Randomised Contol Trials

Question 0

What is a clinical trial?

Answer 0

Planned experiment involving patients which can be experimental or observational

Question 1

Define and describe the purpose of clinical trials

Answer 1

Determine most appropriate treatment method for future patients with given medical condition
Provide reliable evidence on treatment efficacy and safety

Question 2

Explain the disadvantages of non randomised clinical trials

Answer 2

May have known or unknown confounders present in the study

Question 3

Outline the steps involved in a Randomised Control Trial (RCT)

Answer 3

Identify a source of eligible patients
Invite eligible patients to the trial
Allocate participants fairly to either treatment
Follow up participants in identical ways
Minimise losses to follow up and maximise compliance with treatments
Analyse data and obtain results

Question 4

Discuss the advantages of ‘random allocation’ and ‘blinding’ to minimise confounding and bias in the estimation of treatment effects

Answer 4

Random allocation - remove confounders, both groups are as similar as possible
Blinding - removes selection bias

Question 5

Describe the ‘placebo effect’ and what a ‘placebo’ is, and how a ‘placebo’ addresses the ‘placebo effect’

Answer 5

Placebo - inert substance which looks, tastes and is packaged identically to the normal drug
Placebos are used to remove placebo effect from trial

Question 6

Describe suitable outcome measures for clinical trials

Answer 6

Use relevant, objective, sensitive, reliable, valid and practical outcome measure that are defined before the start of the trial
Assessor should be blind to treatment status

Question 7

Discuss how to deal with ‘losses to follow up’ and ‘non-compliance’

Answer 7

Losses to follow up - opting out can be reduced if sufficient and clear information about what will be involved is given to patients before they agree to participate and the follow up schedule is practical and not too onerous
Non-compliance - can be reduced by clear, simple instructions and with checks such as count tablets, blood and urine tests

Question 8

Differentiate between ‘explanatory’ and ‘pragmatic’ trials and be able to explain the meaning of the term ‘intention-to-treat’ analysis

Answer 8

Explanatory (as treated analysis) - includes only those who completed follow up and complied to both treatments, compares physiological difference in treatment effects. Prone to selection bias/confounding, not as realistic.
Pragmatic (intention-to-treat analysis) - includes everyone (compilers and non-compliers), preserves randomisation, representative of routine clinical practice, more realistic size of effects.

Question 9

Discuss the ethical principles involved in medical research involving human subjects

Answer 9

Beneficence - do good
Non-maleficence - do no harm
Autonomy of patient (valid consent) 
Justice (fair allocation) 
Clinical equipoise

Question 10

Describe the issues that should be considered for a clinical trial to be regarded as ethical

Answer 10

Clinical equipoise
Scientifically robust
Valid consent
Ethical recruitment (doesn’t exclude anyone, from population where treatments will be provided)