2 - Clinical Trials Flashcards
What is the gold standard for clinical trials?
Blind randomised controlled trial as blinding reduces bias, random minimises confoundiing and comparison with a control enables additional therapeutic benefit
What is the definition and purpose of a clinical trial?
- Form of planned experiment which involves patients and is used to decide the most appropriate method of treatment for future patients
- Used to collect evidence of the efficacy and safety of the treatment in testing
- After results you then look at 95% CI to see if statistically significant and if p>0.05 due to 1 in CI then can reject null
What does efficacy and safety mean when testing a treatment in a clinical trial?
Efficacy: ability of the intervention to improve health
Safety: ability of the intervention to do no harm
In order to be a fair comparison of efficacy and safety what three conditions must a clinical trial satisfy?
RANDOMISED CONTROL TRIAL
What are the different phases of drug development?
- Research: look at lots of compounds and animal testing may be implemented. Screening of different compounds through HTS
- I: small no of healthy volunteers
- II: small no of patients with disease
- III: large no of patients with disease and first control
- IV: long term safety after approval
What are the disadvantages of non-randomised clinical trials and the use of historical controls in a clinical trial?
- Non-random: allocation bias and confounding
- Historical controls: selection less defined, old group may be treated differently (e.g different hospital protocols decades ago), less information about confounders, unable to control confounders
What are the steps involved in a RCT?
1. Define the factors: disese of interest, treatments being compared, outcomes being measured, possible confounders, eligible patients
2. Conduct the trial: identify a source of patients and invite/consent eligible patients to the trial. Allocate the patients in a random way to stop allocation bias and confounding, e.g random number generator. Follow up patients and minimise loss
3. Comparison of Outcomes: is there an observed difference, is it statistically significant, is it clinicall important or a big enough difference, was the study design good
What is the p value?
p<0.05 as the null hypothesis is out of the CI so cannot reject the null
Why must outcomes be defined before a clinical trial?
- Prevent data dredging and repeated analysis
- Created a protocol for data collection and agreed criteria for measurement of outcomes
What are the different type of outcomes measured in a clinical trial?
- Primary outcome: main outcome and preferably the only one
- Secondary outcome: any other outcomes of interest e.g side effects
What are some features of an ideal outcome to investigate?
- Relevant
- Valid
- Sensitive
- Specific
- Cheap
Best outcomes should be followed up for a long time but often too expensive
When in a clinical trial should you measure outcomes?
- Baseline at beginning to look for differences in groups
- During the trial to see if patients are being harmed or disadvantaged
- Final measurement at the end
What are the advantages of random allocation?
- Random allocation allocates participants to treatments fairly, e.g equal number of smokers in each group
- Better with larger studies and historicals that use random allocation can be used
Why may the clinician or the patient knowing the treatment allocation cause bias in the results?
What is blinding and the purpose of it in a clincial trial?
- Used to minimise measurement bias, allocation bias and stop patients altering their behaviour
- Difficult to do if treatment is surgical, if two treatments give different side effects or alternative medicine
What is a placebo and what is the placebo effect?
Placebo: inert substance made to appear identical to the active formaltion to cancel out placebo effect. Used to see if difference between treatment and non-treatment is due to new treatment or coincidence/behaviour
Placebo effect: patient’s attitude to their illness/their illness itself may be imporved if they feel something is being done about it
What is an explanatory trial?
- Trials that only analyse those who completed follow up and fully complied. This is As-treated analysis
- Compares physiological effects of treatment better but loses randomisation
What is a pragmatic trial?
Analysis is done according to allocation regardless of follow up/compliance. This is Intention-To-Treat analysis
- Preserves randomisation, minimises selection bias and confounding. Gives more realistic sizes of effects
What analysis is used in a clinical trial?
Intention-to-Treat
What are the collective and individual ethics of using humans in medical research, and why do RCTs still run even though they do not satisfy these ethics?
- Declaration of Helsinki: the health of my patient will be my first consideration
What are some issues the Research Ethics Committee may have when deeming whether a clinical trial is ethical?
What is clinical equipoise?
- When there is reasonable uncertainty or genuine ignorance about the better treatment or intervention
- Need to have this to launch a RCT
- Cannot withold a well established treatment
How is valid consent gained for a RCT?
What is the role of the Research Ethics Committee?
Make sure the dignity, rights, safety and well being of participants is the primary consideration of any research study
What are they key points for interpreting a clinical trial?
