Trials

Question 1

What is a clinical Iran

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 give medical condition

Question 2

What is efficacy

Answer 2

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

Question 3

What is the difference between efficacy and effectiveness

Answer 3

Efficacy= testing in gold standard conditions. Effectiveness is about real work effects. Effectiveness is important in reality from a treatment perspective. Efficacy is important to the drug company.

Question 4

What is safety

Answer 4

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

Question 5

Are inclusionand exclusion criteria

Answer 5

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Question 6

Whar are reasons for pre defining outcomes

Answer 6

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Prevent data dredging, repeated analysis, protocol for data collection, agreed criteria for data ollection, agreed criteria for measurement and assessment of outcomes

Question 7

What is the issue with having multiple outcomes

Answer 7

Efficacy= testing in gold standard conditions. Effectiveness is about real work effects. Effectiveness is important in reality from a treatment perspective. Efficacy is important to the drug company.

Question 8

What are primary and secondary outcomes

Answer 8

Primary -preferably only one primary outcome, used in sample size calculation
Secondary outcome: other outcomes of interest, often includes occurrence of side-effects

Question 9

What are types of outcomes

Answer 9

Patho-physiological variables eg tumour size
Clinically defined eg death (mortality), disease (morbidity)
Patient focused e.g. (qol, psychological wel being, social well being)

Question 10

What are features of an ideal outcome

Answer 10

• 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 11

Describe=robe teh timing of measurements

Answer 11

• [Baseline measurement of relevant factors] – monitoring for inadvertent differences in groups
• Monitoring outcomes during the trial – monitoring for possible effect,
i.e. is one group being disadvantaged? – monitoring for adverse effects,
i.e. are individual patients being harmed?
• Final measurement of outcomes
– comparing final effect of treatments in trial

Question 12

How do we show comparability between groups

Answer 12

• We need to try to ensure groups compared are as equivalent as possible.
• One way of demonstrating ‘comparability’ between groups is by collecting baseline data on characteristics that we think may relate to both the condition and the outcomes we are investigating.

Question 13

What is baseline data

Answer 13

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Question 14

What are important ethical considerations fo a trial to go ahead

Answer 14

What are the most important ethical considerations for any trial to go ahead:
• Trials of new drugs may do harm
• So…you should only conduct a trial if you are genuinely in ‘clinical equipoise’ and don’t know what is best treatment for patients.
• Patients/participants must understand what participation involves (including known and unknown risks)

Question 15

Descrbe the purpose of. Clinical trial

Answer 15

In order to be able to give a fair comparison of effect and safety, a clinical trial needs to be:
• Reproducible – in experimental conditions • Controlled – comparison of interventions • Fair – unbiased without confounding
N.B. – clinical trials are subject to random variation ⇒ differences observed in small trials (<1,000) are more prone to ‘chance’

Question 16

Wat is a non randomised rail

Answer 16

• Non-randomised clinical trials involve the allocation of patients receiving a new treatment to compare with a group of patients receiving the standard treatment
BUT
• Allocation bias – by patient, clinician or investigator • Confounding – known and unknown

Question 17

What is on random allocation

Answer 17

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

Question 18

Describe comparison with historical controls

Answer 18

• Comparison with historical controls involves the comparison of a group of patients who had the standard treatment with a group of patients receiving a new treatment
BUT for the ‘standard treatment’ group:
• selection often less well defined, less rigorous
• treated differently from ‘new treatment’ group • there may be less information about potential
bias/confounders
• unable to control for confounders

Question 19

Describe random allocation

Answer 19

“Allocate participants to the treatments fairly”
• Minimal allocation bias – randomisation gives each participant an equal chance of being allocated to each of the treatments in the trial
• Minimal confounding – in the long run, randomisation leads to treatment groups that are likely to be similar in size and characteristics by chance
N.B. – this applies to both known and unknown confounder factors

Question 20

How can knowledge o treatment allocation crate bias

Answer 20

• Knowledge of which participant is receiving which treatment may bias the results of a clinical trial, e.g.
– Patient may alter their behaviour, other treatment, or even expectation of outcome (behaviour effect)
– Clinician may alter their treatment, care and interest in the patient (non-treatment effect)
– Investigator may alter their approach when making measurements and assessing outcomes (measurement bias)

Question 21

What is blinding

Answer 21

Allocate participants to the treatments fairly”
• Remove allocation bias – by ensuring that randomisation gives each participant an equal chance of being allocated to each of the treatments in the trial

Question 22

What are types of blinding

Answer 22

Follow-up participants in identical ways”
• Single blind – one of patient, clinician, assessor does not know the treatment allocation
(usually patient)
• Double blind – two of patient, clinician, assessor does not know the treatment allocation
(usually patient + clinician/assessor)
• Triple blind (term rarely used as ‘double blind’ usually implies all do not know the allocation)

Question 23

Where can binding be difficult

Answer 23

• Surgical procedures
• Psychotherapy vs. anti-depressant
• Alternative medicine, e.g. acupuncture, vs. Western medicine, e.g. drug
• Lifestyle interventions
• Prevention programmes

Question 24

What is confounding

Answer 24

Confounding: 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 factor(s) that influence the outcome.

Question 25

What are the considerations of a rcc

Answer 25

• Identify a source of eligible patients
• Invite eligible patients to be in the trial
• Consent patients willing to be in the trial
• Allocate participants to the treatments fairly, i.e. without bias or confounding
• Follow-up participants in identical ways
• Minimise losses to follow-up
• Maximise compliance with treatments

Question 26

Describe comparison of oucomes

Answer 26

– Is there an observed difference in outcome between
the treatment groups?
– Could the observed difference have arisen by chance,
i.e. is it statistically significant?
– How big is the observed difference between the treatment groups,
i.e. is it clinically important?
– Is the observed difference attributable to the treatments compared in the trial?