EAB: Randomised Controlled Trials

Question 1

what is an RCT

Answer 1

a planned experiment in humans

designed to assess efficacy of treatment or intervention

Question 2

What are RCTs used to evaluate?

Answer 2

• drugs
• methods of diagnosis eg MRI scanner
• methods of organising care
• methods of screening for disease
• methods for disease prevention
• health care policies

Question 3

What is the PICO framework for basic RCT design questions?

Answer 3

• What is the question?
• Who is the population of interest? (P)
• What is the intervention? (I)
• What is comparison? (C)
• How will the outcome be assessed? (O)

Question 4

What are some examples of eligibility criteria?

Answer 4

• Condition e.g. diagnosis
• Age
• Sex
• Other conditions present (co-morbidity)
• Severity of illness
• Where recruited eg hospital or primary care

Question 5

What is the range of outcome measures (5 Ds)?

Answer 5

• Death
• Disease activity or recurrence
• Disability
• Distress
• Discomfort (pain)

Question 6

What is the primary outcome measure?

Answer 6

the primary outcome measure is the main variable of interest that the study is designed to investigate

• Clinically relevant
• Objective (not subjective)
• Easy and accurate to measure
• Independent of treatment

Question 7

What is blinding in a RCT?

Answer 7

Protects against bias in performance of trial and assessment of
outcomes

• ‘Open label’ - no blinding
• ‘Single blind’ - usually the patient is masked to the treatment allocated
• ‘Double blind’ - both the patient and their doctor* are masked to the allocated treatment
• or technician making the measurement

Question 8

How do you determine how many subjects should be used in a trial?

Answer 8

Sample size calculation: must obtain statistical advice

Depends on four measures
- Size of expected effect
- Variability of the outcome measure
- ‘Power’ and ‘significance’

Question 9

How do you calculate the absolute and relative risk reduction?

Answer 9

Question 10

How do you calculate the ‘number needed to treat’ (NNT)?

Answer 10

Number of patients who would have to receive treatment of interest in order to prevent adverse event in one patient.

Question 11

What is the intention to treat analysis? and what does it avoid?

Answer 11

• All individuals who were randomised should be included in the analysis

Avoids bias from drop outs, loss to follow-up and non-compliance

Question 12

How do RCTs offer strong protections against bias (internal validity)?

Answer 12

Trials offer strong protections against bias:

• Random allocation
• Blinding
• Intention to treat analysis
• Pre-specified protocol to guide analysis and reporting

Question 13

What is external validity?

Answer 13

• It is essentially generalisability
• Are the subjects typical of patients usually seen
• Is the treatment typical of treatment delivered in most practices
• Pragmatic and explanatory trials

Question 13

what are 3 trial types

Answer 13

• multi arms trials
• cross over trial
• adaptive trial

Question 14

what is a mutli arm trial and why is it used?

Answer 14

multi-arm trials have 3 or more groups

ie: control, experimental treatment 1 and experimental treatment 2 groups

multi arm trials are more efficient

Question 15

what is a cross over trial

Answer 15

patients randomised to intervention/control and then after a wash-out period, they swap groups

Question 16

What the trial protocol?

Answer 16

The protocol is a document that describes exactly how a clinical trial will be conducted

Question 17

what does a trial protocol specify in advance

Answer 17

• the objectives
• study design,
• methodology,
• statistical considerations and
• organization of a clinical trial

Question 18

what is trial protocol supplemented by?

Answer 18

Supplemented by a statistical analysis plan (SAP)

Question 19

what is a case report form?

Answer 19

• collect patient data, usually electronic, has info for the specific
  measures.
  
  • standard CRF preserves study data and maintains quality (reliable, valid, few missing values) and integrity

Question 20

What is a Clinical Trials Unit (CTU)?

Answer 20

specialist units which have been set up with a specific remit to design, conduct, analyse and publish clinical trials

Question 21

How can we be confident with the reporting of trials?

Answer 21

The CONSORT Statement
- 25 item checklist
- offers a standard way for authors to prepare reports of trial findings
- facilitates complete and transparent reporting
- reduces the influence of bias on their results
- aids critical appraisal and interpretation.

Question 22

What is the risk of bias assessment tool (RoB 2 tool)?

Answer 22

Five domains:

• Bias arising from the randomisation process
• Bias due to deviations from intended interventions
• Bias due to missing outcome data
• Bias in measurement of the outcome
• Bias in selection of the reported result