Clinical Trial

Question 1

What is a 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

What is the purpose of a clinical trial?

Answer 2

To provide reliable evidence of treatment efficacy and safety.

Question 3

What is efficacy?

Answer 3

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

Question 4

What is safety?

Answer 4

The ability of a healthcare intervention not to harm a defined group under specific conditions.

Question 5

What is the difference between primary and secondary outcomes?

Answer 5

Primary outcome - preferable only one. Used in the same size calculation.

Secondary outcome - other outcomes of interest. Often includes side effects

Question 6

What are different types of outcomes?

Answer 6

Patho-physiological -e.g. tumour size

Clinically defined - e.g. death, disease, disability

Patient focused - e.g. quality of life, psychologic well-being, social well-being, satisfaction

Question 7

What are some features of an ideal outcome?

Answer 7

Appropriate and relevant

Valid and attributable

Sensitive and specific

Reliable and robust

Simple and sustainable

Cheap and timely

Question 8

What things does a clinical trial need to be to be able to give a fair comparison?

Answer 8

Reproducible - in experimental conditions

Controlled - comparison of interventions

Fair - unbiased without confounding

Question 9

What are non-randomised clinical trials?

Answer 9

They involve the allocation of patients receiving a new treatment to compare with a group of patients receiving the standard treatment.

But, you get allocation bias and confounding factors.

Question 10

Why is non-random allocation bad?

Answer 10

Allocation of participants to treatments by a person, historical basis, geographical location, convenience, numerical order ect. leads to the potential for allocation (aka selection) bias and confounding factors to unwittingly cause unidentified differences between the treatment groups being compared.

Question 11

How do most trials normally allocate patients to groups?

Answer 11

3rd party, computer generated random allocation, accessed by phone / internet.

Question 12

When is it difficult to make trials blind?

Answer 12

Surgery

Psychotherapy vs antidepressants

Alternative medicines

Lifestyle interventions

Prevention programs

Question 13

What is ‘confounding’?

Answer 13

a situation in which a measure of the effect of an intervention (or exposure) on an outcome is distorted by the association of that intervention with other factors(s) that influence the outcome.

Question 14

What is ‘bias’?

Answer 14

systemic distortion in allocation / measurements ect.

Question 15

What things do you have to consider in a randomised control trial?

Answer 15

The disease of interest

The treatments to be compared

The outcomes to be measured

Possible bias and confounders

The patients eligible for the trial

The patients to be excluded from the trial

Question 16

What is the placebo effect?

Answer 16

Even if the therapy is irrelevant to the patient’s condition, the patient’s attitude to his or her illness, and indeed the illness itself, may be improved by a feeling that something is being done about it.

Question 17

What is a placebo?

Answer 17

A placebo is an inert substance made to appear identical in every way to the active formulation with which it is to be compared.

Question 18

How can you minimise less of follow up?

Answer 18

Make the follow-up tactical and minimise inconvenience.

Be honest about the commitment required from participants.

Avoid coercion or inducements.

Maintain contact with participants.

Question 19

Why might patients not comply with their treatment?

Answer 19

Mis-understood instructions.

Not like taking the treatment.

May think treatment is not working

May prefer another treatment

Can’t be bothered

Question 20

What is the difference between an explanatory trial and a pragmatic trial?

Answer 20

Explanatory trial - “as-treated” analysis.
Analyses only those who complied with treated so, it compares the physiological effects of the treatment.
BUT, loses effect of randomisation.
Tend to give larger sizes of effect

Pragmatic trial - “intention-to-treat” analysis.
Analyses according to the regional allocation to treatment groups (regardless of if completed follow up or adhered to treatment).
Compares the likely effect of using the treatments in routine clinical practise. ALSO preserves effects of randomisation.
Tend to give small and more realistic sizes of effect.

Clinical trials should normally be analysed on an “intention to treat” basis.

Question 21

What is clinical equipoise?

Answer 21

Clinical equipoise is the assumption that there is not one ‘better’ intervention present during the design of a randomised controlled trial.
A true state of equipoise exists when one has no good basis for a choice between two or more care options.

Question 22

What does the research ethics committee focus particularly on?

Answer 22

1. Scientific design and conduct of the study
2. Recruitment of research participants
3. Care and protection of research participants’ confidentiality
4. Informed consent process
5. Community considerations