Читать книгу Cobert's Manual Of Drug Safety And Pharmacovigilance (Third Edition) - William Gregory - Страница 27

After the appropriate pharmacology and toxicology testing in vitro and in animals, development of small-scale and sometimes (even at this early stage) larger-scale manufacturing procedures, and other preparatory testing, the drug is ready to be used in humans in the so-called “first in human” study. Permission must be requested from the regulators to proceed. In the United States, a company (sometimes an individual investigator or an academic center) submits an Investigational New Drug Application (IND) to the Food and Drug Administration (FDA). The IND contains preparatory data that support administration of the investigational medicine to humans. The EU Regulation requests a Clinical Trial Application (CTA) dossier, made available to all concerned Member States through a single submission portal (2019); one single authorization is given for all concerned countries before starting the clinical trial. Elsewhere, an equivalent data package is submitted to the local health authority. This package ordinarily contains data that are proprietary and not available to the public. In addition, the submitter includes in the package a protocol for a clinical trial in humans. Outside the US, this administrative package is categorized as a “CTA”. In some countries, the regulator must issue a positive opinion to the applicant before the first human trial can begin and in others, there is a waiting period and if no refusal to proceed is received from the authority, the trial may begin. In such situations, “CTA” may refer to clinical trial authorization.

In rare instances, a physician may request an Emergency Use IND for a specific patient. In the US, this is handled by the FDA. Drug trials are heavily regulated, and multiple layers of protections and precautions have been developed to protect the subjects. These include investigational review boards, data safety monitoring boards, sponsor and health authority scrutiny, and some level of public notification and publicizing of the study on the Internet (e.g., clinical trial registries). Trials are divided into four phases, although there is usually some overlap.

Academic centers are doing more and more of this work as well as other earlier discovery research. The goal has been to create a multi-disciplinary approach from lab to bedside for new and better therapies. This is now called Translational Research and many medical centers now have departments of Translational Research.