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  • ETH5: Is IGG used for patients/people that are especially vulnerable?
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Is IGG used for patients/people that are especially vulnerable?

Authors: Plamen Dimitrov, Anelia Koteva

Internal reviewers: Pseudo99 Pseudo99

The need to test new drugs continues and will continue to be associated with increased demand for clinical trial participants who are vulnerable in a number of ways. First, medicine is a very complex field, not easily understood by the average person. Study participants often have neither sufficient knowledge to determine the best course of action for treating or preventing a disease, nor the necessary expertise to reasonably assess the hazards and risks borne by them in the experiment. Rather, they are placed in a position of dependence – depending on clinician researchers to advise them correctly. A second source of vulnerability is a function of the fact that study participants are often people having problems for which they are seeking a solution. These individuals place their lives in the hands of medical staff, trusting that researchers will act in the participants’ best interest. Third, as far as clinical trials usually take place in a healthcare setting, researchers are in the position to easily gain access to sensitive information that may expose the participants in the study to social or economic risks, such as the presence of diseases that could have a negative impact on the public attitude towards the patient, namely his/her productivity, hence, employability, and, thus, contribute to deepening stigmatization. Fourth, clinician researchers, by virtue of their expertise and status, may abuse their position by exerting pressure on the patient and making him/her agree to the proposed intervention, even through the use of dishonest and unethical methods as coercion, deception, fraud and other forms of manipulation. As a result, patients may be reluctant to exercise their right to autonomy and, consequently, acquiesce to everything required of them – even when it may not be in their best interest. A fifth source of vulnerability when recruiting volunteers to participate in scientific experiments for testing new therapeutic alternatives could be generated by the need to balance between the patient’s right to personal choice, his/her financial needs and the enthusiasm of researchers. Hopeless and desperate patients, not having enough money to pay for expensive treatment, may find it more beneficial to involve in a free trial of the new technology. Such situations normally raise the following ethical issues, i.e. to what extent has voluntary participation been guaranteed by researchers, especially in cases where clinician researchers may be quite enthusiastic and may, therefore, influence the decision of the patient by assuring him/her of the benefits and safety of a completely new, still unproven, therapy as well as how to ensure that potential risks are not to be belittled by the particular individual. Sixth, in the event of early diagnosed patients with anticipation for progressive deterioration over time, the practice of drawing up a legal document called “advance directive” is usually preferred – a written document, in which, while still healthy, a person without prominent cognitive dysfunctions but expected future ones formulates his/her future treatment preferences and desires. In similar situations, where it may take a period of several decades between an individual’s preclinical diagnosis and the onset of clinical symptoms, there is a risk of discrepancy between the present and future “self” of the patient in the changed environment, posing the question how relevant with regard to a particular moment in the future would be the preliminarily given consent/refusal expressed by a person in the advance directive and whether earlier treatment preferences must always be respected by the medical personnel. Here the concept of future-oriented autonomy collides with the welfare of the patient. A seventh source of vulnerability is associated with the adopted practice of legal representation in the event of incompetence, which raises the question if an agent/representative of the patient would always act in the interest of the patient and how this could be ensured. Eighth, patients’ vulnerability may be generated by excessive stereotyping and infantilization of the adults, especially through the application of restrictive procedures, such as the so-called “double consent” where consent is sought by the family, while the subsequent validation/approval of the consent (i.e. “assent”) – by the patient himself/herself, quite analogous to the procedures in children.


In the event of diagnosed with AD individuals stands out the conflict between the right to autonomy of a patient and the limits of his/her capacity/competence – an issue that has been widely discussed in bioethics literature, however, without reaching unanimity. The positions of the authors are diverse, mostly depending on the adopted viewpoint. No universal prescriptions for action exist.


Under the legal doctrine, each subject shall be presumed competent until proven otherwise. For example, in law, unable to make a decision shall be considered the person who is unable to understand the information obtained and cannot hold it long enough (i.e. remember  it), cannot use it or weigh it up as part of the decision-making process and is unable to communicate (express) his/her choice either by speech, or through sign language (for example by blinking eyes or squeezing a hand)[1].


Apart from the purely legal nature of the term “competence”, in the literature prevails the view[2] that the progressive brain damages and ensuing cognitive and emotional disorders, accompanied by sensory impairment and dependence on family and caregivers, require careful and cautious application of the doctrine of competent, voluntary, informed consent in research on adult subjects given the consideration that the mental decline may affect a patient’s ability to understand the medical alternatives by reducing the individual sense of caution and reasonable judgment of the potential risks and burdens associated with the intervention.


Even the prodromal stage of Alzheimer’s disease, popular as MCI, might impair the capacity of patients to give consent. Distinguishing between competent and incompetent subjects is quite a complex process and despite standardized assessment tools, the question remains unresolved as to what upper limit of potential risk should be allowed and whether informed consent should be permitted in high-risk scientific research. Partial answer to this dilemma is contained in the current international codes and guidelines, including the Declaration of Helsinki and the Council for International Organizations of Medical Sciences Guidelines (CIOMS)[3] dealing with issues, such as research in vulnerable populations. They make it obvious that the balance between risks and benefits is especially important in the discussion on non-therapeutic vs. therapeutic research, where only minimal risks are allowed if the research won’t be of benefit to the subjects involved.


Some authors[4] try to distinguish between an ideal, abstract model of autonomy and actual autonomy. Typically, an abstract model assumes the possession of a set of ideal capabilities that an autonomous agent is supposed to have, namely the ability to function as an independent and rational subject in his/her choices and actions, who knows his/her own desires and preferences, being fully competent in the decision-making process. These features, however, present a standard model, difficult to follow in some cases, such as Alzheimer’s disease. The abstract, ideal definition is replaced by a new concept, popular as “actual autonomy” that views the individual as an owner of a particular history of development, personal beliefs, convictions and values, and who does not ​​exist in isolation but in a dynamic relationship with the social world.


In accordance with the above, George Agich notes that although not exhibiting ideal capacity for giving consent due to existing memory deficit, confusion and disorientation, most volunteers participating in clinical trials of drugs are conscious subjects reported to be in excellent or good health, cognizant of everyday life, having their own preferences for specific foods, clothing, persons and activities and demonstrating relatively preserved capacity to interpret information and ask questions.


It would therefore be incorrect for dementia patients to always be deemed completely devoid of decision-making capacity. Moreover, if the information is presented slowly and repeatedly in a non-stressful manner, even people suffering from significant cognitive decline can grasp it. Thus, in compliance with the principle of autonomy, a cornerstone principle of medical ethics, it would be essential that procedures for informed consent be developed sensitive to preserving maximum freedom for the subject over his/her own body. According to the ethical guidelines of the Alzheimer Society of Canada[5], while still intact, the individual’s freedom should not be limited by restrictive measures; rather, he/she should be given a choice and opportunity to decide. This position is shared in other guidance documents[6], adding that a person with preserved competence has the right to make even such a decision that may be perceived by others, including the health personnel, as unreasonable or irrational, with the particular individual not to be categorized as lacking capacity merely because the health professional has deemed his/her decision unwise.


[1]Reference Guide to Consent for Examination or Treatment”, second edition, Department of Health, United Kingdom, July 2009, p.9, available at: .

[2]Dementia – Caring, Ethics, Ethnical and Economical Aspects: A Systematic Review”, Chapter 36 “Ethical and Societal Issues in Dementia”, p. 446, volume 3, June 2008, SBU Statens beredning för medicinsk utvärdering (The Swedish Council on Technology Assessment in Health Care), available at: .

[3] Ibid, p. 445, available at: .

[4] Agich, G., “Alzheimer Disease: Therapeutic Strategies”, edited by E. Giacobini and R. Becker, Boston, 1994, available at: .

[5] Sevick, M-A., T. McConnell and M. Muender, “Conducting Research Related to Treatment of Alzheimer’s Disease: Ethical Issues”, Journal of Gerontological Nursing 29(2), February 2003, pp. 6-12, available at: .

[6]Reference Guide to Consent for Examination or Treatment”, second edition, Department of Health, United Kingdom, July 2009, p. 10, available at: .

Dimitrov P, Koteva A Result Card ETH5 In: Dimitrov P, Koteva A Ethical analysis In: Jefferson T, Cerbo M, Vicari N [eds.]. Use of Intravenous immunoglobulins for Alzeheimer’s disease including Mild Cognitive Impairment [Core HTA], Agenas - Agenzia nazionale per i servizi sanitari regionali ; 2015. [cited 30 October 2020]. Available from: