Clinical Trials Flashcards
Define clinical trial.
Any form of planned experiment which involves patients and is designed to find the most appropriate method of treatment for future patients with a given medical condition
Name two things that can arise from non-random allocation.
Allocation biased means
Confounding
What two things does a clinical trial determine about a treatment?
Safety
Efficacy
What do you use to determine who should take place in a clinical trial?
Inclusion and Exclusion criteria
Why should outcome measures before interpreting the results of a RCT?
Which outcome measure is used in calculation of sample size?
In order to avoid the risk of drawing false conclusions by testing every variable until a statistically significant one is identified.
Primary outcome measure
Give some types of outcome.
Tumour size Thyroxine level Biomarkers Death (mortality) Disease (morbidity) Disability
What makes an outcome specific and sensitive?
Reliable?
Chosen method of measurement can detect changes accurately.
Outcome measurable by different people in various settings but will give similar results
What affects follow up length?
What is a disadvantage of a long follow up length?
Depends on the treatment being trialed - cancer - want to follow up for years to see mortality etc
Dermatological - want to follow up for shorter amount of time
More costly
How may we show comparability between groups?
What is the point of doing this?
Collect baseline data/demographics on characteristics that may relate to the condition and outcome.
To show that the two groups other than the treatment being received were equivalent.
What is meant by clinical equipoise?
Issues with this?
Genuine uncertainty/ general ignorance on part of the expert medical community about the comparative therapeutic values of each arm of the clinical trial.
What constitutes “reasonable uncertainty”?
Individual or whole community is uncertain?
What is being tested in each of the following stages of a clinical trial?
Preclinical phase.
Phase I.
Phase II.
Phase III.
Phase IV.
Pharmacology
Animal toxicology
PK PD Major Side effects
Effects and dosages
Common side effects
Comparison with standard treatments
Monitoring for ADRs
Potential new uses
What is meant by a fair clinical trial.
Unbiased
No confounding
What does allocation bias open the doors for?
Behaviour bias (Pt may change their behaviour if they know which treatment they are receiving) Non-treatment effect (clinical may alter treatment, care and interest in the patient) Measurement bias (investigator may alter their approach when making measurements and assessing outcomes)
What is the difference between allocation concealment and blinding?
Allocation concealment occurs before randomisation
Blinding occurs after randomisation
Give two ways to reduce allocation concealment.
Sealed opaque envelope
Remote randomisation - allocation done by third party
Give example where blinding is difficult.
What does blinding ensure?
Antidepressants vs psychotherapy
Surgical procedures
Reduce outcome measurement bias
What are some ways to minimise follow up loss?
How can you maximise adherence?
Make the follow up practical and minimise inconvenience.
Be honest about commitment needed from participants
Maintain contact with participants.
Monitor levels of drug
Simple instructions
Ask them about the side effects or effects of the drug
What is the difference between a pragmatic and a explanatory trial?
Explanatory trial - estimates efficacy - benefit treatment produces under ideal conditions
Pragmatic trial - estimates effectiveness - benefit produces under routine clinical practice
Why is randomisation not preserved in explanatory trials?
Which type of trial shows generally increased effect of treatment?
Because non-compilers are not accounted for
Non-compilers are going to be SYSTEMATICALLY different from compliers
This leads to selection bias and confounding.
Explanatory trial
What type of analysis is carried out by each type of trial?
Explanatory trial - as treated analysis
Pragmatic trial - intention to treat analysis
What is collective ethic?
How may this clash with individual ethic?
All patients should have treatment that are properly tested for efficacy and safety.
Because RCTs can not guarantee beneficence
May cause harm
Allocate randomly
Place burdens and confer benefits
What are some things that need to be considered in order for a trial to be considred ethical?
CSEVV
Clinical equipoise Scientifically robust Ethical recruitment Valid consent Voluntariness
Name 3 things that make a RCT scientifically robust.
Ways to monitor health and well being of participants
Can justify use of comparator and placebo
Addresses a relevant issue
What is valid consent?
What is voluntariness?
Verbal and written
Freedom to opt out
Cooling off period
Precursor to consent to be valid - freedom from coercion and manipulation
