L8 - clinical trial and study design

Question 1

What do clinical trial investigate?

Answer 1

Mostly treatment options and treatment efficacy

Question 2

What are the advantages of clinical trials over observational studies?

Answer 2

Reduce effects of small sample size, recall bias, lack of impartiality, cause/association, patient selection bias, confounding, lack of precision

Question 3

Define bias

Answer 3

A systematic error in design, conduct, analysis of a study which produces an incorrect estimate of a treatment effect/an exposure’s effect on an outcome

Question 4

Define confounding

Answer 4

When a variable/factor is related to both the study variable and the outcome, so the effect of the study variable on the outcome is distorted

Question 5

What is a clinical trial?

Answer 5

A planned experiment in humans designed to measure the effectiveness of an intervention: a new drug, a surgical procedure, vaccine, complementary therapy

Question 6

What are the main features of a clinical trial?

Answer 6

Define intervention, define comparator, define inclusion/exclusion criteria, randomise the source population into control and intervention groups

Question 7

How to combat selection bias and imbalance between the control and intervention groups in an RCT?

Answer 7

Computer generated random numbers, block randomisation, stratification, minimisation adaptive stratification

Question 8

How could measurement bias be reduced?

Answer 8

Blinding, clear endpoint selection, minimise loss to follow up, record side effects of the treatment in all patients, take note of the intention to treat and whether the treatment is tolerable

Question 9

What are the phases of clinical trials?

Answer 9

1,2,3,4

Question 10

What occurs in the stage 1 trials?

Answer 10

Testing safety, small number of people, healthy volunteers

Question 11

What occurs in stage 2 trials?

Answer 11

Testing efficacy, continue to look at safety, hundreds/10s of people with the condition

Question 12

What occurs in stage 3 trials?

Answer 12

Comparison with current standard of care/placebo, looks at how well the treatment works in real life (effectiveness), monitors side effects, several thousand patients

Question 13

What and when do stage 4 trials occur?

Answer 13

After drug has been marketed

Measures side effects in various populations, identifies even rare side effects

Question 14

What should length of follow up be?

Answer 14

Long-term

Question 15

How do you judge whether the sample size is large enough?

Answer 15

Prospective power calculations: a=0.05, chance of obtaining a false positive (T1 error) and b = 0.1-0.2 chance of obtaining a false negative (T2 error)

Question 16

What is the equation for number needed to treat?

Answer 16

1/absolute risk reduction

Question 17

How is reporting bias reduced and managed?

Answer 17

Sub-groups within the experiment should be large and few so as not to increase chance effect, selective reporting should be reduced through trial registration and the CONSORT statement, results should justify conclusions of the study

Question 18

What processes are there to ensure trials are ethical?

Answer 18

regulation aims, reviewing, registration of the trial, independent scientific review, research ethics committee, government and international guidance, data monitoring committee, informed consent from participants