Lecture 6 - Clinical Pharmacology Flashcards
how is safety or efficacy studied?
clinical trials
what are clinical trials?
controlled human studies to assess dosage, administration, safety, and efficacy
when do clinical trials occur?
following considerable pre-clinical development, optimization, and animal testing
how many phases are in clinical trials?
three
what is a phase one clinical trial?
small scale (dozens of subjects), testing for tolerable dosing ranges, bioavailability, and excretion
what is a phase two clinical trial?
intermediate scale (hundreds of subjects), testing for efficacy (sometimes several different dosages), monitoring for safety in greater numbers of patients
what is a phase three clinical trial?
large scale, randomized, double-blinded trial, compared against a placebo or current accepted treatment
what is a phase 4 clinical trial?
postmarketing surveillance, common repository to collect rare adverse events
systematic differences between baseline characteristics of the groups that are compared
selection bias
systematic differences between groups in the care that is provided, or in exposure to factors other than the interventions of interest
performance bias
systematic differences between groups in how outcomes are determined
detection bias
systematic differences between groups in withdrawls from a study
attrition bias
systematic differences between reported and unreported findngs
reporting bias
it is very important to have a randomized, double-blind experiment to reduce:
bias
what is the placebo effect?
expectations can significantly impact treatment outcomes (can account for up to 20% of an observed effect)
the placebo effect emphasizes the need to include ______ in clinical trials
placebo controls
an approach to combine data from multiple trials, often after a drug has been approved
systemic reviews and meta-analysis
systemic reviews use explicit and reproducible methods to:
systematically search, critically appraise, and synthesize on a specific issue
this approach can increase confidence in our view of the effectiveness of a drug, and help guide future policy regarding drug use
systematic review
data generated from systematic reviews are generally expressed in:
forest plots
the ratio of the event rate in treatment vs. control
the odds ratio
for a drug to be useful, it has to have a beneficial effect, but also be:
tolerable
following administration of a single dose, a _____ precedes the onset of the drug effect
lag period
the range between tolerability and utility can be quantified as the:
therapeutic index
what is the “effective dose 50”?
the dose where 50% of the population experiences a therapeurtic effect
what is the “toxic dose 50”?
the dose where 50% of the population experiences an adverse effect
in patient studies, effect or toxicity is often described using a:
quantal dose response curve
type of graph which shows the cumulative number of patients who have a pre-defined response to a drug
quantal dose response curve
why is a big therapeutic index good?
it means the drug is tolerated with minimal toxicity and gives a lot of flexibility for dosing
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)
can the therapeutic index be used as a rigid criteria for administration in a clinical setting?
no
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
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
it takes between ______ to reach drug steady state
4-5 elimination half life’s
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
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
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
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
such drugs with a ‘maximal dose’ strategy are typically used for:
antibiotics
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
how is relative risk reduction calculated?
relative risk reduction (RRR) = 1 - ((event rate in the treatment group) / (event rate in the control group))
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)
what is the absolute risk reduction?
describes the absolute number of cases that are prevented by taking a drug
how is the absolute risk reduction calculated?
absolute risk reduction (ARR) = event rate in the control - event rate in the treatment group
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
the NNT is calculated as the:
inverse of the absolute risk reduction (NNT = 1/ARR)
relative and absolute risk reduction can be used to express:
how effective a drug is at reducing an undesirable event
