Randomised Control Trials

Question 1

What is an uncontrolled trial?

Answer 1

everyone gets the treatment

Question 2

What is a controlled trial?

Answer 2

treated group compared with untreated group

Question 3

What are the types of controls?

Answer 3

• geographic (patients with same disorder seen at another hospital without new intervention)
• historical (patients with same disorder seen in past before use of new intervention)
• randomised (allocations to group determined by chance)

Question 4

What is the benefits of randomised controls?

Answer 4

Proper randomisation helps ensure groups receiving treatment A is similar to B

• avoids selection bias
• happens after groups determined eligible

Question 5

What are the 2 types of blinding?

Answer 5

• single blind when patients don’t know what treatment they are on
• double blind when observers and patients do not know

Question 6

What is a parallel group controlled trial?

Answer 6

When effect of a treatment is not reversible

- randomise individuals into 2 groups (treatment A and B), then record outcome for each

Question 7

What is a crossover controlled trial?

Answer 7

When effect of treatment is reversible
- randomise individuals into 2 groups (treatment A and B), record outcome of each, put on other treatment then record outcome

Question 8

What are the advantages of crossover trials?

Answer 8

• each patient has own control
• small sample size to get same observation numbers
• better for subjective measurements

Question 9

What are the disadvantages of crossover trials?

Answer 9

• more time consuming

- carry over effects of one treatment (wash out period prevents this)

Question 10

What are cluster randomised trials?

Answer 10

randomise pre-existing groups to 1 of 2 treatments

• avoids contamination
• enhances compliance

Question 11

What are the phases of developing and evaluating a new drug?

Answer 11

Preclinical

Phase 0-4

Question 12

What is the preclinical phase?

Answer 12

Non human study

• in vitro and in vivo animal experiments
• preliminary efficacy/toxicity/pharmacokinetic info

Question 13

What is Phase 0?

Answer 13

First in-human trials

- small no. of subjects given sub therapeutic dose of drug to determine pharmacodynamics and kinetics

Question 14

What is Phase 1?

Answer 14

Screening for safety

• test on healthy volunteers for dose ranging
• determine if safe to check for efficacy

Question 15

What is Phase 2?

Answer 15

Assess efficacy and safety

• can it have a therapeutic effect
• design as case series or randomised controlled trial

Question 16

What is Phase 3?

Answer 16

Assess efficacy and safety

- randomised controlled trial on large no. of patients determining therapeutic effect

Question 17

What is Phase 4?

Answer 17

Post marketing surveillance

- safety surveillance

Question 18

What is the advantage of registering clinical trials prospectively?

Answer 18

• assist planning new trials
• avoid unnecessary research duplications
• encourage research group collaboration

Question 19

What is the relative risk?

Answer 19

risk of death in treatment group/risk of death in control group

risk of death in treatment group = no. of deaths in treatment group/no. of patients in treatment group

• same for risk of death in control group
• if no effect of treatment RR=1
• if RR is 0.86, treatment makes it 14% less likely to have a certain disease

Question 20

What is intention to treat?

Answer 20

Comparison of all subjects based on treatment group assigned, regardless of compliance
- poor compliance = reduced ability to detect treatment difference

Question 21

What is on treatment?

Answer 21

Comparison of subjects who took treatment

Question 22

How is compliance maximised?

Answer 22

• selection of patients (not too ill)
• double blind design
• run in period where all get treatment

Question 23

What is number needed to treat?

Answer 23

• average number of patients who need to treated to prevent additional bad outcome

Question 24

What is absolute difference in risk?

Answer 24

= risk of death (control) - risk of death (treatment)

Question 25

Why is it bad if the sample size is too small?

Answer 25

Study does not have enough power

Question 26

What is meta-analysis?

Answer 26

Purpose to bring together all evidence to more powerfully estimate effect size

Question 27

What are the issues in meta-analyses?

Answer 27

• heterogeneity (variation in study results)

- publication bias (studies with more favourable results more likely to be published)