Design, conduct, analysis and reporting of a multi-national placebo-controlled trial of activated protein C for persistent septic shock.
The role of drotrecogin alfa (activated) (DAA) in severe sepsis remains controversial and clinicians are unsure whether or not to treat their patients with DAA. In response to a request from the European Medicines Agency, Eli Lilly will sponsor a new placebo-controlled trial and history suggests the results will be subject to great scrutiny. An academic steering committee will oversee the conduct of the study and will write the study manuscripts. The steering committee intends that the study will be conducted with the maximum possible transparency; this includes publication of the study protocol and a memorandum of understanding which delineates the role of the sponsor. The trial has the potential to provide clinicians with valuable data but patients will only benefit if clinicians have confidence in the conduct, analysis and reporting of the trial. This special article describes the process by which the trial was developed, major decisions regarding trial design, and plans for independent analysis, interpretation and reporting of the data.
Finfer
Simon
S
Critical Care and Trauma, The George Institute for International Health, University of Sydney, Sydney, NSW, Australia. sfinfer@george.org.au
Ranieri
V Marco
VM
Thompson
B Taylor
BT
Barie
Philip S
PS
Dhainaut
Jean-François
JF
Douglas
Ivor S
IS
Gårdlund
Bengt
B
Marshall
John C
JC
Rhodes
Andrew
A
D018806:APACHE; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic / Q000941:ethics / Q000379:methods; D004345:Drug Industry / Q000941:ethics; D006801:Humans; D015337:Multicenter Studies as Topic / Q000941:ethics / Q000379:methods; D010919:Placebos; D011486:Protein C / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic / Q000941:ethics / Q000379:methods; D011994:Recombinant Proteins / Q000627:therapeutic use; D012107:Research Design; D012772:Shock, Septic / Q000188:drug therapy* / Q000401:mortality; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D014486:United States Food and Drug Administration
D000890:Anti-Infective Agents; D010919:Placebos; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated