학술정보센터
한의약융합데이터 콘텐츠 바로가기
Leader’s Interview
Home > 학술정보센터 > Leader’s Interview
| Prof. Andrew Moore (1) |
|
About Prof. Andrew Moore
Director of Pain Research,
Chairman of the International Association
Founding editor of the evidence-based journal – Bandolier,
Q1. Can you introduce your unit and your people and team at Oxford?
Sure. We’ve been working together as a group on really back thirty-five or forty years awfully long time. It was because there was a chap in Oxford called John Lloyd, who was, the person who started pain units in England. He really knew we had to do something. He’d say, “These people are suffering; I don’t know what to do, but we’ve got to do something.” So, we began to meet and do things like clinical trials and at that time, I was a practicing biochemist and ran the biochemist labs and we were doing pharmacokinetics of opioids and other drugs, clinical trials and so on.
We were very anaesthetically based. Come about 1994, I was in Florida; I listen to a guy called Abe Sunshine talking about clinical trials of aspirin. And he was talking about why some of them worked and why some of them didn’t work. I sat in the back in this really large auditorium and I thought, “This is a really important point, we’ve gotta understand this.” So, what we tried to do then, was to move this about end of the 80’s, very early 90’s was to start moving towards, trying to understand more about what clinical trials can do and how they work, rather than just carrying on doing clinical trials without thinking.
So we collected together about 25,000 randomised controlled trials with pain as an outcome. The idea was we needed to start doing systemic reviews; this was before evidence-based medicine was evidence-based medicines.
Basically, it took off from there. We did a various stages of people who are very famous now come through and work with us. Sometimes we had a large group sometimes a smaller group. But, when we started looking at doing systemic reviews, we found the methods didn’t work for us. And there were things going on that we thought were wrong. There were all of these stages where we had to say, “This is wrong, how do we make it right? How do we make this better?” It’s moved. Over 20 years to get to a stage where we, beginning to feel we’re comfortable. And our group these days is quite small in Oxford because we’ve got the PaPas group with Christopher Eccleston, Anna Hobson who runs it and maybe more people there I assume with myself, there’s Phil Wiffen, who used be the deputy director of the UK Cochrane centre, he’s a pharmacist and he’s been working with us for ages. There’s a superb woman called Sheena Derry, who is a zoologist and by training and she’s also a clinical pharmacologist as well now. she’s just “bee’s knees”, and I don’t know whether that translates into Korean, but it just means she is absolutely wonderful doing systemic reviews. So, we’ve got this team there and we get people coming through and training and maybe doing one or two reviews. Sometimes more and sometimes they keep coming back so they’re with our group in the UK. We have tons of people around the world who are our associates in Germany and Canada, Switzerland, none in Korea yet.
We’ve been to Southeast Asia a few times but not to Korea to try and you know, tell people about evidence based medicine and what we can do with it and hope we can try and get people involved. But it’s proving quite a hard work. Anyway, that’s where we are. So now, we’re sort of an international virtual association of people who are interested in making things better.
Q2. You’ve been funded by various pharmaceutical companies for your research. How do you keep yourself clean?
It’s a very simple thing. There’s an old saying, “When you sup with the devil, you use a long spoon.” Now, we’ve been working with the pharmaceutical industry for many, for decades. We had a very simple rule when we started. That is, if you did research, whether it’s clinical trial or something else, we had the absolute right to publish the results.
When you have that rule, some people won’t work with you because they want the absolute right to publish the results or not. We won’t work with people like that. So, if you’re a pharmaceutical company and you want to work with us, that’s lovely. But, at the end of the day, the results are going to be published whether you like it or not. And that perhaps explains so few pharmaceutical companies work with us.
But, the reasons why we do it are really important. Because if you’re looking at clinical trials, you can look at a published paper, but that’s done to a formula and what if the formula is wrong? If the formula is wrong, there’s no way to unpick it because you don’t have the data. So you need access to the data in the clinical trial at the level of the individual patient. And the only you know, the only trials that are done these days are done by pharmaceutical companies. So you’ve got to cozy up to them and make them understand why allowing us to have the data and to reanalyze it in ways they may not like is good for them. We’ve been quite good with that over the years. We’ve managed to get rather large amounts of data, including data that would’ve otherwise remained unpublished.
And it’s been important because looking at that has allowed us to concentrate on some really important issues like issues around trial results. What happens when people drop out of trials? Now, typically in trials, people use the last observation carried forward (LOCF) method.
I mean it’s fine if 2% of the people drop out of trials. It doesn’t make any difference on what you do. But if 60% of the people drop out of trials, which happens for instance with opioids and chronic musculoskeletal pain, it means that, if you don’t take it out and you just use this LOCF method, then what you have is a result which is based on hypothetical data. So, we have gone back and looked at it and what we find is that using other methods where you define an outcome as one that patients want, so that’s more than 50% pain intensity reduction, and also they have at the end of the trial to continue to be still taking the medicine. Then you get completely different results. Sometimes trials which said this drug is wonderful actually showed this drug is significantly worse than placebo. So, that’s a big effect.
And similarly, we’ve been able to demonstrate, we’ve been able to look at different outcomes to see which is best, which is more sensitive, whether the ones that patients want are measurable. Really importantly, the relationship between improvement in pain and improvement for instance, in chronic pain, in terms of the sleep deprivation that people get in their sleep in the depression, or the fatigue, the quality of life levels which have gone down and also the ability to work. And the answer is that we’ve able to demonstrate whenever we’ve done it, is that when you improve the pain all these other things come back to normal. It’s most impressive. So, what we’ve been able to demonstrate is that it’s that pain is the thing and, and this works.
We’ve done that because we’ve individual patient level data from pharmaceutical companies usually for which they have paid, but we have had the absolute right to publish. So on that basis, it’s all transparent. You all know what’s happened, the data are there, you can look at it and say, “Well, have I done it wrong?” Nobody’s come along yet and said we’re doing it wrong. Frankly, they never will cause I don’t think we’re doing it wrong in ways that we can see. But we carry on looking for things that might’ve made us come to the wrong conclusion. What we’re looking for is the truth.
Q3. Do you think other pain research units have the same rule as yours?
It is very difficult. Without wanting to be a bad boy, I think that there is a lot of nonsense talked about industry but at the same time, there are people who do clinical trials with industry where they’re not being published, although that’s almost impossible now because we’ve changed the ground rules. But I’m not convinced that everything is completely clean. But you can only look after the bit of the world that you look after. I can’t change the rule of the world.
Q4. As a biochemist, how did you come to work in this field, evidence based medicine and pain research?
I actually went up to Oxford to read medicine, then I changed because it was more interesting to read biochemistry. And the professor of biochemistry at that particular time was Professor Hans Krebs of the Krebs cycle, it was a very exciting time. Then I did a DPhil, which is a PhD in the hospital, which are the joint University-hospital biochemistry department. While I was there, I was asked to involve myself in analytical biochemistry as I was a wiz at measuring things. So I got involved with, in monera ’s metabolism and diagnosis and then I was involved, I was asked to stay on and be a biochemist.
Q5. Because you are an excellent student?
Maybe because I’m awkward. Basically, what they wanted me to do was to go onto the wards and find way in which biochemistry can help medicine. So I had 13 years absolute wonderful time. I had the only laboratory in Oxford. So anybody who wanted to do research had to come to me. Any -ology, we did fabulous stuff. It was very exciting. As a part of that, I got involved with the department of anaesthetics, in terms of measuring opioids, venteril for its instance and buprenorphinelater, and then morphine and its glucuronides we developed big interests in pain and anaesthetics. And although I went and then did some other things, by about, including starting a diagnostics company and running it up to a moderate size in a short time, my interest was always in analysis. Particularly, how you get the right result. That’s a really important thing. And so, back in 1990, there about as we were still putting all this stuff together about pain and how we looked at it, it just became evident that, you know, this was gonna be a big thing and I just decided that I would support myself but get involved in this, which is what I did and then I ended up writing an evidence-based newsletter Bandolier, many went on the web and then became very successful. At one stage, we had millions of people going in there every month.
Q6. Right. I myself had a great help from your site.
Thank you very much. I mean we’ve stopped now, because we’re tiny and we were doing it ourselves. We would never get funding for it.
Q7. It’s a pity.
It was a pity. But we’re trying to do things now, we’re beginning to investigate whether we can do something with wikipedia. Might be helpful. With all of this work that we did and Cochrane, and so on, it’s just more than enough work to be carrying on with. It’s very important and I like it. It’s enormous fun.
Q8. Could you tell me briefly about your yesterday's presentation? (Speed onset is a key determinant of efficacy for oral NSAIDS in acute pain.)
Absolutely. It is one of these things that came from a conversation with a pharmaceutical company about aspects of interests and how and whether individual patient data analysis could look at it. So what we’re having conversation with Rickitt Benckiser was, we’ve done work with them before and they were saying they wanted to try and show, how could they show what was on individual data analysis. We had the data, and I think we saw some of the pictures there. We were able to demonstrate beautifully what was going on, we went and did some additional analysis looking at that, pharmacokinetics of oral analgesics, particularly oral ibuprofen where there was a lot of data.
What one sees is that with standard acid ibuprofen, it has a peek possible concentration about 90 or 120 minutes. If you use one of the fast acting ones, which is ibuprofen salt or a liquid gel capsule, it’s about 20 to 30 minutes. We had noted that a 30-year-old paper had indicated that there was a relationship between pain and early possible concentration levels. So, we did a big analysis and what we showed was that the faster the pain goes down over the first hour, the better the overall pain relief and the longer the pain relief lasts. So it wasn’t just that going in faster became faster, going in faster really was determining the way in which this worked. Possibly because of some kinetic event that you’re driving the drug into the place where it works and therefore getting better effect. We were able to take another trial and do the same again. And got exactly the same results. It’s very interesting. So that, for example, 200-mg of fast-acting ibuprofen is, gives you the same analgesic response as 400-mg of ibuprofen acid, the standard formulation; it’s a good stuff. If you’re able to get the, at least the same, if not a little bit better analgesia with a half the dose, well of course that’s really major safety consideration for what is an over the counter medicine used by millions of people.
Q9. Can you tell me the analgesic with faster onset keeps the analgesic effect longer. But, till when?
I don’t believe we’ve got enough data on that yet. But for example, ibuprofen normally would last about 4 to 6 hours, but for the fast-acting drug, what we’re seeing is that half the people had not re-medicated, needed another analgesia.
Q10. No pain at all?
By and large, they weren’t needing any pain relief to be on 8 hours.
(다음 편에 계속)
|