Clinical Trial Design Flashcards
Why are clinical trials important?
Provide evidence
List some problems with Observational Studies
Replication of observational studies is difficult due to bias/ different criteria.
Causation vs correlation
Who regulates clinical trials?>
MHRA
What do the MHRA test for?
Efficacy- compared with placebo and compared with another drug
Safety
Describe volunteer studies phase 1
Clinical pharmacology in normal volunteers generating pharmacokinetic, metabolic and pharmacodynamic data.
How many volunteers are involved in phase 1?
Approx 100
Describe volunteer studies phase 2.
Clinical investigation to confirm kinetics and dynamics in patients (who may have renal/liver/GI absorption problems)
How many volunteers are involved in phase 2?
Approx 500
What does phase 2 allow for?
Provides some evidence of efficacy and identifies a likely dosage range
Describe phase 3 of clinical development.
Formal therapeutic trials where efficacy will be established and evidence of safety obtained
How many volunteers are involved in phase 3?
Approx 1000 - 10000
Describe phase 4 of clinical development.
Post-marketing surveillance to produce evidence of long term safety
Who mioght be involved for phase 4?
May involve tens or hundreds of thousands of patients world wide
Define pilot studies,
Not to estimate outcome, but to test study design
Describe what is meant by double blind.
patient/doctor blinded
Describe what is meant by single blind.
Patient blinded
Describe Randomised Control Clinical Trial
Patients assigned at random to either treatment(s) or control
List some disadvantages of Randomised Control Clinical Trial
Subjects may not represent general patient population
Recruitment
Acceptability of Randomization Process
Administrative Complexity (randomisation methods etc)
Give some examples of commonly used phase 3 trial designs.
Parallel
Withdrawal
Group/Cluster
Randomized Consent
Cross Over
Factorial
Large Simple
Equivalence/Non-inferiority
Sequential
What does a superiority design show?
Show that new treatment is better than the control or standard (maybe a placebo)
What does an inferior design show?
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)
How would you design a clinical trial?
Hypothesis
Endpoints
Number of subjects?
Safety endpoints?
List some possible end points
Death
No of hospital admissions
Lowering of blood pressure
List some ethics which must be considered.
Consent
Ethics committee
Placebos
Children
Study design
‘Policing’ studies
MHRA/CSM/EU
Insurance
The Law
Overall, why do we need clinical trials?
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
What is P > 0.05 ?
P > 0.05 is the probability that the null hypothesis is true.
Usually taken as significant
