02322nas a2200457   4500000000100000008004100001260001700042653001100059653003300070653002200103653001100125653001300136653001900149653002000168653004700188653001800235653001400253653002000267653002000287653003300307653002500340653002600365653001700391653001800408653001100426100001300437700001500450700001600465700001700481700001500498700001400513700001600527700001600543700001600559245014000575250001500715300001200730490000700742520107400749020004101823       2008                            d  c12830659714610aHumans10aRandomised Controlled Trials10aTreatment Outcome10aApache10aPlacebos10aQuestionnaires10aResearch Design10aUnited States Food and Drug Administration10aUnited States10aProtein C10aTherapeutic use10aClinical Trials10aMulticenter Studies as Topic10aRecombinant Proteins10aAnti-Infective Agents10aSeptic Shock10aDrug Industry10aEthics1 aBarie P.1 aDouglas I.1 aGardlund B.1 aFinfer Simon1 aRanieri V.1 aRhodes A.1 aThompson B.1 aMarshall J.1 aDhainaut J.00aDesign, conduct, analysis and reporting of a multi-national placebo-controlled trial of activated protein C for persistent septic shock  a2008/10/08  a1935-470 v343 a<p>
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.
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