Clinical trial design

Question 1

Discuss the uses of a clinical study. 


Answer 1

• Does it work?
• What dose is therapeutic?
• What dose is toxic?
• Is it safe?
• Is it necessary? Compare to industry standard

Tests efficacy and safety of a potential new drug

Question 2

Discuss the basic considerations involved in trial design. 


Answer 2

What controls are needed
Define clinical endpoints
Hypothesis
Number of subjects required
Choice of subjects e.g. age, race, gender
Safety endpoints
Exclusion and selection criteria

Question 3

Discuss the importance of statistical power

Answer 3

Tells if there is a significant effect, not just by chance

p<0.05 usually taken as significance, P<0.001 very significant

Question 4

Give a famous example of a cohort study

Answer 4

Tuskegee Study of Untreated Syphilis (1932 to 1972)

Question 5

What are the different stages in drug development?

Answer 5

• Drug discovery – discovery of new candidate medications
• Phase I volunteer studies - clinical pharmacology in normal volunteers generating pharmacokinetic, metabolic and pharmacodynamic data.
• Phase II development - Clinical investigation to confirm kinetics and dynamics in patients with ailment
• Phase III clinical development - Formal therapeutic trials where efficacy will be established and evidence of safety obtained
• Phase IV surveillance - Post-marketing surveillance to produce evidence of long term safety

Question 6

What is a double bind clinical trial?

Answer 6

Double blind: neither patient or doctor knows what drug the patient is on

Question 7

Whats a single blind clinical trial?

Answer 7

Single blind: patient doesn’t know what they’re on

Question 8

Whats a prospective clinical trial?

Answer 8

– Prospective: watches for outcomes, such as the development of a disease, during the study and relates it to other factors such as a suspected risk or protection factor.

Question 9

Whats a retrospective clinical trial?

Answer 9

– Retrospective: data is collected from case records after treatment is given

Question 10

Whats a cross over clinical trial?

Answer 10

– Cross-over design: patients take both treatments, new trial drug and previously licensed drug, one after the other following a wash out period

Question 11

What are some disadvantages of randomised control clinical trials?

Answer 11

• Generalizable Results?
o Subjects may not represent general patient population
o Tend to be better at complying
• Recruitment
o Twice as many new patients needed for the study
• Acceptability of Randomization Process
o Some physicians will refuse (PFO closure)
o Some patients will refuse (want treatment)
• Administrative complexity (randomisation methods)

Question 12

Whats the difference between superiority and non-superiority trials?

Answer 12

Superiority Design: Shows that new treatment:
o Is better than the control or standard (maybe a placebo)

Non-inferiority: Show that the new treatment:
o Is not worse that the standard by more than some margin
o Would have beaten placebo if it had been included (regulatory