Ruth Macklin, Double Standards in Medical Research in Developing Countries, Cambridge, Cambridge University Press, 2004.
Randomised clinical trials (RCTs) constitute a world-wide acknowledged standard of proof to decide about the efficacy of a drug. Their implementation involves many different ethical dilemmas (e.g., in what conditions it is fair to allocate treatments are random?), but most of these are well known and several agreed guidelines exist to sort them out whenever they appear. At least, in countries where serious institutional review boards (IRBs) are in operation to monitor the trials. But RCTs are also an industrial procedure that the pharmaceuticals should use very often to make their business grow. And since there are many countries in which the absence of serious IRBs is positively correlated with a lower cost of RCTs, there is an strong incentive for the industry to conduct their trials there. There is a single methodological yardstick, RCTs, that guarantees the cogency of the results of the test, making it acceptable for Western regulatory agencies. But there is often a double ethical standard to conduct the trials, since the subjects of the experiment will be treated very differently depending of its geographical location. This is the topic of Ruth Macklin’s path-breaking essay. Her goal is to debunk the various ethical arguments provided to justify the existence of such double-standards and argue for a unified system of ethical guidelines to conduct medical research in our world.
The subject under discussion is mapped in chapter 1. Macklin defines there what she takes to be a developing country in this context: namely, a country in which there are fewer opportunities for the majority of the population to access the successful products of research. This implies that clinical trials provide a unique occasion for them to gain access to new drugs, even in the testing stage. Which also puts these people in a position of inferiority regarding the pharmaceutical companies when it comes to negotiate the details of the trial. The case in point that brought international attention to the problem was a 1997 study of maternal-to-child HIV transmission conducted in a developing country: the contrasting drug was a placebo instead of the best available treatment, as it should have been according the developed world bioethical standards. Macklin introduces here the Declaration of Helsinki, issued in by the World Medical Organization in various amended versions, which she will critically use – together with other similar texts – as a framework for carrying out the discussion in the rest of the book. Her aim is to improve these ethical research guidelines in a way that is “usefully prescriptive without being hopelessly aspirational” (p. 30).
Chapter 2 discusses the problem of the standard of care, which mainly appears in the following circumstances: on the one hand, what sort of drug (if any) should be provided to the control groups in countries where no alternative treatment is available for the study subjects; on the other hand, what level of medical attention should be provided to them beyond the actual goals of the study? Macklin surveys the debate on what should the standards be and presents an ample review of the guidelines provided by various organizations. She undermines here the various arguments for a double standard (e.g., “something is better than nothing”) on considerations both of principle and practical which are expanded in the following chapters.
In Chapter 3, Macklin addresses the issue of distributive justice by contextualising the idea to the area of scientific research. She argues in favour of a moral imperative to provide post-trial benefits to research subjects, drawing from various arguments ranging from equity as maximization to compensatory justice. In this light she reviews many guidelines again, criticizing those that leave room for the opposite conclusion. Yet even if her point is granted, there is the open question of what sort of benefits should be provided. A similar conclusion is reached in the following chapter through an analysis of exploitation. Macklin proposes a definition (p. 101) in which the key point is the lack of adequate compensation to research subjects due to their lack of, so to speak, bargaining power. This definition is extensively contrasted with the guidelines, but now Macklin obtains more concrete conclusions as to the practical implications of the analysis. The entitlement to post-trial benefits is now defended as the proper measure to prevent exploitation. And these benefits appear to be mostly an easier access to the resulting drugs. But Macklin also focuses on the circumstances in which consent may be exploitative – the list of particular circumstances in which exploitation in international research is likely to happen is particularly illuminating in this respect (pp. 118-122).
Chapter 5 then analyses the possible safeguards to guarantee that consent is properly granted and the subjects’ rights are duly protected during the trial. After some illustrations showing the need for such safeguards, Macklin argues for a universalistic conception of consent grounded in individual autonomy against group- or gender- biased definitions, defended on a cultural relativistic basis. In a similar spirit, Macklin defends the convenience of extending the competences of IRBs beyond its actual boundaries, so that they can survey privately sponsored trials abroad when no reasonable alternative is provided.
Chapter 6 focuses on how to make drugs affordable. Its moral implications are already clear at this stage: it would make less defensible the use of placebo in clinical trials conducted in underdeveloped countries and would substantiate the idea of post-trial benefits. Four complementary strategies are discussed: differential pricing in essential drugs; prior agreements to make the drug under trial available in the countries where it is conducted; joint initiatives of international agencies and private-public partnerships to produce affordable drugs; and the manufacture of generic copies of patented drugs for poor countries. Macklin presents different examples of each strategy, emphasizing their more positive prospects.
Chapter 7 returns to matters of principle and restates the case already made using the human rights vocabulary, acknowledging its role as a global standard for international organizations. The eighth and final chapter discusses how to develop research guidelines in accordance with all these considerations, using a quite realistic approach.
Macklin’s effort deserves all praise since she takes into account most of the many possible approaches to her subject and builds a unified and coherent case. Though Macklin navigates at ease in the endless details of the various declarations and proposals discussed, it is not difficult to get lost: the analysis is necessarily brief to keep the essay’s extension within reasonable limits, so many arguments are just outlined and the reader is referred to an ample bibliography to complete them. In this respect, a general references section (instead of one at the end of each chapter) would have been helpful. Yet, the thorough index appended somehow compensates for this and makes the book really accesible. All in all, it is a great survey of a terribly complex issue and it will greatly improve its discussion from now on.
As to the cogency of Macklin’s proposal of a unified standard for medical research, it is difficult not to be sympathetic and the arguments she provides may well ground a wide consensus. Yet, this is a book in which bioethical discussion very often yields policy recommendations, and in this respect I sometimes miss a more concrete discussion of how these would work under different circumstances. Since case studies are for Macklin a good enough ground to build her arguments for or against different policies, I would have liked a case-based analysis of the efficacy of her own proposals, i.e., one in which agents are not motivated by ethical considerations alone but also by their particular interests in the many scenarios in which these proposals should be implemented. Obviously, this is too much asking of a book which is mostly intended as an essay in applied ethics. Yet, when this field is expanded to encompass all the circumstances that she (wisely) takes into account, the argument necessarily becomes something more than ethics and a more interdisciplinary discussion would do much to strength her conclusions, making them more credible. Anyhow, this is a pioneer work and it is fair to say that it just makes this very discussion possible.
Randomised clinical trials (RCTs) constitute a world-wide acknowledged standard of proof to decide about the efficacy of a drug. Their implementation involves many different ethical dilemmas (e.g., in what conditions it is fair to allocate treatments are random?), but most of these are well known and several agreed guidelines exist to sort them out whenever they appear. At least, in countries where serious institutional review boards (IRBs) are in operation to monitor the trials. But RCTs are also an industrial procedure that the pharmaceuticals should use very often to make their business grow. And since there are many countries in which the absence of serious IRBs is positively correlated with a lower cost of RCTs, there is an strong incentive for the industry to conduct their trials there. There is a single methodological yardstick, RCTs, that guarantees the cogency of the results of the test, making it acceptable for Western regulatory agencies. But there is often a double ethical standard to conduct the trials, since the subjects of the experiment will be treated very differently depending of its geographical location. This is the topic of Ruth Macklin’s path-breaking essay. Her goal is to debunk the various ethical arguments provided to justify the existence of such double-standards and argue for a unified system of ethical guidelines to conduct medical research in our world.
The subject under discussion is mapped in chapter 1. Macklin defines there what she takes to be a developing country in this context: namely, a country in which there are fewer opportunities for the majority of the population to access the successful products of research. This implies that clinical trials provide a unique occasion for them to gain access to new drugs, even in the testing stage. Which also puts these people in a position of inferiority regarding the pharmaceutical companies when it comes to negotiate the details of the trial. The case in point that brought international attention to the problem was a 1997 study of maternal-to-child HIV transmission conducted in a developing country: the contrasting drug was a placebo instead of the best available treatment, as it should have been according the developed world bioethical standards. Macklin introduces here the Declaration of Helsinki, issued in by the World Medical Organization in various amended versions, which she will critically use – together with other similar texts – as a framework for carrying out the discussion in the rest of the book. Her aim is to improve these ethical research guidelines in a way that is “usefully prescriptive without being hopelessly aspirational” (p. 30).
Chapter 2 discusses the problem of the standard of care, which mainly appears in the following circumstances: on the one hand, what sort of drug (if any) should be provided to the control groups in countries where no alternative treatment is available for the study subjects; on the other hand, what level of medical attention should be provided to them beyond the actual goals of the study? Macklin surveys the debate on what should the standards be and presents an ample review of the guidelines provided by various organizations. She undermines here the various arguments for a double standard (e.g., “something is better than nothing”) on considerations both of principle and practical which are expanded in the following chapters.
In Chapter 3, Macklin addresses the issue of distributive justice by contextualising the idea to the area of scientific research. She argues in favour of a moral imperative to provide post-trial benefits to research subjects, drawing from various arguments ranging from equity as maximization to compensatory justice. In this light she reviews many guidelines again, criticizing those that leave room for the opposite conclusion. Yet even if her point is granted, there is the open question of what sort of benefits should be provided. A similar conclusion is reached in the following chapter through an analysis of exploitation. Macklin proposes a definition (p. 101) in which the key point is the lack of adequate compensation to research subjects due to their lack of, so to speak, bargaining power. This definition is extensively contrasted with the guidelines, but now Macklin obtains more concrete conclusions as to the practical implications of the analysis. The entitlement to post-trial benefits is now defended as the proper measure to prevent exploitation. And these benefits appear to be mostly an easier access to the resulting drugs. But Macklin also focuses on the circumstances in which consent may be exploitative – the list of particular circumstances in which exploitation in international research is likely to happen is particularly illuminating in this respect (pp. 118-122).
Chapter 5 then analyses the possible safeguards to guarantee that consent is properly granted and the subjects’ rights are duly protected during the trial. After some illustrations showing the need for such safeguards, Macklin argues for a universalistic conception of consent grounded in individual autonomy against group- or gender- biased definitions, defended on a cultural relativistic basis. In a similar spirit, Macklin defends the convenience of extending the competences of IRBs beyond its actual boundaries, so that they can survey privately sponsored trials abroad when no reasonable alternative is provided.
Chapter 6 focuses on how to make drugs affordable. Its moral implications are already clear at this stage: it would make less defensible the use of placebo in clinical trials conducted in underdeveloped countries and would substantiate the idea of post-trial benefits. Four complementary strategies are discussed: differential pricing in essential drugs; prior agreements to make the drug under trial available in the countries where it is conducted; joint initiatives of international agencies and private-public partnerships to produce affordable drugs; and the manufacture of generic copies of patented drugs for poor countries. Macklin presents different examples of each strategy, emphasizing their more positive prospects.
Chapter 7 returns to matters of principle and restates the case already made using the human rights vocabulary, acknowledging its role as a global standard for international organizations. The eighth and final chapter discusses how to develop research guidelines in accordance with all these considerations, using a quite realistic approach.
Macklin’s effort deserves all praise since she takes into account most of the many possible approaches to her subject and builds a unified and coherent case. Though Macklin navigates at ease in the endless details of the various declarations and proposals discussed, it is not difficult to get lost: the analysis is necessarily brief to keep the essay’s extension within reasonable limits, so many arguments are just outlined and the reader is referred to an ample bibliography to complete them. In this respect, a general references section (instead of one at the end of each chapter) would have been helpful. Yet, the thorough index appended somehow compensates for this and makes the book really accesible. All in all, it is a great survey of a terribly complex issue and it will greatly improve its discussion from now on.
As to the cogency of Macklin’s proposal of a unified standard for medical research, it is difficult not to be sympathetic and the arguments she provides may well ground a wide consensus. Yet, this is a book in which bioethical discussion very often yields policy recommendations, and in this respect I sometimes miss a more concrete discussion of how these would work under different circumstances. Since case studies are for Macklin a good enough ground to build her arguments for or against different policies, I would have liked a case-based analysis of the efficacy of her own proposals, i.e., one in which agents are not motivated by ethical considerations alone but also by their particular interests in the many scenarios in which these proposals should be implemented. Obviously, this is too much asking of a book which is mostly intended as an essay in applied ethics. Yet, when this field is expanded to encompass all the circumstances that she (wisely) takes into account, the argument necessarily becomes something more than ethics and a more interdisciplinary discussion would do much to strength her conclusions, making them more credible. Anyhow, this is a pioneer work and it is fair to say that it just makes this very discussion possible.
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