Potential U.S. Supreme Court Case on Nigerian Drug Trial Presents Mixed Picture for Global Health

August 27, 2009

A still from the movie “The Constant Gardener,” starring Rachel Weisz and based on the book by John le Carre, which was reportedly inspired by the Pfizer case.

In 1996, Pfizer conducted a clinical trial of Trovan, a new antibiotic, on children during an outbreak of bacterial meningitis in Kano, Nigeria. Eleven children died and others were left badly injured, according to trial participants. In 2001, 30 Nigerian families sued in U.S. federal court, arguing that Pfizer deviated from its clinical trial protocol and failed to inform the children or their guardians of Trovan’s life-threatening side effects or that Médecins Sans Frontières was providing the conventional, proven treatment for bacterial meningitis for free at the same site. Pfizer has denied wrongdoing. Years of litigation followed over whether the case should be heard in U.S. courts. Earlier this year, a U.S. appeals court ruled that the Pfizer case could proceed.

The U.S. Supreme Court is now deciding whether to hear the Pfizer case. If the Court hears the case, and there is a good chance it will, the Court will be asked to decide two important questions: (1) whether Pfizer acted in sufficiently close concert with the Nigerian government to be considered a “state actor” and, thus, possibly liable under the U.S. Alien Tort Statute (ATS) and (2) whether nonconsensual human medical experimentation violates customary international law. These questions sound pretty technical, but the Court’s answers could have significant practical implications for corporate responsibility, development, and global health.

Implications for Corporate Responsibility under International Law
Corporations, and private actors generally, are not subject to international law except in a few well-defined instances – war crimes, piracy, airplane hijackings, slave trade, and genocide. International law applies more broadly to countries (“states” in international law speak), however, and U.S. courts have found corporations liable under the ATS for violations of international law when a corporation acted in sufficiently close concert with a state that it was behaving like a “state actor.” U.S. courts have differed, sometimes significantly, on the degree of state involvement necessary for a corporation to be considered a state actor and which violations of international law are actionable. The Pfizer case presents the perfect opportunity for the Supreme Court to resolve those questions.

A Supreme Court decision in Pfizer could significantly affect the availability of civil lawsuits against corporations for international law violations. The U.S. is the only country that allows its courts to hear civil lawsuits by non-residents against corporations for international law violations committed in a foreign country. Indeed, after lying largely dormant for nearly 200 years after its enactment in 1789, the ATS has become a popular tool for lawyers and international human rights organizations to ask U.S. courts to decide corporate responsibility for Apartheid, slave labor in World War II Japan and Germany, Holocaust victims’ missing Swiss bank assets, mass environmental accidents in India, and many other claims.

Why do foreign plaintiffs bring U.S. ATS cases for harms suffered abroad? At least three reasons. First, there is, in some cases, no alternative. Lawsuits alleging corporate involvement in ethnic-cleansing or human rights abuses cannot be brought in countries where such acts are ongoing. Second, there may be advantages to U.S. courts and laws over the domestic alternatives. U.S. courts may be less biased and susceptible to corruption. U.S. laws offer: liberal evidentiary discovery rules; jury trials, punitive damages, and higher average compensatory damage awards; class actions; and contingency fee arrangements. Third, there are advantages for plaintiffs to ATS claims. Personal injury laws require that claims be brought within a defined period of time after the alleged violation; the ATS contains no such statute of limitations and U.S. courts have not agreed on what time limit, if any, should apply.

Why did the Pfizer plaintiffs bring their ATS suit in the U.S.? Many of the plaintiffs in Pfizer brought their lawsuit initially in Nigerian courts; it was dismissed in 2003 (the plaintiffs argue because of corruption). In 2007, 11 years after the Trovan clinical trial, the Nigerian government launched several lawsuits on its own behalf; Pfizer settled for a reported $75 million. That settlement includes a Pfizer-Nigerian government administered $35 million fund for Trovan trial participants, but the government’s cases were not brought on behalf of those trial subjects and do not resolve all their claims in the U.S. lawsuit.

Implications for International Development
Like many things in life and law, the benefit of corporate ATS liability for development is a question of degree – the question at the heart of Pfizer.

Liability for well-defined and recognized international law violations is an important source of corporate accountability. It may deter companies from supporting or participating in torture, forced labor, and gross human rights violations as well as doing business with government regimes such as those in Sudan and Myanmar that regularly commit repressive acts against their own citizens.

Some have argued, however, that ATS litigation discourages international trade and foreign direct investment in the developing countries that most need it. Uncertainty regarding the parameters of corporate liability under the ATS breeds lawsuits. Even when corporate defendants prevail, they incur substantial litigation expenses and years of negative publicity. ATS suits can be abused by plaintiffs’ attorneys seeking to extract large settlements and corresponding fees from deep pocket corporate defendants.

Implications for Global Health
An increasing number of clinical trials are conducted internationally and, in particular, in developing countries. The reasons are manifold: spiraling trial costs and difficulty of recruiting large numbers of treatment-naïve people in developed countries; strategic interest in emerging markets like China and India; and, in some instances, more conducive regulatory environments for clinical research.

The Pfizer case has implications for most clinical trials being conducted internationally. The U.S. represents roughly half of the world’s pharmaceutical market in terms of revenue. The overwhelming majority of actors in this industry – from multinationals to small biotechs to developing country producers – have some U.S. presence that could subject them to U.S. courts’ jurisdiction and, thus, to potential ATS litigation. The issue of informed consent arises in every clinical trial involving a human subject. Under the reasoning of the Court of Appeals in the Pfizer case, most, if not all, entities conducting clinical trials will qualify as “state actors” and, thus, are potentially liable under ATS. Clinical trials are heavily regulated; outside of the U.S., health infrastructure is often government-run. Most of the alleged involvement of the Nigerian government in Pfizer – requesting FDA authorization to export an experimental drug, approval of clinical trial protocols, and the conduct of the trial at a government facility – will be true for many international clinical trials.

In some respects, the effect of Pfizer on international clinical trials would be unremarkable. Organized international efforts to prohibit nonconsensual human experimentation began 60 years ago. There are numerous international legal instruments that require informed consent from clinical trial subjects. While these instruments were not, heretofore, actionable in U.S. courts, companies have long been liable under domestic laws for obtaining informed consent. Further, while the FDA permits data generated through clinical research conducted in foreign countries to support applications for FDA approval of new drugs, it requires, among many other things, that data come from clinical trials in which subjects gave their informed consent.

In other respects, Pfizer may have significant positive and negative consequences on global health.

It is not clear whether failure to obtain informed consent in international clinical drug trials is a widespread problem. If it is, potential ATS liability may provide additional incentive to do so, help protect patients, and have systemic benefits for global health. Some claim that the Trovan trial left northern Nigerians distrustful of Western medical interventions and is partially to blame for the 2003 Nigerian boycott of polio vaccination. That boycott led to a polio outbreak that cost US$500 million to control and ended the hopes of eradicating polio in this decade.

The Pfizer case may also have negative effects on global health. ATS liability, and clinical trial liability more generally, is a risk for sponsors of clinical trials. Win or lose, ATS suits are expensive and trial sponsors would need to insure against that risk. ATS liability exposure will not keep large pharmaceutical companies from conducting clinical trials abroad generally. It may, however, discourage clinical trials in developing countries and for medicines for neglected diseases.

It is not yet clear what happened in the Trovan trial. If trial subjects are adequately protected, it is a good thing when companies test life-saving products for use in vulnerable populations like children and in settings like Nigeria. There are more than 300 products for neglected diseases under development around the world. Even with expected attrition in that pipeline, many of those products will need to be tested in the particularly poor developing countries in which neglected diseases are endemic and on the highly vulnerable clinical trial subjects who suffer from those diseases. Potential ATS liability is most likely to arise and be the greatest in this context in which the question of what qualifies as fully informed consent is not always simple. Insuring against large ATS liability exposure would stress the already insufficient funding that exists to support clinical development of these products. Beyond the issue of costs, overly prescriptive and cookie-cutter approaches to informed consent would unduly delay or preclude much-needed research on vulnerable populations in developing countries.

For more on Tom’s research, watch his YouTube Interview.

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11 Responses to “Potential U.S. Supreme Court Case on Nigerian Drug Trial Presents Mixed Picture for Global Health”

L. J. B Says:
August 28th, 2009 at 12:38 pm

This very interesting blog entitled \Potential US Supreme Court Case….\ examines thoroughly the legal and practical issues involved in the Pfizer Nigerian drug testing case. As it is made clear the legal issues of the case are very complex. However,if Pfizer acted under the rules and the supervision of the State of Nigeria and the US FDA it is difficult to see how the US courts are justified to hear the case. If the \informed consent\ requirements of the FDA are met it seems to me that there is no reason for the US courts to interfere. The true motivation for introducing the case here might be the potentially higher legal fees and larger compensation.

Furthermore, it appears to me that the Global Health interests and the development of potentially more effective and more economical drugs for the treatment of many diseases prevalent especially in Africa and in the developing countries should carry an overriding consideration also. Of course the observation of reasonable safety rules should be a must.
KI Says:
August 28th, 2009 at 6:03 pm

The blog by Tom Bollyky entitled “Potential U.S. Supreme Court Case on Nigerian Drug Trial Presents Mixed Picture for Global Health” covers a very complex issue in great details, illuminating most of the key components of the case clearly.The testing and evaluation of a new drug is of great importance. It contributes greatly to the progress in global health care. However, it has complex intertwining issues of local, international and US laws, health care, health regulations and financial support.
Melinda Moree Says:
August 29th, 2009 at 6:09 pm

Thanks for updating us all on this very important case. In some ways it is old news. As someone who ran a product development partnership (Malaria Vaccine Initiative) we sought out clinical trial insurance for trails in developing countries even before the Pfizer case. My experience lies more in vaccines so it may indeed be biased. But doing clinical trials in developing countries is far more costly than doing clinical trials in the U.S. or Europe. Our clinical trials all had between 3-7 different Institutional Review Boards reviewing informed consent and the conduct of the trial in addition to an independent Data Safety and Monitoring Board.

It is true, however, that most developing countries do not have the regulatory infrastructure to review and oversee complex clinical trials–especially for novel compounds. Most product development partnerships would gladly support the national IRBs but the potential for conflict of interest is just far too great for this to be a solution.

Some groups do a great job of educating the community on the clinical research and this education really does lead to consent that is informed. Many, however, do a fairly poor job. Dissemination of best practices might help those who want to do better.

I can’t really speak to the fine points of the legal ramifications of the Pfizer case. In the final analysis, I believe there must be a way for individuals anywhere in the world to have access to justice if they are misled or if sloppy research is conducted. Clinical research depends on the pact between researchers and those being experimented upon that the potential benefit will outweigh the potential risk and that each participant will be protected from any known harm. If that pact is broken or is even perceived to be broken companies, researchers and those who will benefit from new products will all suffer.
Tom Bollyky Says:
August 31st, 2009 at 9:51 am

Thanks for the comments, particularly Melinda’s great insights based on her first-hand experience.

From a policy perspective, the Pfizer case, to me, boils down to how to best reconcile the important needs to protect highly vulnerable trial subjects, provide redress when those individuals are not protected, and not discourage the clinical trials that must be conducted with highly vulnerable populations in developing countries in order to develop desperately needed treatments for neglected diseases. This blog is meant to raise the question of whether ATS suits in U.S. courts are the best vehicle for that reconciliation. What are the alternatives? Could such suits be part of a larger solution if combined with other initiatives, such as the dissemination of best practices that Melinda suggests? Or, are the potential downsides of ATS suits too great? I would love to know what more of those working in the field think.

Melinda is correct, of course, that product development partnerships have long obtained clinical trial insurance for their trials in developing countries. The potential difference after Pfizer is a matter of degree. ATS cases have proven expensive to litigate and have resulted in awards and settlements in the $100 million range. Large settlements and awards will breed more suits. More lawsuits, high litigation costs, and sizable potential damages mean significantly larger clinical trial liability, particularly for trials in developing countries and with vulnerable populations, which, in turn, could result in potentially much higher clinical trial insurance costs for those trials. There could also be potential costs in time and money for the defensive practices that might become necessary in light of that larger clinical trial liability.
Robert Reinhard Says:
September 1st, 2009 at 11:56 am

I come from recent experience in environmental liability lawsuits under this statute where Unocal, for example, or Rio Tinto have been sued in U.S. courts for alleged environmental harms. The ATS seems a crude instrument in those cases and in these clinical trial situations to achieve the aim of protecting local populations from corporate acts that within countries are best the subject of regualtion and local enforcement. A Ford “pinto” type award is not the best means to guide corporate responsibility because it still leaves open the problems of prescriptive consensus best practice, norms of behavior and the input of local populations to craft rules affecting them. The norms of best clinical trial practice are better articulated by groups such as the Nuffield Council and similar authorities with conversion to in-country requirements. I would add that although informed consent is required, it’s not always adroit. In the US, courts have ruled that consent is not to be confused with a contractual obligation and issues of redressing harm or compensation for injuries in a trial are from resolved. These issues the Nuffield guidelines and the revised Declaration of Helsinki have tried to address more thoroughly.
jon merz Says:
September 1st, 2009 at 5:07 pm

I thought this case settled 2 months ago…

http://mediaroom.pfizer.com/portal/site/pfizer/index.jsp?ndmViewId=news_view&newsId=20090730005769&newsLang=en
Pharm Anyachor Chike Says:
September 2nd, 2009 at 3:10 am

As a recent Pharmacy graduate here in my country, Nigeria, i find it particularly unpleasant that the litigation has really been \snail-paced.\ I’m quite sure that if it was in countries like the US, UK or other developed nations, the suit would have run its full course.
Clinical trials are not to be toyed with & it would be greatly unfair in the sight of the entire world that a big company like Pfizer would take advantage of the high level of illiteracy & corruption in my country inorder to pass clinical trials and make lots of money from Trovan.
I’m quite aware that lots of risks are assumed in these trials but the questions still are these:
Were the patients or guardians adequately informed?
Were there aspects of the trials not completely understood by the patients due to a possible language barrier or even illiteracy?
Did Pfizer Global use the usual \aura\ indicative of some big companies to intimidate the patients thus leaving them with no options?
Did any form of bribery & corruption occur between Pfizer & some eminent Nigerians who really ought to have known better?
Meanwhile thank you CGD, Tom, Melinda and all the others for your interest in our case.
Pharm Anyachor Chike
Bill Savedoff Says:
September 2nd, 2009 at 3:19 pm

I’m wondering, at the end, whether the Supreme Court decision would really make a difference to overall clinical trial practices in developing countries since it seems to hinge on the degree of state involvement. In other words, couldn’t one implication be that pharma companies would find ways to explicitly distance themselves from the government so as not to face this kind of liability?
Guiyuoneiros Says:
September 3rd, 2009 at 12:02 am

This is not so much about a sanctifying informed consent but as the Nigerians will correctly claim, about negligent manslaughter and falsification of an ethics committe approval.
Megan M Richards Says:
September 3rd, 2009 at 3:22 pm

This is a highly complex issue of bioethical nature. Therfore, there is no definative right or wrong answer/ solution. The situation includes following both US and international laws. If true informed consent was given and the risks were clearly stated, then Pfizer has committed no crime. It is near impossible to determine the possible side effects of a medication on humans without first conducting a clinical trial. Development of medicine and clinical trials to implement them are necessary for the forward progression of medicine and the protection of human life. However, if consent was obtained wthout fully informing the subjects, then pfizer should be found guilty. Clinical trials are always risky. Subjects need to understand the potential risks and benefits to the extreme before agreeing to take part in the trial.

If the subjects truely were not informed, but had received a cure, would they still be filing suit?
Tom Bollyky Says:
September 8th, 2009 at 10:48 am

Thanks for the great comments. Just three quick responses.

1. Pfizer’s settlement with the government of Nigeria and the state government of Kano does not resolve the U.S. litigation because those cases were brought on behalf of those governments, not the trial subjects, and do not resolve all the families’ claims in the U.S. lawsuit.

2. My colleague Bill Savedoff asked the excellent question of whether drug firms will be able to limit the effect of the Pfizer case by distancing themselves from developing country governments when they conduct their clinical trials in those countries in the future. The answer will depend on what the Supreme Court, if it takes the case, decides with respect to the degree of state involvment necessary for a corporation to qualify as a “state actor” and, thus, be liable under the ATS. It is worth noting, however, that much of the Nigerian government’s involvement alleged in this case to establish that Pfizer is a “state actor” would be largely unavoidable in conducting a foreign clinical trial — requesting for FDA authorization to export an experimental drug, approval of clinical trial protocols, and the conduct of the trial at a government facility.

3. Several commentators have asked about the facts of the case, what sort of consent was actually given. The short answer is that we don’t know. Non-lawyer readers may be surprised that after 8 years of litigation, much expense, and now a potential U.S. Supreme Court case, no court yet in this litigation has made any factual determinations. The ligitation, to this point, has all been about jurisdiction, venue, and which law should apply. Under the current procedural posture of this case, U.S. courts, including the U.S. Supreme Court, must assume the plaintiffs’ allegations are all true. The facts, if the case proceeds and does not settle, would be determined at trial. It is difficult, however, to imagine that this case will ever get that far. If the Supreme Court does not hear the case, or it does and Pfizer loses, Pfizer is very likely to settle rather than try before a jury a case that involvies badly injuried and/or deceased children from a developing country, alleged malfeasance of a big multinational corporation, and a clinical trial incident that reportedly inspired the movie the “Constant Gardener.”