PAS - Clinical Trial Phases Flashcards
list phases of clinical trials - (5)
preclinical
phase 1
phase 2
phase 3
phase 4
preclinical phase of testing?
laboratory and animal studies used to assess the biological activity and safety of the drug
phase 1 of testing? - aims? participant criteria? method?
- aims to assess safety, dosage, toxicity & side effects
- see if pharmacokinetics differ much from animal to humans
participant criteria: small group (20-80) of healthy volunteers with uniformity (age, sex, health), unless its experimentation for toxic drugs (e.g. for HIV/ cancer)
- exclusion criteria - women of child-bearing age, children
method: small number of healthy volunteers, starts with a fraction of the dose tolerated in animal models, slowly increased to find a safe tolerated dose
- takes 3-6 months, performed at a single centre
phase 2 of testing?
aims to assess efficacy and further evaluate safety
participants - larger group (100-300) of patients with the disease/condition
method:
- early phase with 20-200 people with relevant disease = establishes therapeutic benefits, dose range, may be single blind where only the patient knows
- late phase = 50-500 diseased volunteers, double-blind trial compared with a placebo or standard drug
- takes 6mths-2yrs, 35% success rate
outcomes:
- assess efficacy against a defined therapeutic endpoint
- detailed pharmacodynamic and pharmacokinetic data
- establish safe dose and dosage for future trials
phase 3 of testing? - aims? participant criteria? method/ outcome?
aims to confirm efficacy, monitor side effects, and compare with standard treatments
participants:
- large scale 250-1000 patients with condition
- multicentric to ensure ethic and geographical variations
method:
- randomised controlled trial, double-blinded
- recording all adverse drug reactions
- statistical evaluation of all clinical data to gather data for drug approval
- takes up to 5yrs with 20% success
phase 4 of testing?
aims for post-marketing surveillance to collect information on long-term effectiveness and safety
participants: general patient population
no fixed duration, reporting of all adverse effects
- helps detect rare adverse effects, drug interactions
the role of different parties in clinical trials
patient/ healthy volunteer
clinical pharmacologist, investigator and team
- assess treatment, record adverse effects
sponsor
- funding and resources
- responsible for trial = design, management and oversight
- files papers to legal and regulatory authorities
chief investigator
co-ordinator
research ethics committee & regulatory authorities
- REC supervises and monitors each step, safeguards welfare and rights of volunteers, reviews trial protocol
- RA has legal authority on the outcomes of the trial, ensures compliance
process of running a randomised controlled clinical trial
develop protocol - objectives, patient criteria, design, methodology
ethics approval by REC (research ethics committee)
following experiments on lab/ animal models in the pre-clinical phase, recruit participants using inclusion & exclusion criteria for phases 1-4
randomisation of participants into treatment and control groups
implement single/ double blinding, collect baseline and follow-up data according to protocol
- review safety data, record adverse events
- use statistical methods to compare outcomes between groups
- electronic data collection
- report/ publish findings
study closure
what is good clinical practice (GCP)?
international standard for designing, conducting, recording, and reporting trials involving human participants
involves anonymity, confidentiality, data protection/ security and consent for participants
parallel trial design?
participants are randomly assigned to one of two or more groups, with each group receiving a different intervention or treatment
each participant receives only one type of treatment throughout the study period
pros:
- simple design, easy to implement
- shorter study duration
- less risk of carryover effects from treatment
- suitable for a wide range of interventions
cons:
- requires a larger sample size
- differences between groups can affect outcomes - randomisation helps minimise this
crossover trial design?
each participant receives multiple treatments in a sequential manner - participants are randomly assigned to receive different treatments in a specific order, with a washout period in between to minimize carryover effects
pros:
- within-subject comparison, each patient serves as their own control
- smaller sample size
cons:
- longer study duration, multiple periods
- more complex to implement and analyse, requires careful planning for different periods
- not appropriate for treatments with long-lasting effects
