Drug development and clinical trials Flashcards
What measures can be used during drug development to measure progress?
Biomarker: readily measurable marker of response
Surrogate: biomarker used for regulatory approval (e.g low BP lowers risk of cerebrovascular event)
Outcome: how the patient feels/ functions/survives
Phase 0
Non clinical, and is predictions for humans
data from non human animals, probable mechanism of action. essentially hypothesising.
Phase 1
Tolerability, healthy
Start small doses, and slowly increase until adverse effects noted. Learn about single and multiple dose PK and adverse effect PD
Phase 2
Effectiveness, unhealthy
2A: proof of concept; yes/no point
2B: learn dose response curves, effective doses and target concs.
Phase 3
Safety, done on 1000 patients plus
Learn adverse effects, method effectiveness. Learn PD and PK covariates
Phase 4
Post marketing
Confirm effective doses and common adverse effects.
Learn uncommon adverse effects. Learn pharmacoeconomics.
What do ABCS stand for in clincal trial design?
Assignment
Blinding
Comparison
Sequence
Assignment
Best method is randomization of who gets what. May stratify or balance.
Blinding
Open; single blind; double blind; triple blind?
Comparison
Can compare active things: dose levels, cocnc levels and biomarkers
Can compare against placebo
Can compare against the standard treatment eg cancer
Types of sequence
Parallel: Compare different subject groups
Crossover: compare patients with themselves. Do one treatment, then another
Titration: Similar to crossover but test different doses in the same patient. Forced of flexible
What are the two types of analysis perspective
Intention to treat: use of effectiveness, a pharmacoeconomic perspective. Bias as unsure if patient followed regime, good for economics.
As treated: method effectiveness, development science perspective
