Therapeutic Dogmas and EBVM Flashcards
Arrange the types of studies relative to level of evidence from highest to lowest?
Meta-analysis Clinical trial Disease model Case reports PK study with surrogate endpoints PK study without surrogate endpoints In vitro study Expert opinion
Describe meta-analysis
A retrospective statistical analysis encompassing multiple studies
Results must be normalized to a common scale
If disease severity differs between studies (severe hypertension versus mild hypertension) then this value may be expressed based on standard deviation or relative risk reduction of the response
Describe clinical trial
Prospective study of the naturally occurring disease
Required by the FDA for approval of the drug
A good clinical trial should be randomized and state the number of animals used. It should also be controlled
A negative control is a placebo, a positive is another drug that is known to be effective (established drug comparison)
It should also be masked (see below for definition)
Describe a disease model
Disease is induced in a research animal to mimic naturally occurring disease
This is not naturally occurring, you are causing a disease
For example, placing heartworms in a jugular vein of a dog
Describe case reports
Medical cases with the naturally occurring disease and they are reporting on the response
Describe PK study with surrogate endpoints
Pharmacokinetic studies (mathematically) define the disposition of drug in the body
Surrogate parameter: A parameter that is a substitute for a specified response under study
There is something to link the concentrations to for a clinical outcome
For example, time above MIC is a surrogate parameter for cure rate using beta-lactam antibiotics
Describe in vitro study
May give reason to suspect the therapy will work
In vitros tend to have a lower level because there are so many things that actually go into a disease that this model does not address
In vitros can lead to in vivo studies to see if they still work
For example, in vitro inactivation of endotoxin by polymyxin B and colistin in mastitic milk
Describe expert opinion
Lectures; consultations
Review articles/text books
Consensus guidelines
Describe the difference in a hypothesis versus a theory according to the Scientific Method.
Hypothesis: an unproven probable explanation of why something occurs
Take this and test it. If it passes and the data supports it, it becomes a theory
Theories are not necessarily facts, they are continued to be tested until it becomes a fact
There is evidence supporting a theory
Just because evidence doesn’t work for everything doesn’t mean it’s false
Why is Expert Opinion one of the lowest levels of evidence?
It is an individual expert so it is one person’s opinion and subject to their biases
Rand the types of expert opinion as to their evidence quality?
Lectures and consultations have the lowest evidence
Review articles and textbooks are the second best option
Consensus guidelines are the best evidence quality
What is a “surrogate parameter” relative to the use of the term in pharmacokinetic studies?
A parameter that is a substitute for a specified response under study
There is something to link the concentrations to for a clinical outcome
For example, time above MIC is a surrogate parameter for cure rate using beta-lactam antibiotic
What is the difference between a positive control versus a negative control in a clinical trial?
Positive control is an established drug comparison, so it is a drug that is known to be effective
Negative control is a placebo
Why is a meta-analysis one of the highest levels of evidence regarding research articles?
It looks at multiple studies and normalizes them to a common factor. From that, they try to derive an outcome.
It may take 10 or 15 studies and combine them into one statistical analysis
Differentiate a single-masked versus a double-masked study design.
Single masked: owner unaware of which treatment is being applied
Double masked: owner and clinician unaware of which treatment is being applied
