Big drug companies are conducting clinical trials in Africa with no consideration for ethics, the health of patients or the relevance of the drugs to the needs and the pathology of the continent. Nobody is testing traditional medicine to see if it works, and how.
Novofir is an antiviral drug developed by the United States biopharmaceutical company Gilead Sciences to combat Aids. The US government and the Bill and Melinda Gates Foundation paid for the organisation Family Health International to carry out clinical trials in Nigeria. But in March 2005 serious ethical shortcomings caused their suspension. Trials were also halted in Cameroon (February 2005) and Cambodia (August 2004) (1), but continue in Thailand, Botswana, Malawi, Ghana and the US.
In 2001 30 Nigerian families sued another US pharmaceutical company, Pfizer, in New York over trials of Trovan, an antibiotic to combat meningitis. In the course of the study, during an epidemic in 1996, 11 children out of 200 died and others suffered brain damage and paralysis (2).
The developing world is now a place where pharmaceutical companies ignore ethical considerations and the health of patients. Without the informed consent of their subjects, who receive only the most basic information and usually inadequate therapeutic supervision, they conduct clinical trials with limited benefits to specific patients or the local population as a whole.
Before any new medicine is approved and marketed, it must go through formal, rigorous clinical trials designed to establish tolerance and assess its effectiveness. It is estimated that almost 100,000 such trials are carried out worldwide each year, 10% of them in developing countries and 1% in Africa. During the 1990s the number of foreign trials financed by US public and private funding reportedly rose from 271 to 4,458 (3).
The concept of evidence-based medicine, using statistics and testing, has prevailed in the West since the end of the 19th century (4). The first formal statement of ethics was the Nuremberg code, adopted after the trials of Nazi doctors in 1947. But the postwar spread of medical ethics was slow to encompass pharmaceuticals, and regulation only developed in reaction to scandals and accidents.
International declarations extended and refined the code: the 1964 Helsinki declaration defined the main ethical principles of medical research and the 1981 Manila declaration dealt with clinical studies in developing countries. They insist that trials should be confidential, and that those conducting them should be competent and should protect their subjects, whose consent they have secured. These were only recommendations and no sanctions were proposed.
An antiseptic, Stalinon, killed 102 patients in France in 1955; thalidomide was responsible for 12,000 foetal abnormalities between 1957 and 1962; a powder, Morhange, poisoned 145 infants and killed 36 in 1972. Scandals such as these led to the regulation of clinical trials. But not until 1988 did the Huriet-Serusclat law lay down an authoritative code of ethics – implicit recognition that clinical trials had been conducted illegally for two decades.
Africa’s few medical and pharmaceutical regulations date from the colonial era and are now obsolete or ill-adapted to current circumstances. There is increasing danger that ethical considerations will be ignored as drug companies relocate tests to a continent where costs can be five times less than in developed countries. Since African disease rates, especially infectious ones, are higher and symptoms have not been weakened by repeated intensive treatments, epidemiological conditions are more favourable for trials. The weakness of local health structures generates a docile patient pool, making the process easier.
Africa is a perfect environment in which to circumvent ethical principles. During the trials of Trovan, there was no formal consultation with the Nigerian authorities or Nigeria’s ethical committee about the information given to families involved or about securing of their consent. The tests of Tenofovir on 400 Cameroonian prostitutes between July 2004 and January 2005 failed to meet ethical requirements.
Tenofovir reduces transmission of SIV, the equivalent in monkeys of HIV. The manufacturers decided to conduct trials among a high-risk group – sex workers in a country with a high rate of HIV infection – to find out if it might work on human beings. Only information in English was given to the volunteers, many of whom were French-speaking and illiterate. The anti-Aids organisation Act Up-Paris and Cameroon’s Network for Ethics, Rights and Aids (Reseau Ethique Droit et Sida), claim that some of the women thought they were receiving a vaccine. Those who were given a placebo (5) did not receive any advice on Aids prevention or medical follow-up, which did not worry Cameroon’s national ethical committee. As Fabrice Pilorgé of Act Up points out: “There is an obvious conflict of interest between offering prevention and testing a preventive medicine – the test is only valid if the women are exposed and become infected.”
A recommendation made by the World Medical Association in the Helsinki declaration was that ethical committees should examine the experimental protocol before any study, checking that it is relevant and appropriate to the social and economic context in which it is to be conducted. Over the past decade, such committees have sprung up across Africa, but can still lack the necessary expertise and funding (6).
Not only does Africa have its own pathologies, but conditions under which drugs are administered and their side effects monitored are problematic. It is reasonable to ask whether any trials conducted there are relevant to African needs. Out of 1,450 new medicines marketed between 1972 and 1997, only 13 were for tropical diseases (7). Since trials are determined, financed and organised by the pharmaceutical industry, decisions as to which drugs should be tested and how are inherently biased. African governments find it difficult to develop clear, coherent policies that would allow them to have real control over the activities of profit-driven drug companies.
The mismatch between the poverty of developing countries and the power of the medical industry exacerbates the conflict between scientific and commercial interests. By the end of the 1990s the pharmaceutical industry’s global turnover ($480bn) was greater than the GDP of all the countries of sub-Saharan Africa ($380bn).
Scientifically, it is possible to justify the trial of Trovan on the grounds that it allowed the effectiveness of the drug to be tested under consistent conditions on a suitable number of subjects. But the study overlooked the fact that the cost of the product and the limited chances of its commercialisation without state subsidy make its use in Africa highly unlikely.
The appropriateness of Tenofovir in an African context was similarly ignored. If the trial confirms that it prevents HIV transmission, it will be marketed as a prophylactic against Aids. But it is not a realistic one in a continent that struggles to treat its sick and to promote the cheap and more widely available condom. Experience in malaria prevention demonstrates the impossibility of persuading healthy people to take medicine every day for the rest of their lives, especially if it is expensive. Some conclude that trials of Tenofovir were done in developping countries, among prostitutes, to secure quick, clear results without administrative complications or excessive costs.
Some scientists, such as Philippe Kourilsky, director of the Pasteur Institute in Paris, maintain that the health crisis in the third world is so urgent that it justifies the relaxation of regulations (8). But to override the precautionary principle – under which the harm trials cause would demand their regulation despite the absence of scientific consensus – because of cost would imply that different criteria apply to different parts of the world (9). In the rich world all that matters is that the product works. Among the poor, safety would be subordinated to the ability to pay, forcing them to make do with what they can afford, whatever the result of trials.
The result is strategic imperialism, which imposes rules upon the poor without their consent. Kourilsky’s insistence that it would be “ideological imperialism to apply the rules of the rich to those who are not in a position to endorse them” permits an unacceptable relativism. Third parties, especially those who make the rules, cannot decide who can endorse those rules.
If they are to meet their health needs, Africans must be able to conduct their own trials. The issue is all the more important since it affects traditional medicine, which is cheaper and more widely accepted. Clinical tests proving the uselessness or effectiveness of these traditional remedies could enhance heritage and allow an indigenous pharmaceutical industry to emerge.
There are many African plants with reputed anti-infection, anti-inflammatory and diuretic properties that might be used against infections, rheumatism, hypertension or cardiac insufficiency; some might prove as important as quinine extracted from cinchona bark, aspirin from the willow, reserpine from an African Rauwolfia, and anti-cancer agents that have been derived from the Madagascar periwinkle.
Only drugs that meet Africa’s needs should be tested there. They should satisfy specific criteria determined by their potential use. They should be effective and, given the inadequacy of local mechanisms to monitor side effects, harmless. They should be accessible, and easy to distribute, prescribe and administer. They should have a long shelf-life and encourage patient adherence to treatment, compensating for weaknesses in the health system. But the priority is to allow local communities to make their own decisions about trials, oversee and carry them out, allowing developping countries to make independent use of clinical research.
* Jean-Philippe Chippaux is a doctor and director of research at the Institute of Development Research at Dakar in Senegal. He is the author of ‘Pratique des essais cliniques en Afrique’ (IRD Editions, Paris, 2004)
(1) Complément d’enquête, France 2, 17 January 2005.
(2) The case remains unresolved.
(3) US department of health & human services, Washington, 2001.
(4) See Harry M Marks, The Progress of Experiment: Science and Therapeutic Reform in the United States, 1900-1990, Cambridge University Press, 2000.
(5) To verify the effectiveness of the drug, those participating are divided into two groups, one of which receives a dummy tablet that does not contain the active ingredient.
(7) See Patrick Trouillet, C. Battistella, J. Pinel, Bernard Pécoul, « Is orphan drog status beneficial to tropical disease control ? », Tropical Medecine and International Health, Oxford, 1999, 4, p. 412-420.
(8) Philippe Kourilsky, Vaccination : quand l’éthique devient immorale, Pour la Science, Paris, 2004.
(9) See the report to the French prime minister, Philippe Kourilsky and Geneviève Viney, Le principe de précaution, Odile Jacob and Documentation française, Paris, 2000.