How COVID-19 has changed pharmacovigilance
The race to provide vaccines and treatments for coronavirus has seen a number of COVID-19 drugs reach the market in record time. Darcy Jimenez explores how drug safety can be best ensured during this time, and how the pandemic has catalysed innovation in the area
In the months since the coronavirus pandemic began, a number of COVID-19 medicines have been made available to the public at faster rate than would usually be possible, as drug regulators’ approval processes have been expedited in response to the demand.
Numerous countries have granted emergency use authorisation of new vaccines that are much needed, but for which very little data on adverse events (AE) is currently available. Ensuring the safety of these new drugs remains a priority – but are pharmaceutical companies’ pre-pandemic methods up to the task? At a time when medicines are needed so urgently, what steps must be taken to ensure pharmacovigilance remains effective?
Three coronavirus vaccines have now been authorised for use in the UK, and several more are at advanced stages of development worldwide. Acknowledging the need for a robust COVID-19 vigilance plan, the MHRA published a report detailing its approach to the post-authorisation safety monitoring of new vaccines, and wrote that it “oversees the manufacturers’ legal responsibilities to undertake such vigilance”.
Joe Rymsza, Vice President of Pharmacovigilance and Regulatory Technology Solutions at IQVIA, tells Pharmafocus that prior to the pandemic, pharmacovigilance was an area that had seen very little innovation. Drug safety has been thrust into the spotlight as the world watches and waits for coronavirus vaccines and treatments, and pharmacovigilance has had to evolve as a result.
“There’s not a day that goes by where you don’t see on the BBC, or CNBC, or other media outlets, the discussion revolving around the safety and efficacy of the drugs,” Rymsza says, “which really is ensuring that safety remains a critically important operational function within drug development organisations.”
Dr Andrew Garrett is Executive Vice President of Scientific Operations at ICON plc, which provided clinical trial services to Pfizer and BioNTech for their investigational COVID-19 vaccine programme this year. Speaking to Pharmafocus, Dr Garrett explains that while pharmacovigilance reporting standards have remained unchanged, the task of submitting vaccine safety data to regulators has been challenging, and has required new approaches.
“In the case of the Pfizer-BioNTech vaccine, the data had to be monitored and cleaned each day, meaning that for a trial of this scale, we had over 1,000 ICON personnel assigned, managing the collection and quality of the data,” he says. “In addition, approximately 90% of the trial monitoring was conducted remotely – at over 150 study sites set up in the US, Latin America, Europe, and South Africa. We took a global approach to solve this challenge – for example, utilising a team in Japan to provide remote monitoring capabilities to cover sites in the Americas, to make the most of different time zones.
“Working remotely allowed us to be much more agile with our resource assignment, and technology has played an enormous role in making what we achieved possible.”
Rymsza says that the urgency of the pandemic has prompted companies producing COVID-19 drugs to explore technological solutions for monitoring their safety.
“All of a sudden, the volume of adverse events was going to grow exponentially associated with the introduction of the vaccines, as well as the delivery and administration of these vaccines to billions of people,” he says. “So now you have people not only thinking ‘how do we do that?’, but also they’re coping with the dilemma that there aren’t enough trained professionals in the world that are available to do the manual processing of the adverse events associated with the vaccines.
“[Pharmacovigilance] has historically been a very conservative part of the organisation, and one that has not been on the forefront of innovation relative to their use of technology, so the automation of intake is something that accomplishes two benefits,” Rymsza explains. “One is, it produces a result often with a much higher degree of accuracy and precision than can be done by a human. Similarly, their use of the technology is really critical to overseeing the increased volume of data that’s being generated as a result of the global vaccine distribution.”
Adverse event reporting (AER) is one of the most time- and resource-consuming activities that regulatory bodies and drug companies must undertake, and involves the receipt, triage, entry, assessment, distribution, reporting, and archiving of AE data from numerous sources. According to Rymsza, the artificial intelligence (AI)-enabled automation of AER is a solution to the additional challenges the pandemic has presented to an already process-heavy area.
AI allows companies to collect and prepare adverse event data from a wide range of sources – including healthcare professionals, vaccine centres, social media, and news articles – quickly and accurately. Smart algorithms can scan countless documents and social media content to identify even obscure references to products and adverse events, with more accuracy and speed than is possible for human readers. AI-powered automation tools can also be used to automatically translate files in different languages, saving pharmacovigilance professionals a considerable amount of time and money, and significantly reducing the risk of errors.
Rymsza explains: “Essentially, you automate that intake, bring it into the system, do algorithmic processing of it using technologies like machine learning and natural language processing to extract the information from it, and expedite the preparation of the adverse event for someone to review.”
In Europe, the French Ministry of Health has implemented adverse drugs monitoring technology on a national level to improve the safety of the country’s vaccination programme. The Medication Shield technology, rolled out by Synapse Medicine in collaboration with regional pharmacovigilance centres (CRPVs) and the French National Agency for Medicines and Health Products Safety, is designed to increase the safety of COVID-19 vaccines in France by managing real-time adverse drug reaction signals on a reporting portal.
Medication Shield automatically encodes adverse drug reaction (ADR) signals into a standardised international terminology (MedDRA), and ranks them by severity. As a result, CRPVs are able to analyse adverse event data faster and more easily, and can prioritise the most severe and pressing cases presented to them. This, in turn, enables health authorities to more quickly identify potential safety issues with drugs and take corrective measures if necessary. The monitoring technology recently enabled France to issue the first pharmacovigilance signal related to hypertension associated with the Pfizer vaccine.
The UK government has also adopted advanced technology to assist in the processing of adverse event reports relating to COVID-19 vaccines, paying GenPact UK £1.5 million to develop a powerful, vaccine-specific AI tool to sift through ADRs.
The need for new technological solutions to the growing volume of AE data for coronavirus vaccines is made clear in the procurement contract for the AI programme. The UK drugs regulator MHRA states: “It is not possible to retrofit the MHRA’s legacy systems to handle the volume of ADRs that will be generated by a COVID-19 vaccine.
“Therefore, if the MHRA does not implement the AI tool, it will be unable to process these ADRs effectively. This will hinder its ability to rapidly identify any potential safety issues with the COVID-19 vaccine and represents a direct threat to patient life and public health.”
The MHRA also told the Financial Times that it expects between 50,000 and 100,000 ADR reports for every 100 million vaccine doses delivered to patients over a six to 12-month period.
Using smart technology to manage the AER process not only simplifies what can be laborious and time-consuming work for humans, but can also help to reassure members of the public who are concerned about the safety of newly developed drugs. Alongside the logistical challenges posed by an overwhelming demand for COVID-19 vaccines, public hesitancy has become a significant obstacle in vaccinating vulnerable populations, with scepticism highest among black, Pakistani, and Indian communities – the ethnicities which are more likely to suffer severely from coronavirus.
The UK’s Scientific Advisory Group on Emergencies (SAGE) said in a document prepared in January that ethnic minorities have “historically been under-represented within health research, including vaccines trials, which can influence trust in a particular vaccine being perceived as appropriate and safe”. There is a responsibility for drug companies and regulators to show that new COVID-19 treatments and vaccines are undergoing rigorous safety testing, and that adverse event data is being collected and processed as quickly and accurately as possible.
Dr Garrett explains that vaccine trials are larger than most clinical development programmes, and therefore have a much higher chance than usual of detecting both common and very rare adverse events.
“The chances of observing at least one “’1 in 10,000” very rare event (per the WHO definition) is 78% with 15,000 participants receiving an experimental vaccine,” he says. “Even with a large clinical trial with a thousand patients in a group, the corresponding chance is less than 10%.
“Furthermore, the regulators have also been reviewing data on a rolling basis, while the standard pharmacovigilance process requires the submission of SUSARS (Suspected, Unexpected Serious Adverse Reaction) within seven days – so safety evaluation is not something that is ever left until the end.
“Of course, as vaccines are rolled out widely via within-country vaccination programmes, events will be recorded that are confounded with the nature of the prioritisation – the comorbidities associated with the elderly and the clinically vulnerable,” Dr Garrett adds. “Disentangling the effects can be a challenge, but this is why regulators such as the EMA have a pharmacovigilance plan for authorised vaccines.”
Rymsza believes that the automation of AER is ultimately where the pharmaceutical industry is headed: “Once you get enough data in the engine, you’ll be in a situation where the engine is able to be trained in a way that you can determine not only what the product and the potential adverse event is but be able to automate, ultimately, the reporting of that to the relevant health authorities.
“In certain cases, we’ll be in a mode, probably a year from now, where there’s enough data that comes from the various surveillance programmes that are underway to actually automate the assessment processes as well.”
Adopting advanced technological solutions to perform vigilance tasks efficiently could hold the key to improving the public’s trust in the COVID-19 vaccines and other medicines that are being recommended to them. COVID-19 has forced drug companies to innovate in this way – and while the industry may have been heading towards an AI-focused future already, the pandemic has sped up the process.
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