L10- randomised controlled trials

Question 1

What does ‘scientifically proven to work’ mean?

Answer 1

That it has been compared against another treatment and is better e.g. relative risk

Question 2

What study is analogous to a RCT, except that treatment/exposure is not allocated unlike a RCT?

Answer 2

Cohort study, therefore it is an analytical study not an experimental study like a RCT

Question 3

Define a clinical trial

Answer 3

Any form of PLANNED EXPERIMENT which involves patients and is designed to elucidate the most appropriate method of treatment of FUTURE PATIENTS with a given medical condition

Question 4

What is the purpose of a clinical trial?

Answer 4

To provide reliable evidence of treatment efficacy and safety

Question 5

Outline the major steps involved in a RCT

Answer 5

1. Definition of factors
2. Conduct of trial
3. Comparison of outcomes

Question 6

What are the reasons for pre-defining outcomes for clinical trials?

Answer 6

Define what,when and how before trial:

1. Prevent ‘data dredging’ & ‘repeated analyses’
2. Protocol for data collection
3. Agreed criteria for measurement and assessment of outcomes

Question 7

What are the advantages of random allocation?

Answer 7

1. Minimal allocation bias - equal chance of each treatm’
2. Minimal confounding - in the long run, randomisation leads to treatment groups that are likely to be similar in size and characteristics by chance (unknown and known confounding factors)

Question 8

What are the advantages of blinding?

Answer 8

Knowledge of which participant is receiving which treatment may introduce bias e.g.
(i) patients may alter their behaviour, other treatment, pr expectation of outcome
(ii) Clinician may alter their treatment, care and interest in the patient (non-treatment effect)
(iii) Investigator may alter their approach when making measurements and assessing outcomes (measurement bias)
Randomisation without blinding does not avoid allocation bias.

Question 9

What is the ‘placebo effect’?

Answer 9

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 10

What is a placebo?

Answer 10

An inert substance made to appear identical in every way to the active formulation with which it is to be compared, e.g. appearence, taste, texture, dosage regime, warning etc….
The aim of a placebo is to be able to cancel out any ‘placebo effect’ that may exist in active treatment.
Total effect = active treatment effect + placebo effect

Question 11

How can you minimise ‘losses to follow-up’?

Answer 11

1. Make the follow-up practical and minimise inconvenience
2. Be honest about the commitment required from participants
3. Avoid coercion or inducements
4. Maintain contact with participants

Question 12

What are the differences between ‘explanatory’ and ‘pragmatic’ trials?

Answer 12

a

Question 13

What is the meaning of an ‘intention-to-treat’ analysis?

Answer 13

a

Question 14

What are the ethical principles involved in medical research involving human subjects?

Answer 14

a

Question 15

What issues need to be considered for a clinical trial to be considered ethical?

Answer 15

• placebos only used when no standard treatment available

- placebos are a form of deception therefore participants must know that they may receive one

Question 16

What is the role and function of a research ethics committee?

Answer 16

a

Question 17

How does a clinical trial compare to other epidemiological studies?

Answer 17

A clinical trial is like a cohort study except that it is not observational - exposures are allocated by trial investigators

Question 18

Define efficacy

Answer 18

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

Question 19

Define safety

Answer 19

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

Question 20

What are the three things that a clinical trial needs to be in order to give a fair comparison of effect and safety?

Answer 20

1. Reproducible - in experimental conditions
2. Controlled - comparison of interventions
3. Fair - unbiased without confounding

Question 21

What are the differences in small clinical trials (

Answer 21

random variation caused by chance

Question 22

Which stage of drug development and monitoring is clinical trials (comparison with a standard treatment)?

Answer 22

Phase III

Question 23

What are the disadvantages of using historical controls?

Answer 23

1. Selection often less well defined, less vigorous
2. Treated differently form ‘new treatment’ group
3. Less information about potential bias/confounders
4. Unable to control for confounders

Question 24

What is involved in the first step of a RCT: ‘definition of factors’?

Answer 24

Defining:

1. The disease of interest
2. The treatments to be compared
3. The outcomes to be measured
4. Possible bias and confounding
5. The patients eligible for the trial
6. The patients to be excluded from the trial - appropiate to exclude?

Question 25

What is involved in the second step of a RCT: 'conduct of trial'?

Answer 25

1. Identify a source of eligible patients 2. Invite eligible patients to be involved in trial 3. Consent patients willing to be in trial 4. Allocate participants to the treatments fairly i.e. without bias or confounding 5. Follow-up participants in identical ways 6. Minimise losses to follow-up 7. Maximise compliance with treatments

Question 26

What is involved in the third step of a RCT: 'comparison of outcomes'?

Answer 26

1. Is there an observed difference in outcome between the treatment groups? 2. Could the observed difference have arisen by chance, i.e. is it statistically significant (chance, bias, confounding)? 3. How big is the observed difference between the treatment groups. i.e. is it clinically significant? 4. Is the observed difference attributable to the treatments compared to the trial?

Question 27

What are primary and secondary outcome measures for clinical trials?

Answer 27

Primary outcome - preferably one primary outcome - used in sample size calculation Secondary outcome (not main focus, specified pre-trial) - other outcomes of interest - often includes occurrence of side-effects

Question 28

List three broad types of outcomes that can be measure in a clinical trial

Answer 28

1. Patho-physiological e.g. tumour size, ECG changes etc.. 2. Clinically defined e.g. mortality, morbidity, disability 3. Patient-focussed e.g. quality of life, psychological well-being, social well-being, satisfaction (more subjective)

Question 29

What are the features of an ideal outcome?

Answer 29

1. Appropriate and relevant 2. Valid & attributable 3. Sensitive & specific 4. Reliable & robust 5. Simple & sustainable 6. Cheap & timely

Question 30

Describe how an ideal outcome is appropriate and relevant

Answer 30

Relevant to the patient, clinician, society etc... will the results either way actually improve things?

Question 31

Describe how an ideal outcome is valid and attributable

Answer 31

Can any observed effect be reasonably linked to the treatments being compared?

Question 32

Describe how an ideal outcome is sensitive and specific?

Answer 32

Can the chosen method of measurement detect changed accurately?

Question 33

Describe how an ideal outcome is reliable and robust?

Answer 33

Can the outcome be measurable by different people in various settings with similar results?

Question 34

Describe how an ideal outcome is simple and sustainable

Answer 34

Is the method of measurement easy to carry out repeatedly?

Question 35

Describe how an ideal outcome is cheap and timely

Answer 35

Is the outcome excessively expensive to measure

Question 36

When are measurements taken during the clinical trial?

Answer 36

1. Baseline measurement - 2. Monitoring outcomes during trial: (i) possible effect - one group being disadvantaged? (ii) adverse effects - individuals being harmed? 3. Final measurement of outcomes - final treatment effects