Drug Development and Clinical Trials

Question 1

How long does it take for a drug to get from discovery to market?

Answer 1

10 years
3 million dollars per drug
9/10 tested in humans never reach the market

Question 2

What are the phases of drug development?

Answer 2

Phase 0-predictions for humans
Phase 1-tolerability
Phase 2-effectiveness
Phase 3-Safety
Phase 4-post marketing

Question 3

What is a biomarker?

Answer 3

Readily measurable marker of response

Question 4

What is a surrogate?

Answer 4

Biomarker used for regulatory approval

Question 5

What is the outcome?

Answer 5

How the patient functions/feels/survives

Question 6

What is the difference between learn and confirm in terms of drug development?

Answer 6

Learn-exploration of the unknown and develop hypothesis/model
Confirm-develop confidence and test hypothesis

Question 7

Describe phase 0-predictions for humans

Answer 7

Data from animals
Probable mechanism of action
Likely effective concentrations
Routes of elimination and how it is absorbed

Question 8

Describe phase 1-tolerability

Answer 8

Start with small doses
Increase slowly and stop when adverse effects are noted
Learn about the drugs pharmacokinetics and dynamics

Question 9

Describe phase 2-effectiveness

Answer 9

2A) proof of concept, yes/no decision point

2B) learn dose response curve, learn effective doses, learn target concentration

Question 10

Describe phase 3-safety

Answer 10

Learn adverse effect in target population and confirm effective doses and PK/PD covariates (age, sex, other drugs etc)

Question 11

Describe phase 4-post marketing

Answer 11

Confirm effective doses
Confirm common adverse effects
Learn uncommon adverse effects
Learn "use effectiveness"
Learn pharmacoeconomics

Question 12

What is the definition of an alternative medicine?

Answer 12

Not a medicine that is known to be safe and effective

Question 13

What are the four major elements in the design of a clinical trial?

Answer 13

Assignment
Blinding
Comparison
Sequence

Question 14

What is first come first served assignment and how does it cause bias?

Answer 14

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

Question 15

What is the way to assign patients without bias?

Answer 15

Randomised, balanced (even numbers active and placebo) and stratified (confounding factors separated such as males and females)

Question 16

What are the possible ways to blind a study?

Answer 16

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

Question 17

What are the possible comparison groups for a study?

Answer 17

Active, placebo or standard treatment

Question 18

What are the different active comparison groups?

Answer 18

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

Question 19

What are the two types of standard treatment comparison groups?

Answer 19

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

Question 20

What are the three varieties of sequence of drug delivery?

Answer 20

Parallel, crossover, titration (forced or flexible)

Question 21

What is a parallel sequence?

Answer 21

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

Question 22

What is a crossover sequence?

Answer 22

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

Question 23

What is a titration sequence?

Answer 23

Fixed sequence of doses (forced)

Starting with a low dose and only increased if desired response not reached (flexible)

Question 24

What are the two analysis perspectives?

Answer 24

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