Читать книгу Cobert's Manual Of Drug Safety And Pharmacovigilance (Third Edition) - William Gregory - Страница 29

Phase II trials are done after the drug has successfully passed through all or parts of phase I trials. Phase II trials are usually performed in patients afflicted with the disease for which that drug was developed. Whereas phase I trials are usually done for tolerance and safety, phase II trials are done for both efficacy and safety. The goal is to find the minimal effective dose that retains efficacy with the minimum number of AEs and safety issues. These studies may also continue the ADME investigations of phase I. In addition, they may also be used to develop safety and efficacy markers and tests for subsequent larger phase III trials. The studies may include up to hundreds of patients and are usually double blinded and controlled. They may run several weeks or months.

Sponsors and investigators participating in phase II trials must pay particular attention to toxicity because unexpected SAEs, including deaths, may occur. Severe and unexpected toxicity may force the immediate stopping of the study or a midstream alteration of the protocol and informed consent. Patients in phase II trials usually are not compensated for their participation, although they routinely receive study medication and study-related medical care.

Special studies may be done in phase I, II, III, or IV, such as drug-interaction studies (sometimes in healthy volunteers, sometimes in patients with the disease), food or alcohol interaction studies, and evaluation studies in renal failure or liver failure patients. These special studies, however, are usually required for the MAA or NDA submission and so must be done at some point.

Some drugs or products, e.g., oncology drugs or herbals, may not fully undergo phase I and II testing as is classically done and as described above. Oncology drugs, which are often very toxic, are rarely studied in normal subjects, but are used directly in patients with malignancy. Similarly, “orphan drugs”, which are drugs developed for rare diseases, may undergo abbreviated testing. The FDA Orphan Drug Designation program provides orphan status to drugs and biologics which are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the US, or that affect more than 200,000 persons but are not expected to recover the costs of developing and marketing a treatment drug. A similar situation exists in the EU where an orphan drug designation is given to products aimed at treating diseases that afflict no more than 5 in 10,000 people or where the potential profit is insufficient to justify research and development costs.