Medical products are intended to treat and make people feel better. But sometimes, they can also cause harm. The concern for drug safety gets aggravated during health emergencies, such as the ongoing COVID-19 pandemic – countries have to introduce new medicines and vaccines based on limited clinical trials and without full scientific information about the extent to which the new products are effective and safe. If the product causes an adverse effect, it could erode the trust of consumers and patients in government-regulated products and the health care delivery system at large, which can set back not only efforts for managing emergency health situations, such as COVID-19 but also for long-running disease programs, such as TB and HIV/AIDS, and for routine health care.
Countries must have systems in place to ensure that medicines are safe, effective, of good quality, and used appropriately. This presents challenges for many low- and middle-income countries (LMICs), which often have weak systems for doing so. Despite recent progress, many LMICs have underinvested in medical product regulatory systems, including pharmacovigilance (PV) systems with the legal mandate to enforce adverse event monitoring, reporting, and mitigation.
In August, USAID Medicines, Technologies, and Pharmaceutical Services (MTaPS), a program implemented by a consortium of global, regional, and local partners led by Management Sciences for Health, hosted a webinar on how pharmacovigilance systems mitigate risks and help build trust in new medicines, vaccines, and technologies and the tools countries can use to establish and operate PV systems.
Below are highlights from the webinar.
Clinical trials don’t tell the whole safety story
The development of PV systems started out some 50 years ago with a World Health Organization (WHO) program for international drug monitoring, which has evolved over the years. Efforts initially focused on adverse drug reactions, but today, “PV methods focus on safety surveillance and efficacy throughout the lifecycle of products and include product quality issues and medication errors. The growing availability and use of medicines underscore the need for better monitoring and safety,” said Andy Stergachis, professor of pharmacy and global health and director of the Global Medicines Program at the University of Washington, an MTaPS partner.
Much remains unknown about the safety profile of medical products at the time of market approval, particularly in real-world conditions and especially in resource-poor settings and understudied populations, Stergachis pointed out. Preclinical and clinical studies have inherent limitations as less-common safety issues may not be detected in clinical trials that operate with a limited number of patients and for a limited time. For example, most clinical trials exclude pregnant and nursing women and children.
“The rush is on to introduce new or repurpose medical products to combat COVID-19. But there are real issues with efficacy and adverse effects, especially in underserved populations,” Stergachis said.
Steps to establishing a functioning PV system
A functioning PV system involves people, functions, and structures working well together, including patients, manufacturers, health facilities, a central PV unit, and regulatory agencies. WHO developed a baseline of minimum requirements for a functioning PV system in 2010, including a national reporting system and communications strategy.
It’s also key for country PV systems to be able to share their data with a wider audience, including contributing to the global adverse drug reaction database, said Comfort Ogar, principal technical advisor for MTaPS. That means they must align with global standards and guidelines, which is one of the areas MTaPS helps countries work on.
In 2018, WHO launched the latest version of the Global Benchmarking Tool for evaluation of national regulatory systems, which was an important step toward aligning approaches for benchmarking regulatory systems. The tool helps countries assess the capabilities of their regulatory system, which includes PV, and sets a clear path for improvement using institutional development plans.
“Our first level of support in establishing PV systems is ensuring that there is a legal framework on which to build PV activities,” Ogar said. "That’s followed by strengthening the human resources of a central PV center, defining clear roles, and building the necessary technical skills and infrastructure to do the work – collection and analysis of data, risk evaluation, reporting, and use of data for decision-making to update treatment guidelines."
A PV system is particularly critical during health emergencies. “It’s important that a system should be able to quickly respond to issues, as adverse effects can quickly derail a system, especially if there are rumors around a medicine,” she said. “It’s important to have a system in place that can quickly collect, analyze, and disseminate relevant data. This is what pharmacovigilance systems should be about.”
Utilizing technology for PV
PV systems are helping to address a need for another infectious disease in Mozambique. According to Dr. Jamal Mario, head of the PV unit of the National Directorate of Pharmacy, the country introduced new clinical standards for the use of dolutegravir-based treatment for HIV in March 2019 but needed to keep an eye out for potential adverse effects, including neural tube defects. MTaPS supported the government in establishing an active surveillance system for the drug, including getting ethics approval, developing a data collection protocol, and deploying PViMS, a web-based tool for data collection and analysis. The team trained several health workers on the activity.
By July 2020, more than 1,800 patients were enrolled in the monitoring cohort.
“There is increased confidence and capacity within the PV team to establish similar systems for other new medicines, such as COVID-19 treatments and vaccines,” Mario said.
Establishing procedures, training users for pharmacovigilance
In the Philippines, active drug safety monitoring and management (aDSM) have strengthened the National TB Control Program. Dr. Mary Rosary Santiago, TB technical officer for the USAID-funded and FHI 360-led TB Innovations and Health Systems Strengthening program in the Philippines, explained how the aDSM program has helped the country identify and manage adverse events and collect data on novel regimens and new and repurposed TB drugs.
In 2017, new guidelines for treating multidrug-resistant TB were released, but health providers had not yet gained confidence in the new regimen. Staff had been trained on how to use PViMS but were not regularly generating data. The TB Innovations and Health Systems Strengthening program worked with the National TB Control Program to develop new policy guidelines for aDSM, with expanded training for PViMS use for frontline health workers.
"Case reporting has increased dramatically, with reports from nine regions in the country. Almost all reported events have had clinical significance," said Dr. Santiago.
When COVID-19 hit, the National TB Control Program instituted a hotline and telemedicine to continue to gather information on adverse events and to make sure TB treatment was uninterrupted during the pandemic.
PV systems a must to monitor new and existing medicines on markets
PV plays a critical role in helping countries quickly establish the safety profile of a product through systematic data collection and analysis of adverse effects.
“The role of PV is not necessarily in taking medicines off the market or making changes to guidelines. It’s also to make sure drugs on the market continue to be safe and maintain a favorable benefit-risk balance,” emphasized Ogar in her remarks wrapping up the webinar.
Read more about MTaPS’ PV work and support to countries.