Drugs Testing in Nigeria - Essay Example

?Ethical Dilemma – Drugs Testing in Nigeria Introduction and Situational Analysis In 1996, Pfizer Inc., one of the world’s largest pharmaceutical companies, was attempting to complete the clinical trials of one of its major new compounds. Named Trovan, the product was designed as a new antibiotic which, researchers believed, would effectively treat pneumonia, meningitis, to name but a few of the 16 infectious diseases it was targeted to treat. It was estimated that the market value of this new drug would be in excess of $1 billion. Trovan had already undergone clinical trials on animals and on adult human patients. It had not yet been tested on children, and from tests which had been carried out on young animals, researchers had some reason to believe that the drug might cause damage to joints. There was evidence that using Trovan could lead to problems with joints, tendons and bones, and even perhaps cause liver damage. Led by Scott Hopkins, the team developing Trovan were anxious to carry out controlled clinical trials of the drug on children, in order to conclude whether it could safely be marketed as a treatment for diseases in children. While they believed that further refinement of the drug would make it much safer for children, they would need firm evidence in order to obtain approval from the United States Food and Drug Administration (FDA) for it to be marketed. At around the same time, in February 1996, there was a serious outbreak of meningitis in the area around Kano, a major city in northern Nigeria. Soon, over a hundred children were being brought to the basic local hospitals every day, and by March 3, 1,273 deaths had been reported, with some accounts putting the total at closer to 10,000 (Spar and Day, 2006, p.11). As most of the children infected with meningitis would certainly die if given no treatment, Hopkins looked upon the outbreak as ‘a unique opportunity to test Trovan pills on children’, and ‘since Nigeria had both a raging epidemic and a distinct absence of personal injury lawyers, a drug trial there would be far more efficient’ than in the United States (Spar and Day, 2006, p.2). Meningitis outbreaks are fairly common across a large area of sub Saharan Africa during the dry season, when cold weather, malnutrition, and urban overcrowding can lead to the disease spreading rapidly among children. Epidemics of meningitis are caused by a particular strain of the bacteria, and the Trovan researchers had reason to believe, after extensive testing, that their new drug would be effective against that strain. It is worth understanding the processes which a drugs company needs to complete if it intends to market a drug in the United States, because, as we will see, it is questionable whether the situation at Kano provided an opportunity to carry out a satisfactory trial of Trovan on children. When a new compound is being developed, the pharmaceutical company responsible for it lodges an investigational new drug application, or IND, with the FDA. Having obtained this, the company is authorised to begin conducting clinical tests, which may be rolled out to many scenarios and over thousands of patients before a drug seeks FDA approval to be marketed. While such approval is sought within the United States, or from the appropriate authorities in other countries, it does not preclude a pharmaceutical company from carrying out clinical trials overseas. Indeed, it is even possible for a drugs company to conduct all of their clinical testing overseas, and only when the research gathered has shown the drug to be both safe and effective, for it to be submitted to the FDA for approval. In the case of Trovan, the new drug already had an IND, had already been subject to extensive clinical trials within the US, and so the team developing it were perfectly entitled to add a trial in Kano to its IND, or, alternatively, to carry out the tests in Nigeria and, if the results were positive, submit this data to the FDA subsequently. Pfizer would also have to meet some conditions under Nigerian law in order to conduct a clinical trial of Trovan at Kano, although such conditions are somewhat less comprehensive than those demanded by law in the United States and Western Europe. Pfizer would, however, have to submit its plans for a trial to the deliberation of a committee at the hospital, and would also need to obtain consent from every patient involved, and, if they were minors, from their parents or guardians. This consent had to be ‘informed’, in that the person responsible would need to be made fully aware of the nature and implications of their decision. At this stage, it should be understood that the conduct of clinical trials overseas, and especially in developing countries, is by no means an uncommon practice among leading pharmaceutical companies. Indeed, between the mid-1980s and the mid-1990s, overseas clinical trials had increased 10-fold. Writing in 2006, Shah noted that major drug manufacturers such as GlaxoSmithKline had already been carrying out about 30-50% of their experiments in developing countries, and were planning to boost this figure up to 67% in 2006. The advantages of such overseas trials, as seen from the perspective of the drug companies, are manifold. In the United States and western Europe, doctors are highly-paid, which drives up the costs of performing clinical trials in these countries, and patients in these regions are suspicious of taking new drugs. Americans buy, on average, in excess of 10 prescriptions annually, but less than 1 in 20 are prepared to take part in clinical research’ (Shah, 2006, p.4). In many developing nations, by contrast, the presence of cheap personnel and less stringent official regulations makes them attractive to the drugs companies as sites for clinical trials. Indeed, GlaxoSmithKline’s CEO estimated in 2004 that moving just 30% of its remaining domestic clinical trials overseas would save the firm more than $200 million a year. Furthermore, the carrying out of tests using patients in different environments and from different ethnic groups can also produce more reliable results. While pharmaceutical companies often claim that the trials they carry out in developing countries are conducted to the same high standards that they would be subject to at home, due to the lack of regulation in many of these regions, there is no way on knowing to what extent this is the case. However, the existing medical facilities at Kano were incredibly basic, and insufficient to meet the needs of the local population even when there was not an epidemic to be dealt with. Indeed, Spar and Day (2006) report that the ‘Kano Infectious Disease Hospital, the most likely site for a clinical trial, was viewed by aid workers as one of the worst hospitals in the world’ (p.9). It suffered from a lack of beds, doctors, nurses and medicines. Therefore, the team from Pfizer had to consider the current lack of facilities, and the very limited period of time in which they could set up a trial. It should be noted that when a clinical trial is carried out in the United States or western Europe, it has usually been in planning for up to a year or more. In this case, the researchers from Pfizer had only a matter of weeks to make decisions and organize a trial. The team at Pfizer had to decide whether a trial in Kano was the right decision. In terms of meeting Nigerian conditions, they were confident that they would be able to gain the consent of the committee at the Kano hospital. In terms of finances, the cost of holding a trial in Nigeria would be deeply insignificant for such a major pharmaceutical company, especially when set against the cost of conducting a clinical trial domestically. In terms of actually working towards marketing Trovan, Pfizer had to consider whether the FDA would accept any results from a trial in Kano. Perhaps crucially, ‘Whatever the risks of a clinical trial were, Pfizer executives and investors knew the price of delay – an estimated $1.3 million per day in unrealized sales’ (Spar and Day, 2006, p.11). As Spar and Day (2006) put it, if the trials went wrong, ‘the cure in this case might well prove far more dangerous than the disease’ (p.2). Nevertheless, ‘Trovan promised a quick cure in a bottle of pills. Scores of lives, and millions of dollars, were seemingly on the lines’ (p.11). Many commentators would later conclude that the latter took precedence in the decisions of Pfizer executives. Stakeholder Analysis Pfizer Inc., was founded in 1849 has long been one of the world’s leading pharmaceutical companies, and has since become the world’s largest. In 1995, it enjoyed a net income of $1.6 billion and employed nearly 44,000 people. To keep its business profitable, Pfizer depends on producing new drugs for marketing mostly in developed countries. Once a new drug has been approved for marketing by the U.S. Food and Drug Administration, the company which produces it only has a patent on it for 20 years, and so such companies have to continually discover new compounds and manufacture new products if they to survive. For this reason, much of the investment in the pharmaceuticals industry is channelled into the research departments of companies such as Pfizer. At the beginning on 1996, Pfizer was working on 15 compounds which were nearing the end of development, and a further 48 in the early stages. Pfizer had made heavy financial investments in Trovan and Viagra, a drug which has proven to be an effective treatment for many cases of erectile dysfunction in men. For Pfizer therefore, carrying out trials at Kano which could lead to the approval of Trovan for marketing in the United States would allow them to immediately begin making huge profits from years of research on the promising drug. Not carrying out a trial at Kano would probably mean that the marketing of Trovan would need to be put on hold for some months or even several years, as adequate research was gathered elsewhere. The children on whom the clinical trial was to be conducted were living in Nigeria, the most populous country in Africa, but also one of the poorest, despite the massive oil revenues, which in 1995 had amounted to $10.4 billion. Indeed, in the same year, the corrupt and unstable Nigerian government invested just 0.1% of it the GDP, some $21 million, on health care in the country. Children who became infected with meningitis in the country therefore had little chance of survival without medical treatment, and the latter was so scarce and ineffective that the situation was bleak for the families affected. The facilities at Kano were fundamentally insufficient, with only an overburdened hospital and a Doctors Without Borders team. The latter could not cope with the demand for treatment, and so for many families who arrived in Kano, there was little choice over whether to allow Pfizer to try the new drug on their children. Analysis Based on Ethical Theories Noble laureate Joshua Lederberg declared, ‘The blood of those who will die if biomedical research is not pursued will be on the hands of those who don’t do it’ (Shah, 2006, p.x). However, the way in which such research is pursued, and the circumstances in which trials are conducted, is crucial. In terms of analysing this ethical dilemma based on various ethical theories, we can begin by dividing a deontological approach on the one hand, which judges the morality of the action based on how far it conforms to rules and duties, from teleological and consequentialist approaches, which would judge the rightness or wrongness of a decision on the basis of its eventual outcome. Beginning with a deontological approach, the only firm rules that Pfizer had to conform to if they would be acting in Nigeria would be those of the local authorities, and then of any codes of international medical ethics. The team met the conditions of the Nigerian authorities by seeking and acquiring the approval of a committee at the Kano hospital. Existing conventions on medical ethics might provide some guidance when adopting a deontological viewpoint. Such declarations and conventions are not formally binding, but provide fairly clear guidance. Perhaps the first codification of international medical ethics is the Nuremberg Code of 1946, produced in response to the horrors of Nazi medical testing in the 1940s. This Code states that ‘medical research involving human subjects is only justified if there is a reasonable likelihood that the populations in which the research is carried out stand to benefit from the results of this research’ (Spar and Day, 2006, p.8). However, as Joe Stephens (2000) makes clear, clinical trials carried out by wealthy firms in developing countries ‘help speed new drugs to the marketplace – where they will be sold mainly to patients in wealthy countries’. Shah (2006) develops this theme further still, when she asserts that ‘those [drugs] that aid the poorest are generally of little interest to drug companies, which commit themselves to the financial needs of their investors’ (p.xiii). There are several articles of the Helsinki Declaration on medical ethics which seem to have been contravened by the Pfizer team in this case. Article A5 states that ‘In medical research on human subjects, considerations related to the well-being of the human subject should take precedence over the interests of science and society’, suggesting that the Pfizer team should have considered whether they could provide better care than could already be given to infected children. Likewise, article B17 states that ‘Physicians should abstain from engaging in research involving human subjects unless they are confident that the risks involved have been adequately assessed and can be satisfactorily managed’. With scant medical resources in Kano already stretched up to and beyond breaking point, the team from Pfizer had to consider whether their arrival in the hospital compound would divert what resources there were from the care of the sick. Shah (2006) suggested that although many patients in poorer countries are doubtless helped by clinical research, as trials ‘become an ever-larger cash cow for strapped hospitals and clinics, a larger proportion of scarce resources gets diverted away from providing care’ (p.xii). Yet an another article of the Helsinki Declaration that was probably contravened by Pfizer in this situation was article B20: ‘The subjects must be volunteers and informed participants in the research project’. In this example, as will be seen below, it seems that Pfizer could not guarantee this. Moving on to theories which would judge the morality of Pfizer’s decision based on its outcomes, an action can be considered teleological when it is carried out for the sake of its result. In this case, while Pfizer argued that the rate of children who died in its care at Kano was lower than the rate among infected children being treated using other methods, many children seem to have received insufficient care, and the trial was not being carried out mainly for their wellbeing and recovery, but so that the drug could be sold in western countries, for the benefit of children thousands of miles away. Some would consider this a good outcome, in that Trovan, if proved successful, would save lives in the future. This would include those who subscribe to a consequentialist approach, but these people would have to conclude that Pfizer’s decision was the wrong one, given that Trovan was never actually marketed for children. It was deemed unsafe by the FDA. From ever perspective, Pfizer made the wrong decision. It did not comply with existing standards of international medical ethics, and its actions were not vindicated by a future, greater good, because Trovan has been deemed unsafe for children to consume. Conclusions and Recommendations Pfizer got approval from the committee set up at the Kano hospital, and acquired FDA approval to export Trovan to Nigeria, but there remains a serious question as to whether they should go given the terrible conditions on the ground. In the same compound at Kano where Pfizer set up their testing centre was another clinic being run by the humanitarian charity, Doctors Without Borders. The latter flies medical personnel to wherever health crises are unfolding in the world, with the sole objective of providing care and saving lives. The Pfizer clinic at Kano was open for just three weeks, and some of the team returned only once thereafter to check on the progress of their patients. A doctor who had been working at Kano with Doctors Without Borders at this time was furious with this behaviour: ‘I would take away their medical licenses’ (Stephens, 2000). For Joe Stephens (2000), Pfizer were ‘using Nigeria’s meningitis epidemic to conduct experiments on children with...a drug not yet approved in the United States’, part of ‘a booming, poorly regulated testing system that is dominated by private interests and that far too often betrays its promises to patients and consumers’. It was suggested earlier that by going to Kano, Pfizer’s trial might have the undesirable effect of draining scarce resources and personnel away from other vital healthcare. It seems that this anxieties were well-founded. Stephens (2000) found that ‘Hospital officials have the researchers two of the best-maintained patient wards, including much of the compound’s coveted bed space’, while Pfizer also diverted key staff from other tasks by offering them double pay. When carrying out medical tests using human subjects, a key issue of obtaining ‘informed consent’ from all patients and/or their representatives. However, a Nigerian technician who took part in the Pfizer trial at Kano reported that the ‘patients did not know if it was research or not’ (Stephens, 2000). Pfizer spokespeople have claimed that local nurses explained what was happening to the parents of all the children, but crucially, Pfizer has been unable to produce signed consent forms, and even if they were able to do so, given the widespread illiteracy in the area, few enough people would have been aware of exactly what they were signing. Beyond the dilemma of whether or not to go to Nigeria in the first place, it has been suggested that once established in Kano, the conduct of the Trovan trial was haphazard and riddled with mistakes. 198 children suffering from meningitis were taken in by the Pfizer team over the course of a fortnight, but Stephens (2000) reports that they neglected to regularly test the blood of some patients, while others were kept on Trovan even after their condition had seriously deteriorated over the course of several days. Indeed, when FDA officials came to scrutinise documents from the Kano trial, they came across dozens of issues which could not be resolves, and refused to allow Pfizer to market Trovan to children in the United States. Trovan has not turned out to be the miracle drug that the development team at Pfizer were hoping for. In its first year on sale, Trovan drugs worth $160 million were sold, but within just 16 months, there were a staggering 140 reports of liver problems, the US restricted sales and the EU suspended them outright. Pfizer clearly made the wrong decision in authorising and carrying out the Trovan test in Kano. In future, they should carefully consider the situation on the ground, whether they can be worked with effectively, and whether they will be able to conform to all standards of medical ethics before they authorise a clinical trial in a developing country. References Shah, S. (2006). The Body Hunters: Testing New Drugs on the World’s Poorest Patients. New York: The New Press. Spar, D. And Day, A. (2006). Drug testing in Nigeria (A). Harvard Business School. Stephens, J. (2000). Where Profits and Lives hang in the Balance; Finding an Abundance of Subjects and Lack of Oversight Abroad, Big Drug Companies Test Offshore to Speed Products to Market. Washington Post. Read More