HL Deb 19 May 2004 vol 661 cc845-68

7.44 p.m.

Earl Howe rose to move, That an humble Address be presented to Her Majesty praying that the regulations, laid before the House on 1 April, be annulled (S.I. 2004/1031) [4th Report from the Merits Committee].

The noble Lord said: My Lords, the regulations to which this Prayer relates are primarily aimed at transposing into UK law the provisions of the EC Clinical Trials Directive 2001. I first became aware of the directive in the middle of last year when the Government were consulting on its implementation. At that time the concerns we were hearing were mainly those of the medical research charities and academics who were fearful that a combination of bureaucracy, excessive costs and procedural inflexibility would finish off a great deal of collaboratively funded non-commercial clinical research in the UK. It is fair to say that, thanks to the work of Ministers and officials, to which I pay tribute, those worries have diminished somewhat.

There is still a concern, reflected in the recent report of the Merits Committee, about what effect a commission directive on good clinical practice might have on the UK when it is eventually issued. There is also a strong feeling that the aims and content of the directive should be reviewed by the Commission at the earliest opportunity, particularly in relation to noncommercial clinical trials. The Minister may care to comment on those matters. However, some of the other earlier points of contention are no longer so salient and I do not intend to spend time on them now.

The concerns that I want to raise this evening fall under two main headings: the rules for clinical trials as they affect mentally incapacitated adults and the future independence and functions of research ethics committees. The way that these two issues have been treated in the regulations has, in my view, profound implications for the future of clinical trials in this country. I hope that the Minister can provide some sturdy reassurances on these matters. He needs to know that there is real dismay and alarm out there, to a degree that I am not certain I can reflect adequately in the space of a few minutes.

Let me start with mental incapacity. Paragraph 2 in Part 1 of Schedule 1 introduces into UK law for the first time the concept of a legal representative who may give consent for an adult lacking capacity to be entered into a clinical trial. It is the physician with responsibility for the adult's healthcare who is given the power to choose who should act as the person's legal representative in cases where this is not already clear. In the absence of anyone able to assume the role of personal legal representative, the physician may himself act in that role or alternatively may nominate anyone he chooses from the hospital or healthcare provider concerned.

It seems extraordinary that this element of the regulations should have been brought forward in advance of the introduction of the Mental Incapacity Bill. The whole area of medical research and mentally incapacitated patients is surely one to which only primary legislation can do full justice. The safeguards that should govern medical research in these circumstances need to be examined with the greatest care by both Houses of Parliament. Changing the law to enable one adult to decide what happens to another adult is a major matter. It is not a change appropriate to regulations.

Equally, it is a change that is fraught with danger. One cannot just appoint anyone to take a decision about whether a person should take part in a clinical trial. Clinical trials carry risks as well as potential benefits. The person taking the decision must be capable of weighing the risks and benefits dispassionately to determine whether participating in the trial is in the patient's best interest. Publicly available clinical trial data is not always a reliable indicator of risk.

The decision maker needs to make an informed judgment as well as to be independent of the process. Is the patient's doctor independent of the process? If he is a hospital doctor and the researchers are friends and colleagues working alongside him, he may well not be independent in the truest sense. What about a nominee of the NHS trust? I am very worried that the regulations before us leave it completely open as to who exactly may find himself taking what could be momentous decisions on behalf of a mentally incapacitated individual. Technically, the regulations would allow the receptionist on an A&E ward to act as the decision-taker.

If there are worries about mentally incapacitated adults in clinical trials, greater still are the worries relating to trials done on children where parental consent is not sought. As someone recently put it to me, if the researchers are in a hurry to find people to take part in a trial, they surely will not go to the family for consent. They will go straight to the doctor who is looking after the patient. What if the family find out too late what has happened and the trial had turned out badly? Mark my words, the moment a decision of this sort goes wrong, the balloon will go up. Negative publicity about a clinical trial could set back medical research for as long a time—and as badly—as the events at Alder Hey.

Why have the Government rushed into this and why have they not waited for the Mental Incapacity Bill for a full debate? The EU Clinical Trials Directive was designed as a harmonising measure, but the emphasis within it is very much on the protection of those who act as research subjects. It is therefore ironic in the extreme that Ministers should have allowed the protection of children and mentally incapacitated adults to be left so wide open.

Let me move to the issue of research ethics committees. These regulations are supposed to embody the content of the EU directive, but they are stuffed full of measures that are completely absent from the EU legislation. A prime example is the creation of the United Kingdom Ethics Committee Authority.

Who comprises this new authority? It consists of the Secretary of State for Health, the National Assembly for Wales, Scottish Ministers and the Department of Health, Social Services and Public Safety for Northern Ireland. With a make-up like that, I defy anyone to say that this is not a political body. It clearly is.

What powers does it have? It has the power to set up an ethics committee, abolish an ethics committee, recognise an existing committee, decline to recognise one or revoke a recognition of a committee if it is necessary or expedient to do so. In other words, the authority can abolish any ethics committee for any reason at all and set up another one whenever it chooses.

It also appoints the chairman, vice-chairman, alternative vice-chairman and all the members of NHS ethics committees. One of the key characteristics of ethics committees is their independence from politics, whether national, local or commercial. Indeed, independence of our ECs is an express requirement of the directive. We are looking here at the politicisation of ethics committees and hence the removal of their independence. I know that the Minister disputes that interpretation, but what other conclusion can we reach when the UKECA is being given such sweeping powers?

The creation of UKECA has enormous implications for medical research. Already over recent months we have witnessed the migration of large amounts of clinical trial work from the UK to other countries in Europe. The moment that foreign regulatory authorities start to regard UK ethics committees as lacking in independence there will only be one consequence. We shall see the flight of clinical trials from this country accelerate.

Setting up UKECA in this form is not only unnecessary but also potentially very damaging to our national interests. Of all countries in the world with a reputable medical research sector, the UK is alone in its decision to exercise political control over its ethics committees. It is a mistake.

There is a further respect in which the regulations unnecessarily restrict the freedom of ethics committees. The Helsinki Declaration contains a set of ethical principles to which all clinical trials must adhere. That declaration is referred to in Schedule 1, but it is defined in the terms of an out-of-date version.

Why does that matter? The Helsinki Declaration was radically rewritten in 2000. The importance of that rewrite is demonstrated sufficiently by one example, that of research subjects who lack capacity. On this issue, the 2000 version says: These groups should not be included in research unless the research is necessary to promote the health of the population represented and this research cannot instead be performed on legally competent persons". That restriction does not appear in the earlier version of the Helsinki Declaration; nor does it appear in Schedule 1 of these regulations.

The regulations are broadly enough written that if, for example, someone was trying out a new antibiotic for chest infections and had access to a captive population of demented patients on a geriatric ward, it would be permissible to use them. An ethics committee that looked to the 2000 version of the Helsinki Declaration and decided not to permit such a trial to go ahead would be open to legal challenge.

Why are committees being forced into this position? Even ethics committees in Scotland are having their hands tied in this fashion, despite the fact that Scottish law—the Adults with Incapacity (Scotland) Act 2000—runs expressly contrary to the regulations on this important issue.

We have already seen the way that the wind is blowing for ethics committees. COREC—the Central Office for Research Ethics Committees—has taken upon itself to decide that most research ethics committees will not in future be allowed to review clinical trials, even though they may have done so up to now without a problem. Only those RECs that are recognised under the regulations will be allowed to do so. The basis of recognition is still unclear.

I have received representations from a number of RECs around the country who are appalled and bewildered at COREC's approach, which they strongly believe puts at risk the future of phase one drugs trials in the UK.

It is perhaps not appreciated that up until now the system of ethical approval for clinical trials has effectively amounted to a dual safeguard on patient safety. In the past, when a proposal came forward for a clinical trial to be carried out in a number of centres, a multi-centre REC would initially review that research proposal and the local REC would then review it as suitable for local application. While this second review had an obvious time cost attached to it, its benefits for patients were repeatedly proven.

I have been given numerous examples of errors and avoidable disasters identified by a local REC in research proposals that had previously been vetted and passed. If the new rules had been in operation, these avoidable errors would not have been identified. Only a few committees—but 30 out of some 200—are being allowed to look at research proposals, with the result that local RECs can only act as rubber stamps. If a research proposal has been agreed by a more remote committee elsewhere, there is no opportunity for a local committee to make a site-specific assessment of that proposal.

Why are so many RECs being denied recognition? As far as I am aware, nobody has assessed them to be incompetent to do the job that they have been doing hitherto. We are looking at centralisation for its own sake. Nothing in the directive obliges us to adopt this kind of approach.

It is an approach that has the potential not only to curtail and destabilise clinical trial work in this country, but on top of that to place patients at unnecessary risk. But when RECs have tried to put this point of view to COREC, their letters have either not been answered or been dismissed out of hand. That cannot be the way to carry on.

I view these regulations with deep misgivings. In the words of one ethics committee that has written to me, they represent hasty, poorly consulted and poorly drafted legislation. By and large this is not the fault of the European directive. The fault lies at home.

If they act quickly, Ministers can still put things right. But time is now of the essence. I beg to move.

Moved, That an Humble Address be presented to Her Majesty praying that the regulations, laid before the House on 1 April, be annulled (S.I. 2004/1031). [4th Report from the Merits Committee]—(Earl Howe.)

8 p.m.

Lord Clement-Jones

My Lords, I rise also to support the humble Address that the noble Earl, Lord Howe, has put forward.

We are all agreed that this is a deeply unsatisfactory means of incorporating an EU directive into UK law. We are having to pray against a set of regulations, rather than having primary legislation with a Bill that we can amend as we go along and probe the Government's gold-plating of an EU directive in this way. We either have to swallow it whole or we have to spit it out whole.

Unfortunately, I share the opinion of the noble Earl, Lord Howe, that these regulations are extremely defective—perhaps not on the original grounds put forward by many research institutions and even the pharmaceutical industry itself, but for many of the reasons set out by the noble Earl. Some of the directive's defects result from the very little consultation done by the European Commission. Some of the saving grace of the situation is that the regulations may be amended in due course, as the Government themselves have admitted.

In passing, I would commend some of the words used by the Merits of Statutory Instruments Committee, chaired by the noble Lord, Lord Hunt, when it invited the Government to explain to what extent and how the many concerns raised about the directive and these regulations have been met and whether any remain outstanding. But, of course, the initiative had to remain with the Opposition in ensuring that a Prayer was laid to have the debate. Again, that is deeply unsatisfactory.

I thank the Minister for his very close personal interest in the discussion on these regulations, and for his updating correspondence as the regulations have been changed in response to many of the concerns. As the noble Earl, Lord Howe, said, there have been concerns that the regulations could impinge on current practices and that, rather than achieve the goal of harmonising and simplifying the conduct of clinical trials in Europe, it would make them increasingly difficult to conduct and create a more risk-averse culture, in the words of Cancer Research UK.

As is well known, we have a very high proportion of the worldwide spending on pharmaceutical research—indeed, some 9 per cent—and we have a higher proportion of publicly funded collaborative clinical trials than other European countries. So if these regulations are defective, the effects on the UK will undoubtedly be greater. We are a world leader and therefore our position could be at risk.

We also have a situation where many clinical trials in the UK are undertaken by independent, non-commercial and non-profit institutions on the basis of educational or unrestricted research grants. Again, that position must be safeguarded in these regulations.

It is very interesting to note that the European Organisation for Research and Treatment of Cancer has raised a number of issues concerning the way in which research is carried out as part of clinical trials which may be part of the ordinary course of treatment. It is very difficult to judge on the face of it whether its concerns are met by the amendments made to the regulations, but it says: In some instances … the pharmaceutical industry may provide the drug(s) and help academic research usually because the drug(s) has a recent marketing authorisation. The industry may not be willing to do so in the future if this is perceived by competent authorities as some sort of sponsorship of the trial. So in the worse case scenario (industry cannot provide the drug and marketed drugs cannot be used but in their registered indication/ schedule) 61 per cent of all EORTC trials won't take place anymore". I know that there have been discussions, and the note put together by the Department of Health and the MRHA seems to negative that, I think at paragraph 6. However, it is precisely those detailed but extremely important areas that need to be teased out in the course of discussion today. There are a number of other aspects as well.

There has been considerable discussion about the aspect of single sponsorship. There was concern that the EU directive required a single sponsor for research and that that was incompatible with the UK tradition of collaborative, multi-centre, publicly funded clinical trials where pharmaceutical companies may sponsor academic institutions through research grants or where academics may jointly administer a clinical trial within the NHS. It appears on the face of it that the regulations have been amended to ensure that that is not as rigid as it appears at first sight. It would be helpful if the Minister would give us assurances us that that situation has been cured.

Then again, a lot of concerns have been raised about the increased cost of running clinical trials and the fact that the regulations will increase those. If there are additional costs, they will not increase patient protection. That was certainly the assessment of Cancer Research UK of the MRHA partial regulatory impact assessment. Higher costs in turn will lead to fewer trials and fewer opportunities for research across the board. Generally, there is a belief that the new processes for monitoring, authorising and administering trials may well discourage researchers from undertaking clinical trails, simply as a result of the additional paperwork and the administration required. I believe that many of those concerns have been allayed but I would like to hear from the Minister in what respect he believes that that is the case.

The noble Earl, Lord Howe, raised a number of points that seemed to me not to have been addressed adequately, which revolve around a number of very important areas. He made a powerful case in respect of the three areas he mentioned. On the question of the independence of research ethics committees, I shall not go through the entire argument that he made; it would be fruitless to do so when he has made it so well. However, the fact is that UKECA has the power effectively to control the RECs. UKECA has the power to set them up, as the noble Earl said, to abolish them, to make restrictions on their work and to appoint all their members. As has been pointed out, that does not seem to square with the EU clinical trials directive itself. If that is not gold-plating and if that is not the Government taking an opportunity to control RECs, I do not know what is.

I believe that the Minister has given assurances that appointments to RECs will be made locally, but he has not explained quite how that is going to happen. As the Minister knows, I have raised a number of questions about the Central Office for Research Ethics Committees and its operation, particularly about its seeming inability to consult adequately over a very wide range of extremely important areas, particularly in terms of standing operating procedures, training and accreditation. There is considerable concern about COREC's role. If COREC is effectively to supervise that local appointment, that will be of some considerable concern to research ethics committees. That relationship is not good; I hope the Minister is fully aware of that.

There is a potential conflict of interest between COREC's role as an appointer or at least an approver of appointments and the fact that the head of COREC reports to the person with responsibility for oversight of research and development in the NHS. That does not seem a particularly apposite place for the head of COREC to report to. Those are considerable points.

The noble Earl, Lord Howe, mentioned the important point about the out-of-date ethical guidelines. I hope that the flexibility indicated in the Minister's correspondence that there may be amendments to the regulations in due course will cure that problem. But the 1996 version of the Helsinki declaration is far less adequate than the 2000 version. The noble Earl, Lord Howe, gave a clear example.

At the moment it would be possible for a pharmaceutical company to sponsor trials of a new drug in this country which it had no intention of marketing here. There would be no ability for the research ethics committee to turn down such a proposal for research in those circumstances because it would be permissible under the 1996 declaration, so there are considerable flaws in that situation. The noble Earl, Lord Howe, made a strong case on the legal representatives for adults who lack capacity and children for whom no one has parental responsibility.

I recognise that the Government have made welcome changes to the regulations and that to some extent we are in an interim situation. I also recognise that in EU terms, in the words of the saying, we would not have started from here. But the Government must bear responsibility for the additions, changes and inconsistencies that they are responsible for drafting into the regulations. That is the fundamental area on which these Benches object to the regulations.

Lord Carter

My Lords, I shall say a few words on the regulations as a result of my chairmanship of the Joint Select Committee on the Draft Mental Incapacity Bill. In our deliberations we gave a great deal of thought to the problem of research on people who lack the capacity to give consent to that research as a result of physical or mental impairment. I would like to say a few words about the relationship of those regulations to our considerations on the draft Mental Incapacity Bill.

The main reference to the role of ethics committees seems to be in Regulation 15(5) and 15(7) on page 17. Regulation 15(5)(h) states: if the subjects are to include persons incapable of giving informed consent, whether the research is justified having regard to the conditions and principles specified in Part 5 of Schedule 1"— I shall comeback to that because it is a crucial part of the regulation. It also requires the ethics committee, if it does not have a member with professional expertise in the treatment of conditions where there is research on people with impairment, to add someone with that ability to the committee.

The most important provisions are in parts 1 and 5 of Schedule 1. As we heard, part 1 defines a legal representative. I shall not say any more about that—I shall leave the Minister to reply to the cogent points made by the noble Earl, Lord Howe. The crucial part of the regulations regarding people who lack capacity is on page 44 in part 5 of Schedule 1, "Conditions and principles which apply in relation to an incapacitated adult". It sets out clearly the 11 conditions and four principles.

I wish to draw particular attention to condition 9, which applies to an incapacitated adult who is to take part in research. It states: There are grounds for expecting that administering the medicinal product to be tested in the trial will produce a benefit to the subject outweighing the risks or produce no risk at all". I presume that the subject is the person with incapacity who is taking part in the trial.

That answers the point made by the noble Earl, Lord Howe, about the group with dementia having a flu drug or an antibiotic tested on them, because under condition 9 it has to produce a benefit for the person taking part in the trial. If that is the case, does that mean that clinical trials of medicines cannot be conducted to give benefit to a class of people with a clinical condition, for example, Alzheimer's? Must they be conducted only on people who lack capacity if the clinical trial is of benefit to the individual incapacitated person who is taking part in the trial? As the measure is worded, presumably it will not be possible to give a placebo to an incapacitated person who is participating in a trial.

I turn briefly to the Joint Select Committee report on the draft Mental Incapacity Bill. The committee flagged up the possible effects of European directives on medical research. Paragraph 285 states: Our attention has also been drawn to the European Clinical Trials Directive 2001 … While this Directive is limited to trials of pharmaceutical products"— which is what we are talking about— it is possible that future European Directives may extend to other forms of medical research and trials of innovative treatment. There is therefore an argument to include in the draft Bill"— or the full Bill when it finally comes forward— requirements for the authorisation and supervision of research involving people without capacity to consent, in order to comply with the Clinical Trials Directive and any relevant future European Directives". That was the point that the noble Earl, Lord Howe, was making about primary legislation. I shall leave the Minister to deal with that.

We in the committee were concerned about forbidding research on people without capacity where that research would not benefit them directly but would benefit others. I used the example of Alzheimer's disease in that regard. We were thinking here not of trials involving drugs but research on the results of blood samples, DNA samples and other comparatively harmless aspects of research that might be required to be carried out on someone with a condition such as Alzheimer's disease. That research might not benefit the people who were giving the blood sample or whatever, but would perhaps be of benefit to the class of people as a whole. We said in paragraph 283: When a person lacks the capacity to give consent, they should only be involved with medical research, if it is either in their best interests"— which I think is in the regulations where reference is made to it being of benefit to them directly— or if it is the only method of conducting research into their particular condition and everyone involved with the person is satisfied that this is a non-exploitative proposal which will not harm or distress the individual involved".

8.15 p.m.

Earl Howe

My Lords, I am grateful to the noble Lord for giving way. That is a rather different point from the requirement in the Helsinki Declaration. That says that mentally incapacitated patients should not be included in research at all unless the research is necessary to promote their own health, and you cannot do the research on any mentally competent adult. So there is, as it were, a double condition on it.

Lord Carter

My Lords, I was just about to come to that point. I shall deal with that in a moment.

So far as I can see the regulations seem to move away from the approach I have just described by requiring that the clinical trial of a medicine can be of benefit to the individual with incapacity only if he or she is included in the trial. That tightens up the controls as compared to what we were saying in our report. I can understand that where trials of medicines are concerned but I am not sure that it is applicable in the case of blood or DNA samples.

To conclude, we on the Select Committee were concerned to set out the key principles that should be observed when considering research on those lacking the capacity to consent to the research. That is the point that the noble Earl, Lord Howe, has just made. We set out at paragraph 289 what we thought were the key principles enshrined by the World Medical Association. They should include the following: research involving people who may be incapacitated must be reviewed by a properly established and independent ethics committee and can only proceed if ethical permission is granted". That is in the regulations. The paragraph continues, where a person has the capacity to consent then his decision whether or not to partake in research must be respected". That is in the regulations.

Paragraph 289 continues, considerable care should be taken to ensure that under these circumstances consent to participate was freely given and not a consequence of coercion. The inclusion of people in research, who lacked the capacity to consent, must only occur when such research has the potential for direct benefit to those with that particular problem and could not have been done through the involvement of those with capacity". I think that answers the point that the noble Earl, Lord Howe, has just made.

Paragraph 289 continues, those undertaking research involving people lacking the capacity to consent must respect any indications that a person did not wish to participate (i.e. was dissenting)"— I believe that is in the regulations— and any discomfort or risk involved in the research must be, at the most, minimal". We then go on to state in some detail what should be in the codes of practice to accompany the Mental Incapacity Bill.

As far as I can see, the regulations are in line with the recommendations that we made, with the exception, as I have said, of the provision that research has to be for the direct benefit of the person without capacity who was taking part in the clinical trial of drugs, as a result of decisions that are taken by others on his behalf. I think that I can understand the reasoning regarding drug trials, but in the wider area of research it would have to be considered for the benefit of a whole class of people, not just for individuals.

Baroness Knight of Collingtree

My Lords, I have read carefully the wordy statutory instrument right through, and it gives me cause for severe concern about the principle that it establishes.

However disappointing this may be to scientists whose primary, and certainly not ignoble, aim is to discover cures for sick people, it can never be right in any circumstances to use mentally handicapped people as experimental material without their consent. Most cannot give it anyway, but that is no excuse. Hitler did that and the world rightly condemned him. It appals me that we now propose to emulate him.

There are pages and pages of S.I. 1031 devoted to the ethical committees, the strict regulations, the investigators, the licensing authorities and the official guidelines, but the bottom line is that mentally handicapped people are to be used for research and experimentation without their agreement. Nothing in the so-called "safeguards" alters that.

Yet, the statutory instrument acknowledges that the experiments that it permits might well be sufficiently dangerous to the human guinea pig as to cause death. The document actually says that. On page 27, it specifies what should happen, when death of the subject results", which brings me to another point. On page 4 the statutory instrument calls the person undergoing such research a, human subject". Well, that rather gives the game away. Once one starts referring to human beings as "human subjects", it is clear that one regards them as sub-standard objects. We really cannot agree to that.

Some people are concerned that the regulations for legal interpretation are flawed because they are so wide and institute a major change in the law. My noble friend Lord Howe dealt brilliantly with that point, which I know is causing considerable concern outside this House. Other people are prepared to agree with the proposals as long as such research can only be allowed if it will benefit the person who is actually enduring the experiment. The noble Lord, Lord Carter, drew our attention to Part 5, paragraph 9, on page 44, and said that the point may be covered by that part of the statutory instrument. That is disputed outside and we must be clear that, so far, it has not managed to ease the concern that has been expressed.

I have to admit that, even if there was action both on that point and the legal point, I would still have objections to the statutory instrument, because I have much bitter personal experience of how promises in this place are broken to achieve objectives. When we were debating the Abortion Bill in 1967—and I remember it vividly, because it was the first major Bill in which I was involved—it got through Parliament because certain firm promises were made.

"There will never be abortion on demand if we pass this Bill," they said. "Never. What an extraordinary suggestion!" And yet everybody knows we certainly have abortion on demand today. "The number of abortions will not rise at all," they said. "They will just happen in nice, clean hospitals instead of on nasty, dirty kitchen tables. It will be perfectly alright and the numbers will not rise." Will not rise? I understand now that we have so far got rid of 6 million babies. Nobody suggests we ever did that prior to the Abortion Bill.

There was another argument, and I put forward a particular amendment about this point. "Using aborted babies for experimentation," they said, "will never be allowed. Never." Well, everybody knows that it happens all the time today, in spite of that promise.

I remember, too, that they said "Why do you worry the House in this way? Of course abortion will not be carried out for minor medical deficiencies in the child." Remember the case of the child recently aborted because he had a cleft palate? That is not the first case. Members opposite may frown, but I am only telling the truth. These things were told to us when we were debating that Bill and, because of the promises made, the Bill was passed. Every single promise has been broken. This experience teaches me that, however well intentioned, such promises, I am afraid, are made to be broken.

We should not be muddled about what we mean by "research". If an Alzheimer's sufferer has been given all available medicines for that condition and is still no better, and then another medicine comes on to the market, it cannot be called research to offer that medicine to him or her, suggesting that the new tablet might help. That is not research. That is trying a new tablet, and maybe it will help. But it was research when a group went to Porton Down, having volunteered to be tested in an endeavour to find a cure for the common cold, and were subsequently given sarin.

It is incorrect to claim that scientists will be able to do research only if we permit these changes. Only last week, doctors at the Brain Research Institute at the University of California announced that they had made a significant breakthrough in the treatment of Alzheimer's, achieved without any of the changes now before us. It was an extremely important and interesting development of the knowledge of what happens to the brain in Alzheimer's, so it is not the case that only these researches are going to help.

I invite the Minister to alter slightly the reply he gave to me on 5 May. He said: Those conducting trials must obtain informed consent from all participants".—[Official Report, 5/5/04; col. 1097] Would that it were so. If this were the case, your Lordships would be blessed by my silence. It is the crux of my case that the statutory instrument says exactly the opposite.

Finally, I found it rather sneaky to introduce this statutory instrument—initially, as my noble friend Earl Howe has said, clearly part of the draft Mental Incapacity Bill—on the very day the House rose for the Easter Recess. If the Government hoped that that subterfuge would mean it would not be noticed in the plethora of bonnets, eggs and 10 days off, they were wrong. But it so easily could have slipped through because of the way it was introduced. I was informed in an Answer to a Written Question that this happened because there was a directive from our masters, the EU. Well, in my eyes, that does not improve it.

8.30 p.m.

Lord Turnberg

My Lords, I want to speak briefly in favour of the regulations as they stand. First, the noble Earl, Lord Howe, raised some important questions about mentally incapacitated patients and ethics committees. I do not want to enter too far into the debate about mentally incapacitated patients. The noble Lord, Lord Carter, dealt with them at least in part and I shall read his comments with interest. I shall also be interested to hear what the Minister has to say.

However, I must point out that if research on mentally incapacitated patients were not done, we would never develop new treatments for Alzheimer's disease or other mental illnesses. It is therefore essential that we undertake research on them in one form or another. If they cannot give consent, we have a catch-22 situation; they cannot give consent, yet research is essential if we are to treat them. For reasons other than wanting to find a treatment for mentally incapacitated patients, no one in his right mind would want to undertake research on patients who could not give their consent. It is done on patients who are able to give consent. Indeed, giving a cancer therapy or nasty treatment to mentally incapacitated patients without their consent would never get past first base with any ethics committee. Therefore, one would want to undertake only research for those particular patients and I am not sure that the background to the points raised by the noble Earl is correct.

With regard to the ethics committees, we have a problem with multi-centre trials, which is why there has been an attempt at rationalising the situation. It is that research or a set of researches goes to a multi-centre research ethics committee and then to a whole series—perhaps 20, 30 or 40—of research ethics committees at the local level. That means that it can take, and has taken, up to two years before a trial can begin. That delay is of course unconscionable and it is the reason why there has been an attempt to rationalise the process so that there is a limited number of ethics committees. How many ethics committees do we really need to undertake ethical review? I am not therefore entirely in tune with what the noble Earl has suggested.

I believe that the regulations do a reasonable job of achieving the two major aims; maintaining the safety of patients engaged in clinical trials, which is paramount, while ensuring that good, valid clinical research can be pursued without unnecessary—unnecessary—hindrance.

These regulations are infinitely better than what was once threatened in the draft directive which emanated from the European Commission. I want to place on record my unbound gratitude to my noble friend the Minister and his officials for the enormous amount of work he did in heading off the Commission. He did so by drawing its attention to the potential damage to its proposals for research.

There are several links in the chain which binds researchers and which ensure that clinical trials are conducted safely and ethically. First, those who fund non-commercial research, largely the Medical Research Council and the medical research charities—here I must express and interest as scientific adviser to the Association of Medical Research Charities —put proposals for grants through a rigorous appraisal using independent referees. That involves an assessment of whether the research is reasonable and can be expected to produce reasonable results that are favourable to patients, and so on. Then, of course, all proposals must be subjected to close examination by research ethics committees. That is not a trivial process, especially for multi-centred trials. Then a sponsor must take responsibility for monitoring the research to ensure that it is being done safely and responsibly. Of course, the employers—the universities and the NHS—have a legal responsibility for the behaviour of their employees. They, too, have codes of good practice for this purpose.

All those safeguards already exist in one form or another. The regulations now bring them together in a legal framework with the Medicines and Healthcare products Regulatory Agency—the MHRA. It will obviously be important that the MHRA consults widely with the research and other communities and that it does not wield a heavy axe. I am reasonably confident that it will behave appropriately.

I believe that the regulations are a reasonable and rational set of proposals. It seems that, within the research community at large—although not everyone is ecstatic about everything; they never are—the vast majority are heaving a collective sigh of relief that what we now have is acceptable and infinitely preferable to what we might have had in the Commission's original proposals. That, too, is the view of the medical research charities, which have the patient's view right at their heart. They are, after all, set up by, and are entirely dependent on the support of, the patients, and they, too, are keen to see these regulations in place.

Lord Warner

My Lords, I am glad to have this opportunity to explain the Government's position on these regulations, which transpose the Clinical Trials Directive into UK law. The regulations came into force on 1 May 2004. I have to say to the noble Baroness, Lady Knight, that I do not believe we were trying to slip anything through by subterfuge. The material in these regulations has been around for an extremely long time and has been much debated. I shall try briefly to take people through some of the history.

The Government support the aims of the directive. They are: to protect the safety, rights and integrity of trial participants; to ensure that the results of trials are reliable; and to facilitate the development of new medicines within the European Community. Listening to some parts of the debate, it would be easy to forget those objectives.

We successfully negotiated a model for regulation similar to that already in place in the UK, and we resisted attempts in Brussels to introduce unnecessary bureaucracy and an overly prescriptive approach to regulation. I am particularly grateful to my noble friend Lord Turnberg for his kind remarks about the work that the Department of Health carried out in this area.

I believe that the regulations achieve a proper balance. They safeguard the rights of clinical trial participants and minimise the regulatory impact on those who carry them out. We have asked the Pharmaceutical Industry Competitiveness Task Force, the Biosciences Leadership Council, the Department of Health and the MRC to monitor the impact of the directive on different sectors. We have a good Department of Health and MRC joint working party, which involves a wide range of research interests, and we shall look to that to continue to help us in this area.

We shall continue to work with all the sectors to keep issues under review. I can assure noble Lords that my door is always open if people want to bring to our attention their concerns. However, we must give the regulations a chance to work. We need to let them bed down and not become too excited about all the terrible things which people think may happen. We must see them working in practice, and we believe that they will be a good set of regulations.

Clinical trials make an important contribution to public health. They are the scientific basis for the use of new medicines and for new ways of administering existing medicines. The noble Earl, Lord Howe, referred—I thought, slightly excitedly—to the number of clinical trials that are fleeing from this country. The evidence suggests that the number of clinical trials conducted in the UK has not decreased. It is true that the number of clinical trials worldwide has increased and to some extent it is inevitable that the UK percentage in that larger volume of clinical trials may have reduced. The Pharmaceutical Industry Competitiveness Task Force (PICTF), which I mentioned earlier, is monitoring the number of trials and the reasons why companies may use other countries as well as the UK. The reasons are multi-faceted.

The clinical trials also contribute considerably to our economic wealth. The UK pharmaceutical industry produced a positive trade balance of £2.6 billion in 2002 and the industry spent £3 billion on clinical trials in the UK in 2001 alone. So there are some very substantial economic factors involved in this as well as benefits to patients.

The regulations mainly reinforce current clinical trial practice in the UK. The major changes are that studies in healthy volunteers require an authorisation from the MHRA; investigational medicinal products must be manufactured to good manufacturing practice standards and the manufacturer must have a manufacturing licence; and each trial must have a sponsor who takes responsibility for it. The regulations allow a group to share those responsibilities. The regulations place our ethics committee system—I shall refer to ethics committees again later—on a statutory basis for the first time. It is easy to overlook that in view of some of the remarks made this evening.

By clarifying the law we expect to create confidence in the public mind about the value of clinical trials and the safety of participating in them. This is essential if we are to see more and more patients in this country benefiting from clinical trials. The regulations provide a framework within which ethics committees can make independent decisions. They help to ensure that all UK trials of medicines provide reliable results and minimise risks by requiring that the principles of good clinical practice are followed. They protect participants from poor quality or badly prepared medicines by requiring the manufacture of investigational medicinal products to international standards of good manufacturing practice. They provide for inspections by the MHRA to ensure that the principles of good clinical practice and good manufacturing practice are being followed, which will improve the overall quality of UK clinical trials and help to identify misconduct. If misconduct persists or there is fraudulent conduct, the regulations provide powers of enforcement on a proper statutory basis.

Turning to the protection of incapacitated adults, I thought that the noble Earl was unnecessarily pessimistic and I certainly side more with my noble friend Lord Turnberg on his interpretation of what the regulations do to protect incapacitated adults. In my view, they protect adults incapable of giving informed consent effectively; for example, those with severe Alzheimer's disease should be able to benefit from the research but in a protected way. The regulations do not permit experiments on incapacitated people without proper consent. I object to the comparison of the regulations to the activities of Hitler. I thought that was a little excitable. The noble Baroness alluded to the arrangements in the regulations being on a par with, and not far distant from, those activities. If she would like to clarify her position, I shall be glad to hear her.

Baroness Knight of Collingtree

My Lords, I am grateful to the Minister. I said—I stress this time and again—that I was worried about the principle. The principle is that mentally handicapped people can be used for experimentation without their consent. That was the line that I was following. That was exactly what was done in Nazi Germany. That is the point I was making.

8 45 p.m.

Lord Warner

My Lords, if that is not linking the regulations to what was done in Nazi Germany, I do not know what is.

The regulations restrict clinical trials on incapacitated adults to life-threatening or debilitating conditions from which the subject suffers. That is referred to in Schedule 1, Part 5, paragraph 11. I believe that that means that the kind of chest condition that the noble Earl, Lord Howe, mentioned would not be covered in these circumstances. The decision whether to consent to, or refuse, participation in a trial will be taken by a "legal representative" who is independent of the research team and can represent that person's presumed wishes. But they do not prevent incapacitated people participating in trials with the proviso that they can benefit or suffer no harm. I believe that my noble friend Lord Turnberg made the point very well about Catch-22 situations. I do not believe that we want to prevent incapacitated people securing the benefits from participating in clinical trials.

These regulations provide a cascade system for seeking informed consent, first from a person whose relationship to the person makes them suitable to act as their legal representative; then from the doctor primarily responsible for the person's treatment and finally from a person nominated by the relevant healthcare provider. In the last situation a health service body can be expected to have a list of suitable nominated persons. In Scotland, except in cases of emergency treatment, the legal representative will be the person who is able to consent to treatment under the Adults with Incapacity (Scotland) Act 2000.

The noble Earl, Lord Howe, raised the issue of why we proceeded in advance of the Mental Incapacity Bill. We had no option but to include arrangements for incapacitated adults because the directive specifically required the implementation by member states by 1 May 2004. I know that the wording of the directive is being considered very carefully with the draft Mental Incapacity Bill.

To respond to other points, the directive makes clear that incapacitated adults can participate in trials. There must be grounds for expecting that administering the product will benefit the patient, as my noble friend Lord Carter suggested. There may be grounds for so expecting if there are good reasons for expecting that the treatment may benefit the class of patients to which he or she belongs. That enables patients to participate on that basis.

A number of noble Lords raised the subject of the Helsinki Declaration 2000. There were wide-ranging discussions during the development of the directive on the reference to the declaration. The member states agreed that the directive should not be included in the articles of the direction, but only in the recitals. That was because the declaration would prevent placebo control trials, which would be disadvantageous to patients in our view.

A number of noble Lords raised the subject of minors. The regulations also provide additional protection for a minor where that person is under 16 years of age. We expect more children to be asked to participate in clinical trials as part of an international initiative to provide medicines suitable for children that are fully licensed. We do need clear rules in this area.

A number of noble Lords raised concerns about the implications of the regulations for the work of ethics committees. I say to some noble Lords that it is simply fantasy that UK Ministers are going to control appointments to research ethics committees. We do not have that system now. We have had to put UKECA in place because under the directive there has to be a UK body to oversee the establishment, recognition and monitoring of ethics committees. There is no statutory body at the moment in that area.

Lord Clement-Jones

My Lords, does not the directive specify an independent body? On what basis does UKECA qualify as such?

Lord Warner

Well, my Lords, UKECA is there to ensure that an activity is now being conducted, as in the past, through COREC to ensure that that work takes place. But COREC is not a statutory body; it operates under a contract between it and the Department of Health and the NHS research and development department. That is a long-established arrangement and involves a non-statutory body. Therefore, to provide proper accountability, we have established UKECA to ensure that there is a process to appoint a body to undertake that task. I would say that COREC is independent and that UKECA is not involved in the appointment of ethics committees.

Perhaps I may continue with my line of argument. We had to have a body established under the regulations. As I said, COREC has existed for some time and does pretty well the same job that it has been doing for some lime. As my noble friend Lord Turnberg said, there has been a need to consider how some ethics committees were working. There has been a need to group some of those activities in a particular way.

Of course, sometimes when there is change in such areas, not everyone who is affected by the change sees things the way that COREC sees them. So concerns have been expressed in some quarters about how COREC has been operating. But it operates under contract; we monitor its work closely; and we take account of concerns that are expressed. The arrangements are in place for recognising phase 1 ethics committees. COREC is in urgent discussion with those committees to ensure that they can continue to operate under the regulations. We will be examining the workings of COREC as it undertakes the new work following from the regulations. But if there are concerns, we will of course listen carefully to them, as we have been doing so far.

Lord McColl of Dulwich

My Lords, I thank the Minister for giving way. Why cannot we have a statutory body that does not involve politicians? We have a number of such statutory bodies, such as the GMC. Why cannot we have something like that? Does the Minister not realise that people will be suspicious?

Lord Warner

My Lords, I recognise that people may be suspicious, but we need to have a UK-wide body, which is why we have brought together the health Ministers in UKECA. However, after the debate I will certainly consider what noble Lords have said. That issue has not caused concern so far and I do not believe that people think that UKECA will go round making appointments to local ethics committees. If there are concerns about perception, we will consider them, but we need a statutory body under the terms of the regulations that is UK-wide.

Investigators and trial sponsors together must record and report serious unexpected adverse reactions to trial medicines under the regulations. MHRA assessors will look for signals indicating individuals who are at risk and consider whether the trial should be modified or stopped. Safety data from trials in each of the 25 member states will be entered into a European pharmacovigilance database that will track safety in clinical trials in its population of more than 400 million people. That provides a new, important safeguard for people in the UK. That is a powerful engine for picking up adverse reactions and concerns about drugs available in the European Union.

I turn to some concerns that had been expressed here and by the statutory instruments merits committee about the good clinical practice directive. I thank the merits committee for drawing the House's attention to its concerns about that directive. In particular, it asks when it is likely to be available and what will be the likely effect of such a directive concerning the regulations.

We delayed transposition of the directive into UK law for two main reasons; namely, the European Commission's delay in finalising two Commission directives and our need to consider the impact on academic research, to which a number of noble Lords have alluded.

While the Commission has published a directive on good manufacturing practice, which is acceptable to the UK, it has not yet adopted its directive on good clinical practice. There is no indication when it will circulate a revised draft. The draft directive would have put not just the principles of good clinical practice into operation, but would also have put detailed guidance into binding legislation. That approach was unacceptable to us, and we said so—so did other countries, I am pleased to say. The delay has resulted therefore from the UK's and others' expressions of concerns.

In the absence of an agreed Commission directive, I had to decide that the most sensible approach was, as in other countries, to include in the UK regulations the principles of GCP adopted by the International Conference on Harmonisation (ICH), which were agreed as the standard for Europe in July 1996.

Currently, the pharmaceutical industry follows those ICH principles and academic researchers follow the Medical Research Council (MRC) guidelines based on the same principles. Effectively, we are changing nothing from the present arrangements in the UK.

However, the Merits Committee recognised that there is a risk that the Commission will seek to issue a final GCP directive that does not include the principles of GCP as we have stated them. We shall just have to wait and see what happens, but we will continue to make our position clear on this issue to the Commission. I have nothing further to report on smoke signals coming out of Brussels on this issue.

In February, I wrote to Members of this House and the other place to explain how I was taking the matter forward and my reasons for doing so. I have also had constructive meetings with Members of both Houses who have specific interests in clinical research, as well as with representatives from a large number of medical research charities, the Association of the British Pharmaceutical Industry and the BioIndustry Association. Each of those stakeholders has helped us in that area of activity.

We also delayed introducing the regulations to be able to respond fully to the concerns of the academic research community. As part of that process, either I or my predecessor met senior representatives of the universities, the Royal Colleges, the medical charities, the MRC, the British Nursing Association and other groups with particular interests in clinical research. The MRC prepared a helpful report which identified the major areas of concern. I shall not go into detail, but that is when we set up the joint project between the Department of Health, the MRC and other interests in order to tackle some of those issues.

I am also glad to say that along the way we have had discussions with Universities UK, which has just issued a joint statement with the Department of Health that is on the department's website. It recognises that the regulations do not change the underlying allocation of responsibilities in the partnership between universities and the NHS. That was an area about which there was some concern and misunderstanding.

The MHRA has run a consultation and communications programme since the first draft of the directive in 1997. It has hosted conferences and workshops to disseminate information; distributed the formal consultation on the draft implementing regulations to more than 3,000 organisations; and it is using its website and that of the DH/MRC project to ensure that stakeholders learn of the different developments. We have put a great deal of effort in trying to explain these changes and to take people on board and understand what the new regulations are about. Given this range of consultation, it is inevitable that we have not made everyone content. I suspect that one or two of the people who have been less satisfied may have come to the attention of some noble Lords.

In conclusion, I believe that we have made every effort to respond to the concerns of stakeholders. The approach that we have taken demonstrates the commitment of the Government to clinical research, which was demonstrated again today with the opening of the UK cell bank in Hertfordshire. We want a robust regulatory framework that will strengthen the UK's reputation for clinical trials. I am grateful for the help and support that we have had from a wide range of stakeholders. Perhaps I may be permitted to draw Members' attention to the supportive press notice put out by Cancer Research UK when the regulations were published.

Ultimately, protection of individuals in clinical trials must be our priority. I recognise the concerns in this area that were expressed by a number of noble Lords, but I consider that the regulations strike the right balance between protecting public health and enabling high-quality trials in the UK. We shall look carefully at the points made by noble Lords and if there is any further reassurance I can give after reading Hansard, I shall do so, but the Government beg to oppose the Motion.

Baroness Knight of Collingtree

My Lords, perhaps I may intervene before the noble Lord sits down. To my certain knowledge, he has never been impolite in any way and I know that he would never wish to mislead the House. Can I not ask him again to reconsider his Answer to me on 5 May? He said: Those conducting trials must obtain informed consent from all participants. Patients are provided with detailed information on the nature of the trial and have the right to withdraw at any time".—[Official Report, 5/5/04; col. 1097.] Is that not true only of some of the people who undergo those clinical trials? Is it not the case—we have seen it again and again throughout our discussion of the S.I.—that some people will undergo clinical trials who have not given permission? I am sure that the noble Lord would wish to make that clear.

Lord Warner

My Lords, I shall certainly go away and look at that Answer. As the noble Baroness says, it is never my intention—quite the reverse—to mislead Members of this House, or anybody else for that matter. My recollection of my Answer is that it interpreted the regulations in the form in which the legal representatives were operating them, whereby consent would be given where an incapacitated person is involved. However, I shall look carefully again at the Question of the noble Baroness and my Answer. If I have misled the noble Baroness, I shall certainly correct the matter.

Earl Howe

My Lords, I thank all noble Lords who have taken part in this debate, including the Minister for his reply. I recognise that the Minister has tried in his characteristic way to be helpful. Indeed, he has been illuminating in a number of important respects, but in other respects, I have to confess, his reply was disappointing. I do not intend to call a Division on my Prayer to annul, because there is a convention in the House that we do not do so and because the consequences of overturning a measure that implements an EU directive would be extremely problematic. However, if those constraints did not exist, I would seriously have considered asking the House for its opinion on the two or three serious issues that I attempted to raise. As it is, we may have to follow up some of those outstanding issues in writing.

I noted what the Minister said about UKECA and the appointment of members of ethics committees. Regulation 7, read in conjunction with Schedule 2, makes it quite clear that UKECA is the body that appoints the members of NHS ethics committees. The Minister said that that will not happen in practice. If the intention is to make all appointments locally, why vest the power of appointment in Ministers? There is absolutely no need to do that. Indeed, one can have a statutory body to supervise research ethics committees, but as my noble friend Lord McColl said, it does not have to consist of Ministers. The HFEA is a good example of such a body to add to the one given by my noble friend. It is at arm's length from Ministers, but it is nevertheless statutory.

Apart from that, I repeat that UKECA has the power not to recognise any committee of which it does not approve for any reason and to set up a committee in its place. In practical terms, that is a strong power. Why give Ministers those powers when the directive does not require it?

Turning briefly to the issue of incapacitated adults, I listened carefully to what the noble Lords, Lord Carter and Lord Turnberg, had to say, and I am grateful to both of them. The problem, from my perspective, lies with the concept of the legal representatives. In her very powerful way, my noble friend Lady Knight voiced some worries about how these regulations might, in practice, be implemented, and I hope that the Minister will take those concerns on board.

What troubles me is that the regulations embody a major change in the law. To my mind, the key point is that anyone taking a decision on behalf of an incapacitated adult to enter that adult into a clinical trial should be both independent and capable of weighing up the risks and benefits for the patient in an informed and dispassionate way. The whole concept of "legal representative", as set out in the regulations, seems to be fraught with difficulties. If you want to find the right sort of person to act as a legal representative—someone capable of ensuring that taking part in a trial is or is not in a patient's best interests—you need an independent third party. You should not look to a doctor or the staff of a hospital trust to act in that role. The responsibility should surely be in the hands of a lay person, possibly under the jurisdiction of the Court of Protection. Apart from anything else, I question whether doctors should be burdened with onerous decision-making of this kind. I say again that these are not matters that are appropriate to regulations.

I was not happy with the answer the Minister gave on the Helsinki Declaration. Indeed, I could not completely follow it, and I may wish to pursue that point with him, if he will allow me to do so.

Once again, I thank all noble Lords who have taken part in the debate. It is unsatisfactory to have to leave matters here, but for tonight, at least, we must do so.

I hope and trust that the Minister will be receptive to further approaches outside the Chamber. In the mean time, I beg leave to withdraw the Motion.

Motion, by leave, withdrawn.

House adjourned at eight minutes past nine o'clock.

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