Early clinical trials, the advent of biologics and the IBD Nurse and how the clinical presentation of IBD has changed over a 46-year career: The interviewee in this issue is Professor David Rampton, who has had a long career as an IBD clinician and researcher in East London. Respected by colleagues and patients alike, his career has spanned an era during which much has changed in IBD.
|David Rampton © David Rampton
Where have you worked during your career?
I did my undergraduate training at Oxford and did what is generally called a PhD, but which is called a DPhil there, from 1967 to 1970. I did my clinical training at University College Hospital in London and graduated in 1973. I'm afraid we medical students then were mostly rather over-privileged and lacking in diversity of any type – almost all my fellow students were white males. Now I work at the Royal London Hospital, part of Barts Health, in an area of tremendous ethnic and cultural diversity. We have a new building with a burgeoning gastro service. When I arrived as a full timer at London in 1989 there were three gastroenterologists and, terrifyingly in retrospect, we all did everything, including liver disease. Now there are about 20 of us, of whom six do mostly IBD. I'm semi-retired now: I do one IBD clinic per week during which I'm scheduled to see about 16 patients, and I attend a weekly lunchtime clinical meeting and usually our imaging MDT.
Who inspired/inspires you?
I've been inspired by several people; conversely, I have also worked for people whose methods I have tried not to copy. I think my single greatest inspiration was John Lennard-Jones (known universally as 'L-J') for his enormous contribution to our understanding and management of IBD in its earlier years as a sub-specialty, but most importantly for his tremendous example as a clinician who listened to his patients, and for his integrity and lack of showmanship. He was thoroughly committed; he had a gentle but very persuasive way about him; he was tall and thin and serious. I first came across him when I was a medical student: at the end of our 6 weeks on his clinical firm he wrote a note to each of us personally, saying that we had done well and wishing us good luck in our career – he was top of his field but that he bothered to do that says a lot about him as an individual. I used to see L-J periodically at meetings in later years, and he always took the time to say hello and ask how things were going. He gave often slightly disorganised and rather low-key talks with somewhat understated, old-fashioned slides, but they had all the meat in them. Sadly, he died in April this year at the age of 92.
Some of your research interests have centred on alternative treatments. Could you tell us a bit about your different research interests?
When I started in IBD, clinical research was mostly observational and epidemiological; clinical trials were small scale and usually investigator initiated. Immunology was in its infancy and just starting to be applied to IBD, in which much of the basic research focussed on the pathophysiology of the disease.
My first research interest in gastroenterology was looking at the production of eicosanoids by rectal mucosa in IBD and its relationship to sodium transport using rectal dialysis, which was a technique I learnt from an endocrinologist at UCH called Charles Edmonds. Later I had a couple of research fellows who studied eicosanoid and reactive oxygen metabolite release from incubated colonic biopsies. We also did a series of minor therapeutic trials in UC, including with an anti-oxidant combination called selenium-ACE, an anti-thromboxane agent called Ridogrel and, in collaboration with Chris Hawkey, a leucotriene B4 inhibitor, benoxaprofen: But none of them worked. In the very early days we thought prostaglandins were bad for the gut, so we did a trial with high-dose aspirin – this made patients much worse, which retrospectively fits with what we now know about what prostaglandins do.
Later on, my daughter developed psoriasis, and one day she asked me if I had ever heard of aloe vera, as she had tried it and found it to melt her psoriasis away, so I wondered whether it might work in UC and we set up a placebo-controlled trial. But it was very difficult to make the placebo – if you’ve drunk aloe vera you’ll know it’s very bitter and viscous and has little lumps in it. We had to get a food chemist in Wales to make a placebo and managed to do a controlled trial involving about 30 patients. We found that aloe vera was better than placebo in mild to moderate colitis and was about as effective (using historical controls) as a 5ASA.
Around that time, patients in the clinic were repeatedly telling me that psychological stress made their symptoms worse, so in the early 2000s we did a series of studies in patients with UC to explore how this might happen, using an experimental stress test. Participants in these studies had rock music played through a headphone into one ear and folk music into the other, and simultaneously had to do an IQ test for 40 minutes. You can imagine that this dichotomous listening test would be quite stressful, and it certainly was – and it increased rectal mucosal production of oxygen species and TNF. More recently, we did a series of studies assessing the prevalence of mood disturbances in patients with IBD and their influence on disease course.
In the last few years, the pleasure of doing research, especially clinical trials, has, I'm afraid, been a bit compromised by increasing amounts of regulatory bureaucracy. I do hope that in the future this doesn't act as too much of a disincentive to gastroenterologists setting out on a research career.
You supervised quite a lot of PhDs and many of them have gone on to be quite successful in their own right. What do you think is the secret to being a successful PhD supervisor?
Well, to put it the other way round, I could see what would make an unsuccessful supervisor – if you’re very busy with your own career, whizzing about the world, you can’t help your PhDs as much as they need, especially at the outset. I think the secret is to see PhD students regularly, once a week or more often in the early days, once a fortnight when they’re well established. You should involve them in other departmental activities and have regular informal as well as formal interaction with them, with lots of encouragement. And if you don’t read their draft PhDs promptly when they eventually write them up before submission, you're failing in your responsibilities. I found being a PhD supervisor hugely good fun and very stimulating – although it can at times be frustrating! And it's very gratifying to see clinical research fellows go from being very much amateurs in IBD when they start their research phase to pretty competent IBD doctors after 3–4 years of weekly clinics. Most of them become IBD specialists in their consultant lives.
What have been the biggest changes that you have seen in clinical IBD over your career?
The advent of the IBD nurse has made a huge difference. I was rather slow on the uptake and didn’t realise what an enormous difference specialist nurses could make to the provision of care for patients. And patients are unanimous in saying how wonderful it is to be able to telephone or email the hospital at any time, and speak to a specialist nurse who knows them and has the appropriate advice for them. And of course, in doing this, as well as their many other activities, IBD nurses very much relieve the workload of the other people in the IBD team, including the consultants. In the 1990s, long before IBD nurses existed, I had a fantastic secretary called Trudy who, in time, in effect became an IBD nurse: she could deal with most of the queries as they came through and was very good at it. But in those days we only had about three options for treatment – take a course of steroids, increase your dose of 5ASA or come to the clinic.
The recognition of the need to give more holistic care has been an important development, as of course has the advent of new drugs, especially biologics. When I started, we had steroids and 5ASA and later azathioprine. Because of the limited options available, therapeutic decision-making was easier then than it often is now.
I think that IBD in those early days was not only less common than it is now, but was also usually less complex. There are theories to explain why IBD has become more common but I don’t know why it seems to have become more complex, at least in its gut manifestations. One of the reasons why we seem to see more intra-abdominal complications now might be because we are slower to operate. I think we sometimes procrastinate too long, prolonging drug treatment, including with biologics, rather than quickly operating. On the other hand, we don’t tend to see complications such as arterial thrombosis as often nowadays. I remember a patient years ago who lost his arm after an arterial thrombosis, and another who had a sagittal vein thrombosis. Those are described complications of IBD, but I haven’t seen them for 20 or 30 years. Perhaps anti-TNFs are reducing the risk of that type of systemic complication.
Having a colonoscopy, I suspect, is much less unpleasant now than it was when I learnt it in the late 1970s. We were self-taught: the scopes then available were very floppy and each procedure took up to an hour and a half, and many needed radiological screening to complete.
What was the advent of biologics like?
I found it quite frightening and tended to be a bit more cautious about using them than others. Even just before that, when cyclosporine came along, I was slow to start using it. In those days, we used to use heparin and it seemed to work in some people with steroid-refractory severe colitis. But one of the advantages of research fellows is that they teach you. Peter Irving, who was working with me as a research fellow at that time, one day said, “Why don’t you try cyclosporine, you old fuddy-duddy?” and of course it worked.
And a similar thing happened with biologics. Fortunately James Lindsay was already here at the Royal London when biologics came in and he could lead me by the nose as it were. But I am still quite cautious of them – they do of course occasionally have very unpleasant side effects. I am also old fashioned in that I was brought up in the era of Helicobacter, when if a regimen for Helicobacter eradication didn’t have a 90%–95% cure rate, it was thought to be useless. This may explain why I still find it difficult sometimes to get excited about new drugs for IBD producing remission rates of 30% and response rates of 50%–60%, without cure, at huge cost and with potentially severe side effects.
What do you see as the role of patient groups?
I have been involved for many years with what was originally the National Association for Colitis and Crohn's Disease (NACC) and is now Crohn’s & Colitis UK. L-J was a co-founder of NACC and I first became involved with it when he came over to Newham Hospital in the 1980s to set up the East London group within NACC. Regrettably it’s still a small minority of patients with IBD who join Crohn's & Colitis UK formally, although I think a far higher proportion use their website. It’s been a tremendous educational resource, now provides about half a million pounds of funding for research annually, and has done a lot of lobbying nationally and locally to improve IBD services.
What does the future hold for clinical IBD?
In addition to having optimal conditions as an epidemiologist in a Scandinavian country, it is an advantage that you always obtOn the down side, while evidence-based medical practice is of course very sensible in principle, I'm a bit anxious about the increasing reliance on algorithmic decision-making: Will we need humans to look after patients at all in 30 years? I was brought up in medicine in a different day, when physicians practiced using a combination of instinct, knowledge, compassion and experience. Of course, that did sometimes lead to wrong decisions and was not always safe. Inevitably, as time goes by, algorithm-driven computerised processes will take an increasing role in clinical decision-making, perhaps incorporating information about individual patients' genome and microbiome so as to provide carefully personalised treatment. In 50 years, what doctors and nurses do will be very different from what we do now. Although many of our current roles may be taken over by technicians, or even machines, I continue to believe that the contact between the doctor or nurse and the patient, in the clinic room, is fantastically important, especially for patients with a chronic disease. In that respect we are irreplaceable. If for patients with IBD it all comes down to sitting in front of your computer, plugging in your blood results and faecal calprotectin and then picking up from the pharmacist whatever the computer prescribes, I think we will lose aspects of care that contribute to patients’ well-being.
You still do a clinic every week – why?
It's selfish really, I hugely enjoy it. I’ve still got patients who used to come in the mid-80s to Newham Hospital who came across to the Royal London when I moved there and lots from the early 90s, whom I know very well. It’s like being a GP, but less frightening. When you’re a GP it must often be hard to tell what’s really serious because there is such a broad range of clinical problems you have to deal with, whereas in IBD the range is very narrowed down. It’s also a great privilege to be able to see people, and get to know them quite well, all the way from diagnosis to, well hopefully rarely, the grave. And it’s socially very enjoyable too, except there just isn’t quite enough time, with only 10–15 minutes for a clinic follow-up slot. I do accept that increasing demand means that the way that we run clinics will have to change, with more patients being cared for in the community with apps and so on.
How do you manage work-life balance – now and before retirement?
Before retirement, work and life were not in balance: I spent far too long dealing with work, whether I was in the hospital or at home. To semi-retire 8 years ago was an excellent decision, and allowed me for the first time to enjoy fully other aspects of life.
What do you do now when you’re not working?
A range of things, depending in part on the season: seeing my increasingly ancient children, relatives and friends, listening to music and playing the piano (alone and as a too-loud accompanist), fly-fishing, walk-running in the countryside, reading, trying to learn another language or two, making (insufficient) use of London's cultural opportunities and a bit of consultative and charitable work.
How can people strike a life-work balance, and become successful?
I'm not sure it's possible. Medicine is a vocation: if you're not fully committed to it, you may not be able to do it well.
What’s been your involvement with ECCO?
I think I didn’t go to the first meeting, when it was much, much smaller than it is now, but I went regularly thereafter. I was one of the National Representatives for UK for a few years. I continued going to the meetings after that, and have been a member up until a year or two ago. ECCO has done a fantastic job in developing knowledge and practice of IBD across Europe – no other organisation remotely rivals it.
What’s next for you?
More of the same I hope.
Charlotte Hedin, Y-ECCO Member
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