Pharmaceutical Companies vs. the State: Who Is Responsible for Post-Trial Provision of Drugs in Brazil? Daniel Wei L. Wang and Octavio Luiz Motta Ferraz

Introduction This paper discusses so-called post-trial access to drugs for patients who participated in clinical trials in Brazil.1 Brazil is currently a relevant country for the pharmaceutical industry due to the dimensions of its actual and potential market. As a consequence, the number of pharmaceutical trials has been rising. It is the largest market for pharmaceutical companies in Latin America,2 the 8th biggest in the world3 and second only to China among the so-called BRICS’s4 emerging countries.5 The demand for pharmaceutical products in the country has been increasing by double digits over the last few years, reaching 20% in 2008.6 Not surprisingly, we are also witnessing a steady increase in the number of applications by national and international pharmaceutical companies before ethical research authorities for authorization to perform clinical trials of drugs.7 The ethical guidance for clinical trials in Brazil is arguably one of the clearest in the world in attributing to research sponsors the responsibility for providing post-trial drugs to patients who participated in their experiments. What is more, Brazilian courts in some cases have considered that the guidance for clinical trials, as well as the research protocols and the terms of informed consent based on the protocol, can be judicially enforced against pharmaceutical companies. According to some Brazilian courts, therefore, there is not only an ethical duty to provide post-trial access, but also a legally enforceable right of patients who participated in the trials. In addition to these lawsuits claiming post-trial access against pharmaceutical companies, there are also lawsuits claiming the same against the Brazilian State. This litigation is based on the Federal Constitution, which states in article 196 that “health is a right of all and a duty of the State.”8 Brazilian courts have been interpreting the right to health as a judicially enforceable right against the State, and this has encouraged a massive number of lawsuits demanding drugs that are not provided by the public health system, including experimental drugs. In most cases patients have been successful against the State.9

Daniel Wei L. Wang is a Ph.D. in Law Candidate at the London School of Economics and Political Science. He holds a Master of Science in Philosophy and Public Policies from the London School of Economics and Political Science and a Master in Law from the University of Sao Paulo. Octavio Luiz Motta Ferraz, Ph.D., is an Assistant Professor at the University of Warwick. He holds a Ph.D. in Law from the University College of London; a Master in Medical Ethics and Law from King’s College London; and a Master in Law from the University of Sao Paulo.

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In Brazil, therefore, patients who participate in clinical trials can sue, with a high probability of success, either the pharmaceutical company (litigation “A” in Figure 1) or the State (litigation “B” in Figure 1) to force them to keep providing the experimental drug. This has triggered, in turn, further lawsuits in which either the state or the pharmaceutical company, when sued by the patient, sue each other trying to transfer the responsibility to provide the experimental treatment. There are thus cases in which pharmaceutical companies, when sued by patients, tried to bring the state into the lawsuit to replace it as the defendant (litigation “C” in Figure 1) and also cases in which the state, after judicially condemned to provide post-trial treatment, sued the pharmaceutical companies that conducted the trials claiming that Brazilian guidelines attribute to them the responsibility for this provision (litigation “D” in Figure 1). This paper first discusses the international guidelines on post-trial access to drugs, and the intricate moral issues that it raises. Then, it analyzes the Brazilian guidelines, their interpretation by courts, and the judicialization of the right to health in Brazil, which has forced health authorities to provide experimental treatments to patients. We then discuss the cases in which the public health system is trying to claw back the amount spent with the judicially ordered provision of post-trial drugs to patients from pharmaceutical companies. In conclusion, we argue that the current system may not be adequate and raise important and complex issues that should be considered carefully.

Post-Trial Access to Drugs: The Moral Debate and International Guidelines Once a clinical trial is concluded and the experimental medicine tested shows improvement in the condition of some or all the participants, should it continue to be provided to those participants? If so, who should be financially responsible for such provision? Figure 1 3 Types of Litigation

Here are some moral reasons that could support the duty to provide post-trial treatment. One argument is that stopping the treatment once the experiment is over is akin to treating patients as mere means to the end of testing a drug, which would amount to exploitation and unfairness.10 This may also undermine the appropriate level of trust between patients and researchers and become an obstacle for future research within that community.11 Another argument is that for some cases stopping the treatment after the trial may be harmful to the patient, with the exacerbation of symptoms and the creation of resistant viruses or bacteria. If researchers and sponsors have a duty to do no harm to the patient, then the treatment should not be withdrawn in such cases.12 A further argument is that “justice as reciprocity” requires that those who were exposed to the risk and inconvenience of serving as participants in research to the benefit of both the entire world population and the pharmaceutical companies deserve some kind of compensation for that, and the continuation of treatment is the appropriate compensation, especially in countries where cash payments are forbidden, such as in Brazil.13 But there are also strong arguments against this obligation. The most common is that the costs of the commitment to continuously provide the tested treatment for patients may be too burdensome and impair the progress of future research, no matter who is sponsoring the research, whether the government, universities, charities or pharmaceutical companies.14 This obligation would make it difficult to undertake research because the potential costs of such a duty could be prohibitive; this could lead to an overall decrease in the number of trials,15 particularly in two cases: (1) drugs for chronic diseases, for which long term therapeutic intervention is necessary16; and (2) so-called orphan drugs (drugs for rare diseases), which have a small pool of potential patients. Moreover, the financial cost of supporting posttrial treatments may divert resources from other potential studies into the continuous supply of treatments that may be very expensive and offer only marginal benefit.17 The second argument is that reciprocity does not implicate the duty to provide unrestricted treatment. Patients who participate in trials are somehow privileged because they have access to new technologies and medical innovations that can improve their condition in situations where they would not otherwise have had access to regular health care or where the conventional treatments bring no hope.18 It could

pharmaceutical firms and the right to health on • summer to This paper first discusses the international guidelines post-trial2012 access

drugs, and the intricate moral issues that it raises. Then, it analyzes the Brazilian guidelines, their interpretation by courts, and the judicialization of the right to health in

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thus be argued that receiving cutting edge technology that would not be available outside of clinical trials, albeit for a determined period, is already a fair compensation for the risks they have taken and a reward for the benefits they have provided for the rest of society. Moreover, in some countries participants are paid to take part in a trial, which could also be regarded as fair compensation, depending, of course, on the amount related to the risks involved. There are also cases in which the rationing of drugs is inescapable, and it could be called into question why those who had the opportunity to participate in a trial should have preference in receiving the drugs over others in the same situation who did not participate in the research, but would have done so if they could have.19 A good example is the case of epidemics such as HIV in Africa in which the number of people willing to participate in trials is much higher than the places available for participation in the research.20 Reciprocity, it might be argued, requires that those who make a social contribution through accepting the burdens and risks of research should receive benefits in return, but not by disproportionately increasing the burdens on others.21 Thirdly, when the patient is adequately informed that no post-trial treatment will be offered but still accepts to participate in the research, it could be considered paternalistic to interfere with decisions that individuals had taken consciously and rationally.22 But this would not be a strong argument if the participant accepted the deal simply because there was no better one available, which is often the case. Finally, in some cases studies are not conclusive concerning the efficacy and safety of the products tested. The fact that some patients had better results using the experimental treatment does not necessarily mean that it should be prescribed to them or to other patients in the same situation. The result could be statistically insignificant and other risks related to the use of the drug may be difficult to control out of a research context. In this case, a duty to provide posttrial treatment in every case can even be harmful to the subject.23 The heated moral debate on this topic is somehow reflected in the international guidelines for clinical trials using human beings. The Helsinki Declaration: Ethical Principles for Medical Research Involving Human Subjects is an international guideline adopted by the World Medical Association in 1954 and regularly updated since then. This document establishes the guidelines that should be followed by research involving human beings. In the 2000 update, the Helsinki Declaration included a provision — Principle 30 — that addresses the issue of post-trial access: “At the conclusion of 190

the study, every patient entered into the study should be assured of access to the best proven prophylactic, diagnostic, and therapeutic methods identified by the study.”24 This statement, although using the expression “assured access” rather than “provide,” could be understood as creating an open-ended obligation to provide care for patients that participate in research on those who were conducting the research and/or its sponsors. Hence, a large debate regarding Principle 30 took place after the Declaration was issued, especially due to the opposition of pharmaceutical companies and the U.S. Department of Health and Human Services.25 Following the controversy, in 2004 the World Medical Association recognized that a clarification of Principle 30 was necessary (Workgroup Report on the Revision of Paragraph 30 of the Declaration of Helsinki) and in the same year a Note of Clarification was added to the Declaration in the 55th World Medical Association Conference. In this Note of Clarification, the World Medical Association affirmed that “[p]ost-trial access arrangements or other care must be described in the protocol of the study so the ethical review committee may consider such arrangements during its review.”26 This Note of Clarification has therefore weakened the previous obligation, transforming it into a duty only to inform the relevant ethical committees whether the provision of post-trial treatment will be undertaken or not. It cannot be interpreted, thus, as stating any open-ended substantial obligation on sponsors or researchers to provide post-trial access.27 This understanding was maintained in the last update, in 2008, which says: The design and performance of each research study involving human subjects must be clearly described in a research protocol. (…) The protocol should describe arrangements for post-study access by study subjects to interventions identified as beneficial in the study or access to other appropriate care or benefits (Principle 14).28 In the 2008 version, there is also a reference to the principle that patients who entered into the study should be able to participate in the benefits that result from it. It does not, however, express as clearly as Principle 30 of the Helsinki Declaration did, that patients should be assured of post-trial access. According to the 2008 document: At the conclusion of the study, patients entered into the study are entitled to be informed about the outcome of the study and to share any benjournal of law, medicine & ethics

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efits that result from it, for example, access to interventions identified as beneficial in the study or to other appropriate care or benefits. (Principle 33).29 Another international organization concerned with research ethics, the Council for International Orga-

depend on a number of factors (including but not limited to the results of a trial), research protocols should typically describe the duration, extent, and financing of such continued access. When no arrangements have been negotiated, the researcher should justify to the ethics review committee why this is the case.31

Even though there is no consensus among the existing guidelines on this topic, it seems that most of them recognize that care for patients after the trial has to be considered and discussed in advance by researchers and sponsors, and made transparent to patients and ethical commissions. nizations of Medical Sciences (CIOMS) issued a document called International Ethical Guidelines for Biomedical Research Involving Human Subjects. Although it focuses mainly on the benefits of trials to the population of developing countries where these experiments take place, in the Comments to Guideline 10 there is a short reference to the benefits for individual research participants: Additionally, if an investigational drug has been shown to be beneficial, the sponsor should continue to provide it to the subjects after the conclusion of the study, and pending its approval by a drug regulatory authority.30 There are other guidelines that are issued by national commissions, such as the U.S. National Bioethics Advisory Commission and the British Nuffield Council, which are also used as international references for clinical research. These guidelines state that post-trial treatment is essential, albeit complicated, and that an open-ended obligation to provide it would have several drawbacks, being too burdensome on sponsors. They do not create a duty on researchers and sponsors to provide post-trial access, but they are nevertheless advised to examine such a possibility in advance and to negotiate a plan for such provision, making it transparent to patients and ethical commissions. According to the American commission: Researchers and sponsors in clinical trials should make reasonable, good faith efforts before the initiation of a trial to secure, at its conclusion, continued access for participants to needed experimental interventions that have been proven effective for the participants. Although the details of the arrangements will

The Joint United Nations Programme on HIV/AIDS (UNAIDS) issued in 2000 a guideline specifically concerning HIV preventive vaccine research which affirmed, under guidance point 2, that “Any HIV preventive vaccine demonstrated to be safe and effective (…) should be made available to all participants in the trial in which it was tested (…).”32 Moreover, there is also the demand that post-trial access has to be discussed prior to the start of the research.33 However, even these guidelines that affirm that post-trial access should be provided rarely define who should fund or provide the treatment and for how long.34 In conclusion, even though there is no consensus among the existing guidelines on this topic, it seems that most of them recognize that care for patients after the trial has to be considered and discussed in advance by researchers and sponsors, and made transparent to patients and ethical commissions.35 In the current practice of drugs’ experiments around the world, most research protocols identify mechanisms for access to post-trial treatments. The mechanisms include the following: (1) referral of research participants to continued treatment through their regular public or private health care provider; (2) enrollment in other research studies; (3) subsidized purchase; (4) free of cost provision of the treatment by the sponsor for a short term; (5) provision of unused or unopened drugs; (6) creation of a fund for the participants’ treatment through donations of nongovernmental organizations, developed countries and the pharmaceutical industry; (7) creative strategies such as the selling of artwork from the research host country; (8) collaborative partnerships with local governments and other organizations; or (9) a mix of two or more mechanisms.36 According to Seema Shah et al., more than 70% of the HIV studies involving anti-retroviral treat-

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ment in their sample referred to mechanisms concerning post-trial treatment.37 According to Sonia Dainesi, researchers, members of ethical review boards, patients, and sponsors agree that post-trial access should be provided to patients by sponsors at no charge.38 They disagree, however, about the duration of the provision. Sponsors considered that the drug should be provided until it becomes available in the public health system or the market; members of ethical review boards argued that it should continue as long as patients can benefit from it; patients argued it should be provided for life.39 The arrangements for post-trial access are more complicated in cases where the host country is poor and cannot provide adequate health care to research participants. The mechanism of referring research participants to continued treatment through their regular health care provider is precluded because they could be either inexistent or ineffective. For example, the debate on post-trial access started with HIV drug trials in poor countries, and it raised concerns that those who were subjects of the experiments would not be able to benefit from them, and neither the communities and countries where they lived, since treatment would be too expensive to ever become available regularly in the health system. Nevertheless, the importance of this issue is not restricted to developing or underdeveloped countries. Every health system, even in the wealthiest countries, has budget constraints and thus cannot afford to provide all the treatments that would potentially enhance people’s health. Especially in the case of experimental treatments, the health care provider, either public or private, tends to exclude coverage of experimental treatments. Unrestricted provision of still unproven and possibly cost-ineffective technologies adds additional cost pressures to health care systems already strained under limited budgetary resources, even to those in the developed world.40

A Right to Post-Trial Access to Drugs in Brazil? Pharmaceutical Companies’ Responsibility for Post-Trial Access The Brazilian National Health Council, through Resolution 196/1996, declared that research involving human beings has to ensure to subjects “the benefits resulting from the research project, in terms of social return, access to procedures, products or research agents.”41 The Council also issued another resolution — 251/1997 — which applies specifically to drug experiments, stating that

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access to the medicine being tested must be assured by the sponsor or, if there is no sponsor, by the institution, researcher, or promoter in the event that its superiority over the conventional treatment is proven.42 The Brazilian National Health Council further issued Resolution 404/2008 stating the opinion that the Note of Clarification on the Principle 30 of the 2000 Helsinki Declaration should be repealed because the original text is more protective of patients’ rights. Hence, in contrast to most international and national guidelines on the topic, Brazilian ethical guidelines give patients a very clear entitlement to post-trial access, and the responsibility for its provision is clearly attributed primarily to the research sponsor (pharmaceutical companies in most cases). Such a clear guidance attributing a strong responsibility inevitably raised a heated debate. Pharmaceutical companies argued that this guidance would discourage scientific research in Brazil43 and that these resolutions are not legally binding because the Brazilian National Health Council has no legal power to produce law or administrative acts.44 Some decisions by the Brazilian Courts have stated nevertheless that the pharmaceutical companies do have the legal duty to provide post-trial treatment, and one guideline from one of the judges of the Brazilian Federal Supreme Court (BFSC) — the highest court in the Brazilian Judiciary branch — indicates that such legal duty exists.45 But no concrete case has yet been decided by the BFSC recognizing such a legal duty. Public Health System’s Responsibility for Post-Trial Access In Brazil there is a universal public health system — the Unified Health System (Sistema Unico de Saude) — funded by general taxation and free of charge at the point of provision. What is more, the Constitution affirms in its Article 196 that “Health is a right of all and a duty of the State.”46 The constitutional right to health has triggered intense litigation focused mainly on the provision of drugs not provided by the public health system.47 Moreover, the Brazilian courts are generally prone to order the state to provide these drugs, including those that are still experimental.48 This phenomenon is often called, with a somewhat derogatory tone, the “judicialization of health.” The courts’ broad interpretation of the right to health in Brazil, encompassing the right to receive experimental drugs from the public health system, has incited patients who participated in clinical trials to sue the State to keep receiving tested medicines whose journal of law, medicine & ethics

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provision was interrupted once the experiment was concluded. As courts have been deciding in favor of patients and against the State, the health system was obliged to buy and provide experimental treatments to these patients. Responsibility for Post-Trial Access in Courts The Brazilian guidelines on post-trial access and the constitutional norms on the right to health raise the question of who is legally responsible, if anyone, for providing the drugs for patients who participated in clinical trials and still need the treatment. Is it the responsibility of the State, under its duty to guarantee the right to health, or is it that of the pharmaceutical companies based on their responsibility for the welfare of those who contributed to their research? In the case 1.001.032.528 (State of Rio Grande do Sul),49 Schering Corporation was considered responsible for providing post-trial treatment to a HIV patient who participated in the trial of some of its drugs and reacted very positively to the tested treatment. The company was found liable in both the lower and the Court of Appeal of the State of Rio Grande do Sul. During the judicial process, the pharmaceutical company suggested a compromise with the patient: Schering Corporation would provide the drugs for two months, and after this period, the patient would have to sue the Brazilian public health system in order to keep receiving treatment. In the end, the pharmaceutical company agreed to supply the drugs to the patient and the case was closed.50 In the case Caua (State of Rio Grande do Sul — December, 2008),51 the judge in a lower Court of the State of Rio Grande do Sul decided that Genzyme Corporation was responsible for keeping the supply of Laronidase (Aldurazyme) to a child suffering from Mucopolissacaridose Type 1 who had participated in the drug’s clinical trial sponsored by the pharmaceutical company. The experiment was successful and the treatment was eventually registered at the Brazilian Health Surveillance Agency (Agencia Nacional de Vigilancia Sanitaria). However, in spite of the fact that the term of consent signed by the patient stated that post-trial treatment would be provided, the company stopped providing the drug to the patient. The child’s parents successfully sued the State of Rio Grande do Sul claiming that the constitutional right to health encompasses the duty of the public health system to provide access to experimental treatment that was proved to be effective in improving the patients’ health condition. Subsequently to being found liable, the State sued the pharmaceutical company sponsoring the trial claiming that it should bear the responsibility for providing the drug and that this duty could

not be transferred to the State. It also accused that pharmaceutical company of orienting patients to lodge lawsuits against the State in order to exonerate itself from this responsibility. Thus, the State aimed at making the pharmaceutical company liable for compensating the public budget for the amount spent with the judicially ordered provision of post-trial access. The State’s claim was successful. The decision was based on the resolutions 196/1996 and 251/1997 of the Brazilian National Health Council; moral and legal principles; and the document of informed consent, which affirmed that the treatment would continue to be offered to patients after the end of the trial, without any reference to limits on such provision. According to the judge, both the State and the pharmaceutical company have the duty to protect the citizens’ right to health. However, in the case of post-trial provision, the State’s duty is subsidiary to that of pharmaceutical companies that sponsor the trial. The judge affirmed that the pharmaceutical company’s responsibility does not cease with the conclusion of the trial because, according to the rules of clinical trials in Brazil, treatment has to be supplied for as long as the patient needs it. Genzyme Corporation was then held liable to pay to the State of Rio Grande do Sul the amount spent to provide the experimental treatment to the child who participated in the research it was sponsoring.52 The pharmaceutical company appealed — Appeal 70031235633 — but the Court of Appeal confirmed the decision. The case, however, is not over yet since the pharmaceutical company appealed to the Federal Supreme Court, and a final decision is pending. The State of Sao Paulo Secretary of Health has recently lodged a lawsuit against pharmaceutical companies that conducted experiments with patients who suffered from mucopolissacaridose. After the end of the trial, patients sued the State claiming that the government should provide the experimental treatment. The patients won the case and the State spent around U.S. $5 million providing these drugs. The State of Sao Paulo wants compensation for the amount spent on these drugs.53 The State claims that pharmaceutical companies are encouraging patients who participated in their trials to lodge lawsuits against the public health system as a way of transferring their responsibility for post-trial provision to the State. This case has not yet been decided. The Brazilian Federal Supreme Court (BFSC) has not decided any case of post-trial access yet, but one of its judges, Min. Gilmar Mendes, has already made a clear statement on this topic. The BFSC organized in 2009 a “public hearing” to discuss the “judicialization of health” with doctors, public health specialists,

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legal scholars, and civil society. This is a fairly new procedure that the court can use to consult experts and stakeholders in order to gather information and elicit debate on important and complex questions that figure very often in litigation. In a group of several cases decided by Judge Gilmar Mendes after the public hearing, the decisions established some guidelines54 concerning the provision of drugs by the public health system, and in one of these guidelines, it is said that the State should not be judicially obliged to provide experimental treatments, since it is the company sponsoring the trial that has the duty to continue their provision to the patients who participated in it even after the trial is completed. However, it is important to reiterate that this is the position expressed only by the Chief Justice and no case concerning access to posttrial treatment has been decided by the STF so far.

were tested in clinical trials they have participated in. Based on the Brazilian constitution and on the National Health Council resolutions, courts have so far been accepting patients’ claims and ordering the State and the pharmaceutical companies to provide these patients with the tested treatment in the quantity and duration they need it. These decisions are too few, and not yet confirmed by the Supreme Federal Tribunal, for us to draw any strong conclusion from them; yet, compared to the international guidelines and the practical experience of other countries, these decisions are very generous to patients in terms of post-trial access. The current situation is not adequate because it creates (1) legal uncertainty from the perspective of the sponsors and the State, and (2) refusals from trial sponsors to provide post-trial access except when there is a

There is no clear definition about who should eventually be responsible for post-trial access in Brazil — the State or the research sponsor. According to current case law, whoever is the respondent in a lawsuit will be held to have open-ended responsibility for the provision of post-trial treatment. This means that it is the patient, in the moment of choosing the respondent to his lawsuit, who has the power to choose who will pay for post-trial treatment (either the State or the sponsor), since courts will often judge against either defendant. This creates a confusing situation in which both the State and the sponsors know they can be fully responsible, but at the same time they also know that the other can be fully responsible too. The Brazilian National Council of Justice (CNJ) also issued a recommendation — Recommendation 30/2010 — that says that courts, before deciding cases involving claims for the provision of drugs, should analyze whether the patient has participated in a clinical trial and is demanding a drug tested in this trial. In this case, the government should not be obliged to provide it, because it is the pharmaceutical company’s responsibility to do so.55 It is important to remark that the guidelines of the STF and the recommendation of the CNJ, although they may be indicative of how future cases will be judged, are not binding on decisions of any court, not even the STF itself, and thus the result of forthcoming litigation is still uncertain.

Conclusion In Brazil, patients have been suing the State and pharmaceutical companies in order to receive drugs that 194

judicial order. There is no clear definition about who should eventually be responsible for post-trial access in Brazil — the State or the research sponsor. According to current case law, whoever is the respondent in a lawsuit will be held to have open-ended responsibility for the provision of post-trial treatment. This means that it is the patient, in the moment of choosing the respondent to his lawsuit, who has the power to choose who will pay for post-trial treatment (either the State or the sponsor), since courts will often judge against either defendant. This creates a confusing situation in which both the State and the sponsors know they can be fully responsible, but at the same time they also know that the other can be fully responsible too. Even though patients know they will probably win, no matter against whom they are litigating, the fact that both of them are potentially fully responsible for post-trial treatment may create incentives for them to attribute to each other the responsibility for fulfill-

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ing this right rather than organizing a scheme for its provision without the need of a judicial order. If this situation persists, access to post-trial treatment may become litigation dependent and only those patients who have access to justice will have access to the treatments tested on them, which is either unfair because not all patients will be able to go to court, or wasteful because every experiment with human beings will end up in the courts. Moreover, an open-ended obligation to provide post-trial treatment may have several drawbacks that ought to be considered, no matter who bears responsibility — the State or the pharmaceutical company. On the one hand, when courts attribute this responsibility to the public health system, as pharmaceutical companies argue they should, the government is often obliged to supply experimental treatment that could not (or should not) be funded by the public system for cost effectiveness and fairness reasons.56 In other words, the public health system would be providing drugs without having agreed to it or having carried out the necessary analysis of their priority and their relevance to the population as a whole. This is already happening on a significant scale with non-experimental drugs, as the phenomenon of the “judicialization of health” illustrates. Given that health care rationing is inescapable, this form of compulsory provision through court orders is morally questionable since it forces the public system to give preference to the needs of those who have the opportunity to participate in a trial over the health problems of other citizens. A group should not be deprived of treatment because their need is less salient than that of research participants.57 On the other hand, if pharmaceutical companies are considered responsible for open-ended provision of post-trial access, which is currently the most common scenario as seen above and one that may be consolidated by future decisions, there is the concern whether this would undermine future research in Brazil. Such an open-ended responsibility of pharmaceutical companies was never recommended by any international or other national ethical guidelines and the literature on this topic has never described a country with such an extensive obligation of post-trial access. Most of the guidelines and commentators recognize that researchers and sponsors cannot ignore their responsibility and abandon their patients after the trial is over. However, the guidelines and commentators are also very wary of attributing to them the sole responsibility for treating people because it could be unrealistic, unsustainable, and also a disincentive for scientific research.58 In practice, the pharmaceutical companies, in spite of normally addressing the

post-trial access issue, never intended to undertake an open-ended obligation to provide the drugs tested in their clinical trials to their test subjects around the world, and if this obligation were to become consolidated in Brazil, then there could be a “research drain” to other countries with less demanding obligations. The potential negative consequences of such a system have been noted above. Whether they will materialize or not is something that we can unfortunately not know before (and unless) the system is consolidated and in place for longer. In conclusion, for the reasons already stated above, the Brazilian model for post-trial access — whatever the content of future decisions — is unique when compared with the experience of other countries and thus should be followed with attention by future research in order to assess its consequences for patients, research sponsors, and the public health system. References

1. In this paper we will not analyze the responsibility for compensating or restoring the situation of patients for research-related injuries. The obligation in these cases is much less controversial. (See D. Schroeder, “Post-Trial Obligations,” Eletronic Journal of Communication Information & Innovation in Health 2, no. 1 [2006]). The duty to provide post-trial benefits for countries or communities will also not be discussed in this paper. On this topic, see CIOMS, International Ethical Guidelines for Biomedical Research Involving Human Subjects, Council for International Organizations of Medical Science, Geneva, 2002; C. Pace et al., “Post Trial Access to Tested Interventions: The Views of IRB/REC Chair, Investigators and Research Participants in a Multinational HIV/AIDS Study,” AIDS Research and Human Retroviruses 22, no. 9 (2006). 2. K. Ribbink, “Ola Brazil: Latin America’s Biggest Market Accelerates,” Pharma Voice, January 2011. 3. IMS, “Pharmerging Shake-Up: New Imperatives in a Redefined World,” IMS Health, 2011. 4. BRICs stand for Brazil, Russia, India, and China – four of the leading emerging economies in the world. 5. See IMS, supra note 3. 6.  Id. 7.  M. Lima, “Ponto de vista – pesquisa clínica no Brasil,” Scentryphar Clinical Research, 2005, available at (last visited May 9, 2012). 8.  Brazil, Federal Constitution at Article 196, available at (last visited May 22, 2012). 9. O. Ferraz, “Brazil. Health Inequalities, Rights and Courts: The Social Impact of the Judicialization of Health,” in A. Ely Yamin and S. Gloppen, Litigating the Right to Health (Cambridge: Harvard University Press, 2011). 10. NBAC, Ethical and Policy Issues in International Research: Clinical Trials in Developing Countries, Volume 1 – Report and Recommendation of the National Bioethics Advisory Commission, Bethesda, 2001; M. Merritt and C. Grady, “Reciprocity and Post-Trial Access for Participants in Antiretroviral Therapy Trials,” AIDS 20, no. 14 (2006): 1791-1794; D. Schroeder, “Post-Trial Obligations,” Electronic Journal of Communication Information & Innovation in Health 2, no. 1 (2006): 63-73; see R. Saver, “At the End of the Clinical Trial: Does Access to Investigational Technology End as Well?” Western New England Law Review 31, no. 2 (2009): 411-451, at 439. 11.  Id. (Schroeder); Id. (Saver), at 439.

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S Y MPO SIUM 12. C. Grady, “The Challenge of Assuring Continued Post-Trial Access to Beneficial Treatment,” Yale Journal of Health Policy, Law and Ethics 5, no. 1 (2005): 425-436; J. Millum, “PostTrial Access to Antiretrovirals: Who Owes What to Whom,” Bioethics 25, no. 3 (2009): 145-154. 13. See NBAC, supra note 10; Merritt and Grady, supra note 10. 14.  Id. (NBAC); see Schroeder, supra note 10. 15.  Id. (Schroder); Nuffield Council on Bioethics, The Ethics of Research related to Health Care in Developing Countries, 2002; J. Ananworanich et al., “Creation of a Drug Fund for Post-Clinical Trial Access to Antiretrovirals,” The Lancet 364, no. 9428 (2004): 101-102. 16. J. R. McMillan and C. Conlon, “The Ethics of Research Related to Health Care in Developing Countries,” Journal of Medical Ethics 30, no. 30 (2004): 204-206. 17. See Saver, supra note 10. 18.  Id. 19. See Merritt and Grady, supra note 10, at 1792. 20. Id. 21.  Id., at 1793. 22. See Saver, supra note 10. 23. V. Harada, “Introduction,” in Guarantee of Access to Post-Clinical Trial Drugs, Brazilian Association of Clinical Research Organizations, Sao Paulo, 2011; F. G. Eliaschewitz, “Access to Post-Clinical Trial Medication,” in Guarantee of Access to PostClinical Trial Drugs, Brazilian Association of Clinical Research Organizations, Sao Paulo, 2011; S. Dainesi, “Guarantee of PostStudy Access,” in Guarantee of Access to Post-Clinical Trial Drugs, Brazilian Association of Clinical Research Organizations, Sao Paulo, 2011. 24. World Medical Association, Declaration of Helsinki, 2000, available at (last visited May 22, 2012). 25. CMAJ, “Editorial,” Canadian Medical Association Journal 11, no. 169 (2003): 997. 26. World Medical Association, Workgroup Report on the Revision of Paragraph 30 of the Declaration of Helsinki, 2004, available at (last visited May 22, 2012). 27. J. Blackmer and H. Haddad, “The Declaration of Helsinki: An Update on Paragraph 30,” Canadian Medical Association Journal 173, no. 9 (2005): 1052-1053. 28. See World Medical Association, supra note 24. 29. Id. 30. CIOMS, International Ethical Guidelines for Biomedical Research Involving Human Subjects, Council for International Organizations of Medical Science, Geneva, 2002. 31. See NABC, supra note 10. 32. UNAIDS, Ethical Considerations in HIV preventive vaccine research: UNAIDS Guidance Document, 2000. 33. See Schroeder, supra note 10. 34. N. Sofaer and D. Strech, “Reasons Why Post-Trial Access to Trial Drugs Should, or Need Not Be Ensured to Research Participants: A Systematic Review,” Public Health Ethics 4, no. 2 (2011): 160-184.

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35. Z. Zong, “Should Post-Trial Provision of Beneficial Experimental Interventions Be Mandatory in Developing Countries?” Journal of Medical Ethics 34, no. 3 (2008): 188-192. 36. S. Shah, “Planning for Posttrial Access to Antiretroviral Treatment for Research Participants in Developing Countries,” Health Policy and Ethics 99, no. 9 (2009); see Millum, supra note 12; NABC, supra note 10; J. Ananworanich et al., “Creation of a Drug Fund for Post-Clinical Trial Access to Antiretrovirals,” The Lancet 364, no. 9428 (2004): 101-102. 37.  Id. (Shah). 38. See Daneisi, supra note 23. 39. Id. 40. See Saver, supra note 10, at 412-413, 446. 41. The Brazilian National Health Council. Resolution 196/1996, at Article III.3. 42. Article IV.1. Our free translation, from Portuguese, that reads as follows: l - Assegurar por parte do patrocinador ou, na sua inexistência, por parte da instituição, pesquisador ou promotor, acesso ao medicamento em teste, caso se comprove sua superioridade em relação ao tratamento convencional. 43. See Harada, supra note 23. 44. Â. F. C. Kung, “Guarantee of Post-Study Access: Legal Aspects,” in Guarantee of Access to Post-Clinical Trial Drugs, Brazilian Association of Clinical Research Organizations, Sao Paulo, 2011. 45. On these cases, see D. Wang, Health Economics, Policy and Law Journal (2012, in press). 46.  B razil, Federal Constitution at Article 196, available at (last visited May 22, 2012). 47. See Ferraz, supra note 9. 48. F. Vieira and P. Zucchi, “Distorções causadas pelas ações judiciais à política de medicamentos no Brasil,” Revista de Saúde Pública 41, no. 2 (2007): 214-222. 49.  S tate of Rio Grande do Sul Court of Appeal, Case no. 1.001.032.528, Agreement signed on July 15, 2010. 50. For more information on this case, see Defensoria Pública, available at (last visited May 8, 2012). 51. The complete version of the decision is available online, in Portuguese, available at (last visited May 8, 2012). 52. Id. 53. G overno de Estado de Sao Paulo, “Casa Civil,” available at (last visited May 8, 2012). 54. See Wang, supra note 45. 55.  B razilian National Council of Justice, Recommendation 30/2010, at I, b, 4. 56. B. R. S. Junior, “Acesso às drogas na pesquisa clínica,” Revista Bioética 15, no. 2 (2007): at 261. 57. See Millum, supra note 12, at 154. 58. See Grady, supra note 12; Shah, supra note 36, at 1560.

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