Читать книгу Cobert's Manual Of Drug Safety And Pharmacovigilance (Third Edition) - William Gregory - Страница 24

As opposed to “unexpected”, “expected” refers to an event that is noted in the investigator brochure or labeling (Package Insert or SmPC). One complication is that two different reference documents (labels) are available for marketed drugs for expectedness. One is the regulator-approved prescribing information (e.g., Package Insert or SmPC, etc.), which may vary from jurisdiction to jurisdiction, and the other is the company’s core safety information (CCSI). The latter is provided to regulators, but it is a company-driven document that does not ordinarily need approval by regulators. Usually, these are quite similar if not identical, but not always. The CCSI contains the company position on the minimum safety information that should be in every regulator-approved label wherever the product is authorized for marketing. An event/reaction not found in the CCSI may be included in the regular-approved label, but not vice-versa. If the event/reaction is not found in the SmPC, it is considered unlabeled. If it is not found in the core labeling, i.e., the product’s CCSI, it is unlisted. If it is not found in the PI or SmPC, etc. it is unlabeled. The CCSI is used to determine “listedness” for periodic aggregate reports in the post-marketing phase.

Thus, an event in the United States is expected or unexpected depending on whether it is found in the reference safety information (RSI): the investigator’s brochure for unapproved products or the FDA-approved labeling for marketed products. In the European Union, it is the same for unapproved products, but for marketed products, an unexpected event/reaction may be unlabeled (not in the SmPC) or unlisted (not in the CCSI).