Imagine this all-too-common scenario. You are the head of a mid-sized pharmaceutical company and one of your most successful post-marketed drugs is up for its annual Periodic Adverse Drug Experience Report (PADER). Upon draft of this required annual report, you learn that there are multiple “safety signals” that were missed throughout the year. What you thought would be a routine PADER now involves a complex and confidence-eroding situation where your firm has to answer for these crucial mistakes to the FDA inspection team. Wouldn’t it have been nice if you could have had an effective safety signaling process in place throughout the year to avoid the stress and potential violations that may be associated with this?
Safety signaling has evolved over the years to utilizing the most high-tech safety signaling tools. This blog post is aimed to provide a basic introduction as to what a safety signal is, why safety signaling is important, and how one in the field of Pharmacovigilance would go about conducting a safety signal workup once the safety signal “bells” start ringing.
What is a Safety Signal?
First off, there have been various definitions of what one considers a safety signal so for the purpose of this blog, I identify a safety signal as any reported information that has the potential to jeopardize the benefit-risk profile of a post-marketed drug. Typically, three or more adverse events are identified in order for a safety signal to generate. This takes into account the seriousness of these events, as well as the quality & source of the information from which these events were obtained. A few examples of where potential safety signals may originate from are Individual Case Safety Reports, Drug Regulatory authorities, Literature Searches, Clinical studies, Scientific Conference where a poster presentation or case report was presented which included your respective product, and last but not least, the media.
When should the “bells” start ringing?
Any time you have a cluster of similar adverse events arrive, it would be highly recommended to further investigate the severity of these events, the location or country of origin, as well as comparing the frequency of these events to your safety data from your previous month. A fatal outcome of any adverse events should be an immediate alarm “bell”. Maintaining a watchful eye for any Hepatic, Renal and Cardiac adverse events that are described to be life-threatening and intervention was required. Unexpected events, as well as “unusual” expected adverse events (i.e. unusual progression of disease), are also cues to maintain a high level of alertness to ensure these adverse events do not go unaddressed.
How to conduct a Safety Signal Workup
First and foremost, DSN recommends you establish a written easily-accessible standard operating procedure that outlines every step and scenario one may have to take and face once the safety signal “bells” start ringing. Next, it is crucial to safety signaling that your safety database has the capabilities for your team to run accurate and up-to-date reports. We recommend your data is backed up by a modern virtual safety database (cloud hosted). You may have the ability to have your safety data system conduct automated searches for disproportionalities or run periodic reports specific to adverse events you’ve picked out or noted to be of importance to the safety profile of your product. Once you have your requested data (or are handed the data which prompted you to conduct a safety signal workup), you now have to engage in the challenging exercise of data interpretation. This is where deep experience is a plus, as interpreting the many complex layers of data and patient impacts can seem daunting. If you’re working with a drug safety partner, they can be responsible for analyzing the safety signals, identifying any concerning patterns, and determining whether the workup needs to be escalated further within your organization.
Why is it important to have a safety signaling process in place?
Risk minimization! You’ve worked too hard to get your drug to this point of its lifecycle to jeopardize the outcome. Your benefit-risk profile has always been viewed as balanced and neglecting a potential risk to the population that you serve through your drug will not go unnoticed in this environment. Signal detection and assessment is a crucial process to maintaining a favorable benefit-risk profile and should be lifelong for every medicinal product.
Hopefully you’ve found this blog helpful in understanding safety signal detection and why it is important. If you’d like to talk more about your specific situation or challenges with signal detection, we’d love to connect. Let’s talk!
Ricardo Velazquez, MD
DSN Lead Medical Reviewer