Emulating a trial of joint dynamic strategies: An application to monitoring and treatment of HIV‐positive individuals
Ellen Caniglia
(1, 2)
,
James Robins
(1)
,
Lauren Cain
(1)
,
Caroline Sabin
(3)
,
Roger Logan
(1)
,
Sophie Abgrall
(4)
,
Michael J. Mugavero
(5)
,
Sonia Hernández-Díaz
(1)
,
Laurence Meyer
(6)
,
Rémonie Seng
(6)
,
Daniel Drozd
(7)
,
George Seage Iii
(1)
,
Fabrice Bonnet
(8, 9)
,
Fabien Le Marec
(8, 9)
,
Richard Moore
(10)
,
Peter Reiss
(11)
,
Ard van Sighem
(11)
,
William Mathews
(12)
,
Inma Jarrín
(13)
,
Belén Alejos
(13)
,
Steven G. Deeks
(14)
,
Roberto Muga
,
Stephen Boswell
,
Elena Ferrer
,
Joseph J Eron
(15)
,
John Gill
,
Antonio Pacheco
(16)
,
Beatriz Grinsztejn
(16)
,
Sonia Napravnik
(15)
,
Sophie Jose
(3)
,
Andrew Phillips
(3)
,
Amy Justice
(17)
,
Janet Tate
(17)
,
Heiner C. Bucher
(18)
,
Matthias Egger
(19, 20)
,
Hansjakob Furrer
(20, 21)
,
Jose M. Miro
(22)
,
Jordi Casabona
,
Kholoud Porter
(3)
,
Giota Touloumi
(23)
,
Heidi Crane
(7)
,
Dominique Costagliola
(24, 25)
,
Michael S. Saag
(5)
,
Miguel Hernán
(1)
1
Harvard T.H. Chan School of Public Health
2 New York University School of Medicine
3 UCL - University College of London [London]
4 Hôpital Avicenne [AP-HP]
5 UAB - University of Alabama at Birmingham [ Birmingham]
6 UP11 - Université Paris-Sud - Paris 11
7 University of Washington [Seattle]
8 CHU Bordeaux - Centre Hospitalier Universitaire de Bordeaux
9 BPH - Bordeaux population health
10 Johns Hopkins University School of Medicine [Baltimore]
11 AMC - Academic Medical Center - Academisch Medisch Centrum [Amsterdam]
12 UC San Diego - University of California [San Diego]
13 ISC - Instituto de Salud Carlos III [Madrid]
14 UC San Francisco - University of California [San Francisco]
15 UNC - University of North Carolina [Chapel Hill]
16 FIOCRUZ - Fundação Oswaldo Cruz / Oswaldo Cruz Foundation
17 YSM - Yale School of Medicine [New Haven, Connecticut]
18 University Hospital Basel [Basel]
19 ISPM - Institute of Social and Preventive Medicine [Bern]
20 UNIBE - Universität Bern = University of Bern = Université de Berne
21 Inselspital - Bern University Hospital [Berne]
22 University of Barcelona
23 University of Athens Medical School [Athens]
24 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
25 SU - Sorbonne Université
2 New York University School of Medicine
3 UCL - University College of London [London]
4 Hôpital Avicenne [AP-HP]
5 UAB - University of Alabama at Birmingham [ Birmingham]
6 UP11 - Université Paris-Sud - Paris 11
7 University of Washington [Seattle]
8 CHU Bordeaux - Centre Hospitalier Universitaire de Bordeaux
9 BPH - Bordeaux population health
10 Johns Hopkins University School of Medicine [Baltimore]
11 AMC - Academic Medical Center - Academisch Medisch Centrum [Amsterdam]
12 UC San Diego - University of California [San Diego]
13 ISC - Instituto de Salud Carlos III [Madrid]
14 UC San Francisco - University of California [San Francisco]
15 UNC - University of North Carolina [Chapel Hill]
16 FIOCRUZ - Fundação Oswaldo Cruz / Oswaldo Cruz Foundation
17 YSM - Yale School of Medicine [New Haven, Connecticut]
18 University Hospital Basel [Basel]
19 ISPM - Institute of Social and Preventive Medicine [Bern]
20 UNIBE - Universität Bern = University of Bern = Université de Berne
21 Inselspital - Bern University Hospital [Berne]
22 University of Barcelona
23 University of Athens Medical School [Athens]
24 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
25 SU - Sorbonne Université
Ellen Caniglia
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Michael J. Mugavero
- Fonction : Auteur
- PersonId : 853788
Laurence Meyer
- Fonction : Auteur
- PersonId : 756223
- ORCID : 0000-0001-5707-2062
- IdRef : 077686659
Fabrice Bonnet
- Fonction : Auteur
- PersonId : 855374
- ORCID : 0000-0001-5927-4178
- IdRef : 060714034
Roberto Muga
- Fonction : Auteur
Stephen Boswell
- Fonction : Auteur
Elena Ferrer
- Fonction : Auteur
John Gill
- Fonction : Auteur
Beatriz Grinsztejn
- Fonction : Auteur
- PersonId : 956650
Jordi Casabona
- Fonction : Auteur
- PersonId : 898915
Résumé
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.