ISO 9001:2015   |   ISO 27001:2013

Advanced Signal Detection: Tools, Triage & Escalation – MMS Attends In-Person Training Course Offered by DIA

by Kulin Mehta

Posted on 6/1/2016 10:08 AM

The day you stop learning is the day you stop growing. The ongoing pursuit of knowledge makes us not only more agile but also gives us the right tools and skill sets to evolve and enhance productivity. Nurturing the corporate values of “Strive for Good Science” & “Value Talent”, MMS has always fostered an environment of continuing education allowing employees to sharpen their skills with up to date knowledge and information from the pharmaceutical and regulatory world. What better way to learn than a conference where you meet, network and brainstorm.

I recently got an opportunity to represent MMS Holdings at the DIA in-person Training Course ‘Advanced Signal Detection: Tools, Triage and Escalation’ at the DIA Global Center, Dupont Circle, Washington DC on a bright, sunny spring day! Certainly the timing was great as DC was wrapped under a canopy of cherry blossoms. The conference also comes at the time when MMS is currently evaluating tools to support signal detection across our post-marketing pharmacovigilance activities, and we were excited to contribute our expertise to the interactive dialogue at the conference.

The two day training agenda on advanced signal detection was led by the esteemed faculty at DIA James Buchanan, PharmD, Drug Safety Consultant, Covilance LLC. The conference consisted of pharmacovigilance and drug safety focused industry members from a variety of pharmaceutical companies such as Amgen, Gilead Sciences Inc, Genentech to name a few. The first session covered some of the basic fundamentals of signal detection. Citing some real life examples of post-approval drug-induced liver toxicity (DILI) such as Bromfenac withdrawal & clinical trial unexpected serious adverse reactions such as the Bial BIA 10-2474 trial, the presenter highlighted the importance of signal detection in the lifecycle of a drug. It is a regulatory requirement for the industry to have a system in place and procedures for systematic signal detection that are adequately documented in formalized procedures (CIOMS Working Group VIII Report, 2010).

The sessions were highly interactive with ongoing Q & A’s with the presenter. On a more technical and practical application perspective, the presenter trained the attendees on the interpretation of data mining outputs that contained signal scores using the frequentist and Bayesian methods (MGPS/BCPNN). This was followed by a hands-on exercise session. A signal management system is comprised of key facets that include maintenance of a signal detection tool kit; interpretation, triage and prioritization of signals; evaluation and decision making on risk minimization strategies; and finally the documentation and tracking of signal detection activities. Day 1 wrapped up with best practices on the use of publicly available adverse events datasets such as the US FDA AERS & WHO Vigibase. MMS was able to share in our group session some of the best practices and tools we have used for systematically tracking safety signals and the challenges associated with the same.

Day 2 of the advanced signal detection session involved signal evaluation of the drug-event pairs and various types of causality assessment methods such as the Naranjo ADR probability scale, French imputability method and the Bradford-Hill causality criteria. There was an open discussion between the various industry representatives on the best practices adopted by each for their signal detection methods and the challenges faced. One of the important steps for signal detection is causality assessment that relies hugely on expert judgement; however, this comes with interpersonal variability. MMS has learned that it is very crucial to establish consistency in the assessments of safety signals. Some of the algorithmic methods involving data mining do help achieve consistency in evaluation of signals; however, clinical judgement is indispensable. The conference ended with a final session on the various benefit-risk frameworks, safety specification and risk characterization, GVP module IX signal detection requirements, signal analysis, and finally the quality requirements to meet industry standards for a signal detection system.

This DIA conference was extremely informative and granular in addressing the technical requirements for ensuring high quality signal detection systems. I was happy to represent MMS at this in-person DIA Training Course to share our experiences in supporting this area to ensure the long term safety of products in the market.

Regulatory Submission Support Based on Strong Science and Strength of Process. The difference is in the data!