New Drug Application - Clinical Trials

Clinical Trials

The legal requirement for approval is "substantial" evidence of efficacy demonstrated through controlled clinical trials. This standard lies at the heart of the regulatory program for drugs. It means that the clinical experience of doctors, the opinion of experts, or testimonials from patients, even if they have experienced a miraculous recovery, have minimal weight in this process. Data for the submission must come from rigorous clinical trials.

The trials are typically conducted in three phases:

• Phase 1: The drug is tested in a few healthy volunteers to determine if it is acutely toxic.
• Phase 2: Various doses of the drug are tried to determine how much to give to patients.
• Phase 3: The drug is typically tested in double-blind, placebo controlled trials to demonstrate that it works. Sponsors typically confer with FDA prior to starting these trials to determine what data is needed, since these trials often involve hundreds of patients and are very expensive.
• (Phase 4): These are post-approval trials that are sometimes a condition attached by the FDA to the approval.

The legal requirements for safety and efficacy have been interpreted as requiring scientific evidence that the benefits of a drug outweigh the risks and that adequate instructions exist for use, since many drugs are toxic and technically not "safe" in the usual sense.

Many approved medications for serious illnesses (e.g., cancer) have severe and even life-threatening side effects. Even relatively safe and well understood OTC drugs such as aspirin can be dangerous if used incorrectly.