1. Randomised control trials

Question 1

define the term clinical trial

Answer 1

any form of planned experiment which involves patients and is designed to elucidate the most appropriate method of treatment for future patients with a given medical condition

Question 2

describe the purpose of a clinical trial

Answer 2

to provide reliable evidence of treatment EFFICACY (improves health of a defined group under specific conditions) and SAFETY (does not harm a defined group under specific conditions)

Question 3

name 2 disadvantages of non-randomised clinical trials

Answer 3

Comparison of Ps receiving a new treatment to Ps receiving standard treatment after they have been allocated to either group:

1. ALLOCATION BIAS - by P, clinician or investigator (eg putting all healthier Ps in 1 goup)
2. CONFOUNDING FACTORS - known and unknown

Question 4

how is a randomised control trial different to a non-RCT

Answer 4

participants are allocated to either treatment group randomly - have equal chance of receiving drug or placebo

Question 5

what is the difference between statistical significance and clinical importance when comparing RCT outcomes

Answer 5

• statistical significance: could the observed difference have arisen by chance (look at p value and CIs)?
• clinical importance: how big is the observed difference between the treatment groups?

Question 6

name 3 disadvantages of treatment allocation being open label (not blind)

Answer 6

may bias results of clinical trial, e.g.

1- BEHAVIOUR EFFECT: P may alter their behaviour, other treatment or even expectation of outcome

2- NON-TREATMENT EFFECT: clinician may alter their treatment, care and interest in P

3- MEASUREMENT BIAS: investigator may alter their approach when making measurements and assessing outcomes

Question 7

what is a placebo and the placebo effect

Answer 7

Placebo = inert substance made to appear identical in every way to the active formulation with which it is to be compared, e.g. appearance, taste, dosage regime…

Placebo effect = improvement in a P’s condition due to the feeling that something is done about it

Question 8

what is the difference between explanatory and pragmatic trials

Answer 8

• explanatory trial = ‘as-treated’ analysis, i.e. only look at data of Ps who have adhered to treatment - compares physiological effect of treatment
• pragmatic trial = ‘intention-to-treat’ analysis, i.e. look at data of all Ps whether they have adhered or not - compares likely effects of using treatments in routine clinical practice and preserves effects of randomisation

Question 9

what is the major drawback of explanatory trials

Answer 9

loses effects of randomisation - non-compliers likely to be systematically different from compliers: selection bias and confounding

Question 10

what is clinical equipoise

Answer 10

when there is reasonable uncertainty or genuine ignorance about the better treatment or intervention