Use of pragmatic and explanatory trial designs in acute care research: lessons from COVID-19
Jonathan Casey
(1)
,
Laura Beskow
(1)
,
Jeremy Brown
(2)
,
Samuel Brown
(3)
,
Etienne Gayat
(4, 5, 6)
,
Michelle Ng Gong
(7)
,
Michael Harhay
(8)
,
Samir Jaber
(9, 10, 11)
,
Jacob Jentzer
(12)
,
Pierre-François Laterre
(13)
,
John Marshall
(14)
,
Michael Matthay
(15)
,
Todd Rice
(1)
,
Yves Rosenberg
(16)
,
Alison Turnbull
(17)
,
Lorraine Ware
(18)
,
Wesley Self
(1)
,
Alexandre Mebazaa
(4, 5)
,
Sean M Collins
(1)
1
Vanderbilt University [Nashville]
2 NINDS - National Institute of Neurological Disorders and Stroke [Bethesda]
3 University of Utah
4 MASCOT (UMR_S_942 / U942) - Marqueurs cardiovasculaires en situation de stress
5 Hôpital Lariboisière-Fernand-Widal [APHP]
6 Service d'Anesthésie-Réanimation [AP-HP Hôpitaux Saint-Louis Lariboisière]
7 Albert Einstein College of Medicine [New York]
8 University of Pennsylvania
9 PhyMedExp - Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046]
10 CHRU Montpellier - Hôpital Saint Eloi
11 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
12 Mayo Clinic [Rochester]
13 UCL - Université Catholique de Louvain = Catholic University of Louvain
14 St. Michael's Hospital
15 UC San Francisco - University of California [San Francisco]
16 NHLBI - National Heart, Lung, and Blood Institute [Bethesda]
17 JHU - Johns Hopkins University
18 Vanderbilt University Medical Center [Nashville]
2 NINDS - National Institute of Neurological Disorders and Stroke [Bethesda]
3 University of Utah
4 MASCOT (UMR_S_942 / U942) - Marqueurs cardiovasculaires en situation de stress
5 Hôpital Lariboisière-Fernand-Widal [APHP]
6 Service d'Anesthésie-Réanimation [AP-HP Hôpitaux Saint-Louis Lariboisière]
7 Albert Einstein College of Medicine [New York]
8 University of Pennsylvania
9 PhyMedExp - Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046]
10 CHRU Montpellier - Hôpital Saint Eloi
11 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
12 Mayo Clinic [Rochester]
13 UCL - Université Catholique de Louvain = Catholic University of Louvain
14 St. Michael's Hospital
15 UC San Francisco - University of California [San Francisco]
16 NHLBI - National Heart, Lung, and Blood Institute [Bethesda]
17 JHU - Johns Hopkins University
18 Vanderbilt University Medical Center [Nashville]
Michelle Ng Gong
- Fonction : Auteur
- PersonId : 1302167
- ORCID : 0000-0001-7952-5384
Samir Jaber
- Fonction : Auteur
- PersonId : 183664
- IdHAL : samir-jaber
- ORCID : 0000-0002-7257-8069
- IdRef : 060380829
Pierre-François Laterre
- Fonction : Auteur
- PersonId : 1321013
- ORCID : 0000-0001-5712-7449
Alexandre Mebazaa
- Fonction : Auteur
- PersonId : 757056
- ORCID : 0000-0001-8715-7753
- IdRef : 070282609
Sean M Collins
- Fonction : Auteur
- PersonId : 796739
- ORCID : 0000-0002-5151-6360
Résumé
Unique challenges arise when conducting trials to evaluate therapies already in common clinical use, including difficulty enrolling patients owing to widespread open-label use of trial therapies and the need for large sample sizes to detect small but clinically meaningful treatment effects. Despite numerous successes in trials evaluating novel interventions such as vaccines, traditional explanatory trials have struggled to provide definitive answers to time-sensitive questions for acutely ill patients with COVID-19. Pragmatic trials, which can increase efficiency by allowing some or all trial procedures to be embedded into clinical care, are increasingly proposed as a means to evaluate therapies that are in common clinical use. In this Personal View, we use two concurrently conducted COVID-19 trials of hydroxychloroquine (the US ORCHID trial and the UK RECOVERY trial) to contrast the effects of explanatory and pragmatic trial designs on trial conduct, trial results, and the care of patients managed outside of clinical trials. In view of the potential advantages and disadvantages of explanatory and pragmatic trial designs, we make recommendations for their optimal use in the evaluation of therapies in the acute care setting.
Format du dépôt | Fichier |
---|---|
Type de dépôt | Article dans une revue |
Titre |
en
Use of pragmatic and explanatory trial designs in acute care research: lessons from COVID-19
|
Résumé |
en
Unique challenges arise when conducting trials to evaluate therapies already in common clinical use, including difficulty enrolling patients owing to widespread open-label use of trial therapies and the need for large sample sizes to detect small but clinically meaningful treatment effects. Despite numerous successes in trials evaluating novel interventions such as vaccines, traditional explanatory trials have struggled to provide definitive answers to time-sensitive questions for acutely ill patients with COVID-19. Pragmatic trials, which can increase efficiency by allowing some or all trial procedures to be embedded into clinical care, are increasingly proposed as a means to evaluate therapies that are in common clinical use. In this Personal View, we use two concurrently conducted COVID-19 trials of hydroxychloroquine (the US ORCHID trial and the UK RECOVERY trial) to contrast the effects of explanatory and pragmatic trial designs on trial conduct, trial results, and the care of patients managed outside of clinical trials. In view of the potential advantages and disadvantages of explanatory and pragmatic trial designs, we make recommendations for their optimal use in the evaluation of therapies in the acute care setting.
|
Auteur(s) |
Jonathan Casey
1
, Laura Beskow
1
, Jeremy Brown
2
, Samuel Brown
3
, Etienne Gayat
4, 5, 6
, Michelle Ng Gong
7
, Michael Harhay
8
, Samir Jaber
9, 10, 11
, Jacob Jentzer
12
, Pierre-François Laterre
13
, John Marshall
14
, Michael Matthay
15
, Todd Rice
1
, Yves Rosenberg
16
, Alison Turnbull
17
, Lorraine Ware
18
, Wesley Self
1
, Alexandre Mebazaa
4, 5
, Sean M Collins
1
1
Vanderbilt University [Nashville]
( 168363 )
- Nashville, Tennessee, TN 37240
- États-Unis
2
NINDS -
National Institute of Neurological Disorders and Stroke [Bethesda]
( 211879 )
- 35 Convent Drive, Bethesda, MD 20892-3701
- États-Unis
3
University of Utah
( 300863 )
- 201 Presidents Cir, Salt Lake City, UT 84112
- États-Unis
4
MASCOT (UMR_S_942 / U942) -
Marqueurs cardiovasculaires en situation de stress
( 1005039 )
- Hopital Lariboisière - Centre Viggo Petersen
41, Bd de la Chapelle
75475 Paris Cedex 10
- France
5
Hôpital Lariboisière-Fernand-Widal [APHP]
( 300128 )
- 2, rue Ambroise - Paré 75475
- France
6
Service d'Anesthésie-Réanimation [AP-HP Hôpitaux Saint-Louis Lariboisière]
( 1004940 )
- rue Ambroise Paré, 75010 Paris
- France
7
Albert Einstein College of Medicine [New York]
( 418975 )
- 300 Morris Park Avenue Bronx, NY 10461
- États-Unis
8
University of Pennsylvania
( 115889 )
- 3451 Walnut Street, Philadelphia, PA 19104 | 215-898-5000
- États-Unis
9
PhyMedExp -
Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046]
( 1100749 )
- 371 Avenue du Doyen G. Giraud, CHU Arnaud de Villeneuve, Bâtiment INSERM Crastes de Paulet - 34295 Montpellier Cedex 5
- France
10
CHRU Montpellier -
Hôpital Saint Eloi
( 303483 )
- 80 avenue Augustin Fliche
34090 Montpellier
- France
11
CHRU Montpellier -
Centre Hospitalier Régional Universitaire [Montpellier]
( 258773 )
- 191 avenue du doyen Gaston Giraud 34295 Montpellier
- France
12
Mayo Clinic [Rochester]
( 157897 )
- 200 First St. SW
Rochester, MN 55905
- États-Unis
13
UCL -
Université Catholique de Louvain = Catholic University of Louvain
( 92863 )
- Place de l'Université 1 - 1348 Louvain-La-Neuve
- Belgique
14
St. Michael's Hospital
( 301756 )
- Ontario
- Canada
15
UC San Francisco -
University of California [San Francisco]
( 190541 )
- 505 Parnassus Ave, San Francisco, CA 94143
- États-Unis
16
NHLBI -
National Heart, Lung, and Blood Institute [Bethesda]
( 346808 )
- P.O. Box 30105
Bethesda, Maryland 20892
- États-Unis
17
JHU -
Johns Hopkins University
( 7668 )
- Baltimore, Maryland 410-516-8000
- États-Unis
18
Vanderbilt University Medical Center [Nashville]
( 148597 )
- 1211 Medical Center Drive Nashville, TN 37232
- États-Unis
|
Langue du document |
Anglais
|
Vulgarisation |
Non
|
Comité de lecture |
Oui
|
Audience |
Internationale
|
Nom de la revue |
|
Licence |
Paternité - Pas d'utilisation commerciale - Pas de modification
|
Date de publication |
2022-07
|
Volume |
10
|
Numéro |
7
|
Page/Identifiant |
700-714
|
Date de publication électronique |
2022-06-28
|
Domaine(s) |
|
Mots-clés (Mesh) |
|
DOI | 10.1016/S2213-2600(22)00044-3 |
Pubmed Id | 35709825 |
PubMed Central | PMC9191864 |
UT key WOS | 000835334000017 |
Fichier principal
2022 Casey et al., Use of pragmatic.pdf ( 61.1 Mo
)
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1-s2.0-S2213260022004362-main.pdf ( 33.4 Ko
)
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- CC BY 4.0
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