2 - CML and Imatinib Flashcards

1
Q

cml

A

chronic myelogenous lukemia

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2
Q

cause of cml

A

uncontrolled proliferation of myeloid cells

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3
Q

chronic phase

A

3-5 years

proliferation occurs but diseases controlled

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4
Q

acute/blast phase

A

extreme proliferation

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5
Q

treatment for cml

A

imatinib

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6
Q

3 steps of translational pipeline

A
  1. discovery
  2. development
  3. delivery
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7
Q

delivery

A

regulatory approval

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8
Q

imatinib pre clinical trials

A
  1. test on pure protein (kinase assay)
  2. test if it inhibits proliferation of BCA-Abl +ve cell lines
  3. test in primates
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9
Q

phase 1 trials

A
  • interested in toxicity, tolerated dose and pharmokinetics of drug
  • either on healthy people or cml patients
  • dose is slowly increased
  • no. of people trialled slowly increased
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10
Q

phase 2 trial

A
  • test patients with disease
  • small study
  • interested in finding biological response
  • finding optimum dose
  • sometimes randomised control trial
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11
Q

biological response to imatinib

A

found in phase 2 trials

haematological and cryogenic response
- no more Philadelphia chromosome

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12
Q

phase 3 trial

A

we know drug is safe and how it is processed by the body

full scale RCT
e.g. 1000 cml patients
cost effectiveness tested by NICE

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13
Q

rct

A

randomised control trial

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14
Q

how do observational studies generate hypothesis

A

they identify patterns and trends in populations

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15
Q

rational drug design

A

designing small molecules that are complementary to biomolecular target
better than trial and error
requires knowledge of disease mechanism

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16
Q

which phase of trials tests to find the optimum dose fo drug

A

phase2

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17
Q

advantages of randomisation

A

eliminates bias in treatment assignment
facilitates blinding/masking
maximises statistical power

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18
Q

3 types of randomisation

A

simple - use random no. generator
blocked
stratified

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19
Q

which types of randomisation do you use if you have a small smaple size

A

blocked or stratified

20
Q

advantages of blinding/masking

A

prevents patients/care-givers knowing which intervention was recieved

21
Q

3 types of blinding

A

open-label
single-blind
double-blind

22
Q

define bias

A

unintentional adjustment in design/conduct of a trial

23
Q

how do you avoid bias

A

blinding/randomisation
allocation concealment
standardised procedure
standardised equipment

24
Q

problems with bias

A

may cause unreliable results

25
what is 'intention to treat' (ITT) analysis
'once randomised, always analysed' all patients allocated to original groups are included accordingly in analysis even if they drop out
26
advantages of ITT analysis
provides unbiased comparisons | avoid effects of cross-over and drop-out
27
what is NICE
a rationing body to reduce variation in access to new interventions
28
what does NICE stand for
national institute for health and care excellence
29
how does NICE evaluate economic considerations for new drugs
NHS cost savings HTA - health technology assessment CEA - cost effective analysis
30
how is HTA for
to calcute if the money for the drug production is really worht it
31
how do you calucate HTA
life expectancy in years x HR-QoL
32
how is QoL measured
EQ-5D questionnaire
33
what are the 5 domains of health
``` mobility self-care usual activities pain/discomfort anxiety/depression ```
34
what does QUALY stand for
quality adjusted life years
35
'currency' of health
QUALYs
36
QUALYs
length of life combined with quality of life | life expectancy x HR-QoL = QUALYs
37
ICER - incremental cost effectiveness ratio | what is it and what is it used for
statistic used in CEA to summarise cost effectiveness of a health care intervention
38
how do you calculate ICER
cost of new intervention - cost of old intervention divided by QUALYs of new intervention - QUALYs of old intervention
39
how does ICER tell you how cost-effective a treatment is
if the ICER is less than £20,000 per QUALY gained, then the NHS deem it cost effective
40
what is CEA
cost effective analysis the comparative analysis of alternative courses of action in terms of both cost and consequences for health
41
describe the CEA graph
HR-QoL on y-axis time on x-axis area between curves for treatment A and B = QUALYs gained
42
transgenes
introduction of genes from a different source into a cell
43
techniques used to create transgenes
transfection | transduction
44
uses of transgenes
researching function of gene/protein gene editing gene therapy
45
what kind of sequences are introduced into cells
cDNA CRISPR constructs promoters
46
steps for creating transgenes
1 - purify mRNA from target cell 2 - convert mRNA --> cDNA using RT 3 - selectively amplify gene of interest (PCR) 4 - add restriction enzyme sequence 5 - use plasmid --> promoter sequence drives transcription of cDNA 6- GFP used to show localisation of gene in cell 7- transfection/injection/infection into nucleus
47
3 ways to transfect cDNA into nucleus
electroporation lipid-mediated transfer CaPO4 transfer