Cumulative Safety Report

Preapproval reports include IND Annual Reports in the U.S. and Annual Safety Reports (ASRs) in Europe. Some of these documents may provide cumulative information, while others contain aggregate information specific to the reporting period. Postapproval cumulative reports of safety include NDA Periodic Adverse Drug Experiences Reports (PADERs) in the U.S. And Periodic Safety Update Reports (PSURs) in many other countries, including in Europe.

Main focus of a cumulative safety report is serious, unexpected adverse events. All spontaneously reported adverse events are included in a cumulative safety report. For clinical study and literature cases, only those judged to be related to the medicine by the reporter and the pharmaceutical company are typically included. PSURs and NDA Periodic Adverse Drug Experiences Reports (PADERs) submitted to FDA differ considerably in terms of content.

The reporting and regulatory environment in which these efforts occur is not uniform worldwide:
• The U. S. Food and Drug Administration (FDA) generally requires NDA Periodic Reports quarterly during the first 3 years after the medicine is approved, and annual reports thereafter.
• The European Medicines Evaluation Agency (EMEA) requires PSURs every 6 months for 2 years, annually for the 3 following years, and then every 5 years (at the time of renewal of registration).
• In Japan, the authorities require a survey on a cohort of a few thousand patients established by a certain number of identified institutions during the 6 years following approval, with systematic information reported annually on this cohort. Regarding other post approval experience, adverse reactions that are nonserious, but both mild in severity and unlabeled,must be reported every 6 months for 3 years and annually thereafter.
Although the frequency of reporting may diminish with time as the benefit-risk profile of the product becomes better understood, cumulative safety reports are submitted to regulators for as long as the medicine is marketed anywhere in the world.