Lecture 6 - Clinical Pharmacology

Question 1

how is safety or efficacy studied?

Answer 1

clinical trials

Question 2

what are clinical trials?

Answer 2

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

Question 3

when do clinical trials occur?

Answer 3

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

Question 4

how many phases are in clinical trials?

Answer 4

three

Question 5

what is a phase one clinical trial?

Answer 5

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

Question 6

what is a phase two clinical trial?

Answer 6

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

Question 7

what is a phase three clinical trial?

Answer 7

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

Question 8

what is a phase 4 clinical trial?

Answer 8

postmarketing surveillance, common repository to collect rare adverse events

Question 9

systematic differences between baseline characteristics of the groups that are compared

Answer 9

selection bias

Question 10

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

Answer 10

performance bias

Question 11

systematic differences between groups in how outcomes are determined

Answer 11

detection bias

Question 12

systematic differences between groups in withdrawls from a study

Answer 12

attrition bias

Question 13

systematic differences between reported and unreported findngs

Answer 13

reporting bias

Question 14

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

Answer 14

bias

Question 15

what is the placebo effect?

Answer 15

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

Question 16

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

Answer 16

placebo controls

Question 17

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

Answer 17

systemic reviews and meta-analysis

Question 18

systemic reviews use explicit and reproducible methods to:

Answer 18

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

Question 19

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

Answer 19

systematic review

Question 20

data generated from systematic reviews are generally expressed in:

Answer 20

forest plots

Question 21

the ratio of the event rate in treatment vs. control

Answer 21

the odds ratio

Question 22

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

Answer 22

tolerable

Question 23

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

Answer 23

lag period

Question 24

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

Answer 24

therapeutic index

Question 25

what is the “effective dose 50”?

Answer 25

the dose where 50% of the population experiences a therapeurtic effect

Question 26

what is the “toxic dose 50”?

Answer 26

the dose where 50% of the population experiences an adverse effect

Question 27

in patient studies, effect or toxicity is often described using a:

Answer 27

quantal dose response curve

Question 28

type of graph which shows the cumulative number of patients who have a pre-defined response to a drug

Answer 28

quantal dose response curve

Question 29

why is a big therapeutic index good?

Answer 29

it means the drug is tolerated with minimal toxicity and gives a lot of flexibility for dosing

Question 30

what is a drawback to a large therapeutic index?

Answer 30

there may be a lot of individual variability in drug response (what is toxic for one person, may not be toxic for somebody else)

Question 31

can the therapeutic index be used as a rigid criteria for administration in a clinical setting?

Answer 31

no

Question 32

in most clinical situations, drugs are administered in a series of ______ or ______ to maintain a ______ concentration of drug associated with the therapeutic window

Answer 32

repetitive doses, continuous infusion, steady-state

Question 33

how is the steady-state or target concentration maintained?

Answer 33

the rate of drug administration is adjusted so that the rate of input equals the rate of loss

Question 34

it takes between ______ to reach drug steady state

Answer 34

4-5 elimination half life’s

Question 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:

Answer 35

loading dose

Question 36

what is a loading dose?

Answer 36

one or a series of doses given at the onset of therapy with the goal of achieving the target concentration

Question 37

for a limited number of drugs, some effect of the drug is easily measured and can be used to optimize dosage using:

Answer 37

a trial-and-error approach

Question 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:

Answer 38

efficacy and prolong drug action

Question 39

such drugs with a ‘maximal dose’ strategy are typically used for:

Answer 39

antibiotics

Question 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:

Answer 40

toxicity rather than efficacy

Question 41

how is relative risk reduction calculated?

Answer 41

relative risk reduction (RRR) = 1 - ((event rate in the treatment group) / (event rate in the control group))

Question 42

why might reporting the relative risk reduction be considered misleading?

Answer 42

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)

Question 43

what is the absolute risk reduction?

Answer 43

describes the absolute number of cases that are prevented by taking a drug

Question 44

how is the absolute risk reduction calculated?

Answer 44

absolute risk reduction (ARR) = event rate in the control - event rate in the treatment group

Question 45

what is the number needed to treat (NNT)?

Answer 45

the NNT is defined as the number of patients who need to be treated to prevent one additional bad outcome

Question 46

the NNT is calculated as the:

Answer 46

inverse of the absolute risk reduction (NNT = 1/ARR)

Question 47

relative and absolute risk reduction can be used to express:

Answer 47

the effective a drug is at reducing an undesirable event