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Stat Med. 2019 Jun 15;38(13):2428-2446. doi: 10.1002/sim.8120. Epub 2019 Mar 18.

Emulating a trial of joint dynamic strategies: An application to monitoring and treatment of HIV-positive individuals.

Author information

1
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
2
Department of Population Health, School of Medicine, New York University, New York, New York.
3
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
4
University College London, London, UK.
5
APHP Hôpital Avicenne, Bobigny, France.
6
School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
7
Inserm, Université Paris Sud, Orsay, France.
8
University of Washington, Seattle, Washington.
9
Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
10
School of Medicine, The Johns Hopkins University, Baltimore, Maryland.
11
Academisch Medisch Centrum Geneeskunde, Amsterdam, The Netherlands.
12
Department of Medicine, University of California San Diego Health, San Diego, California.
13
National Center of Epidemiology, Instituto de Salud Carlos III, Madrid, Spain.
14
School of Medicine, University of California, San Francisco, San Francisco, California.
15
Germans Trias Hospital, Barcelona, Spain.
16
Fenway Health, Boston, Massachusetts.
17
Hospital Universitari de Bellvitge, Barcelona, Spain.
18
Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
19
Southern Alberta HIV Program, Calgary, Canada.
20
Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
21
School of Public Health, Yale University, New Haven, Connecticut.
22
Universitätsspital Basel, Basel, Switzerland.
23
Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
24
Division of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.
25
University of Barcelona, Barcelona, Spain.
26
Institut Català d'Oncologia, Barcelona, Spain.
27
Department of Hygiene, Epidemiology and Medical Statistics, Athens University Medical School, Athens, Greece.
28
University Pierre and Marie Curie, Paris, France.
29
University of Alabama at Birmingham, Birmingham, Alabama.
30
Harvard-MIT Division of Health Sciences and Technology, Boston, Massachusetts.

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 inference; dynamic regime; joint treatment strategies; marginal structural model; no direct effect

PMID:
30883859
PMCID:
PMC6499640
[Available on 2020-06-15]
DOI:
10.1002/sim.8120

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