Clinical Trials

❘❙❚■ Chapter 16 | Multicenter TrialsFigure 2. The typical life cycle of a multicenter clinical trial.Study initiationStudy sponsor andcoordinating center meetStudy feasibility and thedraft budget for the trial arediscussed, and the outlineof the trial protocol is draftedDiscussion of study detailsThe study design is formulatedand the timeframe, objectives,target population of patients,recruitment criteria, statisticalanalysis plan, and personnelfor the project are decided onTrial funding securedStaff recruitmentThe lead PIs, trial steeringcommittee members, CECmembers, and DSMBmembers are recruitedDetailed protocol agreedStudy progressionData monitoringThroughout the study,the CEC reviews adverseevents, data are entered/cleaned/verified, and interimanalyses are carried outfor the DSMB, which canrecommend that either thetrial continues, continueswith protocol ammendments,or discontinues forsafety reasonsInterim monitoring visits tosites scheduled as neededSafety orrecruitmentrateconcernsNo safety orrecruitmentrateconcernsCoordinating center activitiesSites and local PIs are selected,and invitations to participateare sentRandomization arrangementsmade, case report forms finalizedand printed, and databasescreated for data entryProtocol regulatory approvalEthics submission to nationaland regional regulatory bodies(eg, FDA)Protocol approved ± amendmentsTrial protocol registeredStudy commencementRoll-in phase (optional)After the first few patients fromeach site are enrolled, each siteis visited to verify that all isgoing according to protocolMonitoring/retraining visitsas neededCoordinating center activitiesEdit-queries are raised,newsletters are distributed,and a frequently asked questionslist with answers is producedfor staff at all sites to establishcommon standards andcommunicationFurther patient enrollmentStudy completionInterim investigators’ meeting,often half-way or more to targetrecruitment (optional)Recruitment discontinuedas interim results showsignificant treatmentdifferences or the targetrecruitment is reachedFollow-up phaseClose-out visit to each siteTrial recruitment suspendedReview lessons learned fromincomplete trial and considerpublication of difficultiesSite eligibilityInvestigators meet to discussthe protocol and each center’sinterest in the studyOptional feasibility studiescarried out for recruitmentat each centerLocal ethics/researchboard submissionLocal protocol approval± minor local protocolamendmentsSites and local PIs registeredwith coordinating centerSite preparationInitiation visits andsite trainingAdministration completedDocumentation and ethicsapproval are checkedCenters authorized toenroll patientsAnalysis and conclusionData entry/cleaning/verification/analysisEvents adjudication/analysisDatabase lockedResults reviewed by thesteering committeeInvestigators’ meetingPresentation/publicationof resultsThe first results are presentedto investigators, then publicpresentations are given andresults are submitted forpublication. Discussionsabout further trials toextend the work may followCEC = clinical events committee; DSMB = data and safety monitoring board; FDA = US Food and Drug Administration;PI = principal investigator.158