Randomised trials and other evidence

Question 1

To distinguish intention-to-treat and on-treatment analyses.

Answer 1

ITT = ANALYSED BASED ON THE GROUP ALLOCATED, NOT ON WHO ACTUALLY TOOK THAT TREATMENT
OT = WHO ACTUALLY TOOK THE TREATMENT

Question 2

Why are new treatments generally tested in randomised controlled trials?

Answer 2

To determine whether they are better than the existing treatments. To show small effects, studies must avoid bias.

Question 3

What are single and double blinding?

Answer 3

Single blind – the participant does not know if they are in the treated or control group (a placebo is given)
Double blind – neither the participant nor the doctor
knows

Question 4

What bias does blinding prevent?

Answer 4

Observer bias - avoids knowledge of treatment influencing:

• patient’s assessment of response
• doctor’s assessment of response
• patient’s decision to withdraw from trial
• doctor’s decision to withdraw patient from trial

Question 5

What is a cross-over RCT?

Answer 5

Allocate half to group A (treatment group) and the other half to group B (control group). Group A has a treatment period, then control period and group B has a control period, then the treatment period.

Question 6

When are parallel RCTs done?

Answer 6

When effect of treatment is curative e.g. – antibiotics for infection, chemotherapy for cancer

Question 7

When are cross-over RCTs done?

Answer 7

When treatment is reversible – for example, analgesics for chronic pain (e.g. osteoarthritis), inhaler for asthma, drug to lower blood pressure

Question 8

Advantages of cross-over trials over parallel group trials? (4)

Answer 8

Fewer participants
Avoids “scores” for quantifying subjective symptoms (e.g. pain)
Compares 2 drugs in the same individual (not one drug in person A and one in person B)
Can omit non-compliers in the analysis (because each participant is his/her own control)

Question 9

Name two interventional trial study designs.

Answer 9

Parallel group randomised trial

Cross-over randomised trial

Question 10

Name two observational trial study designs.

Answer 10

Cohort (or prospective) study
Case control (or retrospective) study

Question 11

Describe a cohort study.

Answer 11

Take a group of people
Categorise each according to the exposure (e.g. smoker or non-smoker)
Follow them up
Identify those who develop the disease

Question 12

Benefits of cohort studies. (2)

Answer 12

Can generate useful summaries

Rigorous

Question 13

Describe a case control study.

Answer 13

Take samples of people who have the disease (cases) and who do not (controls)
Determine whether the cases are more likely to have been exposed

Question 14

Disadvantages of cohort studies. (4)

Answer 14

Long duration (many years)
Large size (thousands of individuals)
Need large numbers (tens of thousands)
Susceptible to confounding

Question 15

Advantages of case control studies. (2)

Answer 15

Quick

Need small numbers

Question 16

Disadvantages of case control studies. (2)

Answer 16

Susceptible to bias, especially recall bias

Susceptible to confounding

Question 17

Advantages of RCTs. (1)

Answer 17

They eliminate bias

Question 18

Disadvantages of RCTs. (4)

Answer 18

• Expensive
• Maintaining high compliance difficult
• They seldom exceed five years in duration (not well suited to long term effects)
• Unsuited to behavioural exposures (smokers v non smokers, take v not take the contraceptive pill)

Question 19

What is the most appropriate study design to answer the question?
- Does vitamin D reduce the risk of hip fracture in elderly people?

Answer 19

Parallel group trial

Question 20

What is the most appropriate study design to answer the question?
- Does the measles/mumps/rubella vaccine cause autism?

Answer 20

Case-control study

Question 21

What is the most appropriate study design to answer the question?
- Does the contraceptive pill cause breast cancer?

Answer 21

Cohort study

Question 22

What is the most appropriate study design to answer the question?
- Do margarines with added sterols or stanols lower serum cholesterol?

Answer 22

Cross-over trial

Question 23

What is the most appropriate study design to answer the question?
- Does mental stress increase a person’s risk of myocardial infarction?

Answer 23

Parallel group - counselling v no counselling after MI

Cohort study - level of mental stress measured at outset

Question 24

What is the most appropriate study design to answer the question?
- Does driving my car after drinking a pint of beer
increase my chance of an accident?

Answer 24

Case control study

Cross-over trial (with surrogate endpoint)

Question 25

What is the meaning of P=0.05?

Answer 25

There is a 5% probability that this result (or one more extreme) could have arisen by chance if there was no genuine association at all.

Question 26

What does P<5% or <0.05 mean?

Answer 26

STATISTICALLY SIGNIFICANT
It does not mean the association is 95% likely to be causal. It does not exclude bias. It only applies to a study testing a prior hypothesis.

Question 27

What is a 95% confidence interval?

Answer 27

We are 95% certain that the “true” answer lies within the specified limits

Question 28

The larger the number treated, the _______ the confidence interval.

Answer 28

Narrower

Question 29

Do different causes of a disease usually interact additively or multiplicatively.?

Answer 29

Multiplicatively