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 [email protected] 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 [email protected] 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 [email protected] 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 [email protected] 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 [email protected] 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
[email protected] for permission to reprint and/or distribute.DLT
example:DLT was defined as any one of the following: (a) ANC