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Paediatric Medicines

Volume 684: debated on Monday 3 July 2006

rose to ask Her Majesty’s Government, in the light of the report of the European Union Committee on Paediatric Medicines: Proposed EU Regulation (20th Report, HL Paper 101), what steps they are taking to ensure that the proposed European Union regulation on medicinal products for paediatric use will meet satisfactory ethical standards on implementation, that the incentives proposed will be effective, equitable and proportionate and that the working of the regulation will be rigorously reviewed.

The noble Baroness said: My Lords, we are here to discuss our recent report on paediatric medicine. The Commission’s proposal for regulating medicinal products for paediatric use reached Sub-Committee G in December 2004, and by the summer of 2005 it was clear that the UK Government wanted to achieve the approval of the document by the end of the UK presidency.

The main elements of the proposal were, first, a package of rewards and incentives to encourage the pharmaceutical industry to test products for use in children across the European Union and to develop and/or adapt them to paediatric use. Secondly, the European Medicines Agency would appoint an expert paediatric committee to oversee and assess paediatric investigation plans for developing medicinal products for children. Thirdly, a European clinical trials network would be set up to foster communication and collaboration on paediatric studies throughout the EU. Fourthly, authorisation procedures would be based on the Community’s clinical trials directive and details of paediatric trials would be entered on the European clinical trials database. Medicines tested for paediatric use would be sold with a special label indicating that fact.

Sub-Committee G appreciated the potential value of encouraging the clinical testing of medicines for paediatric use across the EU market. However, there were ethical and practical concerns and a decision was taken to undertake a brief inquiry. We received a wide range of evidence from interested parties including, most helpfully, from Professor Sir Cyril Chantler, the chairman of the Great Ormond Street Trust. We also saw the results of the consultation carried out by the Healthcare Products Regulatory Agency. We also had a good deal of correspondence and a very useful evidence session with the then Minister of State at the Department of Health, the right honourable Jane Kennedy MP, and her officials.

As our report shows, we were convinced that there was a real and urgent need for this regulation. More than half of all the medicines currently given to children and 90 per cent of those given to newborn babies have never been tested for that use. Furthermore, not only can the results of tests of medicines in adults not be extrapolated reliably for their use in children, but children can react very differently to drugs according to their age, among other factors. Many drugs are formulated in a way that does not suit children—in particular, very young children. Moreover, the pharmaceutical industry can find it relatively unrewarding to do the necessary but expensive research needed to produce or adapt medicines for children’s use because the market is relatively small and complicated. Meanwhile attempts by member states to encourage it to do so have not been successful.

But we concluded that the proposed package of rewards and incentives, although based on a successful scheme in the United States, was something of a leap in the dark. Under the scheme, pharmaceutical companies can expect an extension of the sole right of sale of their product if they do the research required to prove the product’s efficacy in treating children. But we could not judge with confidence whether the proposed regulation would have the desired result, whether the manufacturers would be insufficiently, reasonably or even excessively rewarded and what the effect on health service budgets would be. We also understood that some member states opposed any delay in the release of medicinal products to the generic manufacturers, who are significant players in new member states in eastern Europe.

As the December 2005 Council meeting approached, it was clear that member states were ready to approve the proposal. We were aware of the weight of professional opinion in this country that the proposal should be implemented as soon as possible. We concluded that it would not be sensible to stand in the way of such an agreement and, exceptionally, agreed to lift scrutiny in advance of publication of the report. Political agreement was secured by the UK presidency at that Council meeting.

Two issues still concerned the committee. The first was whether the guidelines for the detailed application of the regulation really would take on members’ concerns about the consent of minors, the rights of children and their parents, the proper publication of all the research projects in a transparent way and product information and labelling. The second was the legal base for the new regulation. On the matter of guidelines, we had been partially reassured by meeting the officials dealing with the details under comitology procedure. They clearly understood the committee’s concerns and assured us that these matters were being pursued by them in committee. It was also agreed by the Minister that, as a condition of lifting scrutiny, officials would brief Sub-Committee G on the development of the guidelines once the regulation was adopted and that the Government would hold the Commission to its commitments to give a full review of the working of the regulation and on access to the database. The Minister further agreed that when the operation of the regulation came under review—which might be in six or 10 years’ time—our successors would be briefed on the practical operation of the guidelines. I hope the Minister can confirm tonight that that approach still reflects the Government’s intentions.

I now turn to the matter of legal base, which is always of importance to the Select Committee. There was some concern that the Government, despite their judgment that the proposed legal base—Article 95 of the EC Treaty—was not appropriate, were preparing to give political consent to the regulation so long as they lodged a minute statement officially recording their objection. We understand that that was done and that several relevant rulings have since been given by the ECJ. Can the Minister bring us up to date on this matter?

After the report had been published, a final and unexpected coda to our deliberations was provided by the representations from the Association of the British Pharmaceutical Industry to the effect that the amount of time allowed for companies to make application for the right to conduct tests was insufficient, particularly in the years immediately following implementation of the regulation. We understand that a European Parliament common position to that effect was adopted on June 1. We also understand that the Government endorse that position, and it would be helpful if the Minister could explain the latest position.

I have tried to give an overview of our report. I am confident that other members of the sub-committee will be able to fill out many of the details. It was a piece of work to which every member brought real personal commitment and knowledge. I am delighted that this debate has attracted speakers who were not members of the committee. I cannot close without thanking the committee secretary, Gordon Baker, and his staff for all their support. As Mr Baker may have to leave us before another of these occasions occurs, I should put on record our very real appreciation of his hard work, cheerful disposition and impressive drafting skills that have been of such immense service to the committee and to all its members.

My Lords, I congratulate the noble Baroness, Lady Thomas of Walliswood, and her committee on a thorough, commendable and—dare I say?—readable report. I also congratulate her on her excellent introduction.

I find it remarkable that although we go through such an elaborate and robust system of testing drugs before they are used in adults, many drugs given to children have not been tested in children at all. Before a new drug can be given to an adult, it has to go through several phases of trials to assess its safety and efficacy in treating the disease for which it is prescribed. However, the practice in children, more often than not, has simply been to scale down the adult dose according to weight and age on the basis that a child is just a small adult and ignoring the fact that a child’s metabolism may be quite different from that of an adult. The reason for that is that very few drugs have been tested in children, so unfortunate paediatricians have to rely on their experience and prescribe off licence or not prescribe at all. Every day, paediatricians face the dilemma of whether it is more unethical to prescribe a drug that has not been tested or to deny treatment to a sick child. They do not have the comprehensive information on risks and benefits that would allow them to make an informed judgment. For example, 90 per cent of drugs used in the very emotive group of patients—the neonatal babies in intensive care—are unlicensed or off-label medicines. Therefore, the new EU regulations that are designed to encourage the testing of drugs in children are welcome. Indeed, they are essential.

The regulation follows fairly closely changes introduced in the United States that were shown to be effective in increasing the number of drugs tested. I understand that some 30,000 children in the US have been entered in clinical trials. This is an extremely sensitive area because no parent wishes to see his child used as a guinea pig, but if that idea is followed through to its logical conclusion, every child becomes a guinea pig if the drugs have not been tested properly. It can be argued that not to do proper studies in children is unethical. The answer lies in sensitive and carefully managed systems of consent and extreme care with safety issues, which are covered by ethics committees. The evidence is that these issues can be fully taken into account with due care. One study by the National Perinatal Epidemiology Unit in Oxford retrospectively questioned 100 parents of neonatal babies who had been in a controlled trial of extra-corporeal membrane oxygenation. They were asked whether they had had any qualms about their babies being involved in the trial and none said that they regretted it, even though some babies in this group of extremely ill neonates had died. So it can be done, and with carefully conducted controlled trials it is now possible to treat so many forms of childhood leukaemia so well and new ways of treating childhood asthma have become possible. So I am sure that the new EU regulation, which offers some important inducements to the pharmaceutical industry, will be well received. Although it may be a great leap of faith, we have the evidence of some success, at least, from the American experience.

Paediatricians are now well set up to undertake trials in the UK with children in a sensitive and highly ethical way. The guidelines from the Royal College of Paediatrics and Child Health, which have been helpfully appended to the report, give some confidence. They describe how it is possible to obtain consent from a child who is able to give consent, and recommends that that should be the normal course, and only if the child is unable to give consent—too young—should parental consent triumph.

It will be important for government guidelines to be constructed in such a way as to give reassurance to parents and children as well as to paediatricians, and that they ensure full transparency. They should also encourage rapid and wide dissemination of results so that drugs which are shown to be of value can be used as soon as possible, and those that are not can be avoided.

Finally, this regulation is welcomed by paediatricians and I hope that the Government will move quickly so that it can be adopted.

My Lords, I thank the noble Baroness, Lady Thomas, for her chairmanship of the committee and the way she introduced the debate this evening, Gordon Baker for his advice and guidance, and Sir Cyril Chantler for his expert opinions. The problem of funding complete trials of adult medicines used for children means that thousands are being prescribed “off-label” therapies that have not been licensed for such use.

Paediatricians and paediatric pharmacists are faced with the difficulty of prescribing and supplying medicines for children without the support of clinical trial evidence, which is available for adult medicines from the specification of product characteristics supplied by the manufacturer.

At least one unlicensed or off-label drug is received by 11 per cent of children treated at home by their GP, 67 per cent of children in hospitals across Europe,70 per cent of children in paediatric intensive care and, as we have heard from the noble Lord, Lord Turnberg, 90 per cent of babies in neonatal intensive care.

A study by the University of Liverpool found that 6 per cent of children had suffered adverse reactions to an off-label medicine, and French research has suggested that the risk of serious side effects is up to three times higher.

The use of off-label and unlicensed drugs to treat children is widespread and occurs in medical and surgical wards as well as with critically ill children. Off-label use occurs more frequently—drugs are being used in children at ages for which they have not been licensed and evaluated—at doses greater than that recommended by the manufacturers and for indications outside the terms of the product licence.

The committee’s conclusion is that there is an overwhelming and urgent need to take effective action at European level to govern clinical trials in children and the authorisation of medicinal products for paediatric use with the minimum delay.

The EU regulation recognises that paediatric licensing is essential for all categories of medicines for children. This includes new medicines yet to be authorised, existing medicines under patent protection and those where patent protection has expired. It attempts to use both obligation and incentives and rewards to achieve this.

Children are subject to many of the same diseases as adults and, as would be expected, are treated with the same drugs. The absence of paediatric testing and labelling causes significant risks for children. Inadequate dosing information exposes them to adverse reactions that could be avoided if such information were provided in product labelling. The absence of paediatric testing and labelling may also expose children to ineffective treatment through under-dosing or may deny them the benefit of therapeutic advances because physicians choose to prescribe existing, less effective medication because of insufficient paediatric information about a new medication.

The medical community has shown increased concern about the lack of information for over 20 years. My own experience within a dental environment has shown me that different drugs work in different ways at different ages. Children are defined as “someone under 19”. It seems obvious to me that the pharmaceutical companies should ideally provide information about how drugs work in several stages of childhood. A drug will have a variable effect on a neonate, a newborn infant, a one to four year-old, a four to 10 year-old, a 10 to 13 year-old and a 13 to 19 year-old, but they are all classified as “children”.

It is difficult enough for pharmaceutical companies to undertake adequate phased testing of drugs for adults. To have to evaluate a medicine for the six additional categories that I have listed would take many years and bear a disproportionate cost, perhaps even making it impracticable to consider the use of the drug for children.

The impact assessment of the proposed EU regulation estimated that to deal with the increased number of applications, the EMEA budget would have to be increased by between 67 to 150 per cent, or €130 million to €195 million, the cost to the pharmaceutical industry being about €4 million per product.

It is proposed that medicines and products covered by existing patents, or granted market exclusivity by supplementary protection certificates under existing EMEA authorisation procedures, shall be entitled to a six-month extension of the market exclusivity and an additional two years’ market exclusivity to which orphan medicinal products are entitled under existing EMEA authorisation procedures, making 12 years in all.

Ten years of data protection for new paediatric studies would also be granted to off-patent medicinal products developed specifically for use in children. Products developed under this provision would be granted paediatric use marketing authorisation. Historically, this has been successful in the USA, which introduced the “paediatric rule” and the “paediatric exclusivity” provisions, adopted in 1998 and 1997 respectively. This legislation provides six months’ exclusivity in return for conducting paediatric studies and has been highly effective in generating paediatric studies on many drugs and in providing useful new information in product labelling.

Some categories of drugs and some age groups remain inadequately studied despite these new incentives, but suggestions have been made for modifications to the paediatric exclusivity provision that may address these gaps.

For some products and for some age groups the incentives provided have not produced proposals to conduct paediatric studies. The incentive is not adequate for old antibiotics and other drugs lacking market exclusivity or patent protection because these products are not eligible for any exclusivity under the current paediatric exclusivity provision.

While the incentive provided by paediatric exclusivity provision has been adequate for many products, it has naturally tended to produce paediatric studies on those products where the exclusivity has the greatest value, and not on those which no longer have patent protection or exclusivity, or small markets.

My time is up. Manufacturers should be encouraged with further incentives to study those drugs that provide the greatest health benefit to children, including those that are not eligible for incentives in the current situation. I hope our report will influence further consideration of this situation.

My Lords, as a member of the sub-committee, I add my tributes to the noble Baroness, Lady Thomas, and Gordon Baker. I am always totally amazed how even my modest comments can be turned into erudite recommendations. I have particular declared interests in children and health and I must say that the work on the report gave me equal proportions of satisfaction and dismay. I had satisfaction that, at last, paediatric medicines are being addressed, but dismay that, having reached the 21st century, there is still so far to go, although I am encouraged by the contribution of the noble Lord, Lord Turnberg, who seems to think that at least something is moving forward.

We have heard several times that children are not small adults. We heard from the excellent evidence of Sir Cyril Chantler that there are two major problems with the use of unlicensed medicines: how children's metabolism deals with the drug, and the effect on the child. The European Commission stated that 50 per cent to 90 per cent of all medicinal products used in the paediatric population have never been studied or authorised for use. Consequently, among the long list of problems outlined by Sir Cyril and well known to those dealing with children is the control of pain. Were the situations where children suffer to happen to adults, they would simply not be accepted. There would be a major campaign. We hope that our report will help the Government to take forward this important issue of paediatric medicine.

As with all pharmaceuticals, the need for rewards and incentives is a major driver. The noble Baroness, Lady Thomas, and the noble Lord, Lord Colwyn, have both outlined the issues; the noble Lord, Lord Colwyn, did so in detail. It is therefore enough for me to observe that it appears that, without the intervention of this directive, children's medicines will be developed by market forces rather than any altruism or proper concern for our most precious asset: our children. That is why the directive is vital.

There is a similar issue with research where, under the directive, the European Medicines Agency will oversee and co-ordinate the tasks envisaged by the proposed directive, but the Royal College of General Practitioners questioned whether it would be best placed to provide the proposed scientific advice, which would be a significant undertaking. Unfortunately, the sub-committee was unable to judge from the evidence that we received whether the proposed funding framework would be adequate. What progress has been made in that area and on the need for a separate Community-funded programme of research?

The sub-committee was much exercised about the ethical considerations of consent. Although agreeing that the health and welfare of children must be the overriding priority for conducting paediatric trials, in her evidence the Minister drew a distinction between what she described as a properly informed decision and one that might be no more than what she called a whim.

We were troubled by that issue. I add my concern that children be consulted appropriately by those who understand how to communicate with them, not by those who have a vested interest in getting a particular answer. Anything that the Government can do to progress that would be most welcome.

In the short time available, I also mention labelling—a topic on which I spent much time as a member of the board of the Food Standards Agency. It is equally important that we get that right for children's medicine. We hope that the Government will be active at EU level and in the UK to ensure that products are labelled in a way that indicates their suitability for children, taking into account their size and development, and in a way that parents can understand and is distinctive.

If we get all that on track, it will be of little use if the Government do not get right the services for specialist paediatric groups—those services in which the medicines will be used. Stepping outside the brief of the sub-committee, I take this opportunity to urge the Government to speed up their major review of cardiac surgery for specialist care. I know that the Government have started that but, although Scotland, Wales and Ireland have already moved to a high level of care for all, rather than a postcode lottery, we in England still have no clear plan for central funding and standards.

I realise that the Minister may not be able to answer that point this evening; if he is not, could he write to me to explain how the proposed working party is progressing? Paediatric medicines will then have a proper context for progress.

My Lords, may I speak for the children? I am the father of three and the grandfather of one. My three children have now grown up, but I have a grandson of just four years old and I wonder whether we are taking their interests as fully into account as we should. Of course, we all wish them well; of course we all want them treated, especially when they are very ill. That is usually when untried and untested medicines are offered.

I am very troubled by the arrangements for testing medicines on small children—and tested they must be, as my noble friend Lord Colwyn made clear. Medicines do not react in the same way for small children as they do for adults. It is no longer possible simply to prescribe a dose for an adult and then scale it down appropriately for a young person. That technique, which may have been widespread in the past, is now widely accepted as unacceptable.

There are real difficulties in testing drugs on small children. Despite what some of the evidence before the sub-committee suggested, I do not believe that it is really possible to obtain informed consent from a very young person. We were told that, in some circumstances, it was possible to obtain that consent from, say, only a 10 year-old child. I have grave doubts about that proposition. I know that the noble Baroness, Lady Howarth, thinks rather differently—she is, of course, an expert in these matters—but if I cast my own thoughts back to all those years ago, if I can, when I was that young, and more relevantly to my own children when they were that age, I do not think it is possible to obtain informed consent from a child of that age, especially if they happen to be ill, and even more so if they are very ill and we are offering them a medicine that is not properly trialled.

It is recognised that nowadays a large number of small children, especially very small children, are given medicines off-label—in other words, they are not adequately tested. Nor is it easy to obtain the consent of the parent to such things when, for example, the child is very ill. I ask your Lordships to consider how they would react if, their child desperately ill and they at the extremities of distress, they were asked to give consent to the use of an untried medicine. They would hasten to agree, would they not? I dare say I would have done so had I been in that circumstance. We have a very real difficulty. I am glad that the European Commission is addressing this problem, and I hope that the medical profession will take account of the serious difficulties that confront us in this matter.

My Lords, I, too, thank my noble friend Lady Thomas for chairing the inquiry, and our remarkable Clerk, Gordon Baker, for his superb drafting of the report.

It is undoubtedly worth saying how wide the support has been generally for the regulation. Broadly speaking, the medical profession and others have really wanted it, as the noble Lord, Lord Turnberg, has made clear. As we have also heard, however, several issues concerned us. My noble friend Lady Thomas alluded to the fact that drugs are not tested on children, as did the noble Lord, Lord Colwyn, who commented that the pharmaceutical industry does not find it worthwhile to do some of the research. The noble Lords, Lord Turnberg and Lord Colwyn, both spoke about the ethics of prescribing and providing drugs for children that were not tested on children. There were also concerns about further incentives for the pharmaceutical companies and general issues around testing on children, and we have just heard the comments of the noble Lord, Lord Trefgarne, who is very worried about children being able to give consent. Perhaps the issue of children’s consent is the one that troubled us the most, as the noble Baroness, Lady Howarth, has said. It certainly troubled me the most.

The clinical trials directive requires that a person with parental responsibility, or a legal representative, must give informed consent to any trial involving a minor, whereas the explicit wish of a minor to refuse to participate or to be withdrawn from clinical trials “must be considered”. A clinical trial has to be designed to minimise pain and discomfort, fear and other foreseeable risks in relation to the disease and the developmental stage of the child concerned. We drew the attention of Professor Chantler, the chairman of Great Ormond Street Hospital, who gave evidence to us, to that statement. He was very firm about this. He argued, contrary to the view of the noble Lord, Lord Trefgarne, that,

“one would be surprised how it is possible to find out what is in the child’s interest from the child’s point of view in very young children: you just have to find more imaginative ways of communicating with them. The notion that you would do something to a child that did not involve the child’s consent is not acceptable”.

He continued—I do believe it is worth quoting:

“Obviously there are occasions, I know, where doctors and nurses have to do things and the child does not want them done and the child may cry, but you pay a terrible price for that. I constantly as a paediatrician was upset by people saying to children, ‘This isn’t going to hurt.’ Of course it is going to hurt. Once you say it is not going to hurt and then stick a needle in them and they cry, two things have happened: one is the child has suffered pain which you might have been able to find a way of avoiding—and we are better at that now—but, perhaps more importantly, you have lost that child’s trust forever. It is a very serious matter to do something to a child that does not have the child’s consent. Participation in a trial, I think, would require the child’s consent as well as the family’s”.

Professor Chantler thinks that the guidance will need to be strong enough. We do not yet have that guidance. We await the guidelines and, like my noble friend Lady Thomas, we very much hope that the Government will watch this closely and ensure that the guidelines make it explicit that the child’s wishes have to be more than taken into account; they have to be recognised. But it is a complicated issue. We still live in a society where children’s views are often insufficiently taken into account. The first work—20 years ago—by Richard Nicholson showed, in research ethics committees looking at research on children, that consent was less likely to be given to research on children if a nurse was present, regardless of whether she spoke. It suggested that there were various people around who were quite prepared to carry on doing things that some of us now might not find acceptable. Children have views, so we have to clarify the extent to which the child’s view is to be taken into account.

When the Minister came to speak to us, she was not worried that the child’s views must be considered, but wanted to draw a distinction between a properly informed decision by a child and one that might be no more than a “whim” on the day concerned. The noble Baroness, Lady Howarth, has already drawn our attention to that. There are two problems with it. The first is that adults are allowed to be subject to whims or fancies in consent to research; and so one has to ask why children should not be. Secondly, there is a real problem, on which Priscilla Alderson has been the great expert, about consent from children. What if the child has just had enough? Children who are very sick sometimes express the view that they have just had enough and want no more done.

We were much reassured by Sir Cyril Chantler and by the Minister’s assurances to us. However, until we see the regulations and guidance, and until we know that the database on research in children will be freely available, we cannot rest completely. Children’s interests must be taken into account. I hope that the Minister will be able to give us the Government’s reassurance on this matter.

My Lords, I must first apologise for being a few minutes late. My excuse is that I have just flown in from Montreal and am slightly disoriented. However, I thank the noble Baroness, Lady Thomas of Walliswood, for chairing this splendid committee and for coming to such sensible conclusions. It is good to acknowledge too the work of Sir Cyril Chantler, with whom I had the great privilege of working closely for many years at Guy’s Hospital. He is a most remarkable person.

I remember a couple coming to Sir Cyril with their child who was in renal failure. He not only carefully explained the situation to the parents but involved the child in the discussions. Afterwards, the parents were slightly embarrassed and said, “Doctor, we hope you don’t mind us asking the question, but before you begin treatment, could we take the child to Lourdes?”. Sir Cyril characteristically said, “No; that is absolutely fine. You see, we’re going to need all the help we can get”. The parents noticed that in the eyes of this great man there was a tear, and it was very helpful to them. Incidentally, the child went to Lourdes and no sooner had they arrived than they received a telegram saying “Come back. We have found a kidney”. A kidney transplant was carried out and the child was successfully treated. So it was a great end to that story.

We also dealt with the subject of whether a child should be informed of what is coming. One should never say, “This isn’t going to hurt”. Sir Cyril again comes to mind. My youngest child has a severe heart problem and hated the way in which doctors would say “This isn’t going to hurt you at all”, after which they would stick in a needle which would be extremely painful. So we hit on the bright idea of getting Sir Cyril always to take the blood from my daughter—which for years, as noble Lords can imagine, he did perfectly.

One conflict which has been discussed is whether children can really give consent. There are of course two sides to it. As my noble friend Lord Trefgarne pointed out, it is hard to imagine how the parent of a child who is desperately ill or perhaps dying feels when a doctor asks, “Do you mind if we try out this new drug on your child?”. But in this day and age we simply have to involve both the parents and the child in the decision-making process. So the more expert we get at communicating with the young, the easier this process becomes.

Perhaps I may emphasise what was said by the noble Lord, Lord Turnberg. Drugs have different effects on children. Surprisingly, adults are sometimes more sensitive to a drug than are children. A larger dose of belladonna is required for children.

Once again I apologise for being late and I want to express my thanks to the noble Baroness, Lady Thomas of Walliswood, for this splendid report.

My Lords, before the Minister replies, perhaps I may say that it would have been extremely useful to have been told that the noble Baroness, Lady Finlay, was not going to speak in the debate. When I rang the Whips’ Office at 10 o’clock this morning while giving an anaesthetic in Harley Street, I was told that I had nine minutes in which to speak. When I spoke to my own Whips’ Office this afternoon I was told that I had seven minutes, and when I came into the debate this evening I found that I had five minutes. But now the Minister has all of 20 minutes in which to reply, while I have had to cut major sections of my speech. It is very unsatisfactory.

My Lords, perhaps I may respond to the noble Lord’s point. As is normal in such circumstances, about two speakers were scratched before the noble Baroness herself was due to speak and the usual channels were informed. I am terribly sorry. In future I shall ensure that other noble Lords are informed, but we were not told that the noble Baroness had been scratched until after the noble Lord had himself spoken in the debate.

My Lords, perhaps I may speak very briefly. I was stuck on the M4 because of a four-car accident, but I tried to get here as fast as I could. I ran up the stairs to join the debate, but realised that it would have been impolite to speak.

Perhaps I may take a moment to address the differences in neonates at term and the even greater differences in preterm neonates. I hope that the Minister will tell us how he intends to inform the public that the culture of research needs to change so that people understand that there are good outcomes from good research and that everyone benefits.

My Lords, noble Lords will be pleased to know that I am not going to speak for 20 minutes; even I recognise that you can have too much of a good thing. I am pleased to have the opportunity to set out the Government’s views on the new European regulation on medicinal products for paediatric use which comes into force later this year. I am grateful, as are other noble Lords, to the noble Baroness, Lady Thomas of Walliswood, for her sub-committee’s report and the opportunity she has provided for noble Lords to discuss this important issue. I certainly have a personal interest in the subject; it is one I have had for some time.

I should like to make it clear at the outset that the Government have been supportive of legislation in this area for a number of years and welcome the efforts made by the Commission to progress this regulation. It was a key priority during the UK presidency last year and I am pleased that political agreement was achieved during our presidency. The Government have been concerned for many years about the lack of medicines authorised and formulated specifically for paediatric use for the reasons mentioned by a number of noble Lords this evening. Because of our concerns, we took steps at the national level within the existing regulatory framework: first, to produce in the short to medium term an increase in appropriately labelled and formulated medicines for children; and, secondly, to increase information on the paediatric use of medicines for prescribers, carers and patients through the children’s British National Formulary. I should add that this is probably one of the most useful things I have done as a Minister. There may not have been many of them, but the BNF was one of them. Thirdly, we have ensured that appropriate standards are met for the conduct of clinical trials of medicines involving children.

However, the Government have always considered that a pan-European legislative solution was required to address the current situation. The regulation responds positively to concerns expressed by all member states, including the UK. We were not alone in wanting to address this issue. We recognised the need for a regulatory approach that includes both incentives and requirements to ensure that new medicines along with medicines already on the market meet the specific needs of the paediatric population while also ensuring that children are not subjectedto unnecessary clinical trials or delaying the authorisation of medicines for adults. That second issue has been around for some time and has had to be addressed and dealt with. I am very pleased to report that a Second Reading agreement was reached on the regulation in the European Parliament on 1 June 2006. This means that the regulation will come into force later this year.

One important outcome of the regulation—indeed, one of its objectives—will be an increase in the number of clinical trials in children. Some people, understandably, have expressed concerns about involving children in clinical trials. But let us be clear: if a medicine is to be used in children, the only way of determining whether it will be beneficial and safe is by conducting clinical trials in children, as my noble friend Lord Turnberg so clearly expounded. These trials in children will make an important contribution to public health by providing the scientific base for authorising new essential medicines, particularly for inadequately treated diseases. Equally important, the trials will provide information on when not to use medicines in children, and why.

In recognition of the importance of clinical trials in children, the Government launched the Medicines for Children Research Network last year to provide a world-class health service infrastructure to support high-quality trials of medicines for children. We want to do this job well and that is why we have involved the experts in this network.

A number of noble Lords have raised issues around the ethical considerations. Involving children in clinical trials clearly raises a number of ethical issues. I should like to emphasise that the Government attach the greatest importance to ethical standards, an area which I know is of particular interest to the House not only in this debate but more generally. The rules governing the conduct of clinical trials are both detailed and specific. The paediatric regulation contains a range of measures specifically to safeguard those participating in paediatric clinical trials. These are over and above the high standards introduced by the clinical trials directive to protect minors. The directive requires that ethical and procedural criteria specific to children are in place before entering them into a trial.

The Government believe that the protection of those participating in clinical trials must be the overriding priority and believe that the safeguards laid down in the clinical trials directive and the measures in the new regulation provide a secure framework to ensure that the health, welfare and rights of children participating in clinical trials are protected. I reassure the noble Lord, Lord Trefgarne, that the clinical trial on a minor may be undertaken only if—and I give one example—the informed consent of the parents or legal representative has been obtained. Consent must represent the minor’s presumed will and may be revoked at any time without detriment to the minor. The explicit wish of a minor who is capable of forming an opinion and assessing this information to refuse participation or to be withdrawn from the clinical trial at any time is considered by the investigator. That is already provided for. I rather share the views quoted bythe noble Baroness, Lady Neuberger, of Cyril Chantler—to whom a number of noble Lords have paid tribute today and who has probably seen more children undergoing great suffering than any of us. I rather share his view that with appropriate creativity and patience we can secure informed consent from many more children than has often been the case. Certainly the clinical trials directive does nothing—quite the opposite—to ensure that we work hard at securing children’s consent in these often very difficult sets of circumstances.

Perhaps I may reassure the House that, in addition, the European Commission, in consultation with member states, is preparing a guideline on the ethics of conducting clinical trials in children. The commission intends to publish the draft guidance in the autumn for consultation before it is finalised and in place when the new regulation on medicines for paediatric use comes into force.

This guideline, along with others that are being developed, will be important in setting out how the regulation will work in practice. I will mention the other guidelines later, but I can reassure the House unequivocally that the Government would not have supported a proposal with implications for conducting clinical trials in children if we were not absolutely convinced from all the expert advice we have received that this was the right thing to do.

A number of noble Lords mentioned incentives. The proposed incentives under the regulation stimulated much debate in Europe, but most people accept that incentives are necessary. The Government carefully considered the implications of the proposed incentives and agree that it is important to provide fair incentives to the research-based pharmaceutical industry to stimulate the necessary research. It was clear from the range in the commission’s impact assessment of the regulation and the Government’s partial regulatory impact assessment that it was not possible accurately to estimate the impact on the NHS at the present time. Because of this uncertainty, the Government felt it was important to make the case for a robust review of the economic and health benefits of the regulation, and this was agreed.

The European Commission will provide a general report within six years of the regulation entering into force. That will include a detailed inventory of all medicinal products authorised for paediatric use under the regulation and, if sufficient data have accrued, the commission will provide a report on the economic impact of the rewards and incentives along with an analysis of the estimated consequences for public health. If the data are insufficient to allow a robust economic and public health impact assessment at this stage there is the possibility of conducting a further review within 10 years of the regulation entering into force.

I can assure the House that the Department of Health will monitor the impact of the incentives. As set out in our response to the scrutiny committee’s report, we will also update the regulatory impact assessment once the data are available, and make this information available to the committee. I can certainly give the noble Baroness, Lady Thomas, the reassurance that she was seeking. I can also reassure her that we now accept that Article 95 of the treaty is an appropriate legal basis for the regulation.

As I mentioned earlier, specific guidance will be developed to underpin the regulation in a number of areas including, for example, the rules of procedure for the paediatric committee and guidance on the required format and content of an application for agreement of a paediatric investigation plan. The European Commission will have responsibility for developing the guidelines in consultation with the member states. Let me reassure my noble friend Lord Turnberg that the Government will ensure that all stakeholders, including healthcare professionals, parents, patient organisations and the pharmaceutical industry are able to provide input at the appropriate stages.

The UK led the development of European guidance on the conduct of pharmacovigilance in children. This was recently finalised following a period of public consultation and underpins the strengthened requirements for paediatric pharmacovigilance which are set out in the regulation and will reinforce the use of medicines in children.

The House will be aware of the extensive consultation on the regulation that was conducted by the European Commission, the Department of Health and the MHRA—the Medicines and Healthcare products Regulatory Agency. Consultation responses, including those from paediatricians and other healthcare professionals, indicated strong support for the new legislative framework. The Select Committee’s own inquiry and report on the regulation welcomed the proposed legislative framework. I cannot answer the question of the noble Baroness, Lady Howarth, on the cardiac working party, but I will certainly write to her.

In conclusion, I believe the proposal strikes the right balance between protecting public health through the development of properly tested and formulated medicines for children and assuring high-quality paediatric clinical trials in the UK. The proposal is long awaited, and we are pleased that the new regulation will become a reality in the very near future.

My Lords, before the noble Lord finally sits down, I should like to add my appreciation of the work of the Clerk to the Committee, Mr Gordon Baker, which I omitted to do during my earlier remarks.

My Lords, I beg to move that the House do now adjourn during pleasure until 8.55 pm.

Moved accordingly, and, on Question, Motion agreed to.

[The Sitting was suspended from 8.50 to 8.55 pm.]