Study Designs - Lecture Twenty-One

Question 1

Only thing better than a randomised controlled trial?

Answer 1

Having more than one randomised controlled trial

Question 2

Observational analytic studies

Answer 2

Cross-sectional
Cohort
Ecological
Case-control

Question 3

Intervention analytic studies

Answer 3

Randomised controlled trials

Non-randomised controlled trials

Question 4

Randomised

Answer 4

Participants randomly allocated to groups

Question 5

Controlled

Answer 5

There’s a comparison (control) group

Question 6

Trial

Answer 6

Testing effect of treatments/interventions

Question 7

What is the exposure determined by in observational studies?

Answer 7

Luck, environment, by people themselves

Question 8

Why do we randomise?

Answer 8

People who decide to take a treatment are often different to those who don’t e.g. age, sex, health risks, views of the health professions treating them, health beliefs and habits

Question 9

Random allocation

Answer 9

Each participant has an equal chance of being in either group, if enough people are randomised then both known and unknown confounders should be balanced

Question 10

Variants of randomisation

Answer 10

Cluster

Stratified or Block Randomisation

Question 11

Cluster

Answer 11

Entire practices are randomised to treatment or control. All participants in each practice get the same intervention and GPs don’t have to do different things for different patients.

Question 12

Stratified or Block Randomisation

Answer 12

Participants are randomised to treatment or placebo in blocks (or strata) at each hospital. Differences between hospitals will be balanced between treatment and control groups

Question 13

Cross-over studies

Answer 13

Each person gets both treatments - confounding is effectively eliminated, however, this can only be done for long-term conditions and treatments that are not curative

Question 14

How do we preserve the benefits of randomisation

Answer 14

Concealment of allocation

Intention-to-treat

Question 15

Concealment of allocation

Answer 15

Make sure that people can’t cheat and pick the treatment that they prefer, otherwise bias could be introduced

Question 16

Intention-to-treat analysis

Answer 16

Once participants have been randomised, you don’t change the groups

Question 17

Intention-to-treat analysis information

Answer 17

Analyse participants as randomised
Reflects the ‘real-world’: people often don’t take treatments
Difficult if data are missing – you can’t analyse data you don’t have

Question 18

Per-protocol analysis information

Answer 18

Analyse as treated (not necessarily as randomised)
Lose the benefit of randomisation
Can be appropriate for efficacy trials

Question 19

Potential source of bias

Answer 19

Lack of blinding
Loss of follow-up
Non-adherence

Question 20

Lack of blinding

Answer 20

If participants (or researchers) know which treatment they are on, they may act differently

Question 21

Loss of follow-up

Answer 21

If people withdraw because of side effects, we may underestimate the harms of treatment.
Confounding and bias may occur if there is loss to follow-up

Question 22

Non-adherence

Answer 22

If people don’t take the treatment, we will not learn about its true benefits and harms

Question 23

Non-adherence

Answer 23

Participants often don’t do what you ask them to: Some only take some treatment or stop it altogether, some don’t turn up for appointments, or some take alternative treatments (including the intervention or control). If there is too much non-adherence, it is difficult to interpret the study

Question 24

Strengths of randomised controlled trials

Answer 24

The best study design to test an intervention
Well conducted studies should eliminate confounding and bias
You can calculate Incidence, Relative Risks, and Risk Differences
The strongest design for testing cause-and-effect associations

Question 25

Clinical equipoise

Answer 25

Genuine uncertainty about benefit or harm of intervention

Question 26

Unethical to

Answer 26

Give known harmful interventions to people
Give interventions known to be less effective than current treatments
Waste resources and risk harm if we already know the answer

Question 27

Practical issues about randomised controlled trials

Answer 27

Can be very expensive

Often funded by pharmaceutical companies

Question 28

Practical issue: Can be very expensive

Answer 28

May need large numbers of participants
Ensure complete follow-up
Can take a long time

Question 29

Practical issue: Often funded by pharmaceutical companies

Answer 29

Potential for big profits if the drug works

Unlikely to fund studies of cheap treatments with little chance of profit

Question 30

Limitations of randomised controlled trials

Answer 30

Often no representative

Not efficient for rare outcomes