clinical trials

Question 1

Define and describe the purpose of clinical trials

Answer 1

define: 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”
purpose: to provide reliable evdence of treatment efficacy and safety

Question 2

Consider who should participate in a clinical trial

Answer 2

inclusion criteria- age, sex, health status

exclusion criteria- elderly, immunocompromised, children, other disease

Question 3

why pre define outcomes?

Answer 3

– prevent ‘data dredging’, ‘repeated analyses’
– have a clear protocol for data collection
– agreed criteria for measurement and assessment ofoutcomes

Question 4

Describe how we demonstrate two (or more) groups are equivalent…for a fair trial

Answer 4

• collect baseline data eg. bmi/smoking/age/gender/class

Question 5

Describe key ethical considerations in trial design and conduct

Answer 5

Trials of new drugs may do harm • 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 6

Explain the disadvantages of non-randomised clinical trials

Answer 6

• Allocation bias – by patient, clinician or investigator

* Confounding – known and unknown

Question 7

advantages of random allocation

Answer 7

• 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

Question 8

safety

Answer 8

the ability of a healthcare intervention not to harm health

Question 9

Describe the ‘placebo effect’, what a ‘placebo’ is, and how a ‘placebo’ addresses the
‘placebo effect’

Answer 9

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

placebo effect- “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

Discuss how to deal with ‘losses to follow-up’

Answer 10

loss to follow up-
• Make the follow-up practical and minimise inconvenience
• Be honest about the commitment required from
participants
• Avoid coercion or inducements, but can
recompense participants for their time/trouble
• Maintain contact with participants

Question 11

secondary outcome

Answer 11

– other outcomes of interest – often includes occurrence of side-effects

Question 12

types outcomes

Answer 12

pathophysiological eg. tumout size

clinically defined eg. death/mortality

patient focused eg. quality of life

Question 13

features of ideal outcome

Answer 13

appropriate, valid, sensitive and specific, reliable, simple and sustainable, cheap and timely

Question 14

what is a non randomised clinical trial

Answer 14

Non-randomised clinical trials involve the allocation
of patients receiving a new treatment to compare
with a group of patients receiving the standard
treatment

Question 15

what is non random allocation

Answer 15

Allocation of participants to treatments by a person, historical basis, geographical location, convenience, numerical order

Question 16

what is non random allocation

Answer 16

Allocation of participants to treatments by a person, historical basis, geographical location, convenience, numerical order

Question 17

what are historial controls

Answer 17

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

Question 18

disadvantages of historial controls

Answer 18

• selection often less well defined, less rigorous
• unable to control for confounders
• treated differently from ‘new treatment’ group • there may be less information about potential bias/confounders

Question 19

definition random allocation

Answer 19

Allocate participants to the treatments fairly

Question 20

how does open label treatment allocation introduce bias

Answer 20

– 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

advantages of blinding

Answer 21

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

when is blinding difficult

Answer 22

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

Question 23

define confounding

Answer 23

a factor that is associated with the disease
AND the outcome of interest, and this association is
separate to the relationship between the risk factor (or
intervention) being investigated.

Question 24

define bias

Answer 24

systematic distortion in allocation/measurement

Question 25

ethical considerations placebo

Answer 25

• A placebo should only be used when no
standard treatment is available
(‘Declaration of Helsinki’ 2013, paragraph 29)
• Use of a placebo is a form of deception
• Therefore, it is essential that participants in a
placebo-controlled trial are informed that they
may receive a placebo

Question 26

why is there loss to follow up

Answer 26

– their clinical condition may necessitate their removal
from the trial (appropriate)
– they may choose to withdraw from the trial (unfortunate)

Question 27

why are people non adherent

Answer 27

– they may have mis-understood the instructions
– they may not like taking their treatment
– they may think their treatment is not working
– they may prefer to take another treatment
– they can’t be bothered to take their treatment

Question 28

how to minimise non adherence

Answer 28

• Simplify instructions
• Ask about adherence
• Ask about effects and side-effects
• Monitor adherence, e.g. tablet count, urine level,
blood level
• Understand it is never possible to achieve 100%
adherence

Question 29

what is an explanatory trial

Answer 29

“as treated analysis”

• Analyses only those who completed follow-up
and adhered to treatments

Question 30

disadvantages explanatory trial

Answer 30

• Compares the physiological effects of the treatments BUT loses effects of randomisation • Non-adherers are likely to be systematically
different from those adhering to treatment ⇒
selection bias and confounding

Question 31

what is a pragmatic trial

Answer 31

“intention to treat analysis”
• Analyses according to the original allocation
to treatment groups (regardless of whether they completed follow-up or adhered to treatment)

Question 32

pros pragmatic trial

Answer 32

• Compares the likely effects of using the
treatments in routine clinical practice ALSO preserves effects of randomisation →
minimal selection bias and confounding

Question 33

compare pragmatic (intention to treat) and explanatory )as treated)

Answer 33

• ‘As-Treated’ analyses tend to give larger sizes
of effect
• ‘Intention-to-Treat’ analyses tend to give
smaller and more realistic sizes of effect

Question 34

steps of RTC

Answer 34

• disease
• treatments
• elegible patients (inclusion criteria)
• exclusion criteria
• outcomes measured
• bias and confounderrs