Clinical Trial Design

Question 1

Why are clinical trials important?

Answer 1

Provide evidence

Question 2

List some problems with Observational Studies

Answer 2

Replication of observational studies is difficult due to bias/ different criteria.
Causation vs correlation

Question 3

Who regulates clinical trials?>

Answer 3

MHRA

Question 4

What do the MHRA test for?

Answer 4

Efficacy- compared with placebo and compared with another drug
Safety

Question 5

Describe volunteer studies phase 1

Answer 5

Clinical pharmacology in normal volunteers generating pharmacokinetic, metabolic and pharmacodynamic data.

Question 6

How many volunteers are involved in phase 1?

Answer 6

Approx 100

Question 7

Describe volunteer studies phase 2.

Answer 7

Clinical investigation to confirm kinetics and dynamics in patients (who may have renal/liver/GI absorption problems)

Question 8

How many volunteers are involved in phase 2?

Answer 8

Approx 500

Question 9

What does phase 2 allow for?

Answer 9

Provides some evidence of efficacy and identifies a likely dosage range

Question 10

Describe phase 3 of clinical development.

Answer 10

Formal therapeutic trials where efficacy will be established and evidence of safety obtained

Question 11

How many volunteers are involved in phase 3?

Answer 11

Approx 1000 - 10000

Question 12

Describe phase 4 of clinical development.

Answer 12

Post-marketing surveillance to produce evidence of long term safety

Question 13

Who mioght be involved for phase 4?

Answer 13

May involve tens or hundreds of thousands of patients world wide

Question 14

Define pilot studies,

Answer 14

Not to estimate outcome, but to test study design

Question 15

Describe what is meant by double blind.

Answer 15

patient/doctor blinded

Question 16

Describe what is meant by single blind.

Answer 16

Patient blinded

Question 17

Describe Randomised Control Clinical Trial

Answer 17

Patients assigned at random to either treatment(s) or control

Question 18

List some disadvantages of Randomised Control Clinical Trial

Answer 18

Subjects may not represent general patient population
Recruitment
Acceptability of Randomization Process
Administrative Complexity (randomisation methods etc)

Question 19

Give some examples of commonly used phase 3 trial designs.

Answer 19

Parallel
Withdrawal
Group/Cluster
Randomized Consent
Cross Over
Factorial
Large Simple
Equivalence/Non-inferiority
Sequential

Question 20

What does a superiority design show?

Answer 20

Show that new treatment is better than the control or standard (maybe a placebo)

Question 21

What does an inferior design show?

Answer 21

Show that the new treatment-
-Is not worse that the standard by more than some margin
-Would have beaten placebo if a placebo arm had been included (regulatory)

Question 22

How would you design a clinical trial?

Answer 22

Hypothesis
Endpoints
Number of subjects?
Safety endpoints?

Question 23

List some possible end points

Answer 23

Death
No of hospital admissions
Lowering of blood pressure

Question 24

List some ethics which must be considered.

Answer 24

Consent
Ethics committee
Placebos
Children
Study design
‘Policing’ studies
MHRA/CSM/EU
Insurance
The Law

Question 25

Overall, why do we need clinical trials?

Answer 25

Patients may get better or worse despite drug therapy

There may be a placebo effect

Clinical practice needs to be ‘evidence based’

Drug companies have competing interests

Protect the public

Provide evidence to help rational prescribing

Question 26

What is P > 0.05 ?

Answer 26

P > 0.05 is the probability that the null hypothesis is true.

Usually taken as significant