Svensson Lec 7 Flashcards
what are the 3 levels of risk-benefit analysis that can occur related to drug therapy?
accessibility, acceptability, applicability
what is accessibility?
FDA evaluates benefits/risks for the population
what is applicability?
Provider evaluates benefits/risks for a patient
what is acceptability?
Patient evaluates benefits/risks in terms of personal values
State 3 elements of info needed for application of an investigational new drug with FDA.
- animal pharmacology and toxicology
- manufacturing information
- clinical protocol and investigator information
What are the steps to predict the first dose in man for a new drug?
- Determine NOAEL in appropriate animal species
- Calculated human equivalent dose (HED) from appropriate species
- Determine a safety factor ( usually 10 )
- Divide HED by safety factor to determine max recommended starting dose
what is NOAEL
- no observable adverse effect level
- highest dose where it has no effect
what is MABEL?
- Minimal anticipated biological effect level
- Needed to result in biological effect in participants of a clinical trial
Identifying primary reasons adverse drug events are often not detected until after the drug is approved and marketed for a period of time.
- rare events vs. patient numbers in clinical trails
–> Only 10,000 or less people studied and sometimes we don’t get information until 100,000s of people - common events vs. patient numbers and duration in clinic trials
Provided key info about potential pharmaceutical excipients determine whether or not preclinical studies are needed in dosage form.
- GRAS
- generally recognized as safe
- a group of compound whose safety in humans has been established through careful studies or widespread use
- if included in a drug formulation as excipients, specific toxicology data is not needed for those compounds
Name 5 categories of preclinical studies completed for new drug development.
- acute studies
- repeated dose studies
- genetic toxicity
- reproductive toxicity
- carcinogenicity
what are acute studies?
- effect of single dose
- at least 2 species
what are repeated dose studies?
- length depends on anticipated therapy
- at least 2 species
what is genetic toxicity?
- determine likelihood compound is mutagenic or carcinogenic
what is reproductive toxicity?
- needs depends on target population
- multiple species