9/3 in class lecture 1 overview of required reading ch.1

Acute toxicity

determine no-effect and maximum tolerated doses

Subacute/subchronic toxicity

Administration for 2 to 12 weeks

Chronic toxicity

Administration for > 6 months; for drugs that will be
used for extended periods of time

Reproduction

mating behavior, birth, birth defects, postnatal development

Carcinogenicity

2 years; when drug will be used for extended periods of time

Mutagenicity

in vitro and in vivo tests

IND (Investigational New Drug application)

used to begin clinical investigation of a drug/biologic

A request to the FDA for permission to begin clinical trials in humans

Requirements for testing in humans

informed consent; approval by the sponsoring
institution, the institutional review board (IRB), and the FDA

Phase 1 Trial (20-100 volunteers)

assess safety and tolerability, not efficacy

Carried out in healthy volunteers, 60%-65% of drugs move onto next phase

Phase 2 Trial (100-300 patients)

assess effectiveness of drug on particular disease or condition to determine therapeutic dose and dose scheduling/frequency

-30% of drugs move onto next phase

phase 2 trials carried out in

randomized, double-blind studies

Phase 3 Trial (1000’s patients)

assess both safety and efficacy, placebo and standardized treatment

-58% of drugs move onto next phase

New Drug Application (NDA

a formal application submitted to the FDA requesting approval to market and sell a new drug in the United States

can take month-years, 90% approved

Phase 4 Trial

monitoring a drug AFTER it has already been FDA-approved and is being used by the general population

-helps identify rare ADR

During clinical trials,

all ADRs must be reported to the FDA