Drug Development and Clinical Trials Flashcards
How long does it take for a drug to get from discovery to market?
10 years
3 million dollars per drug
9/10 tested in humans never reach the market
What are the phases of drug development?
Phase 0-predictions for humans Phase 1-tolerability Phase 2-effectiveness Phase 3-Safety Phase 4-post marketing
What is a biomarker?
Readily measurable marker of response
What is a surrogate?
Biomarker used for regulatory approval
What is the outcome?
How the patient functions/feels/survives
What is the difference between learn and confirm in terms of drug development?
Learn-exploration of the unknown and develop hypothesis/model
Confirm-develop confidence and test hypothesis
Describe phase 0-predictions for humans
Data from animals
Probable mechanism of action
Likely effective concentrations
Routes of elimination and how it is absorbed
Describe phase 1-tolerability
Start with small doses
Increase slowly and stop when adverse effects are noted
Learn about the drugs pharmacokinetics and dynamics
Describe phase 2-effectiveness
2A) proof of concept, yes/no decision point
2B) learn dose response curve, learn effective doses, learn target concentration
Describe phase 3-safety
Learn adverse effect in target population and confirm effective doses and PK/PD covariates (age, sex, other drugs etc)
Describe phase 4-post marketing
Confirm effective doses Confirm common adverse effects Learn uncommon adverse effects Learn "use effectiveness" Learn pharmacoeconomics
What is the definition of an alternative medicine?
Not a medicine that is known to be safe and effective
What are the four major elements in the design of a clinical trial?
Assignment
Blinding
Comparison
Sequence
What is first come first served assignment and how does it cause bias?
This covers a range of assignment possibilities that could lead to bias such as giving patients in the morning active treatment and afternoon patients placebo
What is the way to assign patients without bias?
Randomised, balanced (even numbers active and placebo) and stratified (confounding factors separated such as males and females)
What are the possible ways to blind a study?
Open-everyone knows everything
Single blind-patient doesn’t know
Double blind-patient and investigator don’t know
Double dummy-when two physically different treatments compared
Triple blind-someone fucks up and nobody ever knows who got what
What are the possible comparison groups for a study?
Active, placebo or standard treatment
What are the different active comparison groups?
Dose control (RDCT)- multiple doses compared Concentration control (RCCT)- used to reduce the influence of differing pharmacokinetics in individuals. Concentration is individualised to target concentrations. Biomarker control (RBCT)- subjects randomised to a target biomarker level and the dose is adjusted to reach target biomarker
What are the two types of standard treatment comparison groups?
Non-inferiority-this drug is no worse than the drug we already use
Add on-look what happens when we add our treatment on to the standard one
What are the three varieties of sequence of drug delivery?
Parallel, crossover, titration (forced or flexible)
What is a parallel sequence?
Different treatments assigned to different groups of subjects. Good for does the drug work but not good for learning about what dose is needed for certain effects
What is a crossover sequence?
Uses two or more treatments in each subject allowing individual dose response curves to be observed. Good for determining dose response. Bad because there may be treatment carry over effects and multiple treatments there is a higher drop out rate
What is a titration sequence?
Fixed sequence of doses (forced)
Starting with a low dose and only increased if desired response not reached (flexible)
What are the two analysis perspectives?
Intention to treat:”use effectiveness” only considers treatment assignment so has underestimation bias
As treated: “method effectiveness” takes into account what the patient actually took for treatment so is better
