§ Motion made, and Question proposed, That this House do now adjourn.—[Mr. Thompson.]lb/>6.38 pm
§ Mr. Jack Ashley (Stoke-on-Trent, South)
The story of Opren is remarkable because it is a study of contrasts. A meteoric rise in popularity was followed by a dramatic collapse of confidence after nearly 3,000 adverse reaction reports, including 76 deaths. For some, it is a totally discredited drug; for others, it is still a big advance in arthritic treatment. It was produced by a company called Dista that was respected by the Committee on Safety of Medicines, yet its parent company in the United States of America, Eli Lilly, was investigated by the Food and Drug Administration and accused of deliberately concealing adverse reactions.
The way in which the CSM dealt with Opren raises issues crucial to drug safety. I have given the Minister for Health, whom I am glad to see here, notice of my major points, especially seven vital questions, and I would appreciate direct replies. Opren has caused immense disquiet amongst patients and it has shaken public confidence in the safety of drugs. No doubt it has also caused concern among drug companies.
Three hundred million NHS prescriptions are issued every year, and 4,912 drugs are on the market. Few individuals can assess the safety of the drugs prescribed. Nearly all of them are totally dependent on doctors, who in turn are very dependent on the CSM. So the responsibility of the CSM is enormous. What resources are available to fulfil this responsibility? The CSM has a mere 15 pharmacists and £1 million worth of resources at a net cost to the Government of £250,000. Compare the trifling £1 million spent on the CSM with the £1,000 million spent on the drugs that it monitors.
Ministers mouth the platitude that there is no safe drug and that we must balance the benefit and the risk. We know that, but they seem to assume that the use of this phrase exculpates them from all responsibility. They are wrong. Their job is to ensure that the balancing is properly carried out. My first question to the Minister is whether he agrees that the gross and net expenditure on the CSM is wholly inadequate in comparison with its responsibility for drug safety, and if so, what is he going to do about it. The main adverse effects of this drug were on the elderly and we want to find out whether the CSM could have foreseen them, and whether it should have suspended the drug earlier.
It is difficult to unravel those questions because of the deplorable secrecy and shiftiness of Ministers at the DHSS, who have sought to withhold vital information from Parliament. In a parliamentary question last December I asked whether the clinical trials had included old people, and the evasive reply from the Under-Secretary of State was that in its application for a product licence the company gave information about the drug and the elderly. I followed that up a few weeks ago with the crucial question whether the information provided by the company showed any significant difference in the reactions of elderly and younger people to the drug. This time the scandalously stonewalling reply from the Minister for Health merely referred me back to the earlier reply. Of 1099 course, the earlier reply did not contain the information, or there would have been no need to ask the second question.
Consequently, Parliament does not know whether the clinical trials for Opren included the elderly and, if they did, what the results were. It is preposterous that Parliament should not know. Members are entitled to this information, and my second question is whether the Minister is prepared to disclose it. Clinical trials are the means by which companies enter a lucrative market place. Unlike the American Food and Drug Administration, the CSM does not have the resources to carry out thorough investigations into them. The data of clinical trials should be publicly available, so that at the first hint of concern there can be independent investigation by professionals. My third question to the Minister is, will he make freely available the essential details of the clinical trials which companies submit to the CSM in support of their application for product licences?
Whether or not the company had given information to the CSM about the enhanced risks for the elderly, the CSM should have been aware of them, because Dr. Hamdy's research work, published in July 1981, showed that the drug persisted in the elderly and had a greatly prolonged half life. Dr. Hamdy said that the findingsmay have profound therapeutic implications.Although the company referred to those findings in a general "blurb" sent to GPs, it did not emphasise them, nor did the reference have CSM backing, nor was it in MIMS, the GPs' "bible". It should be the CSM's responsibility to warn GPs. Incredibly, 12 months elapsed before clear and specific instructions were given to GPs to halve the dose. The CSM accepted that Dr. Hamdy's study was a good one. It implied a grave danger to the elderly, yet for a whole year the drug watchdog failed to bark. My fourth question to the Minister is, why?
Dr. Prescott, a toxicologist who was formerly a member of the CSM toxicology sub-committee, said that Dr. Hamdy's research would have led him to advise reduced dosage for the elderly immediately. He alwayswanted to err on the side of safety rather than chance it.The CSM chanced it and decided to wait and see what would happen. What happened was that there was a flood of suspected adverse reaction reports from doctors—3,827 of them by January 1983, including 76 deaths. My fifth question is, what advice does the Minister give to the CSM if there is any doubt about safety—take precautionary action, or wait and see?
The pattern of reporting adverse reactions to Opren illustrates the fundamental weakness of the existing voluntary system—the so-called yellow card system. In the 18 months from October 1980 to March 1982, 28 deaths linked with Opren were reported to the CSM. Yet, in the four months from the end of March 1982 to the beginning of August, 33 deaths were reported. The difference was that before the publicity doctors were not suspicious about Opren, but the yellow card system relies on doctors voluntarily reporting their suspicions. Most of them tend to get suspicious later rather than sooner.
Suspicion is an emotional and unscientific basis for drug safety. Our inadequate system of drug safety will be 1100 improved only with a more effective method of post-marketing surveillance—one based on full and accurate reports of all medical events happening to a sample of patients.
The Government are supporting some research in this area but their commitment is relatively small. My sixth question is, does the Minister agree that independent—not drug company—post-marketing surveillance based on the reporting of events is essential for drug safety, and, if he does, will the Government devote more resources to it?
Since Thalidomide there has been a succession of drug sagas of which Eraldin, hormone pregnancy tests, Debendox and Opren have been the most publicised. Good drugs have a crucial role to play in modern medicine, but the good drugs, and the good companies, are being damaged by scandals emerging because our safety precautions are inadequate.
I repeat my call for an independent inquiry into drug safety. We need to assess the strength and weakness of our present system and the likely value of the new systems being developed; we need to look at new ways of balancing drug benefit and risk; and we should consider what information we need, how we get it, and what use we should make of it. In particular, we should reassess whether the present practice of a drug being available for everyone or suspended completely is the correct one. Such a wide-ranging inquiry could and should radically alter our approach to drugs and enable us to derive more benefit at less risk.
Finally, I want to refer to a separate but related matter. "Panorama" did two splendid programmes on Opren and revealed a disturbing picture of the relationship between drug companies and the medical profession. If "Panorama" is right, there is no doubt that some people in the medical profession are bribed by the drug companies. My seventh question is, does the Minister accept this charge, and, if so, what does he intend to do about it?
§ Mr. John Farr (Harborough)
I congratulate the right hon. Member for Stoke-on-Trent, South (Mr. Ashley) on once again using his initiative to express concern about something in a specialised field that he has championed over many years, in this case the misuse or misapplication of the drug Opren. I intended to listen to him in any event, but as we have plenty of time it might interest him and the House to know that about 15 months ago I consumed, at regular intervals, great quantities of Opren.
I was taking the drug under a doctor's prescription and was on it for about three months. I suffered a great deal of discomfort. If this had happened to an older person or to someone who was more infirm, the effect could well have been fatal. I was reasonably fit but my skin suffered the most tremendous prickling sensation and burning. I could not go into any form of sunlight without having my hands covered. Of course, I did not associate the most unusual discomfort with the drug because I was eating food normally and I had taken the drug on doctor's advice. I thought at first that there must be something unusual in the local sunlight and then that the discomfort was caused by another complaint. Eventually the pain was so intense that the only way I could recover was to go indoors out of the sun.
As I said, I was put on Opren by my doctor. At no time did he warn me that it might have ill effects. At no time was I led to believe by him or by anybody else that it had 1101 not been properly tried and tested and had not passed the tests with flying colours. Therefore it is important that the questions that the right hon. Gentleman has raised are answered. It is of critical importance that we know why in Opren's case it was put on the market and prescribed by British doctors without its performance, which was suspect abroad, being properly taken into account. How can it be in this modern age that people in Britain are still not adequately protected by the law and can still be exposed to drugs that are not and never have been fit for human consumption?
I endorse 100 per cent. what the right hon. Gentleman has said. His questions must be answered. I want to know what account was taken of overseas experience in the use of Opren, and also to what extent general practitioners are pressurised by financial inducements to prescribe Opren and other drugs. From what I have learnt I believe that in many cases the drug companies and those who push these doubtful drugs offer large financial margins to doctors and others who prescribe them. That is totally wrong. Once again I congratulate the right hon. Gentleman on performing a public duty in raising the matter.
§ Mr. David Crouch (Canterbury)
I find it hard to speak in this debate, which I do not think will be short because the right hon. Member for Stoke-on-Trent, South (Mr. Ashley) has had the advantage of capturing time, and he does so on a very important subject. I find it difficult to speak because, as the House knows, I am a director of a drug company, not a small company and one not unrelated to this drug because it is a producer worldwide of an anti-arthritic drug. I will not say that it is similar because it is not, in chemistry, in any way similar to Opren, but it treats the same illness. I make no comment about that drug now. I am touching wood that it is found not to have ill effects.
I find it difficult to speak too because the use of Opren seemed almost indefensible when one had seen the "Panorama" programme. I welcome that programme, Anyone who is concerned about sick people must welcome any revelation about treatment offered to them that may be dangerous and may even cause loss of life, as is alleged by the right hon. Gentleman and has been reported in the press. We know that all drugs can be dangerous. A person can commit suicide with an overdose of aspirin. Yet aspirin is one of the most valuable drugs available to mankind as a pain reliever. It is a simple drug which has been on the market a long time and does not require a prescription. I would prefer that aspirin could only be bought from pharmacists but it is possible to buy it elsewhere. It is available for someone to overdose himself with, even by mistake. However, I do not want to labour the case of aspirin because we are talking about another drug—a new drug.
We shall be hearing shortly from the Minister about Britain's system for the protection of the public, the patient and the medical profession against the misuse of drugs, their wrong promotion and the marketing of any medical product which is unsafe. It is strange to think that it is only in recent years that a strict system, known as the Committee on Safety of Medicines, has been set up. That was the result of the Thalidomide scandal. Not only are the House, the public and the press worried about the Thalidomide scandal; so are the medical profession and the drug industry.
1102 It can be said that the drug industry seeks to make profits. One can extend that phrase and say that it seeks to make profits out of the sick because drugs are sold not to fit people but to sick people. Thank God we have a system whereby drugs can only be sold to sick people on prescription through their medical practitioner or prescribed to them in hospital.
The right hon. Member for Stoke-on-Trent, South is one of the fairest and most reasonable Members of Parliament who, at the same time, has a sword of righteousness in his hand which he always uses with wisdom and good sense. He has acknowledged that drugs are an advantage. Good, proven and tested drugs are an advantage to mankind as life savers, pain relievers and pain killers. A great advance has been made in the last 50 years and the life of many in the Western world has been prolonged. Our hospitals, largely in the mental health area but in other areas as well, have been emptied. When I was a boy one of the great illnesses that one worried about was consumption. Chest hospitals are largely empty now, thanks to the great developments that stemmed from Alexander Fleming's invention of penicillin.
Enormous advances in pharmaceutical research have been made very quickly, moving further and further from the advances of Fleming and others. It is perfectly true that money for drug research in our society comes from the profits of the drug companies and not from Government grants. As we heard on the "Panorama" programme, medical research professors in America acknowledge that if it were not for the grants that they get from the drug industry they would not be doing the research that they are. Research in the drug industry is largely done in the drug companies. They come to the Secretary of State for Social Services and the Minister for Health to justify their profits every year in the light of their research and development programmes.
Successive Ministers of both parties have always recognised that certain profits are justifiable. Without them we would not have the drug industry that we have in Britain, which is among the world leaders in research achievement. Britain's achievement in the pharmaceutical industry is far greater than anything in the Soviet Union. The innovation, inventiveness and research that has been achieved is truly remarkable.
The Government must ensure that excessive profits are not made and that they make a regular surveillance of the drug companies' figures, both British and foreign—American, Swiss, German and others—which operate in Britain. Incidentally, those foreign companies operate in Britain because they find that there is a reservoir of scientific knowledge coming out of our schools, technical colleges and universities which enables the developments in research to proceed. Some of the principal drug companies in the world choose to base a large part of their research in the United Kingdom rather than in France or Germany. Yet West Germany is an important country in this development and Switzerland is famous for its activities in this area.
The Government have more than simply a financial responsibility on behalf of the people. Most drugs sold in this country today are sold through the National Health Service. The private sector is very small indeed. We know that the drug bill is big. It is 10 per cent. of the NHS bill. Ministers watch it like hawks and it is right that they should do so. Ministers also take into account the fact that 1103 the industry makes a considerable net contribution to the net balance of payments of over £500 million a year—if I have my figures right. It is an exporting industry.
However, the Minister and the Government have another responsibility—to ensure that drugs that are marketed are safe and do not produce ill effects. All drugs can cause ill effects, if one takes too many or if they are prescribed for persons for whom they are not suitable. My hon. Friend the Member for Harborough (Mr. Fan) has suffered from Opren. We cannot talk about that now because I am not a scientist but I know that many others have suffered the side effects that he suffered from because I have seen television programmes and reports.
The Government must watch new drugs to know of the side effects before the drug is released to the public. That can be done only by extensive research in the industry and that is done. The Committee on Safety of Medicines sits a long time—years—before it allows a drug onto the market. It usually takes a company about 10 years to process a new drug and it takes about 12 years in all before it can be passed by the Committee on Safety of Medicines and released to the public. It is a matter of testing, testing, testing. Let us not mince words. That testing is done on animals, and then on human beings, but not without their permission, and only under the strictest medical surveillance.
§ Mr. Ashley
The House is always interested to hear the hon. Gentleman speak on drugs, because of his expertise, and he is entitled to go as wide as he wishes, but tonight I have made some serious allegations about Opren, the Committee on Safety of Medicines, and drug safety. We expect the Minister to reply, but would the hon. Gentleman care to comment on some of the allegations that I made?
§ Mr. Crouch
I apologise to the right hon. Gentleman. Perhaps I have digressed. I apologise to the House. I also apologise to the right hon. Gentleman because he spoke before me tonight, and I did not hear the first three questions that he put to the Minister. I hope, therefore, that he will forgive me. I shall have to leave it to the Minister to reply. He is in a better position than I am to reply, and I would not be so bold as to seek to reply. However, perhaps I might comment on one matter that the right hon. Gentleman raised—the over-promotion of the drug Opren.
Another issue which came from the "Panorama" programme was that there was not complete disclosure of the side effects that had been discovered in the United States. I cannot comment on the latter point, but I take it that that did happen. From what I have read, it seems that statements were made in the United States about side effects which were not fully disclosed in the marketing of the drug in this country. I can only say that I am appalled if that is true. I am appalled because there is no future for this industry, of which I have described the good side, if it ever falls by as much as a millimetre in its integrity in front of the public, or Parliament, or the Parliaments of other countries. All are concerned in the matter.
The programme also described the apparent junketing of a company—not this company, but an Italian company—taking the Orient express to Venice to talk to doctors, rather than talking to them in Manchester—as I think one of the doctors said could have been done, although he added, with a smile, "I don't think that I 1104 would have gone to Manchester, rather than to Venice." Even so, it stretches my credulity to think that a junket on the Orient express is the way to promote an idea among rheumatology consultants. It is a pity.
It is true that the Association of British Pharmaceutical Industry, the ABPI, has a strict code of practice for its members about how to present their case to the medical profession. The only trouble is that they are not allowed to advertise to the public, and I do not believe that they should ever be allowed to indulge in public relations. That also came out in the programme.
The doctor's judgment in prescribing medicines must be his medical judgment, based on his medical knowledge and his knowledge of his patient. It is true that some drugs prescribed for one patient are never prescribed for another, because when the doctor looks up the medical history and sees certain conditions in the person's health and history he will know, by knowing the side effects that are notified on the data sheets of the drug, that perhaps those drugs are suitable for patient A, but not suitable for patient B, or not in that dosage, or should perhaps be given at another time of day, and so on.
I have the highest regard for the medical profession's approach to the whole drug question. What worries me about promotion is how to bring to the notice of the medical profession the developments in the drug world.
§ Mr. Crouch
If the hon. Lady wishes to intervene, I shall willingly give way to her because of her professional interest.
§ Mrs. Dunwoody
It is not my profession, but I am most grateful to the hon. Gentleman for giving way. Will he acknowledge that if anyone wants to know what drugs are available there is an excellent British national formulary that all doctors can use?
§ Mr. Crouch
The hon. Lady is quite right. I imagine that she is talking about the BP—the British pharmacopoeia.
I have found—I am sure that the hon. Lady has found it in her shadow responsibility—that general practitioners are busy people, and that after 20 or 30 years of practice they are often 20 or 30 years out of date with the latest developments. Of course, one of the ways they get their information is by mail, by reading The Lancet, the BMJ, and the advertisements.
However, we come back to the point: what goes into those advertisements must be most carefully scrutinised and controlled, and if there has been any lack of control in the case of Opren of what could be said, if there was a falling from the highest standards by the company, it is up to the Government to spot it or to the trade association involved. Failure by one part of, or one company in, the drug industry is in a way a reflection on the whole. That is why I said when I rose to speak tonight that this is a difficult subject for me to speak on.
I am grateful to have had this opportunity to make a small contribution to the thoughts and concern about this matter. I am as concerned as anyone else, because I want to defend the integrity of the industy. If the industry's integrity has been harmed by this, I hope that the Minister will tell us that he and the Government, together with the industry and the medical profession, will tighten up the controls so as to prevent any such tragedy from occurring again.
1105 I give warning to the Minister, the Government, and the House. They should remember the words that were spoken by Professor Wright of Leeds university, a consultant rheumatologist interviewed in that programme. He said—I quote him very loosely—that the system of control is basically right and that the Committee on Safety of Medicines is basically a good system, but he added that we must not stifle research. We must not do that, because it has been such an advantage to mankind to have had that development in this field. We do not want to stifle it, but at the same time we must ensure that it proceeds safely for us all.
§ Mrs. Gwyneth Dunwoody (Crewe)
I am grateful to my right hon. Friend the Member for Stoke-on-Trent, South (Mr. Ashley) for raising this matter. He has a long record of commitment to important matters, and I am second to none in my admiration of the work that he does in this House and outside. He has raised a number of questions which have wide implications, and I hope that the Minister will address himself to some of them.
First, I make no criticism of the Committee on Safety of Medicines. I know Professor Goldberg to be a man of honour and high intelligence, and I am sorry that he feels that by selective editing some of his recent remarks were perhaps misinterpreted. However, there may be a good case for looking at the powers of the committee. It seems that in this country we do not have sufficient independent research or independent access to information about drugs. We all know about the problem of the drugs cocktail and the constant flow of adverse drug reaction bulletins that are sent to general practitioners. I should like the Government to commit themselves to a much wider system.
There is a specific role for the pharmacist in this connection. A working party set up by my group of the national executive committee of the Labour party has been considering ways in which drug use can be recorded by the pharmacist. As the Minister knows, in many instances in hospitals the pharmacist has easy access to the consultant who is doing the prescribing, and he has the right to discuss most of the implications of the use of drugs as well as the cost and any adverse reactions that are recorded. The private pharmacist does not have that help.
There may be a good case for moving to a system whereby pharmacists record the history of individual patients' drugs. Busy general practitioners, of whom the hon. Member for Canterbury (Mr. Crouch) spoke, will often prescribe drugs but not necessarily give all the relevant information about the effect of that drug. They may mean to, but they may not have the time or always succeed in conveying the full message.
It is important that the pharmacist should fulfil the role of counsellor and should be able to use his highly specialised knowledge to assist patients to understand the implications of the drug and the effects that it could have when taken in conjunction with other substances.
I shall return to the subject of the Committee on Safety of Medicines. I am not always an uncritical admirer of the Food and Drugs Administration in the United States, but that organisation has different and in some instances wider powers. Does the Minister intend to look at the powers of the Committee on Safety of Medicines to see whether they should be strengthened? If it had teeth with which to bite some of the pharmaceutical companies, we should not be in our present position in relation to some substances. Will 1106 he talk to the Department of Education and Science on the important subject of who actually does the research into individual drugs?
The hon. Member for Canterbury, who is a man of great honour and who I know would not seek to mislead the House, said that he was satisfied that many multinational drug companies operate in this country and manufacture drugs here because they know that our universities have a pool of expertise and academic brilliance. I do not disagree. It supports the argument that a great deal of the research should be taken away from the drug companies.
If all the information about every drug, good or bad, in all its clinical tests were made available through the universities, we might avoid some of the difficulties that have arisen through substances producing adverse reactions. I hope that the Minister will say that he is not content simply to talk about the difficulties that have arisen in this company, but will give some undertakings.
What does the Minister believe to be the future of pharmacists in this country? Is he prepared to see them undertake a wider role? Will he undertake to look seriously at the system of post-marketing surveillance to ensure that a great deal more is done than at present? Often, the doctors, who should most rapidly report adverse drug reactions, are so deeply involved that it is only when a number of cases are brought to their attention and they publish their findings that other members of the medical profession join in and say, "Yes, that is true. There is some evidence of that reaction." That may be too incomplete a method of ensuring the patient's safety. I should like to see the role of the Committee on Safety of Medicines strengthened and widened so that it could consider all these aspects. It should have a much stronger say in what happens in relation to the pharmaceutical industry.
We are in a difficult position. Throughout the world there is a tendency to rush to pharmaceutical products. Companies which operate here will want the right to advertise their products. I believe that the figure of 10 per cent., which is what the companies are allowed for advertising their products, is too much. General practitioners could not open their front doors 30 years ago because of the number of advertisements that had fallen through the letter box. Companies are now more sophisticated in their approach. They offer free luncheons and rides on the Orient express.
Recently in Liverpool a company advertised a visit to the Henry Ford yacht, a masterpiece of 1930s luxury. It was an Italian company which was operating in this country and seeking to attract the attention of British doctors. It sent out a leaflet which described the size, the shape, the carpeting and decor of the yacht, but said nothing about the drug and barely mentioned its trade name, although of course it did mention the name, because that is the rationale of all the advertisements. There is a good case for telling the companies that they must spend far less money and certainly have no justification for producing magazines and offering railway jaunts and dinners to groups of doctors. That is one way in which companies seek to push their products.
If a company has useful clinical information to pass to the medical profession, it should not need to use such methods. One should say to the companies, "If you are dealing with the medical profession and have information which is of use to it in its job, surely you are prepared to 1107 behave in a dignified and sensible way and not seek to bribe it with the easy handout," and I believe rather degrading and constant hospitality.
There is a good case for much tighter controls of the pharmaceutical industry. I hope that we shall have a chance to talk about some other aspects of its behaviour tonight, and that when the Minister replies he will give us one or two simple answers to the questions that my right hon. Friend the Member for Stoke-on-Trent, South has asked. They were important and on a subject that has a direct effect upon the lives of many people in this country.
§ The Minister for Health (Mr. Kenneth Clarke)
I congratulate the right hon. Member for Stoke-on-Trent, South (Mr. Ashley) on winning time for a debate on this important subject. I agree with him and other hon. Members who have spoken that the history of the use of Opren in this country is tragic, particularly for some of the patients who were treated with the drug and for their families and friends.
We shall probably never know the exact number of people who suffered serious injury, side effects or death as a result of the use of the drug, because precise causation is often difficult to establish and one does not know the full extent of the notification that was received. Possibly some of the deaths that were suspected of being linked with adverse reactions to the drug were not actually caused by the use of the drug and perhaps the patient died of some other condition. Nor do we know to what extent we received full notification of all the side effects, or whether doctors recognised that the patient was suffering from a side effect of the drug.
An unacceptable amount of suffering from the side effects of the draug was caused. We all express our sympathy, and in some cases, unfortunately, our condolences, to those people who feel that they were the victims of a tragedy.
I began by saying that the history of Opren was a tragedy. However, I believe that it was not a scandal. I hope to be able to persuade the House of that. It is quite untrue for the right hon. Member for Stoke-on-Trent, South to say that Ministers at the DHSS have been holding back information or have not been forthcoming about Opren's history. I shall be forthcoming this evening and give as full and detailed history of the introduction and use of the drug as I can. It is an advantage that I shall not be edited by television producers or be subject to some of the other misfortunes that those who try to explain their position inevitably experience in this kind of case. I am grateful to the hon. Member for Crewe (Mrs. Dunwoody) for saying that she did not lend her weight, as official Opposition spokesman, to some of the strong attacks made on the Committee on Safety of Medicines and its members.
The House should recognise the committee's great work on behalf of the community. Professor Goldberg and his distinguished colleagues put a great deal of untiring effort into their work. We are fortunate in having genuinely leading experts giving their services to the committee, and irresponsible attacks upon them may deter some of them from giving up several days each month from other valuable professional work. The extent of their 1108 duties is considerable. The committee licenses about 200 drugs each year, and it monitors the safety of about 16,000 products currently in use.
The number of products that give rise to difficulty is trivial. There is the occasional spectacular, well-publicised case, but that does not provide the basis for attacking the integrity and the good work of the committee, or, as I hope to demonstrate, the system itself.
Britain has one of the most effective monitoring systems in the developed world. I am satisfied that the committee monitored the drug Opren throughout its history and advised action on occasions when it had the scientific evidence to justify doing so. I understand the anxiety that we all feel, with the benefit of hindsight, about the adverse reactions that were experienced. But much of the strident criticism that is now being aimed at the committee and our system of monitoring is based heavily on the wisdon of hindsight. Some people are searching for scapegoats and some of the critics fail to understand either the scientific background or the sequence of events.
Before leaving the subject of the Committee on Safety of Medicines, I want to deal with the right hon. Gentleman's suggestion that the committee lacks the resources to carry out its tasks successfully. People have made completely uninformed attacks suggesting that the CSM was suffering from Government cuts in expenditure, was not vetting the yellow cards sufficiently quickly and other populist nonsense. None of this was promulgated by hon. Members in the Chamber, but there is one notable absentee who made several of those points.
The resources of the CSM have risen during the period that the Government have been in office, as has its gross expenditure, from £l.1 million to £1.2 million. In addition to this central expenditure, the committee has the valuable resource of all doctors throughout the country co-operating in our notification system, which is usually referred to as the yellow card system. I am quite satisfied that the committee has adequate resources to fulfil its task of considering applications, which is why it has been so successful in the case of most new drugs brought into Britain.
When the right hon. Gentleman compared the committee's expenditure with the total expenditure on all research and development of all drugs in Britain by pharmaceutical industries, he was not comparing like with like. We have no reason to believe that the £1.2 million and the number of pharmacists are not adequate to fulfil the task.
In case anyone thinks that my thanks to and praise of the CSM show that I am wholly in its pocket, and an uncritical Minister monitoring its activities, I must tell the House that I have discovered that I am the first Minister for Health who has not followed its advice. In one recent case I refused a licence to a drug known as Depro Provera, contrary to the committee's advice. A hearing is being organised to produce further information on that drug and its side effects. The Government are not wholly uncritical—they exercise their judgment in all cases.
Having dealt with the system and its record, may I say that there is an important general principle to be made about the marketing of any new drug. It is never possible, and will never be possible, to produce and market a new drug that is 100 per cent. safe. The right hon. Gentleman regards that remark as a platitude. He expected that I would say that, but it is not a platitude. That truth is not widely enough appreciated by the general public.
1109 My hon. Friend the Member for Harborough (Mr. Farr) reacted on the basis that, because he had suffered unpleasant side effects from the photosensitivity of his skin caused by a drug, that proved that it must be wrong that, in a civilised developed country, it is possible to market a drug that produces side effects. I am afraid that, given the nature of drugs and drug therapy, it is not possible to market drugs without side effects. All products, without exception, cause adverse side effects in some patients. I recall something that the late Sir Derek Dunlop said. He played a great part in setting up the CSM. He said something like, "Show me a drug that has no side effects and I will show you an inactive drug." The Times' leader put it more dramatically by saying that all drugs were poisonous. To some extent, that is true. They are introduced into the system to produce a chemical reaction which, on balance, has beneficial effects. It is a controlled toxicity in the drug that produces a cure or relief from the symptoms being suffered.
The judgment that must be made about every drug that is developed, given that all drugs have adverse side effects, is complex and difficult in every case. We must decide whether the benefit of the drug is greater than the risk of adverse reactions. The benefit depends on how effective the drug is, how serious the disease or condition being treated is, and what the consequences will be if the condition is left untreated. With adverse effects, we must understand the nature, the extent, the number and the frequency and how far the effects can be reversed in the patients who suffer them. The balance between advantages and disadvantages can vary according to how serious the disease is, how effective the treatment is and how great the risk is to the patient.
One extreme example is that a drug that may be used to treat a terminally ill cancer patient can acceptably have frequent and serious side effects because the relief it gives justifies running the risk of some rather unpleasant side effects.
There are common drugs in everyday use that are known to have adverse side effects on some patients.
§ Mr. Clarke
That is an accurate example. Aspirin can cause internal bleeding in a proportion of those who take it. It affects only a minority, but the risk is acceptable because the drug is useful. It is sold over chemists' counters without a prescription. Seasickness pills can cause drowsiness, and it is dangerous to drive after taking them. Penicillin can cause a nasty adverse reaction in a minority of people unlucky enough to be sensitive to it. It is well known that the contraceptive pill carries the risk of thrombosis in some women. All those risks are known to have been experienced by patients, but each of the drugs has been judged to be acceptable because the risk is so small when compared to its benefits for the community.
Every time a new drug is submitted by a company, a judgment must be made about its side effects. If it is wholly free of side effects, it is probably useless and will not do any good, but, whatever side effects it causes, these must be balanced against the benefits that it will bring, to see whether its use is acceptable and desirable.
§ Mrs. Dunwoody
Does the Minister accept that he is making a valid case for much better reporting of the use 1110 of new drugs? If people take new drugs there must be close monitoring. Is there not a role for the pharmacists as well as the doctors?
§ Mr. Clarke
There is validity in both those points. I shall be explaining the system of reporting, and I was interested in what the hon. Lady said about the role of the pharmacist. In judging the monitoring system, and the licensing system of testing, my point is that it is a difficult judgment to make between the benefits and disadvantages, and I am sure the hon. Lady accepts that.
In looking at the advantage-disadvantage balance on Opren, let us not forget another feature of the drug when it was in use. It was a very effective drug in the treatment of arthritis and osteoarthritis. It did not cure the disease, but for some patients it had very beneficial effects in relieving the symptoms and improving the quality of life.
Opren belongs to the class of drugs known as non-steroidal anti-inflammatory drugs. It was about the twentieth of that kind to go on the market. Many patients who tried other variants of the drug found that it was in practice far more effective in reducing symptoms than others.
Somebody who worked in my constituency told me that in practice it was found to be good for relieving suffering from psoriasis, because the very effect that it had of reducing photosensitivity in some patients was helpful in treating psoriasis. All hon. Members who take an interest in the subject, and I would guess the right hon. Member for Stoke-on-Trent, South himself, found that, when Opren was withdrawn, they had many complaints from patients who objected to the withdrawal of the licence from a drug that had greatly increased the quality of their life. They had been crippled and disabled from arthritis and obtained more relief from Opren than they otherwise could have obtained.
Other hon. Members may not have had this experience, but a young taker of Opren told me that the dramatic improvement in his condition that the drug had achieved in his opinion justified his carrying on taking the risks of possible side effects, which, in any event, he was not experiencing. If he stopped taking the drug there would be a deterioration in his condition and a relapse into pain and suffering. Opren was beneficial and was welcome while it was available to many patients.
Hon. Members have spoken about the amount of advertising, but one has to distinguish between advertising and the publicity that the media gave to Opren, with news stories describing it as a "wonder drug", when it first came on the market and gave relief. The right hon. Member for Stoke-on-Trent, South may have experienced this himself, because he sent a letter to my right hon. Friend the Secretary of State on 5 January which touched on this point. It set out his various complaints, which he has put forward today. Having given all the reasons why he felt that the drug should never have been licensed or should have been withdrawn quickly, he concluded one paragraph by saying:Some doctors feel that Opren need not have been withdrawn if the CSM had responded promptly to warnings about dosage. If they are right, the CSM must accept responsibility for the possibly unnecessary withdrawal of a valuable drug.I fear that I must accuse the right hon. Gentleman of trying to have it both ways by saying that the CSM is wrong both for withdrawing the drug and for withdrawing it when it could have been valuable if the dose had been reduced. It is worth remembering that this was a beneficial drug.
§ Mr. Pavitt
The Minister has referred to the promotion of Opren. What powers does he have on promotion? By coincidence, I have today sent the Minister a letter about another "wonder drug" for rheumatism. What powers does he have with regard to drug companies and new drugs in controlling their advertisements which may be claiming far more than is clinically possible?
§ Mr. Clarke
I shall deal with that point later. I agree that it is important, and other hon. Members have touched on it. I shall explain the legal position and the powers of the Department. The Department itself does not have powers, but the Association of British Pharmaceutical Industry and the British Medical Association have a role to play.
There is an allegation about the way that the committee dealt with Opren and the company. The committee has been charged with serious errors by the right hon. Member for Stoke-on-Trent South and by some outside who agree with him. There is a claim that the committee should not have licensed the drug on the evidence available to it in 1980.
Incidentally, I point out to my hon. Friend the Member for Harborough that we were the first country to license the drug, so talk about overseas experience is irrelevant.
Another charge against the CSM is that it was duped by inaccurate data from an unscrupulous company. The third general allegation is that the CSM should have acted earlier to withdraw the drug or limit its marketing when it began to receive reports of adverse reactions.
I shall deal first with the background to the drug, which is, as my hon. Friend the Member for Canterbury (Mr. Crouch) said, a lengthy one. In 1974 the Ministers who comprised the licensing authority sought the advice of the committee on an application by Lilly Industries Ltd. for a clinical trials certificate for the drug later known as Opren. This was to enable trials to take place on the drug as a treatment for rheumatoid arthritis. The drug had already been tested for toxicity in animals and the tests showed results similar to other drugs in this class, including effects on the liver and kidneys and gastro-intestinal tract. However, the toxic effect on the gastro-intestinal tract of Opren was less than from other such drugs.
The drug had also been given to healthy human volunteers in single dose studies. The committee took into account the advice of its expert sub-committees and recommended that the clinical trials should be approved, and this was accepted by the licensing authority. After 1974, the authority accepted seven and rejected one application for variations in the clinical trial certificates to cover other conditions. From 1974, therefore, clinical trials were steadily authorised.
In 1977, Lilly Industries applied for a product licence for Opren for relief of symptoms in rheumatoid arthritis and osteoarthritis. This application was passed by the licensing authority to the CSM for advice, following our system. The committee considered evidence from the company on 14 clinical studies undertaken in the United Kingdom in six hospitals and one general practice, in which 291 patients received the drug for periods ranging from six days to 12 months or more. The tests were carried out in what is known as double blind trials, in comparison with other anti-inflammatory and analgesic drugs and placebos. The committee also took into account the results 1112 of similar tests in the United States, covering just over 200 patients in 38 different medical centres, for varying periods.
Having looked at that information, submitted with the licence application, the committee deferred its decision to obtain further information on adverse effects noted in a minority of patients. Adverse effects were always known to exist with the drug, in particular what is known as onycholysis, which is adverse reaction of the nails on the hands and the feet, and photosensitivity, which is increased skin sensitivity to sunlight. That was the adverse reaction that my hon. Friend the Member for Harborough had the unpleasant experience of suffering when he later took the drug.
Those side effects emerged from the clinical trials sufficiently clearly for the committee to seek further clarification on the problems of drug safety. In February 1980, it considered further evidence from the company, which covered 330 patients in the United Kingdom and 1,681 patients in the United States, Canada and Mexico. Of these patients, 620 had taken Opren for more than a year and 39 had taken it for more than two years. The committee noted that the incidence and severity of photosensitivity and onycholysis varied widely at the various centres where the trials were held. On average, some photosensitivity had been reported in nine per cent. of American patients and 3.6 per cent. of United Kingdom patients, and onycholysis in 8.7 per cent. of American patients and 1.2 per cent. of United Kingdom patients.
The committee also took into account evidence of the efficacy of the drug in the treatment of the conditions of rheumatoid arthritis and osteoarthritis. It concluded that the drug should be granted a licence. This advice was accepted by the licensing authority and a licence was granted in March 1980 for its use as a prescription-only medicine. The licence and its product particulars included data on the product approved by the committee, covering contra-indications and precautions and warnings of possible side effects. Our system involves—in this case as in all others—all practitioners being given a copy of the data sheet incorporating this information from the licence. All doctors received a copy of the data sheet including special information about the use of the drug in patients with impaired liver or kidney function and indications about possible side effects, including gastro-intestinal bleeding, photosensitivity and onycholysis. The product was supplied to hospitals from May 1980 and to general practitioners from October 1980.
I have given a full description of the clinical trials and the evidence that was obtained. That was the evidence and the position on this drug when our Committee on Safety of Medicines gave advice which was accepted to give a product licence to this drug. We were the first country to give a licence. That was the full extent of the information then available. I know of nothing to suggest that any other information was available at the time but was withheld from the committee. In the light of knowledge and information available at that time the House, I think, should judge that the committee was right in giving the advice that it did, coupled with the data sheet, incorporating warnings, that was provided. To a layman, the warnings sound quite serious. They were warnings about gastro-intestinal bleeding. But drugs of this sort, including aspirin, will cause gastro-intestinal bleeding in some people.
1113 That was not the most serious problem. Photosensitivity and onycholysis sound bad but in most patients the effects were not severe. There turned out to be a wide range in the level of severity. Some of the increased sensitivity to sunlight involved no more than the patient becoming lobstered. There were far more extreme examples in some cases. My hon. Friend the Member for Harborough obviously had an unpleasant experience. In many cases, however, the photosensitivity and the damaged nails were not too serious. With the data sheets giving a warning, it was thought right to continue to monitor the problem.
Various points have been made about the data available to the committee when licensing a product. There has been mention of clinical trials being conducted specifically on the elderly. With hindsight, the history of this drug shows that it was among the elderly that the casualties and the worst experiences arose. It is, however, a sensible proposal. Often, when drugs are tested on younger and fitter patients, they later give rise to more serious problems among the elderly and the frail.
Even then, this apparently sensible proposal raises difficult scientific issues, not least because the testing of products on the elderly makes it more difficult to sort out cause and effect. Elderly patients, on average, tend to have weaker kidneys and livers. They tend to die of and suffer from other conditions. It is difficult to conduct clinical trials on the elderly from which one can draw exact conclusions. The Committee on Safety of Medicines is currently considering the problems involved. The Government are consulting the industry and those concerned on the point. The right hon. Member for Stoke-on-Trent, South has made a point of some value for the future.
The right hon. Gentleman asked about the confidential-ity of the data submitted to the licensing authority by a drug company in support of a product licence application. He says that we have not been as forthcoming as we might have been and that more detailed data should have been issued. The information that we get is the company's property. We have to accept that there can be legitimate arguments of commercial confidentiality when a company submits details of its clinical trials. Companies will not want to disclose results of work already done if it becomes immediately available to competitors.
My hon. Friend the Member for Canterbury said that the successful development of drugs, with the profits produced, provides the finance for further research and development. If commercial confidentiality is breached, the risks are great that someone will steal the product. If the Government were to insist on total disclosure, I can foresee the first Adjournment debate when an hon. Member would be saying on behalf of a British pharmaceutical company that our crazy system of disclosing clinical data had enabled a foreign company to steal a great British breakthrough in the development of a new drug. We have to be careful about disclosing all the data.
Much of the information is very technical. Disclosure of data showing apparent problems and harmful effects on animals is likely to give rise to unnecessary alarm among the more gullible readers of some of our more popular and sensational newspapers whenever a new drug is produced.
Many hon. Members have expressed concern about the monitoring of Opren after licensing. What went wrong, if anything went wrong—if I am right in saying that the 1114 licensing decision was correct taken in the light of the data I have described—in monitoring Opren after licensing? It is argued that the Committee on Safety of Medicines failed to act quickly enough in response to further information about Opren as it became available. I shall be dealing later with the mechanics of monitoring. The yellow card system has been much criticised. In this case, it succeeded at an early stage in identifying Opren as a particular problem.
In the first 12 months after marketing, the committee received an unprecedented number of adverse reaction reports. About 2,000 had been submitted by doctors by August 1981. That is a large number. Of those, however, nearly 1,500 related purely to reaction of the skin and nails. These were predictable from the clinical trials. In particular, the skin reactions were not generally serious and stopped if the patient ceased taking the drug or used a sun-screen.
My hon. Friend the Member for Harborough said that he gained relief by going indoors and staying out of the sunlight. His complaint was that the cause of the problem was not detected quickly enough and he had no warning. However, quite a number of patients were gaining such relief from the drug that they took the advice to use sunscreens and to stay out of sunlight which meant that the adverse reactions were not serious. The company agreed to send doctors further information on the skin reactions so that more could be done to pick up the reasons why patients were suffering unpleasant side effects.
More seriously, by August 1981, nearly 200 of the reports related to gastro-intestinal problems mainly in the elderly. This is a side effect common to all drugs in this class, including aspirin. However, the number of reports was worrying. The result was that, following discussions with the company in August 1981, the company provided the Committee on Safety of Medicines with studies of the handling of the drug by elderly patients which the company thought might be the cause of the gastro-intestinal problem.
I mention this because the fact that the Committee on Safety of Medicines had not stepped in, in the autumn of 1981, is criticised. To get the time scale right, it is worth noting that West Germany, which has a vigorous system of drug control, licensed the product in February 1981. Denmark, not a backward country, licensed the product in July 1981. The British had licensed it first. No one else was picking up the things it is now claimed should have been picked up if only the matter had been properly examined in this country.
A key point in the allegations of the right hon. Member for Stoke-on-Trent, South and of the press is that the committee should have recommended action against Opren in October 1981 when a study made by a Dr. Hamdy was presented to it by the company, showing accumulation of the drug in elderly patients. Dr. Hamdy had given a paper on the subject at a seminar organised by the company in Paris in June 1981. The right hon. Gentleman is mistaken in saying that it was published in July 1981. It was in fact, given at a seminar.
The committee was in regular contact with Lilly at that time, although Lilly is criticised by some for not handing over the report by Dr. Hamdy. In July 1981 officials were meeting Lilly to discuss skin reactions and reports of gastro-intestinal bleeds in some patients. There is no record of any reference to accumulation in the elderly.
In August, officials again met Lilly. The company suggested that it had studies on accumulation that 1115 explained the gastro-intestinal bleeding. Later in August, Lilly discussed the company's warning letter to doctors about skin reactions. Then on 7 October 1981 Lilly handed to officials three drug accumulation studies which included Dr. Hamdy's. That is the narrative. There was no delay.
One thing to notice is that they were still discussing skin sensitivity, which never became serious. If that was the only problem, we would still be licensing it. Gastro-intestinal bleeding was the subject of the discussions, which did not turn out to be a serious problem either. The three studies, still not published, were handed in October 1981.
The three studies did not all come to the same conclusion. A study was carried out in London by Dr. Hamdy. There was a study on similar lines by Dr. Kamal and Dr. Koch and a preliminary report on a study on patients in Basingstoke and in Indianapolis, in the United States of America. The studies suggested that the drug might accumulate in elderly people but the evidence from Basingstoke and Indianapolis was conflicting.
The key point is that the studies did not contain any specific evidence that the drug was harmful. What they were concerned with was the time that it remained in the body of the elderly person and the various effects this could have. This is the key point because the press and others are making a great deal of the report from Dr. Hamdy showing that the drug was dangerous and should have been acted on. Dr. Hamdy's report was published much later in 1982 in the European Journal of Rheumatology and Inflammation.
The last paragraph of the summary of Dr. Hamdy's technical paper states:It is concluded that the high plasma benoxaprofen levels achieved, combined with the slow clearance rates and long half-lives, indicate that it may be possible to administer benoxaprofen"—which is Opren—less frequently, or at lower doses, to elderly patients. More work is needed to determine whether this prolonged half-life is matched by an equally prolonged therapeutic effect.Dr. Hamdy was referring to the prospects of giving elderly patients smaller doses and still getting the beneficial effects.
That report, presented with other conflicting ones, at a time when the Committee on Safety of Medicines was discussing with Lilly the prospects of gastro-intestinal bleeding, which did not turn out later to be the key problem, is relied upon by some of these clever fellows in the newspapers. They are saying what a dreadful committee we have in Britain and how it failed to act, and how advice should have been given to withdraw the drug at that stage. The politest thing one can say is that that is the wisdom of hindsight by people who are not trained to know better in that area.
In October 1981, on the basis of the data available at the time on Opren, there was no significant evidence of the real problem—the one that led to its withdrawal—of reactions in the liver and the kidneys, particularly in elderly patients. Taking this into account, and the safety record of similar drugs, it appears to me that the Committee on Safety of Medicines acted in October 1981 as it must always act—rationally, based on the scientific data that were then available.
1116 I must move on quickly—although I do not apologise for taking up time because I was accused earlier of being one of those Ministers who withheld the details about this saga from the House.
The final act in the Opren tragedy occurred in May 1982. At that time, when the Americans were licensing the drug—a passing reference to the Food and Drugs Administration, which has been praised in comparison to our own by some critics of the Opren story—Dr. Taggart of Belfast published his reports of deaths from jaundice in five patients over the age of 80 who had been receiving Opren.
By that time the yellow card system was beginning to suggest that there could be a serious problem of adverse reactions in the elderly affecting the kidneys and the liver. Nevertheless, the yellow card system did not confirm that Opren was significantly more toxic than similar drugs. In his key work, Dr. Taggart was fortunate, or unfortunate, enough to have the coincidence of having five patients who had all been taking Opren in the same way dying in a similar way shortly after each other. This illustrates the difficulty of determining cause and effect because the difficulty with elderly patients over the age of 80—a sad fact of life—is that they tend to die anyway of other causes. It is when a number of them die together, in similar ways, and they all happen to have been taking the same drug that a doctor can form a conclusion.
I think that Dr. Taggart had been sending in his cards of individual cases, but it took him several months to work out the connection or possible connection between these deaths. In fact, it was when he published his report in May 1982 that the floodgates of notifications opened. Other doctors then began to recognise the symptoms and were able to make the same connection. The committee, being concerned, recommended a halving of doses in the over-65s, pending further evidence. The evidence came in quickly through the much-mentioned yellow cards and by late July was reasonably conclusive, and the licence was suspended. I asked the committee to review the licence, but by early August it was withdrawn. The company voluntarily first withdrew all stocks of the drug from pharmacists and finally, a month later, cancelled their licences.
Looking back, I think it can be seen that the CSM's monitoring of adverse reactions throughout the two years the drug was on the market identified a number of serious side effects arising from Opren. It continually reassessed the risk-benefit ratio of the drug in the light of that evidence until eventually the safety problems seemed to outweigh any possible benefit and it was immediately taken off the market. I simply do not accept—that narrative will have to be examined by the House and the public—that there was any avoidable delay in detecting and acting on the evidence on Opren.
Indeed, premature action on drugs can cause different problems. The suspension or revocation of a licence for a drug, which many people still believe is doing a great deal of good, on a mixture of inadequate or incomplete data or on some sort of hunch can cause only unnecessary alarm and worry to patients and sometimes deprive the community of useful drugs. If suspicions about a drug were later to be groundless, I am sure that the committee and everyone else would face publicity suggesting that we deprived the community of a valuable drug by acting on inadequate data.
1117 Attacks have been made on the company. The right hon. Member for Stoke-on-Trent, South said that the company has been attacked in America for giving misleading information. I should like to deal with the allegations against Lilly Industries Ltd.
First, it is said that it should have been noticed that Lilly Industries Ltd. was under attack in America. One must get the timetable straight on that allegation. The allegations made against Lilly Industries Ltd. in America about its failure to disclose to the FDA arose only after the Committee on Safety of Medicines had licensed the drug on its product application in 1980. More important, we and the committee are quite satisfied—and the evidence I have given supports that conclusion—that nothing was withheld from the CSM by the United Kingdom subsidiary.
The allegations made against the parent company in America have been the other way round compared with those which have been made in the debate. It appears to be alleged that the United Kingdom company did not pass over information promptly enough to the United States parent company on adverse reactions. However, the investigations in Congress came to no conclusion about that allegation. I am in no position—nor is anyone else in the United Kingdom—to pass judgment on incidents in the United States when no definite conclusion has been reached following investigations in Congress. I must again emphasise that we have no complaint against Lilly (UK). We have no evidence to suggest that anything was withheld from ourselves or the Committee in the course of the product application.
A great deal has been said about the monitoring system after the introduction of the drug. In this debate no one has laboured the arguments that were advanced earlier about the yellow cards being out of date or cuts in expenditure and other entirely inaccurate attacks. In monitoring the side effects of drugs we rely to a large extent on notifications by doctors, which are put on cards, and on studying literature. The hon. Member for Crewe has said that this is not adequate. The doctors who prescribe the drug and give it to patients are in the best position to notify. Our system of notification is more developed than that in any other country and was reasonably effective in picking up the data required in the Opren case. If I may say so, I entirely agree with the constructive suggestion made by the hon. Member for Crewe about pharmacists. The Committee on Safety of Medicines is actively considering the possibility of accepting reports from pharmacists on adverse reactions to add to the data that we receive from doctors.
Improvements can be made to the yellow card system. For example, it can be computerised and we can speed up the handling of the data. There were no significant delays in dealing with Opren, although I accept that there were delays in dealing with other drugs at one point because of the flood of cards that came in. However, nothing occurred on that front which had an effect on the decisions or the timetable at any stage.
Monitoring adverse effects does not really depend on the colour of the form or the type of form on which the doctor notifies. It does not depend either on the filing system or the way in which the forms are handled in the office. The problem of monitoring drugs is well illustrated by the history of Opren. The difficulties that have arisen in the cases in which the right hon. Member for Stoke-on-Trent, South has taken such an interest are those which tend to arise when the right connection has not been made 1118 quickly enough between the drug and unexpected symptoms in a particular category of patients. It is easy with hindsight to say that the connection should have been made but it is exceedingly difficult to make it and to draw the link.
Patients often suffer from a multiplicity of conditions and the relevant symptoms could be caused by many factors. It takes some time before anyone is put on guard. A great deal has to be done in monitoring the literature. It is necessary to await publication in journals of theories or beliefs held by doctors who have noticed some connection while dealing with their patients. A link that is suggested in an article that appears in a journal enables general practitioners to make the link with their patients in a case which has previously been puzzling or baffling them. It was the publication by Taggart of his article in the British Medical Journal, after he had spent months deciding whether he had something worth publishing himself, which led suddenly to the connection being made throughout the country. It was only two or three months before the product was off the market and detection had been made.
My hon. Friend the Member for Canterbury has cited the Soviet Union's record on research and development. Given the record of innovation of our drug industry and our success in keeping disasters of this sort to the minimum, I do not believe that considerable sponsoring of research work in universities or employing pharmacists ourselves will produce any great substitute for the present system. Problems will occur and they will be detected at ground level. We are not complacent about the system; it must be improved. Some variants are needed.
Although it can be improved, our yellow card system is unequalled in most western European countries, in the United States and in Japan. We are not complacent and the Committee on Safety of Medicines has established a working party under the chairmanship of Professor Graham Smith to consider proposals for improving the present system. I shall consider carefully any recommendations that the committee may make in the light of the report. I shall also consider carefully any suggestions that are submitted by hon. Members.
§ Mrs. Dunwoody
I am happy to have that undertaking. It is a positive move. I have listened carefully to the Minister. Has he not been proving clearly throughout the saga of events that Dr. Taggart's evidence was the first entirely independent submission to be published? Was he not right in saying that the company had certain indications? I accept that the doctor who undertook the study drew the wrong conclusion, but is the Minister not really saying that Lilly sat on certain available research for some months because it had drawn entirely different conclusions? Has the Minister not made the case conclusive for independent clinical investigation? Surely this is what is wrong. The Committee on Safety of Medicines has to rely on the company for so much of its evidence that these difficulties inevitably occur.
§ Mr. Clarke
The independent element is the reporting carried out by medical practitioners and the publications in the journals, which can be submitted by anyone who believes that he detects in practice a clinical relationship between the drug and the product. Dr. Hamdy cannot always be described as independent because he presented his findings at a seminar that was organised by the 1119 company. On the other hand, it is rather difficult to attack the company for using Dr. Hamdy's report when he was not independent. It was the company which sponsored the production and publication of the report which is now said to condemn it. I have given the narrative of contact with the Government.
We know that Dr. Hamdy's report did not refer to deaths from jaundiced livers and kidneys. The discussions that were going on with the company and the Government were all about internal bleeding and photosensitivity. When the company finally produced Dr. Hamdy's report it was with two other reports. There was no reason why it should keep back any other reports. As I have said, the reports were inconsistent. I do not think that all the conclusions can be drawn that the hon. Lady suggested, but I shall reflect on her arguments.
Advertising has nothing to do with the Committee on Safety of Medicines, it being the joint responsibility of the Department and the industry. At no time did the Department receive any complaint about the advertising of Opren. There is some wisdom in considering the advertising campaign with hindsight. Complaints were made, and properly so, and were directed to the Association of British Pharmaceutical Industry. Successive Governments have relied on the restraining influence of the voluntary code of practice that is run by the association. Very few cases give rise to concern or to complaints but I am sure that the association is as anxious as the Government to ensure that excesses are not committed, that advertisements are not misleading and that promotion does not go too far.
§ Mr. Clarke
I agree that occasionally one finds excesses in the promotion of drugs. Most hon. Members react on occasions to the heavy over-promotion of drugs. However, one must remember that some of the promotion takes place abroad. Therefore, an Italian company that offers places on a yacht in the Mediterranean is—
§ Mr. Clarke
With my old hat on, I am glad to hear of a boat putting into the Mersey Docks and Harbour Company. It is extremely difficult to control the promotional activities of an Italian company. Nevertheless, advertising can be controlled, but the judgments are not so much about advertising as about taste.
As my hon. Friend the Member for Canterbury said, if an organisation believes that it has a great breakthrough and has got in in advance of other drugs in the same market, it cannot be criticised for spreading information of those advantages widely and trying to bring them to the notice of GPs quickly and dramatically. The ABPI and the voluntary code of conduct attempt to cope with the lack of taste and judgment that is occasionally shown by companies that go too far.
§ Mr. Crouch
In a debate such as this, there is a great deal of interest outside in what my hon. and learned Friend the Minister says. When he mentions an emotive word such as "advertising", will he stress that, whereas it might be thought that drugs can be advertised to the public, it is not possible? That is not allowed. The only advertising is the giving of information to the medical profession.
§ Mr. Clarke
I agree with my hon. Friend. Moreover, active advertising is subject to the law that governs all advertising.
It is also important to remember that advertising and promotion sometimes has news value. Often, the best advertisement that drugs obtain is from reports on television and in newspapers. It is extremely difficult to control that. For example, I am told that one of the episodes of the "Panorama" programme which attacked Opren and its history was followed the next night by another programme that announced a new wonder drug that cures arthritis. Such drugs are vigorously promoted with exotic news stories by the same sections of the media that will all too often rapidly condemn the side effects of the same new drug when that is the story a year or two later.
§ Mr. Pavitt
At the moment, 6 million journals are sent out annually to pharmacists. The British Medical Association's complaint has been that advertising tends to be more and more commercial and less and less to do with information. Will the Minister consider strengthening the monitoring code of practice? Will he consult the Association of British Pharmaceutical Industry in banning the use of the words "new", "unique" and "wonder drug" from promotional material?
§ Mr. Clarke
The House should accept that the ABPI is as anxious as the Government and the House to act against legitimate complaints. It must also be borne in mind that the advertising is aimed at doctors, who are a comparatively sophisticated audience. An advertisement's straightforward description of a product as a wonder drug might not cut much ice with a GP. "Wonder drug" is typical of the type of phrase that is used in newspaper reports to describe the latest research work that has been found in the United States.
Moreover, doctors are sophisticated customers. A doctor's main concern, irrespective of whether he has been taken on the Orient express to Venice, is to find the right drug for his patient. Few doctors—I hope none—knowingly prescribe an inferior product. The doctor who chooses to prescribe a highly promoted drug rather than an equally efficacious alternative is still looking after his patients' best interests. If he had no faith in the product, he would not prescribe it.
§ Mrs. Dunwoody
The Minister is not a naive man—he is not even a simple one. He knows that the central purpose of all the nonsense that is sent out to doctors is to drive home the trade name. It is intended to drive home a name that is picked because it is simple. The material is intended to drum in awareness of a product that would otherwise have a long Latin name. The Minister knows the purpose of the publicity. It is to ensure that when a doctor writes a prescription, he writes in the word that is quick, simple and easy to remember. That has nothing to do with his estimation of how useful the drug is.
§ Mr. Clarke
I accept the hon. Lady's description of part of the purpose of advertising. Nevertheless, the fact remains that, for example, a consultant rheumatologist will prescribe a drug that he believes is most efficacious for this patient. He will not be swept away by the type of promotion that might lead a less educated person to use a domestic product.
1121 The ABPI deals with complaints and is as anxious as we are to ensure that the lapses in taste which occasionally occur are checked so far as possible.
Clinical trials that are conducted by GPs have also been attacked. It has been suggested that some of those clinical trials—not the ones that are conducted by the CSM—have no meaningful element of research or fact finding and amount to no more than blatant advertising. We have given ministerial undertakings to put those trials on a respectable basis through a code of practice that is administered by the industry. Several drafts have been prepared by the ABPI in consultation with the BMA and the Royal College of General Practitioners. The Department has made many suggestions and amendments to those drafts and general agreement has now been obtained on most points.
The code of practice will contain provision for approval of an independent and properly constituted ethical committee. Arrangements will be set out for medical approval of the trial protocol and will deal with patient selection and patient consent. My Department still has to clear up with the medical and pharmaceutical professions some aspects of the supply of medicines to patients for the purpose of the trials and remuneration to doctors for their administrative tasks. I give that as an illustration of an area that has come under considerable question recently, where we are acting together with the two professions and the ABPI to draw up a sensible code of practice to stop excesses.
I hope that everyone concerned—the industry, the Committee on Safety of Medicines and the medical profession—will accept that there are some valuable lessons to be learned from the Opren tragedy. As I have explained, I do not believe that in the real world we can ever be certain of avoiding such problems. It is inevitable that, unfortunately, whatever improvements we effect in 1122 our system, there will be other problems in years to come. It is almost certain that there will be another such incident sooner or later.
However, with the help of the Committee on Safety of Medicines and other advisory bodies, we can minimise the chances of such an incident occurring once more. That is the tragic, but comparatively small, price we pay for products that are improving the quality of life, as my hon. Friend the Member for Canterbury said. When one looks objectively at the advantages and disadvantages of the development of new drugs, one realises that it is a price that we must be prepared to pay for the greater benefit of all. Otherwise, the great improvements in the quality of life that many drug products bring would not be enjoyed either at all or as quickly as they are.
For example, the alternative course would be to refuse to license new drugs in this country. If anyone demands 100 per cent. certainty, the only way to do so is to refuse to license new drugs until they have been used on hundreds of thousands of patients in other advanced countries. That would achieve greater safety, but British people would be deprived of the value of those drugs for many years, with the consequential toll of misery and possibly deaths from the disease and conditions that remained untreated.
Our policy is based on confidence in the expertise of the Committee on Safety of Medicines and the controls imposed by the licensing system, plus a constant effort to improve it and to learn from experience. Most of those who are experienced and who practise in this field, particularly the vast majority of the medical profession and its well-informed patients, will agree with the policy that we follow and the balance that is struck in trying to achieve the highest safety for new drugs when they are introduced.
§ Mr. Ashley
I warmly welcome the working party that is looking into improvements and the change in attitudes to clinical trials for the elderly. However, sufficient resources are still not being allocated to drug safety. I shall continue to press the Minister on that in future.