VPT 311: General and Systemic Veterinary Pharmacology (2+1)

CLINICAL TRIALS

• In each of the three formal phases of clinical trials, volunteers or patients must be informed of the investigational status of the drug as well as the possible risks and must be allowed to decline or to consent to participate and receive the drug.
• In phase 1, the effects of the drug as a function of dosage are established in a small number (25-50) of healthy volunteers. If the drug is expected to have significant toxicity, as is often the case in cancer and AIDS therapy, volunteer patients with the disease are used in phase 1 rather than normal volunteers.
• Phase 1 trials are done to determine whether humans and animals show significantly different responses to the drug and to establish the probable limits of the safe clinical dosage range.
• These trials are nonblind or "open"; that is, both the investigators and the subjects know what is being given. Many predictable toxicities are detected in this phase.
• Pharmacokinetic measurements of absorption, half-life, and metabolism are often done in phase 1.
• Phase 1 studies are usually performed in research centers by specially trained clinical pharmacologists.
• In phase 2, the drug is studied in patients with the target disease to determine its efficacy.
• A modest number of patients (100-200) are studied in detail. A single-blind design is often used, with an inert placebo medication and an established active drug (positive control) in addition to the investigational agent.
• Phase 2 trials are usually done in special clinical centers (eg, university hospitals).
• A broader range of toxicities may be detected in this phase.
• In phase 3, the drug is evaluated in much larger numbers of patients with the target disease-sometimes thousands-to further establish safety and efficacy.
• Using information gathered in phases 1 and 2, phase 3 trials are designed to minimize errors caused by placebo effects, variable course of the disease, etc. Therefore, double-blind and crossover techniques are frequently used.
• Phase 3 trials are usually performed in settings similar to those anticipated for the ultimate use of the drug. The investigators are usually specialists in the disease being treated.
• Certain toxic effects, especially those caused by immunologic processes, may become apparent only in phase III.
• Phase 4 begins once approval to market a drug has been obtained.
• This constitutes monitoring the safety of the new drug under actual conditions of use in large numbers of patients.
• The careful and complete reporting of toxicity by physicians after marketing can reveal some side effects may after chronic dosing.
• Several hundred thousand patients may have to be exposed before the first case is observed of a toxicity that occurs with an average incidence of 1 in 10,000.
• Phase 4 has no fixed duration