Clinical Trials Flashcards
What are the stages of clinical trials? What is the regulatory body in Canada?
CTA
Phase 1: pharmacological studies
Phase 2: Preliminary clinical efficacy
Phase 3: extensive clinical trials
What are first in man trials?
Studies healthy volunteers with single and multi-doses
Start at 1/10th of the NOAEL and escalate
No more than 3 dose increments in one subject
Monitor for AEs and biochemical response markers
What is the purpose of Phase I studies?
Pharmacologic profiling
Safe dose escalation to pharmacodynamic activity and/or toxicity
What are the subjects of Phase I studies?
Normal volunteers
Desirable to use patients
20-100 subjects, generally
What is the setting of phase I studies?
No concomitant therapy unless mandatory
2-4 weeks washout of prior drugs
Start dose based on animal NOAEL
Prolonged placebo-controlled
What are proof of concept tests?
In phase II studies,
first use of patients
establish efficacy within boundaries of AEs and key parts of mechanism of action
Is it practical to achieve the target efficacy?
Early signs of safety concerns in organ systems?
What is the difference between Phase IIa and IIb?
IIa: examines dose-response relationships, efficacy and safety variability across patient subgroups, special population pharmacokinetics and metabolic pathways
IIb: narrows the target population and route of administration for a controlled trial
What is the purpose of phase II trials?
Explore early efficacy and safety in patients
early ADME data to guide phase III trial design
What are the subjects in phase II trials?
Ordinarily only targeted disease/condition
Late phase II patients may have disease/therapy in addition to the targeted disease
Seldom more than 200 patient subjects
What happens during phase IIia and IIIb?
finalization of formula draft product monograph
assess potential safety problems
1000-3000 patients with specific disease
measures quality of life
What are the goals of phase III trials?
Large controlled trials in patients with disease
generally longer duration
clinically meaningful endpoints
trial design planned with FDA
What are the subjects in phase III trials?
Two or more multi-center trials with several thousand patient-subjects
Rigorous exclusion/inclusion criteria
Placebo and/or active drug-controlled design
What do phase III studies end with?
1 or 2 double blinded, randomized, placebo controlled, multicentre clinical trials
What do the medical officer, chemistry, and pharmacology/toxicology authorities do?
Assess:
MO: drug safety and efficacy
Chemistry: drug purity, stability, sterility
Pharm/tox: pre-clinical pharmacologic, safety, and PK data
What do statistics, biopharmaceutics, and project management authorities do?
Assess:
stats: drug efficacy
biopharmaceutics: drug metabolism and drug-drug interactions
project management: coordination and industry liason
