Caroline Monchaud1, Benoît Marin, Marc Estenne, Pierre-Marie Preux, Pierre Marquet. 1. 1 INSERM UMR-S850, CHU Limoges, Université de Limoges, France. 2 Service de Pharmacologie, toxicologie et pharmacovigilance, CHU Limoges, France. 3 Unité Fonctionnelle de Recherche Clinique et de Biostatistiques, CHU Limoges, Limoges, France. 4 Service de Pneumologie, Hôpital Universitaire Erasme, Université Libre de Bruxelles, Bruxelles, Belgium. 5 Address correspondence to: Pierre Marquet, M.D., Ph.D., INSERM UMR-S850, Faculty of Medicine, University of Limoges, 2 rue du Dr Marcland, 87025, Limoges Cedex, France.
Abstract
BACKGROUND: In lung transplantation, diverse clinical events may impact patient outcome. In clinical trials comparing intervention strategies, single primary endpoints require large populations, or long study durations, whereas composite endpoints (CEPs) do not take into account the respective impact of their components on patient survival. The objective of this study was to propose consensus recommendations on endpoints for clinical trials on immunosuppressants in lung transplantation. METHODS: The consensus process was managed through the Internet using the Delphi method. Forty experts were invited by the pilot group with the help of the International Society for Heart and Lung Transplantation and The Transplantation Society. In the first round, a questionnaire was made available to the experts to complete, and the responses were analyzed. In each next round, a new questionnaire was developed from the previous responses and sent to the panel members. RESULTS: Consensus between 17 experts was achieved after five rounds. Two score-type CEPs were defined for immunosuppressive drug efficacy (7 items) and for toxicity (15 items). Death related to graft loss or immunosuppressive drug toxicity was attributed a maximum weight of 100. The weights of the items included in the efficacy and toxicity CEPs ranged between 10 and 80 and between 25 and 70, respectively. The CEP scores are calculated by adding the weights of all the items composing them, without exceeding 90 as long as the patient is alive. CONCLUSION: This consensus conference proposed two score-type CEPs including relevant endpoints. After validation, they should allow clinical trials with higher statistical power, improving the evaluation of the interventions tested.
BACKGROUND: In lung transplantation, diverse clinical events may impact patient outcome. In clinical trials comparing intervention strategies, single primary endpoints require large populations, or long study durations, whereas composite endpoints (CEPs) do not take into account the respective impact of their components on patient survival. The objective of this study was to propose consensus recommendations on endpoints for clinical trials on immunosuppressants in lung transplantation. METHODS: The consensus process was managed through the Internet using the Delphi method. Forty experts were invited by the pilot group with the help of the International Society for Heart and Lung Transplantation and The Transplantation Society. In the first round, a questionnaire was made available to the experts to complete, and the responses were analyzed. In each next round, a new questionnaire was developed from the previous responses and sent to the panel members. RESULTS: Consensus between 17 experts was achieved after five rounds. Two score-type CEPs were defined for immunosuppressive drug efficacy (7 items) and for toxicity (15 items). Death related to graft loss or immunosuppressive drug toxicity was attributed a maximum weight of 100. The weights of the items included in the efficacy and toxicity CEPs ranged between 10 and 80 and between 25 and 70, respectively. The CEP scores are calculated by adding the weights of all the items composing them, without exceeding 90 as long as the patient is alive. CONCLUSION: This consensus conference proposed two score-type CEPs including relevant endpoints. After validation, they should allow clinical trials with higher statistical power, improving the evaluation of the interventions tested.