4 clinical trials and post-market surveillance Flashcards
what is the clinical trial application (CTA)?
-pre-clinical trial application consultation meeting (to make sure they have all the documents and requirements)
CTA is composed of three modules (parts):
-module 1: contains administrative and clinical information about the proposed trial (outline procedure)
-module 2: contains quality (chemistry and manufacturing) information about the drug product to be used in the proposed trial (formulation and active ingredient)
-module 3: contains additional supporting quality information
-protocol approval by the ethics committee
what is the declaration of helsinki (clinical trials)?
-world medical association (WMA) in 1964
-ethical principles for medical research involving humans
-need to protect the health and interests of research participants
-also, confidentiality of personal information of research subjects
what is phase 1 of clinical trials?
-is it safe in humans?
-length of study: several months (<12 months)
-normally 20-80 healthy volunteers (need to get baseline)
-people with certain conditions can participate in phase 1 (that disease that the drug is meant for)
-randomized double-blind placebo-control studies (meaning nurse and patient both dont know)
-dose-escalation approach: dose is escalated with new volunteers (start with lowest dose)
-identify any potential dose-limiting doses (and MTD)
what is phase II of clinical trials?
-approximately 70% of drugs from phase I move to this phase (FDA 2018)
-therapeutic exploratory trial (does it have an effect?) (using safe range found in phase I)
-minimize the number of patients exposed to ineffective or overly toxic treatments (make sure proposed have an effect)
-length of study: 1-2 years
-study participants: 100-500 volunteers who have the disease/condition
what is phase III of clinical trials?
-approximately 33% of drugs from phase II move to this phase
-treatment benefit to a specific population?
-length of study: 1-4 years
-study participants: 300-3,000 volunteers who have the disease/condition
-less common and long-term side effects can be detected
what is post-market surveillance (phase IV)?
-monitors the safety of drugs once they reach the market after the successful completion of clinical trials
-to identify previously unrecognized adverse effects as well as positive effects
-in canada, hospitals are required to report all serious adverse drug reactions within 30 days to health canada (anyone can report)
-health canada collects and evaluate the reports, and may issue a safety review (ex: stop marketing, etc)
what was thalidomide original made for?
1956: nonbarbiturate hypnotic sedative (top-selling sedative) in Europe (helps sleep)
1960: used to treat morning sickness during pregnancy application for thalidomide hit Frances Oldham Kelsey’s desk at FDA
-this is why phase IV is so important
what is phocomelia? (thalidomide disaster)
phocomelia syndrome is a rare birth defect characterized, in most instances, by severe malformation of the extremities. Infants born with this condition will have arms and/or legs that are severely shortened or sometimes completely absent
was thalidomide all bad?
no, it was a racemic mixture
