A Brief Review of Clinical Trials: What do the Different Phases Mean?

It may be difficult to interpret the data depending on what stage of development a particular compound resides, such as Phase IIb versus Phase IV. So let's be concrete on what each stage of clinical development REALLY means from a pharmacology point of view with a summation question at the end:

Ok, once a drug is judged ready to be studied in humans, a Notice of Claimed Investigational Exemption for a new drug (IND) must be filed with the FDA. The IND includes (1) information on the composition and source of the drug, (2) manufacturing info, (3) all data from animal studies, (4) clinical plans and protocols, and (5) the names and credentials of the physicians who will conduct the trials. Once submitted,

PHASE 1. The effects of the drug as a function of dosage are established in a small number of healthy volunteers. This is done to determine whether humans and animals show significantly different responses to the drug and to establish the probable limits of the safe clinical dose range. The trial is "open" which means both investigators and subjects know what is being given. Basically two questions are being asked here: 1- Is it safe and 2- what are the pharmacokinetics?

PHASE 2. The drug is studied for the first time in patients with the target disease to determine its efficacy. Small numbers are studied in GREAT detail. Usually performed in special clinical centers such as University Hospitals. QUESTION- Does it work in patients?

PHASE 3. The drug is evaluated in much larger numbers of patients. Many times this number is in the thousands, to further establish efficacy and safety. These trials are designed to minimize the errors caused by placebo effects, variable course of disease, and so on. Phase 3 are usually performed in settings similar to those anticipated for the ultimate use of the drug. If phase 3 results meet expectations, application will be made for permission to market the new agent. QUESTION- Does it work double blind?

PHASE 4. Monitoring of the new drug under actual conditions of use in large numbers of patients. Physicians report any adverse side effects over long term dosing in large, large patient numbers. Any side effects are noted and submitted to the FDA. SUMMARY- All perscribed clinical drugs are essentially in this phase. They are monitored for long term use effects, if any.