L8 Clinical trial PHASE 1-3 Flashcards
aim of phase 1 [2]
- safety and tolerability
- PKPD of drug: MTD, dose range, ADRs, route of administration
all subjects of phase 1 must be _____
VOLUNTEERS
criteria to select volunteers/patients for phase 1? [3]
- usually male unless disease is gender specific
- free of substance abuse
- no clinical or laboratory abnormalities
who conduct phase 1?
specialist and pharmacologists
is phase 1 an open or closed trial?
open
what kind of drug cannot be tried on healthy volunteers in phase 1?
- Drugs that are too toxic eg anti-Cancer drugs
- Those that affect germline cells
- Drugs to treat rare genetic conditions
Eg. Anti-HIV drugs
aim of phase 2
efficacy and safety IN PATIENTS
Is phase 2 open or closed trial?
closed aka controlled [have placebo]
whats the difference between open and closed trial?
open: both doctor and volunteer knows what drug you’re taking
closed: volunteer OR doctor doesnt know [single or double blind]
why do we sometimes need a Phase IIa?
it acts as a PILOT clinical trial to evaluate efficacy and safety so do on small grp of patients first
causes of bias in clinical trial
- bias
- belief
- choice and preferences
ways to eliminate biases [4]
- run-in period [to allow patient to return to ‘normal’ state, esp for the illness that come and go]
- randomisation
- blinding
- placebo
why do we need randomisation [2]
- avoid bias
- provide basis for statistical testing
why do we need a run-in period? [2]
- study compliance
- exclude those with high placebo effect
In phase IIb, do we compare drug with placebo or current drugs in market?
BOTH. placebo to see if it works. current drug is want to see if more effective/ less ADR than current drug
does placebo have clinical effect?
yes, it can have clinical effects
what is wash out period? why is it needed?
when patients were on pre-trial medicine. needed to ensure effects of treatment is not carried over to the next
do all outcome measures need to be scientifically measurable?
no but need to be measurable.
what is aim of phase 3?
larger scale of phase 2: more countries, more subjects –> determine if there is safety and efficacy issues in people
what are the pre-clinical trial info requirements? [6]
- general pharmacology PKPD
- acute toxicity LD50
- Chronic toxicity [done in 2 animal species]
- Reproductive toxicity
- carcinogenicity and mutagenicity
- chemical/pharmaceutical data
how do we measure safety and tolerability of drug during phase I?
-measure and check vital functions: CNS/CVS/lungs
- blood and urine test: drug concentrations
- other parameters: weight/height/body temp etc
phase 1 trial can be done at comfort of volunteer’s home. T/F?
False. should be in in-patient clinic w comprehensive medical surveillance, emergency and intensive care facilities
what are some common medical emergencies from drugs?
syncope, hypotension, anaphylaxis, cardiopulmonary arrest, multiple organ failure
types of hypersensitivity [2]
Localised: rhinitis, asthma, rash etc
Generalised: anaphylactic shock
