Randomized controlled trials

Question 1

What is done in a phase 1 trial?

Answer 1

• Clinical pharmacology and toxicity
• Determine if the drug can safely be given to humans, and what dosage levels can be given without causing serious side effects.
• Usually conducted on volunteers

–may involve anything from 20 to 80 normal volunteers and patients.

• Drug metabolism and bioavailability.
• If drug proves safe in healthy volunteers, phase 1 trials will next be run in patients.

Question 2

What is done in a phase 2 trial?

Answer 2

•Initial clinical investigation for treatment effect

–Small number of closely-monitored patients receive the drug.

–Safety and effectiveness evaluated

–Will involve 100-200 patients.

Question 3

What is done in a phase 3 trial?

Answer 3

• Controlled evaluation of treatment
• Compares the new treatment to the current ‘best practice’ treatment(s) in a substantial number of patients.
• Often simply called clinical trials or controlled clinical trials.

Question 4

What is the 4th phase of trials?

Answer 4

• postmarketing surveillance
• Monitoring of adverse reactions and long-term consequences of use
• refine prescribing indications by documenting rare complications, subgroups of patients with poor response.Why do we use controlled trials?

Question 5

why not use an ‘open’ trial? (open means blinding isn’t used - people know what treatment they are recieving/giving)

Answer 5

•Uses of open trials

–monitored use of new treatment

–established safety, acceptability

–response may be due to

»placebo effect

»Hawthorn effect

»selection bias- doctor cannot select the particular patient for the trial

»observer bias (esp when response subjective)- you cannot say that ‘oh this result isn’t because of the drug, we won’t report that ‘

–response cannot be measured against an accepted standard

Question 6

what is ethical equipoise?

Answer 6

there must be genuine uncertainty as to whether the new treatment is better or not

Question 7

generally clinical trials have low internal or low external validity?

Answer 7

generally they have low external validity - they are designed to show that A is better than B - so a risk of say 7.5 is not a risk relative to the world risk, it’s risk in comparison to another factor.