Svensson Lec 7

Question 1

what are the 3 levels of risk-benefit analysis that can occur related to drug therapy?

Answer 1

accessibility, acceptability, applicability

Question 2

what is accessibility?

Answer 2

FDA evaluates benefits/risks for the population

Question 3

what is applicability?

Answer 3

Provider evaluates benefits/risks for a patient

Question 4

what is acceptability?

Answer 4

Patient evaluates benefits/risks in terms of personal values

Question 5

State 3 elements of info needed for application of an investigational new drug with FDA.

Answer 5

1. animal pharmacology and toxicology
2. manufacturing information
3. clinical protocol and investigator information

Question 6

What are the steps to predict the first dose in man for a new drug?

Answer 6

1. Determine NOAEL in appropriate animal species
2. Calculated human equivalent dose (HED) from appropriate species
3. Determine a safety factor ( usually 10 )
4. Divide HED by safety factor to determine max recommended starting dose

Question 7

what is NOAEL

Answer 7

• no observable adverse effect level
• highest dose where it has no effect

Question 8

what is MABEL?

Answer 8

• Minimal anticipated biological effect level
• Needed to result in biological effect in participants of a clinical trial

Question 9

Identifying primary reasons adverse drug events are often not detected until after the drug is approved and marketed for a period of time.

Answer 9

1. 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
2. common events vs. patient numbers and duration in clinic trials

Question 10

Provided key info about potential pharmaceutical excipients determine whether or not preclinical studies are needed in dosage form.

Answer 10

1. 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

Question 11

Name 5 categories of preclinical studies completed for new drug development.

Answer 11

1. acute studies
2. repeated dose studies
3. genetic toxicity
4. reproductive toxicity
5. carcinogenicity

Question 12

what are acute studies?

Answer 12

• effect of single dose
• at least 2 species

Question 13

what are repeated dose studies?

Answer 13

• length depends on anticipated therapy
• at least 2 species

Question 14

what is genetic toxicity?

Answer 14

• determine likelihood compound is mutagenic or carcinogenic

Question 15

what is reproductive toxicity?

Answer 15

• needs depends on target population
• multiple species

Question 16

what is carcinogenicity?

Answer 16

• only for compounds used in chronic or recurring conditions