Adverse drug reactions reduced by nearly one third after genetic testing, major trial results to show

Exclusive: Ahead of publication of the PREPARE study, the UK trial lead said the results will be "fantastic" news.
scientist using pipette in laboratory

Carrying out pharmacogenomic testing before prescribing commonly prescribed drugs can slash adverse drug reactions by 30%, results of a major international study will show.

Munir Pirmohamed, NHS chair of pharmacogenetics at the University of Liverpool and UK lead investigator on the ‘PREPARE’ (Preemptive Pharmacogenomic Testing for Preventing Adverse Drug Reactions) study, told delegates at the Royal Pharmaceutical Society’s annual conference that results of the trial were “fantastic” and it was time to implement routine pharmacogenomic testing in the NHS.

The 36-month PREPARE study included 6,950 participants and was conducted in clinical sites across seven European countries, including the UK. Participating countries were randomised to start with either implementing pharmacogenomics-guided prescribing or with standard of care for 39 routinely prescribed drugs — including codeine, clopidogrel, escitalopram, flucloxacillin and simvastatin.

Speaking at the conference on 11 November 2022 in London, Pirmohamed said that final results from the PREPARE trial were expected to be published in The Lancet “in the next few weeks”, but he was able to present some top-line findings.

“The underlying message is that, by undertaking the pharmacogenomic panel approach, we were able to reduce ADRs [adverse drug reactions] by 30%,” he told delegates at the conference.

“I do not know another intervention that is able to reduce ADRs by 30% … it is a fantastic result and provides the evidence that it is now time for implementation.”

Overall, he said, “around 22% of data identified through the trial was actionable in some way — for example, having to reduce the dose or change the drug — which was in keeping with known frequencies in the literature”.

Pirmohamed said that, in 70% of cases in the trial, clinicians decided to change the prescription or dose after seeing the results of a patient’s pharmacogenomic test. In the 30% of cases that they did not, he said that the main reason was that they felt they did not have enough time to read the guidance provided.

Participants who were genotyped in the study were each given a card containing a QR code which, on scanning, would take them to a secure website which would tell them their genotype as well as what to do in terms of if they had that particular variant.

“They could go from one doctor, to a pharmacist to another pharmacist etc. and basically say, I’ve got this card, can you look at it before you give me a drug — and some people did do that,” explained Pirmohamed.

In the UK, pharmacogenomic testing in the health service has been largely restricted to detecting rare genetic diseases, such as Huntingdon’s disease, or before initiating a specific type of chemotherapy. However, The Pharmaceutical Journal revealed in October 2022 that the first-ever NHS pilot of routine genetic testing to guide drug choice in primary care will begin in early 2023 in north-west England.

Speaking to The Pharmaceutical Journal after his presentation, Pirmohamed said that he believed the PREPARE study had provided the evidence needed to justify implementing pharmacogenomic testing across the NHS.

“You can do pilot after pilot after pilot, but actually, now is the time to implement it,” he said.

“We can never have a perfect system right away — you can’t have the perfect be the enemy of the good — and so we do need to implement something and then [we can] make sure that things are working and where they aren’t, we can improve it iteratively.

“The PREPARE trial results provide even more evidence for a pharmacogenomics panel, where you do multiple genes, multiple variants, multiple drugs, and showed that you can produce a clinically relevant endpoint, which is a reduction in adverse drug reaction.”

Commenting on the results, David Wright, head of school of healthcare at the University of Leicester said the results of the PREPARE study mirrored what was already known about the benefits of pharmacogenomics. 

“It is great that we now have EU data from a robust study to demonstrate its benefit within the European context. Other countries within the EU are, however, ahead of us with respect to [pharmacogenomics] implementation and I would argue that the time is definitely now within the UK. I am delighted that this research corroborates that.”

Last updated
The Pharmaceutical Journal, PJ, November 2022, Vol 309, No 7967;309(7967)::DOI:10.1211/PJ.2022.1.165981

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