July/August 2024 • PharmaTimes Magazine • 28-30
// LIFE //
A story of our times
30 years at the forefront of pharmacovigilance – Saad Shakir’s remarkable journey
When Saad Shakir embarked on his undergraduate medical degree at the University of Baghdad in the 1970s, he didn’t consider a career in pharmacovigilance.
He didn’t even know what it was. He was focused on learning medicine, completing his degree and gaining the vital experience needed to ensure he delivered quality medical care to patients.
In 1980, Saad moved to Scotland to undertake his postgraduate training in general medicine at Glasgow teaching hospitals.
He passed his postgraduate exam and became a member of the Royal College of Physicians. While training in general medicine Saad was introduced to the understanding of the safety of medicines at the clinical pharmacology unit at Glasgow Royal Infirmary.
This awareness sparked his interest in pharmacovigilance and drug safety.
“Medicine has always been rooted in evidence,” he explained. “But there was a change in the application of evidence evaluation, acceptance of new ideas, new approaches and the evaluation to research, across all disciplines. It opened my eyes, and I became more vigilant towards drug safety and what goes into it.”
Saad giving a presentation at University Hospital of the Ludwig Maximilian University of Munich
Line of duty
These early influences and inspiration from his uncle, a dermatologist and Head of the Army Medical Corps, ignited a passion for safeguarding public health.
This month (June 2024), Saad celebrates 25 years as Director of the Drug Safety Research Unit, a leading pharmacovigilance and pharmacoepidemiology centre.
For more than 40 years, the DSRU has conducted a broad range of safety, effectiveness and drug utilisation studies and studies, to support risk management and risk minimisation of medicines.
The DSRU uses real-world data to conduct studies and systematic reviews to understand the safety of medicines and to understand the risk-benefit balance of medicines and vaccines.
Before joining the DSRU, Saad worked in hospitals and as a GP for many years.
He left Scotland for London in 1991 where he took up his first fully focused role in pharmacovigilance at the Medicines Control Agency (MCA), now known as the Medicines and Healthcare products Regulatory Agency (MHRA).
Saad reflects: “I continued to practice as a GP while working in pharmacovigilance until 2017. Working clinically for 31 years has certainly enriched my pharmacovigilance work.
“Even though pharmacovigilance is data-based, it’s all for the safety of the patient.”
From the MCA, Saad moved for a short period to several roles within pharmaceutical organisations including Glaxo, Wellcome and Sanofi. Despite an abundance of funding and a drive for progress, he admits the pharmaceutical industry wasn’t for him.
In 1999 he received a call from Professor Ron Mann, who was the then Director of the DSRU.
“Ron called me to tell me he was retiring and asked would I consider applying for the role. It offered me an opportunity to stay within the field I was inspired by and wanted to make an impact within, but in a different environment.
“I’ve always loved and cherished independence – when I moved from being a medical registrar to work at the UK regulatory authority and appraisals were starting to become a regular occurrence, initially I was uncomfortable with the fact that someone else was appraising me.
“The DSRU’s independence and the fact that we are the ‘checks and balances, the appraisers’ appealed greatly to me.
“But did I expect to be here 25 years later? Who does? I had a vision and a strategy for the first year or so. But after a few years, I realised this would be my main career role.”
He added: “The DSRU has defined me professionally to a large extent – 25 years working in the same unit – I’ve spent more than half my career in the same place. In fact, many people I work with now won’t know what I did before.”
New order
More than 30 years in any field is a long time and changes will inevitably occur, but nothing moves as fast as the medical landscape and pharmacovigilance is no exception.
Perhaps the biggest change has been the move from the reactive firefighting approach in regulatory decision-making to a proactive way of working. In addition, there is an ongoing move to expand the data sources used in pharmacovigilance to more than just spontaneous reporting.
Studies from the DSRU have explored this topic, showing the trends in sources that support product withdrawals. For example, the use of observational studies to support product withdrawals has increased considerably.
Between 1999 and 2001, it supported 17% of withdrawals, between 2002 and 2011, it supported 26% of withdrawals and an even a larger proportion by 2012 to 2016.
The real-world studies used include cohort, case-control, or other epidemiologic study designs.
Saad said: “Pharmacovigilance has changed considerably in the last 30 years. We’ve gone from a reactive discipline to a more proactive, expansive sector. The DSRU is now a multi-service provider, a broad pharmacoepidemiology unit with multiple research and monitoring safety methods.
‘The DSRU has defined me professionally –
25 years working in the same unit – I’ve spent more than half my career in the same place’
“Spontaneous reporting was and still is the bedrock of pharmacovigilance, but we need more than one method to robustly analyse and understand the safety of a medicine. Over the last three decades or so, the inclusion of real-world data has come to the fore, though the expansion is work in progress.”
Saad believes evidence from observational studies is key to understanding the effectiveness and safety of medicines and vaccines in the real world. They are not competitive but complementary to clinical trials.
He added: “While observational studies have not been usually conducted in drug development, they have started to attract more attention. Real-world data are no longer seen as secondary with no place in drug development, which feels very rewarding.
“Observational studies are often overshadowed by the prominence of RCTs, which are seen as the gold standard of the efficacy of drugs in development, but real-world data is more representative of the population that the drug will serve.
“UK observational studies, in particular, have been considered as some of the best in the world and with good reason. Our NHS system allows for longitudinal follow-ups that simply aren’t possible in many other countries.”
Tales of the unexpected
For the world of pharmacovigilance, the pandemic was a baptism of fire.
The field and its scientists were placed under the spotlight in a way that many had not experienced before. The public learnt about health regulators and their roles, and terms such as ‘adverse events’ became part of general society’s vocabulary.
The demand for information was high and everyone in pharmacovigilance had to find ways to ensure the monitoring of the safety of COVID vaccines and medicines and subsequent data were robust and available as quickly as possible.
Saad said: “Up until that point, it may be fair to say that pharmacovigilance was an unknown entity by many people, even in medicine, and perhaps an underappreciated field by those who did know it. But COVID changed that.
“In a contradictory way, the pandemic was a good, silver lining for pharmacovigilance. Everyone who comes across pharmacovigilance will very quickly, almost instantaneously, say how important it is and those who work with us know the vital role we play.
“But it’s not widely known as some other aspects of medicine are. But once the lockdown started, almost every person in the country, in their living rooms each evening, was hearing information about pharmacovigilance.
Saad at Medical Training Teaching Hospital, Baghdad, in 1976
‘The biggest change has been the move from the reactive firefighting approach in regulatory decision-making to a proactive way of working’
“People’s perceptions of pharmacovigilace have changed, and they started to realise what it entailed and why it was and still is so important to carry out post-authorisation studies on our medications.”
When the pandemic hit, the DSRU team pivoted and threw everything at the country’s vaccine effort.
“The early months of COVID were a big challenge – we just didn’t have the observational data relating to new COVID vaccines and later COVID medicines. All the information was from clinical trials, which are very good for effectiveness and efficacy, but safety outcomes are better studied by real-world studies.
“But actually, it was perhaps our finest hour,” Saad added. “We diverted all our resources to understand and contribute to the understanding of the safety of COVID-19 vaccines and medicines. And I’m proud that we rose to the occasion.”
DSRU experts conducted formal benefit-risk assessments on the drugs proposed to treat COVID, including remdesivir, lopinavir and hydroxychloroquine/chloroquine and conducted post-authorisation safety studies on all the COVID vaccines approved in the UK, including a major study on the AstraZeneca vaccine.
Back to the future
“I work with a great team, and I am enjoying what I do,” Saad said. “And there is a lot on the horizon – the data revolution isn’t going to stop. The whole world, including healthcare, is being digitalised. The more data sources we have, the more we can contribute to the understanding of the safety and effectiveness of medicines.
“We will move away from relying just on spontaneous reporting of suspected adverse drug reactions to multiple epidemiological, genetic, pharmacological and clinical research methods, and evaluate the information together.
“We are exploring how artificial intelligence and machine learning can help us in analysis and interpretation of these more complex data sources.
“There’s also a realisation by research funders, health systems managers, politicians and clinicians about the importance of real-world data. It is all very exciting.”
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