Lecture 2_Pre-clinical studies & clinical trials Flashcards
(18 cards)
What are the major stages in the drug development pipeline?
Discovery, target validation, lead identification, lead optimisation, pre-clinical safety, Phase I–III clinical trials, and post-marketing lifecycle management (V)
What is a New Molecular Entity (NME)?
A Drug compound with a unique chemical structure that has not been previously approved for human use
What is the main purpose of pre-clinical studies?
To examine a drug’s safety, efficacy, and potential risks before human trials
What are the key types of pre-clinical tests?
Toxicology, pharmacokinetics (PK), pharmacodynamics (PD), off-target effects, genotoxicity, carcinogenicity, immunotoxicity, and reproductive toxicity
What are the four types of pre-clinical study approaches?
In vitro (in glass), in vivo (in living organisms), ex vivo (outside the organism), and in silico (computer simulations)
What is an example of a failed pre-clinical to clinical translation?
TGN1412 caused severe adverse reactions in humans due to species differences not predicted in pre-clinical models
What is Good Laboratory Practice (GLP)?
A set of guidelines to ensure the reliability and reproducibility of pre-clinical studies
What are key GLP requirements?
SOPs, documentation, QA procedures, equipment calibration, and staff training
What are the main phases of clinical trials?
Phase I: Safety and dosage in healthy volunteers (20–100 people).
Phase II: Efficacy and side effects in patients (100–500 people).
Phase III: Large-scale effectiveness and adverse effects (300–5000 people).
Phase IV: Post-marketing safety surveillance.
Phase V: Ongoing lifecycle monitoring
What is the focus of Phase Ib trials?
Safety and pharmacokinetics in patients, often providing early efficacy and biomarker data
What is required before clinical trials can begin in Australia?
Approval via the CTN or CTX scheme through the TGA, HREC review, informed consent, and adherence to GCP guidelines
What is informed consent in clinical trials?
A process ensuring participants understand the purpose, risks, and benefits before agreeing to take part
Why is Australia an attractive location for clinical trials?
Due to world-class infrastructure, skilled researchers, a diverse population, strong IP laws, stable governance, and streamlined TGA regulation
What is the success rate from Phase I to regulatory approval?
About 70% of drugs progress from Phase I to II, 33% from II to III, and 25–30% from Phase III to approval
In Vitro pros and cons
Pros: Evaluate biological effects without confounding variables, Can do larger number of subjects than if done in animals
Cons: Cannot replicate the conditions that occur inside a living organism.
In Vivo Pros and cons
Pros: In context of living organism, can observe interactions within system.
More likely to translate to real life
Cons: Ethics
cost and time
Ex Vivo pros and cons
Pros: Precise control over experimental conditions
Less need for live animals
Cons: Do not fully replicate the complex interactions
Tissues and cells ex vivo have limited lifespan - issue reflecting long term responses
In silico pros and cons
Pros: Can rapidly analyse large datasets, lower cost
Cons: May be oversimplification
Accuracy dependant on quality and completeness of data
