Preclinical testing
- animals only
- lots of safety tests
- Subacute toxicity (days to 6 months)
- chronic toxicity
- only about 5 drugs will make it past this phase
- all go to FDA after this for the investigational phase
Important limitations to preclinical testing
- time consuming and expensive ($50 mill per successful drug, 2-5 years to collect and analyze data)
- large number of animals are used (increased efforts to use in vitro methods, but those are severely limited)
- extrapolation of toxicity data from animals to humans is not completely reliable
In this phase, we are looking to see if the drug is safe. We are looking at healthy people taking the drug, not the drug response. Exception is in cancer and HIV meds. Small amount of people
Phase I
How many people are used in Phase I of clinical testing
20-100
What is the exception to phase I clinical trials
HIV and cancer meds
This phase checks to make sure it works, testing efficacy by giving to sick people. A medium number of people being tested
Phase II clinical trials
How many people are tested in the phase II clinical trial
100-200
This phase tests safety and efficacy. Double blind studies with a greater number of people. This phase tells us common side effects of the drug
Phase II clinical trial
How many people are used in the phase III clinical trial
1000
After you go though phase I-III clinical trials, what happens
Can then submit new drug application to FDA
How many drugs make it past the clinical trials and to the market?
5000 in preclinical…5 in clinical…1 makes it past FDA
If a new drug is on the market, does that mean its the best one there is
No, sometimes they don’t know the long term side effects of a drug that is new to the market
Less than _______ of the drugs tested in clinical trials reach the marketplace
1/3
3 confounding factors in clinical trials
- variable natural history of most disease
- the presence of other disease and risk factors
- subject and observer bias (patients are influenced by the placebo effect )
Variable natural history of most diseases
- must use large enough population
- also use a crossover design which consists of alternating periods of administration of test drug, placebo preparation (control), and the standard treatment (positive control)
The present of other diseases and risk factors
Health person on Abx vs HIV person on Abx will respond differently
Subject and observer bias
Patients are influenced by the placebo effect
Is it better to compare a new drug to one that is already on the market or to a placebo?
Both. This helps factor in the placebo effect, and also helps compare it to something effective that is already on the market
Pure food and drug act of 1906
Makes sure product is pure and what the package says it is
Federal food, drug, and cosmetic act of 1938
In reaction to a series of deaths associated with sulfanilamide that was marketed before it and its vehicle were adequately tested
FDA and thalidomide
Animal tests showed it to be a nontoxic hypnotic
- a lot of birth defects in pregnant women
- inhibited growth of new blood vessels
- lead to Kefauver-Harris Amendments of 1962
Kefauver-Harris amendments of 1962
Thalidomide causing severe birth defects
-required more extensive testing of new drugs for teratogenic effects
Drugs for rare diseases
Orphan drugs
Affecting fewer than 200,000 people in US.
-difficult to research, develop, and market
-little attention or funding
The study of genetic basis for variation in drug response
Pharmacogentics
