Читать книгу Cobert's Manual Of Drug Safety And Pharmacovigilance (Third Edition) - William Gregory - Страница 70

In practice, the laws and regulations often leave areas of ambiguity. No law or regulation is ever able to predict or account for every conceivable circumstance that may arise. Where feasible, a “guidance” or some other agency document is issued to clarify issues. However, it is a complex, time-consuming, and difficult bureaucratic process to create laws, guidances, and regulations, and there is always a time lag between the need for a clarification and the publication of such.

For example, the definition of serious would seem fairly clear:

Any adverse drug experience occurring at any dose that results in ... death, a life-threatening adverse drug experience, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity or congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered a serious adverse drug experience when, based upon appropriate medical judgment, they may jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.

In fact, several areas are unclear, and there is a long series of dialogues, publications, and meetings to address such ambiguities:

Is staying in a hospital emergency room overnight considered inpatient hospitalization (and thus a serious adverse event, SAE)? The consensus: No.

Is a preplanned inpatient hospitalization that occurs after an adverse event (AE) but perhaps for a totally separate condition considered inpatient hospitalization (and thus a SAE)? The consensus: No.

What is an “important medical event”? Is thrombocytopenia, if the count is 5,000 platelets per microliter? Yes. 50,000? Probably yes. 350,000 (where the normal is up to 400,000)? Probably no.

What is “medically important” or “significant”? There is no clear consensus on this. It is left to individual reviewers’ and reporters’ judgments.

Thus, in circumstances where there is no clear answer, the best approach is to take the most conservative course of action and “overcall”:

If the question is between serious and non-serious, prefer serious.

If the question is between reporting and not reporting a case to the health authority, prefer reporting.

Calls to the agencies are possible to ask such questions, but it is not always possible to reach the right person to have a policy question answered. Most agencies discourage this practice as it would be burdensome to them. If one does succeed in getting an opinion from an agency on a tricky issue, try to get a written confirmation. If that is not possible, write detailed minutes of the telephone call and file them with the case. For cases submitted to multiple health authorities around the world, it is not practical to call each authority to get an answer, and it is possible the answers would be contradictory. Again, the best course of action is the most conservative and, thus, defensible course.