Endpoints in Clinical Trials ASENT终点的临床试验剂.pptVIP

Fundamentals of Clinical Trials Endpoints Betsy Garofalo MD Michigan Technology and Research Institute Clinical Trial Features Study objective – hypothesis testing Type of study comparisons Primary and secondary endpoints Measures taken to minimizing bias Treatment groups (drug control), dosage and dose regimen Objectives and Endpoints by Phase Phase Objective Efficacy/Endpoint Phase I Safety evaluation Patient tolerance None Phase II Identify efficacy endpoints and doses for Phase III “Exploratory” Primary Secondary Phase III Efficacy Safety Evaluate for general use Primary- Indication Secondary- may be described in label Phase IV Expand efficacy safety Expand patient reported outcomes Endpoint Definition “Results, condition or events associated with individual study patients that are used to assess study treatments” Characteristics of Endpoint Measures Easy to diagnose Easy to identify no evaluator judgment needed Free of measurement error Reliable with repeated measure Internal validity Directly linked to property of interest External validity Ability to generalize to a wider population Characteristics of Endpoint Measures Clinically relevant Influence Rx choices by physicians and patients “How” and “When” to prescribe the drug Surrogate Endpoint Surrogate endpoint – used instead of direct endpoint – ex BP or Cholesterol LDL Reduction as 1? endpoint as opposed to a reduction in CV morbidity or mortality “The difference between a surrogate and a true endpoint is like the difference between a check and cash. You often get the check earlier but then, of course, it may bounce.” Primary, Secondary, Tertiary….. Primary – single (may be co-endpoint) endpoint parameter for rejection of the null hypothesis – regulatory implication in PhIII Secondary- other endpoints pre-specified, may be powered for hypothesis testing Tertiary – exploratory and all other Example Epilepsy “Event” of interest: Seizures Maintain seizure diary for study Video EEG in infan