Clinical Drug Trials

Question 1

clinical trials

Answer 1

4 phases

Question 2

FDA approval

Answer 2

after three phases of clinical trials

Question 3

1906

Answer 3

federal pure food and drugs act

-modern era of FDA begins

Question 4

1962

Answer 4

FDA required proof of efficacy

Question 5

rational drug design

Answer 5

based on bio mechanisms, drug receptor structure, and drug structure

Question 6

lead compound

Answer 6

chemical compound that has pharm or bio activity and whose chem structure is used as starting point for chemical modifications in order to improve potency, selectivity, or pharmacokinetic parameters

Question 7

preclinical safety

Answer 7

estimate risk associated with drug exposure

Question 8

acute toxicity

Answer 8

two species, two routes

-no effect dose and max tolerated dose

Question 9

subacute toxicity

Answer 9

three doses, two species

-2 weeks to 3 months

Question 10

chronic toxicity

Answer 10

rodent and nonrodent for > 6 months

-

Question 11

effect on repro performance

Answer 11

two species

-effects on mating behavior, birth defects, etc.

Question 12

carcinogenic potential

Answer 12

two years, two species

Question 13

mutagenic potential

Answer 13

genetic stability and mutations in bacteria or mammalian cell cultures

Question 14

investigative toxicology

Answer 14

determine sequence and mechanisms of toxic action

to discover genes, proteins, pathways involved

Question 15

no effect dose

Answer 15

maximum dose at which toxic effect not seen

Question 16

minimum lethal dose

Answer 16

LDmin

-smallest dose observed to kill experimental animal

Question 17

median lethal dose

Answer 17

LD50

-dose that kills 50% of animals

Question 18

limitations to preclinical testing

Answer 18

• cost and time
• number of animals used
• extrapolation of values to human system

Question 19

crossover design

Answer 19

patients receiving each therapy in sequence so patients serve as own controls

Question 20

single blind study

Answer 20

only health professionals know identity of treatment

Question 21

double blind study

Answer 21

neither patient or health professional know identity of therapy
-third party holds code identification of medication and clinical data

Question 22

investigational new drug

Answer 22

means by which investigators obtain permission from FDA to proceed with drug distribution

IND - commercial and non-commercial

Question 23

institutional review board

Answer 23

IRB - assure appropriate steps are taken to protect rights safety and welfare of humans participating in research

Question 24

phase 0

Answer 24

microdosing
-subpharm doses administered to humans

toxicology safety testing

low cost

Question 25

phase 1

Answer 25

first stage of drug testing in humans

• to determine difference in humans and animals
• also establish limits of safe clinical range

health individuals

absorption, half-life, and metabolism

Question 26

phase 2

Answer 26

small group of patients with target disease (100-200)

efficacy, dose requirements, and toxicities

single blind

Question 27

phase 3

Answer 27

after effectiveness, dose, and toxicity determined

to further establish drug safety - large group of patient (300-3,000)

crossover and double blind

evaluate overall benefit-risk ration of drug

most expensive

Question 28

new drug application

Answer 28

by manufacture to FDA for license to market the drug for specified indication

after completion of phase 3 trials (typically)
-unless serious disease (still in phase 3) or life-threatening (still in phase 2)

Question 29

phase 4

Answer 29

begins after approval to market drug

post marketing study with purpose to continue to monitor safety of new drug under actual conditions in large number of patient