[Fwd: The 4 Phases of Clinical Trials (US information)]

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--- What the 4 Phases of Clinical Trials Mean (US information)

Date: 21 Sep 2000 15:13:17 GMT

Newsgroups: alt.support.arthritis

As the topic of clinical trials seems to come up around here a lot, I

thought

this excerpt of an article on the topic from the Motley Fool would be of

interest.

<<The Clinical Trial Process

The drug approval process starts in the laboratory. After discovering a

promising compound, studies using the compound in cell cultures,

isolated

tissues, and laboratory animals are conducted. This gives researchers a

pretty

good idea of what to expect in human trials. On average, only one

compound in a

thousand will actually make it to human testing. Assuming the data is

promising, the company makes the decision whether to begin the long and

costly

process of getting the compound to market. Since most drug companies

have

multiple candidates, the company must take into account the size of the

potential patient population, whether the market for that particular

drug is

already well-served, and the company's financial situation, all of which

will

factor in to the decision to begin clinical trials. Because most

companies file

for and receive patents for the commercial use of the compound that they

are

developing during pre-clinical trials, the patent clock usually starts

ticking

at this point. Patents generally last between 17 years for those dated

before

June 7, 1995, and 20 years for patents granted after that date. The

pre-clinical trials for most drugs average about five years. Also, the

patent

protection for the drug, generally lasting 17 years, begins to tick once

the

compound begins pre-clinical trials. The pre-clinical trials for most

drugs

average about five years.

Assuming the company decides to pursue human studies, it must first

submit an

Investigational New Drug application to the FDA for approval. The IND

becomes

effective 30 days after receipt by the FDA (assuming the FDA does not

require

further information), and must be filed annually thereafter until the

completion of clinical testing. The IND must provide pre-clinical data

of

sufficient quality to justify the testing of the drug in humans. About

85% of

all IND applications move on to begin clinical trials. Assuming the

company

receives FDA go-ahead, the company will move the drug on to Phase 1

testing in

human subjects. At this point, the compound has a one in five chance of

eventually reaching the market, and will normally take another five to

nine

years to reach that destination.

Phase 1

Phase 1 trials concentrate on developing the drug's safety profile. The

human

subjects in the study are normally healthy volunteers, though sometimes

patients who have terminal illnesses and have no other therapeutic

alternative

will take part in Phase 1 studies as well. The sample is normally not

more than

100 patients in Phase 1. The basic goal of Phase 1 is to determine how

the drug

is absorbed, distributed in the body, metabolized, and excreted. The

duration

of the drug's effects are also measured. Phase 1 testing ranges from one

to

three years, on average.

Assuming the data from Phase 1 are positive and the safety of the

compound is

established, the drug moves on to Phase 2 testing. If the company moves

on to

begin Phase 2 trials, the drug's chance of eventually making it to

market

improves to just under 30%.

Phase 2

Phase 2 trials consist of small, well-controlled experiments to continue

to

evaluate the drug's safety and assess side effects. The drugs are given

to

volunteers (usually between 100 and 300 patients) who actually suffer

from the

disease or condition being targeted by the drug. This phase is where the

optimal dosage of the drug is established. Also, statistical end points

are

established for the drug that represent the targeted favorable outcome

of the

study. The current standard of care for the medical condition can be

used as a

benchmark in setting the end point. Phase 2 trials last an average of

two

years.

A drug that moves on to begin Phase 3 testing has about a 60% chance of

actually being approved by the FDA.

Phase 3

Phase 3 testing is intended to verify the effectiveness of the drug

against the

condition that it targets, based on the statistical end points

established in

Phase 2. The study also continues to build the safety profile of the

drug and

record possible side effects and adverse reactions resulting from

long-term

use. Phase 3 studies are tightly controlled, double-blind studies with a

sample

size of at least 1000 patients. If the drug proves to be effective in

this

stage, the trial is deemed successful (pivotal). Normally two pivotal

trials

are required to ensure the validity of the studies, although if the

results are

extremely strong, one may suffice. Phase 3 testing averages between

three and

four years.

Assuming the drug reaches the desirable end point in Phase 3 trials, the

company will then file a New Drug Application, which can contain 100,000

pages

of data supporting the efficacy and safety of the drug. At this point,

the drug

has better than a 70% chance of being approved by the FDA.

Approval of the NDA can take anywhere from two months to an extreme of

several

years (in the case that the FDA requests additional information), with

an

average wait of between 18 and 24 months. Upon approval, the company may

begin

to market and distribute the drug.

Phase 4

Once the drug is on the market, the company must continue to perform

observational studies in an ongoing evaluation of the drug's safety

during

routine use. The company also attempts to monitor any usage of the drug

for

conditions other than the approved medical indication. If the drug is

being

successfully used for off-label indications, the company will often

initiate

further clinical trials for those indications in order to widen the

potential

market for the drug. The company cannot advertise or endorse off-market

use of

the drug, however.

For the Investor

The clinical trial process is costly as well as time-consuming.

Estimates as to

the cost of pushing a drug through clinical trials range from between

$350

million and $500 million. Investors interested in early stage companies

should

factor in the costs, risk, and extended time to market required for FDA

approval. >>

Here is a link to the actual article, which is quite interesting:

http://www.fool.com/m.asp?i=129604

The Motley Fool website will require you to register, but it is free.

You will find the message boards particularly interesting if you are

researching individual biotech or pharmaceutical firms.