Contemporary strategies to improve clinicaltrial design for critical care research: insightsfrom the First Critical Care Clinical TrialistsWorkshoplists Workshop

Michael Harhay (1) , Jonathan Casey (2) , Marina Clément (3) , Sean Collins (2) , Etienne Gayat (4, 5) , Michelle Ng Gong (6) , Samir Jaber (7, 8) , Pierre-François Laterre (9) , John Marshall (10) , Michael Matthay (11) , Rhonda Monroe (12) , Todd W Rice (13) , Eileen Rubin (14) , Wesley Self (2) , Alexandre Mebazaa (5, 15)

1 University of Pennsylvania
2 Vanderbilt University Medical Center [Nashville]
3 Hôpital Privé Jacques Cartier [Massy]
4 Service d'Anesthésie-Réanimation [AP-HP Hôpitaux Saint-Louis Lariboisière]
5 MASCOT (UMR_S_942 / U942) - Marqueurs cardiovasculaires en situation de stress
6 Albert Einstein College of Medicine [New York]
7 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
8 PhyMedExp - Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046]
9 UCL - Université Catholique de Louvain = Catholic University of Louvain
10 Keenan Research Centre of the Li Ka Shing Knowledge Institute [Toronto]
11 UC San Francisco - University of California [San Francisco]
12 HFSA - Heart Failure Society of America
13 Vanderbilt University School of Medicine [Nashville]
14 ARDS Foundation - Acute Respiratory Distress Syndrome
15 Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]

Background: Conducting research in critically-ill patient populations is challenging, and most randomized trials of critically-ill patients have not achieved pre-specified statistical thresholds to conclude that the intervention being investigated was beneficial. Methods: In 2019, a diverse group of patient representatives, regulators from the USA and European Union, federal grant managers, industry representatives, clinical trialists, epidemiologists, and clinicians convened the First Critical Care Clinical Trialists (3CT) Workshop to discuss challenges and opportunities in conducting and assessing critical care trials. Herein, we present the advantages and disadvantages of available methodologies for clinical trial design, conduct, and analysis, and a series of recommendations to potentially improve future trials in critical care. Conclusion: The 3CT Workshop participants identified opportunities to improve critical care trials using strategies to optimize sample size calculations, account for patient and disease heterogeneity, increase the efficiency of trial conduct, maximize the use of trial data, and to refine and standardize the collection of patient-centered and patient-informed outcome measures beyond mortality.

Mots clés: Acute respiratory distress syndrome; Clinical trials; Sepsis; Critical care

Domaines: Santé publique et épidémiologie

Michael Harhay, Jonathan Casey, Marina Clément, Sean Collins, Etienne Gayat, et al.. Contemporary strategies to improve clinicaltrial design for critical care research: insightsfrom the First Critical Care Clinical TrialistsWorkshoplists Workshop. Intensive Care Medicine, 2020, 46, pp.930-942. ⟨10.1007/s00134-020-05934-6⟩. ⟨hal-02488650⟩