Case Unit 2: CML and Imatinib Flashcards
What are observational studies and what are they used for?
Studies where no intervention is carried out
Identify patterns
Used to generate research hypotheses
Starts the ‘translational pipeline’ that leads to development of new therapies
Example of an observational study that generated a hypothesis
It was observed that patients with CML had a small chromosome. This led to the hypothesis: CML is caused by a change in chromosomal structure
Example of how knowledge of a disease mechanism led to rational drug design?
It was known that CML was caused by a reciprocal translocation, leading to production of the Philadelphia chromosome which contained the BCR-ABL fusion gene
The fusion gene coded for a faulty tyrosine kinase receptor that was never ‘switched off’
Led to development of a tyrosine kinase receptor inhibitor (Imatinib)
What happens during Phase I of clinical trials?
First time the drug is tested in humans
Tested in healthy humans or patient volunteers
Incremental increases in dose given to detect tolerated dose
Used to discover pharmacokinetics and toxicity
What happens during Phase II of clinical trials?
Drug tested in patients - they do NOT stop their current treatment
Used to find the optimum dose
Can be a randomised control trial
What happens during Phase III of clinical trials?
Large scale, multi centre randomised control trials
Placebo controlled
Establish efficacy of new treatment over current treatment
What is Intention-to-treat analysis? (ITT)
All participants who start taking part in the study will have their results included in the analysis, even if they
- withdraw midway through
- do not comply with the treatment
- do not have their results followed up
- refuse treatment
- violate protocol
Pros of ITT Analysis
Results of the study will be close to real-life expectations if the treatment is used, e.g. if many people drop out of the study, many people may stop taking the treatment in ‘real life’
No bias in which results are included or not
Minimises the chance of claiming the drug is effective when it actually isn’t (Type 1 error)
Cons of ITT Analysis
The estimate of the treatment effect is an underestimate due to ‘dilution’ of drop outs
Increases the chance of claiming the drug is not effective when it actually is (Type 2 error)
May cause results from different treatments to appear similar when they are not
What is gel electrophoresis?
Analyses product of PCR to shows whether a DNA/RNA sequences is present in a sample
Steps of gel electrophoresis
Sample deposited into wells in the gel Current run through gel Negatively charged DNA fragments move towards positive electrode Smaller fragments move faster Bands compared to template
Who are NICE and what do they do?
National Institute for health and Care Excellence
They advise the NHS on which treatments they should spend their budget on
Judge value of treatment using health technology assessment (HTA) and cost-effectiveness analysis
What is cost-effectiveness analysis?
Compares the cost and health outcomes of new treatment (A) against existing treatment (B)
Cost in terms of £
Health outcome measured in terms of QALYs gained
What are QALYs?
Quality-Adjusted Life Year
How are QALYs calculated?
Life expectancy (years) X health related quality of life (scale of 0-1)
