Clinical 101: Clinical trial endpoints: Selection, analysis and interpretation

Clinical 101:Clinical trial endpoints: Selection, analysis and interpretationElizabeth Garrett-Mayer, PhDHollings Cancer CenterMedical University of South CarolinaDecember 10, 2013San Antonio Breast Cancer Symposium - Cancer Therapy and Research Center at UT Health Science Center Dec10-14, 2013This presentation is the intellectual property of the author/presenter. Contact her at garrettm@musc.edu for permission to reprint and/or distribute.Classic Phases of Drug DevelopmentPhase I: dose finding and safety evaluationsize: small. 10-50 patients

Phase II: preliminary efficacy and further safety evaluationsize: medium. 20-100s of patients

Phase III: comparative efficacy trial size: large. 500 to 1000s of patients

San Antonio Breast Cancer Symposium - Cancer Therapy and Research Center at UT Health Science Center Dec10-14, 2013This presentation is the intellectual property of the author/presenter. Contact her at garrettm@musc.edu for permission to reprint and/or distribute.2Phase I Trials: Dose FindingSan Antonio Breast Cancer Symposium - Cancer Therapy and Research Center at UT Health Science Center Dec10-14, 2013This presentation is the intellectual property of the author/presenter. Contact her at garrettm@musc.edu for permission to reprint and/or distribute.Phase I trialsGoal: find the best dose/schedule to move to phase II.

Old school chemotherapeutics:the highest tolerable dose is the most efficaciousbased on the assumptions of increasing dose-toxicity relationshipincreasing dose-efficacy relationship

San Antonio Breast Cancer Symposium - Cancer Therapy and Research Center at UT Health Science Center Dec10-14, 2013This presentation is the intellectual property of the author/presenter. Contact her at garrettm@musc.edu for permission to reprint and/or distribute.Dose relationships

San Antonio Breast Cancer Symposium - Cancer Therapy and Research Center at UT Health Science Center Dec10-14, 2013This presentation is the intellectual property of the author/presenter. Contact her at garrettm@musc.edu for permission to reprint and/or distribute.TerminologyDose limiting toxicity: DLT (*endpoint*)the definition of (serious) adverse events that are considered sufficiently toxic to want to limit their occurrenceOften any grade 3 or 4 SAE.Sometimes grade 4 with certain grade 3 SAEs.In most phase I studies, DLTs in cycle 1 affect dose escalationSan Antonio Breast Cancer Symposium - Cancer Therapy and Research Center at UT Health Science Center Dec10-14, 2013This presentation is the intellectual property of the author/presenter. Contact her at garrettm@musc.edu for permission to reprint and/or distribute.DLT example:DLT was defined as any one of the following: (a) ANC