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Journal of Bioethical Inquiry

, Volume 15, Issue 4, pp 589–602 | Cite as

What Is the Good of It—Ethical Controls of Human Subject Health Research?

Curtin University Annual Ethics Lecture
  • Robert FrenchEmail author
Original Research
  • 102 Downloads

Abstract

The term “ethics” covers a multitude of virtues and possibly some sins where ethical perspectives differ. Given the diversity of ethical philosophies there is a question about what common ground can, or should, inform health research ethics. At a minimum it must be consistent with the law. Beyond that, ethics embraces a variety of possible approaches. This raises the question—what criteria are applied in determining the appropriate approach and what standards by way of quality control are applied to its decisional application by ethics committees or other authorities exercising responsibility in this difficult area. The particular issue of ethical perspectives on the use of “big data” in medical research also raises complex issues for consideration.

Keywords

Human research ethics Bioethics Big data Consent Privacy Research ethics 

Introduction

There is a Latin saying, framed by the Roman poet Terence, “Quot homines tot sententiae”—which means there are as many opinions as there are people. It is applicable to a variety of fields of intellectual and moral endeavour. The ethics of human subject medical research is one of them. It accommodates varying approaches to decision-making. That variability raises the question—what is the good of it? A second question follows—how does one judge whether an ethicist involved in bioethical research approvals is good at what he or she is supposed to do? Then there is the question of transparency—how is one to know how bioethics decision-making is done and particularly in human research ethics committees which tend not to publish reasons for their decisions? A recent case study leads into some general reflections about these topics.

The Contestability of Ethical Decisions—A Randomised Sham-Control Case Study

On 2 November 2017, a paper published in The Lancet reported the results of a study of the benefits of using stents to treat stable angina caused by severe single vessel arterial blockages (Al-Lamee et al. 2017). From the two hundred patients who participated, 105 of them, randomly selected, underwent the insertion of a stent in their blocked arteries by way of a catheter threaded through the groin or the wrist. The remaining ninety-five underwent the insertion process but, unknown to them, no stent was implanted. Six weeks later both groups reported comparable improvements in chest pain frequency and performance times on treadmill tests.

The patients were provided with a leaflet and oral advice before they agreed to participate. The leaflet informed them that they would be randomly allocated to receive either implantation of a coronary stent along with medication or medication treatment alone. They were also told that they would not directly benefit from the study (Al-Lamee et al. 2017).

It is in the public interest for cardiologists and their patients to know that stenting may not provide any real benefit for a significant portion of patients suffering stable angina. The study which has led to the exposure of that possibility is not the first to have used sham-control surgical procedures (Cobb et al. 1959).

The critics of such trials contend that they create a risk of harm with no corresponding benefits to subjects in the control group. They cannot readily be reconciled with the physician’s duty of personal care (London and Kadane 2002). Supporters contend that it is unethical not to conduct rigorous evaluation of innovative surgical procedures (Beecher 1961) and that randomized sham-controls with double blinds provide the highest quality evidence of surgical efficacy. It has also been argued that the placebo effect, which may be manifested in control subjects, constitutes a real benefit and should be placed in the mix of risk–benefit assessment when applying ethical guidelines (Brim and Miller 2013).

Approval for the study in The Lancet was given by the London Central Research Ethics Committee.1 Dr William Boden, professor of medicine at Boston University School of Medicine was quoted in a news report on the study in the New York Times on 2 November 2017, as saying that ethics boards at many American hospitals would probably resist giving approval to such trials subjecting patients to fake procedures. He contended that they flew in the face of applicable guidelines (Kotata 2017). Nevertheless, guidelines issued by the Council of Ethical and Judicial Affairs of the American Medical Association state that such a trial is justified as long as no other design can yield the requisite data:

When a new surgical procedure is developed with the prospect of treating a condition for which no known surgical therapy exists, or when the efficacy of an existing surgical procedure comes into question, a study design using surgical placebo controls may be justified if it is known that the disease being studied may be susceptible to a placebo effect and the risks of the surgical placebo effect and the risks of the surgical placebo control operation are relatively small. (Tenery et al. 2002, 305)

Bioethics is a moving feast catering to different tastes. The debate about randomized sham-control trials of surgical procedures is an example of the contestability of particular applications of ethical guidelines in human subject research. Guidelines tend to be broadly expressed. There is ample room for reasonable, competent people acting honestly and diligently to come to quite different conclusions about how they apply to particular cases. Further, there is more than one ethical philosophy which may be brought to bear within the broad framework of existing guidelines. Other variables may come into play in diverse cultural settings.

Deontology and Utilitarianism

Two important strands in ethical philosophy are the deontological and utilitarian. The deontological ethicist judges choices by rule or principle-based criteria not necessarily dependent upon the outcome of those choices. Some courses of action are morally forbidden regardless of their benefits. Deontology is not monolithic. It may encompass different sets of values. For one prominent Australian bioethicist, the applicable principles are derived from underlying concepts of “inherent wrongness,” “profound respect for human life,” and “deep respect for the human spirit,” as well as “metaphysical reality” (Somerville 2000).

By way of contrast, a utilitarian ethicist will focus on goals or desired outcomes and judge actions by the extent to which they advance those goals (Singer 2000). An action is ethical if it produces an increase in the happiness of all who are affected by it which is equal to or greater than the increase of the happiness which would be provided by any alternative action. In the context of randomized sham-control studies of surgical procedures, a deontologist emphasizing a duty to protect patients as research participants may be in conflict with the utilitarian who might be inclined to give greater weight to securing accurate data regarding potential benefits for patients at large.

There may be divergences within philosophies. Deontological ethicists may adopt different views depending upon the rules or principles to which they adhere. And even with a set of criteria, there may be different ideas of the application of those rules or underlying values, such as “inherently wrong” or “deep respect for the human spirit.” Utilitarians might have different ideas of what constitutes “benefit” or “happiness” and the scales on which two hypothetical outcomes are to be weighed against each other.

Informed Consent, Crossing the Boundaries of Deontology and Consequentialism

There are, as the international historical development of bioethical guidelines demonstrates, important and widely accepted propositions which cut across the boundaries of ethical philosophies. The general requirement that the subject of a medical research study should give informed consent before participating in it is one of them. The person whose consent is sought must competently reach a voluntary decision which is sufficiently informed about the process in which he or she is invited to take part. It is not simply a matter of saying “yes” after having been told about the nature of the study. There is, for example, an acknowledged risk that consent will be influenced by what has been called “therapeutic misconception.” That is the misconception that the proposed study is designed with the primary goal of directly benefiting the participants or that they could obtain more benefit than scientifically expected. Patients may fail to understand information about the trial in which they have been invited to participate. That misunderstanding may be based on overestimation of the benefits, underestimation of the risk and a failure to understand randomization. They may hear what they want to hear. As Swift and Huxtable observe in a substantial piece on the ethics of sham surgery:

… “misunderstanding” about research may be a “persistent and incorrigible feature of people’s participation in research.” This may be because of the deep trust people place in research and in those who conduct it. (Dixon-Woods quoted in Swift and Huxtable 2013,182)

In this connection it may be noted that the information leaflet given to patients in the study in The Lancet made a clear statement of the lack of any direct benefit to the patient (Al-Lamee 2017).

Even closer scrutiny of consent, where consent is sought, will be relevant if a study is carried out in circumstances where the subject is under some form of duress—in particular, prisoners who may harbour a hope for some benefit which the researcher cannot promise. Prisoner studies are mentioned below.

The National Statement on Ethical Conduct in Human Research (NHMRC National Statement 2007a) issued by the National Health and Medical Research Council (NHMRC), the Australian Research Council (ARC) and the Australian Vice-Chancellor’s Committee (AVCC) requires consent based on mutual understanding between researchers and participants. Participants should have the opportunity to ask questions and to discuss the information with others if they wish (NHMRC National Statement 2007b). The National Statement is fairly detailed in the kind of information that should be communicated to participants and, in particular, provides that:

No person should be subject to coercion or pressure in deciding whether to participate. Even where there is no overt coercion or pressure, consent might reflect deference to the researcher’s perceived position of power, or to someone else’s wishes. Here as always, a person should be included as a participant only if his or her consent is voluntary.

Cultural Diversity and Bioethics

I have referred to the variables of and within ethical philosophies which may be at play in bioethical decision-making. A further emerging variable which detracts from the universality of bioethical principles appeared, evidently for the first time, in the UNESCO Universal Declaration of Bioethics and Human Rights in 2005. It is found in Article 12, headed “Respect for Cultural Diversity and Pluralism.” Article 12 provides:

The importance of cultural diversity and pluralism should be given due regard. However, such considerations are not to be invoked to infringe upon human dignity, human rights and fundamental freedoms, nor upon the principles set out in this Declaration, nor to limit their scope.

Article 12 recognizes a tension between endeavours to universalize bioethical principles in response to the globalization of medical research and human rights on the one hand and, on the other, different views of what is ethical and what is not according to particular cultural and historical perspectives. On one view, allegedly universal principles of bioethics have been nurtured in an Anglo-American cultural incubator and are concerned principally with questions generated by developments in modern science and technology which are not priority issues in many parts of the world. Indeed, the term “moral imperialism of Western bioethics” appears as a heading in a paper on the topic published in 2013 (Chattopadyay and De Vries 2013). The tension is made explicit in the qualification in Article 12 of the UNESCO Declaration. That qualification invites a determination of whether relevant cultural norms and practices may violate human rights and whether they deserve the otherwise generally mandated respect (Macklin 2014).

A further sub-variable may be generated by the often dynamic and heterogeneous nature of culture. Cultures are not necessarily defined by a static set of attributes. They can evolve, sometimes quite rapidly, in response to changing circumstances, including, today, the ubiquity of social media and electronic communications.

Bioethics and Big Data

The landscape of ethical concerns also changes with new scientific and technological developments. One of those is the use for medical research and like purposes of so-called “big data.” The term “big data” covers what has been described as “a vast variety of phenomena found in the analysis of large data sets” (Mittelstadt and Floridi 2016, 447). Relevantly to biomedical research, it may be derived from clinical trials, genetic and microbiome sequencing data, biological specimens, electronic health records, and administrative hospital records. It may also be derived from social media, personal health monitoring technologies (including wearable devices), online forums, and search histories. There are “data brokers” who collate and sell information based upon social media, online purchases, insurance data, medical devices, and clinical data provided by public health agencies and others (Mittelstadt and Floridi 2016). The analysis of big data may yield publicly useful information with predictive value. It may also yield information of essentially commercial value for the identification of developmental and marketing priorities by pharmaceutical companies and others. Mittelstadt and Floridi in a comprehensive review article published in 2016 cautioned that:

While promising on many fronts, biomedical Big Data, and the findings derived from it, may raise a host of ethical concerns stemming from the sensitivity of data being manipulated and the seemingly limitless potential uses and repurposing, and implications of data that concern individuals as well as groups (Mittelstadt and Floridi 2016).

Big data raises a unique set of ethical challenges. It is important not to try to shoehorn responses to those challenges into an ill-fitting framework of principles devised to regulate qualitatively different activities of the kind already discussed. The concept of informed consent is not readily transferred to the use of a medical database to which an individual has contributed. As Mittelstadt and Floridi’s literature review suggests, single instance use consent is difficult. The use of big data is intended to reveal unforeseen connections. Single instance consent for each use may be impractical. A general preauthorization is an alternative, even though it might be seen as limiting the autonomy of the person whose data is being used.

The Australian National Statement dealing with consent to the future use of data and tissue in research provides that the consent to be given by the person whose data is to be collected may be specific, extended, or unspecified. Those terms represent a broadening hierarchy of consents (NHMRC National Statement 2007b).

The difficulty of limited consent is compounded in principle as well as in practice if informed consent requirements are applied to the building of information relevant to an individual, into a large data set with information from other individuals. Any controls on the construction of such data sets would no doubt have regard to public benefits to be derived from their use against the possible adverse impacts on an individual and the practical difficulties obtaining individual consents.

Where individual genetic information is built into a data set covering a population or a particular subset of a human population there may be ethical objections taken to its use for particular purposes. If, for example, a database of isolated nucleic acid samples taken from a number of individuals discloses a range of mutations indicative of a susceptibility to a particular condition, some of those individuals may be concerned about particular uses of their information. That concern might be extended to the claiming of intellectual property rights giving the researching entity a power to determine who would or would not have access to the benefits of the research. Some ethnic groups may be concerned that studies of the genetic makeup of their communities could yield information that members of that group would regard as communal property to be used for the benefit of the group but not for the world at large without their consent. This overlaps with the notion of ownership of information provided by individuals or groups and the extent to which that informs the use of such information.

These are just a few of the concerns which arise in the context of big data and illustrate the proposition that human subject medical research bioethics is a large, complex field of activity. It is also a field well populated by a burgeoning ethics industry.

The Ethics Industry

There is a complex infrastructure of ethics screenings and approval mechanisms in Australia and around the world which support countless decisions which may permit, prevent, or constrain medical research involving human subjects in a variety of ways.

There is an ethics industry with educational, advisory, and adjudicatory elements across many areas of human activity not limited to medical practice and research. The field is as dynamic as the world in which it finds its place. In 2003 when preparing a commentary on a paper to be delivered to a Judges’ Conference by Professor Margaret Somerville, I came across a website set up by an organization based in Pennsylvania called “Ethics Quality Inc” offering “ethics and culture management services” and advertising ethics training aids for employees (French 2003). One of those aids, which was then priced at $12.95 with discounts for volume over two dozen, was promoted thus:

This handy four page, 8½ x 11” color laminate highlights eleven deductive and five inductive fallacy categories, and over 40 specific lower forms, totalling over 101 of the most common logical fallacies and ethical lower forms. The shortest path to improving organisational ethics is to prevent these forms from corrupting the ethical reasoning process. To prevent them, one must first be aware of them. Put this laminate into the hands of all employees, and ethics will improve. (Cited in French 2003)

A more recent search has failed to turn up this website. It seems that laminated ethics may have gone the way of VHS videos.

A website search of “medical ethics training tools” today discloses a variety of ethics educational services in relation to research generally and in relation to healthcare and medical research ethics specifically. There are online courses for ethics committees and researchers. One site offers “Bespoke Ethics Training—With the Ethics Centre (previously known as St James Ethics Centre).” It offers a free ethics helpline under the designation “Ethi-call.” It is advertised as providing a confidential and safe space for people to explore ethical challenges and seek support to make sound, ethical decisions. Virtual reality-based simulations or games designed for medical ethics training are also available.

Ethic—Qualifications and Standards

The ethicist, acting alone or in conjunction with others as a member of an institution or health research ethics committee, seems to have become a kind of societal gatekeeper or secular priest. The question must be asked—on what basis does society entrust important decision-making to individual ethicists or ethics committees whose reasons for their decision do not generally appear in the public domain? What are their necessary qualifications? What standards of competence and integrity are to be applied to the discharge of their duties? There is no clear answer. In relation to bioethics, it is useful to place the question in its evolutionary historical setting, which includes both medical practice and research. Boundaries between practice and research are not always well defined. The 2015 edition of the Manual for Practitioners published by the Swiss Academy of Medical Sciences (Swiss Academy of Medical Sciences 2015) quotes a nineteenth century observation that the practice of medicine amounts to a “continued series of experiments on the lives of our fellow creatures” (Maclean 1818). It is encouraging that the history of bioethics indicates a convergence in relation to practice and research upon common themes of patient welfare, autonomy, and risk assessment, as well as societal benefits. On the other hand, as relatively recent history shows, the path towards that convergence has been punctuated by appalling episodes of suffering inflicted on tens of thousands of people in the name of medical experimentation.

The Primacy of Patient Welfare in Bioethical History

A long-standing common requirement of medical practice is that doctors attend to the welfare of their patients. The Code of Hammurabi, promulgated in about 1750 BCE, decreed that a surgeon who treated a patrician for serious injury and caused his death was liable to have both his hands cut off. The same penalty applied to a cataract removal resulting in loss of the eye (Johns 1904). Patient welfare, at least of the upper classes, was plainly a priority.

A broadly expressed and more durable norm directed to patient welfare, dignity, and privacy was reflected in the Hippocratic Oath. The oath has been described as having two primary aspects—a private statement of obligation to the medical profession and the oath-taker’s teacher and a public promise to all whom the oath-taker met and, particularly, the sick. Sworn before all the gods and goddesses, it included the promises:

I will use treatment to help the sick according to my ability and judgment; but never with a view to their injury and detriment. I will not administer a drug to cause death, even if asked to do so; … I will keep pure and holy both my life and my art … And whatever I may see or hear in the course of my professional activities … I will never divulge, but treat as holy secrets. (Craik 2015, 86)

The oath was an expression of a basic ethic of medical treatment. Its central elements of respect for the welfare, dignity, and privacy of the patient have a certain timelessness about them. It was invoked and extended by an American military tribunal at Nuremberg in 1947 in the formulation of seminal ethical principles relevant to experimentation on human subjects—the Nuremberg Code.

There is a long history of human subject experimentation. The seventeenth and eighteenth centuries saw the rise of experimental pharmacology including chemical analysis, animal experiments, and human research. Andreas-Holger Maehle, a reader in history of medicine at the University of Durham in England who has published an account of that period, describes experimentation with key drugs including opium. He describes “some hints at ethical considerations” in contemporary accounts of human experiments with opium noting that the transition from its therapeutic to its experimental use was often smooth or blurred (Maehle 1999). The consents which were obtained for experiments were of doubtful quality. He wrote:

Contemporary sources briefly discussing experiments on hospital patients in general such as the Thoughts on Hospitals (1771) by the young Manchester surgeon John Aikin (1942–1822) or the well-known Medical Ethics (1803) of the latter’s prominent physician-friend Thomas Percival (1740–1804) do not in fact mention information or consent of the test persons. Aikin assured his readers that all precautions were taken and that the subjects would be the first to benefit from new forms of treatment. (Maehle 1999, 194)

Maehle went on to say that the concept of an informed consent in the modern sense was clearly formulated only in the late nineteenth century after abuses in experimentation on hospital patients had become a public issue. Ultimately, in both animal and human experimentation with opium, ethical attitudes prevailed. This did not prevent extensive and sometimes dangerous trials (Maehle 1999). The relatively embryonic ethical awareness to which Maehle referred was to persist and later to mature. However, until relatively recently, it did not apply to all and particularly not to captives. It was the conduct of experiments on captives, particularly in Nazi Germany and World War II that led to the development of comprehensive modern bioethical codes and guidelines.

Experiments on Prisoners

Historically, captives were seen as a legitimate subject of medical investigation unfettered by undue ethical sensitivities. There are various accounts from ancient times of prisoners being used to test poisons and being subjected to vivisection. In eighteenth century Europe, prisoners were exposed to sexually transmitted diseases, typhoid, and scarlet fever (Moreno 2005). Nazi doctors during World War II carried out horrific experiments on concentration camp inmates. Japanese doctors engaged in similar atrocities with a particular focus on the deliberate infection of prisoners with biological agents.

In the United States before and after World War II there was experimentation on prisoners sometimes with and sometimes without their consent. Prisoners at Stateville Penitentiary in Illinois in the 1940s were offered the opportunity to be infected with malaria and subjected to testing of sometimes dangerous antimalarial drugs. Prisoners were offered remissions in their sentences if they participated (Alving et al. 1948). The prisoner participants recorded data on one another, administered the mosquito bites and experimental drugs, and helped decide who was admitted to the project and who was eligible for early parole as a result of participation. The project was described in a study published in 2009 as one in which “research and punishment were completely interpenetrating and mutually reinforcing” (Comfort 2009).

A more notorious medical research project was carried out between 1946 and 1948 on prisoner populations in Guatemala to test medication for sexually transmitted diseases. The study population included more than 5,500 Guatemalan prisoners, sex workers, soldiers, children, and psychiatric patients. Roughly one quarter of them were deliberately infected with syphilis, gonorrhoea, and cancroid. All were enrolled in the experiments without their consent. A study published by Ivan Semeniuk and Professor Susan Reverby of Wellesley College brought the experiments to public attention in 2010 (Semeniuk and Reverby 2010). Secretary of state, Hillary Clinton, and human services secretary, Kathleen Sebelius, subsequently apologized to the government of Guatemala and the survivors and descendants of those infected, condemning the experiments as “clearly unethical.” They said in a joint statement:

Although these events occurred more than 64 years ago, we are outraged that such reprehensible research could have occurred under the guise of public health … We deeply regret that it happened and we apologise to all the individuals who were infected by such abhorrent research practices. (McNeil 2010, A1)

Nazi Doctors Trial

While the Guatemalan experiments were being conducted, the practice of medical experimentation by Nazi doctors on unwilling human subjects during World War II came before an American military tribunal at Nuremberg in 1947. It was the first of a series of twelve trials of representative Nazis conducted in addition to the major war crimes trials which were heard before the international military tribunal. In what came to be called the “Doctor’s Trial,” there were twenty-three defendants, twenty of whom were accused of murder and torture in the conduct of medical experiments on concentration camp inmates. Murder had already been characterized by the international military tribunal as a crime against humanity. Sixteen of the defendants were convicted. Five were hanged, and the rest were sentenced to terms of imprisonment.

A theme of the prosecution case was the relevance of the Hippocratic Oath to human subject experiments. Andrew Ivy, a distinguished physiologist called as a prosecution witness, described the oath as the “Golden Rule” of the medical profession in the United States and throughout the world. Relevantly to experimentation, he contended that the physician conducting an experiment must have respect for the life and the human rights of the experimental patient.

Ivy had prepared for the trial three ethical principles concerning experimentation with human beings. These were adopted in December 1946 by the American Medical Association. They required consent, knowledge-based experimentation, and risk–benefit assessments. They were said to reflect an understanding already shared by everyone in practice in the medical community.

The Nuremberg Code

The tribunal in its judgment expanded upon the Ivy document and set out ten principles which became known as the “Nuremberg Code.” It was seen by some as a starting point of modern biomedical ethics. Indeed, one noted medical ethicist, Dr Arthur Caplan, at a conference in 1989, asserted that “[t]he whole discipline of biomedical ethics arises from the ashes of the Holocaust” (Caplan 1989).

The code required informed voluntary consent. The proposed experiment had to be such as to yield fruitful results for the good of society unable to be obtained by other methods. It had to be based on animal experimentation and a knowledge of the natural history of the disease or other problem being studied. It should be conducted so as to avoid all other physical and mental suffering and injury. It prohibited experiments if there was reason to believe that death or disabling injury would occur—subject to a qualification where the physicians were the subjects. The risk of the experiment was not to exceed what could be justified by the humanitarian importance of the problem to be solved by the experiment. The subject was to be at liberty to bring the experiment to an end. The investigator had to be prepared to terminate the experiment at any stage (Trials of war criminals 1949). The Nuremberg Code is seen as a seminal document in the history of twentieth century biomedical ethics.

The Case of the Japanese Doctors—A Different Kind of Ethical Reasoning

Official post-war responses to Nazi and Japanese doctors were strikingly different. Unlike the Nazi doctors, the Japanese doctors who experimented on prisoners were not prosecuted for war crimes. A decision was made that the information derived from their human biological warfare experimentation would be kept in “intelligence channels.” A taskforce of the State-War-Navy Coordinating Committee reviewing the use of the material admitted that the experiments were similar to those for which the Germans had been tried for war crimes. However, they justified their refusal to prosecute by stating, inter alia:

The value to the U.S. of Japanese [biological warfare] data is of such importance to national security as to far outweigh the value accruing from “war crimes” execution. (Brody et al. 2014, 220)

An interesting historical review of the contrasting American response to Japanese medical experimentation, published in 2014, rejected the suggestion that there had been a lack of ethical perception in the American response arguing:

Contrary to [the] claim that no ethical thinking appears in the American documents on Japan, there was no lack of ethical perception. The Americans clearly saw a problem requiring ethical justification. Although today we regard their ethical thinking as seriously flawed; nevertheless, it was a form of ethical reasoning. (Brody et al. 2014, 227)

The authors concluded that it was essential to condemn both the Japanese war criminals and the Americans who covered up their crimes. However, they added:

To pursue a deeper understanding is not to rationalise or justify the atrocities but to identify the historical and ethical causes of why things went so terribly wrong. However faulty the ethical reasoning employed in the cover-up, by studying it we gain important insights into where such flawed reasoning may next be applied today and tomorrow. (Brody et al. 2014, 229)

Ethical reasoning, as I have already observed, may cover a multitude of virtues but may also sanction what in retrospect are vices.

The Declaration of Helsinki

The next significant international document on bioethics relevant to human research after the Nuremberg Code was the Declaration of Helsinki, published by the World Medical Association in 1964. It was described in its preamble as “a statement of ethical principles for medical research involving human subjects, including research on identifiable human material and data.”

The declaration required voluntary informed consent by individuals participating in medical research. That informed consent extended to the use of identifiable human material or data such as material or data in biobanks (Brody et al. 2014). The declaration dealt with the use of placebos in terms wide enough to cover surgical placebos:

Where for compelling and scientifically sound methodological reasons the use of any intervention less effective than the best proven one, the use of placebo, or no intervention is necessary to determine the efficacy or safety of an intervention and the patients who receive any intervention less effective than the best proven one, placebo, or no intervention will not be subject to additional risks of serious or irreversible harm as a result of not receiving the best proven intervention. (Declaration of Helsinki (World Medical Association, 1964) art33)

Controversially the declaration allowed a degree of freedom to physicians to omit the application of consent procedures in special circumstances.

In 1975, the declaration was revised to require the assessment of research protocols by an independent research ethics committee. It was revised again in 1983 and 1989. Today, it is considered as a highly significant document of ethical principles for medical research involving human subjects, including research on identifiable human material and data (Guraya et al. 2014).

The Evolution of International Guidelines for Biomedical Ethics

A number of other international instruments relating to biomedical research were issued in the last decade of the twentieth century. In 1993, the Council for International Organizations of Medical Sciences in collaboration with the World Health Organization issued International Ethical Guidelines for Biomedical Research Involving Human Subjects. In 1997, the Council of Europe adopted a Convention for the Protection of Human Rights and Dignity of the Human Being with Regard to the Application of Biology and Medicine.

In 2000, the World Health Organization issued operational guidelines for ethics committees that review biomedical research. The document described the purpose of an ethics committee in reviewing biomedical research as contributing to safeguarding the dignity, rights, safety, and well-being of all actual or potential research participants. It stated that the goals of research, while important, should never be permitted to override the health, well-being, and care of research participants. Ethics committees were expected to provide independent, competent, and timely review of the ethics of proposed studies. In their composition, procedures, and decision-making they were to have independence from political, institutional, professional, and market influences. They also needed to demonstrate competence and efficiency in their work. Members were to have initial and continuing education regarding the ethics and science of biomedical research.

An important development in the globalization of bioethics principles was The Universal Declaration on Bioethics and Human Rights, promulgated by UNESCO in 2005. In the foreword, it is asserted that for the first time in the history of bioethics, member states committed themselves and the international community to respect and apply the fundamental principles of bioethics set forth within a single text. The declaration has as one of its purposes that scientific research and development should “occur within the framework of ethical principles set out in this Declaration ….” It created a large framework within which health research may be undertaken. The principles, like their predecessors, are pitched at a level of generality which will allow for a range of different ethical perspectives to be brought to bear in particular cases.

Relevant aspects of the UNESCO principles include:
  1. 1.

    Priority given to the interests and welfare of the individual.

     
  2. 2.

    The application and advancement of scientific knowledge, medical practice, and associated technologies so as to maximize direct and indirect benefit to patients, research participants, and other affected individuals and minimize possible harm to them.

     
  3. 3.

    Respect for personal autonomy to be respected. Special measures to protect those not capable of autonomy.

     
  4. 4.

    Prior free, expressed, and informed consent required from persons subject to scientific research.

     
  5. 5.

    Research on persons lacking capacity to consent to be done only for that person’s direct health benefit and under authorities and protections provided by law where there is no research alternative of comparable effectiveness.

     
  6. 6.

    Research on such persons absent direct health benefit only to be undertaken by way of exception with the utmost restraint, exposing the person only to a minimal risk and minimal burden.

     
  7. 7.

    Respect for the privacy of persons and the confidentiality of personal information.

     
  8. 8.

    Respect for the fundamental equality of all human beings in dignity and rights.

     
  9. 9.

    No discrimination against or stigmatization of any individual or group on any grounds, in violation of human dignity, human rights, and fundamental freedoms.

     
  10. 10.

    Respect for cultural diversity and pluralism.

     
  11. 11.

    Solidarity among human beings and international cooperation to be encouraged.

     
  12. 12.

    The promotion of health and social development for their people is a central purpose of government that all sectors of society share.

     
  13. 13.

    Sharing of the benefits of scientific research.

     
  14. 14.

    Due regard to the impact of life sciences on future generations, including their genetic constitution.

     
  15. 15.

    Protection of the environment, the biosphere, and biodiversity.

     

Large Words of Indeterminate Meaning

There are many words used in the various principles referred to above which have a wide range of meanings and possible applications. The choice of meaning or application may depend upon the particular ethical perspective of the person making the choice. They may also be informed by that person’s cultural background. Terms used in the Universal Declaration include: “interests,” “welfare,” “direct benefit,” “indirect benefit,” “harm,” “autonomy,” “free and informed consent,” “privacy,” “confidentiality,” “dignity,” and “just and equitable treatment.”

They are words which tend to indicate evaluative conclusions about outcomes rather than means of achieving them. Against that background, the problem posed by the title to this lecture can be framed by asking—if I were a researcher seeking to work within those principles and seeking advice about a proposed investigation, what kind of person, with what qualifications, approach, and standards of conduct, practising under the designation “ethicist,” would I turn to for advice? The question is not just one which arises within the framework of the Universal Declaration. It arises in a concrete way under Australian domestic law.

The Growth of National Regulation

The history of bioethics includes the history of domestic statutory and non-statutory regulation of human subject medical research. It is sufficient to refer to a few examples of current arrangements in comparable countries. They are indicative of the pervasive global, albeit not universal, character of bioethical principles today. In the United States, bioethical principles are found in the Health Policies and Procedures Relating to Research in Human Subjects, issued by the National Institute of Health, which began to be developed in the 1950s. The first United States law requiring informed consent for human subjects was enacted in 1962 (the Kefauver Harris amendment). The National Research Act was enacted in 1974, with regulations made under it for the protection of human subjects of biomedical and behavioural research. Comprehensive regulation of human subject research developed apace over the following years in the United States and many other countries (Care Act 2014). Canada currently has in place the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans. It was issued by the Canadian Institutes of Health Research (created by the Canadian Institutes of Health Research Act 2000), the Social Science and Humanities Council, and the National Science and Engineering Research Council of Canada. The statement was updated in 2012 (Millum 2012). In both the United States and Canada, ethics review of research is a condition of federal government funding.

In April 2001 a directive was issued by the European Parliament and the Council of Europe (European Parliament Directive 2001/20/EC). It was stated to be a directive “on the approximation of the laws, regulations and administrative provisions of Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use.” Article 1(2) of the directive states that:

Good clinical practice is a set of internationally recognised ethical and scientific quality requirements which must be observed for designing, conducting, recording and reporting clinical trials that involve the participation of human subjects. Compliance with this good practice provides assurance that the rights, safety and well-being of trial subjects are protected, and that the results of clinical trials are credible.

Article 6(1) of the directive provides that:

For the purposes of implementation of the clinical trials, Member States shall take the measures necessary for establishment and operation of Ethics Committees.

The article requires that ethics committees give their opinion before a clinical trial commences on any issue requested. It sets out the various matters to be considered by ethics committees and provides, in Article 6(5):

The Ethics Committee shall have a maximum of 60 days from the date of receipt of a valid application to give its reasoned opinion to the applicant and the competent authority in the Member State concerned.

The Directive has been implemented in the United Kingdom by the Medicines for Humans Use (Clinical Trial) Regulations 2004.

The Health Research Council Act 1990 (NZ) established a health research council and an ethics committee. The function of the committee includes the provision and review of ethical guidelines for the council. It can also provide advice to ethics committees established by other bodies on membership, procedure, and standards. In appointing members to the committee, the council must have regard to the need for a diversity of knowledge and experience in relation to “ethics, philosophy, law, theology, nursing, women’s health, patient advocacy and titanga Maori.”2

Australian National Law and Guidelines

The National Health and Medical Research Council Act 1992 (Cth) (NHMRC Act 1992) has as one of its objects the provision of a national body, namely the council, to pursue activities designed “to foster consideration of ethical issues relating to health”. The chief executive officer of that body has as one of his or her functions to inquire into, issue guidelines on, and advise the community on “ethical issues relating to health”.3 He or she is required by the Act to issue human research guidelines. They are to be developed by another body created under the Act, the Australian Health Ethics Committee, and are to be provided by it to the NHMRC.

The composition of the Australian Health Ethics Committee, according to the Act, requires that it have among its membership “a person with knowledge of the ethics of medical research.” There are other statutes with similar requirements such as the Gene Technology Act 2000 (Cth) which provides for the appointment of a Gene Technology Ethics and Community Consultative Committee .4 Human research guidelines under the NHMRC Act were issued in 2007 in the form of the National Statement (NHMRC National Statement 2007a). Its purpose is to promote ethically good human research. It is designed to clarify the responsibility of institutions and researchers for the ethical design, conduct, and dissemination of the results of human research and review bodies in the ethical review of research (NHMRC National Statement 2007a).

The National Statement is to be used to inform the design, ethical review, and conduct of human research that is funded by, or takes place under the auspices of, any of the bodies that have developed it, not only the NHMRC, but also the ARC and the AVCC. It is comprehensive. It identifies values and principles of ethical conduct and the themes of risk, benefit, and consent in research ethics. It identifies ethical considerations which are specific to particular research methods or fields and ethical considerations specific to various classes of participants (NHMRC National Statement 2007b). It also sets out the processes of research governance and ethical review (NHMRC National Statement 2007a). Importantly, it provides that:

Each member of an ethical review body is responsible for deciding whether, in his or her judgement, a proposal submitted to the review body meets the requirements of this National Statement and is ethically acceptable.

Each member of a review body is expected to become familiar with the National Statement, consult other relevant guidelines, prepare for and attend scheduled meetings of the review body, and attend continuing education or training programs on research ethics at least every three years. Any actual or potential conflict of interest is to be disclosed. The National Statement provides that human research ethics committees should endeavour to reach decisions by general agreement, albeit that need not involve unanimity.

While members of research ethics committees, including ethicists on those committees, are accorded considerable guidance by the National Statement, it does allow for the variables mentioned earlier in this lecture to come into play.

The Utility of Bioethics

As appears from the preceding history and the discussion around it, ethics in its application to medical practice and research covers a multitude of virtues and, depending upon some viewpoints, a number of vices. The definition of “ethics” in the Australian Oxford Dictionary offers two meanings:
  1. 1.

    The study of morals in human conduct; moral philosophy.

     
  2. 2.

    The rules of conduct recognised as appropriate to a particular profession or area of life.

     

The second definition is perhaps the most relevant to a consideration of the purposes and usefulness of ethics in medical practice and research. What are recognized as “appropriate rules of conduct” in the context of medical practice and human subject research will depend upon a consensus of ethicists and researchers informed by the general principles which have emerged as constant features of recent international bioethical guidelines and guidelines adopted within other comparable countries. It may be accepted that in their application, principles such as those contained in the UNESCO Declaration and in the Australian Statement may accommodate a variety of possible ethical choices. To say that is not to imply they are some kind of Rorschach blot into which people can read whatever they want.

The potential variability of ethical opinions is acknowledged in the National Statement:

Research, like everyday life, often generates ethical dilemmas in which it may be impossible to find agreement on what is right or wrong. In such circumstances, it is important that all those involved in research and its review bring a heightened ethical awareness to their thinking and decision-making. The National Statement is intended to contribute to the development of such awareness. (NHMRC National Statement 2007a)

There are important considerations to which any researcher and biomedical ethicist must direct his or her attention. Those important considerations relate to the interests and welfare of participants, respect for their personal autonomy, and assurance that, as a general rule, their prior informed and voluntary consent to the study procedures has been obtained. There is also a common requirement of assessment of direct and indirect benefit to participants and the minimization of possible harm to them. Respect for their privacy and confidentiality of their personal information is another important element. All of this can be brought under the general rubric of the dignity and integrity of the human being who agrees to participate in the relevant study. There may be different ways of thinking about and applying those requirements as elaborated in the relevant ethical guidelines. Those general considerations, however, provide an indispensable framework of general application for ethical decision-making. To that extent it may be said that from both a deontological or utilitarian perspective they serve important purposes.

Professional Standards for Ethicists

Professional standards for ethicists may be derived from standards applicable to any professional advisor or decision-maker in what amounts to a position of trust. They include:
  1. 1.

    honesty;

     
  2. 2.

    objectivity;

     
  3. 3.

    independence;

     
  4. 4.

    competence;

     
  5. 5.

    diligence.

     

Honesty requires that the opinions expressed by an ethicist are his or her own opinions and not a statement of what he or she thinks that somebody might want to hear. An honest ethicist should also make clear the assumptions upon which he or she operates in offering ethical opinions, particularly any important personal values which may inform such assumptions.

Objectivity in the provision of opinions on ethical matters may be compatible with the particular theoretical approach and normative framework of the ethicist but involves an acceptance that this may give rise to outcomes that are not necessarily reflective of his or her personal preferences.

Independence is related to objectivity. It is an instrumental criterion. It involves the absence and avoidance of any conflict of interest that might compromise the ethicist’s ability to offer honest or objective opinions.

Competency may be judged by reference to a person’s awareness of and experience in the application of widely accepted guidelines. It may also be judged by reference to the theoretical and normative framework in which a particular ethicist operates. The fact that utilitarian and deontological ethicist might proffer different solutions to the same ethical problem does not mean that one is competent and the other is not. Each provides a competent, ethical solution if the solution is provided by reference to all the relevant facts and reflects the application of principles and modes of analysis consistent with generally accepted principles of bioethics and the theoretical and normative framework of the ethicist providing the opinion.

Diligence requires the ethicist to ensure that he or she is informed of all facts relevant to the opinion to be offered or the approval to be granted or withheld, and to carefully apply to them the relevant modes of analysis and normative framework.

Those standards may be seen to overlap. In part they depend upon the notional assessment of reputable peers. As already stated, they are characteristic of the standards of conduct applicable to many professional advisors.

Conclusion—an Imperfect but not Meagre Ethical Universe

The German poet, philosopher, historian and playwright, Friedrich Schiller, wrote:

Let no man measure by a scale of perfection

The meagre product of reality

In this world of ours.

The content and application of modern biomedical ethical principles to human subject research cannot be measured on a finely calibrated scale of perfection. However, as its history and content and extraordinarily wide acceptance indicates, it is far more than a meagre product of reality. It is an essential protection for individual human dignity in the service of the public interest.

Footnotes

  1. 1.

    London Research Ethics Committee (Reference 13/LO/1340).

  2. 2.

    Health Research Council Act 1990 (NZ) s 5, s 125, s26(2)

  3. 3.

    NHMRC Council Act 1992 s 7(1)(a)(v)

  4. 4.

    Gene Technology Act 2000 (Cth) s 108(3)(m)

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Copyright information

© Journal of Bioethical Inquiry Pty Ltd. 2018

Authors and Affiliations

  1. 1.Chancellery, M460AThe University of Western AustraliaPerthAustralia

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