Randomised Controlled Trials

Question 1

What are the essential elements of randomised controlled trials (RCTs)?

Answer 1

• Randomised: participants randomly allocated to groups (of being assigned the intervention or being the control)
• Controlled: always have a comparison (control) group
• Trial: testing effect of treatments/interventions
  - Involves two ‘arms’ (intervention and control arms)

Question 2

What is confounding?

Answer 2

Confounding is when people are not comparable between the groups (ie. one group has more people over 50, or more males than females).
- To try and get rid of confounding we go to the effort of randomising the groups and using large numbers of people
- This is so that when we get the result, we know it is due to the intervention, and not any other factors within the group

Question 3

Randomisation/random allocation vs. random selection

Answer 3

Randomisation/random allocation:
- Equal chance for each participant to be in either group (getting people who are already in the study and randomly allocating them into intervention or comparison group)
- If enough people are randomised, should have the same proportion of confounder in each group
- This applies to known and unknown confounders
- Successful randomisation means confounding is an unlikely reason for differences in outcomes between groups
- Can tell if randomisation worked by looking at the baseline characteristics (gender, age, ect)

Random selection:
- Randomly selecting people to come into the study

Question 4

Are there variants of randomisation and different ways of doing it? If so, what are they?

Answer 4

Yes,
EG. Cluster, stratified, block

Could be that you need to randomise groups rather than individuals

Question 5

How do you protect randomisation?

Answer 5

Large numbers:
- Randomisation more likely to lead to balanced groups with large numbers of participants
Concealment of allocation:
- Important that allocation sequence is concealed and unpredictable so that people can’t game the system and introduce bias
Intention-to-treat analysis:
- Analyse as randomised (ie. if they are in the intervention group, analyse the results with them in the intervention group, even if they didn’t take the intervention/medication properly and are looking more like the comparison group)
- Pre-protocol is another way people can be analysed and this is analyse as treated (ie. if they were originally in the intervention group but then didn’t take it as prescribed, analyse them in the comparison group). This way is generally frowned upon, but it has its place

Question 6

What are the potential sources of bias in a RCT?

Answer 6

Blinding:
- Means keeping them in the dark so that they are not treated any differently whether they are in the control or the intervention group
- Can be challenging to achieve in practice because:
- can be obvious which group participant is in
- safety concerns
Loss to follow-up:
- Similar problem as cohort studies (people move away, die, don’t want to participate anymore)
Non-adherence:
Participants don’t do what they’re supposed to do (this can include doing what the other group is doing - getting the intervention [bc say they heard good things from their friend in the intervention group] or getting what controls do)

Question 7

What are some advantages and important issues of RCTs?

Answer 7

Advantages:
- Best way to evaluate an intervention (due to randomisation)
- Can calculate incidence (and therefore RR and RD)
- Strongest design for demonstrating a causal assosciation (but only if done correctly/well)
Ethical issues:
- Need to have clinical equipoise (genuine uncertainty about benefit ogham of intervention)
Practical issues:
- Resource intensive (randomisation more likely to be successful with large numbers, same issues as prospective cohort studies)
Also:
- Exposure needs to be modifiable
- Highly selective (often a very select group of people included and can affect generalisability)

Question 8

What is the heirachy of evidence

Answer 8

From worst to best, the ranking of the study types

• Ecological
• Cross-sectional
• Case-control
• Cohort
• RCT

BUT… this is only a guide. A study done well is always better than a study done poorly

Question 9

Cohort vs. randomised controlled trials (RCTs)

Answer 9

Cohort:
Ascertain exposure status, then find out outcome(s)

Randomised Controlled Trials:
Randomly assign exposures status, then find out outcome(s)