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RESEARCH ETHICS: SOME BACKGROUND Richard Carpentier, Santiago, November 3, 2011 Introduction • I would like to ground my intervention on the one hand in a conception that makes essential distinctions between ethics and morality and on the other in medicine as a moral profession insofar as there is a large moral consensus on medicine as seeking essentially to benefit the patient. • Historically, there is evidence that ethics and medicine evolved in parallel in Greek culture and that they nurtured each other. • Ethics learned from medicine the uniqueness of persons and situations as well as appropriate perception being the condition of an appropriate response. It also learned that the real person is the basis for moral judgments. • Medicine learned about appropriate goals for life, service to the state and a good life being paramount. ETHICS AND MORALITY The Ethical Intention • Ricœur defines the “ethical intention” as aiming at the “good life” with and for others, in just institutions. • Oneself as Another, 1992, 172. Paul Ricœur, 1913-2005 Ethics and Morality I propose to reserve the term “moral” as the fix reference term and to assign to it a double function, that to point to the region of the norms, said otherwise what is allowed or forbidden, on the one hand, and on the other the sense of obligation as the subjective face of a relationship of a subject to the norms. As far as I am concerned, this is the fixed point, the hard nucleus. De la morale à l’éthique et aux éthiques, undated conference, Montréal Paul Ricœur, 1913-2005 Ethics and morality • Ricœur roots the norms in real life and desire, as did Aristotle but he is also careful to insert them in concrete situations. • This way, morality is preceded and followed by ethics, both as a guide and a reality check. • So, as we move forward with our discussions, we are reminded of the importance of these distinctions and of the fact that ethics and morality are different but both important and complementary. Ethics and morality • But if morality is to be the real thing as Ricœur says, we need to look back at how we think about it. • Time is short here, but I want to introduce an important idea which should get us thinking. • The last decades have seen a return of ethics in the forefront. Especially an ethics characterized by a imperialism of principles and an abandonment of the real person in concrete situations. • A rationalistic ethics, oblivious of morality and of what are the real springs of action, be it our upbringing in a family and society, our nervous system and the inner organization of our brain with its ancient structures explaining emotions, desires, fear, etc. Morality is from Unconscious Origin • The head is ever the dupe of the heart. (102) • A man often believes himself leader when he is led; as his mind endeavours to reach one goal, his heart insensibly drags him towards another. (43) • Maximes François de La Rochefoucauld (1613 –1680) Disappearance of the Real Person In the 1780’s, the moral agent as traditionally understood almost, if not quite, disappeared from view. The moral agent’s character, the structure of his desires and dispositions, became at best a peripheral rather than a central topic for moral philosophy. Alasdair MacIntyre, How Moral Agents Became Ghosts, Synthese, 1982, 53, 295 Alasdair MacIntyre, 1919- The Art of the Right Perception • Wherefore the greater complexity these ills requires a more exact method of treatment. For it is necessary to aim at some measure. But no measure, neither number nor weight, by reference to which knowledge can be made exact, can be found except bodily feeling (aisthêsis). • Ancient Medicine, chapter 9 Hippocrates, Ancient Medicine, Trans. WHS Jones, Chapter 9. CLINICAL RESEARCH AND VULNERABILITY Back to patients • As we move to the topics of tomorrow presentations, we are reminded of the specificities of the patient population, being cancer patients. There are general characteristics of patients in general and of their attitude towards participation in clinical research, captured in the following survey results which apply especially well to cancer patients. • Harris Interactive, New Survey Shows Public Perception of Opportunity to Participate in Clinical Trials Has Decreased Slightly From Last Year, Healthcare News 5(6) June 27, 2005. % 2004 % 2005 If I had a terminal illness 72 72 If I thought the drug might cure me 71 67 If there were no other medical options available to me 67 66 If I knew there were no risks involved 67 61 If I thought the drug/treatment would help me 57 61 If the treatment were free of charge to me 64 53 If my doctor recommended it 54 47 If I received money for participating 56 46 If I knew the risks associated with the treatment 49 45 If I thought the drug/treatment would help someone else in future NA 45 If it were convenient for me to participate 53 43 If the location were convenient for me 54 43 If there were minimal side effects associated with the treatment 48 43 If I knew I would receive an active treatment, not a placebo 37 33 If I knew someone else who had the condition being studied NA 30 If I had a condition other than a terminal illness 38 29 If I take a drug/treatment made by same pharmaceutical company NA 28 Would consider participating in clinical research study Why do patients participate? • Not wanting to give up, to help other cancer patients, for their family and to have someone to talk to • Patients in early anticancer trials will take part because of the intense support offered Cox and McGarry. Eur J Cancer Care 12: 114, 2000 Why do patients participate? • “therapeutic misconception” • “many participants believe that clinical trials provide individualized treatment and direct benefit to subjects” • 43% of oncologists enrolled patients…to make sure they got state-of-the-art treatment Lo and Guerin, Cancer Clinical Trials: Proactive Strategies, 2007. Defining vulnerability • Definitions of vulnerability may be inward looking or they may be outward looking. These are somewhat arbitrary categories that I introduce. • For example, being vulnerable may be equivalent to being fragile, inward looking, or to being unable to protect oneself, outward looking. So, not so much a characteristic of the being as a characteristic of the relationship between beings. • You will note that both examples here refer to ‘being’, that is to something essential to who we are, at least in certain circumscribed circumstances. Vulnerability as Incapacity to Protect one’s interests • Vulnerability can be broadly defined as the inability to protect one’s interests. In relation to medical research, vulnerable individuals or populations are at increased risk of being harmed by research due to a decreased capacity to protect their personal interests. Ballantyne, A., Rogers, W., Vulnerability and Protection in Human Research, Harvard Health Policy Review, 8 (1), 2007, 30. Outward looking definition • These definitions are reminding us of an important value in our western culture, that of autonomy, literally the capacity to decide for ourselves, to lay out our own norms. • This has been an important feature of the ethics of research over the last 30 years or so, reinforced by the Belmont Report from the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (1974-1978) that came up with a set of guiding principles: autonomy, beneficence, and justice. Responsibility is for the fragile, the vulnerable Any active responsibility starts with the question: What will happen to him if I do not take care of him. The more the answer is obscure, the more clearly it is presenting itself. Fear that is an essential part of responsibility is not the one that council us not to act, but rather the one that invites us to act. Hans Jonas 1903 - 1993 The Imperative of Responsibility, The University of Chicago Press, 1985. Responsibility is for the fragile, the vulnerable • This fear that we are aiming at is the fear for the object of responsibility. It is an object that is fundamentally fragile for which it is possible to fear something. Hans Jonas 1903 - 1993 The Imperative of Responsibility, The University of Chicago Press, 1985. Inward looking definition • Jonas’ definition gets to the heart of the problem faced when dealing with recruitment of seriously ill patients, that is that they are fragile and they may die, they are essentially vulnerable as they may perish. And that we have a responsibility, as clinicians-researchers and REC members, to protect and promote the fragile, the vulnerable. But the cycle that leads to taking action to protect stars with the perception of the fragility. • And both the risks and the absence or low probability of benefits that are associated with phase 0 and phase 1 cancer trials do exacerbate the vulnerable status of the patient. Ethical Issues in Phase 0 Trials • Early determination whether a new drug is good candidate for further trials • Subclinical dosage means no benefit can be gain • TGN1412 trial in London shows small dosage may have unexpected catastrophic results • Patients in desperate situation will do anything to help themselves and others, compromising the independence of consent Ethical issues in phase 1 oncology trials • Because one of the end points of phase one oncology trials is toxicity, this is one area where voluntary volunteers give their place to affected individuals in phase 1 trials. • There are three primary ethical concerns associated with phase 1 trials Ethical issues in phase 1 oncology trials • 1- The risk to benefit ratio is inherently unfavourable for research subjects • 2- They enroll patients whose ability to provide valid informed consent may be compromised, and • 3- They may take advantage of vulnerable subjects. • In some of these studies, any benefit to the subject is, at best, highly unlikely. Subjects may experience a decline in health status from their participation, no improvements in terms of quality of life, or only a short prolongation of life. Abdoler, E., et al., The Ethics of Phase 0 Oncology Trials, Clinical Cancer Research, 14 (2008, 3692-3. ABOUT RESEARCH ETHICS COMMITTEES Introduction • REC have been establish to introduce independent judgment in the research process after the Second World War and the atrocities o all parties in research (Germany, Japan, US) • We expect a lot from REC, they should know everything, they should be virtuous, ingenious, generous with their time, be independent, etc. • But that is not always the case. Hundreds of visits of RECs in hospitals and universities have shown most of them lack the competence to do their work appropriately. • Another issue is that they are not as independent as we think they are and patients expect they are. Nothing requires them to be independent of institutions where research is carried out. Primary interest of IRB • The primary interest of IRBs is to ensure that the rights and welfare of research participants are fulfilled. All other interests are secondary, including personal or institutional financial gain. When a person's financial concerns have the potential to conflict with the protection of participants, a FCOI exists. Campbell, EG, Concerns about IRBs in the enterprise of clinical research, The Lancet Oncology, 5 (1) 2004, 326. Subjects believe there are safeguards against conflicts of interest • Of the patients surveyed, 62% believed there was an oversight system in place to monitor financial ties. However, when asked, most could not specify a system but suggested that there “must be a process during study implementation,” such as an “independent oversight committee to screen M.D.’s credentials and relationship with drug companies.” One third of the patients did not know whether there was such an oversight system. Hampson, LA et al, Patients’s Views on Financial Conflicts of Interest in Cancer Research Trials, New England Journal of Medicine, 355;22, 2006, 2334. A natural tension within the mission • ‘A natural tension exists as an IRB attempts of fulfill its mission of providing an independent and unbiased evaluation of a study while also insuring appropriate consideration of all relevant risks, benefits, and alternative strategies. IRB members with often critically relevant knowledge of unique issues involved in a protocol under review may be the individuals with the greatest potential for a perceived “conflict,” due to current or past involvement in sponsor-associated research in the particular area.’ • Campbell, Cancer Investigation, 26, 115-117, 2008. REC members financial COI may undermine objectivity • "Financial relationships with study sponsors create competing interests that could undermine the objectivity of the IRB process. Policies and practices regarding the disclosure and management of such relationships among IRB members need to withstand intense scrutiny, and our results suggest that we can do much better. » • EG Campbell, cited in Osterweil, N. Many Clinical Trial Overseers Have Conflicts of Interest ,MedPage Today, November 29, 2006 Conflicts of interest for Research Ethics Committees • … the ethical review of research protocols is generally performed within and by employees of the very institutions in which the research will be carried out, a clear conflict of interest. • T.L. Beauchamp, The (mis)used of informed consent in medical research, Journal of Internal Medicine, 269, 2011, p. 383. When we need to retain the services of the clinicianresearcher • In the case of smaller or regional hospitals, there might occur a conflict originating in the will or need to retain the services of a difficult to recruit specialist. • Very specialized surgeons for examples or anaesthetists are difficult to recruit. If the REB turns down a protocol, they may choose to go elsewhere. THANK YOU!