Study Designs and Use of Placebo

Question 1

What does placebo do?

Answer 1

Always produces some effects, physiological and psychological.
If adverse effects are the same in treatment and placebo you can be sure the effect is not due to the drug.

Question 2

Double-blinded

Answer 2

Both investigator and participants unaware of treatment allocation.
Placebo must look/taste/smell/administer exactly the same as active drug.

Question 3

Parallel trial

Answer 3

Each group receives only one of the treatments.
Subjects recruited in parallel into various groups.
Simple -> preferred option for most trials.
But no within-subject comparison and requires large amount of subjects.

Question 4

Cross-over trial

Answer 4

Group administered one treatment, washout period, then administered other period.
Reduces subjects as each individual acts as their own control -> gives within-subject effect.
May be carry-over effects if wash-out not successful which can invalidate results.

Question 5

Sequential groups

Answer 5

Each group receives one of the treatments but subjects are recruited and treated in sequenced.
Prevents any serious adverse effects happening to multiple subjects treated at same time.
Gives confidence that drug was well tolerated in one group before giving higher dose in second group.

Question 6

Latin square design

Answer 6

Crossover design where each group receives each treatment in a different order.
Determines if same effects are seen when doses/placebo administered in a different order.
Cannot be done in phase I studies due to safety -> requires dose escalation to determine adverse effects.

Question 7

Dose finding trials

Answer 7

Administer increasing amount of drug to identify the particular dose which produces a specific response.

Question 8

Cross-over design with dose escalation

Answer 8

Dose 1 given to Group A, if tolerated Dose 2 given to Group B, if tolerated Dose 3 given to Group C, if tolerated Dose 4 given to Group 1.
If 8 volunteers, 6 on active and 2 on placebo.
Placebo is always the same so 6 placebo compared to 6 active.
Reduces participants and givens a within-subject response, but takes longer.

Question 9

Placebo effect

Answer 9

Large effect seen in first few weeks, largely due to expectation of drug,
Effects drops dramatically after a period of time but active drug effect stays.
Longer term studies required to clearly see the difference between placebo and drug.

Question 10

Placebo run-in

Answer 10

All groups given placebo for a time period before giving active drug to counteract initial placebo effect.

Question 11

Adaptive designs

Answer 11

Interim analyses used to consider dose escalation.
Dose 1 responders kept at same level, non-responders pushed up to dose 2.
Gives all subjects a chance to respond due to individual variability.
Only for non-regulatory/exploratory studies.