B3.044 EBM in Practice: Evaluating New Drugs Flashcards
describe the similarities and differenced between heparin and warfarin
both used to treat arterial and venous thrombi
heparin used for the first 7-10 days, w a 3-5 day overlap with warfarin, which may be continues for up to 6 months
warfarin also used to prevent blood clots in pts with chronic atrial fibrillation
therapeutic goal of warfarin
prolongation of prothrombin time (PT) above normal
1.5-3.5 fold if human tissue thromboplastin is used (basis of the INR)
therapeutic goal achieved in about 1 week
slow onset
what is INR?
international normalizes ratio of test/control
low intensity anti coag = 1.5-2, long term
moderate intensity = 2-3, initially
high intensity = 2.5-3.5, mechanical prosthetic heart valves
why is dosing warfarin difficult?
narrow therapeutic index multiple factors affecting pharmacokinetics -diet -GI status -other drugs -genetics
classify a phase 1 trial by N, study participants, study design, primary objective, duration, cost, and success rate
10-100 subjects usually healthy subjects, except cancer open label pharmacokinetics and safety months to 1-2 years 5-10 million 50%
classify a phase 2 trial by N, study participants, study design, primary objective, duration, cost, and success rate
50-500 patients patients receiving experimental drug randomized and controlled, may be blinded efficacy and dose ranging 1-2 years 20 million 30%
classify a phase 3 trial by N, study participants, study design, primary objective, duration, cost, and success rate
hundreds-thousands of patients patients receiving experimental drug randomized, may be controlled (placebo or comparison), may be blinded efficacy, variability in efficacy 3-5 years 50-100 million 25-50%
classify a phase 4 trial by N, study participants, study design, and primary objective
many thousands of participants patients receiving approved drug open label adverse effects, compliance, drug-drug interactions (post marketing surveillance)
