Kruse Clinical Trials DSA

Question 1

lead compound

Answer 1

chemical compound that has pharmacological or biological activity and whose chemical structure is used as a starting pt for chemical modification in order to imporve potency, selectivity, or PK parameters

Question 2

preclinical in vitro and in vivo studies are performed to evaluate what

Answer 2

safety and toxicity profiles

Question 3

goals of preclincial studies

Answer 3

identify potential human toxicites without human testing
design tests to further define the toxic mechanisms
predict the specific and most relevant toxicities to be monitored in clinical trials

Question 4

in vitro studies

Answer 4

study factors involved in drugs actions (protein binding and pathways it effects)

establish direct drug target or effects at molecular and cellular levels

test in relevant cell lines

Question 5

in vivo (animal testing)

Answer 5

effect of organs on healthy first then disease state animals

drug induced effects in animals can’t be guarenteed to be reproduced in humans

all organ systems studied, and metabolic profile of drug ID’d

If pharm properties are safe and adequate and IF compound produces expected results, lead compuond may be submitted for approval to test in humans

Question 6

no effect dose

Answer 6

max dose at which a specified toxic effect is not seen

lower than threshold of harmful effect

Question 7

minimum lethal dose

Answer 7

smallest dose that is observed to kill any experimental animal under defined set of conditions

Question 8

median lethal dose

Answer 8

dose that kills approximately 50% of animals

Question 9

limitations of preclinical testing

Answer 9

time and cost

number of animals used which is expensive

extrapolation of values (effects on animals may not translate to humans)

rare and adverse events that occur in humans unlikely to be detected in preclinical testing

Question 10

investigational new drug

Answer 10

drug must be subject of an approved marketing app before distributed across state lines

during trials drugs must be transported across state lines

submission of IND is trying to get permission from FDA to proceed with drug dist

commercial and non-commercial research categories
-each IND must contain preclinical data, manufacturing info, clinical protocls, and investigator info

Question 11

IRB

Answer 11

protect rights, safety and welfare of humans participating as subjects in research

• can approve, req modifications or disapprove research
• also called IEC and ERB

Question 12

phase 0 trials

Answer 12

subpharmacological doses of prospective drug candidates administered to human volunteers

• early PK data
• financially adventagious bc cost is low
• good alt when preclinical trials are unreliable

Question 13

phase I trials

Answer 13

• 25-50 volunteers
• first stage of drug testing in humans
• safe clinical dosage range
• usually not blinded
• absorption, half life and metabolism reported
• in patient

Question 14

phase II trials

Answer 14

100-200 subjects

• drug efficacy
• placebo, established activre drug for + control and active investigational agent
• efficacy, dosing, toxicities detected and recorded
• clinical centers like hospitals
• drug failure usually occurs here with toxic effects or not efficacious

Question 15

phase III trials

Answer 15

further establish drug safety and efficacy or large group of pts (300-3,000)

-people with target disease included

cross over double blind design technique

• overall benefit-risk
• most expensive

Question 16

new drug application

Answer 16

application submitted by manufacturer of a drug to the FDA (after clinical trials have been completed) for a licesnse to market the drug for a specified indication

Question 17

phase IV trials

Answer 17

after approval to market

post-marketing study, monitor safety in large number of pts

rare drug induced effects or toxicities can be ID’s with larger pop

no fixed duration