COVID-19 drove an unprecedented level of innovation across multiple stakeholders to deliver effective vaccines in less than one year—a remarkable achievement.  Accelerated vaccine development and approval ensured a heightened focus on the safety monitoring of vaccines placed on the market. Unlike other approved treatments, some of the key challenges in expediting the roll-out of vaccines, includes the inoculation of generally healthy individuals on a global scale, the rate of vaccination administration and the need to gather quality data quickly to ensure swift intervention in the case of a safety crisis.

Despite those key challenges, to date, nearly five billion people worldwide have received at least one dose of a COVID-19 vaccine, equal to almost 64 percent of the world population.  IQVIA Lifecycle Safety has supported the response to the pandemic through its work supporting complex pharmacovigilance activities for several of the approved COVID-19 vaccines and treatments.

Periodic Safety Update Reports (PSURs)

Periodic Safety Update Reports (PSURs) are consolidated pharmacovigilance findings for a drug or a vaccine, which describe the worldwide safety experiences and detail the product’s benefits and risks for a designated time interval post-authorization.

There were several layers of challenges encountered during the preparation of these safety reports for the COVID-19 vaccine trials. The sheer volume of the vaccine data associated with each periodic report presented challenges for data presentation and analysis in a very short space of time. For example, due to the large volume of adverse events received over a short space of time, we encountered challenges with preparation of data listings and tabulations. We found that traditional analytical tools could be improved to handle the review and analysis of large data sets in a short space of time.

Making intelligent connections between IQVIA’s advanced analytics, transformative technologies, breadth of global data and domain expertise, the team was able to quickly route through the challenges stemming from the large volume of data. With extensive data management expertise, IQVIA provided customized solutions for the varying roadblocks in preparing the safety reports. New technology solutions were created to generate and analyze the large volume of data compared to traditional data formats. Expert medical writers were able to interpret and analyze the large collection of data insights to produce high quality aggregate reports through teamwork and close collaboration with sponsor stakeholders.

Proper oversight at the varying stages of development for the reports of such large volumes was a multi-pronged responsibility, requiring agility. It was critical that the team maintain the quality and compliance within the content and quickly take corrective measures when necessary. IQVIA’s global presence allowed for effective coordination of resources across our global teams to work quickly with support through different resources to maintain oversight and business continuity.

Risk Management Plans (RMPs)

A Risk Management Plan (RMP) is an essential and evolving document required in certain countries prior to authorization under the safety surveillance umbrella. The RMP summarizes a product’s safety profile and lists further post-authorization studies as well as any risk minimization measures required to manage the identified risks of the medicine.

For COVID-19 vaccines, marketing authorization holders (MAHs) were encouraged to use the European Union format or any global or core RMPs with standard sections containing safety specifications, pharmacovigilance activities and risk minimization activities and evaluation. Region-specific annexes were included containing epidemiological characteristics, medical practice, ethnicity and limitations of logistics and regulatory systems. Unlike the routine RMPs for other medicines, RMPs for COVID-19 vaccines have stringent timelines due to consecutive submissions, given the dynamic nature of the safety profiles. An additional challenge was that multiple RMPs were being developed in parallel like the European RMP, core RMP and other country specific RMPs. Given the dynamic data inflow, the IQVIA team stayed agile and ready to make appropriate adjustments, per country-specific requirements. Upholding specific and ongoing communication with different functions of the MAH (e.g., safety, regulatory, epidemiology, clinical, non-clinical teams) was very important. Also, the team’s ability to upkeep safety specification updates, routine and additional pharmacovigilance activities and risk minimization activities updates across RMPs in a short timeframe was key to effective document development and dissemination.

Signal Detection

Signal detection is one of the key activities required to monitor product safety during its lifecycle. For COVID-19, it was more critical than ever as these vaccines received an emergency authorization approval in many countries and required more stringent vigilance to ensure the safety of the large recipient population across the globe. Like other documentation and processes, COVID-19 signal detection analysis was extremely challenging due to the large volume of data and complexities of the insights. There were several topics to be analyzed each week and the frequency of analysis for adverse events of special interest (AESIs) and other standard topics were much higher than traditionally done for other medicines.

Like the PSURs, the traditional platform for signal detection analysis was not effective due to the large data volume. The team developed a new technology solution for the needs of COVID-19 signal detection analysis. Given the dynamic and evolving nature of the data, continuous monitoring was necessary to understand the vaccine safety profile.

Cumulative data review at every signal detection analysis added to the list of challenges faced. A well-coordinated and collaborative approach was adopted wherein emerging safety concerns and health authority requests were managed by the sponsor, as per standard procedures described by health authority guidance. In case of any potential signal identified, it was prioritized, evaluated and risk minimization measures were implemented, such as updating reference safety information and the risk management plans.

During the signal detection analysis, the dosage schedule analysis over a period played a vital role to identify any trends in events reported and related to a specific dose number. With the help of new technology, IQVIA performed time to onset analysis with respect to dose details to identify any trends in events or with signals.

Another crucial element was the analysis of Vaccine Adverse Event Reporting System (VAERS) and Eudravigilance Data Analysis System (EVDAS) data:

• For VAERS, bi-weekly disproportionate analysis was performed to identify any signals
• High volume of data during EVDAS analysis was addressed through implementation of a robust process by analyzing EVDAS signals of disproportionate reporting (SDRF=Yes) on a monthly basis.

Together, IQVIA’s signal detection and medical science teams also supported signal detection in for one of the largest ongoing COVID-19 vaccine trials by generating unique reports to identify any safety concern trends in terms of early signals or risks.

With COVID-19 vaccine studies, the team anticipated close scrutiny by regulators, and along with strong interest from the public and media generated the presumed need for extra attention to detail internally at trial sites, resulting in a high number of audits and inspections to ensure compliance in accordance with the international health authority guidelines. IQVIA successfully anticipated and addressed the various layers of challenges and set repeated gold standards in supporting sponsors in nearly twenty COVID-19 vaccine related audits and regulatory inspections.

With more than two decades of experience in monitoring the safety of medicines globally, the IQVIA Lifecycle Safety team played an integral role in the effort to ensure the safety of COVID-19 vaccines to the highest international standards.

If your interested in learning more about this expert team’s capabilities in drug safety analysis and monitoring, please contact us (link to web form)

Covid World Vaccination Tracker - The New York Times (nytimes.com)