Registries that collect information on specific drugs… need to anticipate the need for adverse event (AE) detection, processing, and reporting.
The U.S. Food and Drug Administration (FDA) defines an adverse drug experience as any AE associated with the use of a drug in humans, whether or not considered drug related…
The minimum dataset required to consider information as a reportable AE is indeed minimal, namely (1) an identifiable patient, (2) an identifiable reporter, (3) product exposure, and (4) an event.
All AE reporting begins with a suspicion by the physician (or responsible person who obtains or receives information) that a patient exposed to a medicinal product has experienced some AE and that the event has a reasonable possibility of being causally related to the product being used; this is referred to as the “becoming aware” principle.
Serious AEs (SAEs) include events that result in death, are life threatening (an event in which the patient was at risk of death at the time of the event), require or prolong inpatient hospitalization, result in persistent or significant disability or incapacity, or result in a congenital anomaly. Important medical events may also be considered serious when, based on medical judgment, they may jeopardize the person exposed and may require medical or surgical intervention to prevent one of the outcomes listed above…
Relatedness is a term intended to indicate that a determination has been made that the event had a reasonable possibility of being related to exposure to the product. This assessment of causality may be based on factors such as biological plausibility, prior experience with the product, and temporal relationship between product exposure and onset of the event, as well as dechallenge (discontinuation of the product to determine if the AE resolves) and rechallenge (reintroduction of the product to determine if the AE recurs).
All spontaneous reports have an implied causal relationship as per regulatory guidance, regardless of the reporter’s assessment.
The collection of AE data by a registry is generally either intentionally solicited (meaning that the data are part of the uniform collection of information in the registry) or unsolicited (meaning that the AE information is volunteered or noted in an unsolicited manner and not as a required data element through a case report form).
[I]f some AEs are collected in an intentional, solicited manner (e.g., routine collection of a primary or secondary outcome via an AE case report form) and others come to the registry’s attention in an unsolicited, “spontaneous” way (e.g., when an AE is reported in the course of a registry contact, such as a call to the [clinical trial] sponsor or to registry support staff), then from a practical perspective it is even more important to have a clear process, so that AEs that require reporting are identified.
Once suspicion has been aroused that an unexpected serious event has a reasonable possibility of being causally related to a drug, the AE should be reported to FDA… to the company that manufactures the product, or to the registry coordinating center… A system should be developed such that all appropriate events are captured…
Systematic collection of all AEs provides a unique resource of consistent and contemporaneously collected comparison information that can be used at a later date to conduct epidemiologic assessments.
Reporting AEs without denominator information is less useful from a surveillance perspective since events rates cannot be calculated without both numerators and denominators. The reliability of the denominator should always be judged, however, by considering the likelihood that all events were reported appropriately.
[H]ealth care providers at registry sites should be instructed that if they suspect or otherwise become aware of a serious AE that has a reasonable possibility of being causally related to a drug or product, they should report the event directly to the product manufacturer (who must then report to FDA under regulation)…
For vaccines, the Vaccine Adverse Event Reporting System should be consulted.
[S]ponsors should be careful when combining related terms to avoid… obscuring important overall findings… In addition to monitoring individual AEs, sites and registry personnel should be attentive to toxicities that may cluster into syndromes.
When biopharmaceutical or device companies are not sponsoring, financially supporting, or participating in a registry in any way, AE reporting is dependent upon the “become aware” principle. If any agent or employee of the company receives information regarding an AE report, the agent or employee must document receipt and comply with internal company policy and regulatory requirements regarding AE reporting, to ensure compliance with applicable drug and device regulations.