What are 3 phases an investigational drug goes through prior to submitting a new drug application?

In the United States, it takes an average of 12 years for an experimental drug to travel from the laboratory to your medicine cabinet. That is, if it makes it.

Only 5 in 5,000 drugs that enter preclinical testing progress to human testing. One of these 5 drugs that are tested in people is approved. The chance for a new drug to actually make it to market is thus only 1 in 5,000. Not very good odds.

The process of drug approval is controlled in most countries by a governmental regulatory agency. In the U.S., the Food and Drug Administration (FDA) governs this process. The FDA requires the following sequence of events before approving a drug.

Preclinical Testing: A pharmaceutical company conducts certain studies before the future drug is ever given to a human being. Laboratory and animal studies must be done to demonstrate the biological activity of the drug against the targeted disease. The drug must also be evaluated for safety. These tests take on the average 3 1/2 years.
Investigational New Drug Application (IND): The pharmaceutical company files an IND with the FDA to begin testing the drug in people. The IND becomes effective if the FDA does not disapprove it within 30 days. The IND must include the following information: the results of previous experiments; how, where and by whom the new studies will be conducted; the chemical structure of the compound; how it is thought to work in the body; any toxic effects found in the animal studies; and how the compound is manufactured. The IND must also be reviewed and approved by the Institutional Review Board where the studies will be conducted.
Phase I Clinical Trials: Phase I studies are usually the first tests of a drug under development in healthy volunteers. These studies involve about 20 to 80 volunteers. The tests determine a drug's safety profile, including the safe dosage range, plus how the drug is absorbed, distributed, metabolized and excreted, and the duration of its action. Phase I trials take on the average 1 year.
Phase II Clinical Trials: These are slightly larger studies that are done in patients with the disease for which the drug is intended. This phase is usually designed to identify what are the minimum and maximum dosages. The trials generally involve 100 to 300 volunteer patients and are controlled in design. They are done to assess the drug's effectiveness. Phase II typically takes about 2 years.
Phase III Clinical Trials: These are the definitive, large randomized trials that are submitted to the FDA in order to obtain approval of a drug. This phase examines the effectiveness as well as the safety (adverse events) of the new drug. Phase III trials usually involve 1,000 to 3,000 patients in clinics and hospitals. Patients are usually asked a list of possible side effects, often derived from what was observed in phase II studies. Patients are also free to report any other side effects that occur while they are on the new drug or the placebo (the "sugar pill" that is given to a percentage of patients in a trial study). Phase III takes on the average 3 years.
New Drug Application (NDA): Following the Phase III Clinical Trials, the drug manufacturer analyzes all the data from the studies and files an NDA with the FDA (provided the data appear to demonstrate the safety and effectiveness of the drug). The NDA contains all of the data gathered to date about the drug. (An NDA typically consists of at least 100,000 pages.) The average NDA review time for new drugs approved in 1992 was close to 30 months (2 1/2 years).
Phase IV Studies: Phase IV is any organized collection of data from patients who are taking a drug that has already received approval from the FDA. In Phase IV studies, patients may check boxes on a list (as in phase III studies) or they may just report other symptoms. Phase IV studies are commonly called "post-marketing studies."

Although there are other routes that can expedite the process (referred to as fast-tracking), this is the usual journey for a drug from invention to market in the U.S.

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Volume 1, Issue 3, April 2016, Pages 170-179

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CDER

Center for Drug Evaluation and Research

EIND

emergency investigational new drug

FDA

U.S. Food and Drug Administration

IND

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There are three phases to complete in the clinical trial process before a sponsor can submit their treatments* to the FDA for consideration to be sold on the market. Each stage of a clinical trial has its own purpose in ensuring that a treatment is safe and effective for use by the public.

The purpose of Phase 1 is to ensure that the treatment is safe in humans and to determine how and where it distributes within the body. This testing normally takes place with a small group of healthy volunteers. The trial sponsor monitors for potential “serious adverse events”— that is, any toxic, undesirable, or unwanted effect that causes death or danger to health, like a disability or permanent damage, birth defect, heart attack, or other serious medical condition. At the end of Phase 1, the results are collected, analyzed, and submitted to the FDA for permission to proceed to Phase 2 Clinical Trials. However, if the results show that the treatment was associated with one or more serious adverse events, then the FDA may not give permission to proceed to Phase 2. Normally, testing of that treatment is discontinued or “drops out” of the running for making it to the market. If the trial meets the primary outcome(s), as defined in the initial study design, then the FDA permits the treatment to proceed to Phase 2 Clinical Trial(s).
Sometimes, a potential for treatment of one disease has already been approved for use in treating another disease (for example, a cancer drug may be tested for treatment of Alzheimer’s or macular degeneration). This is called “repurposing” a drug, and sometimes this may shorten the clinical trial, or permit the acceleration into Phase 2 Clinical Trials, because the Phase 1 safety profile has already been tested in the previous clinical trial.

The purpose of a Phase 2 Clinical Trial is to determine the right dosage and effectiveness in treating that particular disease. This testing normally takes place with a larger number of volunteers who have the disease. There are many different ways that a trial sponsor can conduct their trial, but the plan normally involves assigning participants to different treatment groups, where each group can receive different doses or delivery of the treatment. Normally, there is a “control group” that receives either the current standard of care, if another type of treatment is already available on the market for that disease, or a “placebo” treatment, such as a sugar pill or harmless injection that does not contain the treatment.

The health of the group(s) of patients who received the different types of treatment is compared to the control groups. However, if the results show that the treatment did not work better than the current standard of care or even caused acceleration of the disease or other unexpected serious adverse events, the FDA may not give permission to proceed to Phase 3. Normally, testing of that treatment is discontinued or “drops out” of the running for making it to the market.

A Phase 3 Clinical Trial involves a much larger group of volunteers and primarily focuses on determining whether the treatment* would be safe and effective for a wide variety of people. The plan normally involves assigning participants to treatment or control groups. There can be more than one treatment group, especially if the treatment involves a combination of drugs or different components. Again, there is a control group that receives either the current standard of care regiment or a placebo treatment.

After completion of Phase 3 Clinical Trials, the health of the patients who received the different types of treatment are compared to the control groups. If the results show that the treatment did not work better than the current standard of care or even caused acceleration of the disease or other unexpected serious adverse events, the FDA may not give permission to proceed to apply for a New Drug Application (NDA). This special NDA contains all of the discoveries made at every stage of the process (starting from the Basic Research/Drug Discovery through to the results of the Phase 3 Clinical Trials), and is submitted to the FDA for their consideration to approve the sale of the treatment on the market.

After approval by the FDA and manufacturing of the drug on a large scale by the sponsor, the process enters what is called Phase 4 Clinical Trial/Post-Market Surveillance/Report Adverse Events. For at least the entire time a treatment* is on the market, the FDA monitors for public safety and potentially serious adverse events. In particular, the FDA has a service called MedWatch, where health professionals, the sponsor, or anyone in the public can report a serious adverse event they believe is associated with a particular drug or treatment (reports can be made online, by mail or e-mail, or by phone). In addition, there may be mandatory or optional Phase 4 Post-Marketing Clinical Trials to obtain further information about the risks, benefits, and long-term effects, or to test the product in special patient populations. The FDA provides a wide variety of information about all of the drugs currently for sale on the U.S. market (see Sources of Information).

U.S. Food and Drug Administration (FDA); National Institutes of Health (NIH); Center for Information & Study on Clinical Research Participation (CISCRP); Pharmaceutical Research and Manufacturers of America (PhRMA); Tufts Center for the Study of Drug Development [Updated Outlook 2010 and original referenced paper (DiMasi, Joseph A., Ronald W. Hansen and Henry G. Grabowski (2003) “The Price of Innovation: New Estimates of Drug Development Costs,” Journal of Health Economics 22(2):151-85, March)]; and a paper comparing the costs of different studies (Morgan, Steve, et al. “The cost of drug development: A systematic review” Health Policy 100 (2011) 4–17).