Clinical Trials

❘❙❚■ Chapter 16 | Multicenter TrialsCRASH (Corticosteroid Randomisation After Significant Head Injury)trial was a large randomized controlled trial that examined whether aninfusion of corticosteroids can reduce the immediate risk of subsequentdeath and neurologic disability when given to adults with head injury andimpaired consciousness [5]. This large, multicenter trial aimed to gainfeedback from many investigating clinicians, which is particularly usefulsince this intervention is conducted in a relatively high-risk situation [6].• In certain cases, a difference in therapeutic approaches is being testedand multiple centers that have different facilities or access to treatmentsare needed. For example, the PCI-CURE (Percutaneous CoronaryIntervention and Clopidogrel in Unstable Angina to Prevent RecurrentIschemic Events) substudy compared patients given the antiplateletagent clopidogrel or placebo and a routine coronary angiography andrevascularization strategy as needed with patients in the main studycomparing clopidogrel and placebo in a setting of angiography drivenby clinical need only. Therefore, this trial needed centers both withand without access to angiography facilities [13].How is a multicenter trial organized?Once a specific question to test using a clinical trial structure has been identified,there is a well-defined procedure for planning and executing the trial [14].A critical issue in multicenter trials is the coordination of the many investigatorsinvolved, all of whom are adhering to a single protocol. In Figure 1 we outline themain steps and stages involved in a multicenter trial and give a typical timeline forsuch studies. Figure 2 shows a typical organizational structure for a multicentertrial. Such large trials tend to have 5-year timelines, and therefore require anexperienced coordinating team. The skills of such teams are being increasinglyacknowledged and deserve some further explanation [15].Role of the coordinating team in multicenter trialsThe coordinating team for an investigator-led multicenter trial is often attachedto a clinical or academic center. Many essential functions are the same regardlessof whether the trial is single-center or multicenter. However, there are certainaspects that are unique to multicenter trials:• site selection• site recruitment• obtaining national or regional ethics approvals• constructing a multicenter randomization process for patientallocation to treatments156