Signal detection is a process of actively searching and identifying safety signals from a range of data sources. Businesses must be able to manage signal detection and evaluate these to determine the clinical risks associated with multiple impacting factors. Further, benefits, risk balance, and treatment are impacted by the underlying cause, clinical trial data, environmental factors, etc. Opting for signal management means ensuring workflow and process control.
Need for identifying sources of signal detection
The common sources for signals are spontaneous reporting systems that are used by regulators. Likewise, the data from databases like the FDA Adverse Event Reporting System or FAERS, Vigibase, etc. can be used.
Once the drug reaches the market, it will have individual case safety reports called ICSRs. It is tough to review the contents of the reports for adequate signal detection. Hence, prioritization must be done to get an effective evaluation.
Also, the adverse events must be categorized using the MedDRA hierarchy to be able to identify the signals using levels of granularity.
Top Sources for Signal Detection
Top Sources for signal detection can include the following –
- Unsolicited sources like spontaneous reports, literature, social media, etc.
- Solicited sources – Clinical trials, registries, surveys, post-approval safety studies (PASS), epidemiology studies, compassionate use programs, etc.
- Agreements – Safety data exchange agreements like SDEA between two or more organizations.
- Regulatory agency resources like the FDA Adverse Event Reporting System, Eudravigilance, Pharmacovigilance Risk Assessment Committee, or PRAC.
Professional safety signal detection methods
Professional safety signal detection methods can rely on a variety of sources for detection, evaluation, and management through methods like –
- Global safety database listings and tabulation – a collection of information from global literature on aspects like – class effects, drug interactions, etc.
- Blinded/open-label clinical data like DSMB summary, clinical study reports,
- Emerging pre-clinical findings like – teratogenic analysis,
- Regulatory agency information through sources like PRAC findings, FDA, etc.
- Competitive product labeling system.
Why do we need to perform signal detection?
A product that aims to seek marketing approval from regulatory bodies must show a positive benefits-risk ratio. The information on the benefits-risk is reached through years of research through pre-clinical and clinical studies i.e. phase I-IV.
The limited exposure in the clinical trials and with exclusion criteria, lack of long-term treatment effect, and limited concomitant medication exposure, these trials do not reach the exact power to identify the adverse reactions. Thus, there is limited information on the safety and efficacy of the medical product at the time of attaining marketing approval.
To ensure that the benefits-risk ratio stays positive, the Marketing Authorisation Holders or MAHs are expected to identify new sources of information related to the product. This can be attained by attaining active surveillance by expedited reporting and signal detection services.
Professional signal detection services
The safety signal monitoring process has three primary steps –
- Pharmacovigilance signal detection,
- Validation,
- Confirmation.
The process detects the changes in the risks associated with the pharmaceutical product after ICSR. It also helps to offer necessary recommendations about the actions and changes desired by the healthcare industry. On the other hand, regulatory authorities require the signal management processes to be tracked and documented to ensure effective compliance.
With an expert team backing your organization for safety signal monitoring and management, it is easy to determine the signal detection. These agencies can also interact with the customers to develop a solid Pharmacovigilance plan and monitor the processes. For this, they may adopt a combination of proprietary and publically available safety data.
Such professional services are consistently reviewed internally to ensure adequate regulatory compliance at each stage. They also assist your brand with the following –
- Identification of new safety signals or determining the changes in the existing risk concerns. This is evaluated from the ICSR database, literature, regulatory website, etc.
- Utilize a range of in-house tools and databases for signal detection.
- Tracking the signal management processes.
- Review safety signals by the Pharmacovigilance Risk Assessment Committee or PRAC.
- Performing label analysis and updates.
- Provide recommendations from signals assessment, risk minimization, etc.
- Preparing signal management tracker and annual signal reports.
For small businesses, assessment of the signals can be a resource-intensive process and this is why it is important to prioritize the takes to take quick action. After this, other sources must also be systematically analyzed and reviewed. This helps to determine if sufficient evidence of a casualty exists then it is important to notify the concerned regulatory departments within the company.
After the confirmation of a signal, the product can be recalled or withdrawn. Further, information must be conveyed to the customers, solutions must be identified and appropriate actions must be taken.
Methods of signal detection and management
To validate the signal, it is best to establish the fact that the data and evidence collected that supports the signals detected have sufficient evidence that creates a pure causal relationship without confounding factors.
Any evidence of the existing awareness, temporal, and biological relationship must be considered while assessing and validating the signals. Further, regulatory agencies like EMA boast of repositories like the Pharmacovigilance Issues Tracking Tool or EPITT. This is useful for entering validated signals and communicating the Pharmacovigilance and risk management issues between the member states and EMA.
However, signals for which the validation process doesn’t have any causal association are not entered in the EPITT. A validated signal has to be reviewed and assessed.
