Hi, I’m Cat and I’m an MS reporter and I’ve been living with MS for seven years. This episode is a rough guide to clinical trials that aims to set out the simple stuff. What is a clinical trial, why do they exist and how do they work. If you’ve ever wondered about where treatments come from, this is a great place to start.
Cat: So what are clinical trials?
Dr Jeremy Chataway: Yes, so clinical trials are the way as to how we determine whether anything works, whether a medication – doesn’t have to be a medicine – it could be a surgical technique, it could be physiotherapy, whether it makes a difference. And what we do is, we do a comparison against the current standard of care and we do that in a special way to try and avoid bias. I’d just like to talk about some of the vocabulary of trials, because I think that’s important. What’s called randomised and controlled clinical trials. So randomised means that if a person is taking part in a trial, the computer, which is specially set up, will decide if that person will go on the standard treatment or on the new treatment, and it’s done without humans, as it were, being involved to remove the chance of bias. Controlled means that a person can go either on those two, or sometimes more than two different possibilities.
Cat: And why are clinical trials so important?
Dr Jeremy Chataway: Yeah, they’re really important because they help us decide whether something works or doesn’t work. And you might say well, surely that’s obvious and you just give it to people. But in fact, particularly neurological conditions, it’s much more complicated than that because there can be bias. So a person wants it to work, or an investigator wants it to work. We must always compare it against the current standard of care, because also remember, some medications can have side effects attached to them and we really want to make sure when we’re using, for example, monoclonal antibody treatment, that it really works. And so it’s important to do this in a controlled fashion. And then we have security that we know that something has made a difference, rather than not really making a difference.
Dominic: Perhaps you could share with us what the different phases of trials are. Because we all hear one, two, three, four, etc.
Ana Cavey: Okay. So on a trial looking at a compound you’ll do a phase one study. They’re done in very specialist units and they use healthy adults. So they’re always male and they’re looking to see whether the drug is tolerable in a human being. We start getting involved at a phase two level. By that time they’ve got a compound, they know that it’s safe to be used on humans, but they need to know the level or the amount of drug that we need to give to people. So they tend to be only one or two centres, as in one or two units, relatively small numbers of patients. By that it can be anything from five to about 150, but in drug trial terms is relatively small. And they’re just trying to find out whether the drug does what it says on the tin, is it actually going to work as we expect it to do, because the previous studies have all been animal studies and obviously were very different. So phase two, small, usually called proof of concept studies. Then we move on to the phase threes, which is the most common ones and the ones that we get hugely involved in. So they will be large multinational studies involving huge numbers of people. By this time the drug is safe, we know how it’s going to work, we just want to see how it reacts in different people. And the numbers of people involved in that will be several hundred and will be, the studies we get involved in will be Europe, so the whole of Europe and North America and Australia are the usual countries that are involved in those. Phase four studies have always happened but they’re becoming more prevalent, so a phase four is what we call a post-marketing study. So the drug is now licensed, it’s being used in everyday practice, and the companies will follow patients who are on their drug. They want to see what happens to patients long term. Phase three studies will be relatively short. By that I mean, for some of our studies, that can be four or five years, but as you know, MS is with you for a long time.
Ana Cavey: Yeah, exactly. So five years is a snapshot. Some of these drugs we don’t know the long-term implications, we don’t know how people react on them, so the post-marketing are really important studies. They tend to be what we call observational, so the patients will consent to those studies and then every time you come and see your consultant or your nurse, if you mention a side effect or whatever, it’s noted there and we collect the data from there, but post-marketing is really important.
Cat: Who funds clinical trials and who decides what to study?
Dr Jeremy Chataway: So clinical trials are funded by a number of different bodies, if you like. So pharmaceutical companies fund clinical trials, government funding organisations fund clinical trials, and charities fund clinical trials. For example, the MS societies, say, in the UK or abroad. And sometimes individual philanthropists fund clinical trials, but often that’s done through donations to charities. So a variety of different ways, because clinical trials are expensive, so in an academic or clinical setting, what’s called a mid-phase trial, what’s called the phase two trial, will be two or three million pounds. A final phase trial might be five or six million pounds. A commercial trial, for example, the medications we’ve talked about, may be easily 50 or 100 million dollars to bring in through, because on the way a number of medications don’t pass the hurdle and yet a lot of time and money has gone into them. So clinical trials are expensive, but they are utterly necessary.
Cat: Will the findings from any trial always be published, even if they’re not successful?
Dr Jeremy Chataway: Yeah, so this is really, really important, because although disappointing, a negative trial is very helpful because it tells us more about the biology of what’s going on with multiple sclerosis. So now organisations are mandated to register their trial with a number of different registries such as ClinicalTrials.gov, or there’s a European trial registry, and that is mandated before a trial can proceed. And then when a trial is finished they have to post their major results on that trial platform. Also, investigators often talk about their results at conferences, such as the European or American conferences, and generally investigators will publish their trial results. But as I said, the primary results do have to appear in the public domain and that’s very important, and that wasn’t done so well over the previous years, but now it’s a lot better.
Cat: So there you have it. Hopefully that cleared up some of the questions you had around clinical trials. Did anything surprise you from the episode? If so, get in touch. We always love hearing what you’ve got to say. If this episode has been useful and interesting, why not have a look at some of the others which should be on the screen now. Also, subscribe to our channel and come and check it out later!