University’s ‘mission impossible’ professor gives farewell lecture

Staff at the University of Dundee are set to pay tribute to distinguished Clinical Pharmacologist and Pharmacoepidemiologist Professor Tom MacDonald at his farewell lecture tomorrow (20 March). 

Professor MacDonald, who has led some of the most significant research into drug epidemiology in the past four decades and pioneered new approaches, is set to bow out with a lecture entitled ‘From Pharmacology to Clinical Pharmacology… and beyond’.

In an interview before his lecture, he spoke about what has inspired him in his groundbreaking work as one of the world’s leading and prolific clinical pharmacologist and pharmacological epidemiologists, and how the word ‘impossible” is not one he holds in his vocabulary.

“I am pleased to have done things which others said would be impossible to do,” said Professor MacDonald.

“I’ve always felt like the Red Queen in Alice Though the Looking Glass, who did ‘six impossible things before breakfast’.”

His ambition has been founded on his belief in the positive impacts pharmacoepidemiology - research into interactions between drugs and human populations - can have on people and society.

He said: “I've always been interested in drug action and how tiny little things like pills can cause big changes, it can be quite amazing.”

Prof MacDonald’s many achievements include establishing and leading the University’s successful MEMO Research unit with Professor Isla Mackenzie. He also co-chaired the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP). 

His 400-plus contributions to clinical research have been high on impact and relevance to human populations across the world. This clinic-to-pharmacy counter work has included studies into hypertension, cardiovascular disorders, Covid and medicines safety, such as the safety of non-steroidal anti-inflammatory drugs (NSAIDs).

Professor MacDonald began his University career studying Physiology in Aberdeen but moved to Pharmacology. He then studied medicine at the University of Dundee.

Under Denis McDevitt, former Professor of Clinical Pharmacology at Dundee, Professor MacDonald worked on what he described as a “a system to associate adverse events with dispensed prescriptions which eventually became MEMO research”.

Having a CIBA travelling fellowship, enabling him to visit other pharmacological record linkage systems, he then started tackling in Scotland what had previously seemed an impossible dream.

“Record linkage systems are how you take exposure records of prescribing drugs and link them into outcomes,” he said. 

“We received grant funding from the Scottish Chief Scientists Office to do this and that did one of the impossible things which was to put the unique (CHNo) identifier onto prescriptions which meant you could create the links to hospitalisations.

“In 1991, MEMO had the entire community health index in Scotland that enabled such adverse reaction research.”

This made the allocating of drug exposure to patients much easier and the next challenge, which was successfully overcome, was to work on the dosage instructions for individual patients.

Professor MacDonald said challenges would appear at every corner in his research career.

“In pharmacoepidemiology you look at the exposure and drugs – the drugs and output,” he continued.

“The problem is that people who take drugs are ill and those who do not take drugs are not ill. This is just one of the biases to be overcome. Confounding by indication.

“A lot of drug safety research is done on observational data. This is more feasible when examining the unintended effects of prescribing but when you want to try and look at effectiveness, it is much more of a challenge; that is the big problem in Pharmacoepidemiology.

“I gave a lecture at the International Society for Pharmaco-Epidemiology (ISPE) about how we should randomise people within databases to control for confounding but everyone said that's impossible. So, that is what we did over the next few decades and a lot of our big studies which we published were randomising people within databases.

“Where you randomise people, you follow them up by looking at hospitalisations and deaths, and that has worked very well. Everyone else said it couldn't be done but it can be done and that formed the basis of what we now call Remote Decentralised Trials.”

At every turn, Professor MacDonald would face challenges but this this just led to greater determination, and novel ways to ensure the success of the research.

A leading pharmaceuticals company needed research done into the Non-Steroidal Anti-Inflammatory (NSAID) Celecoxib which Professor MacDonald undertook at short notice when the company needed to fulfil a commitment to the European Medicines Agency.

This became the SCOT Study and he said, “They offered a lot of funding to the study and from a standing start we did the study. It took a while to light everything up but got we lots of people from the UK and Europe to help.”

In order to comply with European regulations, some unique issues had to be overcome.

“We set up our own licensed pharmacy for the trial in the Hypertension Research Centre of the hospital. People said that was impossible but that's what made me do it.

 “We also had to set up the pharmacy because some distribution systems wanted to charge us millions, and that wasn’t going to happen. As part of this, we had to do a survey of letterboxes to send parcels because there is no standard size of letterbox in the UK and Europe.”

Reflecting on his career overall and the future of the profession, Professor MacDonald said, “One of the things about being an academic clinician is you never know quite what this month’s priorities are.

“When I started out, I was told by some that Clinical Pharmacology was a dead subject but look at where we are now. There is no perfect drug. Drugs are all the same, people are different. Drugs don’t cause side effects, but people have side effects to drugs and I think understanding that  - profiling people to give them the right drugs – that is going to be the future.”