Flashcards in 1-Clincial Trials Deck (26):
1
Define clinical trial
A planned experiment involving patients and designed to explain the most appropriate treatment for future patients with a given medical condition
2
What is the purpose of a clinical trial?
Provide reliable evidence of treatment efficacy and safety
3
Define efficacy
Ability of a health care intervention to improve the health of a defined group under specific conditions
4
Define safety
Ability of a health care intervention not to harm a defined group under specific conditions
5
What are the disadvantages of comparison with historical controls?
Less information about potential bias
Unable to control for confounders
Selection less rigorous
6
What needs to be defined before a trial starts?
Disease of interest
Treatments to be compared
Outcomes to be measured
Possible bias and confounders
Eligible patients
Patients who need to be excluded
7
What are the steps of conducting a trial?
Identify source of eligible patients
Invite them to trial
Consent willing patients
Allocate patients to treatment
Follow up patients identically
Minimise losses to follow up
Maximise compliance
8
What questions are asked when comparing results of a trial?
Is there an observable difference between treatment?
Could the difference have arisen by chance - statically significant?
How big is the difference between treatments - clinically important?
Is the observed difference attributable to the treatment?
9
What are the types of outcome in a trial?
Patho-physiological (tumour size/ECG change)
Clinically defined (mortality/morbidity)
Patient focused (quality of life/satisfaction)
10
When are outcomes measured in a trial?
Baseline - for inadvertent differences in groups
During trial - side effects, is one group being disadvantaged
Final - effects of treatment
11
What does random allocation lead to?
Minimal allocation bias - each patient has equal chance of being allocated to each treatment
Minimal confounding - groups likely to be similar in size and characteristic due to chance
12
What are the potential consequences of open label treatment?
Behavioural effects - patient
Non treatment effects - clinician
Measurement bias - investigator
13
Define the placebo effect
Patients attitude/illness improves as they feel something is being done
14
Define a placebo
Inert substance appearing identical in every way to active form it is being compared to, aiming to cancel out placebo effect
15
How can compliance be maximised?
Simplify instructions
Ask about side effects
Measure compliance (urine/blood levels, tablet counts)
16
Define as treated analysis
Only including patients who have complied in any analysis
17
What are the disadvantages of as treated analysis?
Loses randomisation (and therefore minimal allocation bias)
Won’t address if there is a reason for low compliance such as negative side effects
18
What is intention to treat analysis?
Analysis according to original allocation of treatment groups regardless of whether they complied or completed follow up
19
What are the advantages of intention to treat analysis?
Compares likely effect of using treatment in routine clinical practice
Preserves effects of randomisation - minimal selection bias and confoundings
20
What is the collective ethic surrounding human clinical trials?
Patients should have treatments properly tested for safety and efficacy
21
What are the individual ethics in relation to human clinical trials?
Beneficence
Non maleficence
Autonomy
Justice
22
What issues must be considered for a trial to be considered ethical?
Clinical equipoise
Scientifically robust
Ethical recruitment
Valid consent
Voluntariness
23
What governs the ethics of clinical trials in the uk?
NHS trust and PCT R and D office
24
What are the roles of clinical trials?
Testing the safety of drug
Phase I - proof of principle
Phase II - Proof of concept and dose range finding
Phase III - pharmoeconomics
25
Describe the regulatory process of clinical trials
MHRA give approval for human clinical trials
Phase III data given to MHRA to be granted a product licence
Wording of packaging and marketing regulated by MHRA, can remove product from market
26