Ethics and Regulatory Complexities for Pragmatic Clinical Trials Somepatientsdonotreceivethebestcarepossible,either

becauseresearchtosupportclinicaldecisionmakingwith high-qualityevidenceis lackingorbecauseevidence-based practicesarenotroutinely implemented.1Pragmaticclini-cal trials (PCTs), which include patients in routine clinical practicesettingsandtypically incorporatecomparativeef-fectiveness research(CER)—that is, comparingthesafety andeffectivenessofdiagnostic,therapeutic,ordeliverysys-temoptions—canhelpovercomethesechallenges.Thead-ventof researchmethods thatusecluster randomization and leverage patient data fromelectronic health records (EHRs) to increase the sample sizeof trials atmuch lower costs isenablingmajornational initiatives togeneratethe dataneededtoimprovecare.TheseincludetheHealthCare SystemsResearchCollaboratory2andthePatient-Centered OutcomesResearchNetwork (PCORnet)