Orders of the Day — Drugs (Adverse Effects)

– in the House of Commons at 12:00 am on 16th March 1977.

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

1.24 a.m.

Photo of Mr Sydney Tierney Mr Sydney Tierney , Birmingham, Yardley

My subject for this Adjournment is the reporting of the adverse side effects of drugs. While the Department of Health and Social Security has overall responsibility for the reporting of adverse reactions, the Committee on the Safety of Medicines—a Government agency—advises the Minister on the safety, the quality and the efficacy of individual drug products for human use. The committee is also responsible for collecting and investigating reports of adverse reactions to drugs already on the market.

The pharmaceutical industry is bound by law to report adverse reactions. A scheme of voluntary reporting by doctors on a yellow card reporting system operates at present. Doctors are asked to record suspected adverse reactions on a yellow card and forward them to the Committee on the Safety of Medicines.

Since the system was established in 1964, it has been recognised increasingly that under-reporting is a major defect, and this is causing concern. For more than 10 years the Committee on the Safety of Medicines has been examining ways of supplementing the yellow card system because that system was not picking up the warning signs early enough.

There is little doubt that the Eraldin tragedy has revealed the serious underlying defects in the reporting system and brought a renewed urgency into the search for an effective system. It is important to strike the correct balance between failing to warn early enough and warning too early, and thus frightening people off. A difficult act of judgment is required in a delicately balanced situation, and everyone agrees that any scheme depends on the willingness and efficiency of doctors who must operate it.

The major problem is to find a scheme which will command the co-operation of the doctors, because their co-operation is vital. The present system does not command their support, and the very serious defects of that are apparent. The annual report of 1975 of the Medicines Commission, in an apparent rap over the knuckles for GPs, said that the fact that Eraldin induced eye damage first came to light as a result of a letter in the Medical Journal. The report went on: Prior to this, only one adverse report had been received by the Committee over a period of nearly three years. Subsequent to the publication more than 200 cases of eye damage were reported retrospectively. This illustrates the great importance of reporting early suspicions. Later, reports of skin rashes, deafness and sclersing peritonitis, a serious stomach complaint, appeared, and in 1975 it was established that there were a number of serious adverse reactions from Eraldin. The drug was withdrawn in July, 1975, and 12 months later the committee sent out a directive reminding doctors that Eraldin was restricted to certain hospitalised patients only. In the directive the committee said it could not be sure that the restrictions were being observed, and it told the doctors again that the drug had been withdrawn.

There was a good cause for such uncertainty. The drug was withdrawn, as I have said, in July, 1975, and in July last year—a year after withdrawal—I received a letter from an Eraldin sufferer in Birmingham who was still taking the drug, 12 months after it was banned. His prescription was renewed without his seeing the doctor. He discovered the facts from his chemist who queried whether he should be taking the drug.

In June the chemists's stocks ran out, and he told this man he would have to get a new prescription. It seems that chemists will continue to prescribe until their stocks run out, even though the drug has been withdrawn. It also seems to us that there are chemists who will not inform a doctor who is making a mistake with his prescription.

The patient, as suggested by the chemist, duly informed his local medical centre in June 1976 about the ban on the drug. I raised this case in the House on 6th August last year. On 11th August, five days later, he received a further prescription for Eraldin—I have a copy of the prescription dated 11th August 1976. It was said in the debate on 6th August that an inquiry would be made into the case. Up to now the individual concerned has received no help or advice from anyone.

Only a couple of hours ago my hon. Friend the Member for Rochester and Chatham (Mr. Bean), who has constituents suffering from adverse reactions, asked me if Eraldin had been withdrawn. I told him that it was banned from general use in July 1975. He informed me that he believes that one of his constituents received a prescription for the drug only last week, and if that turns out to be correct, it constitutes a most serious situation.

We have seen that there are serious defects in the communication system operated as well as in the reporting of adverse reactions. As Dr. William Inman, a principal medical officer at the Committee on Safety of Medicines' headquarters, pointed out at a conference in April 1976, even when adverse reactions are suspected, under-reporting can still occur, and he listed what he called the "seven deadly sins" of doctors in respect of reporting adverse side effects.

Dr. Inman listed them as follows: first, complacency, the mistaken belief that only safe drugs are marketed; second, fear of litigation; third, the guilt about damage to patients; fourth, the ambition of certain doctors to publish a personal series of cases; five, ignorance about what should be reported; six, diffidence about reporting mere suspicions; seven, plain old-fashioned lethargy. One can well understand the human dilemma of doctors in some of these circumstances, if not all, but ways must be sought to establish their fullest co-operation to make any agreed system work in a more efficient manner, which is of paramount importance.

As I have said, there is little doubt that the Eraldin experience introduced a sense of urgency and deep concern to the situation. I was informed by the Minister of State in November last year that the Committee on Safety of Medicines had agreed to set up a research panel of experts to study the basic mechanism of the Eraldin syndrome. It is known that the Medicines Commission is considering issues raised by the Eraldin experience, and it is intended that some recommendations to improve the situation will be forthcoming in 1978.

I welcome the setting up of a select panel if it means that the medical profession is to put its house in order, but it seems to me that it is in a unique position if it can have an investigation of its own shortcomings and act as judge and jury within the situation. The patients, the members of the public who use the drug and consequently are dangerously exposed to adverse reactions, must be very much involved.

Who is going to consult them? Who is ready to receive representations on behalf of Eraldin sufferers? Who is ready to draw upon the valuable information gained from hundreds of reported cases compiled by action groups, solicitors and hon. Members? Surely it would be criminal folly to ignore such a source of evidence and information in attempting to deal with the problem.

I refer again to Dr. Inman. He confirms our own findings that even when adverse reactions are suspected they are still not reported. There are hundreds of cases that have never been reported. They are being found with the help of the Press, and I pay tribute to the Press in Birmingham, which has helped us in our campaign. These people have been found with the help of those outside the medical profession. The West Midlands-based action group, of which I am the chairman, has received over 800 letters from Eraldin sufferers, most of whom have been altered by radio or Press reports, not by the medical profession. This has occurred in different parts of the country. In fact, sufferers have reported their own side effects to people outside the medical profession—that is to Members of Parliament and other individuals who are involved in the campaign.

There must be doctors who have treated patients with Eraldin and are now treating them for some adverse reaction, with the patients remaining unaware of the cause of the side effect. If my hon. Friend agrees with us that these individuals have a right to be informed he should take what action is available to him to get the fullest co-operation from the medical profession to establish the total number of people who are involved with the Eraldin problem.

I have the greatest respect for the public confidence which exists between the medical profession, the drug manufacturers and patients. The quickest way to destroy that confidence is to appear to be lethargic about establishing the truth of the Eraldin tragedy. Pressure is growing all the time. Many eminent people in the medical profession are raising the question of the extent of adverse reaction to drugs.

The Committee of Professors of Clinical Pharmacology and Therapeutics, in evidence to the Royal Commission, said that the evidence of adverse reactions in drugs is unacceptably high. The manufacturer of the drug—ICI—-is still unsure and is still trying to discover the extent of the adverse action to the drug. For some months ICI has stated that 800 people have made claims upon its compensation fund, and that 200 cases have been settled. Last week, at the company's annual meeting, the head of research, Dr. Alfred Spinks, was reported as saying that there were now 1,000 claims, with 300 settlements, and that this could now cost the company up to £9 million in compensation payments.

Undoubtedly the company has accepted that the numbers are higher than its original estimates. I can inform the company that in the past three weeks, after some limited publicity, we have received 200 letters. I receive such letters every day. I received six today. In any area where publicity is given to the effects of Eraldin we get a spurt of correspondence from individuals who, until they read about it in the Press or heard about it on the radio, had no idea that they were affected.

I can put it to ICI that the figure of 1,000 claims will soon be passed because our campaign is succeeding. What ICI and all the other authorities involved must accept, and this includes the Department especially, is that the numbers will continue to grow for a long time yet and that the full seriousness of the Eraldin tragedy will have to be faced sooner or later.

If proper representation for Eraldin adverse reaction sufferers is to be made, if patients generally are to be involved as the people who are dangerously exposed, if the valuable information gained from hundreds of reported cases compiled by the West Midlands action group and others is to be used, if the special knowledge gained by solicitors and by hon. Members in dealing with constituents is to be taken advantage of, if we are to find hundreds of cases which have never yet been reported, and we feel that there are still some few hundred people who are suffering from side effects and are unaware of it, if we are to determine to what extent the drug is still being used and whether it has been completely withdrawn from all stocks, there must be a full and independent inquiry. That is the only way to deal with the matter.

The fullest opportunity can be given for patients and others outside the medical profession to make valid and useful contributions. There is a great need for public participation. In an age when we are always talking about democratic participation in industry and elsewhere, there is need for public participation in the operations and activities of the medical profession, particularly in the realm of drugs. That is the only way to ensure justice and fair treatment for all and to ensure the public confidence is maintained.

Those of us who are involved in this campaign have no wish to vilify anyone, because we understand the delicacy of this most difficult situation. All that we wish to do is to see that the facts are fully faced and the lessons are learned. I appeal to my hon. Friend to set up a fuller and wider inquiry to ensure that the grave problem of reporting drug adverse reactions is more adequately dealt with—and quickly.

1.42 a.m.

Photo of Mr Eric Deakins Mr Eric Deakins , Waltham Forest Walthamstow

I am most grateful to my hon. Friend the Member for Birmingham, Yardley (Mr. Tierney) for raising this important subject this evening. The safety of medicines affects us all and there is increasing recognition that effective modern medicines carry risks which may be serious in a proportion of patients. This has, I know, led to concern amongst hon. Members and in the country at large about the safety of drugs and about the detecting of adverse side effects to drugs. I hope that I can do something this evening to allay this proper concern.

I cannot in the short time available to me in this debate give a full account of the highly devoloped arrangements we have in the United Kingdom for the control of medicines, but I hope to be able to explain to the satisfaction of the House a vital part of those arrangements—the system for detecting and dealing with adverse reactions to medicines. I can assure my hon. Friend that all concerned—Ministers, their expert advisers, the medical, dental and pharmaceutical professions and the pharmaceutical industry—are anxious to do everything possible to improve that system. In this connection, I shall draw to the attention of the recently-established panel of experts the detailed points made by my hon. Friend. There is no doubt that we must have the best possible system for the effective monitoring of serious or unexpected reactions to medicines if we are to ensure that the risks inherent in modern medicines are reduced to the minimum.

The legislative background to the system for detecting adverse reactions to medicines is provided by the Medicines Act 1968, a comprehensive measure under which the Committee on Safety of Medicines, mentioned by my hon. Friend, advises Ministers on the safety, quality and efficacy of medicinal products. Control of medicines is exercised in three main stages: first, before a drug is tested in man; secondly before it is licensed for marketing; and finally through continuous surveillance once it is on the market. A drug which showed unacceptable levels of toxicity in animals or in human clinical trials would not be given a licence.

None the less it cannot be emphasised too strongly that, however effective this control is, there will always be times when adverse reactions to a drug become apparent only after it is in widespread use. The committee therefore has a statutory duty to promote the collection and investigation of information relating to adverse reactions and advises on the most effective post-marketing surveillance possible. At present the surveillance system relies largely on the spontaneous, voluntary and confidential reporting by doctors and dentists of suspected adverse events which are then recorded in a register of adverse reactions established by the committee. Additional data may come from companies marketing a medicinal product, which are bound by law to maintain records of any harmful side effects which come to their attention. Other sources include the Registrar-General, coroners, the World Health Organisation, other drug regulatory authorities, and articles in the professional journals. The committee itself undertakes a number of epidemiological monitoring programmes to supplement the reports it receives.

As I have already indicated, the purpost of the post-marketing surveillance system is to collect and evaluate reports of suspected adverse reactions: it is not designed to establish the precise incidence of reactions. It is often referred to as the yellow card system, as all doctors and dentists in the country are provided with yellow cards on which to make confidential reports of suspected reactions. These account for 75 per cent. of the reports received. A full-time medical staff at the Department's headquarters and 80 part-time doctors throughout the country are employed to investigate the individual reports and to help evaluate whether reported events were due to a particular drug, to the underlying condition being treated or to some other cause. Feedback is important. Every doctor reporting or inquiring about a suspected adverse reaction is given information about the drug in question and related drugs.

Once an association between a medicinal product and a serious adverse event has been established, its gravity and the usefulness of the drug will determine the course of action taken. The manufacturer may be required to modify the product literature or the committee may give warning of the possible hazard, either in one of its leaflets entitled "Current Problems" or in a specific letter to doctors. In more serious cases, the committee may issue an emergency warning leaflet or advise that the drug be removed from the market. In addition, the committee publishes the findings from its studies in the scientific journals.

We can, I think, fairly be proud of the system, which has an international reputation. It has been the model for many other countries and has been a major contributor to the WHO system. Some hon. Members may have seen the letter in The Lancet of 5th February from the German Physicians Centre pointing out that the German approach closely follows ours and suggesting that the system of the Committee on Safety of Medicines ranks first among national centres both in number of reports and quality of evaluation. It also made the valid point that no such administrative measure can be effective unless the doctors concerned are alert to and report possible unexpected events and effects.

An illustration of the operation of the system can perhaps be found in the reporting of suspected reactions to oral contraceptives. Through the reports made to the committee it was possible to establish that increased risk of thromboembolic disease was related to the level of oestrogen content of "the pill" rather than to differences in chemical composition. That finding was made on the basis of what was clearly only a proportion of possible reports but it enabled appropriate advice to be given to the professions, which resulted in a major change in prescribing practice.

A further example of the operation of the system can be seen in the history of the drug practolol. The case of this drug is one that has caused disquiet, not least to my hon. Friend. As he knows from his intensive study of the circumstances, practolol had undergone stringent testing before being marketed for heart disease in 1970. Four years later, after widespread clinical use, it was associated with a number of serious side effects, affecting the eyes, ears, skin and internal organs. Many of the individual symptoms associated with it occur spontaneously. Once the attention of doctors had been drawn to the association extensive and prompt reporting to the committee followed. Many reports concerned symptoms which doctors had seen earlier but had not recognised as being causally linked with practolol. The yellow card reporting system proved invaluable in demonstrating the gravity of the unforeseen and unpredictable practolol syndrome, and contributed significantly to the appropriate action which was taken on it.

A disturbing feature of the practolol case, however, was the time which elapsed before reports of suspected reactions were made to the committee; and it is widely believed that the main weakness of the system lies in a considerable degree of under reporting. That is not because the scheme does not command the support of doctors. There are a number of reasons why doctors do not always send in possible reports. It is often difficult to recognise an association between a suspicious event and a particular medicine, since the symptoms could well have been spontaneous or the patient may have been taking more than one drug. Commonly, individual doctors see only isolated cases and so may not relate the reaction to a drug they do not prescribe widely. In some instances doctors do not make a report because they regard a reaction as being sufficiently well known or they may fear that a useful drug's reputation would be damaged unjustifiably.

Then, too, we must accept that doctors are busy men, and dealing with patients may take precedence over sending in a report. These features do not negate the value of the system. As I have said, its purpose is not to establish incidence, but to provide a pattern of reactions which may be significant in enabling the committee to give an early warning hazard. Nevertheless, doctors are urged to report all cases of suspected reactions and not to wait until a link has been established. I am sure the committee would agree that doctors must be suspicious. They must expect the unexpected.

Ever since the Committee on Safety of Drugs—the predecessor of the Committee on Safety of Medicines—was established in 1963, attempts have been made to improve the operation of the system. Successive Ministers and chairmen of the committees have stressed the importance of close liaison between the medical and dental professions and the committees. Recent steps to promote collaboration include the introduction of a new series of leaflets, "Current Problems", to which I referred earlier, designed to draw attention to problems which do not warrant the issue of an emergency warning leaflet. A revised version of the yellow card has been sent to all doctors twice in the last year and a reminder of the need to report has been included in the prescription pads. Products have been marked as "Recently Introduced" in the Monthly Index of Medical Specialities and this also drew doctors' attention to the need to report to the committee all details of suspected adverse events. A similar reminder is included in the Data Sheet Compendium issued by the Association of the British Pharmaceutical Industry.

In December 1976, the vice-chairman of the committee, Sir Theo Crawford, wrote to all doctors to say that while the committee did not consider there was immediate cause for concern, it wished to stress the importance of reporting all suspected adverse events occurring to patients treated with beta adrenoceptor blocking agents. It is notable that as a result of all these measures there has been a marked rise in the number of reports, particularly in the last quarter of 1976.

While we recognise the value of the present arrangements, I should like to assure the House and my hon. Friend that neither the Department nor its expert advisory bodies are complacent about what is being achieved through the yellow cards. The reporting system is under continuous review and the committee is at present considering ways of supplementing it. For example, certain new drugs might be placed on a special list which would ensure that doctors could prescribe them only if they were prepared to submit records on their use. Other proposals for improved monitoring have been put forward by interested bodies such as the Association of the British Pharmaceutical Industry and the Committee of Professors of Clinical Pharmacology and Therapeutics. These will all be taken into account by the Committee on Safety of Medicines in reaching its conclusions. Practicable conclusions must, of course, have regard to financial constraints, and need to be discussed with the professions and other interested parties, and possibly tested in pilot studies, before they can be adopted. It should not be thought that patients are unnecessarily exposed to risk while these possible measures are considered. Every new drug is individually considered by the committee and where appropriate the committee advises marketing under restricted conditions.

In conclusion, I must remind my hon. Friend that it is not easy to recognise drug reactions, or to establish, without very costly studies, what is the precise incidence of an adverse reaction. Society must accept that in the present state of knowledge powerful drugs may occasionally produce adverse reactions, and it is for doctors to weigh the possible risks against the anticipated benefit from treatment. Some hazardous drugs are lifesaving and their total removal from the market may not be in the best interests of certain patients. Nor must controls be so tight as to prevent innovation in medicine. The essential requirement is to ensure that the measures we take to detect, and warn the profession about, possible hazards are speedy and effective.

In the first place, we must rely on doctors and dentists to report events related or possibly related to medicines; and I urge them to be vigilant and active in this. Without the constant vigilance of the professions and their active participation in the reporting system—in short, without the vital data—the committee cannot give its advice. Given the help of the professions, the committee will, I am sure, continue to fulfil its role in this vital system for monitoring medicines.

Question put and agreed to.

Adjourned accordingly at seven minutes to Two o'clock.