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Drug Regulation

LICENSING AND PROVISION OF MEDICINES INTHE UNITED KINGDOM

An Appraisal

JOE COLLIER

Department of Pharmacology and Clinical Pharmacology,St George’s Hospital Medical Schovl, London SW17 ORE

THREE statutory mechanisms control the provision ofdrugs in the United Kingdom. The bulk of the legislation iscontained in the Medicines Act (1968), which deals with thesafety, quality, and efficacy of medicinal products (drugs). Bya system of licensing, the Act controls the manufacture,marketing (sales, supply), importation, and distribution of"legitimate" drugs. The regulations are administered by theMedicines Division of the Department of Health and SocialSecurity (DHSS) for, and on behalf of, the Health Ministers*(the Licensing Authority). The second statute is thatconcerned with the illicit manufacture, supply, or possessionof drugs as they are used for "abuse". This aspect of drugusage is controlled under the Misuse of Drugs Act (1971)which is administered by the Home Office. The third statute(The NHS (General Medical and Pharmaceutical Services)Amendment [no 3] Regulation 1985) concerns the selectionof drugs for the NHS "limited list"; it allows Ministers ofHealth to restrict the number of licensed drugs in eightselected therapeutic categories which doctors can prescribeunder the NHS. The provisions of this Act are administeredby the Family Practitioner Section of the DHSS, whosenewly formed Advisory Committee on NHS Drugs (ACD)advises the Health Ministers.This article reviews the control of the provision of

medicines under the Medicines Act and the Limited List

Regulations. The first section describes how these controlswork and are used, and the second some weakness of thecurrent arrangements.

*Minister of Health, the Secretary of State concerned with Health in Scotland,and the Minister of Health and Social Services for Northern Ireland.

THE MEDICINES COMMISSION AND SECTION-4 COMMITTEES

The first requirement of the Medicines Act was to establishthe Medicines Commission, a body consisting of not less than8 members, which would advise, and make recommendationsto, Ministers on matters relating to the implementation of theMedicines Act and on drugs generally. The Commission wasspecifically charged (Section 4 of the Act) to establishadditional committees for the proper maintenance of the

regulations of the Act. Accordingly five such committeeswere established: the Committee on Safety of Medicines(CSM); the Committee on Review of Medicines (CRM); theBritish Pharmacopoeia Commission; the VeterinaryProducts Committee; and the Committee on Dental andSurgical Materials. Of these only the CSM and the CRMhandle product licences of medicines for human use.The Commission was also required to receive

representations from manufacturers; and, with regard todrugs, these would usually mean giving hearings or receivingwritten representations from manufacturers aggrieved by therecommendations of one of the "Section 4" committees.The Medicines Commission was established in 1969 and its

present members are:Prof Rosalinde Hurley (chair, a microbiologist and barrister); Mr

J. P. Bannerman (pharmacist); Prof D. N. Baron (chemicalpathologist); Mr P. B. Capstick (Wellcome); Prof W. I. Cranston(physician); Dr B. W. Cromie (chairman, Hoechst UK); Prof P. F.D’Arcy (pharmacist); Prof E. J. H. Ford (veterinary surgeon); DrJ. C. Gould (microbiologist); Dr T. M. Jones (Wellcome); ProfD. R.Laurence (clinical pharmacologist); Dr M. J. Linnett (generalpractitioner); Mrs A. Rees (physicist); Prof J. B. Stenlake

(pharmacist); Mr Gordon Tuck (barrister; Miles Laboratories); DrD. R. Williams (Unilever), and Mr H. Cowan Wilson (veterinarysurgeon).Reportsl on the activities of the Commission give little

detail and deal only with selected topics. The report for 1984has just been published. The Commission met 6 times in1984 and considered 12 appeals (11 hearings, 1 written

representation) related to product licences for drugs forhuman use. In 4 instances the complainant successfullyreversed (to a greater or less degree) the judgment of theoriginal Section-4 committee. The number of such hearingsis increasing each year (there were 7 appeals in 1983). The

1. Annual Reports of the Medicines Commission and Section 4 Committees. HMStationery Office.

13. Greenblatt RB, Dmowski WP, Mahesh VB, Scholer HFL. Clinical studies with anantigonadotropin—danazol. Fertil Steril 1971; 22: 102-12.

14. Wilson MC, Sellwood RA. Therapeutic value of a supporting brassiere in mastodynia.Br Med J 1976; ii: 90.

15 Cuningham K. Lang WR. Result of a blind clinical trial conducted on 50 cases ofhormonal mastopathy. Med J Aust 1962; ii: 341-43.

16 London RS, Sundaram GS, Goldstein PJ. Medical management of mammarydysplasia Obstet Gynaecol 1982; 59: 519-23.

17 Minton JP, Abou-Issa H, Reiches N, Roseman JM Clinical and biochemical studies onmethylxanthme-related fibrocystic breast disease. Surgery 1981, 90: 299-304.

18 Preece PE, Hughes LE, Mansel RE, Baum M, Bolton PM, Gravelle IH. Clinicalsyndromes of mastalgia. Lancet 1976; ii: 670-73

19 Wisbey JR, Kumar S, Mansel RE, Preece PE, Pye JK, Hughes LE Natural history ofbreast pain. Lancet 1983; ii: 672-74.

20 Mansel RE, Preece PE, Hughes LE. A double blind trial of the prolactin inhibitorbromocriptine in painful benign breast disease. Br J Surg 1978, 65: 724-27.

21 Mansel RE, Wisbey JR, Hughes LE. Controlled trial of the antigonadotropin danazolin painful nodular benign breast disease. Lancet 1982; i: 928-31.

22 Hughes LE, Mansel RE. Benign breast disease In. Russell RCG, ed Recent advancesin surgery Edinburgh: Churchill Livingstone, 1982: 114.

23 Visick AH. Measured radical gastrectomy Lancet 1948, i: 505-10, 551-55.24. Horrobin DF. Cellular basis of prolactin action: Involvement of cyclic nucleotide

polyamines, prostaglandms, steroids, thyroid hormones; Na/K ATPases andcalcium, relevance to breast cancer and the menstrual cycle. Med Hypoth 1979; 5:599-614

25 Preece PE, Baum M, Mansel RE, Webster DJT, Fortt RW, Gravelle IH, Hughes LE

Importance of mastalgia in operable breast cancer. Br Med J 1982; 284: 1299-300.26. Preece PE, Mansel RE, Hughes LE. Mastalgia: psychoneurosis or organic disease? Br

Med J 1978; i: 29-30.27. Sundaram GS, Manimekalai S, London R, Sundaram M, Goldstein PJ Fibrocystic

disease of breast, prolactin and vitamin E. Abstracts of 7th International Congress ofEndocrinology. Amsterdam: Exerpta Medica, 1984: 1462.

28. Preece PE, Richards AR, Owen GM, Hughes LE. Mastalgia and total body water. BrMed J 1975; ii: 498-500.

29. O’Brien PMS, Craven D, Selby C, Symonds EM. Treatment of premenstrual tensionby spironolactone Br J Obstet Gynecol 1979, 86: 142-47.

30. Reeves BD, Garvin JE, McElin TW. Premenstrual tension: symptoms and weightchanges related to potassium therapy. Am J Obstet Gynecol 1971; 109: 1036-41.

31 Sitruk-Ware LR, Sterkers N, Mowszowicz I, Mauvais-Jarvis P. Inadequate corpusluteum function in women with benign breast diseases J Clin Endocrinol Metab1977, 44: 771-74

32. Cole EN, Sellwood RA, England PC, Griffiths K Serum prolactin concentrations inbenign breast disease throughout the menstrual cycle. Eur J Cancer 1977; 13:597-603.

33. Walsh PV, Bulbrook RD, Stell PM, Wang DY, McDicken IW, George WD. Serumprogesterone concentration during the luteal phase in women with benign breastdisease Eur J Cancer Clin Oncol 1984; 20: 1339-43

34 Kumar S, Mansel RE, Hughes LE, Woodhead JS, Edwards CA, Scanlon MF,Newcombe RG Prolactin response to thyrotropin releasing hormone stimulationand dopaminergic inhibition in benign breast disease. Cancer 1984; 53: 1311-15.

35 Bohnet HG, Hanker JP, Schweppe KW, Schneider HPG Changes of prolactinsecretion following long-term danazol application. Fertil Steril 1981, 36: 725-28

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Commission also considered parallel imports (as it had in

1983), prescribing drugs that had been "withdrawn", andissues relating to drug trials in healthy volunteers.The Committee on Safety of Medicines was established in

1970. Its functions are to advise the licensing authority onquestions of the safety, quality, and efficacy of new medicinesfor human use, and to promote the collection and

investigation of information relating to adverse reactions.The committee met 11 times in 1984, five of the meetingslasting two days, to enable the committee to complete itsbusiness. It has 19 members:

Sir Abraham Goldberg (chair), Prof A. W. Asscher, Prof A. M.Breckenridge, Dr C. M. Castleden, Mr W. M. Darling, Prof J. W.Dundee, Prof P. H. Elworthy, Prof A. T. Florence, Prof D. G.Grahame-Smith, ProfM. W. Greaves, Dr J. M. Holt, ProfD. Hull,Prof H. S. Jacobs, Dr B. L. Pentecost, Prof M. D. Rawlins, DrJ. W. G. Smith, Prof M. P. Vessey, Dr D. M. B. Ward, andProf H. K. Weinbren.To fulfil its terms of reference the CSM has established

four subcommittees:

safety, efficacy, and adverse reactions (chaired by ProfessorGrahame-Smith; 19 members); chemistry, pharmacy, and standards(chair, Professor Elworthy; 16 members); biologicals (chair, DrJ. W. G. Smith; 12 members); and adverse reactions to vaccines andimmunological products (chair, Prof R. W. Gilliatt; 14 members).

In 1984 the CSM received 112 applications for productlicences (fewer than in 1982 or 1983), of which 29 weregranted on first consideration and a further 25 after a hearingor written representation. Just over half the originalapplications were refused, a proportion which increasesyearly. The mean time to process the applications at present is23 months for new chemical entities, and 16 months forestablished drugs. The delay usually reflects a poor originalapplication; a properly completed application containingadequate data could well result in the licence being grantedwithin about 6 months. In advising to grant a licence, thecommittee decides whether the medicine should be availableon prescription only (POM), over the counter but under thedirection of a pharmacist (P), or in general shops (GeneralSales List). The applicant indicates in his submission whichhe prefers.In addition to assessing applications for new chemical

entities, the CSM can be called upon to assess a new

presentation, new formulation (dosage, colorant, deliverymechanism), or a new indication, or to review the productlicence when it comes up for renewal (a licence expires afterfive years and must be renewed if the manufacturer wishes tocontinue to market it). In general, however, these assessmentsare made by the Medicines Division; the CSM itself is oftennot aware of such "minor" applications.The Committee on Review of Medicines was established in

1975 to review the efficacy, safety, and quality of allproprietary medicines that were given a product licence ofright (PLR) when the Medicines Act came into effect in 1971.The committee met 5 times during 1984. During that time ithad 19 members:ProfO. L. Wade (chairman), Prof A. W. Asscher, Prof T. H. D.

Arie, ProfG. V. R. Born, ProfJ. E. Carless, ProfP Curzen, Dr A. E.Dudley, Dr F. Fish, Prof C. F. George, Mr L. J. Gower, Dr K. L.Granville-Grossman, Prof F. Harris, Dr B. J. Kirby, Prof M. H.Lader, Prof M. J. S. Langman, Prof D. H. Lawson, Prof J.Midgeley, Dr A. T. Proudfoot, and Dr L. E. Ramsay. ProfessorWade retired at the end of 1984 and has been succeeded as chairman

by Professor Asscher.In 1971 there were 39 000 products with licences of right,

but by 1976, 10 000 PLRs had been "voluntarily" with-drawn after the CRM had asked companies to submit

comprehensive information about their products. To review

products, the CRM uses evidence from clinical trials, adversereaction reports, published papers, and the evidence ofprofessional bodies. Each year it calls for review between2000 and 3000 PLRs, and each year about half are withdrawnbefore review is possible. At present about 9000 PLRs remainand to comply with an EEC directive all reviews will have tobe completed by 1990. The 6000 or so outstandinghomoeopathic preparations have a different status and the1990 deadline does not apply to them.Reviewing the PLR demands not only an assessment of the

ingredients, but also determination of the wording of theproduct licence. This aspect is very important, since it is theproduct licence that determines, amongst other things, thecontents of data sheets and advertisements. Many aspects ofthe old PLR data sheets are questionable, particularly the"indications" section, and their review has been welcome.PLR data sheets can be recognised from the product licencenumber given at the end of the text. If the figure immediatelyafter the oblique stroke is a 5 or 6 (most commonly 5), then thedata sheet is for a PLR product. The licensing authority hasasked manufacturers to add the suffix R after the number ofreviewed data sheets, but few do so.Adherence to the Medicines Act.-Adherence by

manufacturers to the provisions of the Medicines Act isoverseen by the Medicines Division of the DHSS. It is they,not the committees, who are responsible for checkingmanufacture, supply, data sheets, advertisements,marketing, &c.

THE NHS LIMITED LIST

The Advisory Committee on NHS Drugs was establishedfollowing the introduction of the NHS Limited List on April1, 1985. Its first meeting was held on June 23 and meetingswill be held monthly at least for the first year and thereafterless frequently. Its terms of reference are:"To advise the United Kingdom health Ministers about the

composition of schedules 3A and 3B to the National Health Service(General Medical and Pharmaceutical Services) regulations 1974,and the corresponding schedules in the regulations in Scotland andNorthern Ireland (except those items which are in schedule 3Abecause the Advisory Committee on Borderline Substances hasadvised that they are not considered drugs in the circumstances ofgeneral practice) in order that drugs to meet all real clinical needs atthe lowest possible cost to the NHS are available under the NHS inthe following categories: mild to moderate painkillers, indigestionremedies, laxatives, cough and cold remedies, vitamins, tonics, andbenzodiazepine sedatives and tranquillisers."The committee is chaired by Dr E. Harris (deputy chief medical

officer, DHSS) and has 14 other members. 7 are hospitalconsultants: Mr N. Badham (ENT), Prof A. Breckenridge (clinicalpharmacologist), Dr D. C. Jones (gastroenterologist), Prof M.Hodkinson (geriatrician), Prof F. Stroud (paediatrician), Prof M.Lader (psychopharmacologist), Dr J. Moore (anaesthetist). 4 aregeneral practitioners: Dr J. Callender, Dr S. Carne, Dr J. Lynch, DrD. Smith. 2 are pharmacists: Dr D. Ganderton, Mr D. Coleman. 1 isa dentist: Prof R. Causor.The Secretariat assumes that most of the applications for drugs to

be made available on NHS prescriptions will be submitted bymanufacturers. However, applications are open to doctors

(preferably as a consortium, such as a drug and therapeuticscommittee), and, like manufacturers, they can do so by sending 25copies of the application to: Advisory Committee on NHS Drugs,Room 620, Eileen House, Newington Causeway, London SE1. Thedata submitted must provide objective evidence that there is a realclinical need for the product which is not met by drugs alreadyavailable under the NHS or is as effective as the available drugs atthe same cost or less (the Medicines Act expressly forbids anyconsideration of cost when the licensing of drugs is reviewed). Thecommittee’s findings will be given to Ministers who will inform the

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applicant, and if necessary arrange an amendment to be laid beforeParliament. It is likely to take 3 or 4 months from the time ofapplication before the drug becomes prescribable. The committee’sfindings will be treated in confidence.

DO THESE ARRANGEMENTS BEST SERVE THE PUBLIC?

There was an obvious need to introduce unifyingregulations, such as the Medicines Act, after the thalidomidedisaster of the early 1960s. Advances in the pharmaceuticalindustry’s techniques, influence, and marketing zest,

together with vastly improving medical knowledge and theemergence of clinical pharmacology as a discipline, meantthat there were good grounds for such an Act matched bysound bases for making judgment. The terms of reference ofthe committees were, however, established in the late ’60sand the demands and expectations of science and society havechanged. Indeed it would be surprising if the originalproposals of the Medicines Act could remain applicable. Inthe light of probable changes, are there aspects of theMedicines Act that need reconsideration?

Terms of Reference of Section-4 CommitteesThe CRM, the CSM, or the secretariat are required to

consider the safety and efficacy of all drugs for which aproduct licence application is made, and it is the

interpretation of these requirements that causes concern. Inanalysing the properties of a drug it is not possible to give anabsolute value to factors such as safety or efficacy, andaccordingly they must be considered in relative terms. Thequestion, however, is: to what should they be related? For anydrug the prescribing physician needs to know the balancebetween the safety and efficacy of that drug, the balancebetween these properties compared to that in other drugs of asimilar therapeutic category (although such comparisons asthey relate to efficacy are expressly forbidden in theMedicines Act), the balance between these properties and thedisease process being treated (for example, how likely is it thatthe drug will make the patient feel worse or better?), andwhether the balance changes with the age of the patient, withthe duration of therapy, when other medicines are taken orwhen secondary diseases develop. To "consider" safety orefficacy is not therefore enough; it would surely be better toconsider a whole range of possible balances, and doing sowould comply with the EECs requirement that "therapeuticadvantage must outweigh clinical riskThe CSM and CRM recognise that if the balance of a new

drug (the "therapeutic advantage") is much greater than foran old preparation (a new opioid that did not cause

dependence, a non-steroid anti-inflammatory drug that didnot cause gastrointestinal bleeding), then the new preparationwould be granted a licence, and the older ones withdrawn.What we do not know is how much difference there needs tobe before such a stance would be recommended.The problem is how best to determine properties such as

efficacy or safety. The Medicines Act requires that the

licensing authority should take efficacy into account, but thisis unsatisfactory. The EEC more realistically demands that itshould be a "therapeutic effect", stressing that"demonstration of a pharmacodynamic effect in human

beings shall not in itself be sufficient to justify anyconclusions regarding any particular potential therapeuticeffect". Unfortunately, however, most of the clinical data

rules Governing Medicaments in the European Community: CouncilDirective of May 20, 1975; 75/318/EEC.

available do not provide a truly objective assessment of thebalance between efficacy and safety. Interestingly, the CSMrecognises this and in many instances recommendations haveto be made on informed guesswork. They argue that if theywere to demand incontrovertible evidence, few applicationswould pass and the whole pattern of pharmaceutical advancewould have to change. Nevertheless, this is exactly what theterms of reference for the Limited List require. It will

certainly raise questions if the criteria for analysis by the ListAdvisory Committee are more discerning and more reliablethan those of the CSM or CRM.

Perhaps one could accept that at the initial application -tothe CSM some leeway could be given for guesswork. In thatcase when the time comes for the licence to be renewed, whennew trials will have been reported and new drugs available,scrutiny should be very close indeed. For the CSM to ignorethis opportunity, allowing renewals to be considered as ofright, seems to waste an opportunity. The EEC certainlyrecognise the need for thorough review suggesting that "theevaluation of harmfulness and therapeutic efficacy may bemodified in the light of new discoveries ... and scientificprogress".

Membership of Committees and Relationships with DrugCompanies

5 members of the Medicines Commission are from the

pharmaceutical industry, 4 members of the CSM haveconsultancies with drug companies, and of the 9 members ofthe ACD who have responded to requests for information, 3have consultancies and 4 shares in pharmaceuticalcompanies. Furthermore, it can safely be assumed that almostall the physicians on the committees will have worked withdrug companies on research projects for which they, theirjuniors, their colleagues or their departments will havereceived payment from industry. The level of payment willvary, as will the commitment to the company; so that for aconsultant who works on an ad-hoc basis with occasional

meetings, the annual figure might be 1000, but for a fullyretained consultant advising on company policy, taking partin meetings, conferences, &c, it could well reach 15,000.Whatever the role, a member of the CSM or CRM wouldcertainly be seen as a very attractive consultant or researcherby many manufacturers. Because it would be practicallyimpossible to find senior doctors without some ties withindustry (indeed such persons would be viewed with

suspicion), it would be unrealistic to consider barringmembership to all with such ties. Equally, it does not seemsufficient to ask a "tied" member to take no part or to leavethe room when the committee is discussing a drug made bythe company to which he or she is affiliated. It should beremembered that at a conscious or subconscious level amember can be just as influential when dealing with a"competitor’s" products; a matter which will continuallyoccur in the ACD where comparisons within groups of drugsare inevitable. Equally the principle of selective exclusionfrom discussion is open to abuse. It would be possible, intheory, for a drug company to "gag" a member by enlistinghim as consultant.For justice to be seen to be done, it would seem proper for

members to declare all links with drug companies and thatsuch declarations should be made public. If any link isdeemed to be such as to be likely to influence judgmentunduly, then the relationship (ie, most consultancies)should be severed for the duration of the membership and fora specified period afterwards.

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ConfidentialitySection 118 of the Medicines Act makes it an offence "to

disclose to any other person any information obtained by, orfurnished to, him in pursuance of the Act", and similarconfidentiality can be expected of members of the ACD. Thislevel of secrecy seems excessive, and is not, I believe, in theinterest of the public.Our major source of information remains Hansard. We

recently learned (Hansard, written answers, Feb 15, 1983, c134) that the Minister of Health was unable to say preciselyhow many elderly people were involved in the trials whichwere submitted by Eli Lilly to support the application for aproduct licence for ’Opren’. Thus we gather that the CSMdoes not abide by the EEC rules for applications whichrequire that with any application the submission shouldinclude "a summary of clinical trial data indicating the agedistribution of the groups of patients being investigated" and"details (ie, age, sex, duration of treatment, side effects)concerning who may be at increased risk-eg, elderlypeople". Could it be that other requirements of theCommission might also be overlooked? More recently(Hansard, written answers, July 11, 1985, c 529) we learn thatwhen reviewing the licences for herbal "and other"medicines the CRM will not require evidence from-formalclinical trials; instead it will "rely, where appropriate, onexisting bibliographical information". The Ministermaintains that this is justified because such medicines areintended for minor, self-limiting conditions. Sadly this

approach seems to reflect more a feeling for politicalconvenience than a concern for patient welfare. Moreover itwould appear to contravene the spirit of the Medicines Actand the letter of the EEC’s regulations which, for a drug to belicensed, requires evidence "based on clinical trials andclinical pharmacology experiments". From the tone of hisreply the Minister seems to be hinting that homoeopathicmedicines will also require only the most perfunctory ofevidence in order to obtain a product licence when they comeup for review after 1990. Many would feel that the licensingregulations for medical products must also apply to

homoeopathics. A clandestine change makinghomoeopathics an exception would be an abuse of Section118.Another aspect of secrecy is that information held by the

, Medicines Division is not routinely shared with equivalentregulatory authorities in other countries. At present the USAand Scandinavian countries circulate reports of their

meetings as they relate to positive judgments (ie, a licencebeing granted), while the Australian authority circulatedetails of both positive and negative outcomes. Ourcommittee could surely move towards this level of

cooperation.

Support by the Medicines Division

The details of the product licence determine the content ofthe data sheet and promotional material. Policing theseaspects of the Medicines Act falls to the Medicines Division

(which employs about 250 people) and does not involve thecommittees. This policing is unfortunately inadequate. In1983 the CSM advised the licensing authority that for allproducts likely to be used by the elderly (over-65s) the datasheets printed in the 1985-86 compendium should containspecific advice on prescribing for the elderly, and that thisshould be included in the dosage and administration sectionof the sheet. Furthermore, since advertisements have to beconsistent with the data sheets, the advice should also apply tothem. The new compendium has just been published and its

contents suggest that this advice was not given the closestattention.There are six data sheets for oral preparations of theophylline-a

compound commonly used in the elderly. Two data sheets make nomention of the elderly (those for ’Lasma’ and ’Slo-phyllin’). In theremaining the advice varies from "a reduction in dosage may benecessary in the elderly" (’Uniphyllin’) or "elderly patients mayrequire lower doses due to reduced theophylline clearance"

(’Nuelin’) to "Theophylline should be administered with caution inelderly patients ... reduction in dosage may be necessary... it maycause a safety hazard in some elderly patients with delayed transittime" (’Theograd’) and finally the rather detailed entry "No specificstudies have been carried out using ’Provent’ in the elderly.However it may be advisable to monitor hepatic function in thesepatients and if there is impairment or evidence of heart failure thenserum levels should be monitored".One might have hoped that advertisements would echo these data

sheets, but whereas the current (1985-86) data sheet for ’Aldactide’(spironolactone+hydroflumethiazide) advises that lower doses

might be used in the elderly, it is the higher dose combination(’Aldactide 50’) that is featured in an advertisement showing oneelderly lady shopping (Update, 1985, 31, opposite p 140) with nomention of the problems relating to the elderly in theadvertisements in the Dosages section.These inconsistencies reflect the attitude of some sections

of the industry to the requirements of the Act. This attitudehas developed presumably because policing is poor. Whetherthis is because the Medicines Division has inadequateresources, or because the Medicines Division is reluctant toconfront the pharmaceutical industry, we do not know. Ineither event it is not in the best interest of patients or doctors.

CONCLUSION

Two committees control the availability of drugs in the UKbut the contrast between their experiences could hardly begreater. The 15-member Limited List Committee (AdvisoryCommittee on NHS Drugs) was formed less than 2 monthsago and has yet to introduce anything tangible. In the mainthe vast committee structure involved in the licensing ofdrugs has functioned for over a decade and has had theexperience of advising governments on drugs policy in thewake of the thalidomide disaster. For one committee it is not

possible to do more than predict, for the other a full appraisalis feasible.For the Limited List Committee the terms of reference

seem sound and worth pursuing, although adherence to theterms might prove difficult. One way that might help thecommittee achieve its end would be to collaborate with theMedicines Division and with those who run thePharmaceutical Price Regulations Scheme (PPRS).However, the secrecy that surrounds all three bodies maypresent difficulties. Fortunately links are already being madewith the PPRS, but whether the Medicines Division can (orwill) collaborate seems in doubt. If the excessive

confidentiality could be reduced it might then also be possibleto make public the findings of the Limited List Commitee, amove that doctors and patients would welcome.The Medicines Commission, the CSM, and the CRM now

seem to need changes in their legal framework and theirmethods of operating. I believe it is time to amend the termsof reference relating to safety and efficacy so that the

requirements of the committee more closely coincide withthose that prescribers need. I believe also that the excessivesecrecy imposed under Section 118 of the Act needs to bereduced so that communication between the MedicinesDivision and the public can approach that which would be

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possible if there were a Freedom of Information Act;legitimate commercial secrets would continue to be

protected.Enforcement needs to be strengthened both inside and

outside the committees. Not to take full advantage of thelicence renewal system seems to waste an opportunity whichshould be taken in the interest of the public. Similarly not toenforce the requirements of the licensing authority as theyrelate to advertising, for example, seems indefensible.

Finally it is no longer possible to ignore the issues raised bylinks between vested interests and the Government’s

advisers. The exact position of a committee member who hasclose ties with a pharmaceutical company needs appraisal.The Medicines Act (Section 3, para 2b) requires "the

Medicines Commission from time to time to review thecommittees established under Section 4 and to makerecommendations to the Ministers with regard to anychanges in their number or function". Such a review is nowdue and should include not only the formal remit of thecommittees but also the wider issues of their functioning.This might well require a critical examination of theMedicines Act itself.

In England Now

IT was, I thought, a fine chance for cooperation with my NHScolleagues. Our teaching district, probably one of the most over-resourced in the country, appeared not to have a BBC/Torchminicomputer to look at the new performance indicators on floppydisks1 that had fallen from on high into the hands of the planningoffice. Could our small, academic department help?

I had answered the phone. Delighted, I said. Come over at once.My own Beeb was in use (I write directly onto it, using Wordstar),but we had bought three, to be able to link into a bigger network inthe future. One has a colour screen, so we could all look at thewonders of DHSS high tech.The district information officer clutched the bright yellow and

blue plastic pack happily. He pulled off the wrapper, releasingseveral booklets, a ring-binder, and the floppy disks. One of the discscalled itself "Welcome", and a blue book gave clear instructions onstarting up."Press Break and B keys together, then release Break and then

B..." We started the cookery. Quickly the screen buzzed into life.The Welcome disk spelled out what it was going to do. "Press’return’ to go on to the next screen", it commanded. "Wonderful,"exclaimed the locum district specialist in community medicine."This is how I like computers."Then suddenly up on the screen: "Error 1060". Showing us all

the wrinkles, I thought. But pressing various keys wouldn’t makethe error go away. We searched through the manuals. No list oferror commands anywhere. We were stuck. The only choice was togo back to the beginning. We pressed the Break key alone, thenrepeated the process, slowly getting to the same place... "Well,perhaps we don’t need a welcome. Let’s go onto another disk," saidthe SCM. I left them to it, returning to work in my own office.Half-an-hour later, two sad faces appeared round my door.

"Couldn’t get any of them to work. Next one we tried, we got to onepoint with a table, and then it just vanished leaving a little white dotat the top of the screen." "Oh well," I said, reassuringly (I thought)."Try ringing up the DHSS. They’ve made such a fuss about thesePIs, Mr Victor Paige having a press conference and all that. They’llsurely have someone at a telephone to deal with the bugs. Any newsystem will have teething problems, and they can’t let a flagshipdistrict like ours be defeated, can they?"

I felt almost genial as I showed them out of the door. But inside, Iwondered how many other people were being put off the newtechnology at a similarly early stage?

MANY years ago I visited Radio City Music Hall in New York, andbecame one of the very few people ever to see a Radio City Rockettetrip and fall on her nose during a high-kicking routine (fortunatelywithout lasting physical damage, though the mental trauma musthave been considerable). I found the experience both interesting andinstructive, and I looked forward to making further suchobservations.

1 Note New performance indicators for NHS: Mr Paige commends his floppy disksLancet 1985, ii: 285.

After an age of waiting, one arrived recently. I live close to aScottish salmon river, where the wildlife includes dippers,goosanders, red squirrels, and red and roe deer. There are otters,and an osprey occasionally comes to fish. At the top of the glen thereis a pair of golden eagles. But, although agreeable, these phenomenaare peripheral. The centre of my attention has always been the flyfishermen, haughty and aloof, who come from South of the borderto spend an expensive week in waders in the middle of the current. Inever wavered in my confidence that one day I would see one ofthem slip on a weed-covered stone and fall headlong.The moment, when it came, provided almost a carbon copy of the

affair in New York. The cries of alarm, the flailing of the limbs, theloss of dignity, and the lack of serious injury were all according topattern; I felt fulfilled. The victim stumbled out with his waders fullof water and his mouth full of deplorable language; I have never seena man so wet.

Unfortunately I had not reckoned with Nemesis, and there was asequel. A few days later, returning from my weekly visit to thesupermarket with a shopping bag in either hand, I tripped over aprotruding flagstone and fell forwards in exactly the same attitude asmy two examplars, breaking my spectacles, cracking a rib, andbursting a bag of tomatoes all over my sweater. Whether this was ajudgment or not, my appetite for this sort of thing has beentemporarily sated.

SERENDIPITY means, of course, the faculty of making happy andunexpected discoveries by accident. There does not seem to be asimilar word in the strictly medical vocabulary. Such a term wouldbe useful. How often have we stumbled on a diagnosis by accidentand then taken credit for a good examination? Like the man whosechest we X-rayed routinely to find a peculiar thin line stretchingfrom one lung to the other through the mediastinum. Technicalfault, said the report, but lungs normal. Only when the patientcommented on the number of technical errors his X-rays caused, didthe penny drop. A thoracotomy revealed a bicycle spoke lyingwithin the chest cavity, a relic of a road accident some thirty yearspreviously. It produced some pleural pain and an interestingpublication.

GAMES EDITORS PLAY

THE Roman goddess Minerva, clad in a smart lightweight suit andplaying for the Brztish Medical Journal, was but one of the factorsthat seemed to stack the odds against The Lancet in this year’ssportive contest between the medical weeklies. Another was thevenue, Regent’s Park, because a large part of the Adam Street teamarrived in a state of collapse after ascending the ninety-seven stepsfrom the local underground. And then there was the presence, in theTavistock Square contingent, of a pair of fit-looking students fromManchester. Happily, the latter agreed to make up numbers on TheLancet side, and the resulting evenly matched competition drewcries of astonishment from the neighbouring Royal College ofPhysicians and zoo. The game was a version of rounders, and theresult was declared an honourable draw; though modesty forbidsmention of the scores.