It takes an average of 12 years for an experimental drug to travel from the lab to the medicine cabinet! Only 5 out of 4,000 compounds screened in pre-clinical testing make it to human testing. Of these, only 20% actually make it to FDA approval for use in the general public.

The objective of clinical drug investigations is to assess whether a drug is of value in the treatment or prevention of a disease or condition, its risks and side effects and the relative relationship of these assessments. Investigations of this nature must be conducted in such a way that the participating subjects or patients are exposed to the fewest possible risks consistent with the anticipated benefits. Prior to initiating a study, every institution participating in a clinical investigation has the study reviewed by an Institutional Review Board (IRB) that reviews the protocol for safety and ethical treatment of human subjects. The IRB and informed consent provide safeguards for the testing of human subjects.

New drug development begins with a “discovery” and pre-clinical research in the laboratory. The drug is first screened and purified and then studied in laboratory animals to assess its safety and biological activity. This process takes an average of 1.5 to 3.5 years. An application for the use of the new investigational drug is then submitted to the FDA for approval for use in humans. When approved, the drug begins clinical trials of which there are four phases.

Phase I lasts an average of one year. During this time, 20 to 100 normal healthy volunteers (those free of abnormalities which may complicate the interpretation of data or might increase the sensitivity of the drug’s toxic potential) are studied. It is, however, permissible, and at times desirable, to include subjects with certain abnormalities for which the drug is indicated. Women of childbearing potential, children, and patients with a serious primary disease are excluded. The trial is usually conducted on an in-patient basis, with few exceptions. The primary objective is to determine the safety and correct dosing of the drug. Seventy percent of drugs successfully complete this phase and go on to Phase II.

The length of Phase II is approximately 2 years. Between 100 to 300 volunteers are evaluated during this period for drug effectiveness and side effects. Patients for early Phase II studies should ordinarily be free of any serious diseases, especially of the kidney, liver, blood or heart. They should not be receiving simultaneous therapy. In general, women of childbearing potential may be considered during Phase II if adequate information on the efficacy and relative safety has been amassed and FDA Animal Reproduction Guidelines have been completed. Sufficient protection against pregnancy should be in place before starting study in the form of hormonal birth control or double barrier method. These criteria are set by the pharmaceutical company or by the IRB. About 33% of the drugs studied move on to Phase III.

Phase III lasts 1 to 4 years with a study group of about 1,000 to 3,000 volunteers. The chief objective of this phase is to verify effectiveness, and monitor adverse reactions from long term use. Patients in late Phase II and Phase III studies may be included if they have concominent diseases and therapy since they would be expected to be representative of certain segments of the population who will be receiving the drug once approved. Sometimes Phase II and III are combined to shorten the approval process on new medicines for serious and life-threatening diseases. Twenty-five percent of these drugs clear this phase and move into the final approval process.

There is a 24 month New Drug Application approval process through the FDA before moving from Phase III into the post-marketing Phase IV. Phase IV are studies initiated after the drug’s approval. It further evaluates the drug’s safety and efficacy in different population groups and under broader conditions of use, such as in children, the elderly and as a followup in the population of its original intened use.