Key Takeaways

• Simplification: The new EudraVigilance (EV) system has simplified the reporting of individual case safety reports (ICSRs) and adverse drug reactions (ADRs), but good pharmacovigilance practice (GPvP) inspections continue to identify both under-reporting and over-reporting.
• Harmonization: Aligning the safety concerns between the product safety update report and the risk management plan remains problematic in the EU; EMA and FDA continue to have different visions, and focus on different products, for signal detection; other global initiatives are working to protect patient safety in countries with limited regulatory and PV resources.
• Risk Communication: Early patient involvement in healthcare development is also shown to improve and expedite identifying risk information and communicating that risk information to the public.

Why this is important: Patient safety largely depends not only upon safe products but also on appropriate (safe) use of these products after they’re approved for the market. “Safe use” is generally defined by identifying and communicating the benefits and risks of that product. Post-market safety monitoring keeps patients safe.

Simplification

Marketing Authorization Holders (MAHs) have a legal obligation to monitor EV data for safety signals about their products. “We are always, especially from the company side, complaining that there are some complexities in the reporting and in the communication with the regulatory authority,” Gaby Danan, Pharmacovigilance Expert (France), suggested. “The new EudraVigilance system for reporting has simplified the reporting.”

In February 2018, an EV signal detection pilot introduced a new Electronic Reaction Monitoring Report (eRMR) tool to make it easier to monitor EV data for signal detection. Through this eRMR pilot, the EV Expert Working Group reported to EMA that many EV users still struggle with the new, simplified access system; and that as MAHs work to identify and remediate causes of duplicate recording, more detailed guidance on MAH expectations for processing duplicate EV cases would be helpful.

Another presentation summarized output from 20 GPvP inspections conducted by the MHRA (UK) GPvP Inspectorate since November 2017, 15 of which included review of simplified ICSR reporting to EV:

• Over-reporting
  • ICSRs derived from literature articles when the product had not yet been placed on the market.
  • ICSRs derived from analysis based on secondary use of data.
• Under-reporting
  • Several non-serious EU ADRs received after November 2017 not reported to EV according to 90-day reporting requirements.
  • Exclusion of ownership of medicinal products in adverse reaction reports from literature articles.

Harmonization

Much like the topic of simplification, pharmacovigilance strategies and processes have been harmonized in some areas but remain lacking in others. “Safety concerns, especially, are differently interpreted by the regulators,” said Danan. “WHO told us that they are willing to implement a new three-year project, Smart Safety Survillance.”

Project 3-S: Smart Safety Surveillance

Access to vaccines has grown in low- and middle-income countries (LMICs), but with no proportionate investments or improvements in pharmacovigilance structures or activities, for the past two decades. This is of particular concern from the PV perspective because the pipeline of forthcoming novel products remains sizeable, and many of these products were developed in well-resourced settings and approved on the basis of safety data that may not be entirely applicable to the population and context of these countries.

Launched in 2017 through a new partnership with The Bill & Melinda Gates Foundation, the WHO Smart Safety Surveillance Project (Project 3-S) proposes to strengthen pharmacovigilance capacity in LMICs and, in the long-term, establish end-to-end safety surveillance of products from their clinical development to the post-market stages. Project 3-S will leverage resources available from the WHO International Drug Monitoring Programme, the Global Vaccine Safety Initiative, Uppsala Monitoring Centre and others; and liaise with other ongoing projects such as the African Medicines Regulatory Harmonization initiative. It will first focus on selected medicines and vaccines scheduled to be introduced in the next few years.

Risk Communication

“There are new ways to improve effectiveness of regulatory decisions, mainly an early involvement of the patient in drug development and beyond drug development, which means during the lifecycle of the medicine,” Danan explained.

Risk Communication Lessons from Patients

• Sharing their real life experience with the implications of regulatory decisions.
• Translating clinical and regulatory outcomes, through this experience, into information.
• Translating that information into language readily understood by other patients.
• Disseminating that information to help other patients and their clinicians.

The health literacy of patients, and their trust in experts and authorities, are essential aspects of this communication environment.