21

Question 1

Three essential elements to a RCT

Answer 1

Randomised:
Participants randomly allocated to groups

Controlled:
There is a control (comparison) group

Trial:
Testing effect of treatments/interventions

Question 2

Randomisation

Answer 2

Question 3

Cohort v RCT

Answer 3

Cohort
Ascertain exposure status, then follow-up to find out outcome(s)
Observational study

RCT
Randomly assign exposure, then follow-up to find out outcome(s)
Intervention (experimental) study

Question 4

What is Randomisation

Answer 4

Participants are randomly allocated to groups

Question 5

Why randomise?

Answer 5

“ Random allocation (also called randomisation) of individuals in the study groups is the only way to ensure that all of the groups are as similar as possible (i.e. exchangeable) at the start of the study”

Question 6

Randomisation / Random Allocation
- how does it prevent confounding

Answer 6

• is enough people randomly allocated, should have the same proportion of the confounded in each group
• this applied to known and unknown con founders
• successful randomisation means confounding is an unlikely reason for differences in outcomes between groups

Question 7

How do we know if randomisation has been successful?

Answer 7

Question 8

Randomisation / random allocation ≠ random selection

Answer 8

Question 9

Variants e.g. cluster randomisation
- RCT

Answer 9

It may be difficult to randomise individuals – randomise groups (clusters) of participants instead e.g. GP practices, hospital wards, schools

Question 10

Preserving the benefits of randomisation - different types of analysis that allows this / dont allow this

Answer 10

Intention-to-treat analysis
- analyse as randomised
- preserves the benefits of randomisation (- regardless whether or not they stuck to that group)

Pre-protocol analysis
- analyse as treated (- treated according to what they actually did )
- tends to be more appropriate for efficacy trials (does this medication work if u take it)
- introduces confounding

Question 11

Potential sources of bias in RCTs

Answer 11

• Lack of concealment of allocation
• Lack of blinding
• Loss to follow-up
• Non-adherence

Question 12

Concealment of allocation
- what does this mean in preventing bias in a RCT

Answer 12

Important that allocation sequence is concealed and unpredictable

Otherwise could game the system and introduce bias

Question 13

Blinding in RCT

Answer 13

How might knowing which group/arm of the study a participant was in affect:
A research team member
- delivering the intervention?
- assessing the outcome?
- analysing the data?

The participant?

State who is blinded (rather than ‘single’ or ‘double’ blinded)

Question 14

What is blinding ?

Answer 14

Blinding is an important way to protect against bias

Question 15

Why blinding might be challenging to active in practice?

Answer 15

But can be challenging to achieve in practice…
• It can be obvious which group participant is in:
e.g. you might be able to get a matching placebo pill but what about surgical or physiotherapy treatment?
• Safety concerns

Question 16

Non-adherence

Answer 16

Participants don’t always do what you ask them to do

Question 17

Strength of RCTs

Answer 17

Randomisation (if done well) maximises the likelihood that potential confounders are evenly distributed between groups

Best way to test an intervention

Can calculate incidence ( so can calculate relative risk and risk difference)

Temporal sequence is known

Strongest design for determining causation

Question 18

Limitations of RCTS

Answer 18

• Not all exposures are suitable to be randomly allocated
• Need to have clinical equipoise

Question 19

Not all exposures are suitable to be randomly allocated
- why

Answer 19

Some exposures cannot be randomly allocated:
• Low birth weight

Some exposures are very difficult to randomly allocate:
• Long-term behavioural changes
• Common exposures in the community (how do you avoid them?)

Some exposures should not be randomly allocated:
• Known harmful toxins or procedures

Question 20

What is clinical equipoise

Answer 20

Genuine uncertainty about benefit or harm of the intervention

Question 21

Why do we need to have clinical equipoise

Answer 21

Unethical to:
• Give a known harmful intervention to people
• Give interventions known to be less effective than current
treatments
• Waste resources and risk people’s well-being if you already
know the answer

Question 22

Limitations of RCT

Answer 22

• Can be difficult to achieve blinding
• Potential for loss-to-follow up and non-adherence
• Resource intensive

Highly selective
Often a highly selected group of people involved in an RCT
• They need to meet all the inclusion criteria
• AND be willing to participate

This can affect generalisability (sometimes called external validity) – do the findings apply to other people?