1.1.2 Clinical Trials II

Question 1

Why do you need to define what, when and how outcomes are to be measured before start of clinical trial?

Answer 1

To prevent:
Data dredging
Repeated analyses

Question 2

What is a primary outcome?

Answer 2

Main goal of your study
Preferably only one
Used in sample size calculation

Question 3

What is a secondary outcome?

Answer 3

Other outcomes of interest

Often includes occurrence of side effects

Question 4

What are 3 different types of outcomes?

Answer 4

Patho-physiological e.g. tumour size, thyroxine level, other biomarkers

Clinically defined e.g. death (mortality), disease (morbiditiy) and disability

Patient-focused e.g. QoL,psychological and social well-being, satisfaction

Question 5

What are the features of an ideal outcome?

Don’t learn all of them just a few examples

Answer 5

• Appropriate and Relevant – to patient, clinician, society, etc.
• Valid and Attributable – any observed effect can be
  reasonably linked to the treatments being compared
• Sensitive and Specific – chosen method of measurement
  can detect changes accurately
• Reliable and Robust – outcome measurable by different
  people in various settings → similar result
• Simple and Sustainable – method of measurement is easily
  carried out repeatedly
• Cheap and Timely – not excessively expensive to measure
  nor has a long lag time

Question 6

When should measurements be taken?

Answer 6

Baseline measurement of relevant factors

Monitoring outcomes during trial, for possible effects and monitoring for adverse effects

Final measurement of outcomes, for final effect of treatments

Question 7

What baseline data should be taken?

Answer 7

Age
Gender
Social class
Ethnicity
BMI
Co-morbidities
Occupational exposures

Question 8

What is the placebo effect?

Answer 8

Therapy can be irrelevant to patients condition, patient’s attitude to illness and the illness itself may be improved by feeling that something is being done about it

Question 9

What is a placebo?

Answer 9

Inert substance that appears identical in every way to active formulation e.g. appearance, taste, dosage, smell

Question 10

What is the aim of a placebo?

Answer 10

Cancel out any placebo effect that may exist in active treatment

Question 11

When can a placebo be used?

Answer 11

Only be used when no standard treatment available

Question 12

What are the ethical issues with using placebos?

Answer 12

Form of deception
Therefore, it is essential participants are informed they may get a placebo

Question 13

Why might you have losses to follow-up?

Answer 13

Clinical condition may mean they have to be removed from trial
(appropriate)

May choose to withdraw
(unfortunate)

Question 14

How can losses to follow-up be minimised?

Answer 14

Make follow-up practical and minimise inconvenience

Be honest about commitment needed from participants

Avoid coercion or inducements but cant recompensate participants for time/trouble

Maintain contact

Question 15

What are some causes of non-adherence with treatment?

Answer 15

• May misunderstand instructions
• May not like taking treatment
• Could think treatment not working
• May prefer another treatment
• Can’t be bothered to take treatment

Question 16

How can non-adherence be minimised?

Answer 16

• Simplify instructions
• Ask about adherence
• Ask about effects and side-effects
• Monitor adherence e.g. tablet count, urine and blood levels

Need to understand never possible to achieve 100% adherence

Question 17

What is an explanatory trial?

Answer 17

As treated analysis- those who did all of the follow ups and adhered

Compares physiological effects of treatments

Loses effects of randomisation

Non-adherers are likely to be systematically different from those adhering to treatment, selection bias and confounding

Question 18

What is a pragmatic trial?

Answer 18

Intention to treat
Analysis according to original allocation to treatment groups

Regardless of follow-up completion or adherence

Compares likely effects of using treatments in routine clinical practise

Preserves effects of randomisation, minimal selection bias and confounding

Question 19

‘As treated’ vs ‘Intention to treat’

Answer 19

As treated analyses tend to give larger sizes of effect

Intention to treat analyses tend to give smaller and more realistic sizes of effect

Question 20

How should clinical trials normally be analysed?

Answer 20

On an intention to treat basis

Question 21

What steps are involved in a randomised control trial?

Answer 21

– The disease of interest
– The treatments to be compared, is this ethical?
– The methods of group allocation and consideration of
blinding
– The patients eligible and excluded
– Baseline data collection
– Outcomes to be measured

Question 22

How is a randomised control trial set up?

Answer 22

• Identify a source of eligible patients and invite
• Obtain consent
• Allocate participants to the treatments fairly, i.e.
  without bias or confounding (randomisation)
• Follow-up participants in identical ways
• Minimise losses to follow-up
• Maximise adherence

Question 23

What should be asked when analysing outcomes of the a randomised control trial?

Answer 23

Is there an observed difference in outcome between treatment groups?

Could observed difference be due to chance

How bis is observed difference?

Is observed difference attributable to treatments compared?