Lecture 6 - Clinical Pharmacology Flashcards

1
Q

how is safety or efficacy studied?

A

clinical trials

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2
Q

what are clinical trials?

A

controlled human studies to assess dosage, administration, safety, and efficacy

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3
Q

when do clinical trials occur?

A

following considerable pre-clinical development, optimization, and animal testing

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4
Q

how many phases are in clinical trials?

A

three

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5
Q

what is a phase one clinical trial?

A

small scale (dozens of subjects), testing for tolerable dosing ranges, bioavailability, and excretion

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6
Q

what is a phase two clinical trial?

A

intermediate scale (hundreds of subjects), testing for efficacy (sometimes several different dosages), monitoring for safety in greater numbers of patients

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7
Q

what is a phase three clinical trial?

A

large scale, randomized, double-blinded trial, compared against a placebo or current accepted treatment

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8
Q

what is a phase 4 clinical trial?

A

postmarketing surveillance, common repository to collect rare adverse events

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9
Q

systematic differences between baseline characteristics of the groups that are compared

A

selection bias

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10
Q

systematic differences between groups in the care that is provided, or in exposure to factors other than the interventions of interest

A

performance bias

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11
Q

systematic differences between groups in how outcomes are determined

A

detection bias

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12
Q

systematic differences between groups in withdrawls from a study

A

attrition bias

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13
Q

systematic differences between reported and unreported findngs

A

reporting bias

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14
Q

it is very important to have a randomized, double-blind experiment to reduce:

A

bias

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15
Q

what is the placebo effect?

A

expectations can significantly impact treatment outcomes (can account for up to 20% of an observed effect)

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16
Q

the placebo effect emphasizes the need to include ______ in clinical trials

A

placebo controls

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17
Q

an approach to combine data from multiple trials, often after a drug has been approved

A

systemic reviews and meta-analysis

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18
Q

systemic reviews use explicit and reproducible methods to:

A

systematically search, critically appraise, and synthesize on a specific issue

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19
Q

this approach can increase confidence in our view of the effectiveness of a drug, and help guide future policy regarding drug use

A

systematic review

20
Q

data generated from systematic reviews are generally expressed in:

A

forest plots

21
Q

the ratio of the event rate in treatment vs. control

A

the odds ratio

22
Q

for a drug to be useful, it has to have a beneficial effect, but also be:

23
Q

following administration of a single dose, a _____ precedes the onset of the drug effect

A

lag period

24
Q

the range between tolerability and utility can be quantified as the:

A

therapeutic index

25
what is the "effective dose 50"?
the dose where 50% of the population experiences a therapeurtic effect
26
what is the "toxic dose 50"?
the dose where 50% of the population experiences an adverse effect
27
in patient studies, effect or toxicity is often described using a:
quantal dose response curve
28
type of graph which shows the cumulative number of patients who have a pre-defined response to a drug
quantal dose response curve
29
why is a big therapeutic index good?
it means the drug is tolerated with minimal toxicity and gives a lot of flexibility for dosing
30
what is a drawback to a large therapeutic index?
there may be a lot of individual variability in drug response (what is toxic for one person, may not be toxic for somebody else)
31
can the therapeutic index be used as a rigid criteria for administration in a clinical setting?
no
32
in most clinical situations, drugs are administered in a series of ______ or ______ to maintain a ______ concentration of drug associated with the therapeutic window
repetitive doses, continuous infusion, steady-state
33
how is the steady-state or target concentration maintained?
the rate of drug administration is adjusted so that the rate of input equals the rate of loss
34
it takes between ______ to reach drug steady state
4-5 elimination half life's
35
the time in which is takes for a drug to reach its steady-state can be too long when the treatment demands for a more immediate therapeutic response; in this case, one can employ a:
loading dose
36
what is a loading dose?
one or a series of doses given at the onset of therapy with the goal of achieving the target concentration
37
for a limited number of drugs, some effect of the drug is easily measured and can be used to optimize dosage using:
a trial-and-error approach
38
some drugs have little dose-related toxicity, and maximum efficacy usually is desired. in such cases, doses well in excess of the average required will ensure:
efficacy and prolong drug action
39
such drugs with a 'maximal dose' strategy are typically used for:
antibiotics
40
with drugs that are difficult to measure, toxicity and lack of efficacy are both potential dangers. in these circumstances, doses must be titrated carefully, and drug dose is limited by:
toxicity rather than efficacy
41
how is relative risk reduction calculated?
relative risk reduction (RRR) = 1 - ((event rate in the treatment group) / (event rate in the control group))
42
why might reporting the relative risk reduction be considered misleading?
it does not convey the magnitude of the baseline risk (it does not capture the difference between a 'large' reduction in something that is very infrequent versus something very frequent)
43
what is the absolute risk reduction?
describes the absolute number of cases that are prevented by taking a drug
44
how is the absolute risk reduction calculated?
absolute risk reduction (ARR) = event rate in the control - event rate in the treatment group
45
what is the number needed to treat (NNT)?
the NNT is defined as the number of patients who need to be treated to prevent one additional bad outcome
46
the NNT is calculated as the:
inverse of the absolute risk reduction (NNT = 1/ARR)
47
relative and absolute risk reduction can be used to express:
how effective a drug is at reducing an undesirable event