Clinical Trials Flashcards
Define a clinical trial
What is the purpose of a clinical trial?
To provide reliable evidence of treatment efficacy and safety
Reproducible - in experimental conditions
Controlled - comparison of interventions
Fair - unbiased without confounding
Define efficacy
Ability of a health care intervention to improve the health of a defined group under specific conditions
Define safety
The ability of a health care intervention not to harm a defined group under specific conditions
What are the phases of drug development?
What are the most important ethical considerations for a clinical trial
Trials of new drugs may do harm
So.. should only perform if you don’t know what is the best treatment for patients
Patients must understand what participation involves
What are non-randomised clinical trials?
Allocation of patients receiving new treatment to compare with patients receiving standard treatment
Allocation by: site; historical controls; system
What are the disadvantages of NRCT?
Allocation bias - by patient, clinician, or investigator
Confounding - known, unknown
Describe the use of historical controls in NRCT
Comparison of a group of patients who had standard treatment with a group of patients receiving new treatment
BUT for historical group control:
- selection less rigorous/ well defines
- treated differently from ‘new treatment’ group
- less information about bias/ confounders
- unable to control for confounders
What is random allocation?
Allocate participants to treatments fairly
What are the advantages of random allocation?
Eliminates allocation bias - each participant has equal chance of being allocated to each treatment
Minimal confounding - in the long run, groups are similar in size and characteristics by chance
What is a confounder
Factor associated with the exposure and is independently a risk factor for a disease
How do we do randomisation?
3rd party
Computer generated random allocation
Accessed by phone/ internet
What is ‘knowing the treatment allocation’?
Knowledge of which participant is receiving which treatment - may bias result of clinical trial
What is behaviour effect?
Patient may alter their behaviour, other treatment, or expectation of outcome
What is non-treatment effect?
Clinician may alter their treatment, care and interest in the patient
What is measurement bias?
Investigator may alter their approach when making measurements and assessing outcomes
What is blinding?
Follow-up participants in identical ways
What is single, double, triple blind?
Single = One of patient, clinician, assessor does not know the treatment allocation
Double = 2 of patient, clinician, assessor does not know the treatment allocation
Triple = all do not know allocation
What is advantage of blinding?
Minimise bias
Make treatment appear identical in every way
What is bias?
Systematic distortion in allocation, measurement, or other forms (e.g. publication bias)
How do we protect against confounding?
Randomisation
How do we protect against bias?
Good randomisation - eliminates selection bias
Blinding - reduce outcome measurement bias
Who should take part in a clinical trial?
All ages, sexes
Healthy volunteers
Those at increased risk
Who should not take part in clinical trial?
Confirmed or suspected immunosuppressive etc.
Significant disease, disorder, or finding
How do we consider ‘outcome measures’?
Pre-define outcomes
Primary and secondary outcomes
Types of outcomes
Features of an ideal outcome
Timing of measurements
Why do we pre-define outcomes?
What are the types of outcomes?
What are the features of an ideal outcome?
How do we show comparability between groups?
Ensure groups compared are as equivalent as possible
Collect baseline data on characteristics we think may relate to both the condition and outcomes
What is ‘placebo effect’?
Even if therapy is irrelevant to a patient’s condition, their attitude/ illness may be improved by a feeling that something is being done about it
What is a placebo?
Inert substance made to appear identical in every way to the active formulation with which it is being compared
What is the aim of a placebo?
Cancel out any placebo effect
How do we deal with ‘losses to follow-up’?
Make follow-up practical and minimise inconvenience
Be honest about commitment required
Avoid coercion or inducements
Recompense participants for their time/ trouble
Maintain contact
How do we minimise non-adherence?
Simplify instructions
Ask about adherence
Ask about effects and side-effects
Monitor adherence, e.g. tablet control
What is an explanatory trial?
As-treated analysis
Analyses only those who completed follow-up and adhered to treatment
What is a pragmatic trial?
Intention-to-treat analysis
Analyses according to the original allocation to treatment groups
Compares likely effect of using treatments in routine clinical practice
Compare explanatory vs. Pragmatic trials
Explanatory: loses effect of randomisation
Larger sizes of effect
Pragmatic: preserves effect of randomisation
More realistic sizes of effect
What are the steps involved in a RCT
1) set up
2) conduct of trial
3) analysis and comparison of outcomes
Describe the set-up of a RCT
Disease of interest
Treatments to be compared
Patients eligible for the trial
Patients to be excluded from the trial
Design questions: allocation (randomisation), blinding
Outcomes to be measures
Describe the conduct of a RCT
Identify and invite of eligible patients
Consent patients
Allocate participants to treatments fairly
Follow-up participants in identical ways
Minimise losses to follow-up
Maximise adherence with treatments
Describe the analysis of RCT
Compare the outcomes fairly intention to treat
- is there an observed difference in outcome between treatment groups?
- could this have arisen by chance?
- how big is it?
- is this attributable to treatments compared in the trial?
