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Core Principles Of Research Ethics

Autonomy And Solidarity - The Struggle Of The Public Interest

Arguably, the dominant post-enlightenment value is ‘autonomy’, grounded in a particular construction of liberalism. However, a relatively short time before this, after World War II, solidarity and welfarism held the same dominant political and philosophical way. Bioethics research (research in medicine, life sciences, and biotechnology) is an area where the movement between the two positions remains extremely difficult to negotiate. This is essentially because individuals wish to hold two contradictory positions: many wish to hold the two positions - I want to be able to receive life-saving treatment for whatever disease or illness I might present to healthcare, but simultaneously I do not want to participate in the research that will ensure the therapies I crave.

Barbara Prainsack and Alena Buyx have done much to develop a new theory of solidarity, and this is gaining traction in bioethics discussions. However, the grip of autonomy is very strong. Thomas Beauchamp and James Childress famously developed a theory of bioethics focusing on “autonomy”, “non-maleficence”, “beneficence” and “justice”. Devised in the 1970s and 1980s, and responding to predominantly interventionist medical research, autonomy is rated highly - as it is in the Nuremberg Code, and in the Helsinki Declaration. Considered against the secondary processing of already gathered data for related research purposes, the dominance of solidarity might be challenged, but in the bioethics paradigm it is almost intractable. One wonders, however, how the collectivist, welfarist citizens of the late 1940s or early 1950s might have seen this modern dominant individualism, and the seeming contradiction of the expressed desires.

When Did Liberalism Lose Its Moorings In Morality?

One approach to this conundrum and paradigm shift might be found in the definition of liberalism. If one looks back to the pre-enlightenment and early enlightenment expressions of liberalism of, for example, John Locke, Ashley Cooper, Third Earl of Shaftesbury, Adam Smith, Immanuel Kant, there is an undergirding commonality of solidarity. Locke’s theory of private property allows an individual to own property on the basis of his or her added value through labor, but only to the extent that there are sufficient resources left available for others. Shaftesbury’s ‘politeness’ is predicated on the interdependency of individuals and their duty to consider the needs of others in forging a polite society (one that could replace the social order removed by civil war and the overthrow of divine right monarchs). Smith, before writing An Inquiry into the Nature and Causes of the Wealth of Nations wrote The Theory of Moral Sentiments which focuses on the necessary shared moral platform created through empathy between individuals. Kant, in the Categorical imperative, whilst fully embracing the enlightenment primacy of the individual, identifies through reason the necessity to hold others as ends in themselves not merely as ends to one’s desires.

One can perhaps go further. Nikolai Kropotkin, the central figure of anarchism, writes his central work Mutual Aid around the imperative of empathy across species; to Kropotkin, anarchism is about individuals taking control of decision-making not only about their own lives, but about their life in community with others. Anarchism has duties to others, and a mutual responsibility of care. Even in his late work on ethics, Jean-Paul Sartre seems to move from the individual as the sole focus of existentialism, to the struggle for the individual to make sense of his or her life in relation to duties to others.

This balanced liberalism - this autonomy in balance with solidarity towards others - can be seen until the 1980s. The political shift to neoliberalism, found in the Monetarism of Margaret Thatcher in the UK and Ronald Reagan in the US, saw a social shift to a liberalism that rejects, rhetorically if not fully in all social policy, the welfarist solidarity of the post-war years. Solidarity is seen as nurturing dependence and a lack of the duty to provide for oneself. One wonders to what extent the excess of the market (culminating in the financial crisis of the early 2000s) was part of the Thatcherism or Reaganomics, but the policies of individualism facilitated a social shift that allowed individuals to reject notions of the collective. This, as in all society, is seen in bioethics. The question is how RECs should respond to this shift, and to the seeming contradictions in reasoning that it produces in relation to health research and healthcare. Is it the role of RECs simply to reflect the dominant culture of the day, or, as a matter of ethics, to challenge it? One of the key areas for this is the appeal to the ‘public interest’ as a justification for overruling the individual interests of a person.

Considering The Public Interest

The public interest is a useful legal tool. It enables judicial or bureaucratic discretion to resolve fact situations that were unforeseen at the time of the drafting of the particular rule. The problem is that because it has an element of pragmatism about it, its operation is not clearly defined. It often operates through a rather Utilitarian calculus of weighing the harm to the individual who will be deprived of a particular right ‘in the public interest’ with a notional sense that the public at large will benefit from the deprivation of that right and that is a desirable situation; the deprivation of rights of one individual or a few individuals is worth sacrificing in the interests of the many.

If one is a Utilitarian, this is perhaps acceptable, although the calculus is often, in the case of the law, applied in a rather vague way; it is almost as if the public benefit part is rather self-evident in the operation of a public interest argument (see for example, the appeal often made to ‘the public interest’ by newspapers or other news media in pursuing a story that intrudes on the privacy of an individual). In a rights-based ethical environment this is much more problematic.

Townend has made a three-stage argument to attempt to operate an appeal to the public interest in a rights-based ethical environment.[1]

Stage One. This is essentially a refinement of the Utilitarian calculation. The problem of the Utilitarian calculation is that it poses one individual’s loss against the potential gain of many; one individual could lose, for example, 100 units of happiness, whereas the ‘public’ made up of 101 individuals might only gain 1 unit of happiness each, but the effect is to tip the balance in favor of the mass. A more balanced approach would be first to weigh the potential loss of the individual against the potential loss to a notional individual member of the public: one balancing with one. If one took the foreseeably worst affected member of the public this might produce the fairest consideration of the public interest argument.

Stage Two. This moves the argument from Utilitarianism to a rights-based consideration. Taking Kant’s Categorical Imperative, an individual must, in making choices, treat others as ends in themselves not merely as means to one’s ends; one should not instrumentalize others. Having made the Stage One calculation, the individual is presented must respond to the question, will you insist on your rights? That rights-claiming is, of itself, an action that is subject to the Categorical Imperative. Confronted with the information that another individual will suffer more as a result of my defending my privacy that I would lose by not defending it, I would have to ask myself if I was merely using the other person as a means to my ends, rather than treating him or her as an end.

Stage Three. Of course, Stage Two produces an individual’s moral response to the dilemma of the appeal to the public interest. Stage Three attempts to universalize that response as a law. Law-making is itself a human action that is subject, in Kant, to the Categorical Imperative. When considering whether to make a law, the law-maker can only place a burden upon an individual that s/he would be bound to accept under the Categorical Imperative. Therefore, if the law-maker sees the need to make a law in a particular area, then s/he can only require of the individual that which morality would also require - as under Stage Two. And the appeal to the public interest is the example of such a requirement; the individual’s rights must be challenged because of the supervening needs of another.

Mark Taylor takes a Rawlsian approach to the construction of the public interest. Rawls relies on the reasonableness of rational actors. Thus, the public interest is constructed by an appeal to what the reasonable person cannot disagree with, even when it is against his or her particular interest. The reasonable person, when confronted with a request in the public interest, might not like the request, as it may conflict with his or her personal desires, but he or she cannot deny that the request is reasonable and should be followed.

The Golden Standard Of Participant Protection - Anonymization And Informed Consent

(Research participant) Autonomy is seen as a central premise of bioethics and of human dignity. One's right to choose to participate in medical research in an informed way, and to be protected from identification within research as far as is possible, is almost unquestioned. It is at the heart of the Belmont Report [2] and the work of Beauchamp and Childress;[3] it is one of the immediate concerns for

RECs in their assessments of research protocols.

Arguably, anonymization and informed consent are seen as default safeguards of participant autonomy. However, neither anonymization nor informed consent are without their conceptual and practical problems.

A. Anonymization

There are a number of problems, at different conceptual levels.

1. Meaning

"Anonymization" is used to mean different things in different jurisdictions and disciplines. In certain settings, it is taken to mean that the participant will no longer be identifiable in the research - i.e. in the raw data and in the processed data and products of the research, the participant will not be identifiable. In other settings, anonymous data might relate to a downstream use of the data - the data, in the hands of the individual in question (perhaps a second researcher using the data gathered by another) holds it without identifiers, but the participant could be re-identified by linking the data to the key held by another. To some, this would describe a form of "pseudonymization" of data; data held in a form that prevents immediate identification of participants without access to a key held separately. These terms are to a very large extent context specific, and the context will define the meaning of the terms. However, this uncertainty of language itself produces confusion.

2. Availability

When data was processed without electronic means, or at least before the linking power of the internet, the concept of removing parts of the data so that the remaining data no longer identified an individual (or perhaps a group to whom the individual belonged) might have been more possible. Of course, it was never completely possible. Data that relates to an individual is a dynamic composite of snips that links together in different ways making individuals more or less identifiable at any given time, depending on who is looking at the data. And equally, it is extremely rare that a single snip alone identifies a particular individual (perhaps in any meaningful sense); personal data is composite and context specific (as Taylor has shown).

First, even one's name, alone, means relatively nothing. The name "David Townend" printed on an otherwise blank piece of paper means nothing on its own. It only resonates and finds identifying meaning when it is linked to other information. Thus, if someone 'googles' his or her own name, in the vast majority of cases, one finds a number of entries for that name. First, that person will know that (almost invariably) not all the references relate to him or her; most often, the name relates to a number of individuals. However, in that realization, there is a second element: each reference gives a context within which the name becomes identified. So, an individual labelled "David Townend" might be a Professor in Maastricht (and because of the long memory of the internet, a Senior Lecturer in Sheffield), a person giving a number of conference papers in relation to Law, a singer in a jazz band, or a bass soloist in a number of choral concerts. Only some people will know that these elements different contexts relate to a particular holder of the name "David Townend", and that they should be distinguished from a host of other "David Townend"s for whom there are results.

The second major observation is that the same information has different value in different contexts. Add the name "David Townend" to a list of students and identify him as the tutor of the group, and the value is increased, but perhaps of little worth; add the tutorial times and the addresses of the people on the paper, and in the hands of a door-to-door sales person, it has a particular value (at those times, no-one is in) whereas in the hands of a house-breaker, the list has another value (at those times, no-one is in!). And arguably, there is no intrinsic value in any particular type of data (e.g. medical or genetic data); even 'sensitive personal data' has different values in different combinations and in different contexts.

This means that in some situations, we over-compensate for the presumed value of data; in other situations, we might under-estimate the value of data.

In terms of the possibility of anonymization of data, the composite, dynamic, context specific nature of data, and the vast amount of data available on-line and on demand, anonymization is perhaps a promise that can no longer be made. It is based on an idea that data sets are fully independent – fully free of external connections. If that were possible, a data-bubble might have sufficient 'snips' removed to render the remaining data without identifiers. However, such bubbles burst. Data sets are not held in perfect isolation of other data, and snips can be linked to identify individuals from other means.

3. Desirability

Anonymization has been (some would argue still is) a great safeguard for identity. However, is it a great safeguard for dignity?

Imagine that one finds that one's tissue and medical data, given for research on the strict understanding that it would be anonymized, has been used for chemical weapons research. To many, such a finding would offend his or her dignity.

Likewise, imagine that one finds that the tumor that has just been found by one's doctors and is inoperable at its stage of growth was seen (as an incidental finding) in a scan that one had as part of a research project one year earlier in a much smaller and operable state. But for the safeguard of anonymity, the researchers would have sent such data to one's personal physician. Again, a safeguard of one's dignity?

Of course, these two examples are not uncontested in themselves, but they are contested, and make the claim to the supervening value of anonymization as a natural safeguard to (medical) research participants itself debatable.

B. Informed Consent

Informed consent is difficult. It is at the heart of the modern consumer (transactional) society. Individuals have freedoms of choice and are accountable for the actions; they have the duty to inform themselves to their own satisfaction before entering a transaction as there will be no appeal to 'I didn't know' in the 'caveat emptor' market. However, there are exceptions to this hard world. Sellers have legal duties, to greater or lesser degrees depending on the jurisdiction, to tell the truth or not to conceal or cloak relevant information. More than that, although increasingly lost as the commercial model roles out under the guise of individual freedom and self-determination, 'professionalism' demands a different relationship between people.

Caveat-emptor-contracting thrives where there is, or is presumed to be, 'equality of bargaining power'. Where there is inequality of bargaining power, some duty of protection is often required of the stronger party at law - a 'fiduciary duty'. In situations where the bargain is forged with, or perhaps because of, an imbalance of power (for example, between doctor and patient, lawyer and client, banker and client, teacher and pupil, guardian and minor or incompetent adult), the stronger party is (most often) required to act in (or to protect) the interests of the weaker party.

Research with human participants arguably (strongly arguably) falls into this fiduciary duty. Researchers have in the vast majority of cases much greater knowledge of the area, it's risks and potential benefits, than the participants in their research. That imbalance, that vulnerability, must be protected. And one major element of this safeguard is to require the researchers to inform the participants about what they are proposing to do and what they expect the outcomes to be - arguably, to give some background about the choices they have made in developing the methodology. They must inform the potential participants to redress the knowledge imbalance and to equip the potential participant to make a real choice about whether or not to participate.

Does this mean "full information"? This is difficult. One must redress the knowledge imbalance, but there are arguably some caveats. First, by definition, in research there can be no "full knowledge"; research is testing a hypothesis about what might be the case. Therefore, there is a gap in the knowledge that is available that is shared by the researcher and the potential participants. So, the informed consent is already not about full information. Second, there are limits on how much information is relevant. As in clinical medicine, choices have to be made in informing potential participants about which information is relevant. Remoteness of risk and proportionality must be in play, with a strong measure of 'reasonableness' to stop the drive to information becoming a requirement to inter-connect all knowledge to the particular research. Again, the standard is not binary - information / not information - it is a spectrum.

This second problem can be seen in the area of biobanking. Biobanks operate on the basis of developing a repository of information for the purpose of 'research' (perhaps with some limits, for example, relating to disease type and the like). Access to the data set to create cohorts for particular research projects then, depending on the model, is made on the basis of the initial, broad consent of the participants to participate in the Biobank for research purposes. This causes problems to some people: informed consent requires detailed information about every research project and broad consent, by definition cannot be informed consent; to others, without broad consent biobanks become impossible to operate. Now, of course, the second argument - the practical argument - whilst important, is not of the same nature as the first. However, 'broad consent' and 'informed consent' are not opposite arguments, as the first argument implies.

When one takes the words, the opposite of 'informed' is not broad but 'uninformed'; the opposite of 'broad' is 'narrow' or 'specific'. Whilst it is conceptually difficult to imagine how one could give 'uninformed consent' as the concept of 'consent' itself seems to require a degree of information - at least to know that consent is required in a particular situation -, it is, arguably, possible to give 'informed broad consent' as well as 'informed narrow consent'. This is because, as we have already admitted, information in consent is not a binary informed / uninformed, but rather a question of being sufficiently informed to make a fair and binding decision. The question then is, 'who judges sufficiency?'

Presently, the sufficiency of information is governed in the most parts by the REC. Researchers produce information sheets and these are scrutinized and accepted by RECs as part of their validation of research. Whereas participants have the opportunity to ask questions of the researcher, and, arguably, to shape the interaction about becoming informed to make the decision to participate, in practice one wonders how far this is a real or free dialogue. Is this problematic? Yes, if it does not fit the needs of the participants.

The information sheets reflect the perceptions of those who write them (and RECs are co-authors of the sheets given their role). However, when one looks at studies of expressed sensitivities of citizens, some people will share those perceptions and concerns, whereas others will not, judging less information to be 'sufficient', and others again will require more or different information. One size does not fit all. And some will make a judgement that informed broad consent is sufficient, others will require informed specific consent.

Why is this a problem? Because increasingly, the size that is adopted does not allow for individual participants to make their choice, and that super-sizing of informed narrow consent makes many new research methodologies impossible when they would be acceptable to some participants - which is, perhaps, ironic, when the purpose of informed consent is to protect participant self-determination.

How Might This Be Solved?

Dynamic consent. Many have written on dynamic consent, and some projects are developing models of dynamic, participant-centred consent. The idea is to develop consent interactions between (potential) participants and researchers that allow the participant to determine the level (and, perhaps, nature) of his or her participation. Such mechanisms could be on-going, perhaps making use of secure internet portals such that individual participants could develop increasingly sophisticated consent profiles as their understanding and relationship with the research (or, for example, Biobank) develops. Likewise, the portal could be used by the researchers or Biobank as an educational or information tool to share findings and discuss methods, even difficulties, with the public.

[1]Townend, D. The Politeness of Data Protection: Exploring a Legal Instrument to Regulate Medical Research Using Genetic Information and Biobanking. Maastricht: Universitaire Pers Maastricht (2012) chapter 4, especially pp. 114–116.

[2] Belmont Report (1979). The Belmont Report: Ethical principles and guidelines for the protection of human subjects of research. hhs.gov/ohrp/humansubjects/guidance/belmont.html (Last visited 1st September 2014).

[3] Beauchamp, T. and Childress, J. Principles of Biomedical Ethics. (7th edition). Oxford University Press, New York.

Further Reading

Beauchamp, T. and Childress, J. Principles of Biomedical Ethics. (7th edition). Oxford University Press, New York.

Belmont Report (1979). The Belmont Report: Ethical principles and guidelines for the protection of human subjects of research. hhs.gov/ohrp/humansubjects/guidance/belmont.html (Last visited 1st September 2014).

Beyleveld, D., Brownsword, R. Consent in the Law. Hart Publishing, Oxford (2007).

Beyleveld, D., Townend, D. “When is Personal Data Rendered Anonymous? Interpreting Recital 26 of Directive 95/46/EC”, Medical Law International 6(2): 73–86 (2004).

European Commission. Horizon 2020 Online Manual. European Commission. https://ec.europa.eu/research/participants/docs/h2020-funding-guide/cross-cutting-issues/ethics_en.htm  

European Commission (2019) Horizon 2020 Programme. How to complete your ethics self-assessment-material guidance. Human embryos & fetuses, page 3. European Commission. Directorate-General for Research & Innovation.

European Commission (2019) Horizon 2020 Programme. How to complete your ethics self-assessment-material guidance. Human beings, page 6. European Commission. Directorate-General for Research & Innovation.

European Commission (2019) Horizon 2020 Programme. How to complete your ethics self-assessment-material guidance. Human cells or tissues, page 12.European Commission. Directorate-General for Research & Innovation.

European Commission (2019) Horizon 2020 Programme. How to complete your ethics self-assessment-material guidance. Personal data, page 16. European Commission. Directorate-General for Research & Innovation.

European Commission (2019) Horizon 2020 Programme. How to complete your ethics self-assessment-material guidance. Non-EU countries, page 25. European Commission. Directorate-General for Research & Innovation.

Faden, R., Beauchamp, T., King, N. A History and Theory of Informed Consent. Oxford University Press, New York (1986).

Prainsack, B and Buyx, A. Solidarity: reflections on an emerging concept in bioethics (2011) Nuffield Council on Bioethics, London.

Prainsack, B and Buyx, A. Solidarity in Biomedicine and Beyond (2017) Cambridge University Press, Cambridge.

Townend, D. The Politeness of Data Protection: Exploring a Legal Instrument to Regulate Medical Research Using Genetic Information and Biobanking. (2012) Universitaire Pers Maastricht, Maastricht. chapter 4, especially pp. 114–116.

Townend, D., Ruyter, K. “Overriding the Impasse of Consent in Biobank Research Through ‘Active Citizenship’: Consent Management Portals and License Structures for Benefit Sharing.” Lex Medicinae 16: 5–23 (2011).

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1. International Ethical Guidelines for Health-related Research Involving Humans, Fourth Edition. Geneva. Council for International Organizations of Medical Sciences (CIOMS); 2016. https://cioms.ch/wp-content/uploads/2017/01/WEB-CIOMS-EthicalGuidelines.pdf.

2. Council of Europe Additional Protocol to the Convention on Human Rights and Biomedicine on Biomedical Research. https://rm.coe.int/168008371a.

3. Explanatory Report to Additional Protocol to the Convention on Human Rights and Biomedicine on Biomedical research: https://rm.coe.int/16800d3810.

4. Declaration of Helsinki (2013). https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/.

5. The Belmont Report. https://www.hhs.gov/ohrp/regulations-and-policy/belmont-report/read-the-belmont-report/index.html.

6. Recommendation CM/Rec (2016) 6 of the Committee of Ministers to Member States on Research on Biological Materials of Human Origin, 2016. https://search.coe.int/cm/Pages/result_details.aspx?ObjectId=090000168064e8ff.

 

  1. Horizon 2020 Online Manual. European Commission. https://ec.europa.eu/research/participants/docs/h2020-funding-guide/cross-cutting-issues/ethics_en.htm  
  2. Human embryos & fetuses, page 3. in European Commission (2019) Horizon 2020 Programme. How to complete your ethics self-assessment-material guidance. European Commission. Directorate-General for Research & Innovation.
  3. Human beings, page 6 in European Commission (2019) Horizon 2020 Programme. How to complete your ethics self-assessment-material guidance. European Commission. Directorate-General for Research & Innovation.
  4. Human cells or tissues, page 12. in European Commission (2019) Horizon 2020 Programme. How to complete your ethics self-assessment-material guidance. European Commission. Directorate-General for Research & Innovation.
  5. Personal data, page 16. in European Commission (2019) Horizon 2020 Programme. How to complete your ethics self-assessment-material guidance. European Commission. Directorate-General for Research & Innovation.
  6. Non-EU countries, page 25. in European Commission (2019) Horizon 2020 Programme. How to complete your ethics self-assessment-material guidance. European Commission. Directorate-General for Research & Innovation.
  7. E-Manual. 2.3.1. Capacity and Vulnerability in research.
  8. The Norwegian National Research Ethics Committees (etikkom.no).  https://www.etikkom.no/en/library/topics/research-on-particular-groups/vulnerable-groups/#Practical.   
  9. Research Ethics Program, UC San Diego. http://research-ethics.org/topics/overview/.
  10. The Belmont Report: Basic Ethical Principles and their Application (educational video): https://www.youtube.com/watch?v=M6AKIIhoFn4&feature=youtu.be.
  11. Health Research Authority, UK:  https://www.hra.nhs.uk/planning-and-improving-research/policies-standards-legislation.
  12. Royal College of Physicians. Guidelines on the practice of ethics committees in medical research with human participants. 4th edition. London: RCP, 2007. https://cdn.shopify.com/s/files/1/0924/4392/files/guidelines-practice-ethics-committees-medical-research.pdf?11143599859970562352.  
  13. Ridt A, Wender D. Risk-benefit assessment in medical research: critical review and open questions. Law, Probability and Risk (2010) 9, 151−177.

Learning Objectives

  • to identify core issues and principles of research ethics
  • to analyze challenges of their practical application
  • to assess the normative framework for research on human participants
  • to apply principles of research ethics to analyze the presented cases

Introduction

This module provides some introductory notes on the core issues in research ethics – informed consent, privacy and confidentiality, risk/benefit assessment, and justice – as well as some insights into challenges while applying them into practice.

Informed Consent

Informed consent is one of the fundamental principles of modern medical ethics, entrenched by national and international laws as well as codes of ethics. It is one of the best known but also one of the most-debated ethical principles in the context of both clinical practice and biomedical research because its implementation still raises practical problems. Informed consent is an important principle in medical ethics because it guarantees a person’s right to self-determination and a decision based on an understanding of relevant information. This principle is also important in terms of the safety of patients.

In order for the consent to be considered credible and valid, several conditions must be met – consent must be given by a competent individual (or their legal representative), consent must be given of free will and before consent is obtained, the individual must be presented with all of the relevant information which could be significant when making a decision about participating in the research project.

The principle on informed consent emerged in the context of medical experiments, but later on its application was extended to research on human biological materials and personal data – which are less invasive in a physical sense but still are sensitive from the privacy point of view. The recent version of the Declaration of Helsinki includes the provision for informed consent in research on identifiable materials and information.

Implementation Challenges Of The Principle Of Informed Consent

1) The amount of information to be provided to research participants: The information provided to potential research participants shall cover a number of issues, i.e. the aims, methods, benefits, risks and discomfort, sources of funding, any possible conflicts of interest, post-study provisions the right to refuse to participate/ withdraw at any time without reprisal, and any other relevant aspects of the study. CIOMS Guidelines present an even more comprehensive list of elements of information, what is on the one hand helpful for both researchers and participants, on the other hand it sometimes results in a document of 20 pages or even more and might lead to confusion. At the same time the results of numerous studies conducted all over the world reveal that individuals participating in medical research often do not understand the key information about the research project. It is not intellectual aptitude and cognitive capacity alone which determine understanding of the information about research, the difference between research study clinical practice (“therapeutic misconception”), or the choice to participate - a number of emotional, social, economic, cultural, psychological and individual factors are also important, namely, the ‘therapeutic’ environment of clinical trials, confidence in healthcare, the culturally determined public perception of physicians, the investigators’ own beliefs and values and even the resources allocated to healthcare.

2) Considering informed consent not merely as a signed document but as an ongoing process, disclosure of information and comprehension of the information provided plays the key role.  The Declaration of Helsinki requires that the physician must seek the potential subject’s freely given informed consent “only after ensuring that the potential subject has understood the information”. Thus, the investigator’s obligation is not only to present and explain the information, but also to ensure that a person has understood it. It is, however, debatable how practicable this requirement is; whether it is achievable at all and what tools investigators should use in order to get a “proof” of person’s understanding.

3) Broad consent in the context of biobanking (see Module “Biobanks”).

4) Research on previously collected human biological material and/or data: Different guidelines provide the criteria for the waiver of consent in studies involving previously collected human biological material / personal data. For example, three conditions under which a REC may waive informed consent are indicated in the CIOMS Guidelines:

  • the research would not be feasible or practicable to carry out without the waiver,
  • the research has important social value, and 
  • the research poses no more than minimal risks to participants.

The Council of Europe Recommendation on Research on Biological Materials of Human Origin[1] provides a more complex set of criteria, which justifies the use of identifiable biological materials/data in a research project without person‘s consent where the attempt to contact the person concerned proves unsuccessful only if:

  • evidence is provided that reasonable efforts have been made to contact the person concerned;
  • the research addresses an important scientific interest and is in accordance with the principle of proportionality;
  • the aims of the research could not reasonably be achieved using biological materials for which consent, or authorization can be obtained; and
  • there is no evidence that the person concerned has expressly opposed such research use.

As the guidelines do not provide with sufficient explanation of the terms “feasible or practicable”, “reasonably”, “there is no evidence”, they seem to remain very much context dependent and decided on an ad hoc basis.

5) Obtaining consent in special situations, e.g. in emergency research (see Module “Research in emergency situations”), research on minors (see Module “Research involving children”), or incapable adults (see Module “Research involving vulnerable groups”).

Privacy And Confidentiality

Confidentiality is an obligation of physicians, investigators and other health care or research staff not to disclose private information without person’s consent.  This is to respect privacy of participants, to maintain trust, and avoid any form of discrimination or stigmatization.

Research design, organizational aspects of the research project or research population and topic as such can be the source of privacy concerns. For example, collection of excessive personal information (“any collection of personal information shall be justified“), undefined or unjustified time of data storage (“personal data should be stored as long as necessary for the purpose of the research project”), or use of contact information of patients merely for the purposes of contacting them to recruit into research study. In some studies, there can be a need to learn the outcomes of patient’s condition even if a person had withdrawn from the project. This requires re-contacting patients to ask for their consent for further collection of clinical data, which could also raise privacy issues.  Studies of research design involving (e-)mailed questionnaires and phone interviews might also be sensitive in terms of privacy and confidentiality as there can be no guarantee that the patient himself or herself will pick up the phone, open an envelope or read an email message. In some studies where targeted population is exposed to relatively short life expectancy there is a risk to contact relatives of a dead person instead of a prospective research participant. That can cause stress to the relatives and bring them unnecessary painful memories.

Issues of confidentiality in research are closely related to the issues of legal protection of personal data due to the development of a legal discourse of data protection. You can read more about personal data protection and implications of General Data protection Regulation for medical research in the ENERI E-Manual.

Risk–Benefit Assessment

One of the primary responsibilities of RECs’ is to protect the rights, safety and wellbeing of research participants. Risk–benefit assessment is of fundamental importance for the ethical review[2].

The concept of benefit in research is twofold - research is aimed to produce scientific and social benefit, on the other hand it can be beneficial to individual research participants. Research participants can benefit either directly (e.g., if a patient is expected to benefit from the intervention studied) or collaterally (e.g., get free medications / examinations, get more attention, experience satisfaction for being altruistic).

Also, several types of risks and burdens for an individual can be distinguished in the context of research ethics:

  • physical (e.g., pain, drug side-effects)
  • psychological (e.g., questions that cause stress, or remind painful experience)
  • social (e.g., stigmatization, loss of privacy or confidentiality)
  • “economic” (e.g., time spent, financial expenses, loss of earnings)

Potential risks to groups (communities, societies, or families) and risks to researchers should be taken into consideration by researchers, RECs and sponsors.

All the international (and probably national) guidelines share the same general principle requiring that “The interests and welfare of the human being participating in research shall prevail over the sole interest of society or science”. However, when addressing the issue of risk/benefit ratio the guidelines use different terminology and frame the requirements in quite different ways. For example, the CIOMS Guidelines require that risks to participants are minimized and appropriately balanced in relation to the prospect of potential individual benefit and the social and scientific value of the research”, the Declaration of Helsinki – that the importance of the objective outweighs the risks and burdens to the research subjects. The Additional Protocol on Biomedical Research frames the requirement for risk/benefit ratio in the following way: “Research shall not involve risks and burdens to the human being disproportionate to its potential benefits”. It also indicates different risk/benefit ratio standard for involvement of persons who are capable of giving their consent into research without direct benefit and those who are not: such a research on persons capable to consent can be conducted only if research poses no more than acceptable risk and acceptable burden for the research participants involved; only minimal risk and minimal burden for the individual for those who are not able to consent.

However, having indicated general principles for the risk-benefit ratio most of the international guidelines do not provide with a more detailed guidance on the risk-benefit evaluation process. Thus it is important to emphasize the CIOMS guidelines which suggest a two-step process for the evaluation of the potential individual benefits and risks of research: first, the potential individual benefits and risks of each individual research intervention or procedure in the study must be evaluated, in a second step, the aggregate risks and potential individual benefits of the entire study must be assessed and must be considered appropriate[3].

Challenges Of Risk-Benefit Assessment

Although general principles have been defined, a number of conceptual and practical issues remain unresolved, e.g. what type of risks should be considered in relation to what type of benefits.  There is still some conceptual misunderstanding and a lack of consensus related to the very central concepts (e.g. the concept of benefit). The evidence reveals that even RECs interpret “benefit” in different ways: some prioritize direct over indirect, some make no difference between them[4]. The terms “acceptable”, “appropriately balanced”, “minimal risk” remain context dependent and are left for the decision of RECs („should be decided by REC and a person concerned“; „what constitutes “minimal risk“ shall be assessed on an individual basis”, etc.).

The complexity of risk-benefit assessment is perfectly reflected by the CIOMS Guidelines: „What constitutes an appropriate risk-benefit ratio cannot be expressed in a mathematical formula or algorithm. Rather, it is a judgment that results from a careful assessment and reasonable balancing of a study‘s risks and potential individual benefits[5].

(You can also see the Modules “Research in emergency situations”, “Research involving children”, and “Research involving vulnerable groups” for risk-benefit assessment in special situations).

Measures Minimizing Risks

There is a number of measures which can serve for minimizing the potential risks, for example:

  • more careful observation of research participants
  • more frequent visits
  • hospitalization (instead of outpatient care)
  • extra phone calls
  • monitoring the study and providing mechanisms for responding to adverse events
  • establishing a Data Safety and Monitoring Committee (DSMC) to review and decide on data on harms and benefits as a study progresses
  •  instituting clear criteria for stopping a study
  • avoiding unnecessary procedures (for example, by performing laboratory tests on existing blood samples instead of drawing new blood, where scientifically appropriate).[6]

The arrangements for the compensation of damage (e.g. civil liability insurance) can serve as a mean to minimize the potential damage.

Justice

The principle of justice refers to the ethical obligation to treat each person in accordance with what is morally right and proper, to give each person what is due to him or her. In the ethics of research involving human subjects the principle refers basically to distributive justice, which requires the equitable distribution of both the burdens and the benefits of participation in research[7]. Differences in distribution must be morally justified among social groups (i.e. vulnerable groups should be specifically protected, but not excluded from the participation in research (see Module “Research involving vulnerable groups”), and among societies. Placebo trials conducted in a third country where standard treatment is not available because of its costs could serve as a typical example of possible injustice and exploitation of economically deprived societies,  e. g., mother-to-child HIV transmission trial in Africa (AZT)[8]. It is also questionable whether it is fair that countries which maintain certain ethical standards and do not permit certain types of research (e.g. involving human embryonic stem cells or conducted on persons incapable of giving consent), would benefit from research conducted in other countries in the future.

The principle of justice also refers to the obligation to share the benefits of research. Benefit sharing can take different formats to protect interests of researchers and research participants in different countries. One way to share the benefits of research is to make the results of research public (registered in a publicly accessible database (DoH, p. 35)) and publishing or otherwise disseminating them (DoH, p.36). Making both positive and negative research results public can prevent people from unnecessary risks and burdens posed by participation in repeated research projects.

[1] Recommendation CM/Rec (2016) 6 of the Committee of Ministers to Member States on Research on Biological Materials of Human Origin.

[2] Ridt A, Wender D. Risk-benefit assessment in medical research: critical review and open questions. Law, Probability and Risk (2010) 9, 151−177.

[3] International Ethical Guidelines for Health-related Research Involving Humans, Fourth Edition. Geneva. Council for International Organizations of Medical Sciences (CIOMS); 2016.Guideline 4. https://cioms.ch/wp-content/uploads/2017/01/WEB-CIOMS-EthicalGuidelines.pdf.

[4] King N. Defining and Describing Benefit Appropriately in Clinical Trials. The Journal of Law, Medicine & Ethics, 28: 332–343. doi:10.1111/j.1748-720X.2000.tb00685.x.

[5] International Ethical Guidelines for Health-related Research Involving Humans, Fourth Edition. Geneva. Council for International Organizations of Medical Sciences (CIOMS); 2016. Guideline 4. https://cioms.ch/wp-content/uploads/2017/01/WEB-CIOMS-EthicalGuidelines.pdf.

[6] International Ethical Guidelines for Health-related Research Involving Humans, Fourth Edition. Geneva. Council for International Organizations of Medical Sciences (CIOMS); 2016. Guideline 4. https://cioms.ch/wp-content/uploads/2017/01/WEB-CIOMS-EthicalGuidelines.pdf.

[7] Casebook on ethical issues in international health research. World Health Organization, 2009. http://apps.who.int/iris/bitstream/10665/44118/4/9789241547727_eng.pdf.

[8] In 1997 US and African researchers conducted a trial to evaluate lower and fewer doses of AZT (ZIDOVUDINE) in Africa. AZT was already known as an efficient medication to prevent mother-to-child HIV transmission, but in this trial a control group was administered placebo.  One of the arguments behind this design was that the regimen for the control group did not differ from the local "standard" because "standard" treatments for AIDS for these women were no treatments at all. But the critics argued, however, that the use of a placebo-controlled study when an effective treatment exists endangered life of hundreds of newborns in developing countries and introduced double standards in developed and developing countries.

See also:

  1. Horizon 2020 Online Manual. European Commission. https://ec.europa.eu/research/participants/docs/h2020-funding-guide/cross-cutting-issues/ethics_en.htm  
  2. Human embryos & fetuses, page 3. in European Commission (2019) Horizon 2020 Programme. How to complete your ethics self-assessment-material guidance. European Commission. Directorate-General for Research & Innovation.
  3. Human beings, page 6 in European Commission (2019) Horizon 2020 Programme. How to complete your ethics self-assessment-material guidance. European Commission. Directorate-General for Research & Innovation.
  4. Human cells or tissues, page 12. in European Commission (2019) Horizon 2020 Programme. How to complete your ethics self-assessment-material guidance. European Commission. Directorate-General for Research & Innovation.
  5. Personal data, page 16. in European Commission (2019) Horizon 2020 Programme. How to complete your ethics self-assessment-material guidance. European Commission. Directorate-General for Research & Innovation.
  6. Non-EU countries, page 25. in European Commission (2019) Horizon 2020 Programme. How to complete your ethics self-assessment-material guidance. European Commission. Directorate-General for Research & Innovation.

Cases and Questions - Core Principles Of Research Ethics

Case 1

A Public Health department of X University is planning to conduct a large-scale population survey (n7000) on the prevalence of genital warts. The questionnaires will be mailed to randomly selected individuals whose personal contact information will be obtained from the Population Register. The aim of the study is to explore the prevalence of the condition in the population, thus both healthy and infected persons can be contacted. Genital warts are caused by the Human Papiloma Virus, which is transmitted primarily by skin-to-skin contact and is commonly associated with improper sexual behavior in public.  

- Would you as a REC member approve such a study? Would you suggest any amendments?