§ 64. Dr. D. Johnson
asked the Minister of Health whether he is aware that 18 months elapsed between the first reports of the deleterious effects of the drug thalidomide appearing in the medical press and its eventual establishment as a highly dangerous drug and consequent withdrawal from the market; and what progress he is making towards the establishment of a form of surveillance over new drugs to ensure that there is no repetition of avoidable incidents such as have been associated with this compound.
§ 3 Mr. Powell
I am informed that thalidomide was withdrawn by the manufacturers within a week of their being advised from abroad of possible teratogenic effects. I am circulating in the OFFICIAL REPORT interim advice which has just been received from the Joint Sub-Committee of the Standing Medical Advisory Committees for England and Wales and for Scotland. My right hon. Friend the Secretary of State for Scotland and I accept the first two recommendations and await the further advice to follow on the third.
Following is the Report:
STANDING MEDICAL ADVISORY COMMITTEES
(England and Wales and Scotland)
Joint Sub-Committee on Safety of Drugs Interim advice to Ministers1. The Minister of Health announced in the House of Commons on 23rd July, 1962, that he was proposing to seek advice through his Standing Medical Advisory Committee on the question of the testing of new drugs generally.2. Since this was a matter which concerned the Standing Medical Advisory Committees for both England and Wales and Scotland it was 52W decided to appoint a Joint Sub-Committee of both Advisory Committees with the following membership:—
- Lord Cohen of Birkenhead, J.P., M.D., D.Sc., LL.D., F.R.C.P. (Chairman),
- Professor S. Alstead, C.B.E., M.D., F.R.C.P., F.R.F.P.S.,
- A. B. Davies, Esq., B.Sc., M.B., Ch.B., M.R.C.S., L.R.C.P.,
- Professor Sir Charles Dodds, M.V.O., M.D., D.Sc., F.R.C.P., F.R.S.,
- J. B. Grosset, Esq., M.P.S., D.B.A.,
- Sir Hugh Linstead, 0.B.E., LL.D., F.P.S., M.P.,
- Professor E. J. Wayne, M.D., F.R.C.P., F.R.F.P.S.,
- Professor G. M. Wilson, M.D., F.R.C.P.3. The Joint Sub-Committee was set up in August, 1962, "to advise the Minister of Health and the Secretary of State for Scotland on what measures are needed:—
- (i) to secure adequate pharmacological and safety testing and clinical trials of new drugs before their release for general use;
- (ii) to secure early detection of adverse effects arising after their release for general use; and
- (iii) to keep doctors informed of the experience of such drugs in clinical practice."4. The Joint Sub-Committee have been considering the present arrangements for testing new drugs for toxicity before they are used in clinical trials. They have had an opportunity of exchanging views with the Medical Research Council's Committee on the methods of testing for toxicity, and have also had some preliminary discussions, which will be continued, with representatives of the industry.
Recommendation5. At present the responsibility for the experimental laboratory testing of new drugs before they are used in clinical trials rests upon the individual pharmaceutical manufacturer and the Sub-Committee advise that it should so remain, for the industry, as a whole, discharges this responsibility effectively within the limits of contemporary knowledge of methods of testing. This knowledge however is being constantly extended by research and we understand it is the intention of the Medical Research Council to give advice and guidance on this subject from time to time.
Recommendation6. The Sub-Committee have carefully considered but firmly rejected as neither desirable nor practicable the suggestion that at this stage of their evaluation the responsibility for testing drugs should be transferred to a central authority.7. Before recording their third recommendation the Sub-Committee wish to make it clear that, although laboratory tests may reveal toxic effects which would in no circumstances justify proceeding to clinical trial, in considering the question of the "safety" of a drug used in the treatment of disease, laboratory testing of the drug is not the only consideration.
- (i) A drug may show no toxic effects in laboratory animals, however complete the
53 experimental testing, and yet in some persons (a) prove toxic e.g. chloramphenicol after short-term use; (b) show adverse reactions when used over longer periods, e.g. thalidomide and peripheral neuropathy, or in special circumstances, e g. thalidomide and pregnancy.
- (ii) A drug may prove toxic for some species of experimental animal, e.g. pencillin for guinea-pigs, and yet prove of inestimable value in the treatment of disease.
- (iii) Every drug however innocuous to the vast majority of persons, may give adverse reactions in the few when administered in therapeutic doses, e g. aspirin which can cause gastric haemorrhage or, very rarely, an asthmatic attack. The frequency of such adverse reactions is one of the factors to be considered in assessing the therapeutic worth of a drug.
- (iv) Drugs which carry a recognised hazard in therapeutic doses may yet be justifiably used in the treatment of disease. But the risk must he related to the benefit which the drug may confer, e.g. whereas a high incidence of adverse reactions can be tolerated if a drug may cure or stay the progress of a grave disease such as cancer or leukaemia, no significant toxicity can be allowed in a new hypnotic for which there are many less toxic equivalents.Again, drugs which may give rise to serious adverse reactions may be justly prescribed for a potentially grave illness in which they produce a specific beneficial response, e.g. chloramphenicol in typhoid fever, but should not be given where specific indications for their use are absent.8. The "safety" of a drug must thus be recognised as relative, not absolute. It depends on (i) its toxicity as revealed in laboratory tests and in its clinical use and (ii) the diseases for which it is being used.
Recommendation9. The Sub-Committee believe that one safeguard (though in view of the facts recounted above only one of many safeguards which may be needed) is that there should be an expert body to review the evidence and offer advice on the toxicity of new drugs whether manufactured in Great Britain or abroad before they are used in clinical trials.10. In the light of further considerations and consultations the Sub-Committee hope to formulate detailed advice on the composition and terms of reference of this advisory body.11. The Sub-Committee will continue their consideration of the general problems of drug safety and of the provisions for testing therapeutic efficiency.
COHEN OF BIRKENHEAD (Chairman) (on behalf of the Joint Sub-Committee).E. L. MAYSTON (Secretary).2nd November, 1962.