Pharmacovigilance may be better known as the science of drug safety. Its activities aim to detect, monitor, assess and evaluate undesirable medical events which are suspected or proved to be related to taking a particular medicinal product. This article will provide a brief lay introduction to the concepts of expected versus unexpected responses to medicines intended for human use.
Classification According To The Product Life Cycle: When Is A Response Considered Expected Or Unexpected?
Before a pharmaceutical product has been placed onto the market, it must successfully pass through a series of clinical trial phases. During this period, the current investigator’s brochure is used as the reference document against which all responses will be considered. At this stage, should a clinical trial participant or patient experience a medical event which does not correspond to those already detailed within the risk information in the brochure, the event will be classed as unexpected. It could be that the risk information was not required; or it may not have been available. Another possibility is that an event arises which presents a more specific risk than those described in the brochure. A case of cerebral thromboemobilsm would be more specific than cerebral vascular accident; if only the latter were described in the brochure then the former would be deemed unexpected. Finally, another possibility would be that the nature of the response is more severe than those contained within the brochure. If the brochure described elevated liver enzymes but a case arose involving hepatic necrosis, then this would be deemed unexpected due to higher severity.
After the product has passed satisfactorily through the clinical trial phases, it may be that the reference document changes. Once it has launched onto the market, it is possible that it could still be the investigators brochure. However, it is also common for the reference document to now be the standard product information. Examples could be any packaging inserts or the summary of product characteristics. If an event presents which is not precisely consistent with whichever reference document applies, it will be classed as unexpected. This includes again instances of escalated severity or greater specificity.
What Are Class Related Adverse Events (AEs)?
These are those Adverse Events which are apparently a risk for each medicinal product within one class of drugs, included on the investigators brochure during pre-marketing or that or the standard product information during post-marketing. Should any Adverse Event not precisely match the risk information within those documents, again it will be classed as unexpected.
Does An Unexpected Event Have to Be Serious?
Good practice would not require an Adverse Event to be of higher severity in order to be classed as unexpected. In all cases, the most important drug safety consideration should be whether or not that event matches with the exact wording of the brochure or standard product information.
What About Unexpected Events in Clinical Trials?
When a medicinal product is being studied within a clinical trial, it could be there that there has been little or no previous human exposure to that product. This is especially true for those products in the pre-marketing stage or the first phase II studies. In such cases, the investigators brochure may not contain any Adverse Events at all. In such cases, all medical events will be without precedent and therefore unexpected. This concept still includes events which could have been reasonably anticipated due to pharmacologic properties of the drug in question. When such events occur, they must be reported and thus then included within the brochure.
What About Variations In Administration, Dosage Or Indication?
Different routes of administration may have different Adverse Events described within the documents; and the same is true for some cases where a product is being evaluated for different indications. This is just one of the reasons why the exact wording of the brochure or product information becomes so important in assessing whether or not any event is expected or unexpected.
As discussed above, an Adverse Event does not need to be serious to be classed as unexpected: it is still nonetheless extremely important. In cases any where there are any remaining doubts as to whether the unexpected or expected classification would be appropriate, it is considered good practice to opt for unexpected. Please note that this brief introduction is intended for the interested lay reader only and as such cannot form any type of professional pharmacovigilance, drug safety, legal or medical advice.
Source by Jon Barton