70 - Clinical Trials in Respiratory Disease

Question 1

Top level of NHMRC evidence

Answer 1

Systematic review of randomised controlled trials

Question 2

Bottom level of NHMRC evidence

Answer 2

Case studies

Question 3

Key marker of airway obstruction

Answer 3

FEV1

Question 4

PICOT

Answer 4

Population
Intervention
Comparator/Control
Outcome
Timing

Question 5

Relevance of PICOT

Answer 5

Ideas for designing a clinical trial.

Question 6

Fluticasone

Answer 6

Anti-inflammatory agent

Question 7

Two broad areas for judging relevance of evidence

Answer 7

Internal validity and external validity

Question 8

Internal validity

Answer 8

The extent to which the results of this study valid for the sample of patients being studied.

Question 9

Questions for determining internal validity
1)
2)

Answer 9

1) How well did the study answer the question it set out to answer?
2) Dependent on appropriate study design, control for bias and confounding variables

Question 10

Aims of randomisation
1)
2)
3)

Answer 10

1) Treatment groups all identical in all aspects other than the intervention
2) Even distribution of potential confounders (even those that are unknown)
3) The primary rationale is to reduce confounding

Question 11

Stratified randomisation

Answer 11

Randomisation stratified by levels of key confounders (EG: randomise subjects within stratum to which they belong, EG: country and smoking status)

Make composition of groups even more similar with respect to key confounders.

Question 12

Design to deal with key confounders

Answer 12

Stratified randomisation

Question 13

Blinding (masking)

Answer 13

Non-awareness of intervention allocation

Rationale is to reduce information bias

Question 14

Levels of blinding

Answer 14

Single blind - Subjects unaware
Double blind - Subjects, investigator unaware
Triple blind - Subjects, investigators, outcome assessors unaware

Question 15

How should outcomes be assessed?

Answer 15

Outcomes determined by strict, standardised, objective criteria.
Centralise the assessment in multi-centre studies to improve standardisation.
Rationale is to reduce information bias

Question 16

How to reduce intention-to-treat bias

Answer 16

Assume that subjects remained in allocated group, regardless of actual treatment.

Subjects who drop out, cross over, etc are almost always systematically different from those who don’t

Question 17

Randomised control trial of drug versus placebo potential source of bias

Answer 17

sick subjects cease new drug due to side effects
• selects for healthier group in drug group, which
experiences less outcomes
• misperception: new drug better than placebo

Question 18

Side-effect of intention-to-treat analysis

Answer 18

Always underestimates the treatment effect.

Less treatment in intervention group than assumed, more treatment in control group than assumed

Question 19

Thing to look for in a clinical trial design

Answer 19

Intention to treat analysis

Question 20

Sample

Answer 20

A subset of the whole population, from which assumptions about the whole population are made

Question 21

P-value

Answer 21

Probability that the observed result is the result of chance.

Question 22

Conventional P-value cutoff for statistical significance

Answer 22

Under 0.05

Question 23

Null value

Answer 23

Value if there were no difference between the groups being compared
EG: 1.0 for ratios (HR, RR), 0 for absolute differences.

Question 24

Number needed to treat

Answer 24

Number of people needed to undergo intervention in order to prevent an outcome in one.

NNT = 1/(absolute risk or rate reduction)

Question 25

A marker of the efficacy of the intervention

Answer 25

Number needed to treat (the lower the better)

Question 26

Things affecting number needed to treat

Answer 26

Relative effect (often constant)
Underlying likelihood of outcome (the lower, the lesser the NNT)

Question 27

What does the effect of underlying likelihood of outcome on NNT say about efficient treatment?

Answer 27

Relative benefits don’t tell everything. If a drug reduces an outcome by 50%, but the outcome appears in 0.5% of the population, NNT will be really high. This shows that the intervention mightn’t be so effective.

Question 28

External validity

Answer 28

How well the results of the trial be generalised to the wider population

Question 29

How can external validity be assessed?

Answer 29

See how concordant the randomised controlled trial subjects and clinical subjects are (according to PICOT)