Signal detection procedures can range from individual case review, trend analysis of case reports to the use of complex statistical methodologies (e.g. Bayesian methods).
The methods used (including periodicity of review) should be determined, for example, by the product portfolio and the number of reports of suspected adverse reactions received.
The MAH should, based on risk assessment, decide what signal detection methods are to be used for which products or types of products, and should document this risk assessment.
All MAHs are expected to have in place systems and procedures for systematic signal detection that are adequately documented in formalised procedures (e.g. SOPs).
Within this documentation it is useful to provide a definition of what constitutes a potential signal, in order to educate all personnel involved in the process and to identify what requires further evaluation.
These documents should also provide detail about the roles and responsibilities of all personnel involved, the sources of information included in the analysis and the methods used for signal detection.
In addition, formal written procedural documents should describe what actions MAHs intend to take based on the outcomes generated from signal detection activities.
This could include escalation procedures following identification of a potential signal, such as further analysis that will be undertaken or referral to a company committee.
Whilst there are no defined minimum requirements for signal detection, whichever method is employed by MAHs for signal detection, certain criteria should apply, namely:
• The method used is appropriate for the MAH’s data set. For example, the use of complex statistical tools may not be appropriate for MAH’s with a small data set.
- That data from all appropriate sources are considered.
- MAHs have systems in place to assure the quality of their signal detection processes.
- That any outputs from cumulative data review are assessed by an appropriately qualified person in a timely manner (and that the QPPV is informed of new information relevant to the evaluation of risk/benefit).
- That the MAH takes timely and appropriate actions and decisions based on the outputs from cumulative data review.
- That the MAH adequately documents signal detection and evaluation.
Signal detection performed only at the time of PSUR production is unlikely to be adequate in most situations.
However, for a generic substance with low numbers of ADRs (and other safety information) generated which is currently on a six-monthly PSUR cycle, this may be appropriate.
