L36 Clinical Trials LA

Question 1

Define a Clinical Trial

Answer 1

• A carefully and ethically designed experiment

- Aimed to answer a precisely framed question

Question 2

What is the purpose of a clinical trial

Answer 2

• To assess the effectiveness and safety of a new drug

Question 3

What is the intended outcome of a clinical trial

Answer 3

• Positive → superior drug to standard treatment
• Non-inferior → equivalent to standard treatment
• Inconclusive → unclear → neither superior nor non-inferior
• Negative → inferior to standard treatment

Question 4

Define in very simple terms:

• Placebo
• Randomise
• Blinding
• Protocol

Answer 4

Placebo = Inert, dummy pill 
Randomise = Allocation to active/dummy treatment by chance
Blinding = One or more parties are unaware of the treatment being given
Protocol = Written document describing the study in detail

Question 5

what is an investigator?

Answer 5

a health care professional responsible for the conduct of the trial at the site

Question 6

what is a QP?

Answer 6

a member of the RPS responsible for the release of investigational medicinal products

Question 7

Give an overview of preclinical animal testing

Answer 7

• testing is on various animal species based on similarities to humans
• Species used based on relevance to humans e.g. beagles for beta-2 agonist drugs
• BUT this is a prediction => animals =/= humans. Prediction may be wrong

Question 8

what is the purpose of animal testing

Answer 8

its done to predict the efficacy of drug candidates -> ADME, PK, PD

predict the toxicity of drug candidates

Question 9

discuss phase 0 of clinical trials.

Answer 9

Involved micro dosing in humans, much lower than phase 1 subtherapeutic doses.

Only PK data collected -> determinant factor for further development stages.

No safety of efficacy data is collected. (no placebo used)

10-15 Healthy volunteers in total

Question 10

discuss phase 1 of clinical trials

Answer 10

initial exposure into man “First-in-man” Healthy male volunteers preferred.

Only exception is cancer patients for cancer drugs.

n=100 => not statistically powered

Performed at a single site -> either in hospitals or by clinicians or in research facilities.

purpose is to determine safety and tolerance and establish human PK and PD.

Placebo is used as a comparator

Question 11

discuss phase 2 clinical trials

Answer 11

initial assessment in the narrowly defined population. e.g COPD at a specific stage.

n= 100-300 => statistically powered.

Double blinded + randomised + placebo controlled study

Conducted in a single hospital by clinicians.

There are two phases 2a and 2b

Question 12

What is phase 2a of clinical trials purpose

Answer 12

2a is to determine the drugs efficacy. It is compared to market leaders.

Question 13

What is phase 2b of clinical trials

Answer 13

Only done if phase 2a passes.

Determining the effective dose range and safety and tolerance.

Question 14

Discuss phase 3 clinical trials

Answer 14

collection of data from a more varied population. confirmation of effective dose range of phase 2.

n= 1000-5000 -> statistically powered.

double blinded + randomised + placebo controlled study and maybe active comparator.

large multinational trials.

Purpose is to provide data on overall benefits vs risks of a drug candidate

subjected to regulatory agencies.

required for application of marketing approval -> Market entry.

Question 15

Discuss phase 4 clinical trials

Answer 15

post marketing surveillance -> an continuous process.

Involves exposure of drug to wider population variables -> provides more safety information.

purpose is to determine drug interactions, adverse events or possible new indications