§ 2.55 p.m.
§ Mr. James Dance (Bromsgrove)
There were two reasons for applying for this debate. The first was to give the clearest and widest warning to mothers-to-be of the great danger to which they might subject themselves and their unborn babies should they take a certain tranquilliser drug thalidomide which is marketed in this country under the name of Distaval. The second reason is more long-term, and it is to find out from my hon. Friend the Parliamentary Secretary whether it will be possible for even more extensive tests to be made on new drugs than are made at present to find out Whether there might be more harmful Side-effects before the drugs are allowed to be put on the market, even if a doctor's prescription is required for their purchase.
I am only a layman on these matters and do not know all the technicalities that are involved, and therefore I shall have to read a certain amount in order to develop my arguments. My attention was drawn to the danger of this drug in the following circumstances. Two of my constituents, husband and wife, wrote to me and asked if I would call to see them, which I did. They then informed me of the following story, which I found quite horrifying.
This lady, before she was to have her baby, was not sleeping very well and had been prescribed this drug by her doctor under the National Health Service. Apparently it was extremely effective, and it gave her very good sleep. She had some of the tablets left over, which she kept in her medicine chest. Then she became pregnant, and for only three nights, I am told, she took one of these pills. When her baby was born, it was so ghastly deformed as to be beyond description. It had only one kidney and the liver was in a terrible state. Since then, it has been proved that this malformation is attributed very largely to Distaval. Here I should like to pay tribute to this lady, for her great 898 courage in bringing this matter forward, in the great anguish of mind which she must feel. As I hope to be able to show, already she has been able to ease the minds of two other ladies, and I hope sincerely that by her courageous action she will help many others in this matter.
As a result of this interview—and, in passing, I should say that this drug was actually withdrawn in November, 1961—I tabled a Parliamentary Question, and my hon. Friend very kindly gave me a very full and explicit answer. As a result of that answer, a lot of publicity came about, not as much as I would have liked, but quite a lot, and again as a result of that publicity I received a number of letters. I am afraid that I shall have to read some of these, because they substantiate my case and prove how little was known and still is known about the dangers of this drug. The first reads as follows:In the Daily Telegraph of 15th May, I read a report of your comments in the House on Monday the 14th instant concerning the effects on unborn children of the drugs thalidomide and Distaval. On 28th January last, my daughter gave birth to her first child who was affected by various limb deformaties. During her pregnancy my daughter was prescribed certain medicines by her doctor, but we do not know, of course, what drugs they contained. There is no family history, on either side, of congenital disability, and my daughter is naturally very anxious for advice as to whether should she have any more children, they would be similarly afflicted.There was doubt in her mind as to what the effect of the drug was.
Another letter I received reads as follows.My heartfelt thanks and gratitude are due to you for your Question in the Commons on Monday. For the first time I released the possible explanation of my baby daughter's heartbreaking congenital abnormalities from which she mercifully died at the age of 2 months. Although I took Distaval for insomnia during most of my pregnancy, this was in no way suspect at the time of her birth, and death last year. I understood from an employee of the manufacturers that Distaval had been withdrawn merely because patients using this drug for long periods had developed slight peripheral neuritis. I still possess a quantity of the tablets and would undoubtedly have used these again for insomnia in any future pregnancy.I do wonder if this matter has received enough publicity. I heard the report by chance in the radio programme 'Yesterday in Parliament', and the only newspaper report which I saw was in the Daily Telegraph which referred to the product as Distabil.899 These cases prove—and remember I did not solicit them, but they came to me as a result of my asking Parliamentary Questions—the grave doubt in the minds of the public about how dangerous these drugs may be.
There have been varying reports about the number of people who have been affected by these drugs. I believe that the generally recognised figures are about 40 for the United Kingdom and about 4,000 for the Continent. I saw a report in a newspaper yesterday suggesting that the figure for Britain is actually much higher, probably about 700. But there may be very many more cases concerning people who do not know the names of the drugs they are taking.
After all, is it not possible that a woman might have a little box of tablets in her medicine chest labelled simply "The tablets. Take one on retiring"? She might not know that the tablets in the bottle are actually Distaval. I am grateful to the Parliamentary Secretary for informing me that the Chief Medical Officer has sent letters to all general practitioners in the Health Service and to medical officers of health and senior medical officers in hospitals drawing attention to the danger about which I am speaking. I hope that they will do their best to bring this danger to the attention of the public and that any doctor who may have prescribed this particular drug, perhaps in years gone by, will check up to see where the tablets are now and will do their best to warn women who are pregnant not to take the drug or there might be dire consequences.
Regarding tests, I have great respect for the pharmaceutical industry, which has spent much time and money on research, and I do not think that we can blame that industry for what has happened. But I would dissociate myself from a remark made in an article in the Birmingham Post yesterday referring to today's debate. The article said:As purveyor of drugs to the National Health Service, the British pharmaceutical industry often has to face thinly-veiled allegations by politicians that it is the chief inheritor pf the Borgias, and that the general public is its victim or, at best, its poison-taster.As I say, I dissociate myself from that sort of remark. It is a first-class in- 900 dustry, well run and with much integrity. The makers of Distaval are a firm of the highest integrity, and I hope that my right hon. Friend will be able to evolve a scheme whereby the testing of these drugs can be intensified. I realise that much is being done but in the letter from one of my constituents, part of which I read earlier, it is also stated:It appears that there are about 250 drug houses in this country and whilst some of them (the majority I hope!) are very jealous of their good reputations"—Indeed they are—many are so small as to have neither the capital nor the facilities to perform the extensive clinical tests.The letter was written, apparently, as the result of a television broadcast my constituent saw from which she quotes a certain doctor as having said:… anyone who wants to is at liberty to put a drug on the market and can keep it there until there is some trouble.That is a terrifying thought. I hope it is not the case, although it is rather borne out by an article in today's Daily Mail which states—University professors Alistair MacGregor, of Aberdeen, and Walter Perry, of Edinburgh, claim in The Lancet that doctors have too little information about new drugs; only three out of every 20 products advertised in a commercial index in 1961 had been adequately tried, they say. The two professors stress that they do not want a change in the law to control drugs: this might generate a false confidence. They want a 'brain centre' to collect and disseminate information about new drugs so that their effects and side-effects can be measured.I hope that my hon. Friend will give that matter consideration and be able to put my unfortunate constituent at ease, because she was upset at the rather alarming statement by a doctor on television. Followed by what I have just read from the Daily Mail, it is rather disquieting. I hope we may have some further assurance on that point.
There has been a suggestion that there might be some form of central committee to investigate these drugs. Having spoken to manufacturers, I gather—I think that my hon. Friend will agree—that there are very grave complications in this. I did a television broadcast on this subject in Birmingham last night and had with me the director of one of the big pharmaceutical manufacturers. We had an interesting talk. The director was most sympathetic. He was horrified 901 about what had been done, but he said that testing was very difficult. All the same, I wonder whether something more cannot be done on these lines. Something on the lines of a central committee was set up in France and the United States, but I do not think it proved very satisfactory. I am informed that France, despite this, has accepted Distaval as a drug. So that idea is not foolproof.
We must think again and find something new. We cannot allow all these new drugs to go on the market when they may have potentially very dangerous side-effects. Quite recently eight drugs have, for varying reasons, been withdrawn. These reasons are not necessarily always dangerous side-effects, but, having spoken to a chemist, I know that two of them had very dangerous side-effects.
I thank my hon. Friend for all the help she has given me in this campaign. I want the widest publicity possible given for this, whatever media are used, and I hope that our good friends in the Press Gallery will help. This is such a terribly serious matter. As I said earlier, I believe there are many women who may have this drug in their medicine chest. It is perfectly adequate, perfectly good and perfectly safe when they are not going to have a baby, but the moment they become pregnant it becomes the most absolute killer with the most ghastly effects. I hope we shall be able to do something to ensure that further tragedies do not occur.
§ 3.8 p.m.
§ Mr. A. E. Cooper (Ilford, South)
I am sure that we are all very grateful to my hon. Friend the Member for Bromsgrove (Mr. Dance) for raising this vitally important subject. I am sure that the whole industry will be satisfied with his praise of the work that it does. I am sure that he intends no criticism of the industry. Although I am concerned in the chemical industry, I am not in any way associated with the pharmaceutical side of it and, therefore, have no interest to declare.
My hon. Friend quoted a letter which appeared in The Lancet on 9th June signed by Professors Macgregor and Perry, but I am afraid he did not quote the most important part of the letter. 902 In dealing with this subject, the professors say:Nevertheless, in our view no system of control could have prevented the tragic results of the widespread use of thalidomide.";that is, Distaval.
We are, therefore, face to face with the very serious situation that we have here a drug which has certain exceedingly valuable properties but has these dreadful side-effects which the professors themselves say no system of control could check. I would emphasise that both France and America have very close government control of the drug industry. The French authorities—this must be emphasised—have already given this drug complete clearance. They were, obviously, quite satisfied with it. There is also no doubt that the authorities in the United States will give the drug complete clearance.
It is, of course, possible—I do not deny this—that there may be some small firms operating in adverse conditions in some part of the country, but, to be frank, I do not know of any. The pharmaceutical industry is one of the most progressive industries in the country, and the clinical control which is exercised over every new drug developed is something which has to be seen in the industry to be believed. For example, only one in 3,000 of the substances tested eventually survives toxicity and clinical tests and is placed on the market. That should be sufficient to illustrate the tremendous care which is exercised in the industry.
I would also emphasise that the British drug manufacturers are some of the finest firms in their industry in the world. Their reputation and integrity stand second to none. Not only do they do an amazing job for this country, but the drugs produced here and exported run into enormous figures. It does harm to the industry and to its reputation to suggest that an incident like this necessarily throws some shadow over the whole industry.
I do not wish to make a long speech about this, because this is a private Members' day when short speeches are the order of the day, but I want to put on record some of the things which have 903 been achieved by the British drug industry over the years. Instead of throwing bricks at this industry, as some Members have done in both Houses, we ought to pat it on the back once in a while.
For example, there is no doubt that since the discovery of the first sulphonamides in 1935 the industry has been responsible for saving more lives than were ever lost in the Second World War. There has been lower mortality and big economic savings in the treatment of infectious diseases. The death rate from childbirth fever—puerperal sepsis—in mothers is 1 per cent. of that prior to the use of sulphonamides. Child mastoid operations have disappeared. Pneumonia is now effectively treated in the home at a greatly reduced cost. The chances of survival from accidents have been greatly improved. Ophthalmia neonatorum and trachoma, major causes of blindness, are controlled. Venereal disease can be effectively treated and pernicious anaemia, diabetes and poliomyelitis are now controlled. There are many more illnesses in medicine which are today effectively controlled by the use of drugs, in the main developed, researched and produced in this country. It would be difficult to exercise any system of control by a Government authority which in my view could give greater security to the people than that exercised by the industry itself.
§ Mr. Cooper
I am not here to defend the use of tranquillisers or slimming tablets, although, heaven knows, my wife tells me that I could do with some. Surely this is a private user responsibility. The matters which we are discussing are much more fundamental.
§ 3.18 p.m.
§ Dr. J. Dickson Mabon (Greenock)
We are all very much indebted to the hon. Member for Bromsgrove (Mr. Dance) for raising this very important matter. I do not intend to join the hon. Member for Torrington (Mr. P. Browne) in calling for the immediate nationalisa- 904 tion of the drug industry, so that the address which we have just heard from the hon. Member for Ilford, South (Mr. Cooper) in a sense may not have been necessary.
As a practising doctor, I appreciate the great amount of work which the pharmaceutical industry has done, but what the hon. Member for Ilford, South said in its defence went almost to the other extreme. The idea of suggesting that the pharmaceutical industry is completely above criticism in this matter seems to me to be far-fetched. It is poor consolation to this unfortunate woman and to many other cases, not necessarily involving death or congenital abnormality, that this should be said when something goes wrong with a new drug. It seems a little unsatisfactory to be told that the reputation and integrity of these firms is beyond question and that the whole thing is an act of God. That is the question: is it an act of God or can something be done to prevent some, at least, of these tragedies?
I do not accept that because there is a system in France which is not very good, and which permitted this drug to be used, we must have a system like it or none at all. I do not accept that under the United States system, particularly having heard about it, clearance will be given to this drug to circulate in America.
The basic point about this drug is that while splendid and very commendable researches were done, they were confined, in the main, to animals and it is not necessarily true that the pattern of behaviour of the drug on the mouse or the rat, or any other creature sacrificed to the needs of medicine to find out how to treat humans, will always be the same on homo sapiens. This is the great criticism which can be laid against this drug and others about which we know there have been scandals in the past and others which, alarmingly, are still to come and from which people must suffer before this problem is settled satisfactorily.
This is what the hon. Member is trying to do and what this lady is trying to do in bringing it to his attention. She does not wish others to suffer unnecessarily. If this Adjournment debate is at all valuable, it will be in setting in process a train of events which may 905 lead to ensuring that, while we cannot altogether avoid all these unhappy circumstances which arise by human error, nevertheless we shall reduce their number appreciably.
This is the point that Professors MacGregor and Perry were trying to make when they said, as the hon. Member quoted, that no system of control could have prevented this accident. Their comment, I submit, is qualitative and not quantitative. If there had been a system of control better than our present negative system, it is possible that, while some damage would unhappily have been done to some people, it would not have been as extensive as it was. This seems to be an eminently good reason for looking at what the hon. Member said this afternoon. The least that he has asked is that there ought to be, in the words of Professors MacGregor and Perry, some "brain centre" for collecting the facts on the effects and side-effects of new drugs.
It is fair that we should consider the question of side-effects. I remember an occasion some time ago when a new tranquilliser drug came on the market. Incidentally, I do not agree with the hon. Member for Bromsgrove that these are the drugs which we ought not to prescribe, or about which we ought to be suspicious. Tranquilliser drugs are extremely useful. They have revolutionised the treatment of mental health. They are in a sense almost translating into life the Mental Health Act.
§ Mr. Dance
But would not the hon. Gentleman agree that they can be very dangerous? These are the drugs which possibly are taken more frequently than drugs which can cure other diseases. I agree that under close medical supervision in a clinic or hospital it is all right to take these drugs, but I am terrified of these tranquillisers going into teen-agers' medicine chests.
§ Dr. Mabon
I endorse that. I was referring to the side-effects of these drugs. There was an occasion in my own experience when the idea was put forward that a certain tranquilliser should be prescribed for a patient whose occupation was that of driving a bus. It took a long time to go round the hospitals to get the opinions of other physicians about how this tranquilliser 906 influenced a person's judgment and technique when under stress. It seems that this idea of having a centre is very good not only from the point of view of the direct danger of the drugs, but from the point of view of the side-effects of taking them.
Like many others in my profession, I am subjected to having to read continually the recurring submissions of different manufacturers as they come across different drugs or present them in different ways. It is commendable that we should have this information, but unhappily it is not adequate. I find that in many cases the drug has not been sufficiently tried, largely because, as the hon. Gentleman said, some of the firms do not have the necessary capital, or the ability to obtain the clinical facilities to carry out adequate tests. I feel that this is particularly important in relation to drugs which could have fatal effects, and I consider that they should not be issued except under a positive system of licensing.
This is the problem which faces the hon. Lady this afternoon. I do not know what advice she has received, but I am most anxious to hear it. This is not a matter for party arguments, but we in the Labour Party have been so concerned about this that in our health programme "Members One of Another", we made a point about it and have further urged that the Medical Research Council—as happens in some of our Commonwealth countries—should be made responsible for the testing of these drugs. The hon. Lady has no doubt heard this many times, and she will doubtless hear it again, but I think that this suggestion is well worth considering along with those made by her hon. Friends.
I know that the hon. Member for Ilford, South (Mr. Cooper) spoke sincerely and genuinely from his point of view, but I hope that the hon. Lady will not emulate him and say that she is satisfied that all is well in this the best of all possible worlds. We do not want this kind of tragedy to be repeated. We know that even under the best possible system mistakes could occur, but we do want to reduce the number of fatalities and any ill-health that may be caused by the premature provision of these drugs for the general public.
907 There is a system in hospitals whereby reputable pharmaceutical firms which are concerned about the possible effects of a certain drug propose that certain special doctors and professors should use this drug on certain patients of the physicians' own choice, and that the results should be collated by the firm. From these results and papers submitted by the selected medical men, the firm is then able to decide whether to market the drug. This is an eminently sensible way of dealing with this problem, and I am suggesting that a system of positive licensing administered by the Medical Research Council would mean that new drugs would be made available with the approval and knowledge of the Medical Research Council. If this is unacceptable, I am sure that the hon. Gentleman's idea of a centre to collect the facts is a sound one, and I hope that the Ministry will look favourably at this suggestion at least. If not, I suggest that it is incumbent upon the Minister to suggest some other system which is not in practice at the moment, otherwise we shall see these tragedies being repeated again and again, and that would be a great sadness.
§ 3.25 p.m.
§ The Parliamentary Secretary to the Ministry of Health (Miss Edith Pitt)
I am grateful to my hon. Friend the Member for Bromsgrove (Mr. Dance) for choosing this subject for debate. Modest though it is, with three contributions plus my own, this has been a useful debate, entirely in the interests of patients. I welcome the opportunity that the debate gives me to discuss this subject, because I know that there is often confusion in the minds of people, particularly lay people, between tests for toxicity and clinical trials. The two are quite distinct.
Tests for toxicity are to determine whether a drug is potentially dangerous. They are conducted in the laboratories of pharmaceutical firms, usually on small animals such as guinea pigs and rats. If no toxic effects are shown as a result of these tests on animals, the drug is then tested in the treatment of humans, on a limited scale and under very strict medical control. It has to be emphasised, however, Chat these latter tests on human beings are clinical trials to test the therapeutic efficacy of the drug, that is, in the language of lay people, to test 908 the value of the drug in the treatment of disease.
If these tests are also satisfactory, the drug will then be released to the medical profession. This is the third step in the well-defined and graduated progress towards the general use of a drug. It is not for the Minister to judge when adequate trials of the safety of a new drug have taken place. It is the manufacturer's responsibility to decide on the extent of safety testing needed before the introduction of any drug is justified, and it is the doctor's responsibility to decide whether he is sufficiently satisfied about the safety of a new drug to justify his prescribing it for a particular patient.
In general, both the British pharmaceutical industry and the medical profession maintain a high sense of public responsibility in this respect. Doctors obtain information about the therapeutic uses of new and existing drugs through professional journals, the Prescribers' Journal, or manufacturers' literature and representatives. An independent professional committee—the Cohen Committee—classifies all proprietary preparations known to be available for prescribing, on an assessment of therapeutic value based on evidence supplied by the manufacturers. Prescribes' Journal and Cohen Committee recommendations are sent to all doctors in the National Health Service.
It is improbable that any effective therapeutic substance is entirely without side-effects. New drugs, if potent, are by their nature liable to exert also effects other than those which they were intended to produce. But these unexpected and unwanted effects may arise in circumstances which, in the light of current medical and scientific knowledge, could not be detected by means of initial testing on animals or human volunteers. It seems to be generally agreed that the risk of hazard to health in the use of new medicines would be reduced if they were all subjected to the widest possible range of toxicological studies and controlled clinical trials.
This, again, is a point that the hon. Member for Greenock (Dr. Mabon) made. The toxicity testing and clinical trials can never be as complete as ideally may be desired or be entirely foolproof. Carefully conducted clinical trials primarily intended to demonstrate the therapeutic efficacy 909 of a new drug may sometimes fail to reveal some real toxic side-effect. This may emerge only in medical practice, possibly after long use in considerable numbers of patients. Thalidomide, or Distaval as it is known in this country—the drug about which my hon. Friend is particularly concerned and which I know is his main reason for seeking this debate—is an example of what I have just tried to explain.
The toxicity tests were carefully conducted and indicated that the drug was apparently safe. The clinical trials snowed it to be a very effective hypnotic and even more effective in some respects than other drugs used for the same clinical purpose. Thalidomide was in clinical use in Germany before it was made available to general practitioners in this country in 1958. It was developed by German scientists, and in this country by the Distillers Company (Bio-chemicals) Ltd., whose research and development teams consist of first-class scientists. The initial animal experimental work designed to elucidate its toxicity seems to have been done meticulously and the preliminary clinical trials of its therapeutic efficacy were carried out by doctors wholly independent of the pharmaceutical firm.
§ Dr. Dickson Mabon
I wonder whether the hon. Lady could tell us how many of the patients involved in the preliminary clinical trials were pregnant.
§ Miss Pitt
No. I am sorry, but I have no figures of patients involved in the clinical trials, and the risk to pregnant women appeared much later, as I have been indicating. In fact, it was only in November, 1961 that reports came from West Germany suggesting an association between this drug and congenital abnormalities. Later similar reports came in from other parts of the Continent. Although up till then there had been no reports of similiar experience of cases arising in Great Britain, the manufacturers in this country decided to withdraw the drug, and they withdrew it, as my hon. Friend said, early in December, 1961.
My hon. Friend asked a Question in the House about this drug on 14th May, and I then stated that the Ministry was taking steps to warn women of the dangers of taking hypnotics in circumstances for which they had not been 910 prescribed. Then, as I promised, a warning was issued through the Press with special reference to thalidomide.
On 17th May the Chief Medical Officer of my Department wrote to all general practitioners and to the medical officers of health of local health and other local authorities and to senior hospital officers asking them to warn women patients of child-bearing age who might have a stock of thalidomide prescribed before its withdrawal not to take it in any circumstances.
Here, perhaps, I may make one seeming domestic point but I feel it is important, and this again is an opportunity for me to repeat the regular general advice of my Department to patients, of which our action on Distaval was only an example, that they should not hoard unused stocks of medicines prescribed for a particular purpose but should throw them away as soon as they have recovered from the illness for which they were prescribed. This, perhaps, sounds wasteful, but I am sure that it is wise.
My hon. Friend and, indeed, all three Members who have spoken referred to this morning's comment in the Daily Mail which arose out of a letter to the editor of The Lancet, which I have read, from two Scottish professors. Some part of what I would have said has been said for me by the quotation made by my hon. Friend the Member for Ilford, South (Mr. Cooper), but perhaps I may add one other point. It is true that this letter is critical of the present machinery for the control of drugs, but at one point the writers say:Tragedies will no doubt continue to occur with new remedies, and this is part of the price to be paid for therapeutic progress, because we cannot, as a community, ask for new drugs without being prepared to accept such risks. We cannot legislate ourselves out of this dilemma.To continue with the general question, I would add that the law relating to the control of medicines is at present being examined in the Departments concerned.
New legislation would be needed to require the safety testing or scrutiny of all new drugs, apart from substances to which Part I of the Therapeutic Substances Act, 1956, applies, before they were introduced. I cannot develop this point at length or you, Mr. Deputy Speaker, would rule me out of order in an Adjournment debate. But even if 911 the Minister were to take powers to establish a new central body with a view to controlling the introduction of all new drugs, it would not be possible to guarantee that every new drug was absolutely safe.
§ Dr. Dickson Mabon indicated assent.
§ Miss Pitt
In the case of thalidomide, it has now been shown experimentally that it will produce deformities in the offspring of one animal species, other than humans, namely, rabbits. Therefore, it might be practicable in future for manufacturers, by devising appropriate testing procedures based on this observation, to detect the possibility of this particularly distressing side-effect in any new substances in this group which may be developed for therapeutic purposes. Perhaps I might interpolate, so that everyone may be quite clear about it, that Distaval is no longer available. But the comment I have just made does refer to substances in the group.
§ Miss Pitt
I shall confirm that point and I shall need to take medical advice to do so. The drug has been withdrawn by the manufacturers and the doctors have been told not to prescribe it. I cannot believe that it is available except in the circumstances of someone still having it on the shelf in the medicine cabinet, about which risk we have all been trying to give publicity.
Quite apart from the humanitarian aspect, it is in a firm's own interest to do all that it can by means of experimental toxicity testing to minimise the risk of side-effects in its products.
In the case of thalidomide the emergence of these distressing side-effects is a matter of deep concern on which the Minister is keeping a close watch. I am sure that it is generally accepted, how- 912 ever, that the choice of drugs is a professional matter which should rest with the doctors and not with the administration.
To keep this matter in proportion, let me end by saying that the development of new drugs has made an inestimable contribution to the nation's health within recent years.