EHA 2010 Annual Meeting, 10-13th June 2010, Barcelona
Dr Stephen O’Brien (Newcastle University, UK)
EHA patient advocacy session: the difficulties increasing patient uptake of clinical trials
I’d like to welcome as the next speaker Steve O’Brien from the National Institute of Cancer Research from Newcastle and we’re going to hear a lot of interesting thoughts about investigator’s perspective on access to clinical trials.
I think this is up my street and it’s a great privilege to be involved with this meeting today. I’ve started almost with a blank sheet of paper preparing and presenting this talk. I give a lot of talks about the results of clinical trials and that kind of thing but this is relatively new for me and I think it’s very important, it’s actually very close to my heart.
There are three hats that I wear which I think are relevant to this discussion. The first is I’m a clinician, I look after patients, I’m a CML doctor essentially in Newcastle in the UK. The second is that I’m an active clinical researcher, I’m the chief investigator for a couple of very large phase III trials in the UK. And the third role that I find myself having these days is as an advisor, a consultee if you like, to our National Institute for Clinical Excellence in the UK, which is the body that evaluates the cost effectiveness of drugs and essentially is the gatekeeper for what we can and can’t use in our clinical practice. And with those three roles I want to present some thoughts to you and at the end of my short presentation present a fairly contentious and novel idea which I’d really very much like your opinions on. Because I face a dilemma as a clinical researcher of doing trials which potentially don’t get through the regulatory approval process and therefore don’t benefit my patients more broadly in the clinic. And it’s something that taxes me quite a lot.
So to start with, I’d just like to tell you about my disclosures, specifically I get research funding and am active as an advisor to pretty much most of the companies that make drugs involved with CML, but don’t have any shares in those companies. Critically the studies that I do, the phase III studies, although much of the funding comes from industry they are independently sponsored by my hospital and independently governed so they are effectively independent studies.
I work in the area of CML and if you’ve been to one or two of the other talks at this meeting you’ll realise that there has been a revolution in this disease over the last ten or twelve years. Historically it goes back over 160 years to the first description in the mid-nineteenth century and these are some of the famous people that have ploughed the way forward in CML, from Nowell and Hungerford up here, who described the Philadelphia chromosome through to colleagues who worked out the molecular biology. And famously now, of course, through to the invention and innovation of Imatinib in this disease.
And we’ve seen some fascinating and very different times in the last five or ten years. It’s very rare that we see cancer drugs on the front page of Time magazine, but this is an article from 2001, only about two years from the introduction of the drug, which highlighted the benefits, potentially, of Imatinib and at that stage we saw lots of articles in the newspaper about limitations of access to drug. A lot of the support groups, the patient advocacy groups that have evolved in oncology over the last few years have developed on the back of the models that CML patients have developed, and Jana’s a very good example of that. There has been a lot of lobbying, a lot of engagement by patients. So the world is very different than even five years ago now in terms of, rightly so I think, the engagement of patients in what we do and how we design studies.
So the study that I’m involved with at the moment is a fairly simple study, it’s comparing Imatinib and Dasatinib; it’s called SPIRIT2, that’s the website if you’re interested and, as of today, we have 225 patients on this study. We’re recruiting a patient today, we have set up the 146 sites in the UK and 73 have so far enrolled a patient. So I’m in daily discussion with my research team about how we can engage patients and clinicians and improve recruitment for this study. We need 800 patients in total. This is a rare disease in the UK with perhaps only 500 – 600 patients per year, so it’s a subject very close to my heart how we can enthuse and engage patients and their clinicians.
So the first question I’d like to pose is why don’t more patients participate? And I guess I come from a background of CML but these points are, I think, fairly broadly applicable. There is a difference, I think, a very significant difference about where patients are in their treatments because if you have already had the disease for some time and have failed the therapy, you’re likely to be much more used to what that disease means to you, be much more knowledgeable about the implications of the various therapies available and used to your clinical team and have developed a relationship of hopefully trust with that team. So that when you come to consider switching therapy you’re well informed and you’re often motivated to try something new because you realise the implications of your first line therapy, for example, not working.
So in the context of CML, getting patients to enrol into some of the studies where second line agents are coming through was not that difficult because patients understood that their first line treatment wasn’t working and were very motivated to try and improve their outcome.
What is more difficult, I find, and it’s the area I work in particularly, is newly diagnosed patients. Here, of course, you have a patient who has little, if any, knowledge of CML at all when they first come to the clinic, and why should they? They’ve just been diagnosed so they’re obviously very upset, they’re overwhelmed with the implications of that diagnosis for the rest of their lives, for their families. And also if you present them with an eight or ten page consent form, of course, that’s very overwhelming as well. It’s overwhelming for most people, it’s the state of the consent forms we have now. There’s also somewhat of an urgency to treat, it’s perhaps not as pressing as in, for example, AML but again in AML it’s quite difficult – you’re taking often sick patients and asking for consent for therapy. So this pressure of time and a feeling of being overwhelmed, I think, is a really practical and important problem.
And also I find that in studies it is so bureaucratic at the moment and clinicians are so pressed that often they don’t think they have enough time or actually don’t have enough time or can’t be bothered to actually consent the patients. So there are real challenges, particularly I think, for newly diagnosed patients.
With regard to the clinician restrictions, these are some of the fairly obvious but practical points that come up. It’s just too much hassle to set up the project, I hear some people saying, and you have to want to do this sort of research as a clinician, especially in the UK, to do it. So having an important question and an important study design is important. Not having enough time or facilities is a very common and fairly obvious complaint. We’re improving that, I think, in the UK and other countries with networks of trials offices and support staff, specialist nurses etc, who can share that burden of counselling and consent to some extent.
And from a patient point of view, I think it’s a real challenge to convey the nature of a research project to a patient in a way that is sufficiently comprehensive but not overwhelming. I really struggle and worry about the nature of our consent forms these days. We are forced more and more by our ethics committees to cover every single possible risk and they end up being very long and wordy and I don’t think always written in the best way. And I find some of them difficult to understand and I don’t think it’s fair to expect particularly a newly diagnosed and somewhat overwhelmed patient to understand them. So I think we need to be much better about providing attractive looking, easy to read and engaging consent forms that are written in a very clear way.
Patients are worried about being a guinea pig in trials and I remember notoriously a few years ago you might remember the Tay Genero disaster, as it was, at Northwick Park in the UK where several young men were given this antibody therapy and many of them nearly died. The week after that I had a patient come to clinic on a completely different drug potentially with a totally different disease saying to me, “It’s a good job I didn’t go into a clinical trial otherwise I’d be dead now, wouldn’t I Doctor?” And of course that’s not the correct perception but the way sometimes the media covers trials is to play up the risk, if you like, rather than to offer some balance. But I think with good explanation that can be overcome. And a colleague has already mentioned the limitations of access if you live far away from a trial centre.
So what can we do to improve? Well, as I say, as a researcher I think about this all the time. The practical things we try and do in the SPIRIT trials in the UK is try and make them interesting and timely and appropriate and, at the moment, I think the questions we’re asking in SPIRIT2 are very timely and interesting. We offer free drug which is a fairly simple but very useful incentive for many hospitals, this is on one arm of the trial, on the newer medication side if you like. We are very active in offering administrative support to sites, so we prepare all their site files for them, we virtually write everything that they need in terms of contracting and just ask them to approve and sign those things. So getting through the paperwork we’re very active with.
And then we try and communicate a lot. I have to say we communicate mainly with the clinicians at site. It’s hard to know how to engage patient groups sometimes, we can of course go through their websites but many if not most patients with a given disease won’t necessarily be internet literate or go to websites or be on email for that matter. So we tend to target our weekly often publicity to clinicians and patients. We have web campaigns, we’re now talking about having Twitter feeds and Facebook and all these things that my children understand and that I resist, but there we are. And in the UK we have a once a year patient and clinician seminar on separate days where we very much engage patients who, of course, already have the disease by and large, not newly diagnosed and try and promote activity and interest in our trials. And, as I mentioned before, I think we need better consent forms.
But there is this aspect that really troubles me about what we do, especially in CML, is that we have some fantastic new drugs and it’s true in many areas of oncology and specifically many areas of haematology – in myeloma, in lymphoma, lots of very exciting drugs. But you’ll have noticed that we’re in a global recession and it really bothers me whether we’re ever going to see these drugs come through into clinical practice. So you’ll have seen these sorts of articles in your own countries I’m sure, this is a selection of news clippings from the British media, and it seems every week there is something in our media about access or limitations of access to drugs. And therefore there’s a gap. You will see a very good example of this, I think, at this meeting. Today and tomorrow you will be hearing, and just last weekend we’re published in the New England Journal of Medicine, the new data with Nilotinib and Dasatinib. These are one year follow-up data; they’re showing cytogenetic and molecular responses, for example. Our NICE organisation in the UK is aware of these data and is evaluating them at the moment. I can virtually guarantee to you that when their appraisals come out next year they’ll say, “Very interesting, the data are too early therefore we’re not going to allow access to these drugs in the UK.” So very exciting, coming out at this meeting, but we’re not going to be able to use these drugs in the clinic, I don’t think, for some years to come because of this gap.
So I think about this all the time and I wonder why we don’t do things differently. Why don’t we ask NICE to allow drugs into clinical practice early, maybe offer some reimbursement to the company, and have the access in the form of some on-going comparative clinical evaluation? And this is the contentious bit – perhaps as a patient or a clinician you would only be allowed access to these new drugs if you participated in a trial. That’s unprecedented and it is somewhat problematic. The cons to that, if you like, are that it’s dubious, I think, ethically to force a patient to go into a programme of research to gain access to a drug. And having a value based pricing model for the industry is relatively untested. We don’t know whether the industry would engage and it’s hard to know where this would lead us in the long term. But as a potential set of advantages it may give early access to drugs for patients. It could give some early revenue for the companies and it would give us some robust and independent long-term data for our regulators and authorities to make decisions on cost-effectiveness.
So I’d be very interested to know your views on that. I’m not aware of any models that do that. We’re discussing it in the UK at the moment but for the time being, despite there being very exciting data at this meeting, we won’t have access to those drugs for a while unless we think about doing things in a slightly different way.
So those are my brief thoughts and thanks for listening.
