Medicines (Children)

HC Deb 19 April 1999 vol 329 cc669-78

Motion made, and Question proposed, That this House do now adjourn.—[Mr. Robert Ainsworth.]

10.8 pm

Mr. Andrew Love (Edmonton)

rose—[Interruption.]

Madam Speaker

Order. Those hon. Members who are leaving will please do so or resume their seats. [Interruption.] How churlish! An hon. Gentleman has the Floor.

Mr. Love

I am grateful for the opportunity to raise the subject of licensing medicines for children, as I believe that it is a very important, if somewhat neglected, issue. I hope in a small way to put that right tonight. I know that the matter is of interest to hon. Members on both sides of the House, as more than 100 colleagues from all parties have shown their support for early-day motion 365, which I tabled a few weeks ago. That motion calls for the Government to take steps to strengthen the regulatory system in the UK, and establish a satisfactory system for testing and licensing treatments for use on children. I repeat that call tonight.

I first looked into this issue as a result of a tragic case in my constituency. Through it, I made contact with the parents of other children who had died following medical treatment and also with Professor Choonara, of Derbyshire children's hospital, who has carried out much of the research into this matter. From his research, I learned, to my amazement, that 25 per cent. of all drugs given to children in hospitals are not licensed for that purpose and that 36 per cent. of all children in hospitals receive drugs in that way.

In addition, a more recent study showed that the figure for newborn babes admitted as patients is even higher: 65 per cent. of all treatments are either unlicensed for that purpose or prescribed off-label, and 90 per cent. of them receive such treatments. I remind the House that those drugs are either totally unlicensed for human administration or licensed solely for use on adults, yet they are still regularly given to children.

My amazement and concern were clearly shared by the Select Committee on Health, whose report "The Specific Health Needs of Children and Young People" was published in February 1997. The Committee's report states: the current system in regard to the testing and licensing of medicines for use by children is unacceptable. The Department of Health is quoted in the report, responding to those concerns by acknowledging that that "unsatisfactory" situation exists. The report goes on to say: The Department and the Medicines Control Agency consider that children should have timely access to safe and effective medicines which have accurate, scientifically justified prescribing information".

I should make it clear that unlicensed and off-label prescribing can bring benefits to some patients, and I am not seeking to deprive children of beneficial treatments, but I believe that those treatments should be administered after a rigorous testing and licensing process. Off-label prescribing may also lead to under-dosing of worthwhile treatments, thus depriving children of the full benefits of a drug.

In my attempt to raise this issue, I have received support from general practitioners and paediatricians, and I express my gratitude to them for that. The present system—or, rather, the lack of one—simply leaves doctors to sink or swim with their own clinical knowledge and judgment. Although that may be sufficient for many doctors to prescribe the correct drug and the appropriate dosage, for others it may not be. I have in mind particularly the GP who is not a specialist in child health, but is expected to take responsibility for prescribing a drug of which he has little knowledge. The point is that, without a proper licensing system, we have no way of independently and scientifically assessing those treatments.

I emphasise that I am simply calling for children to be treated in the same way as adults —as individuals entitled to the best medical treatment available. A doctor's clinical judgment must be based on the information available. A substantial part of that information is provided by drugs manufacturers, after full and rigorous clinical trials on a given treatment. If that is what we expect and receive as adults, why should we not expect and provide the same for children?

This is an issue of consumers' rights and, as such, it is of great concern to the Consumers Association, which has campaigned hard for some time. I believe that paediatricians and GPs should be required to inform patients and, in cases involving children, parents when an unlicensed or off-label drug is given. I look forward to hearing my hon. Friend the Minister's views.

A further consequence of unlicensed and off-label prescribing is the apparent inability to monitor adverse reactions to particular dosages of a drug. The Medicines Control Agency is able to track any adverse reactions as a licensed drug is used and, if necessary, amend the instructions on how it should be administered. When a product is used outside the licence, such monitoring and feedback simply cannot happen, as there is no on-going mechanism within which it can take place.

I would argue, therefore, that children are disfranchised in that process. They have to rely much more heavily than adults on unlicensed and off-label treatments and the treatments that they are given are not subject to the monitoring and on-going review of licensed medicines. Nevertheless, adverse reactions to off-label and unlicensed treatments exist, and I expect that in some cases they are reported to the Medicines Control Agency and the Committee on Safety of Medicines. When I asked the Minister about that, his response was: there is no centrally held record of suspected adverse reactions to medicines. Perhaps he could tell the House tonight what happens to any information that is received. Is it filed, or simply disposed of because no mechanism exists to process it?

The Government are funding a pilot research project into adverse medical reactions in children in the Trent region. The project has been running for six months and funding of £38,000 has already been committed. However, I understand that Trent region is happy to back the research for a further three years, conditional on the Medicines Control Agency funding its share. So far, the agency appears to be unwilling to commit itself. Already, however, the project has shown signs of success, with a 100 per cent. increase in the reporting of adverse reactions in the first six months.

It is also significant that, in June, the Royal College of Paediatrics and Child Health will produce the first national formulary to include data on drugs prescribed for children. It will be funded by the Nuffield Foundation as a one-off edition and will be sold commercially to raise funds for future editions. However, it is hoped that the Department of Health will fund future editions, to be published and updated regularly. To date, the Department has not said that it wants to take on that role. Will the Minister comment?

The use of unlicensed and off-label treatments is not a new problem; it has been recognised and addressed by the United States and the European Union. From April this year, pharmaceutical companies in the United States will be compelled to provide information about the effects of their drugs on children if such a use is likely. Significantly, for such information to be required, the use on children needs only to be "likely". In written questions, I asked the Secretary of State whether the Government would look at the US system. I hope that the Minister will elaborate tonight on that basis.

In 1995, the EU established guidance on the clinical investigation of medicinal products in children, which came into effect in September 1997. I understand that the Government played a major role in developing that guidance, so I presume that the Minister is familiar and broadly sympathetic with its content. As it is guidance and not a directive, it does not compel member states or drugs companies to do anything. Nevertheless, I draw the House's attention to its opening lines: Children should not be given medicines which have not been adequately evaluated for use in that age group. There is a responsibility, shared by applicants and the competent authorities, to ensure that children have timely access to safe and effective medicines which have accurate, scientifically justified, prescribing information. What steps are the Government taking to monitor the application of the guidance to establish which products are licensed in accordance with the guidance and from which drugs companies?

I understand that research will soon be published in The British Journal of Clinical Pharmacology, which looks at practice in licensing at the time the EU guidance was formulated. That research highlights the need for pharmaceutical companies and enforcement agencies to undergo a change in attitude to effect the necessary change in the licensing process.

As compliance with the EU guidance is entirely voluntary, drugs companies have little incentive to apply to license their products in that way. However, a joint British Paediatric Association and Association of the British Pharmaceutical Industry working party was set up and recommendations were made to address the unsatisfactory situation. My concern is that, although those recommendations are worthy in themselves, they are worth little without action to implement them. Experience of the commercial sector suggests that drugs companies ultimately follow the profit motive. Indeed, I understand that they are requesting extended intellectual property rights to encourage the industry to follow the guidance.

Significantly, the US Government have tried such a carrot-and-stick approach—compelling drugs companies to provide information about the effects of their drugs on children, but also offering them the financial incentive of a six-month extension to their patents in exchange for comprehensive paediatric data. Have the Government evaluated the benefits of such a system in the UK?

There is a need for the Government to step in to regulate a situation where the other parties are unwilling or unable to act. The use of unlicensed and off-label treatments in children merits such intervention. I would add also that both the pharmaceutical industry and the medical profession could have addressed the issue some years ago, so any accumulated costs are due to years of inaction.

The reasons for a specific licensing system for children are clear. Physiologically, children and babies differ considerably from adults. I refer again to the EU guidance, which states: The effects of many medicinal products on children may differ considerably from those observed in adults, even when dosage has been adapted to body weight or body surface area.

Drugs affect children differently in terms of side effects and the way in which a child's body absorbs and processes a drug. That must be recognised in the licensing system. Evaluating the suitability of any given drug for children is, therefore, a far more sophisticated process than, for example, simply taking the adult dosage of a given drug and halving it.

The only sensible way forward is to follow the recommendations in the European guidance and to establish clinical trials for drugs that are likely to be used on children. Of course, the participation of any child in such trials would have to be with the full consent of the parents concerned and, where appropriate, with the informed consent of the child. Such a process would have to be carefully monitored at every stage, and any adverse reactions speedily evaluated and treated.

I recognise that the notion of testing on children can, in itself, be seen as alarming because the last thing that anyone would want is to put a child through any kind of hazardous process. However, I believe that this is infinitely better than what we have at present—a hit-and-miss system in which all children are potential guinea pigs without their knowledge or the knowledge of their parents. There is a responsibility on the Government to recognise the need for the education of parents and the wider public about the very good reasons for a proper testing process.

There is an irony here, in that the Medicines Act 1967—which introduced the licensing system—came as a result of the thalidomide disaster, a drug which directly affected children, yet the present system effectively excludes children from the licensing process. That cannot continue to be justified.

Finally, I draw the House's attention to the main reason for this debate—the human cost of not taking any action. Lexie McConnell was nine years old when she died in November 1992. Her immune system collapsed following a steroid overdose after she had been given doses licensed only for use on adults. Lexie was being treated by a specialist at the John Radcliffe teaching hospital in Oxford for a relatively minor eye injury, yet her treatment still went tragically wrong.

If a proper licensing system had been established, Lexie might have received the correct dosage, or she might have been prescribed a different drug altogether. Unfortunately, Lexie's case is not an isolated one. Action must be taken to prevent this kind of failure from occurring in the future. I pay tribute to Lexie's parents, Art and Victoria McConnell—who are present in the House tonight—and to all the other bereaved parents for the dignified way in which they have campaigned on the issue. On their behalf, I strongly urge the Minister to strengthen the regulatory system for children.

10.24 pm

The Parliamentary Under-Secretary of State for Health (Mr. John Hutton)

I congratulate my hon. Friend the Member for Edmonton (Mr. Love) on his success in raising this matter for the House to consider tonight. The subject has been generating increasing interest and concern from both health professionals and the public. I welcome the opportunity afforded by this debate to consider the issue of medicines for children. I thank my hon. Friend for his thoughtful, considered and well-informed remarks.

I shall try to respond to all the points that my hon. Friend has raised, but first let me say that as a father myself, I sympathise deeply with the parents of all the children to whom he referred. No one expects to outlive his or her children, and there can be few more tragic events than the death, for whatever reason, of a dearly loved son or daughter. The pain and anguish in such circumstances I know, from my personal experience, to be immense, and I think that the thoughts of the House will always go out to those in that terrible position.

The treatment of children generally is an emotive issue, as well as an important area of service provision. The Government would be extremely concerned if any section of the public were exposed to treatment that was less well regulated or of poorer quality than that available to others, or denied treatment that should be available.

The role of the Government in ensuring that safe and effective medicines are available for the treatment of those of all ages is primarily regulatory, but the Government also have a role in providing industry and health professionals with advice and guidance. I shall say something shortly about the areas in which the Government can and do encourage those with the initiative to address this important issue, but the initiative for undertaking appropriate development work and conducting appropriate clinical trials rests with the pharmaceutical industry, which, once it is satisfied that a product should be marketed, submits its application to the regulatory authority for the appropriate licence.

It is worth pausing for a moment to note the historical perspective. Until quite recently —in the last 10 or so years—it was considered unethical to conduct the very clinical trials that would have helped to demonstrate the safety and efficacy of medicines for children, and ethical considerations remain an important factor.

For manufacturers seeking to license their products for use in the United Kingdom, the licensing authority currently consists of the Department of Health and the Ministry of Agriculture, Fisheries and Food. Responsibility for undertaking the appropriate assessment of new products and the monitoring of products already on the market resides with the Medicines Control Agency, which acts on their behalf. The agency is responsible for ensuring that medicines on the market in the United Kingdom are safe, of suitable quality and effective for the purpose for which they have been licensed.

The Government recently established the National Institute for Clinical Excellence, which is designed to ensure that every national health service patient in the country is given the most effective treatment available. It will identify best practice and help to spread it quickly, and it will advise doctors and nurses on which treatments work best for patients and the NHS and which do not.

My hon. Friend has expressed concern about the extent to which children may be being treated with medicines not specifically licensed for such use. It would, of course, be a matter of great concern if that led to children being given medicines in circumstances in which their use proves to be hazardous. The safety of all medicinal products licensed for use in the United Kingdom is continuously monitored by the Medicines Control Agency, via a voluntary reporting scheme involving doctors and pharmacists.

Mr. Paul Flynn (Newport, West)

In the last Parliament, I was informed by my hon. Friend's predecessor that the number of people dying from the effects of one widely available drug, paracetamol, had fallen from 57 to 48. Other sources—coroners' courts—showed that the actual number of deaths during the period concerned had been not 48 but 586. Is it not true that now, as then, there is huge under-reporting of deaths that have occurred as a result of the use of medicinal drugs, and that the present system does not depend on the reporting of side-effects and tragedies by doctors? It does not work: it vastly under-reports the number of tragedies.

Mr. Hutton

I am not aware of the parliamentary exchanges that my hon. Friend had with my predecessor in another Administration. I also remind him that we are discussing medicines for children. I am not sure how many of the deaths that he mentioned were children's deaths.

Mr. Flynn

rose—

Mr. Hutton

I hope that my hon. Friend will forgive me if I make some progress, and deal with the points made by my hon. Friend the Member for Edmonton. However, I acknowledge the points that he made, and the seriousness with which he made them.

The yellow card adverse drug reaction scheme, to which my hon. Friend the Member for Edmonton referred, asks clinicians—both GPs and hospital doctors—as well as pharmacists and others to report any suspected adverse reactions to the MCA. Companies are obliged to submit individual reports of adverse reactions and periodic safety update reports containing information relating to suspected adverse drug reactions, drug usage and safety studies, as available, for MCA assessment at regular intervals throughout a product's lifespan.

The data are used to inform both the agency and the manufacturer of the safety profile of the product once it is in use in a wider section of the population than is possible under clinical trial conditions before licensing. Those reports are reviewed by experienced professional staff at the MCA before renewing product licences, a process that occurs every five years in the life of a pharmaceutical product.

My hon. Friend the Member for Edmonton specifically referred to adverse reaction reports for unlicensed medicines and off-label use. I should like to reassure him that the well-established systems for monitoring the safety of marketed medicines cover all patient groups, including children and off-label usage. Clinicians have been reminded of that fact in a bulletin from the MCA, which went to doctors, dentists, pharmacists and coroners; it was issued in September 1997. Nevertheless, a more targeted approach to surveillance of medicines that are used by children is without question fully warranted.

To that end, in addition to the regular reporting arrangements, we have supported an initiative in Trent region—my hon. Friend the Member for Edmonton referred to it —specifically to encourage reporting of adverse drug reactions in the use of medicines in the treatment of children. That scheme has been operating for a little under a year. However, it is reassuring to be able to report that, within the time frame of the project, no major safety issues have been reported.

I am happy to be able to reassure my hon. Friend, and I hope he will recognise, that, in the very act of committing funding to the project, the Government have signalled their determination and willingness to find ways in which to improve the current system. If the scheme proves to fulfil that need in the best way, subject, obviously, to a full and proper evaluation, we shall continue to fund it.

My hon. Friend referred to the work of the Royal College of Paediatrics and Child Health on a national formulary to include data on drugs prescribed for children. He asked a specific question about funding for future editions of the formulary. As far as I am aware, the Department has received no application to fund a future edition, but, if any such request were made, the Department would be very willing to consider the proposal.

My hon. Friend might be aware—I am sure that he is—that the formulary will cover some 300 medicines commonly used in the treatment of the paediatric population. It will include medicines specifically licensed for such use and medicinal products that are not currently licensed for use in the treatment of children, where advice on the appropriate indications and dosage use for different age groups based on other research findings and evidence has been compiled by the joint committee. It is hoped that the formulary will be issued to the health service by the committee in May or June. I am sure that that will be an important and welcome development.

I turn to the specific question of availability of licensed medicines for use in the treatment of children. It is true to say that a sizeable proportion of medicines is available and formally licensed for use in the treatment of many illnesses that can occur in the paediatric population. Indeed, some products have been developed specifically for such use.

There are other products for which specific clinical trials of a product have not been conducted in the paediatric population, but where the manufacturer and the licensing authority have no reason to suppose that its safety and efficacy will be such that it should not be used in the treatment of children. Such products cannot and should not be defined as "unlicensed" for use in the treatment of children.

A further category of products is those where the terms of the licence and the patient leaflet may state that use in children is not for use in the paediatric population. Those medicines can indeed be described as "unlicensed" for such use. Nevertheless, there are circumstances when the use of such medicines may, in the view of a clinician, be justified and, indeed, necessary. In any circumstance where a doctor prescribes for a patient, he or she must assume the responsibility for that action.

In the case of treatment of children with unusual conditions, GPs will usually seek the advice of specialists before prescribing treatment with products that are unlicensed or will have to be used "off-label". Such specialists build up a body of knowledge and expertise in the treatment of children's illnesses and have developed treatment regimes to respond to them. There is also a significant volume of published and experimental data available and schemes are in place which make that information available to prescribers of medicines in the paediatric population.

The wide availability of so-called "specials" manufactured commercially and by the NHS has developed in part as a response to the needs of those specialists. Although such products may not have been subjected to assessment of safety, quality and efficacy by the MCA, manufacturers are required to hold a "specials" licence, to have suitably qualified persons responsible for production and quality control and are subjected to inspection by the agency. Their use is carefully monitored by prescribers, and much of the body of information and advice available to those prescribing for children has been compiled from experience gained in practical usage of those, and formally licensed, medicinal products.

I turn now to the question of what additional action could be taken to improve the availability of medicines licensed specifically for the treatment of the paediatric population. I know that that is a matter of especial concern to my hon. Friend the Member for Edmonton and the parents of the child to whom he referred. The Government share the view of those who have expressed their concerns that a wider range of properly assessed and licensed products for use in the treatment of children of all ages should be available.

My hon. Friend raised a point about the very real value of the use of some of those medicines and I agree with him that, important as this debate is, it must not deprive children of the benefits that use of such medicines can bring. We expect that the pharmaceutical industry shares this view. We would like to see them working constructively with the MCA to provide appropriate data to support inclusion of relevant information in the licence. That will ensure that clinicians have access to clear information about the use of their products in the treatment of the paediatric population. Such information also needs to be available in the patient leaflet for the parent or carer.

So far, I have spoken only of the UK's regulatory position. However, much of the legislation that underpins medicines control in the UK now derives from European directives. While that has contributed significantly to improved standards of regulation throughout Europe, it does also mean that any change to the legislation—for example, any proposal that increased the data required from the pharmaceutical industry on use of their products in the paediatric population—would need to be widely discussed and agreed Europe-wide.

Such discussions have already been initiated and there is already a European guideline which the UK played a leading role in developing, which makes it clear that if a product is likely to be used on children, the regulatory authorities such as the MCA will expect data to be presented from clinical trials in the appropriate age group. The principles set out in the guideline are also being taken forward at an international level through the International Conference for the Harmonisation—the ICH—of technical standards for the registration of medicinal products. The aim is to have an agreed guideline to be adopted throughout the EU, Japan and the USA. However, that is only a guideline and does not have the force of law, as my hon. Friend the Member for Edmonton acknowledged. In the USA, a similar initiative has met with only limited success in encouraging the pharmaceutical industry there to conduct appropriate clinical trials. I can reassure my hon. Friend that we will be looking at the US experience very carefully.

We expect that the pharmaceutical industry will take heed of the European guideline and be prepared to work with us—

The motion having been made after Ten o'clock, and the debate having continued for half an hour, MADAM SPEAKER adjourned the House without Question put, pursuant to the Standing Order.

Adjourned at twenty-two minutes to Eleven o'clock.