Types of Clinical Research Trials

Following a positive outcome in preclinical testing, the sponsoring organization (usually a drug manufacturer) will seek approval to conduct clinical research trials. Once approval has been granted, the sponsor must complete three phases of clinical testing in order for the FDA to approve the new treatment. An optional fourth phase typically follows approval.

For each phase of a clinical research trial, the sponsor hires physicians to conduct the research, prepares a plan (or protocol) that describes the clinical research trial, and submits detailed paperwork to the FDA and IRB to obtain approval to conduct the trial.

Phase I—The process of testing an investigational drug to establish that it is safe for use in humans.

• Scope: A series of small tests to determine how healthy people (those without the condition or illness the drug will treat) react to and are affected by the treatment
• Subjects: Healthy volunteers who are not taking other medicines
• Number of volunteers: Less than 100
• Duration: Several months
• Goal: To determine the optimal dose and establish that the drug is generally safe

Phase II—The process of testing an investigational drug to show it is generally safe and effective in treating or preventing a specific condition or illness.

• Scope: A limited number of studies that help establish the drug’s safety and effectiveness and identify its side effects
• Subjects: Patients who have the condition or illness to be treated
• Number of volunteers: Several hundred
• Duration: Several months to 2 years
• Goal: To understand how the drug affects people who have the condition or illness to be treated

Phase III—The process of testing an investigational drug to show that it is safe and effective in treating or preventing a specific condition or illness.

• Scope: A large number of studies that help establish the drug’s safety and effectiveness and identify its side effects
• Subjects: Patients who have the condition or illness to be treated, who may have other illnesses, and who may be taking medications in addition to the study drug
• Number of volunteers: Several thousand
• Duration: Several months to several years
• Goal: To establish how the drug should be used by doctors in their patients who have the condition or illness to be treated

Phase IV—The process of testing a drug that has been approved and is being prescribed to obtain additional information about the drug.

• Scope: Multiple studies to see how the drug compares to other drugs, to further look at the drug’s safety in very large numbers of patients, to study how the drug affects specific types of patients who were not included in phase III
• Subjects: Patients who have the condition or illness to be treated, who may have other illnesses, and who may be taking medications in addition to the study drug
• Number of volunteers: Several thousand
• Duration: Several months to several years
• Goal: To determine if the drug’s use can be broadened to include more patients and/or if additional safety issues need to be addressed

Phase II and phase III both assess the safety and effectiveness of the investigational drug and often involve controlled studies in which the study drug is compared to a placebo (sugar pill) or to an existing drug. This comparison helps minimize bias in interpreting the study results. However, this does NOT mean that those in the placebo group never receive the investigational medication. For example, the I.M.P.A.C.T. protocol for CSL Behring’s human C1-INH concentrate requires the use of concentrate within 4 hours in any person who does not respond to the placebo. It also allows a second medication dose in anyone who does not respond to the first dose.