810
Wider World
capsules, and solutions. Of all the drugs used in Government hospitals and health units, 93% (costing L4.8 million) were imported, 85% of these originating (in 1975) from Western Europe and the United States.5
PROVISION OF MEDICINES IN A DEVELOPING COUNTRY
JOHN S. YUDKIN Department of Metabolism and Endocrinology, London Hospital Medical College, London E1 2AD
developing countries the money spent drugs could often be used more A large proportion of the to disease. effectively prevent of one developing country is spent on drug budget expensive proprietary preparations for use mainly in the larger hospitals, draining resources from health care in rural areas. A major factor in determining the country’s expenditure on drugs is the promotional activities of pharmaceutical companies; the number of drug company representatives in the country is proportionately five times that in Britain. Many drugs are promoted for diseases for which they are not indicated and in which their use may be hazardous, and information on sideeffects and contraindications is inadequate. Information supplied by drug firms to health workers in different countries must be standardised and the purchase and use of drugs in third-world countries made more appropriate to their needs. Summary
In many on
INTRODUCTION
THE major health problems in many underdeveloped countries are diseases of poverty and lack of sanitation which have almost disappeared from industrialised countries. Implementing the vigorous public health and immunisation campaigns necessary to fight these diseases requires large amounts of money, particularly in countries where 80% or more of the people live in rural areas. But spending on preventive measures frequently suffers because a large proportion of the health budget is used for buying drugs. Few of these countries have their own pharmaceutical industries, so rely on drugs bought from abroad. During a clinical appointment in an underdeveloped country, I studied the purchase, use, and promotion of drugs in that country to determine whether or not the amount of money spent on drugs could be reduced without adversely affecting curative
patient care. HEALTH PROBLEMS AND THE HEALTH BUDGET
The country studied has no substantial industries or natural and over 90% of the total population of 15 million live in villages, mainly engaged in subsistence farming. For many illnesses, the traditional healer is consulted first; Western-style medical care in most cases is provided at healthcentres and dispensaries staffed by medical auxiliaries. Only a third of all consultations take place at hospitals. The expenditure of the Ministry of Health in 1976 (all figures in this paper, unless otherwise stated, refer to the year 1976) was ,30 million (2% of gross national product’>2), of which 5-2 million (17%) was spent on drugs. The annual drug budget has increased cumulatively by one third in each of the last 5 years.3,4 A nationally owned pharmaceutical company at present produces about 7% of the Health Ministry’s drug requirements,’1 mostly by compounding imported raw materials into tablets, resources
Over 75% of the drugs purchased by the Ministry of Health used in hospitals.6 The drug allocation to dispensaries, the village health units staffed by auxiliaries, is 720 000 per year (1.5p for each patient seen). In comparison, four chloroquine tablets cost 2p and twenty aspirin tablets cost 1.7p. Not surprisingly, in many dispensaries the monthly allocation of drugs is consumed within fourteen days and many patients must be sent away untreated. Within the hospital services, the pattern of drug use varies. In small district hospitals over half the drug budget is spent on antibacterial and antiparasitic drugs, while in the national teaching hospital these drugs take only 25% of the budget and 10% is used for tranquillisers, sedatives, and antidepressants. Even the types of drugs within a single therapeutic category are used differently by different types of hospital. In the main national referral and teaching hospital, almost 40% of all drug prescriptions were for expensive proprietary preparations rather than the older (and cheaper’) generic alternatives. In several district and regional hospitals I studied only 5-19% of prescriptions were for proprietary products. are
DRUG PROMOTION
prescribing pattern in the large hospitals in this developing country- which in its emphasis on psychotropic drugs and expensive proprietary forms is similar The
to
that in industrialised countries-appears
to
be
strongly influenced by the promotional activities of the drug companies. These activities are considerable even though the annual drug expenditure is now only about 1.2% of the British National Health Service expenditure on drugs.8 In January, 1977, there were 147 drug company representatives in the country-1 for every 4 doctors (in Britain, the figure is about 1 for every 20 doctors9). Merely maintaining them is estimated to cost around 600 000 per year, and the total spending on promotion is probably substantially higher: in Britain, representatives account for only 40% of drug promotion costs.9 Even assuming that in this underdeveloped country the equivalent proportion is 60%, it may be estimated that the drug companies are spending at least D million per year on promotion and advertising, CO 700 per doctor, or over twice the equivalent sum in Britain1O). Although the market is small, spending power is highly concentrated, many doctors ordering drugs to be prescribed by medical auxiliaries as well as other doctors whole district. Each doctor in the country controls, average, the spending of [11500 on drugs. The estimated ratio of promotion costs to sales is similar to that in Britain but promotion is likely to be more effective; m most underdeveloped countries the drug companies have a monopoly of information since medical journals are not widely available in hospitals and independent assessments of drug efficacy or costs are not supplied by the industry and only rarely by ministries of health. Many drug companies take advantage of their control over the supply of information, frequently promoting hazardous drugs for a range of indications wider than normal for developed countries and omitting side-effects in promotional literature and package inserts. African Monthly Index of Medical Specialities (M.IM.S.,) a publication similar to the British version which is sent to all doctors in the country free of charge every two
within
a
on
811
months, is for many doctors the only source of up-todate information on drugs, their indications, and side-effects. Like the British M.l.M.S., it contains -information supplied by manufacturers but the information differs greatly: indications for drugs are more numerous and contraindications and special precautions less frequently mentioned. Few third-world countries have legislation restricting the stated indications for a drug or making illegal the issue of false or misleading information. SOME OF THE DRUGS PROMOTED
Aminopyrine and dipyrone are antipyretic analgesics which may produce agranulocytosis with a mortality as high as 0.57%." In the United States they are licensed for use only in patients with terminal malignant disease in whom safer antipyretics have been unsuccessful. 12 In African Af.7jM.6’. (November, 1977), 31 preparations containing these drugs are recommended as analgesics for minor conditions. Package inserts claim that they have a "wide margin of safety" (’Avafortan’, Asta Werke) or that their "safety has been proven and confirmed in over 500 publications throughout the world" (’Buscopan Compositum’ containing dipyrone, Boehringer Ingelheim). Few of the packages mention aminopyrine and dipyrone, using instead one of the longer chemical names such sodium 2,3-dimethyl-l-phenyl-5-pyrazolon-4-yl-N-methylaminomethane sulphonate monohydrate. Anabolic steroids may produce stunting of growth, irreversible virilisation in girls, and liver tumours.13-15 They are used in Britain to treat osteoporosis, renal failure, terminal malignant disease, and aplastic anaemia. In African M./.M.S., they are promoted as treatment for malnutrition, weight-loss, and kwashiorkor (’Decadurabolin’, Organon), as appetite stimulants (’Winstrol’, Winthrop), for exhaustion states (’PrimoboIan Depot’, Schering; ’Dianabol’, Ciba Geigy), and for "excessive fatiguability" in school children (’Dianavit’, Ciba Geigy). The use of high-dose oestrogen-progestagen combinations as a "hormonal pregnancy test" is associated with an increased incidence of congenital abnormalities.16-19 In Britain, the indication given for ’Primodos’ (Schering) since 1974 has been for the diagnosis of secondary amenorrhoea of short duration when pregnancy has been excluded. In African M./.M.S. primodos, as well as ’Menstrogen’ (Organon), ’Norlutin’ (Parke Davis), ’Paralut’ (Wallace), and ’Disecron’ (British Schering), is recommended for the diagnosis of pregnancy; the package insert of primodos does not mention the risk of fetal malformation. If a dose of the antihypertensive drug clonidine is missed by as little as 12 h, severe rebound hypertension and sometimes cerebral haemorrhage may result.20-23 It should thus be avoided when patients are likely to take prescribed drugs irregularly. In Africa, transport difficulties and administrative problems may hinder the regular supply of drugs during therapy.In addition, the concept of asymptomatic disease is not widely accepted, pills being taken only for relief of symptoms; in one study only 20% of patients were found to take their tablets regularly.24 Clonidine (’Catapres’, Boehringer Ingelheim) was introduced into the country in 1975; the company distributed free samples of the drug, sufficient for only two or three weeks’ use, before it was available through the Government central medical stores (c.M.s.). African M.l.M.S. does not mention the danger of suddenly stopping clonidine therapy, although British M.LM.S. does; in the manufacturers’ booklet two sideeffects are mentioned--compared to fifty in American advertisements-but not this risk. Boehringer Ingelheim have only now agreed to mention the danger in future package inserts. Several potentially hazardous drugs are promoted for minor indications or with no mention of special precautions or sideeffects : chloramphenicol (’Synthomycetin’, Lepetit) is promoted for use in "respiratory tract, urinary tract, surgical, ears, nose and throat, intestinal and biliary tract, venereal, obstetric, and gynaecological infections"; mesterolone (’Proas
androgen, is suggested for use in "declining physical activity and mental alertness in middle-aged men"; a combination of oxyphenbutazone (100 mg) and prednisolone (2.5 mg) (’Realin’, Ciba Geigy) is recommended for use in "all degenerative rheumatic diseases and non-articular rheumatism, fibrositis syndrome" in a dose of up to four tablets daily; triamcinolone acetonide (’Kenacort’, Squibb), a topical steroid, is marketed for indications which include insect bites and sunburn. Paediatric preparations of tetracycline are marketed by Lederle, Squibb, Pfizer, Lepetit, and Boots without mention of the possible risks or the recommendation, made in Britain, that tetracycline should not be used in children up to 12 years of age. Liothyronine (’Tertroxin’, Glaxo) is promoted for treatment of "lowered metabolic states", contrasting with the British M.l.M.S. indication of "severe thyroid deficiency". Methadone (’Physeptone’, Burroughs-Wellcome), recommended in Britain for severe pain, is included in African M.1.M.S. as a cough suppressant. Clioquinol has been withdrawn in several countries because of a risk of subacute myelo-optic neuropathy;25 Ciba Geigy claim the risk is dose-related, that the disease is confined to Japan, and that they have recommended a maximum total viron’, Schering),
an
dose of 7 g.26 In African M.l.M.S., the recommended maxitotal doses of prophylactic ’Entero-vioform’ (Ciba) and ’Marol’ (Ciba) are 7-14 g and 29.4 g of clioquinol, respectively, and prophylactic ’Mexaform’ (Ciba) does not have a stated maximum dose. Clioquinol is also marketed by Leo, Wyeth, Bayer, Wallace, and Smith, Kline, and French for the treatment of diarrhoea but African M.1.M.S. gives no maximum dose for any of them. mum
OTHER PRESSURES
third-world country, two Ministry of Health jailed in 1973 for accepting bribes; they had purchased sufficient quantities of an antibacterial agent and a tranquilliser made by one large company to last the nation for more than ten years.27,28 In the country I studied, a paper to be presented at a scientific meeting on the hazards of pyrazolone analgesics was withdrawn when the embassy of one industrialised nation suggested that such "criticism" was inappropriate at a time when that nation was financing a major aid programme.29 In
one
officials
were
NATIONAL DRUG PURCHASING AND POSSIBLE ECONOMIES
In 1976, the purchases of drugs by the C.M.S. exceeded drug sales by c.M.s. to Government hospitals and other units by a ratio of almost two to one. The excess is not evenly distributed; for 46 out of a total of 601 drugs purchased, the ratio of current stocks to annual sales is over four to pne. 36 of these 46 drugs are proprietary preparations manufactured by multinational companies. 16 of the 46 overstocked drugs are made by just four Western European companies, which have a total of only 24 drugs on the c.M.s. list. While it may be sensible to purchase large stocks of some drugs, the shelf-life of others, such as insulin or antibiotics, is usually 2-3 years, perhaps less in tropical conditions.30,31 There is 45 years’ supply of injectable rolitetracycline, and 21 years’ stock of cyclophosphamide in c.M.s.. Regional medical officers were recently instructed to use up drugs which were close to expiry date, regardless of cost, to avoid having to dump them. Rational purchasing of drugs could save as much as could more economical prescribing. With the adoption of cheaper generic alternatives instead of proprietary
812
preparations,
I have calculated that the annual
drug
could be reduced by 1.47 million, or nearly 30% of the total. (Full details of these calculations are available from the author on request.).
budget
Occasional Survey A REVIEW OF THE EVIDENCE FOR METHADONE MAINTENANCE AS A TREATMENT FOR NARCOTIC ADDICTION
DISCUSSION
In several developing countries a critical appraisal is being made of the role of curative medical services in the overall improvement of health. This includes attempts to rationalise drug spending by the ministries of healthrestricting the drug list to 100-400 items,32,33 abandoning the use of proprietary names,34-37 and either curtailing the duration of drug patents, or ceasing to grant brand-name patents on drugs.3g The development of national pharmaceutical industries has became a priority in many third-world countries, encouraged by United Nations agencies.39.4o In the interim, ways of reducing the costs of the major items of the drug budget must be found-e.g., by establishing an international drug-purchasing agency which could request tenders for supplying several countries’ drug needs and monitor quality control. There are often strong pressures on health ministries not to restrict spending on curative services. Doctors who have had postgraduate education in industrialised countries may not wish to compromise what they feel is the best treatment of an individual for the theoretical benefit of the whole population. But there is a growing awareness of cost-effectiveness in many developing countries although at present few ministries supply even rudimentary information on drug costs to their doctors. A change in attitudes to prescribing requires changes in medical students’ training in clinical pharmacology41 and textbooks which emphasise cost-effectiveness in therapy.42 Some countries have considered banning the promotion of drugs by company representatives,43,44 and others are curtailing the distribution of free samples and gifts to doctors.37,45,46 To collect, standardise, and disseminate information
drug use, regional cooperative pharmaceutical might be created.4O Alternatively, the World Health Organisation might take on the task of standardising promotional literature, ensuring uniformity in on
centres
information on the use, side-effects, and contraindications of available drugs.47 The drug industry has a role in the improvement of health in the underdeveloped world, but this role is smaller than it would have us believe. Many of the ethical drug companies might welcome controls making promotional excesses unrewarding. Within such a framework, the pharmaceutical industry could demonstrate the contribution which they can make to health care. However, the drug companies must not be permitted to become hazards to health in the underdeveloped world by failing to provide information or by draining scarce resources away from more effective projects. Requests for reprints to J. S. Y., Department of Metabolism and Endocrinology, London Hospital Medical College, Turner Street, Lon-
don E 1
2AD.
REFERENCES
1. Minister of Health. Budget Speech to Parliament; June 1976. 2. International Monetary Fund. International Financial Statistics;
ton, 1977. 3. Planning Officer, Ministry of Health. Unpublished. 4. Gish, O. Planning the Health Sector; p. 172, London, 1975. 5. Annual Statistics. Customs and Excise; p. 54, 1975. References continued at foot of next column
Washing-
MICHAEL GOSSOP
Drug Dependence Clinical Research and Treatment Unit, Bethlem Royal and Maudsley Hospitals, Beckenham, Kent METHADONE maintenance schemes are well established. About 50 000 addicts were receiving treatment in such programmes in the U.S. in 1972.1 The numbers in the U.K. are smaller because of the smaller size of the addict population. However, Home Office figures suggest that between 1970 and 1975 the numbers being prescribed methadone preparations were increasing (reaching 1543 in 1975). Methadone maintenance schemes are regarded as an effective treatment for narcotic addiction (narcotics being defined as opiate and opioid drugs such as heroin, morphine, pethidine, methadone, and opium). The
6. Public Expenditure Supply Votes; vol. III, estimates. 1976. 7. Speight, A. N. P. Trap. Doc. 1975, 5, 89. 8. Priorities in the Health and Social Services: The Way Forward. H. M. Stationary Office, 1977. 9. The Pharmaceutical Industry: a discussion document; p. 25. The Labour Party, London, 1976. 10. Lancet, 1976, ii, 680. 11. Huguley, C. M. J. Am. med. Ass., 1964, 189, 162. 12. Med. Lett. 1973, 15, 4. 13. Johnson, F. L., Feagler, J. R., Lerner, K. G., Majerus, P. W., Siegel, M., Hartmann, J. R., Thomas, E. D. Lancet, 1972, ii,1273. 14. Sweeney, E. C., Evans, D. J. ibid. 1975, ii, 1042. 15. ibid. 1973, ii, 1481. 16. Levy, E.P., Cohen, A., Fraser, F. C. ibid. 1973, i, 611. 17. Committee on Safety of Medicines. Adverse Reaction Series No. 13, 1975. 18. Janench, D. T., Dugan, J. M., Standfast, S. J., Strite, L. Br. med. J. 1977,
i, 1058. Greenberg, G., Inman, W. H. W., Weatherall, J. A. C., Adelstein, A. M., Haskey, J. C. ibid. 1977, ii, 853. 20. Conolly, M. E., Br iant, R. H., George, C. F., Dollery, C. T. Eur. J. clin. Pharmac. 1972, 4, 222. 21. Hunyor, S. N., Hansson, L., Harrison, T. S., Hoobler, S. W. Br. med. J. 19.
1973, ii, 209. 22.
Bailey, R. R.N.Z. med. J. 1975, 81, 268.
23. Yudkin, J. S. Lancet, 1977, i, 546. 24. Materu, N. L. B. Unpublished. 25. Lancet, 1977, i, 534. 26. Pinto, O. de S., Burley, D. ibid. p. 1256. 27. Daily Nation, June 18, 1973. 28. Daily News, July 25,1973. 29. Holmes, J. Circular letter, Feb. 20, 1973. 30. York, P. Unpublished. 31. Steel, J. M., Mngola, E. N. Trop. Doct. 1974, 4, 184. 32. Management Sciences for Health. Procurement and use of medicines in Afghanistan. Boston, 1974. 33. Bibile, S. Case studies in transfer of technology: pharmaceutical policies in Sri Lanka. U.N.C.T.A.D. report TD/B/C.6/21; p.12. Geneva, 1977. 34. ibid. p.13. 35. Lancet, 1977, ii, 602. 36. World Health Organisation. Consultation on the selection of essential drugs. DPM/76.1;p. 21. Geneva, 1976. 37. Lall, S. Major issues in transfer of technology to developing countries. U.N.C.T.A.D. report TD/B/C.6/4;p.53. Geneva, 1975. 38. ibid. p.22. 39. ibid. p.61. 40. Scrip, July 2, 1977, p.16. 41. Herxheimer, A. Lancet, 1976, ii, 1186. 42. Upunda, G., Yudkin, J., Brown, G. Unpublished. 43. Sainsbury Committee. Report of the Committee of Enquiry into the Relationship of the Pharmaceutical Industry with the National Health Service; para. 351. H.M. Stationery Office, 1967. 44. Guardian, Aug. 16, 1977. 45. Lancet, 1977, i, 1016. 46. Lancet, 1976, i, 817. 47. World Health Organisation. Press Release W.H.O./39. Oct. 12, 1976.
Wider World
capsules, and solutions. Of all the drugs used in Government hospitals and health units, 93% (costing L4.8 million) were imported, 85% of these originating (in 1975) from Western Europe and the United States.5
PROVISION OF MEDICINES IN A DEVELOPING COUNTRY
JOHN S. YUDKIN Department of Metabolism and Endocrinology, London Hospital Medical College, London E1 2AD
developing countries the money spent drugs could often be used more A large proportion of the to disease. effectively prevent of one developing country is spent on drug budget expensive proprietary preparations for use mainly in the larger hospitals, draining resources from health care in rural areas. A major factor in determining the country’s expenditure on drugs is the promotional activities of pharmaceutical companies; the number of drug company representatives in the country is proportionately five times that in Britain. Many drugs are promoted for diseases for which they are not indicated and in which their use may be hazardous, and information on sideeffects and contraindications is inadequate. Information supplied by drug firms to health workers in different countries must be standardised and the purchase and use of drugs in third-world countries made more appropriate to their needs. Summary
In many on
INTRODUCTION
THE major health problems in many underdeveloped countries are diseases of poverty and lack of sanitation which have almost disappeared from industrialised countries. Implementing the vigorous public health and immunisation campaigns necessary to fight these diseases requires large amounts of money, particularly in countries where 80% or more of the people live in rural areas. But spending on preventive measures frequently suffers because a large proportion of the health budget is used for buying drugs. Few of these countries have their own pharmaceutical industries, so rely on drugs bought from abroad. During a clinical appointment in an underdeveloped country, I studied the purchase, use, and promotion of drugs in that country to determine whether or not the amount of money spent on drugs could be reduced without adversely affecting curative
patient care. HEALTH PROBLEMS AND THE HEALTH BUDGET
The country studied has no substantial industries or natural and over 90% of the total population of 15 million live in villages, mainly engaged in subsistence farming. For many illnesses, the traditional healer is consulted first; Western-style medical care in most cases is provided at healthcentres and dispensaries staffed by medical auxiliaries. Only a third of all consultations take place at hospitals. The expenditure of the Ministry of Health in 1976 (all figures in this paper, unless otherwise stated, refer to the year 1976) was ,30 million (2% of gross national product’>2), of which 5-2 million (17%) was spent on drugs. The annual drug budget has increased cumulatively by one third in each of the last 5 years.3,4 A nationally owned pharmaceutical company at present produces about 7% of the Health Ministry’s drug requirements,’1 mostly by compounding imported raw materials into tablets, resources
Over 75% of the drugs purchased by the Ministry of Health used in hospitals.6 The drug allocation to dispensaries, the village health units staffed by auxiliaries, is 720 000 per year (1.5p for each patient seen). In comparison, four chloroquine tablets cost 2p and twenty aspirin tablets cost 1.7p. Not surprisingly, in many dispensaries the monthly allocation of drugs is consumed within fourteen days and many patients must be sent away untreated. Within the hospital services, the pattern of drug use varies. In small district hospitals over half the drug budget is spent on antibacterial and antiparasitic drugs, while in the national teaching hospital these drugs take only 25% of the budget and 10% is used for tranquillisers, sedatives, and antidepressants. Even the types of drugs within a single therapeutic category are used differently by different types of hospital. In the main national referral and teaching hospital, almost 40% of all drug prescriptions were for expensive proprietary preparations rather than the older (and cheaper’) generic alternatives. In several district and regional hospitals I studied only 5-19% of prescriptions were for proprietary products. are
DRUG PROMOTION
prescribing pattern in the large hospitals in this developing country- which in its emphasis on psychotropic drugs and expensive proprietary forms is similar The
to
that in industrialised countries-appears
to
be
strongly influenced by the promotional activities of the drug companies. These activities are considerable even though the annual drug expenditure is now only about 1.2% of the British National Health Service expenditure on drugs.8 In January, 1977, there were 147 drug company representatives in the country-1 for every 4 doctors (in Britain, the figure is about 1 for every 20 doctors9). Merely maintaining them is estimated to cost around 600 000 per year, and the total spending on promotion is probably substantially higher: in Britain, representatives account for only 40% of drug promotion costs.9 Even assuming that in this underdeveloped country the equivalent proportion is 60%, it may be estimated that the drug companies are spending at least D million per year on promotion and advertising, CO 700 per doctor, or over twice the equivalent sum in Britain1O). Although the market is small, spending power is highly concentrated, many doctors ordering drugs to be prescribed by medical auxiliaries as well as other doctors whole district. Each doctor in the country controls, average, the spending of [11500 on drugs. The estimated ratio of promotion costs to sales is similar to that in Britain but promotion is likely to be more effective; m most underdeveloped countries the drug companies have a monopoly of information since medical journals are not widely available in hospitals and independent assessments of drug efficacy or costs are not supplied by the industry and only rarely by ministries of health. Many drug companies take advantage of their control over the supply of information, frequently promoting hazardous drugs for a range of indications wider than normal for developed countries and omitting side-effects in promotional literature and package inserts. African Monthly Index of Medical Specialities (M.IM.S.,) a publication similar to the British version which is sent to all doctors in the country free of charge every two
within
a
on
811
months, is for many doctors the only source of up-todate information on drugs, their indications, and side-effects. Like the British M.l.M.S., it contains -information supplied by manufacturers but the information differs greatly: indications for drugs are more numerous and contraindications and special precautions less frequently mentioned. Few third-world countries have legislation restricting the stated indications for a drug or making illegal the issue of false or misleading information. SOME OF THE DRUGS PROMOTED
Aminopyrine and dipyrone are antipyretic analgesics which may produce agranulocytosis with a mortality as high as 0.57%." In the United States they are licensed for use only in patients with terminal malignant disease in whom safer antipyretics have been unsuccessful. 12 In African Af.7jM.6’. (November, 1977), 31 preparations containing these drugs are recommended as analgesics for minor conditions. Package inserts claim that they have a "wide margin of safety" (’Avafortan’, Asta Werke) or that their "safety has been proven and confirmed in over 500 publications throughout the world" (’Buscopan Compositum’ containing dipyrone, Boehringer Ingelheim). Few of the packages mention aminopyrine and dipyrone, using instead one of the longer chemical names such sodium 2,3-dimethyl-l-phenyl-5-pyrazolon-4-yl-N-methylaminomethane sulphonate monohydrate. Anabolic steroids may produce stunting of growth, irreversible virilisation in girls, and liver tumours.13-15 They are used in Britain to treat osteoporosis, renal failure, terminal malignant disease, and aplastic anaemia. In African M./.M.S., they are promoted as treatment for malnutrition, weight-loss, and kwashiorkor (’Decadurabolin’, Organon), as appetite stimulants (’Winstrol’, Winthrop), for exhaustion states (’PrimoboIan Depot’, Schering; ’Dianabol’, Ciba Geigy), and for "excessive fatiguability" in school children (’Dianavit’, Ciba Geigy). The use of high-dose oestrogen-progestagen combinations as a "hormonal pregnancy test" is associated with an increased incidence of congenital abnormalities.16-19 In Britain, the indication given for ’Primodos’ (Schering) since 1974 has been for the diagnosis of secondary amenorrhoea of short duration when pregnancy has been excluded. In African M./.M.S. primodos, as well as ’Menstrogen’ (Organon), ’Norlutin’ (Parke Davis), ’Paralut’ (Wallace), and ’Disecron’ (British Schering), is recommended for the diagnosis of pregnancy; the package insert of primodos does not mention the risk of fetal malformation. If a dose of the antihypertensive drug clonidine is missed by as little as 12 h, severe rebound hypertension and sometimes cerebral haemorrhage may result.20-23 It should thus be avoided when patients are likely to take prescribed drugs irregularly. In Africa, transport difficulties and administrative problems may hinder the regular supply of drugs during therapy.In addition, the concept of asymptomatic disease is not widely accepted, pills being taken only for relief of symptoms; in one study only 20% of patients were found to take their tablets regularly.24 Clonidine (’Catapres’, Boehringer Ingelheim) was introduced into the country in 1975; the company distributed free samples of the drug, sufficient for only two or three weeks’ use, before it was available through the Government central medical stores (c.M.s.). African M.l.M.S. does not mention the danger of suddenly stopping clonidine therapy, although British M.LM.S. does; in the manufacturers’ booklet two sideeffects are mentioned--compared to fifty in American advertisements-but not this risk. Boehringer Ingelheim have only now agreed to mention the danger in future package inserts. Several potentially hazardous drugs are promoted for minor indications or with no mention of special precautions or sideeffects : chloramphenicol (’Synthomycetin’, Lepetit) is promoted for use in "respiratory tract, urinary tract, surgical, ears, nose and throat, intestinal and biliary tract, venereal, obstetric, and gynaecological infections"; mesterolone (’Proas
androgen, is suggested for use in "declining physical activity and mental alertness in middle-aged men"; a combination of oxyphenbutazone (100 mg) and prednisolone (2.5 mg) (’Realin’, Ciba Geigy) is recommended for use in "all degenerative rheumatic diseases and non-articular rheumatism, fibrositis syndrome" in a dose of up to four tablets daily; triamcinolone acetonide (’Kenacort’, Squibb), a topical steroid, is marketed for indications which include insect bites and sunburn. Paediatric preparations of tetracycline are marketed by Lederle, Squibb, Pfizer, Lepetit, and Boots without mention of the possible risks or the recommendation, made in Britain, that tetracycline should not be used in children up to 12 years of age. Liothyronine (’Tertroxin’, Glaxo) is promoted for treatment of "lowered metabolic states", contrasting with the British M.l.M.S. indication of "severe thyroid deficiency". Methadone (’Physeptone’, Burroughs-Wellcome), recommended in Britain for severe pain, is included in African M.1.M.S. as a cough suppressant. Clioquinol has been withdrawn in several countries because of a risk of subacute myelo-optic neuropathy;25 Ciba Geigy claim the risk is dose-related, that the disease is confined to Japan, and that they have recommended a maximum total viron’, Schering),
an
dose of 7 g.26 In African M.l.M.S., the recommended maxitotal doses of prophylactic ’Entero-vioform’ (Ciba) and ’Marol’ (Ciba) are 7-14 g and 29.4 g of clioquinol, respectively, and prophylactic ’Mexaform’ (Ciba) does not have a stated maximum dose. Clioquinol is also marketed by Leo, Wyeth, Bayer, Wallace, and Smith, Kline, and French for the treatment of diarrhoea but African M.1.M.S. gives no maximum dose for any of them. mum
OTHER PRESSURES
third-world country, two Ministry of Health jailed in 1973 for accepting bribes; they had purchased sufficient quantities of an antibacterial agent and a tranquilliser made by one large company to last the nation for more than ten years.27,28 In the country I studied, a paper to be presented at a scientific meeting on the hazards of pyrazolone analgesics was withdrawn when the embassy of one industrialised nation suggested that such "criticism" was inappropriate at a time when that nation was financing a major aid programme.29 In
one
officials
were
NATIONAL DRUG PURCHASING AND POSSIBLE ECONOMIES
In 1976, the purchases of drugs by the C.M.S. exceeded drug sales by c.M.s. to Government hospitals and other units by a ratio of almost two to one. The excess is not evenly distributed; for 46 out of a total of 601 drugs purchased, the ratio of current stocks to annual sales is over four to pne. 36 of these 46 drugs are proprietary preparations manufactured by multinational companies. 16 of the 46 overstocked drugs are made by just four Western European companies, which have a total of only 24 drugs on the c.M.s. list. While it may be sensible to purchase large stocks of some drugs, the shelf-life of others, such as insulin or antibiotics, is usually 2-3 years, perhaps less in tropical conditions.30,31 There is 45 years’ supply of injectable rolitetracycline, and 21 years’ stock of cyclophosphamide in c.M.s.. Regional medical officers were recently instructed to use up drugs which were close to expiry date, regardless of cost, to avoid having to dump them. Rational purchasing of drugs could save as much as could more economical prescribing. With the adoption of cheaper generic alternatives instead of proprietary
812
preparations,
I have calculated that the annual
drug
could be reduced by 1.47 million, or nearly 30% of the total. (Full details of these calculations are available from the author on request.).
budget
Occasional Survey A REVIEW OF THE EVIDENCE FOR METHADONE MAINTENANCE AS A TREATMENT FOR NARCOTIC ADDICTION
DISCUSSION
In several developing countries a critical appraisal is being made of the role of curative medical services in the overall improvement of health. This includes attempts to rationalise drug spending by the ministries of healthrestricting the drug list to 100-400 items,32,33 abandoning the use of proprietary names,34-37 and either curtailing the duration of drug patents, or ceasing to grant brand-name patents on drugs.3g The development of national pharmaceutical industries has became a priority in many third-world countries, encouraged by United Nations agencies.39.4o In the interim, ways of reducing the costs of the major items of the drug budget must be found-e.g., by establishing an international drug-purchasing agency which could request tenders for supplying several countries’ drug needs and monitor quality control. There are often strong pressures on health ministries not to restrict spending on curative services. Doctors who have had postgraduate education in industrialised countries may not wish to compromise what they feel is the best treatment of an individual for the theoretical benefit of the whole population. But there is a growing awareness of cost-effectiveness in many developing countries although at present few ministries supply even rudimentary information on drug costs to their doctors. A change in attitudes to prescribing requires changes in medical students’ training in clinical pharmacology41 and textbooks which emphasise cost-effectiveness in therapy.42 Some countries have considered banning the promotion of drugs by company representatives,43,44 and others are curtailing the distribution of free samples and gifts to doctors.37,45,46 To collect, standardise, and disseminate information
drug use, regional cooperative pharmaceutical might be created.4O Alternatively, the World Health Organisation might take on the task of standardising promotional literature, ensuring uniformity in on
centres
information on the use, side-effects, and contraindications of available drugs.47 The drug industry has a role in the improvement of health in the underdeveloped world, but this role is smaller than it would have us believe. Many of the ethical drug companies might welcome controls making promotional excesses unrewarding. Within such a framework, the pharmaceutical industry could demonstrate the contribution which they can make to health care. However, the drug companies must not be permitted to become hazards to health in the underdeveloped world by failing to provide information or by draining scarce resources away from more effective projects. Requests for reprints to J. S. Y., Department of Metabolism and Endocrinology, London Hospital Medical College, Turner Street, Lon-
don E 1
2AD.
REFERENCES
1. Minister of Health. Budget Speech to Parliament; June 1976. 2. International Monetary Fund. International Financial Statistics;
ton, 1977. 3. Planning Officer, Ministry of Health. Unpublished. 4. Gish, O. Planning the Health Sector; p. 172, London, 1975. 5. Annual Statistics. Customs and Excise; p. 54, 1975. References continued at foot of next column
Washing-
MICHAEL GOSSOP
Drug Dependence Clinical Research and Treatment Unit, Bethlem Royal and Maudsley Hospitals, Beckenham, Kent METHADONE maintenance schemes are well established. About 50 000 addicts were receiving treatment in such programmes in the U.S. in 1972.1 The numbers in the U.K. are smaller because of the smaller size of the addict population. However, Home Office figures suggest that between 1970 and 1975 the numbers being prescribed methadone preparations were increasing (reaching 1543 in 1975). Methadone maintenance schemes are regarded as an effective treatment for narcotic addiction (narcotics being defined as opiate and opioid drugs such as heroin, morphine, pethidine, methadone, and opium). The
6. Public Expenditure Supply Votes; vol. III, estimates. 1976. 7. Speight, A. N. P. Trap. Doc. 1975, 5, 89. 8. Priorities in the Health and Social Services: The Way Forward. H. M. Stationary Office, 1977. 9. The Pharmaceutical Industry: a discussion document; p. 25. The Labour Party, London, 1976. 10. Lancet, 1976, ii, 680. 11. Huguley, C. M. J. Am. med. Ass., 1964, 189, 162. 12. Med. Lett. 1973, 15, 4. 13. Johnson, F. L., Feagler, J. R., Lerner, K. G., Majerus, P. W., Siegel, M., Hartmann, J. R., Thomas, E. D. Lancet, 1972, ii,1273. 14. Sweeney, E. C., Evans, D. J. ibid. 1975, ii, 1042. 15. ibid. 1973, ii, 1481. 16. Levy, E.P., Cohen, A., Fraser, F. C. ibid. 1973, i, 611. 17. Committee on Safety of Medicines. Adverse Reaction Series No. 13, 1975. 18. Janench, D. T., Dugan, J. M., Standfast, S. J., Strite, L. Br. med. J. 1977,
i, 1058. Greenberg, G., Inman, W. H. W., Weatherall, J. A. C., Adelstein, A. M., Haskey, J. C. ibid. 1977, ii, 853. 20. Conolly, M. E., Br iant, R. H., George, C. F., Dollery, C. T. Eur. J. clin. Pharmac. 1972, 4, 222. 21. Hunyor, S. N., Hansson, L., Harrison, T. S., Hoobler, S. W. Br. med. J. 19.
1973, ii, 209. 22.
Bailey, R. R.N.Z. med. J. 1975, 81, 268.
23. Yudkin, J. S. Lancet, 1977, i, 546. 24. Materu, N. L. B. Unpublished. 25. Lancet, 1977, i, 534. 26. Pinto, O. de S., Burley, D. ibid. p. 1256. 27. Daily Nation, June 18, 1973. 28. Daily News, July 25,1973. 29. Holmes, J. Circular letter, Feb. 20, 1973. 30. York, P. Unpublished. 31. Steel, J. M., Mngola, E. N. Trop. Doct. 1974, 4, 184. 32. Management Sciences for Health. Procurement and use of medicines in Afghanistan. Boston, 1974. 33. Bibile, S. Case studies in transfer of technology: pharmaceutical policies in Sri Lanka. U.N.C.T.A.D. report TD/B/C.6/21; p.12. Geneva, 1977. 34. ibid. p.13. 35. Lancet, 1977, ii, 602. 36. World Health Organisation. Consultation on the selection of essential drugs. DPM/76.1;p. 21. Geneva, 1976. 37. Lall, S. Major issues in transfer of technology to developing countries. U.N.C.T.A.D. report TD/B/C.6/4;p.53. Geneva, 1975. 38. ibid. p.22. 39. ibid. p.61. 40. Scrip, July 2, 1977, p.16. 41. Herxheimer, A. Lancet, 1976, ii, 1186. 42. Upunda, G., Yudkin, J., Brown, G. Unpublished. 43. Sainsbury Committee. Report of the Committee of Enquiry into the Relationship of the Pharmaceutical Industry with the National Health Service; para. 351. H.M. Stationery Office, 1967. 44. Guardian, Aug. 16, 1977. 45. Lancet, 1977, i, 1016. 46. Lancet, 1976, i, 817. 47. World Health Organisation. Press Release W.H.O./39. Oct. 12, 1976.
