Evidence heard in Public

Questions 91 - 175



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Oral Evidence

Taken before the Science and Technology Committee

on Wednesday 15 May 2013

Members present:

Andrew Miller (Chair)

Jim Dowd

Stephen Metcalfe

Stephen Mosley

Pamela Nash

Sarah Newton

Graham Stringer

David Tredinnick

Examination of Witnesses

Witnesses: Simon Denegri, NIHR National Director for Public Participation and Engagement in Research and Chair, INVOLVE, and Professor Karol Sikora, Medical Director of Cancer Partners UK and Dean, University of Buckingham Medical School, gave evidence.

Q91 Chair: May I welcome you to the session and thank you for attending? It would be helpful for the record if you would kindly introduce yourselves.

Simon Denegri: Good morning. My name is Simon Denegri. I am the NIHR national director for public participation and engagement in research and also chair of INVOLVE, which is the national advisory group for public involvement in research.

Professor Karol Sikora: I am Professor Karol Sikora, professor of cancer medicine at Hammersmith hospital in west London and dean of the medical school at Buckingham. I am also an oncologist; I have been a consultant in the NHS for 30 years.

Q92 Chair: Thank you. Let me start by simply asking you why patients and, indeed, healthy volunteers choose to participate in clinical trials and what factors might discourage them.

Simon Denegri: The first thing that we ought to say and recognise-it is often understated-is that of course clinical trials would not happen if patients and people did not come forward voluntarily and freely contribute their time. There are a number of reasons why people do that. The first is that there is the opportunity of benefiting from a new treatment or new therapy. There is a very clear sense that comes through in the documented evidence in relation to patients that they feel as though they might get better care. They want to help medical research; they want to help others. They also want to take some control of their disease, and participating in clinical research is one of the ways in which you can do that, or feel that you can do that.

Professor Karol Sikora: Cancer is all I know about, I’m afraid. With cancer, it is rather different. There is a sense of desperation among many patients who have reached the end of the road with conventional medicine. People actively seek out centres where there are clinical trials for cancer. The other thing is that there is an altruistic motive. People will try a new drug, even though it is explained to them that it is unlikely to work for them, but it will give information on, say, the kinetic distribution of the drug in the body, which will be useful to us for further patients. People are very willing to do that.

The problem we have with something like cancer is that you are sometimes raising expectations in these trials in terms of what the patient believes and what you know is the realistic outcome. It is very important from an ethical viewpoint to be completely honest about the likely benefit.

The other problem in clinical trials is that it is about not just length of life, shrinkage of cancer and reduction of blood pressure, but quality of life, and quality of life research is very challenging, mainly because you cannot measure it very easily. In certain types of cancer, there are blood tests that can be done and you can look at the level of growth of the cancer, but what is the quality of someone’s life? There are various indices to try to determine that, but they are not very good. The traditional doctor will say, "How are you feeling today?"-that is a quality of life assessment-but we can do better than that now. Getting a holistic view of how the patient is doing with their disease and how they feel about it is much more challenging.

Simon Denegri: I would not disagree on the quality of life aspects, but specifically on your question about barriers to getting people involved in clinical trials, there are a number. One is that we know that knowledge about clinical research and trials is pretty low in the general population. It probably increases as one becomes a patient, particularly if one has a condition such as cancer or if one is going to be treated for a long period of time. They become initiated in how medicine and medical research happens.

Often patients cite very practical reasons why they cannot take part in a clinical trial or clinical research, and those may be that it is happening too far away from home or does not fit in with their life. These things point to the need to involve patients and the public much more in how we design and deliver research.

Q93 Chair: Is there a lack of public trust in medical research when it is sponsored by industry?

Professor Karol Sikora: I think there is. There is no doubt that industry has a very pervasive influence, and I have to be careful because I know that we have some representatives behind us here. In different ways, it has an effect on the public, and of course the internet has driven a new way of directed consumer channelling. Even though you cannot in Europe put an advert direct to consumers for a drug, the internet is free, and you can put up a website for all the high-cost cancer drugs-each has its own website. Patients, provided they trust their direct clinical advisers in hospital or in general practice, really do not worry too much about that side. In the UK, we have a good ethical structure with the centralisation of research ethics committees, which means that provided the ethics committee is happy, one can only assure the patient that it is likely to be okay, even though the study is funded by industry and it may, if it is positive, result in considerable profit.

Q94 Chair: So even though the patient knows that the driver of the research is a large corporate, because it has the confidence of the doctor whom they trust-

Professor Karol Sikora: Exactly, so the doctor acts as the intermediary. Although it is stated on the consent form that it is sponsored by one of the big companies, they trust the doctor not to do something that would be against their benefit.

Simon Denegri: I agree that the relationship that one has with one’s health professional is pivotal in building that trust and seeing perhaps beyond one’s immediate assumptions about who the funder is, but there is none the less quite a strong public mistrust of industry. If you look back at the Eurobarometer poll 2010 of people’s attitudes to medical research, one of the things that comes through very clearly is people’s concern about the influence of the pharmaceutical industry, and that will feature again in the Health Research Authority’s own public engagement exercise, published on Monday, so I think we are detecting that. As someone who has, as both a patient and on behalf of patient groups, worked with industry, I think it is a real shame. We have some really good examples from individual companies of them coming together with patients and thinking very innovatively about how to work together. From a patient point of view, working with industry collectively, it can feel a bit like going to a party and meeting the same person, and they are repeatedly looking beyond you at someone who is more interesting and valuable. There is a real opportunity with this debate to see the industry change how it relates and changes its body language towards patients.

Q95 Sarah Newton: I like this analogy of being at a party and looking beyond you, and I really want to stick with the idea of patients and why more people do not get involved in clinical trials. In our written evidence, we had a survey from the research group PatientView called, "Sense about Science". It told us that only 35% of patients had participated in a clinical trial and that 14% had been asked to participate but declined to do so. I am wondering about how people will naturally find out how to join a clinical trial.

Simon Denegri: That is a very good question. I think it is quite difficult at the moment for people to find out about clinical research and how to go about going on a trial. In certain condition areas-cancer being one, as are some of the places where we have excellent clinical research networks, such as in stroke and diabetes-the level of knowledge about opportunities is rising, but it is still quite low. Through the National Institute for Health Research, we are leading the "OK to ask" campaign for international clinical trials day next Monday-20 May-which is part of trying to open the conversation much more wider, giving patients the confidence to ask their doctor whether there are trials they might benefit from, and giving clinicians and health professionals the confidence to broach the question. You are right that even in cancer one in three people has had a discussion, and we need to raise the level and amount of that discussion. At the moment, it is quite difficult for people to find a route in. It is quite hit and miss.

Professor Karol Sikora: One of the difficulties in cancer and other areas is that the entry criteria for the trial must be set. One cannot make it all inclusive, so if you are over a certain age, under a certain age, or don’t have an assessable disease, there is absolutely no point in that patient doing a trial. Perhaps we should be a bit more thoughtful about how to offer alternatives if a patient doesn’t suit. Often, the patient may be considered for a trial and investigations may be done, but they are then told, "I’m terribly sorry; it’s not for you. You don’t fit the criteria." That is a let-down for people. If we could have a system in which clinical trials are offered, but there is a back-up if the patient is not suitable, it would be a far better way of keeping the balance of trust.

Q96 Sarah Newton: Could you perhaps expand on that, because it is a really good point? What other ways to help could they be offered? I am sure you are right and that people want to feel that they are not only helping themselves, but contributing to the greater good so that other people do not have to suffer as they are suffering. What other things might they be offered so that they can stay engaged in clinical trials?

Simon Denegri: They may well be able to take part in a questionnaire or survey to improve the service or even the environment they are going into. We must also think about this in a much more long-term fashion by getting people to understand more about research and see it as a potential place where they can participate. They might begin to feel able to ask some very good questions about the evidence underpinning their treatment and have that evidence-based relationship and conversation with health professionals. That is what we want to aim for and aspire to in the long term.

Q97 Sarah Newton: We have received evidence from the UK clinical trials gateway. How do you feel that could be improved as a way of having the sort of dialogue you were talking about and people more prepared to participate in trials?

Simon Denegri: The gateway is a good initiative, and when we tested it with patients and the public at the end of last year, they very much welcomed it. There are two broad issues with it: first, knowledge of it is not great; and, secondly, from a patient perspective, it is a little clunky and does not quite do everything you need. At the moment, you can search generally and nationwide for trials in which you might be able to participate, but you cannot search for trials that are local to you-perhaps 20 or 30 miles down the road-which is a priority for someone with a busy life. We have some near-term things to do to improve it and to make it really fit.

There is a bigger question about what the gateway does with other providers of online technology to enable patients to build research communities. Patients are increasingly outsmarting us when it comes to the use of technology. We need to embrace that in some way and to work with them much more. There have been some great things in the past with the cystic fibrosis website, CFUnite. That is a really good example of the community, including patients, coming together to help people to register for trials and to find out about the evidence. Those are the sort of things we need to harness much more aggressively.

Q98 Sarah Newton: So working in partnership with trusted bodies such as NGOs or charities representing particular groups of people with particular conditions.

Simon Denegri: Yes, but there are also many good private providers, and we should not discount that. I think it is more about the whole community coming together as quite a large collaborative. It doesn’t mean you cannot be competitive, but coming together as a collaborative can produce a sort of learning health system that helps patients to find their way to research much more easily.

Professor Karol Sikora: I think we underestimate the power of the internet and what is going to happen over the next decade. I was giving a talk at my old primary school on Monday, and the amount of IT these seven-year-olds can do is just phenomenal. That generation will be the next generation of patients, and they will be able to access information that our generation certainly could not-and probably still cannot.

The internet will be a very great provider of information to patients. They will look up their specific disease, or have it recorded, and then they will be able to find what trials are available to them. That is probably the brave new world. There will be industrial trials, quality of life trials-all sorts of things-listed that will be personalised to them, because the ones that are not relevant will be taken out. They will be able to see what is available, and the distance as well, because that is obviously important for chronic treatment.

Q99 Chair: You have mentioned the internet a couple of times, Professor Sikora. The problem with some conditions is that the evidence base that is published is pretty thin, and there are some fairly contradictory bits of information. How does one use the internet to get a good picture of what the problem is?

Professor Karol Sikora: You are absolutely right. For cancer, there are 1.4 billion sites now with cancer in them. Some are complete rubbish. Some are completely mad. Some are patent advertising for something.

Q100 Jim Dowd: Did you say 1.4 billion?

Professor Karol Sikora: Exactly. This is on Yahoo! For some reason, Yahoo! has more than Google.

Jim Dowd: Who counted them?

Professor Karol Sikora: It is just amazing. You could not read them all.

The problem we have got for clinical trials is that there are not that many. There are a few good sites now for clinical trials, but they are not personalised: they are not for you-for your illness. The future will be about getting to that point. Who should do that? Whether it should be the Health Research Authority, whether it should be a clinical trials collaborative, or whether it should be organised locally is clearly one of the challenges facing the medical-

Q101 Chair: It just seems to me-this goes way beyond medical research-that peer-reviewed information will have some sort of real, firm kitemark on it.

Professor Karol Sikora: Exactly.

Simon Denegri: We need to think about building up patient knowledge as part of the infrastructure we need to put in place to have a vibrant clinical research community in the UK. One of the ways we do that is to encourage patients-the public-to ask challenging questions. There is a very good campaign run by Sense about Science to ask about evidence. These are the sorts of things that we need to get across to people much more clearly, and equip them and arm them. That can only facilitate them in making a good and informed choice.

Q102 Stephen Metcalfe: Good morning. I fully understand the logic of people looking for trials and trying to find something that will help them. Concern has been expressed, though, that once a participant has taken part in a trial, the results of that are not necessarily communicated back to them, and any potential medical advance that has come from that trial is also not communicated to them, so they do not know what their role was and what benefit there might have been. First, do you accept that and, secondly, how typically is that information communicated back to participants when it is?

Simon Denegri: I absolutely agree with that. When I go round the country doing public meetings, it is one the most common questions and complaints I get from patients-they may have been a trial participant, but no one communicated with them afterwards how that contributed to knowledge about the condition, or how that may or may not have improved treatment, and down to never being thanked for their contribution. I think we do people a real disservice here.

What we do need to do, and have the opportunity to do, is to produce a much stronger overall commitment to patients going into research-a sort of Bill of Rights, if you like, which people like the founders of DIPEx were talking about in the late ’80s-which stretches from having good information to a clear consent process, to being able to find out about the results of a trial, and to being thanked as a basic courtesy when it is finished, because that can only encourage their future participation and encourage them to talk to others who will then participate as well.

Professor Karol Sikora: I think it does reflect the growing up of medical communication with patients. When I began as a consultant, we did not tell people they had cancer, so how could you possibly engage in giving them the results of a cancer trial? But now we are in a totally different information transfer and a much more level playing field, so it is very possible to insist that at the end of a trial, when the results are either published or collated-not all trials are successful, by any means, as you would appreciate-a summary in layman’s terms is sent with a letter of thanks to the patient. That would not cost much and it would be very welcome, I think. As you say, Simon, it would encourage an ethos of searching and wanting to be part of it.

Simon Denegri: I think there are some very good places where people get told before it goes into a publication, and I think that’s great. I know that might be challenging to some academics and researchers, but I think it’s a great example.

Q103 Stephen Metcalfe: I think you are entirely right. That sounds like a potential best practice solution. Are there any occasions when participants don’t want to know the outcome of the trials, or is that very rare?

Simon Denegri: That question is a good one, and I think it goes down to what the conversation is with the patient at the very beginning, and to setting clear expectations. Certainly, I would be very concerned if people were getting letters falling on their doormat, unprompted. I think there needs to be very careful thought about how you share these results with them, because some people would be alarmed, perhaps, and would not want it in that way. But I think it goes down to: what is the conversation with the patient at the very beginning of this research?

Professor Karol Sikora: I think that’s right, and managing expectations is always vital. If someone has metastatic cancer, it is unlikely that they are going to be cured; it is more likely that they will live longer, even if the trial is successful. But people don’t hear that. They hear, "This pill, this injection, is going to cure my cancer," and I think it is up to the clinician running the trial to keep the expectation under control.

Q104 Stephen Metcalfe: Thank you. When you are discussing with potential participants-patients-at an early stage the possibility of taking part in a trial, do you discuss the possibility of sharing their data at some later point, potentially anonymised? In the main, are they happy for those data to be shared?

Professor Karol Sikora: It is very easy to get cancer patients-in fact all patients-into a trial if they trust the treating team; not just the consultant but the whole team, including the nursing staff and other carers. They see that the team wants to do it not just for their own interest, but for the greater good of the whole community and other patients, so most people agree readily. The difficulty comes back, again, to this expectation: are you giving false hope to people by doing it? It is dangerous to do that.

Simon Denegri: I obviously haven’t been in a clinical situation like that, but generically I have been part of dialogue exercises with patients about data. There will always be some people who are concerned about it, and some quite rightly because they have a stigmatised disease and have a life experience that is extremely arduous. But, generally speaking, if you enter into a dialogue with a group of patients, they readily get the idea about data and why data need to be shared, or why it is beneficial to do so, and they will readily buy into that, as long as the rules are clear, the risks are clear and they know where they can get further information.

Q105 Stephen Metcalfe: Okay. So would you say that that situation has been improving over the past x number of years, and that there is more engagement backwards and forwards? What about those patients who have been involved in historical trials, who perhaps weren’t engaged in that same dialogue? Do you think there is any merit in contacting them to ask if their data can now, retrospectively, be shared, or are there too many risks?

Professor Karol Sikora: That is probably quite a difficult exercise. Most patients with chronic disease, whatever it is, are under some form of follow-up, and if they have participated in a trial in the past, the results should be in their medical records. If it has not been done in the same hospital, at least a copy of the results should be there. So then it is up for the follow-up staff-the consultant, the registrars-to give that information if patients want it.

A lot of people are strangely still uninterested in this. They trust the system too much, but I think that’s changing. Younger people want to know more. My generation are on the cusp and the next generation on from me really is not interested-"Whatever you say doctor." But it’s changing, and it’s changing for a much healthier dialogue.

Q106 Stephen Metcalfe: Do you think there is a benefit in going back over historic data and trying to harvest that? Is there anything to be gained, even if was difficult and costly? Is there something in those historic data that would be of benefit?

Professor Karol Sikora: It may create problems. Someone would have to communicate it and it would depend. If the trial was marvellous and the patient had great benefit from it-fantastic; but if it wasn’t it might rekindle unpleasant memories and so on. That is the difficulty, and logistically it may not be that easy. It should be, going forward, because trials are much better documented on a national basis, partly because of the Health Research Authority, but partly because of other structures. You can follow up; you can identify the patient who is in it, so you can get the summary to the patient.

Stephen Metcalfe: One final point, just going back to the idea of recruiting people into trials: the point at which there is the potential to offer someone a trial is the point at which they have probably just been diagnosed with something that is potentially life-changing. Do you think there needs to be a wider public engagement generally about our ability to take part in trials, so that we can improve our knowledge, perhaps in a similar way to the campaign for donor cards that has been run over the years-that actually people just know in the back of their mind that if they were ill they would potentially take part in a trial?

Simon Denegri: I certainly do. I think there is a real, strong case for that. The NIHR "Ok to ask" campaign next week is, I think, the beginnings of a move in that direction. If I would really like to see one thing come out from all the funders and the research community in this, again, going back to my point about seeing public knowledge as part of the infrastructure, I would actually like them to come together in the same way that they come together to build medical research buildings and recognise that this is something to which they should all contribute voluntarily, and work collaboratively to make happen; because I think too often there is a sort of, not quite pointing a finger-that is unfair-but an expectation that the Government or the NHS will do it. I think that is a completely unreasonable expectation. I think we all have to do it, and we have to be aligned in the way we do it.

Professor Karol Sikora: I think the disease-specific charities-dementia, Alzheimer’s, diabetes, cancer-have a very powerful role, but there are other diseases that are perhaps not championed by charities. Hypertension would be one, for example; depression is less championed, and equally valid as a platform for clinical trials. So a solid base, as you suggest, Simon, would be the way forward.

Q107 David Tredinnick: Professor, what information do doctors use when considering treatment options for your patients? For example, to what extent do they use trial results described in the academic literature, NICE guidelines, or systematic reviews?

Professor Karol Sikora: Doctors, really, are stuck with NICE guidelines, and we could not deviate, because the pharmacy will reject if you prescribe a drug outside NICE guidelines. The NICE guidelines are great, and they are very well thought out. The difficulty is they are still too slow for certain drugs, especially in the cancer area. They come too long after the drug has been on the market. So people can pay for the drug. Private patients are getting the drug from their insurer. NHS patients in some places get, and in other places don’t get, so it is a problem.

The academic literature is enormous, as you can imagine. The way in which practice changes: some published papers change practice instantly, but they are very rare. It is a sort of drift through a series of presentations at meetings; and then things change. Herceptin and breast cancer was a classic of a sudden change where every patient-and it was accepted by NICE; this was in 2005-was tested for the receptor to Herceptin, and those who were positive would get Herceptin suddenly. So that was a major change, and everywhere, within a week, practice had changed; but that is incredibly rare. It is a drift over two to three years when things go.

Q108 David Tredinnick: How quickly and effectively is emerging evidence incorporated into clinical guidance such as that produced by NICE? I am thinking of what is happening in the United States with the Consortium of Academic Health Centres for Integrative Medicine-53 centres in north America, including some of the most prestigious, which are now using a model called integrative medicine, defined as "the practice of medicine that reaffirms the importance of the relationship between practitioner and patient, focuses on the whole person, is informed by evidence, and makes use of all appropriate therapeutic approaches, healthcare professionals and disciplines to achieve optimal health" and well-being. Do you see that as, perhaps, a future model for this country?

Professor Karol Sikora: I think it is. There is no doubt that we are all in little silos. I sit in a clinic tomorrow morning, and I just see cancer patients and think about the cancer. But the patient doesn’t just have cancer; they have all sorts of other things. They have social issues, and so on, and a holistic approach, which could involve therapies that are perhaps non-conventional, seems realistic. The difficulty is not the cost, because often the cost is in high-tech medicine rather than in some of these other approaches; the difficulty is changing attitudes and getting out of the hospital and primary care boxes into a seamless flow of patients. As the population gets older, we accumulate chronic diseases because we are successful at keeping people going, so it will be even more important to have a much more holistic approach to integrated care. The current turmoil with accident and emergency is just a reflection of all that coming together. We just do not have systems in place, and we do not have good tools to do clinical trials to measure the effectiveness of the systems.

Simon Denegri: From the point of view of researching patient benefits, I would also start the discussion much earlier and think about the priorities that we set with patients. We have some really good models on that, such as the James Lind Alliance priority setting partnerships model, which is now part of what NIHR does. Patients should be encouraged by the increasing willingness to look holistically at what they need to survive or live with their illness.

Q109 David Tredinnick: Finally, to both of you, the Secretary of State for Health has made it absolutely clear that he wants to put patient choice at the centre of the health service. How important is self-management of health care, particularly for cancer? I am thinking of a presentation I saw by Nicola Gale and Cathy Shneerson at University College hospital London in which they talked about defining self-management of disease. Is that a future paradigm?

Professor Karol Sikora: I think it is. Again, it goes back to the inevitable internet, which we talked about before. All sorts of devices are out there that could be used. Diabetes is a disease that is really up front in this. Diabetes is a biochemical disorder, so it is relatively simple to follow blood sugars and various other biomarkers of response, and so on. Cancer is a bit more complex, but there is no doubt that involving people in understanding not just their illness but how the natural history can flow and how treatments can affect it is going to be very important. Again, people can understand the gadgets now. You cannot do your shopping without understanding at least some basic computer science, so I think it is very much the future, as you suggest.

Simon Denegri: One of the consequences of that, from a research perspective of self-management, is that people increasingly want to self-refer to take part in research, which is one of things that we found from the public survey and the gateway. Actually, people do not want to go through their health professional, because they have not been very helpful to them previously in finding out about trials and research; they actually want to go directly to a clinical trial unit. We need to think that through in terms of the future patient agenda.

Q110 Stephen Mosley: I have just leant on my iPad, and it has moved on.

Following on from the last question, in modern health care there are two principles for evidence-based research, and there is also the patient choice about which we have just heard. Is there some contradiction between them? If people are self-referring and going for a more holistic approach, does that get in the way of evidence-based research?

Professor Karol Sikora: I don’t think so, provided there is time for the professional, whoever it is, to explain the situation. Wanless, in his famous report in 2002, talked about the "fully engaged" patient, and there is no doubt that it is a pleasure to deal with fully engaged patients. The difficulty is that not everyone has the educational level to get to that point, especially with technical details, but provided there is a dialogue between a health professional and the patient, I think all three are possible, including patient choice. On the whole, patients do not choose things that are not recommended by the professional who is looking after them, provided that they seem reasonable and that there is a valid explanation, so I do not think there is a contradiction in that.

Simon Denegri: Neither do I think there is a contradiction between the two. One of the great things about what we have in the UK with the NIHR model is that one of its core principles is that involving and working with patients improves the quality of your research, whatever that research looks like and whatever methodology you use. We have done a very good job of standing by that principle, and I do not see any contradiction whatsoever.

Q111 Stephen Mosley: Whenever I think of medical trials, I cast my mind back a few years to the famous TeGenero case. I was quite surprised when I did my research that it was 2006, a good many years ago; it feels a lot more recent. Do you hear any concerns when you speak to patients that there might be side effects that you are not aware of?

Professor Karol Sikora: In my specialty, because of its nature, people on the whole do not worry too much, because the benefit will far outweigh the downside. If it were a new antidepressant, it could be different. If it were an anti-vomiting agent, for example, would you really want to do that? Again, a full explanation is necessary of why and what possible benefit it could give you, or what benefit it could give to other patients if you enter the trial. That is all about good interaction at the very beginning, when consent is being obtained, to make sure the patient understands the up and the downside of things.

Simon Denegri: I agree. I haven’t really got anything to add to that.

Q112 Stephen Mosley: One of the issues that we have heard is that with rarer and more serious conditions, sometimes you do not have enough of an evidence base to progress trials to a certain point, or to the point where a drug can actually be used. A citizens’ jury convened by the Genetic Alliance UK suggested that, in such conditions, people might be willing to take greater risks, whereas normally you would not allow anything to be used unless it had gone through phase 3 trials. There might be a case, in some rare conditions, for saying that the risks of going ahead are fewer than the risks of not going ahead. Is there any basis behind that?

Professor Karol Sikora: Again, cancer is probably the disease where the benefit would outweigh the risks. It is just about honesty with the patient: "We have this treatment. It may or may not work. We need to assess it properly, and you fit the bill. Would you like to be in the trial?" If you have a reasonable dialogue with people, most agree.

Another approach is going on in some hospitals, where there are several competing trials. I say "competing": there are several trials for exactly the same group of patients. The patient is given a wad of patient-related protocols written in lay language and asked to choose one. That is not so helpful. The patient cannot expect to understand whether a vaccine, a drug or an antibody is better, and they get very confused. I think the information overload can be mitigated by proper counselling with professional staff who understand it fully and explain the choices to the patient, who then makes the ultimate decision.

It is a bit like going to a financial man about pension plans and things like that. It is very complicated. There are risks and upsides, but you have no idea how it will all pan out. It is the same with a patient going into a trial.

Q113 Stephen Mosley: But legally, it cannot be given to a patient until the phase 3 trials have been completed.

Professor Karol Sikora: Exactly.

Q114 Stephen Mosley: Is there an argument for relaxing that case in a few rare situations?

Professor Karol Sikora: Certainly, in cancer, it has been relaxed a bit. If phase 2 is very positive-in other words, if there is a very strong hint of a response-then extended access is usually granted by the company making the drug, and usually used in certain defined ways. The information is still collected, so although it is not a formal clinical trial, the information is of trial quality. The data set filled in and returned for future use, including side effects and response, is centrally collected.

Simon Denegri: I have two thoughts around it. One is that it is symptomatic, and perhaps inevitable, of a more citizen-driven approach to research. You are going to see this desire, and I support it. I think there are two aspects of it. One is a very beneficial one if we can reach a model where patients are regulatory partners. If you talk to patients, they are as frustrated as anybody else about the lengthy consent process. They have very good reality checks, and they should be regarded as partners by the MHRA, the HRA and others.

The second one, about which I have a little bit more worry, is that as long as there is a very solid partnership by those arguing for such change, such as patients, and the makers of the medicine, I feel more comfortable. Where I have a problem is that it is not always clear to me that the patient interest is paramount here. It could be used by some people to argue for a speeding up of the process, because it makes commercial sense. I have worries about that, but as long as the partnership with the patient is solid, I am more comfortable with it.

Chair: Thank you very much indeed. That was extremely helpful. We will now go straight on to our second panel.

Examination of Witnesses

Witnesses: Tracey Brown, Managing Director, Sense About Science, and Dr Helen Jamison, Deputy Director, Science Media Centre, gave evidence.

Q115 Chair: I welcome both of you to the hearing. I would be grateful if you introduced yourselves for the record.

Tracey Brown: I am Tracey Brown from Sense about Science.

Dr Helen Jamison: I am Helen Jamison from the Science Media Centre.

Q116 Chair: Okay. I think you have been listening in to the previous session. Why do you think it is important that information about clinical trials is made open to the public?

Tracey Brown: To start where the previous discussion was, in relation to patients and to those who participate in clinical trials, there is an expectation that what they are doing is contributing to the future treatment of their disease, or at least to its future understanding. It comes as a shock to many patients who are involved in clinical trials to find that some of the information from those has not been shared at all, and therefore, cannot possibly benefit future treatments. It may even result in the same trial being run again in a future group of patients.

Beyond that, there is the issue of that information going on to help researchers to do a number of different things. One is to determine the course of future research, which is to say which trials are beneficial to run. It is highly unethical to run trials, particularly those that put patients at risk, a second time. It is also a very important question, not just for researchers, but for those who are determining which courses of treatment are effective-whether that is individual clinicians or regulators, and we talked about NICE-to determine which things work best and in which kind of patients. That is impossible to do unless you have the full results at your fingertips.

Dr Helen Jamison: I would probably echo a lot of what Tracey said. Although the Science Media Centre is not directly involved in the AllTrials campaign, we are generally very supportive of openness, and that is one of the reasons why we exist. We feel that it is very important that both the public and policy makers, whenever they are making decisions, can do so on the basis of full, accurate evidence that they have available to them. I think there is also a responsibility on the part of those carrying out scientific research and clinical trials to let the public know either how they are spending the money, or the results of what they are doing. We are also finding that a lack of openness can often lead to mistrust and confusion. There are a lot of very good reasons why openness and transparency are important.

Tracey Brown: Chair, can I add a further point? I think there is a misconception about how science advances that lies behind some of the discussion about the issue. We have a pretty robust approach to testing protocols and to the way that clinical trials are designed precisely because people share not just in order to understand the efficacy or the safety of a particular course of treatment, but to understand the best way to research these things and the pitfalls that you might fall into in the course of designing that kind of research. We do not have the modern scientific approach that we have today because everybody has secretly gone off and done things in the cupboard; we have it because people have tested each other’s ideas, pulled them apart and asked if something could have been done better. That is a very important part of scientific medical advance.

Q117 Chair: Interestingly, in the Royal Society report, "Science as an open enterprise" from June of last year, there is a section that argues about transparency engendering public trust, but it goes on to say, "Opening up scientific data is not an unqualified good", citing "the legitimate boundaries of openness which must be maintained in order to protect commercial value, privacy, safety and security." Leaving aside the commercial bits at this stage, and thinking particularly about the patients, don’t you agree that while opening up is a good idea, the prerequisite is better information going to the patient about the meaning of the scientific data?

Tracey Brown: I certainly agree that all forms of communication about these issues carry with them some responsibilities. I feel very twitchy when I hear things like, "Opening up is not an unqualified good." I know what is meant by that in the context of the Royal Society report, but what I am hearing in the context of the AllTrials agenda, which is aimed at solving this horrible problem in medicine of hiding results, is that people hide all kinds of other things behind that. Everybody nods along to the idea that opening up is not an unqualified good, and they mean a number of different things by that: sometimes, they mean that it is a pain in the neck to have to publish trials that did not show that their drug was very effective, and we should watch for that.

Clearly, we do not want a situation where, as a result of the publication of data, people put things into the public domain in binary code, or where there is data dumping, and that somehow ticks a box. We are not looking for a box-ticking exercise; we are looking for outcomes that benefit patients and research. Therefore, yes, we need an intelligent approach. Sometimes, we perhaps need a bit more work to explain it, but that is nothing compared to the job of explaining what is going on when you have only half the information at your fingertips. Think about the challenge that represents when you have something like a scare about a vaccine. It is a huge challenge for independent researchers to come out and explain to the public what is going on, when they themselves might feel nervous about that, because they do not know that they have got their hands on the full information. So, through hiding a lot of this stuff, we are really undermining our ability to have a sensible public discussion.

Q118 Stephen Metcalfe: Sorry, you may already have answered this, and if you did, I apologise because I did not quite hear. Why would someone conduct a clinical trial and then not publish the results? Is it purely and simply because the drug they were trialling was not effective and they do not want to be embarrassed, or are there are other reasons behind this?

Tracey Brown: If you have conducted three trials and two of them make your drug look very good and the other makes it look like it does not do much at all, you are clearly inclined towards the first two. The thing is there are a number of different things going on. We should also not underestimate the lack of compulsion, the laziness and the sloth in these things; there is a bit of that. If you look at the academic publication of trials, it is a better record than the industry-funded trials, but it is not that much better historically-not so that we would want to crow about it. There are issues to do with making the system easy to comply with and making the compulsion stronger overall. But, yes, there are good reasons why people do not want to publish trials that do not make their drugs look good; that is inevitable, particularly if they are in a competitive market. The marginal improvements that one new drug in a "me too" market might offer might be tiny and might, therefore, disappear in a further trial.

Q119 Chair: So you are arguing in favour of full release of information. What impact do you think that would have on the pharmaceutical industry?

Tracey Brown: When you say full release of information, I should just clarify that. It is helpful to think of this at four levels. One is the registration of trials; that is level 1. That has been a problem, certainly historically, although there have been some improvements since the 2007 FDA regulations and other interventions. We do not even have the contents list, if you like, of what has been done, never mind being able to track down some of the results. That is something that reviewers who are looking across a whole range of studies really struggle with; they spend a lot of time just trying to find out what has actually been done but been left in a cupboard somewhere. Registration is about knowing what the trial is for and registering the protocols.

The second level of information, which is what AllTrials is calling for, is the basic summary of the clinical study report. That says what was actually found, what the primary outcomes were and what the protocols were. We would like to see as much information there as possible, but that certainly gives you some indication of what research has been done and how it has been undertaken.

The area for quite a lot of discussion at the moment is what I would call level 3, which is the full clinical study report. That contains in many cases quite a lot. It is a very large report-quite often, it even runs to thousands of pages-and it may contain quite a lot of individual patient data, things that might be tracked to individual patients or other things that constitute reasons why people might be concerned. There is a discussion about the release of those. I just note that we are seeing their release by the European Medicines Agency already for those drugs that they have them for.

Then there is the fourth level, which is individual patient data. A lot of very productive discussion is going on about how to establish good protocols for sharing that among the research community-for example, setting out the same requirements for secondary research as you would for primary research, looking at the same data.

Dr Helen Jamison: There is probably not a great deal that we at the Science Media Centre can comment on from that perspective, because we do not have so much expertise in this area, but I think that one of the things that the pharmaceutical industry might need to consider in a move towards greater openness is the impact in terms of how they communicate the results of those clinical trials and that data. One thing that we have struggled with in the past when responding to controversial and difficult stories in the headlines about clinical trials and other areas more generally is that there is sometimes a reluctance on the part of industry to engage when an issue is on the front pages. Often, that can be the case with scientists and academics who are slightly related to Government as well. The impact of that is that, generally, it leaves a bit of a vacuum at a time when actually more information is needed. At the Science Media Centre, we often become very reliant then on independent academics based in universities. So I think a move towards greater openness on the part of industry would be a very good thing, but it would have to get down to grass-roots level in terms of how they engage with the national news as well as the public and the rest of the scientific community.

Q120 Pamela Nash: Ms Brown, just to be clear, is the aim of the AllTrials campaign to have all four levels published?

Tracey Brown: No, the aim of the AllTrials campaign is to ensure that levels 1 and 2 are published. Levels 1 and 2 do not have a huge amount of practical implication. It’s just a shocker that they are not published already. Levels 3 and 4-level 4 particularly has a certain practical implication, depending on the organisation. The requirements of level 3-what would be an equivalent to a clinical study report; there are such things, but for an academic, for example-just need to be ironed out and worked on. It is not a huge barrier to publishing that information. There is quite important information at level 3 about serious adverse events, for example, that may need to be shared, but that just takes a little more work and thinking about.

We are really pleased that, in signing up to AllTrials, GlaxoSmithKline, for example, committed to publishing a lot of their level 3 data. Obviously, we are going to look at what they encounter in doing that. That is an ongoing discussion with them. A lot of the people who have signed up to AllTrials are committed to that, too, but what we want to do is just to get past the idea that secrecy is okay. That is really the ultimate aim of AllTrials. It is just to find out what people have done and what they have found, at a very basic level, and then we can go on to look at some of the implications of sharing that.

Q121 Chair: Can I just halt things there for a moment? In your written evidence, you say: "For all trials (phase 2 and above) conducted since 1990…Full clinical study reports, or equivalent, should be made publicly available." That is what you are saying, is it?

Tracey Brown: Yes. The thing is that what has come about from that discussion is that because people have not been particularly thinking about publication, within clinical study reports are bits of information that people want to redact. I have set it out as four clear lines of information. The reality is, of course, that it is much messier than that. Clinical study reports contain individual patient data, and there is some discussion about that, but it is the full findings that we would want to see. Having said that, I am now looking at some of the discussion that is going on between some parties about publishing information on serious adverse events-

Q122 Chair: So in the context of level 3 and the word "full", you don’t quite mean that; you mean "qualified full".

Tracey Brown: What we are finding out is that "full" means something different for different people, depending on what they have included in that. I think we need to keep this idea of levels of information to try to have sensible discussions about it, but we need to look at what different parties-the differences between academics and those who are providing regulator information and so on-have got in that "full". We are saying, "Open your box." We do not know however if different people are putting different things in each of the boxes.

Q123 Chair: It would be helpful for clarity if you could reflect on your written evidence and what you have just said, and perhaps drop us a note on that.

Tracey Brown: I will do that, because there have been three very important discussions since the submission of written evidence that I would like to share with you. I will update you on those.

Chair: Yes, indeed. Back to you, Pamela.

Q124 Pamela Nash: That will be helpful. I was going to go on to the criticism from the Medical Research Council, which, as I am sure you are aware, has said that it is not standard practice for full clinical study reports always to be published. Cancer Research UK has said that that might not be a particularly useful document. Is that criticism you recognise? Is that part of the discussions since the written evidence was submitted?

Tracey Brown: The thing that should have been added on the end of everything is, "or equivalent". Once we had that discussion with the Medical Research Council, I think it was happy. As I understand it, its concern was, "We do not want to start asking academics to prepare a regulatory marketing authorisation document that they have no need for," and quite clearly that is not the case. They should not have any problem, because under requirements already in operation, they are supposed to publish their protocols and the primary and secondary outcomes of their trials, so it should not present a problem for them to do that. It might not look like a similar format.

Q125 Pamela Nash: Okay. My understanding is that you are asking for the publication of trials as far back as 1990. Is that correct?

Tracey Brown: A paper is due, so I cannot share figures on this at the moment. Most of the things that doctors are prescribing relate to marketing authorisations that were granted some time ago, and therefore it is reasonable. Where we put a cut-off will probably end up being rather arbitrary, but the rump of currently prescribed medicines were authorised in the time since 1990; obviously, predating all the current discussion that is going on in Europe. It would make sense therefore to have that. We want to be careful about constantly shooting this ball up the pitch, because everything that is being talked about in European regulation at the moment, for example, is about the future. It is not only that in, say, 2014 we are going to have the results of those studies, but it is going to be a long time before the vast majority of what patients are prescribed relates to the post-2014 period of studies. We will continue to prescribe some very successful drugs-apparently successful drugs-from previous times, so that is why it is important.

Q126 Pamela Nash: As a lay person, I would say that it would be easier to bring in rules now for the future, when it would be anticipated that this type of publication would be required. There has been criticism, even looking forward. Cancer Research UK has said that it might take three months’ additional work to produce the information. Is that not something you would recognise? You are saying that you would not anticipate that that burden would be put on researchers.

Tracey Brown: I am not quite sure how it came about that people were thinking that non-commercial researchers would be producing clinical study reports. Clearly, it would be strange to produce a regulatory document, if you were not seeking regulatory approval. If it were the case, I would imagine that it would take that time, but I cannot ever see a situation in which anyone would realistically be calling for the production of those. However, it is absolutely not unrealistic at all to expect anyone involved in clinical research to be able to publish the primary and secondary outcomes and the protocols of their research-effectively, publish their results. They are required to do so. It is not as though this is a requirement that does not already exist in the running of clinical trials. I know that you have the HRA speaking to you later this morning, and they, I am sure, have something to say about the ethical component of running clinical trials, requiring that people undertake those responsibilities. It is just a question of the fact that no one has actually enforced it.

Q127 Pamela Nash: On that point, do you see Government as having a role here in enforcing this or would this be a voluntary register and publication?

Tracey Brown: Ideally, you would want as much to happen, because people know it is the right thing to do, before you start introducing huge sticks and carrots to the whole situation. Also because then you have solutions. If you just, again, look at GSK being involved in this: by being involved, they are innovating things that work for them and we can start looking at how those data can be held, what level of redaction is reasonable, and so forth. However, there are a number of places where this needs then to be reflected in, perhaps not heavy-handed regulation entirely, but also in professional standards, for example. So we need to look at things like what constitutes a breach of professional standards. We need to look at things like what undertakings publishers and journals can make to ensure that trials that are not registered and not giving their top-line reporting do not then get published-or at least that that information is asked for, so there is a trace through.

But I think at some point we need to look at what kind of regulatory mechanisms should be in place for a number of things. One is that we should look at-if there are organisations or individuals who consistently fail to meet those standards-what kind of sanctions might exist for that. I think we need to look at what the regulators are doing to ensure compliance. So the FDA site, ClinicalTrials.gov, for example, could be developed. I think we should have a similar sort of interface, with a site in Europe. I do not understand why we do not yet have that. It is a straightforward interface; it is like a recipe card of the clinical trial, and then you add the bit at the end that says how it turned out. You can upload other information and links there, and so forth.

The thing that it misses is something that our UK Charity Commission succeeds in doing rather well, which is being able to highlight when people start to be late with filing their results. That would be a really simple-you speak to anyone who is reasonably okay with programming a computer and that is not a particularly difficult thing to do. So some sort of automated policing mechanism of the performance would be a really sensible move. It just takes a bit of political will to do it, I think.

Q128 Pamela Nash: You mentioned Europe, but the implications of planning for a trial does not have any borders. Are you speaking to your equivalent in other countries? Is there any vision for international co-operation on publishing trial results?

Tracey Brown: Well, over 300 organisations have signed up to all trials in just a few months, and of those I think over 70 are international bodies, many of which are regulators or organisations with a significant influence on the development of this discussion. Just two weeks ago, all the medical schools, led by Dartmouth medical school in North America, have taken on this role themselves, running an all-trials campaign.

People are pretty serious, in most countries, about sorting this problem out. It is a global issue. I know that some discussion has been had about and I know that the pharmaceutical industry has raised concerns about making the UK an uncompetitive place to do clinical trials. The issue here is not about where you do it. So long as people want to sell their drugs in the UK or in Europe, then wherever they have done the trial, we need to have the results.

Q129 David Tredinnick: I have a couple of questions for Tracey Brown, initially. Do you think that publishing clinical study reports would meet the criteria set by the Royal Society of intelligent openness?

Tracey Brown: As I mentioned, not if they were in binary code, or without the associated bits of software that had been used to process bits of the data. I mean, it depends. We are discovering that-

Q130 David Tredinnick: So it is an interface issue, is it? A presentation issue.

Tracey Brown: It can be, yes. In other cases, it is straightforward. But this really just needs to be worked out. I suppose we are talking about the level 3 of information, also to work out what is a reasonable basis to redact that information.

Q131 David Tredinnick: Are there any conversations with the Royal Society?

Tracey Brown: Well, actually having conversations with people who have that information and are working out on what basis they should redact it. In some cases, people are over-applying, as often happens when they are nervous about a regulatory implication. It may well be that some of the redactions that we are seeing in what is being published in that level 3 are because people are unduly anxious about data protection regulations-as you know, it is a highly punitive system-or because that discussion about what is a reasonable level of disclosure has not happened. But, yes, the principle there is making sure that what you present is something that other people can make sensible use of and make head or tail of.

Q132 David Tredinnick: You have kind of touched on a bit of this before, but is the lack of historical patient consent a problem when it comes to the retrospective sharing of individual patient-level data, and if so, how can that be resolved?

Tracey Brown: That was something that your last panel spent some time talking about. As I have said, there are two separate issues, and I understand that Research Councils UK have been talking about this. You are talking about individual patient data where issues of identification could come up. Nobody is talking about publishing names and addresses. Obviously, what we are talking about is anonymised data, but there may be occasions where the anonymisation is not enough to prevent you from working out where somebody was or the nature of the thing. There is one particular thing that I want to flag up. We need to work out what the protocol is for talking about serious adverse events, because quite often they involve one particular patient. We need to understand. We do not want that information withdrawn from discussion; it is a very important thing. We just need to work out a system whereby people can share that and at what level they can share it.

Q133 David Tredinnick: You said earlier on that information from trials is not being shared. Do you think it is the case that some evidence that is available is ignored? For example, of 156 randomised controlled trials, more have been positive than negative-64 positive and only 11 negative in respect of homeopathic medicine.

Tracey Brown: Do I think-

Q134 David Tredinnick: Do you think that some evidence like that has been ignored, perhaps wilfully, by some organisations? There were 64 that were positive and only 11 negative out of 156 randomised controlled trials conducted on homeopathic medicines.

Tracey Brown: I think you would have to show me the systematic review where you felt that that had been ignored.

Q135 David Tredinnick: Shall I do that? Shall I make sure you get the information?

Tracey Brown: Yes, please do.

Q136 David Tredinnick: One last question: do you think there is too much emphasis on randomised controlled trials and not enough in respect of meta-analysis and patient reported outcomes-actually what patients feel?

Tracey Brown: In this instance, we are talking about what to do with clinical trials and how other kinds of evidence are taken into account. Systematic reviews generally do look at other kinds of evidence, too. I do not think that the remit here could extend to every other kind of research, otherwise we are going to get ourselves in quite a muddle.

Q137 Jim Dowd: I think this is for Dr Jamison, but obviously if you wish to contribute Ms Brown, feel free. I want to look at something you made reference to earlier about the reporting of clinical trials. The vast majority of people, as we all understand, will get their impression not from learned journals and the detailed work and scientific analysis, but from the way it is reported. We have seen episodes in recent years, ranging from BSE and MMR and other issues, which have caused great consternation. In your experience, what sources do journalists use when reporting clinical trials?

Dr Helen Jamison: Most of the national news journalists whom we work with on a regular basis who are producing the reports that have a great influence over the public use quite a number of different sources. They have individual contacts, receive press releases and attend press briefings. Those come from or are with a number of different organisations-so the academic journals themselves publishing the trials, charities that might be involved in the trials, funders and organisations that might have provided financial support, industry, and universities. They also looked at case studies, I think, in quite a number of cases, to get a human interest story from any issues they might be covering.

I think there is a really wide range of sources that national news journalists use when they are reporting on clinical trials, but it is also worth saying that a big proportion of their stories come from the diary stories that they do. Daily news journalists especially often receive press releases from some of the bigger, higher-impact journals such as Nature, Science, the BMJ and The Lancet. Those form a large proportion of the sources from which they get information about clinical trials, but it can be a whole host of different places.

Q138 Jim Dowd: Have you detected a specific difference of approach between specialist scientific journalists and general news journalists?

Dr Helen Jamison: In the UK especially, we are really lucky to have a great group of specialist science and health reporters. I think they are much more keyed in to the scientific process, so they are much more likely to have great relationships and an understanding of the science that is going on within universities and partly within industry. They are definitely following academic journals and clinical trials much more closely than perhaps general news correspondents. General news correspondents may tend to get more of their stories about these issues from the news wires or from stories that very quickly hit the headlines.

The other thing that is worth saying is that, although there is definitely a narrative at the moment where the UK and other countries are concerned about losing specialist reporters in national news outlets, science is pretty healthy in newsrooms across the UK. In the vast majority of cases, if a story was about a clinical trial, even if it became quite a political issue, it would tend to stay with the science and health specialist rather than be taken off them, even if it was to find itself on the front pages. Generally, we are lucky to have a good group of journalists who follow these issues and understand the nuances in quite a lot of detail.

Q139 Jim Dowd: Would greater transparency help or hinder the quality of media reporting?

Dr Helen Jamison: That is a very good question, and it is a difficult one to answer. There is obviously a risk that, if there is more information out there, there is an opportunity for groups and individuals to either misuse that information or for groups who have an agenda to seize on it. But I am not necessarily sure that that would lead to increasingly poor reporting, for some of the reasons that I have just given. Because we have a very good science media environment at the moment, I think that many of the national news journalists who are specialists in this area would be aware of that being a possibility. There are a small number of them who follow issues now so closely, and I think that they would find more information much more useful and would have the time and the inclination to use that information.

It is worth pointing out as well as a caveat to that that there is definitely an increase in terms of the opportunities that new media and the internet bring, and there is definitely a shift towards data journalism and writers mining data to produce stories originally themselves, but at the moment that is still very much largely with science bloggers or science writers. It is also worth saying that I am not sure that a lot of busy national news journalists, who are writing five stories a day, have the time and resources to be able to really delve into the detail of data, unless they have been following an issue for four or five years, or they are writing a special long-form feature piece.

Q140 Jim Dowd: One of the fears that has been alluded to, with greater transparency and greater release of data, is what has been called inappropriate secondary analysis. Do you regard that as a realistic problem?

Dr Helen Jamison: It is a possibility, but I go back to what I just said, which is that I don’t see the natural result of that being poorer reporting. I do not think that we are in the situation that we were in when we had the MMR scandal in the 1990s. Science reporting is much better than it used to be. I think the media have learned a lot of lessons. We cannot guarantee that, if you put more data out there, it will not be seized upon for secondary analysis, or even analysed incorrectly, leading to confusion. That may happen, but I think science journalists are much better prepared for those kinds of issues. I also think it is fair to say that, if you do not put that data out there, it may equally lead to scare stories, mistrust and confusion.

Thirdly, we at the Science Media Centre spend a lot of time working with scientists who are already learning about increasing openness and what that means for them. They are already dealing with similar issues. Many of them have had data and information requested through freedom of information requests; some of them have even had data illegally hacked. Even in the most controversial and difficult situations, when data gets released to the public, we always actively encourage scientists to deal with that and face it head on, rather than hiding it. We are always about greater openness.

In the 10 years that we have existed, we have probably run 700 or 800 press briefings and worked on thousands of stories involving some of the most sensitive and controversial issues you could think of. The vast majority of those instances have always gone very well, and have been positive experiences because of greater openness. We are always actively encouraging experts. Even when there is an issue of data misuse and misunderstanding, the best way to tackle that is to be open rather than secretive about it.

Q141 Jim Dowd: Yes, we had a problem in this place not so long ago relating to the illegal release of data on Members’ expenses.

Tracey Brown: May I add a point? The dangers of not being able to do any kind of secondary analysis far outweigh the prospect of inappropriate secondary analysis. Busy journalists or anyone else looking for guidance on what the evidence is on an issue benefit enormously from having independent voices and analysis. Carl Heneghan, who runs the Centre for Evidence-Based Medicine at Oxford, has spent years trying to discover not just what the results are on Tamiflu but how many pieces of research have been conducted on it. How would you ever expect him to comment on a scare story about the Tamiflu vaccine? We do not even know if it is a scare story or not, because although he has worked so hard to find out what has actually taken place, he is still in a position where he does not fully know. That is the point. We are cutting the legs off our research community as a voice that could come in on a discussion about whether things work or not.

Q142 Jim Dowd: Finally, post-Leveson-it is very recent- you have brought in your 10 principles for best practice. I know it is early days. Has that produced any significant or measurable improvement in the quality of reporting?

Dr Helen Jamison: I think it is very hard to say. I think one thing that has happened is that our guidelines have been welcomed by a lot of people in the field. Whether that translates to them being used on a daily basis only time will tell. It has certainly raised a lot of awareness of some of the issues around good science and health reporting. We are working closely with the BBC College of Journalism on its science training for its journalists. Whether or not we eventually see our guidelines enshrined in any kind of legislation-whatever happens post-Leveson remains to be seen-it has done a lot to raise some of the issues. Most of the time, we actively encourage scientists to deal with the media, with all the things that that means, but it has been a really good chance to raise the issues of how the media report on important science and health issues. I think the guidelines have done that and will keep doing it.

Q143 Chair: But you must remain somewhat frustrated by the headline writers. There was one last year about a particular medical report that struck me. The headline was that, with a particular medication, you were less likely to die, which seemed to me a wonderful offer.

Dr Helen Jamison: That is very true. In the last 10 or 15 years, there have been great drives in the improvement of science and health coverage in the UK. Headlines are one of the big bugbears that still exist. In the guidelines that we produced, headlines were the thing that everybody rowed about the most. There is a lot of strong feeling about headlines. On one hand, we can see that that is the bit that draws the eye to the article and, being realistic, that is the bit that catches people’s attention. We always make a plea to the media that, when they call something a cure or a miracle, they must remember patients. To go back to your earlier points about how patients become involved in clinical trials, many patients speak to the medical research charities or their GP wanting to join a clinical trial for the latest miracle cure, and we haven’t quite won the battle with the headlines, but we will keep trying.

Q144 Graham Stringer: Moving on from Jim’s question about openness, when there is misreporting of clinical trials, how much of it is to do with shoddy journalism, and even if the scientists and clinicians are being open, how much is it to do with them not quite knowing how to frame their results?

Dr Helen Jamison: That is a good question. There are many different reasons that influence how bad or good journalism is. There are three main groups that have a role. The first is journalists, and occasionally it may be shoddy journalism, although in our experience that is rare. Much of the time they are working hard and are under pressure from their news rooms, with competition from their colleagues. That may put them under pressure and lead them to get things wrong and to cut corners, but most of the journalists we know strive to get things right and take their responsibility seriously.

With scientists, some still feel wary of engaging with the new media, so they are likely to run in the opposite direction, or not be well prepared. Again, a lot is changing in that field, and many of them now see that they have a responsibility to engage and are having media training to enable them to engage much better than they used to.

The third important group that plays a significant role but is often more behind the scenes is press officers and communications experts either in universities or industry or at the research funders. As with all professions and so on in life, there are good press officers and bad press officers. Sometimes, misreporting may result from bad press releases. A bad press release may be hype on the part of the organisation, or the scientists might have encouraged it to go beyond because they are excited about what they have found.

There is a real issue, and often when there is a spectacularly bad story, which thankfully happens rarely, it has been a perfect storm of many different factors all playing together to give a bad story at the end, but the different reasons behind that may be complex.

Q145 Graham Stringer: You have made a point about putting out relative as well as absolute figures, and 50% improvement of very little is still very little. Are there any other examples of where you have been able to guide scientists and clinicians to improve the way they communicate, so that you do not get misleading stories?

Dr Helen Jamison: There are lots of ways, either formally or informally, that we guide press officers and scientists on a daily basis, such as making sure they put their work or study into context in terms of whether they have just observed something happening or actually tested it, whether what they found contradicts what is already out there and is unusual or in line with the consensus, making sure they are always up front and open about the caveats and limitations on what they have found, and when they engage with journalists being very clear not only about what they have shown but what they have not shown, so trying to foresee the headlines that might appear the next day saying, "What we have not shown is this."

One thing we are considering and will lead on from our work around Leveson is to adapt the guidelines for journalists as a guide for press and communications officers, and also for scientists, because they apply equally to all three groups when communicating science.

Chair: Thank you very much for a very informative session. We will go straight on to our third panel.

Examination of Witnesses

Witnesses: Bill Davidson, Acting Deputy Director and Head of Research Standards and Support, Department of Health, Peter Knight, Deputy Director, Head of Research Information and Intelligence, Department of Health, Dr Janet Wisely, Chief Executive, Health Research Authority, and Sir Kent Woods, Chief Executive, Medicines and Health Products Regulatory Authority, gave evidence.

Q146 Chair: May I welcome the panel? With four of you, it is going to be quite a tight session to get all the information, so if you feel at the end that there were things that you would like to add, we would welcome a note from you as a follow-up. Would you kindly introduce yourselves, please?

Dr Janet Wisely: Good morning. I am Janet Wisely, the Chief Executive of the Health Research Authority.

Sir Kent Woods: I am Sir Kent Woods, the Chief Executive of the Medicines and Healthcare Products Regulatory Agency, and I am currently also the chairman of the management board of the European Medicines Agency.

Bill Davidson: Good morning. My name is Bill Davidson. I am the acting deputy director and head of research standards and support at the Department of Health.

Peter Knight: Good morning. My name is Peter Knight. I am the deputy director at the Department of Health and head of research information and intelligence.

Q147 Chair: Sir Kent, this is almost one of your last outings in your role, isn’t it?

Sir Kent Woods: It may be.

Q148 Chair: May I start by getting some clarity for us about where responsibilities lie. How do the roles of the HRA, the MHRA and the NIHR differ? Where does the responsibility for the increasing number of clinical trials in the UK ultimately lie?

Dr Janet Wisely: The Health Research Authority has very specific roles within regulation which relate to the approval through the research ethics committees and also access to advice through section 251 of the NHS Act-that is confidential data without consent. Within those regulatory roles, we have a memorandum of understanding to ensure that we do not duplicate the role of the MHRA through the approvals. We also have a much wider role, which is largely about making it easier to do good quality research within the NHS that links to our role to promote and protect the interests of patients and the public in health research. I think we will come to talk about some of the initiatives we have got around advice, guidance and training, and the whole approval processes.

Sir Kent Woods: The MHRA is responsible for the authorisation of clinical trials of pharmaceuticals to be conducted in the UK under the provisions of the clinical trials directive transposed into UK regulations. We also have a responsibility for oversight of good clinical practice in trials and can inspect trials and their conduct. We also have the policy lead in negotiations within Europe on the revision of the clinical trials directive, which is currently under way.

Bill Davidson: The National Institute for Health Research is not separate from the Department of Health. It is the name we give to the funding that we give to research. We give that funding in four main ways: research programmes that involve research projects themselves; infrastructure that supports the delivery of research; through faculty, which is developing people to do the research; and through systems. I am responsible for the elements of the National Institute for Health Research that support research management.

Peter Knight: Building on what Bill has just said, I am responsible for the information part or infrastructure within the NIHR. As Bill has quietly illustrated, there are four component parts, and we represent two of those.

Q149 Chair: The boundaries between the various organisations are pretty complicated. Do you think researchers understand the differing roles? Is it straightforward for them to set up a clinical trial? Can they do it without any knowledge of these respective roles?

Dr Janet Wisely: There are good sources of advice out there. There is the clinical trials toolkit, which is very good at signposting a lot of the advice and guidance. The Health Research Authority recognises that we have a role to provide further support and guidance to researchers. Many do have a good understanding, and others find it difficult to navigate what is a complex system.

I think the regulation is well laid out, and we have submitted to a previous inquiry the boundaries between the roles of the HRA through the National Research Ethics Service, the MHRA, the HFEA and the HTA, which is very clear. Where people have more difficulty is in understanding the boundaries of governance. The Academy of Medical Sciences very helpfully distinguished between the regulation of research and the governance of research, and I think people find it harder to understand some of the boundaries around governance.

The other thing I would add is that, even where people do understand the system, they do not always understand why the system operates as it does, which can lead to a lack of buy-in, so we have recognised through the HRA that, when we deliver the efficiencies, particularly around governance, what is left needs to be much better explained, so that researchers buy into the process. To evidence that, of the 6,000 applications to ethics last year, 1,000 did not meet an initial checklist validation. That is partly about quality control of the applications, and I think it is also about a lack of buy-in to why some of the information is being ask for.

Sir Kent Woods: The point you have raised is very important, Chairman, and we have done a lot over the years since the clinical trials directive was introduced to try to ease the path of researchers, particularly in respect of the regulatory requirements. Janet has referred to the clinical trials toolkit, to which the MHRA contributed. We have a great deal of information on our website. We also work quite closely with the research community through workshops and seminars. We also have a helpline-the clinical trials unit takes about 3,000 phone calls and 3,000 e-mail inquiries a year specifically on the regulatory requirements-and we provide regulatory and scientific advice at various levels, depending on the level of expertise of the applicants and the complexity of the trial.

Bill Davidson: The regulatory framework for research has become increasingly complex, which is one of the main reasons why we established the HRA in 2011. In the Care Bill that was introduced in Parliament last week, the HRA is given a duty to co-ordinate and standardise regulatory practice. There is also a set of duties of mutual co-operation between the HRA and various others with responsibilities in this area, such as the MHRA, in order to bring about some of the simplification that will help the environment for research in this country to flourish.

Q150 Chair: The clinical trials toolkit has a route map, which I have just been looking at, and it is reminiscent of the map of the London underground. It is very elegant and rather beautiful, but it is rather confusing for someone who is not familiar with it. Is it not surprising that there is some confusion out there and that it generates 3,000 phone calls and thousands of e-mails?

Dr Janet Wisely: We think it is complex, and we think that people need to understand it, but it is also a professional activity, so I think we do have a duty to support people through the process. We would also recognise that it is a complex activity to undertake a clinical trial, and however much we improve the efficiencies around approvals, it is still going to be quite a complex task. I was involved in the development of the clinical trials toolkit, too, and we were slightly cautious that mapping it out makes it look like a big picture. But the regulation is well organised, and I think that, in general, people come to us or the MHRA and find ways through that regulatory landscape.

Sir Kent Woods: I would also mention that researchers approaching the regulatory set-up for clinical trials come with very different levels of prior understanding. The most difficult and challenging research groups would perhaps be ones from academia that are relatively new to the clinical trials field and without the resources of a regulatory affairs department behind them, for instance. We try very hard to reach this particular group. We find that that situation applies particularly in cutting-edge areas of research-for instance, stem cell therapy and regenerative medicine-where we are dealing with small groups which are not particularly well resourced, other than for their research capability, and which do not have behind them the infrastructure that would normally help them through. From industry’s point of view, all companies doing trials will have well-established regulatory affairs groups who are very familiar with the landscape. It is the academic community and particularly the smaller biotech companies where we really need to work hard.

Q151 Stephen Mosley: Dr Wisely, the HRA issued a paper on Monday looking at its role in transparency. What types of research will fall within the scope of that transparency document?

Dr Janet Wisely: It is different for different parts. For trial registration, we have said it would be all clinical trials-that is broadly the medicines-but the general principles of transparency would be applied to all the types of studies we review. Those would range from clinical trials, health services research and education-based research.

That does give us challenges, because one of the things we need to do is make sure that the plans for publication are realistic and appropriate for the type of study. We have just done a small audit looking at final reports submitted to ethics committees to see whether, at that point, you could judge whether people had published according to the plans they had set out to ethics committee when they got their ethics committee approval-that is already part of the ethics committee review process. Of 115 studies, 33 had done what they said they would do, in publishing, and two-phase 1 studies-had done likewise, in not publishing; the rest were still talking about intentions. But the person who did that audit was concerned that some of the educational based projects-I think there were 40-had really been very over-ambitious about the plans they had set out to the ethics committee in the first place. So we need to get better at judging at the outset, as well as at the end, and to put in place mechanisms for checking.

I agreed with the set-out of the different layers of transparency. There is no excuse for not registering a clinical trial. We need to be clear what we mean by publication, but again, it must happen. If you are going to draw conclusions, you need some quality check, but just putting the results up there without conclusions is probably okay for quite small studies.

Q152 Chair: Just so we all understand the language, what do you define as a clinical trial?

Dr Janet Wisely: It would be something with a clinical intervention. We have said we will introduce these measures from September, because we need to be absolutely clear what we mean. We will do it based on the integrated research application system through which you generate all your applications in the UK at the moment. You are asked a set of questions at the beginning that determines what data sets you then get asked about. Some are easy: clinical trials of medicinal products is an easy categorisation. Clinical trials-perhaps a surgical intervention or a device study-are also easy. We will then need to define other clinical interventions and get the ethics committee to check that they are happy with that categorisation when they require the study to be registered.

Q153 Stephen Mosley: How would that process work? Would the people doing the trials have to report to yourselves-I know they have to go through the ethics committees-or would you have to go and look at a random subsection?

Dr Janet Wisely: Again, there would be a mix. It would be a condition of the ethics approval. At the time you apply to an ethics committee, it probably would be too early to register, because most applications that get to an ethics committee get a provisional opinion. We do not want to add an extra burden, so that some time after you have got your ethics committee approval you have to come back and tell us that you have registered. It would be a condition of the approval that you register within a time frame that we will have determined by September.

We have simple mechanisms to check at the end of the study whether people have registered and published as they should. We have already found through our audit that it was a quite task to look through the final reports. We need a better framework for those reports, but we might not need to do it on an individual application basis. For some, we will be able to rely on the sponsor.

For instance, when the NIHR funds research, we know that, as a funder, it ensures that studies are registered and published, so we don’t need to double-check. The MRC has got very good rates for publication registering, so it may be that for some we do a random audit within an overall assurance at a sponsor level and for others we do the audit on an application level.

Q154 Stephen Mosley: What will happen if the HRA detects non-compliance?

Dr Janet Wisely: One of the things that we set out in the paper that we published on Monday is that we need to work with those that have the professional accountability to set out what the sanctions would be. For instance, we need to have those conversations with the GMC. From the Health Research Authority’s perspective, for studies that have happened, it is quite difficult for us to have a role beyond identifying it and working with others that have those responsibilities, but we do need to look at what information we may provide to ethics committees in the case of applications from the same sponsor or same individuals-they could be new applications to the ethics committee-and then we may have a role to ask why it has not been published, and we may not be minded to approve another study until the previous one had.

Q155 Stephen Mosley: On a slightly different issue, I know the Academy of Medical Sciences has described the difficulty in researchers gaining R and D permissions from individual NHS trusts as the single greatest barrier to health research. I know that the HRA are going to be running a feasibility study later this year, and there is the streamlining of clinical trial approvals. How is that progressing?

Dr Janet Wisely: We are in the testing phase of an early feasibility study that will be reported to our board on 24 June. Then we will determine whether we move forward to implement any of the proposals or put solutions on other platforms. We are testing, through our Manchester REC-research ethics committee-office, a single validation point. We are testing whether we can get the researcher to put in one application to us for the ethics and the trust R and D approval, so that we can do the validation through the ethics service and that that is accepted by the R and D trust. The basic platform for an HRA assessment must be the single application.

Separately to that, we have recognised that the different components of the R and D trust approval have different issues to look at. They range from things that really should not be done at a local level at all, so we have to find ways of switching off local behaviour-for instance, the duplication of the review of the patient information sheet. The ethics committee is looking at that. There is no justifiable reason for the local R and D approval to do a second review of it, beyond checking the local contact details, so that is a switch-off behaviour. Then there are other areas where we are looking to see where there is a need for a local decision and whether that local decision could be taken based on a central assessment.

So those are areas where we are looking at what the range of the HRA’s role may be. There are various things such as data, radiation, pharmacy issues and suitability of the investigator. We have planning and testing groups that are looking at those different components to see what buy-in there would be for us to be able to do that assessment, so that the local decision becomes one of capacity and capability based on an assessment done by the HRA.

Q156 David Tredinnick: What has been your involvement in the European Medicines Agency’s recent efforts to develop a new policy on access to clinical trial data?

Sir Kent Woods: This is part of a continuing programme on behalf of the EMA to make greater transparent availability of the data they hold. It began with an expanded release of documents programme in November 2010. In the following two years, the agency released 1.6 million pages of documents, so this is a very considerable administrative challenge, and a costly one. The phase that is now under way is that that is being broadened, hopefully to achieve the routine release of the clinical trials data that the EMA holds in relation to specific regulatory decisions and market authorisations, once that decision has been taken. It is not without controversy, and in particular there are competing views about the way in which patient confidentiality can be protected; issues and debate about commercial confidentiality-what is and what is not commercially confidential; legal aspects; and questions about the ways in which the research community will carry out secondary analyses and whether they need some rules and protocols.

The EMA launched that piece of work at a large public meeting at the end of last year. Following that, five working groups were set up to examine the specific subsidiary aspects, as I have described. The working group reports were published at the end of April and there will now be a process of reflection inside the agency to produce a draft policy as to how we go forward. That policy is due be released in June for consultation. We hope that that consultation will close in September and that the agency will be able to set out clearly the way that it intends to go forward from 1 January next year.

Q157 David Tredinnick: The report of the recent European Union research collaboration CAMbrella project about looking at the use of complementary and alternative medicine across Europe, which was funded by several million euros, highlights the need for more comparative effectiveness research into what is called integrative medicine. I mentioned to another panel that integrative medicine is defined by 53 centres of academic excellence in America as-I will abbreviate-a practice that "makes use of all appropriate therapeutic approaches, healthcare professionals and disciplines to achieve optimal health and healing." Bearing in mind the Secretary of State for Health’s decision that patients should be at the centre and have choice in health care, do you think it is appropriate that there should be more research into this area? Under the Health and Social Care Act, patients are going to be asking for a wider range of treatments, and I am not sure that any of the agencies in the United Kingdom have got to grips with that yet. I am really just asking for a broad comment-I know that my question is slightly off the centre.

Sir Kent Woods: The issue of research commissioning, funding and prioritisation does not fall within my remit. I really cannot give you a useful response.

Dr Janet Wisely: I think that from the perspective of, say, an ethics committee, they would want to ensure that any study was ethical. Therefore, if you were setting something up, you would want to look at whether there was a genuine research question to ask and whether it was relevant to the patient and to the public. I think a consideration at that level would really be the only role for the Health Research Authority.

Bill Davidson: I agree with that. It is quite proper that research gets funded on its merits. If there is a rationale for the research, it seems sensible to look into it.

Peter Knight: The same issue. If there is a rationale for the research and it is good quality research, it should be funded.

Q158 David Tredinnick: Thank you.

Going back to my first question, the EMA advisory groups failed to reach agreement on several matters. You touched on the issue particularly with respect to the commercial confidentiality of clinical trial data. Does the Department of Health consider clinical study reports of individual patient-led trial data to be commercially confidential?

Sir Kent Woods: Perhaps I can respond to that first. We in the MHRA would not regard such reports as blanket commercially confidential. There may be elements within the report that could be argued to be commercially in confidence; we would need to be persuaded. In fact, for clinical trial results, our view has generally been that there is very little scope for commercial confidentiality. It tends to be more in the pre-clinical, the laboratory and perhaps the synthesis area-the manufacturing side-where commercially confidential information is contained; but our stance over the years, as we have gone further into this, has been to push back further and further, to ask why, specifically, should specific elements of clinical trial data be considered commercially in confidence. We are far more concerned about personal confidential data than commercial confidential data.

Q159 David Tredinnick: Are you aligning yourselves with Sense About Science, then? Do you take their view? Sense About Science, who presented to us earlier on, take a view that as much medical data as possible should be available. It would seem to be in the public interest-although I am certainly not a spokesman for them.

Sir Kent Woods: I would agree with that architecture of the problem. The first basic piece of information is public knowledge: a particular trial, with a particular protocol, has been embarked on-that ought to be absolutely transparent. Also, the results of the trial, in summary form: we would agree, in order to ensure that people who need to make decisions on the basis of trials, as clinicians, as patients, whatever, have access to the conclusions-the final results of their studies. I think the difficult bit comes when you go firstly to look at the clinical study report in its full detail and, beyond that, the raw data-the individual patient data. I think there are some operational difficulties, and there are also some policy difficulties as to how those are handled.

The clinical study reports, in order to ensure that one is not releasing personal, identifiable data, do need to be quite carefully scrutinised before release, and they may need to be redacted in places; and that is a very labour-intensive process. I mentioned that the EMA had released 1.6 million pages of data over two years. We think that cost somewhere between €2 million and €3 million to do, so it is not simply the principle that we have concerns about: it is the operational practicalities of it, and the justification for the resources that go into it. This is a very laborious process. If there is a simpler way of ensuring that all non-confidential information is in the public domain, it would be a huge help for everybody.

Q160 Chair: Does the Department concur with that?

Peter Knight: It does, and the Department is very clear about the position on patient confidentiality, and that is quite a concern. Listening to the previous panel, I was encouraged to hear about the controlled release and looking at redaction, and that is exactly where the Department would be coming from.

Q161 Graham Stringer: Do you have any outstanding concerns about the draft EU clinical trials regulations? Are you at all concerned about Glenis Willmott’s proposed amendments to those regulations?

Sir Kent Woods: I think that the regulations as proposed by the Commission, which are now going through Council negotiations, are very much in the right direction. They incorporate a number of improvements to the original clinical trials directive, which we, as a member state, have been unhappy with right back to 2004. I think the areas I particularly welcome are around the recognition that there should be some risk proportionality about how clinical trials are authorised, and that there is not a one-size-fits-all approach. Some trials intrinsically present a greater risk to participants and others much less so.

The second area we very much welcome is the move towards the simplification of the process of carrying out a trial in multiple member states. A lot of research is carried out in more than one country, and one of the drawbacks of the original clinical trials directive, essentially giving individual member states responsibility one by one for the trials done in their territory, was to make it very difficult and very cumbersome to apply to do a study in several countries; so we in the UK have been working with other member states very hard in recent years, to try to devise a sort of mutual recognition system-a way of collectively coming to an assessment of a clinical trial application over several countries. Those are now being incorporated into the proposals for the clinical trials regulation. All that is very welcome.

The areas of concern are still under negotiation. Glenis Willmott’s recommendation around the release of the full clinical study report does leave the operational and practical difficulty of how that should be done and by whom. It does not completely get away from the problem I have mentioned of the need to make sure that one is not releasing personal confidential data, and therefore how one is going to do that redaction process. As has been mentioned by previous witnesses, it also gives some difficulties for the non-commercial researcher who would not routinely be preparing a clinical study report of the pattern that is laid down in the ICH guidance. One would have to be very clear as to what the equivalence of a CSR would be for research that is not being submitted for a market authorisation. It might in effect be something like the sort of published report of a study that currently goes into an academic journal. I would be concerned about the burden implied in that recommendation, bearing in mind that one of the main drivers for the revision of the clinical trials directive was to make it simpler and easier to do research in Europe. In the past four or five years the number of clinical trials brought forward on pharmaceuticals in Europe has fallen by 25%, and there is a strong feeling that a significant contributor to that has been the complexity of the legislation. So taking as a starting point the revision of the directive, how can we make this simpler? Adding another layer of complexity is swimming in the wrong direction.

Q162 Graham Stringer: So you are actually saying that you are against mandatory publication of all CSRs?

Sir Kent Woods: I would need to give very serious consideration to how that can be done in a way that is useful to the people who will be drawing on that information and that is operationally feasible, and it will need to protect the patient confidentiality that is potentially embedded in the CSR. These are very detailed reports. They have become more and more detailed as the years have gone by. They are prepared for a specific purpose, which is to help regulatory authorities reach decisions about whether or not that product should have a marketing authorisation. That is the genesis of the CSR. It may not be the best vehicle to use if we are looking for widening transparency.

Q163 Graham Stringer: I do not want to put words in your mouth, and I am sure that you would not like me to, but you are worried about swamping of information?

Sir Kent Woods: Yes, that would be one aspect; it could swamp the end user with a level of detail that is not needed or helpful, and it could make the process of completing clinical research a little bit more burdensome, particularly for organisations that are not set up to put products forward for market authorisation.

Q164 Graham Stringer: You mentioned that you welcomed the fact that the new regulations were more risk based than they had been previously. Do you think they deal as well as they could do, particularly with phase 3 of the trials, with orphan diseases-diseases that not many people suffer from? It is very difficult to get as many people to participate in the trials. Do you think they deal with that situation, or are they going to make it more difficult for those rare diseases?

Sir Kent Woods: I do not see anything in the proposals that would make it more difficult, but, in the case of rare diseases, it is a serious challenge to identify adequate numbers of potential participants and to marshal them into a protocol subject to informed consent. There are already provisions within the existing legislation for circumstances where there are so few patients with the condition that the market authorisation for a product has to be authorised on a lesser level of data than would be the case if this was a common condition. Orphan diseases and treatments of orphan diseases also attract some support in the regulatory system in scientific advice and waivers and fees and so forth. Efforts are already being made to deal with this issue. It is not completely solved but I do not think that the revision as it is currently going is likely to influence this greatly one way or the other.

Q165 Graham Stringer: A final question: are clinical trials likely to change in their structure in the future and are the proposed European regulations likely to be flexible enough to deal with those changes in design?

Sir Kent Woods: That is a very important point. We have seen over the last 10 years that the clinical trials directive has in it some inflexibilities, which we wish to see changed. Therefore, the ability to adapt the regulatory framework more quickly than every 10 or 15 years is important. You are absolutely right that research designs will change. They should change. Indeed, as an agency, we strongly encourage researchers to look at, for instance, adaptive trial designs, which are more efficient in their use of time and in the number of patients they need. We certainly do not wish to inhibit developments in methodology by creating a rigid, inflexible regulatory structure with revision. I think the Commission’s intention is to put some of the key areas of the revision under the provision of delegated legislation, so if it is necessary in the future to further refine various aspects, that can be done without revising the entire legal code.

Q166 Jim Dowd: A couple of you have mentioned the importance of protecting personal data as a priority. The Caldicott 2 review, of which I am sure you are all aware, identified what it felt was a grey area for individual patient level trial data, where patients could be identified despite being technically anonymised. Do you agree with the area that they pointed out?

Peter Knight: Yes, I do agree. I have done a major piece of research around this area over the last few years. It is an area where anonymisation is supposed to be a starting point-you can’t get back to an individual. However, with other data sets that are around and freely available and the risks of re-identifying by meshing those data sets together, it is quite an important aspect to reflect on. Data protection law is one thing we have for protecting that whole area, but we also have both contract law and HR law. Researchers undertaking activity have a duty to ensure confidentiality regardless. That is important in terms of the aspects of the legal framework we operate in. So yes, that area is understood. I think it is more broad than just saying, "What are the data protection aspects of this?" It is about how a researcher receives data, how the disclosure of that data is then within their remit to operate, and what action would be taken if somebody breached that agreement.

Q167 Jim Dowd: Do you feel that the suggestion of an accredited safe haven is a reasonable mechanism for dealing with this?

Peter Knight: Yes, and within the Health and Social Care Act, the health and social care information centre has effectively got that duty. There is also the clinical practice research data link. We have got a process of accrediting the safe haven through what was the National Information Governance Board-its responsibilities have now been transferred to the HRA. Section 251 of the Act sets out the duty of confidentiality, making sure that data is processed in an appropriate, safe and secure way.

Q168 Jim Dowd: We are running short of time, so I will restrict this to one final question. You will be aware of what was identified as the consent for consent difficulty. What action has been taken to address that?

Peter Knight: So the department, working with the Information Commissioner over a number of years, having sought legal advice on this, has set in the NHS constitution a clear position around consent for consent. Consent for consent is broadly about saying, "Can I contact you without having your permission to contact?" That is the anathema of what the problem is.

The Information Commissioner was quite clear: set the expectation of the population about what you are going to do. We have done that as a pledge in the NHS constitution, which sets out that the NHS will contact you about research that is relevant to you and you are eligible to participate in, and then get on and do it, effectively. That is the guidance we received and the position we validated through our legal branch. The constitution is the starting point and that requires then to be cascaded elsewhere, so that GP surgeries are very clearly positioned around what we do with data and the ability to contact you for research through your clinical line of accountability-i.e. the patient and clinician relationship. So that is where the Department has got to.

Q169 Chair: Do you send out guidance to trusts about how they should collect data? As an example, I have come across a situation where the first question on a document was how to opt out, rather than the benefits of being part of a trial.

Peter Knight: Can I just be quite clear? If that is consenting into a trial, absolutely, that is a clear position. If it is about use of data, in legal terms, there is no definition of opt-out. The Data Protection Act is very clear about this: you have the right to object to your data being used in an identifiable form.

Q170 Chair: But that should not be the first question.

Peter Knight: No, no. Absolutely, but it is very important to recognise that the opt-out process is not a legal construct.

Q171 Chair: Sir Kent, you were nodding vigorously.

Peter Knight: And the HRA in guidance terms?

Dr Janet Wisely: For the HRA, the challenge-the frustration for researchers is well understood in the NHS, but Caldicott 2 has laid out a clear framework that really had not changed much from the initial review-is that researchers need a legal basis to access that. So that is consent for consent if you are not part of the clinical team, unless the data are anonymised. We may be able to do further work to identify where researchers-where they are clinicians and are part of the NHS-could be considered as part of a clinical team. I think we could take a more proportionate view there.

I also add that in terms of some work we have done through some patient and public involvement, we are hearing the same as Caldicott did-that people, patients and the public are very comfortable about researchers having access to anonymised data. They are very content with people in the NHS having access to their data, particularly patients for researchers, but there was caution about a wider access potentially from outside the NHS to their notes. I think Caldicott 2 sets out quite a sensible framework.

Q172 Stephen Metcalfe: Once a trial has been completed and the evidence emerges that this can improve outcomes for patients, how quickly and effectively is that information disseminated out to clinicians and incorporated into what could be considered standard medical practice? How is that achieved, and how quickly is it done?

Bill Davidson: One of the things that we did in last year’s Health and Social Care Act was introduce a duty across all parts of the system, not only to promote the conduct of research, but to promote the use in the health service of evidence from research. That duty applies to clinical commissioning groups and to NHS England, so they have a key role in making sure that the activity at the front line is translated into clinical practice. There is also NICE and the guidance that it issues. We heard from a previous witness about some of the time lines there. I do not lead on that and cannot comment on what their normal time lines are, I am afraid.

Sir Kent Woods: Can I perhaps add to that? You focused in your question on the efficacy side. As an agency, we are very much concerned to see that any new evidence on the benefit-risk relationship is communicated to prescribers and patients as quickly as possible. We have well-established communication channels to do that. If there is a new piece of research, or a new regulatory decision on a safety issue, we will put that out through a press release, through the professional bodies, and we will put it on our website. That is, as it were, the immediate output instantaneously.

The second phase is to include it in our regular drug safety update bulletin, which goes out once a month. And then the third is to get it into the standard reference works, like the British National Formulary, which is revised every six months, so that that new knowledge is accessible to clinicians at the earliest possible moment. But it is a real challenge, because the evidence base on any product on the market is constantly being expanded and developed. It is not a once-only judgment about the risk-benefit relationship.

This will evolve over time, as we get more experience in a wider range of patients with more complex conditions, with more co-medication. So our role as the regulatory agency is not just in relation to the company, but it is in relation to the wider public and the health professions to make sure that what we know-our current understanding of the risk-benefit relationship-is actually as widely known as we could possibly achieve.

Q173 Stephen Metcalfe: Anyone want to add to that?

Back to you, Mr Davidson. You said there is sort of an obligation on the commissioning groups, but how are they finding out? What is the actual practical process? Is it something you have to go and search for, or is it being forced down the chain, as this evidence becomes available, that there is an improvement in the way something is treated? How is that getting to the front line, so that we all benefit?

Bill Davidson: That is a good question. One of the key mechanisms is the guidance that is issued by NICE. Kent has described the things that the MHRA does on top of that, through the Formulary.

Q174 Stephen Metcalfe: Sorry, just to interrupt you. How much guidance is issued in any given month or year from NICE, and is it a practical proposition to say, "That’s the way it’s done."? You see the point I am trying to make. Without knowing the scale, it might be impossible for someone to deal with.

Bill Davidson: I can’t say. I am sorry, I cannot comment on NICE.

Q175 Stephen Metcalfe: But that would be the path, right? Sir Kent Woods: If I can comment. For many years I was in clinical practice and I did make use of the outputs of NICE and I have kept, obviously, in touch with their work. Although the volume of guidance and guidelines that comes out of NICE is large, the accessibility, certainly through their website, I have always found to be very good. If I were commissioning a service or if I, as a clinician, was providing a service in a certain area for a certain condition, I would not have any trouble getting into that information, because it is structured in a way which would take me straight to the condition and the particular treatments that were of interest to me.

Chair: Thank you very much for a helpful session. We have one more session in this inquiry. If there is any further information you feel it appropriate to submit, I should be grateful for it. Thank you for your attendance.

Prepared 20th May 2013