Third World Drug Marketing

Just as Neville Chamberlain promised "Peace for our time" in 1938-months before the outbreak of the Second World War-so the World Health Organization (WHO) today proclaims: "Health for all by the year 2000." As a prescription it is admirable; as a prediction it is absurd. Just how absurd is obvious from the remarks of the director of WHO's pharmaceuticals programme, at a recent symposium in Rome:

"Perhaps we should start to think now-or to dream-of a future regulatory system which would facilitate the discovery and introduction on a world-wide scale of drugs important, or essential, to meet real health needs and, at the same time, prevent the international trade of those proven to be harmful to health on the basis of scientific evidence."

Clearly, one must dismiss any possibility of "health for all" in the foreseeable future. When a senior optimist in the World Health Organization suggests that "perhaps" the time has come "to dream" about the provision of essential drugs, and the control of dangerous ones, there is a very long way to go.

The drug multinationals underpin the nasty trade in hazardous pharmaceuticals. Much of the evidence of what these companies do is no doubt hidden or missing. Nevertheless, reports now coming in are frightening enough. Take this example, from an article in New Scientist earlier in the year:

"By now, Gail's condition was critical The infection which started in her mouth had erupted all over her body and doctors found abscesses on her lungs, too. The flesh on her lips and gums fell away, quite diseased, as was part of the exposed jawbone. The Johannesburg team ran a battery of tests, but it failed to find any viral explanation of Gail's condition .. Having eliminated a viral cause ... the team next asked what drugs Gail had taken. She mentioned Cibalgih. There was no need to look any further . . . "

Products similar to Cibalgin-which was withdrawn from the market by Ciba-Geigy several months ago-continue to be sold by drug multinationals throughout the world. These drugs contain dipyrone, and cause agranulcytosis, a disease in which a sharp drop in 'the production of bacteria-fighting white blood cells leads to greatly increased susceptibility to infection. In a careful study of patients treated with these compounds, the incidence of agranulocytosis was nearly I in 100 and the mortality rate about I in every 200.

Dipyrone and related drugs are analgaesics, painkillers about as effective as aspirin. Because a-number of relatively safe alternatives exist, independent authorities are pretty well unanimous that the drug should not be used. A standard British text, Martindale's Extra Pharmocopoeia, emphasizes for example that " . . . the risk of agranulocytosis in patients taking dipyrone is sufficiently great to render the drug unsuitable for use."

By 1977, the WHO reported that eight countries had altogether banned this drug. Elsewhere it was, and still is, liberally available. Gail-whose symptoms were described above-bought her sample from a pharmacy in Mozambique. In neighboring Tanzania, a British doctor, John Yudkin, reported nine such products on the market in 1977; they were made by Asta, Hoechst, Boehringer-Ingelheim, Ciba and Sandoz. In his paper, To Plan is to Choose, Yudkin calculated that the amount of such drugs used in Tanzania in 1976 would have very likely killed 630 people in that year.[1]

These are certainly not isolated cases. A paper published earlier this year by the Regional Office of the International Organization of Consumers' Unions in Penang, Malaysia, reported 20 preparations containing dipyrone and related compounds on the Malaysian market.[2] In neighboring Thailand, some 28 similar preparations are listed in the main prescribing guide. In most cases, the notes for doctors say nothing at all about the possibility of dangerous side effects. Moreover, the package inserts collected recently from some of these include the following:

Two samples of the similar Winthrop product were obtained. The package insert in one stated: 'Conmel is a derivative of aminophenazone. It may, therefore, on very rare occasions product agranulocytosis.' More trenchantly, on a packet supplied as a free sample to a doctor, ran an overprinted message: `Warning: this drug may cause fatal agranulocytosis.'

Many other cases have been reported recently, demonstrating both how undesirable drugs may be promoted in developing countries, and how otherwise satisfactory drugs may be promoted in undesirable ways.

• SMON stands for sub-acute myelo-optic neuropathy, a crippling and sometimes fatal disease of the nervous system. In Japan in the 1960s cases of SMON reached epidemic proportions, affecting an estimated 20,000 to 30,000 people. The disease has been reported in other countries as well. Cases of SMON are clearly associated with the drug clioquinol and its derivatives, particularly when taken in normal or high doses over long periods of time.

  Several countries have had the drug altogether withdrawn not only because of these devastating side-effects, but also because of its highly questionable therapeutic value. In other countries, the use of clioquinol is restricted to a few very specific indications.

  Nevertheless, clioquinol and related drugs are widely available in developing countries. The world sales of a principal manufacturer, Ciba-Geigy, are estimated at U.S.$40 million a year. Two Ciba brands, widely sold in Southeast Asia, are Entero-Vioform and Mexaform. Remarkably, the directions for these drugs given in Malaysia and Thailand suggest their use for "non-specific diarrheal disorders and also as a prophylactic. "

• The antibiotic chloramphenicol, according to Martindale's, "can cause ... severe, irreversible and often fatal aplastic anemia." As such, it should be taken for only the most serious indications, never for minor infections. Virtually all of thenine brands of chloramphenicol sold in Malaysia, and the 30 other brands available in Thailand, advertise a wider application. One product-made in Thailand under license from the Italian firm Zambon suggests Mycochlorin for nearly 50 different conditions (including "measles, chickenpox, tonsilitis, skin diseases, etc.") and promises "an extremely low toxicity."

• The antibiotic tetracycline is generally regarded in the West as contraindicated for children under eight years. or for women more than four months pregnant. The reason is that these drugs tend to retard foetal bone development, and to permanently stain children's teeth. However, Wolfgang Howarka of the International Organization of Consumer Unions, has reported that of the 42 tetracycline preparations in the 1979 Drug Index for Malaysia and Singapore, only two included such a caution. Other preparations including those from Pfizer, Hoechst. Lederle and Dow Lepetit- list dosages for young children in the doctors' prescribing guide.

  Research on the Social Audit report, Insult or Injury?, carried out mainly in India and Malaysia in 1978, turned up a number of other highly questionable incidents. For example:

• With some drugs marked discrepancies exist between instructions in the West and those in the Third World. The maximum recommended dose with Wellcome's migraine drug Migril turned out to be I0mg per week in the USA; 12mg per week in the U.K.; and 24mg per week in Africa and Asia. Similarly, the recommended dose of a Glaxo combination antibiotic, Guanimycin Suspension Forte, was around twice as high in developing countries as in the U.K.

• In the U.S., the Food and Drug Administration requires the drug Meclizine to be contraindicated for women who arc or may become pregnant. Inadequate warnings were found in prescribing literature for the Glaxo version of this drug (Ancoloxin) in India and Pakistan. Glaxo said in 1978 that they would change the offending literature in these two countries, but maintained that elsewhere their prescribing literature compared with that used in the UK. Ancoloxin is recommended simply for control of nausea and vomiting in the U.K. But the caption on a can bought in Malaysia in late 1979 specifically recommends this drug for the control of morning sickness.

The problems created by the drug multinationals in developing countries are not simply the result of the marketing of dangerous or questionable products. For example, serious damage may occur-just as it does with infant formula-when otherwise satisfactory products are given a really hard sell. Just how hard drugs may be sold is probably best illustrated by Yudkin in To Plan is to Choose. Yudkin reported, for example, that Central Medical Stores in Tanzania had in stock a 46-year supply of an injectable antibiotic made by Hoechst-though the shelf life of the drug would be under two years, and probably no more than six months in tropical conditions.

Another example, illustrating what happens on the ground, "as discussed by a nurse who had been working. in Bangladesh. On a recent British radio program, she described how her husband heard a drug company representative try to persuade a young doctor that the drug frusemide (a drug which gets rid of excess fluid in the body) was a very good drug to use on children who had kwashiokor or marasmus. These are serious deficiency diseases, whose symptoms distended belly, wasted muscle on limbs are all too often shown in appeals for famine relief. The nurse explained:

"... my poor husband felt that he had to jump in at that point and say. 'Well, alright, the swelling will go down because you in fact urinate frequently and get rid of the fluid but it ii! kill the child.' And the drug representative said: `Well, the child is going to die anyway.'"

The idea of drug as panacea is simple and dangerous. It can and does produce tragic results at both individual and national health planning levels. Evidence of the tragedy at a national level can be found in the proportion of national health budgets spent on drugs rather than allocated to more useful and equitable preventive and public health measures. In the average developing country, the proportion of the health budget spent on drugs is typically between 30 and 50 percent, As a prescription for "health for all" this is damaging enough. I n light of some of the marketing practices of the drug multinationals, it is simply unconscionable.

But it is one thing to suggest the drug multinationals are largely responsible for all this--and quite another to suggest they can effectively be held accountable. There are several reasons why they can't.

These companies are not staffed exclusively by cynical or malevolent people. The main reason for their sometimes lethal excesses is not bloody mindedness, but the single-minded preoccupation with business objectives.

Beyond this, the multinationality of the drug companies compounds the harm-in particular because this allows an endless, often devious shifting of responsibility. Typically, you ask head office about malpractice in a subsidiary, and you are referred to the subsidiary, which head office says is responsible for management affairs. But if you question the subsidiary, more likely than not you will be referred to head office-and be told that they take overall responsibility for the activity in question.

But even if one does pin someone down, there is no guarantee of a straightforward response. In the absence of overwhelming and irresistible evidence of impropriety, one is more likely to be met with equivocation and excuse than anything else. The classic response of the multinational to an accusation of malpractice is to say "we observe the laws of the countries in which we operate." Given the state of the laws and of law enforcement in many developing countries, this is tantamount to a multinational saying "we obey laws which do not exist."

Under these circumstances, both home and host countries have substantial responsibilities in controlling the excesses of the drug multinationals. But equally, there is a clear role for the World Health Organization. Of particular relevance here is Article 21 of the WHO's constitution, which states:

"The Health Assembly shall have authority to adopt regulations concerning ... advertising and labelling of biological, pharmaceutical and similar products moving in international commerce."

This article gives the World Health Assembly the power to introduce regulations which, if passed by a simple majority, then become binding on all member states-whether they voted in favor or not.

However, this Article has never been Used. Perhaps the time has now come for the WHO to stop dreaming-and to take decisive action to control the multinationals' trade in dangerous drugs.

FOOTNOTES

1 John S. Yudkin, To Plan is to Choose (Mimeographed Paper, 1977.)
2 See Wolfgang Howarka's Dangerous Drugs (IOCU, Penang, Malaysia).

Charles Medawar is Director of the London-based Social Audit, Ltd., an independent, non-profit organization concerned with improving government and corporate responsiveness to the public. He is the author of Insult or Injury? An Inquiry into the Marketing and Advertising of British Food and Drug Products in the Third World (Social Audit, 1979).