This paper discusses so-called post-trial access to drugs for patients who participated in clinical trials in Brazil. 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, the 8th biggest in the world and second only to China among the so-called BRICS’s emerging countries. The demand for pharmaceutical products (...) in the country has been increasing by double digits over the last few years, reaching 20% in 2008. 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. (shrink)

This book was inspired originally by the debates at the turn of the century about placebo controlled trials of antiretrovirals in HIV positive pregnant women in developing countries. Moving forward from this one limited example, the book includes several additional controversial cases of clinical research conducted in developing countries, and asks probing philosophical questions about the ethics of such trials. All clinical research by its very nature uses people to acquire generalizable knowledge to help future people. But what sorts of (...) "use" are morally permissible? What is it to exploit people? Suppose that a trial conducted in a developing country would not be ethically permissible in the developed world. Can we automatically conclude from this that the trial is unethical, that some sort of morally problematic double standard is in operation? Or might the differences in the two settings justify differences in trial design? This collection of philosophical essays examines these important questions about what exploitation is and when clinical research counts as exploitative. -/- "This is an outstanding contribution to the growing literature on the ethics of research with human subjects and a fine example of what bioethics can offer at its best. Anyone with a serious interest in these issues will need to read this book from start to finish." -Daniel Wikler, Harvard School of Public Health "This book contributes significantly to the literature on exploitation in clinical research conducted in the developing world."--Patricia Marshall, Case Western Reserve University . (shrink)

When research concludes, post-trial access to the trial intervention or standard healthcare can be crucial for participants who are ill such as those in resource-poor countries with inadequate healthcare, British participants testing ‘last-chance drugs’ unavailable on the National Health Service and underinsured US participants. Yet, many researchers are unclear about their obligations regarding the post-trial period, and many research ethics committees do not know what to require of researchers. Consequences include participants who reasonably expect but lack PTA to the trial (...) intervention, unplanned financial liabilities for NHS Trusts forced to fund this, negative press and potential to undermine public trust.1–3,iOne reason for the lack of clarity is controversy over whether and when participants should have access, after the study, to the study intervention. At one extreme is the view that continued access should be ensured when the intervention has benefited the participant or when it has proven safe and effective for the participant population, irrespective of the cost and burden of ensuring continued access. At the other extreme is the view that continued access need never be provided so long as non-availability of the study intervention post-trial was adequately disclosed when participants were invited to participate.6 There is also disagreement about when poststudy access to the study intervention should be considered beneficial for participants. The spectrum ranges from the view that the intervention should be regarded as beneficial for a proposed use only after the …. (shrink)

The need for continuing provision of beneficial experimental interventions after research is concluded remains a controversial topic in bioethics for research. Based on the principle of beneficence, justice as reciprocity, concerns about exploitation and fair benefits, participants should be able to have continuing access to benefits beyond the research period. However, there is no consensus about whether or not post-trial provision of beneficial interventions should be mandatory for participants from developing countries. This paper summarises recommendations from international and national guidelines. (...) Ethical principles and practical issues relating to post-trial provision are also discussed. In conclusion, post-trial provision is not necessary in all situations and a set of criteria are proposed to identify the situations that beneficial interventions should be provided beyond the research period. However, mandatory post-trial supply of beneficial experimental interventions should be assured for those who still need and are able to benefit from them but have no alternative access. Mandatory provision is based on universal bioethical principles such as beneficence and justice. Furthermore, difficulties associated with implementation of post-trial provision are not unmanageable. Careful advanced planning and a comprehensive partnership among relevant parties would be very helpful in solving these difficulties in practice, which therefore should not be taken as an excuse to escape post-trial responsibility. (shrink)

In this book by the award-winning author of Just Healthcare, Norman Daniels develops a comprehensive theory of justice for health that answers three key questions: what is the special moral importance of health? When are health inequalities unjust? How can we meet health needs fairly when we cannot meet them all? Daniels' theory has implications for national and global health policy: can we meet health needs fairly in ageing societies? Or protect health in the workplace while respecting individual liberty? Or (...) meet professional obligations and obligations of justice without conflict? When is an effort to reduce health disparities, or to set priorities in realising a human right to health, fair? What do richer, healthier societies owe poorer, sicker societies? Just Health: Meeting Health Needs Fairly explores the many ways that social justice is good for the health of populations in developed and developing countries. (shrink)

How international research might contribute to justice in global health has not been substantively addressed by bioethics. Theories of justice from political philosophy establish obligations for parties from high-income countries owed to parties from low and middle-income countries. We have developed a new framework that is based on Jennifer Ruger's health capability paradigm to strengthen the link between international clinical research and justice in global health. The ‘research for health justice’ framework provides direction on three aspects of international clinical research: (...) the research target, research capacity strengthening, and post-trial benefits. It identifies the obligations of justice owed by national governments, research funders, research sponsors, and investigators to trial participants and host communities. These obligations vary from those currently articulated in international research ethics guidelines. Ethical requirements of a different kind are needed if international clinical research is to advance global health equity. (shrink)

The paper Post-Trial Acces To Treatment (PTA) offers an insight into current corporate policies and corporate best practices relating to the provision of PTA in low and middle income countries based on company sources. In these countries there is a greater appeal for pharmaceutical companies to take responsibility for providing PTA. However, the practice of providing PTA is the exception rather than the rule.

Background : researchers and sponsors increasingly confront the issue of whether participants in a clinical trial should have post-trial access (PTA) to the trial drug. Legislation and guidelines are inconsistent, ambiguous or silent about many aspects of PTA. Recent research highlights the potential importance of systematic reviews (SRs) of reason-based literatures in informing decision-making in medicine, medical research and health policy. Purpose: to systematically review reasons why drug trial participants should, or need not be ensured PTA to the trial drug (...) and the uses of such reasons. Data sources: databases in science/medicine, law and ethics, thesis databases, bibliographies, research ethics books and included publications’ notes/bibliographies. Publication selection: a publication was included if it included a reason as above. See article for detailed inclusion conditions. Data extraction and analysis: two reviewers extracted and analyzed data on publications and reasons. Results: of 2060 publications identified, 75 were included. These mentioned reasons based on morality, legality, interests/incentives, or practicality, comprising 36 broad (235 narrow) types of reason. None of the included publications, which included informal reviews and reports by official bodies, mentioned more than 22 broad (59 narrow) types. For many reasons, publications differed about the reason’s interpretation, implications and/or persuasiveness. Publications differed also regarding costs, feasibility and legality of PTA. Limitations: reason types could be applied differently. The quality of reasons was not measured. Conclusion: this review captured a greater variety of reasons and of their uses than any included publication. Decisions based on informal reviews or sub-sets of literature are likely to be biased. Research is needed on PTA ethics, costs, feasibility and legality and on assessing the quality of reason-based literature. (shrink)

International research, sponsored by for-profit companies, is regularly criticised as unethical on the grounds that it exploits research subjects in developing countries. Many commentators agree that exploitation occurs when the benefits of cooperative activity are unfairly distributed between the parties. To determine whether international research is exploitative we therefore need an account of fair distribution. Procedural accounts of fair bargaining have been popular solutions to this problem, but I argue that they are insufficient to protect against exploitation. I argue instead (...) that a maximin principle of fair distribution provides a more compelling normative account of fairness in relationships characterised by extreme vulnerability and inequality of bargaining potential between the parties. A global tax on international research would provide a mechanism for implementing the maximin account of fair benefits. This model has the capacity to ensure fair benefits and thereby prevent exploitation in international research. (shrink)

In 2006, the Indonesian government decided to withhold avian flu samples from the World Health Organization. They argued that even though Indonesian samples were crucial to the development of vaccines, the results of vaccine research would be unaffordable for its citizens. Commentaries on the case varied from alleging blackmail to welcoming this strong stance against alleged exploitation. What is clear is that the concern expressed is related to benefit sharing. Benefit sharing requires resource users to return benefits to resource providers (...) in order to achieve justice. One benefit sharing tool within health research is the duty to provide a health care intervention which has been proven to be beneficial to research participants after a study has been concluded. This duty is generally known as a post-study obligation. It was enshrined in the Declaration of Helsinki in 2000 and re-emphasized in 2008. Yet, there are few, if any, examples of good practice. In this article, we analyse the obstacles to giving more bite to benefit sharing provisions in health research through ethical review. We conclude that the provision of post-study access to healthcare interventions is not a promising mechanism when monitored through research ethics committees. Alternative benefit provision is preferable if one focuses on achieving compliance. However, even the latter faces challenges, which we address in specific recommendations. (shrink)

El objetivo del presente trabajo es analizar la nueva formulación del principio de acceso posinvestigación en la más reciente (2008) revisión de la Declaración de Helsinki. Se identifican los artículos relevantes de la Declaración y se presentan dos interpretaciones posibles del principio de acceso posinvestigación: una interpretación robusta y otra permisiva, inspiradas cada una por modelos de justicia distintos. Luego, se hace una evaluación crítica de dichas interpretaciones y se intenta avanzar argumentos en contra de la interpretación permisiva. [The objective (...) of this study is to critically analyze the new formulation of the principle of post-trial access in the most recent (2008) revision of the Helsinki Declaration. The relevant articles of the declaration are identified and two possible interpretations of the principle of post-trial access are set out; one robust and one permissive, inspired by different models of distributive justice. A critical evaluation of both interpretations is presented and arguments against the permissive one advanced.]. (shrink)

ABSTRACTMany recent articles argue that participants who seroconvert during HIV prevention trials deserve treatment when they develop AIDS, and there is a general consensus that the participants in HIV/AIDS treatment trials should have continuing post‐trial access. As a result, the primary concern of many ethicists and activists has shifted from justifying an obligation to treat trial participants, to working out mechanisms through which treatment could be provided. In this paper I argue that this shift frequently conceals an important assumption: that (...) if there is an obligation to supply treatment, then any party who could provide it may be prevailed upon to discharge the obligation. This assumption is false. The reasons why trial participants should get ART affect who has the duty to provide it. We should not burden governments with the obligations of sponsors, nor researchers with the obligations of the international community. And we should not deprive a group of treatment because their need is less salient than that of research participants. Insisting otherwise may lead to people being wrongfully deprived of access to antiretrovirals. (shrink)

Care after research is for participants after they have finished the study. Often it is NHS-provided healthcare for the medical condition that the study addresses. Sometimes it includes the study intervention, whether funded and supplied by the study sponsor, NHS or other party. The NHS has the primary responsibility for care after research. However, researchers are responsible at least for explaining and justifying what will happen to participants once they have finished. RECs are responsible for considering the arrangements. There are (...) ethical and practical issues, in particular when participants may wish to continue on the study intervention after the study. There are also various guidelines and legislation. This document presents a framework of questions to help NHS RECs and their applicants. Information on this document’s development is here. (shrink)

Objectives: To report the attitudes and opinions of subjects in US clinical trials about whether or not, and why, they should receive post-trial access (PTA) to the trial drug, care and information. Design: Focus groups, short self-administered questionnaires. Setting: Boston, Dallas, Detroit, Oklahoma City. Participants: Current and recent subjects in clinical trials, primarily for chronic diseases. Results: 93 individuals participated in 10 focus groups. Many thought researchers, sponsors, health insurers and others share obligations to facilitate PTA to the trial drug, (...) if it benefited the subject, or to a therapeutic equivalent. Some thought PTA obligations include providing transition care (referrals to non-trial physicians or other trials, limited follow-up, short-term drug supply) or care for long-term adverse events. Others held, in contrast, that there are no PTA obligations regarding drugs or care. However, there was agreement that former subjects should receive information (drug name, dosage received, market approval date, long-term adverse effects, trial results). Participants frequently appealed to health need, cost, relationships, reciprocity, free choice and sponsor self-interest to support their views. Many of their reasons overlapped with those commonly discussed by bioethicists. Conclusion: Many participants in US trials for chronic conditions thought there are obligations to facilitate PTA to the trial drug at a “fair” price; these views were less demanding than those of non-US subjects in other studies. However, our participants’ views about informational obligations were broader than those of other subjects and many bioethicists. Our results suggest that the PTA debate should expand beyond the trial drug and aggregate results. (shrink)

The issue of benefits in international clinical research is highly controversial. Against the background of wide recognition of the need to share benefits of research, the nature of benefits remains strongly contested. Little is known about the perspectives of research populations on this issue and the extent to which research ethics discourses and guidelines are salient to the expectations and aspirations existing on the ground. This exploratory study contributes to filling this void by examining perspectives of people in low-income South (...) African communities on benefits in international clinical research. Twenty-four individuals with and without experience of being involved in clinical research participated in in-depth interviews. Respondents felt that ancillary care should be provided to clinical research participants, while a clinical study conducted in particular community should bring better health to its members through post-trial benefits. Respondents' perspectives were grounded in the perception that the ultimate goal of international clinical research is to improve local health. We argue that perspectives and understandings of the respondents are shaped by local moral traditions rather than clinical research specificities and require attention as valid moral claims. It is necessary to acknowledge such claims and cultural worlds from which they emerge, thus building the foundation for equal and embracing dialogue to bridge different perspectives and handle contradicting expectations. (shrink)

In this issue, Alex London and Kevin Zollman provide an analysis of an influential approach to the ethics of international research, known as the “fair benefits” approach. According to them, the fair benefits approach suffers from a fatal flaw: it is either too vague to be useful, or worse, is internally inconsistent. The fair benefits approach was developed based on a presentation I gave at a workshop organized in Malawi in March 2001 by the National Institutes of Health Clinical Center’s (...) Department of Bioethics. In this presentation, I made what I still think is a valid point, which was accepted by the diverse group of participants and formed the basis of the subsequent publications: One should not .. (shrink)

It is widely agreed that foreign sponsors of research in low- and middle-income countries (LMICs) are morally required to ensure that their research benefits the broader host community. There is no agreement, however, about how much benefit or what type of benefit research sponsors must provide, nor is there agreement about what group of people is entitled to benefit. To settle these questions, it is necessary to examine why research sponsors have an obligation to benefit the broader host community, not (...) only their subjects. Justifying this claim is not straightforward. There are three justifications for an obligation to benefit host communities that each apply to some research, but not to all. Each requires a different amount of benefit, and each requires benefit to be directed toward a different group. If research involves significant net risk to LMIC subjects, research must provide adequate benefit to people in LMICs to avoid an unjustified appeal to subjects’ altruism. If research places significant burdens on public resources, research must provide fair compensation to the community whose public resources are burdened. If research is for profit, research sponsors must contribute adequately to the upkeep of public goods from which they benefit in order to avoid the wrong of free-riding, even if their use of these public goods is not burdensome. (shrink)

In 2006, the Indonesian government decided to withhold avian flu samples from the World Health Organization. They argued that even though Indonesian samples were crucial to the development of vaccines, the results of vaccine research would be unaffordable for its citizens. Commentaries on the case varied from alleging blackmail to welcoming this strong stance against alleged exploitation. What is clear is that the concern expressed is related to benefit sharing.Benefit sharing requires resource users to return benefits to resource providers in (...) order to achieve justice. One benefit sharing tool within health research is the duty to provide a health care intervention which has been proven to be beneficial (or alternative benefits) to research participants after a study has been concluded. This duty is generally known as a post-study obligation. It was enshrined in the Declaration of Helsinki in 2000 and re-emphasized in 2008. Yet, there are few, if any, examples of good practice.In this article, we analyse the obstacles to giving more bite to benefit sharing provisions in health research through ethical review. We conclude that the provision of post-study access to healthcare interventions is not a promising mechanism when monitored through research ethics committees. Alternative benefit provision is preferable if one focuses on achieving compliance. However, even the latter faces challenges, which we address in specific recommendations. (shrink)

This paper discusses the post-trial access to drugs for patients who participated in clinical trials in Brazil. 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. The Federal Constitution recognizes health as a fundamental right to be fulfilled by the State. Based on the Brazilian constitution and on the National Health Council resolutions, courts have (...) 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. This generous interpretation of the duties of the pharmaceutical companies and the State makes the Brazilian model for post-trial access unique when compared to 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. (shrink)

Este artículo considera el problema de justicia en la investigación biomédica en países en desarrollo. En particular se hace foco en la discusión de si el requisito de poner a disposición toda intervención probada efectiva puede ser considerado como una obligación post investigación de los patrocinadores hacia la comunidad anfitriona. Primero, se discuten las concepciones de la Comisión Nacional de Asesoramiento sobre Bioética (NBAC) de los Estados Unidos y de las guías éticas internacionales sobre la obligación post investigación hacia la (...) comunidad. Luego, se examinan las interpretaciones del modelo de disponibilidad razonable y el modelo de beneficios justos sobre la condición de acceso a los beneficios post investigación. Por último, presento y critico el argumento del carácter contraproducente de la obligación post investigación que afirma que la obligación post investigación limita el desarrollo de la investigación y empeora la situación de las poblaciones de los países en desarrollo. [ABSTRACT] This article refers to the problem of justice in biomedical research in developing countries and in particular it focus in the discussion of whether the requirement of making available any effective intervention could be consider a post-trial obligation of the sponsor towards the host community. First, the National Advisory Bioethics Commission’s (NBAC) conception and the international guidelines’ conception of post-trial obligations towards the community are discussed. Second, the interpretation of reasonable availability model and the fair benefits model of the condition of access to post trial benefits are examined. Finally, I present and criticize the moral counterproductive argument which affirms that post trial obligations towards the community prevent new drug research and make population in developing countries worse off. (shrink)

There is near universal agreement within the scientific and ethics communities that a necessary condition for the moral permissibility of cross-national, collaborative research is that it be responsive to the health needs of the host community. It has proven difficult, however, to leverage or capitalize on this consensus in order to resolve lingering disputes about the ethics of international medical research. This is largely because different sides in these debates have sometimes provided different interpretations of what this requirement amounts to (...) in actual practice. The goal of the discussion that follows is to clarify the nature of this important moral requirement. The first section explains the requirement for responsiveness to host community health needs in the context of international medical research. The second section examines various formulations of this requirement as they are enunciated in some of the core consensus documents in research ethics. The third section then defends a particular interpretation of this requirement, and the final sections examine more liberal alternatives with the aim of highlighting points of agreement and assessing the significance of areas of disagreement. (shrink)