Clinical Trials

Question 1

What is the definition of a clinical trial?

Answer 1

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

Question 2

What is efficacy?

Answer 2

The ability of a healthcare intervention to improve the health of a defined group under specific conditions

Question 3

What is safety?

Answer 3

The ability of a health care intervention not to harm a defined group under specific conditions

Question 4

What are the 4 stages of drug developing and monitoring?

Answer 4

0- pre clinical lab studies (pharmacology and animal toxicology)
1- volunteer studies (healthy volunteers for pharmacodynamics and major side effects)
2- treatment studies (effects and dosages along with common side effects)
3- clinical trials (big trial comparing it with other standard treatments)
4- post marketing surveillance (monitoring for adverse reactions)

Question 5

Who should take part in trials and who shouldn’t ?

Answer 5

Include: target audience

Exclude: elderly, pregnant, immunocompromised, children, those with another significant disease

Question 6

What’s the problem with excluding groups in clinical trials?

Answer 6

Reduced the generalisability of any findings we have

Question 7

Why should you pre-define outcomes?

Answer 7

Prevent data-dredging and repeated analysis

Have a clear protocol for data collection

Agreed criteria for measurement and assessment of outcomes

Question 8

Why have primary and secondary outcomes?

Answer 8

Primary useful in sample size calculation

Secondary in other outcomes of interest and often includes occurrence of side effects

Question 9

What are the 3 key types of outcome?

Answer 9

Pathophysiological e.g. tumour size or thyroxine level
Clinically defined e.g. death, disease and disability
Patient focused e.g. QOL and social well-being

Question 10

What are some of the key features of an ideal outcome?

Answer 10

Appropriate
Relevant 
Valid
Attributable
Sensitive
Specific 
Reliable
Robust
Simple
Sustainable
Cheap
Timely

Question 11

At what times during a trial should measurements be taken?

Answer 11

Prior, for baseline measurements

During the trial for possible effect

Final measurement of outcomes

Question 12

How may you demonstrate comparability between groups?

Answer 12

By collecting baseline data on characteristics that we think may relate to both the condition and outcomes being investigated

Question 13

What are some baseline measurements that may be taken?

Answer 13

Age 
Gender
BMI (height and weight)
Ethnicity
Occupation 
Socioeconomic status

Question 14

Trials should only be conducted if you are in clinical equipoise. What is a clinical equipoise?

Answer 14

Clinical equipoise is the assumption that there is not one ‘better’ intervention present

A true state of equipoise exists when one has no good basis for a choice between two or more care options.

Question 15

What occurs in non-randomised trials?

Answer 15

Involve the allocation of patients receiving a new treatment to compare with a group of patients receiving the standard treatment

Question 16

What are some of the problems of non-randomised trials?

Answer 16

Allocation bias (by patient, clinician or investigator)

Confounding factors (known and unknown)

Question 17

What is a comparison with historical controls?

Answer 17

Comparing a group of patients who had the standard treatment with those receiving the new treatment

Question 18

What is the problem with a comparison with historical controls?

Answer 18

Less well defined, less rigorous selection

Difference in treatment

Less information about potential bias/ confounders

Question 19

What are the pros of random allocation?

Answer 19

Minimal allocation bias

Minimal confounding

Question 20

How can randomisation be done?

Answer 20

Toss of a coin (heads and tails)
Random number tables (odd and even)
3rd party computer generation (most common now)

Question 21

What is open label?

Answer 21

Knowledge of which participant is receiving which treatment

Question 22

What are problems with open labels?

Answer 22

Behaviour effect
Non-treatment effect
Measurement bias

Question 23

What are the types of blinding?

Answer 23

Single
Double
Triple (rare)

Question 24

When may blinding be difficult?

Answer 24

Surgical procedures
Lifestyle interventions 
Prevention programmes
Physiotherapist vs anti-depressant
Alternative medicine e.g. acupuncture vs western medicine

Question 25

What is a confounding factor?

Answer 25

A factor that is associated with the disease and the outcome of interest

This association is separate to the relationship between the risk factor being investigated

Question 26

How do you reduce confounding and bias?

Answer 26

Confounding- randomisation

Bias- randomisation and blinding

Question 27

What is a placebo?

Answer 27

An inert substance made to appear identical in every way to the active formulation with which it is being compared

Question 28

What are the ethical implications of placebos?

Answer 28

Form of deception

Only be used when no standard treatment is available

Participants must be informed of placebo

Question 29

What are appropriate and unfortunate losses to follow up?

Answer 29

Appropriate- clinical condition necessitates removal from trial

Unfortunate- participant may choose to withdraw

Question 30

How do you minimise losses to follow up?

Answer 30

Make follow up practical
Minimise inconvenience
Be honest about commitment 
Avoid coercion 
Maintain contact with participants