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Munir Pirmohamed on Pharmacogenomics on Both Sides of the Atlantic

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At A Glance

Name: Munir Pirmohamed

Title: Professor of clinical pharmacology, Department of Pharmacology and Therapeutics, University of Liverpool; Director of the Committee on Safety of Medicines Regional Monitoring Centre for Adverse Drug Reactions

Background: Medical Research Council Clinical Training Fellow; Personal Chair at the University of Liverpool — 2001

Education: University of Liverpool, Medicine — 1985; University of Liverpool, PhD — 1993

How is the study of pharmacogenomics carried out in Britain at the moment?

There are quite a few groups working on pharmacogenetics, and they’ve been working on that for a long time because the UK has a long history of pharmacogenetics. But I think what has been important recently has been the funding from the Department of Health. Indeed, they’ve just funded six large projects under different areas, and those are available on the website.

There are other funding agencies which are funding large-scale studies, such as the DARE study, which is the arrythmia study that I showed a slide of. All these are very clinically based, to see the utility of pharmacogenetics, and implementation to clinical practice.

Which of these studies do you expect to produce data soonest?

All of them have different aims and so on. Clearly, they have their own outcome measures, et cetera, and they will produce their results in different ways, on different timelines according to the study design. But all of them have defined clinical endpoints which they are looking at. And they are designed with the rigor of clinical trials and that is the issue — study design is crucial in how we look at pharmacogenetics, how we implement it in clinical practice, and build the evidence base that is going to be needed to implement it.

How large are these studies?

They vary. But, for example, the warfarin study is made up of 2,000 patients. The target study, which is on TPMT [will have data from] 1,600 [subjects], there are other studies which are 300, which are much smaller studies because they are looking at rare adverse events.

But most of them are huge studies. For example, there is the epilepsy study — it has different arms, but in all those arms, the overall patient number recruited into those different arms will be about 2,000 as well.

I’m sure the pharmacogenomics community is very interested in the outcomes of these large studies.

Absolutely. And I think we need these large-scale studies to build the evidence base. It’s there for the evidence base.

Are results expected anytime soon?

They’ve just started — they’ve just been funded and they’ve just been started. So clearly, to gather the evidence, one has to do the trials with rigor, and therefore wait for the results.

All of them are due to last three years. We should have results within three years.

You mentioned the NIH’s Pharmacogenomics Research Network during your talk — how does the research situation in the US compare to that in the UK?

We don’t have a specific network. We do have individual researchers, who do talk to each other, but we need a formal structure like the NIH has developed — [a structure that] is not only a network, but I think it needs some funding to go with it as well. I think that is the only way to develop it. But it’s not only the UK, it’s got to be EU-wide as well, because the UK is part of the European Union — it is important to develop a European-wide network. There are very important and very strong groups in pharmacogenetics within non-Britain EU, and it’s important to build a network to bring these research groups together.

Is there interest in forming such a network, or at least the initial stages of one?

There’s always interest, but there’s no funding. And so clearly, there has to be funding developed. But I think the kind of network that we would want within the UK — and I can speak from a UK point of view — is that you have the pharmaceutical industry involved in it as well. I think that’s very important. And the dialogue between academia and pharma is very important.

I don’t think the pharmacogenetics network particularly involves pharma, because it is very much academic based, but clearly pharma doesn’t need money from it, but they can be involved in some of the meetings and so on — that’s very important, we need to learn from each other.

There are different models, for example, the Japanese pharmacogenetics research network is all industry, there is no academia. I think it’s better to have a combination of the two.

To merge the two approaches?

Yes. But to have specific funding for academia to do studies. But also to learn what industry is doing, and then foster collaborations. And the important thing about the NIH network is the knowledge base. I think that’s a fantastic resource that they have. I think we need to develop one like that, or collaborate with them. But I can only speak for myself as an individual researcher. I would be happy to put [effort] into building a pharmacogenomics knowledge base, but whether other researchers there would, I don’t know.

How did you get into pharmacogenomics?

I did my PhD in molecular biology, and that’s where the interest came from. And as a prescribing clinician, I see that drugs cause a lot of problems as [a previous talk at the meeting] highlighted. I see that a lot of people don’t respond to drugs. What we need to do is improve that.

How long until pharmacogenomics reaches a large implementation in the clinic?

That’s the $64,000 question. For certain areas, implementation might be quicker than in other areas. And areas where pharmacogenomics will succeed sooner rather than later is areas where the drugs are of very narrow efficacy or highly toxic, and are narrow therapeutic-index drugs, where we need to be able to improve therapy. Cancer is in this area, HIV is another, some severe drug reactions and so on.

Cancer, HIV — these are areas where pharmacogenomics is most widely studied right now.

Well, it’s been studied in several different areas, cardiovascular, et cetera. But it will be implemented in those areas as well, but I feel that cancer will be the area where it comes into practice first, because of the very toxic drugs it uses.

And there’s a lot of funding available for cancer research. And that’s an important thing.

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