.
Inserm, Université Paris Sud. Orsay, France.
Inserm, Université Paris Sud. Orsay, France.
University of Washington. Seattle, Washington, USA.
Harvard T. H. Chan School of Public Health. Department of Epidemiology. Boston, Massachusetts, USA.
Centre Hospitalier Universitaire de Bordeaux. Bordeaux, France.
Centre Hospitalier Universitaire de Bordeaux. Bordeaux, France.
The Johns Hopkins University. School of Medicine. Baltimore, Maryland, USA.
Academisch Medisch Centrum Geneeskunde. Amsterdam, The Netherlands.
Academisch Medisch Centrum Geneeskunde. Amsterdam, The Netherlands.
University of California San Diego Health. Department of Medicine. San Diego, California, USA.
Instituto de Salud Carlos III. National Center of Epidemiology. Madrid, Spain.
Instituto de Salud Carlos III. National Center of Epidemiology. Madrid, Spain.
University of California. School of Medicine. San Francisco, California, USA.
Germans Trias Hospital. Barcelona, Spain.
Fenway Health. Boston, Massachusetts, USA.
Hospital Universitari de Bellvitge. Barcelona, Spain.
University of North Carolina at Chapel Hill. School of Medicine. Department of Medicine. Chapel Hill, North Carolina, USA..
Southern Alberta HIV Program. Calgary, Canada.
Fundação Oswaldo Cruz. Presidência. Programa de Computação Científica. Rio de Janeiro, RJ, Brazil.
Fundação Oswaldo Cruz. Presidência. Programa de Computação Científica. Rio de Janeiro, RJ, Brazil.
University of North Carolina at Chapel Hill. School of Medicine. Department of Medicine. Chapel Hill, North Carolina, USA.
University College London. London, UK.
University College London. London, UK.
Yale University. School of Public Health. New Haven, Connecticut, USA.
Yale University. School of Public Health. New Haven, Connecticut, USA.
Universitätsspital Basel. Basel, Switzerland.
University of Bern. Institute of Social and Preventive Medicine. Bern, Switzerland.
University of Bern. Bern University Hospital. Division of Infectious Diseases. Bern, Switzerland.
University of Barcelona. Barcelona, Spain.
Institut Català d'Oncologia. Barcelona, Spain.
University College London. London, UK.
Athens University Medical School. Department of Hygiene, Epidemiology and Medical Statistics. Athens, Greece.
University of Washington. Seattle, Washington, USA.
University Pierre and Marie Curie. Paris, France.
University of Alabama at Birmingham. Birmingham, Alabama, USA.
Harvard T. H. Chan School of Public Health. Department of Epidemiology. Boston, Massachusetts, USA / Harvard T.H. Chan School of Public Health. Department of Biostatistics. Boston, Massachusetts, USA / Harvard-MIT Division of Health Sciences and Technology. Boston, Massachusetts, USA.
Abstract
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/μl compared with 500 cells/μl 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.
Keywords
Causal inferenceDynamic regime
Joint treatment strategies
Marginal structural model
No direct effect
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