#15653 - Human Subjects Research Ii - Medical Law

Vulnerable human subjects

Vulnerable research subjects can generally be classified under two broad headings: (1) those who are unable to give informed consent; and (2) those who are vulnerable for policy reasons. Children and incapacitated adults fall under the first category, whereas prisoners, asylum seekers, third world country residents, and junior medical professionals are examples of those whom fall under the second. However, the main issue with classifying vulnerable research subjects by category is that this may hide individual vulnerabilities and may gloss over context-dependent factors.

a) What are the issues?

The main issues concerning research with vulnerable subjects are as follows:

Lack of adequate protection;

Heightened need for the benefits of medical progress; and

Invisibility in terms of research participation - seen but not heard.

b) Sources of legal protection, regulation and governance

The main sources of legal protection come from various pieces of legislation e.g. the Mental Capacity Act, the Data Protection Act, the Human Tissue Act etc. These are then supplemented by various domestic and international guidelines: the Helsinki Declaration, the ICH-GCP Guidelines, the CIOMS Guidelines, the EU Clinical Trials Directive etc.

The main legal and regulatory tools used to manage research in general include: research reporting requirements, monitoring and tracking of research projects and participants, setting standards for institutional responsibility, informed consent requirements, the concept of clinical equipoise, compensation and insurance requirements, research ethics committee approvals and oversight, principles on risk/benefit ratios, payment/inducement restrictions, research suspension powers etc. Additional tools augment the playing field when vulnerable research subjects are involved to ensure their inclusion: proxy consent mechanisms, best interest considerations, altruistic decision making, substituted consent etc.

The common law would also occasionally be relevant. For example, a researcher may be potentially liable in battery or negligence for acts done to incapacitated adults which normally require consent if those acts were not consistent with their ‘best interests’ and the Bolam principle. On this basis, ‘non-therapeutic research’ is very unlikely to meet the ‘best interests’ test. Additionally, one might consider whether the Montgomery test would apply in this context, and whether there should be a recognised fiduciary duty between the researcher and the patient.

c) Ethical accounts of research with vulnerable subjects

i. Consequentialist account

Involving vulnerable patients in research produces the maximal balance of positive value over disvalue for all those affected. The knowledge we learn from exposing a few say, incapacitated adults, to the risk of untested drugs and procedures will help prevent deaths and suffering in a much larger number of incapacitated adults who suffer from the same condition or disease. For example, there is no other way to ensure reliable therapies for Alzheimer’s than to test the therapy on those patients.

The utilitarian argument does not however advocate unconditioned research. The calculus gives weight to the importance of being able to trust that doctors will not seriously harm their patients, and that individuals will not be unfairly singled out for research, and that patients’ individuality and dignity will be respected. Critics would raise that the utilitarian concern for these values unreliably protects them in the face of their overriding concern to maximise good consequences. Furthermore, the utilitarian rarely has proof these values do in fact improve utility. Accordingly, if we take the flaws in utilitarian reasoning seriously, we must reject the pro-research arguments.

ii. Political consensus

Liddell et al. argue that political consensus is a sensible way to establish and assess the fairness and legitimacy of a legal policy given the extensive moral pluralism that characterises debates about bio law. The logic behind this is that it is preferable for the sake of social stability to introduce laws that reflect an overlapping consensus of reasonable moral beliefs rather than assert that one particular moral viewpoint is true and others false. This view assumes of course a stable and acceptable baseline of moral viewpoints in a particular society, which itself may run into troubles if political consensus is to be obtained cross-border (which may be necessary re global health policy).

Expanding on the idea of overlapping consensus, it gives all those affected genuine reason to think that their moral viewpoints have been understood valued and respected. We lacked the detailed empirical data to know whether Lewis is right to think that international agreements that support research with say, incapacitated adults, are merely a front for utilitarianism or whether they were aimed at moral overlap. Liddell et al. seem to think they suggest the latter, especially in light of the extensive conditions and constraints decided upon things like the Helsinki Declaration.

iii. Ethical principalism

Ackerman argues that moral beings have three relevant interests: exercising autonomous choice, securing fair treatment, and protecting and promoting high standards of personal welfare. These interests generate obligations owed by other individuals, including doctors, and putative research subjects:

Autonomous choice - reflected in obligations of interpersonal conduct, including obligations to respect the capacity of persons to deliberate about, and act on, their life plans. In research settings, this is generally given more specific recognition in duties to secure informed consent, and to respect the privacy of persons and the confidentiality of data.

Fair treatment - generates an obligation to distribute the benefits and burdens of cooperative social endeavours so that each person has an equal opportunity to pursue their life plans. In the research setting, this means subjects should be selected in ays that do not impose arbitrary or heavy burdens on specific classes of persons, that subjects with special vulnerabilities should be more strongly protected than less vulnerable subjects, and that the benefits of research should be fairly allocated.

High standards of personal welfare - generates obligations of beneficence. This means doctors and society generally have a duty to avoid designing trials that would deprive individuals of reasonable standards of medical care, to assess the safety and efficacy of standard medical procedures whose value is uncertain, to minimise risk and to avoid exposing any person to serious risks not intended for their benefit. An obligation also exists to provide and enhance the essential conditions its members need to pursue their life plans e.g. health care, of which medical research is a major component.

iv. Kantian obligations

O’Neill explains that Kantian autonomy is very different from the standard bioethical understanding that portrays autonomy as an entitlement to independence and the freedom to make objective choices (which is more like liberty). Kantian autonomy is the obligation to reason rationally; more specifically, an obligation to live a life according to laws or principles which could be chosen by all, or in other words, according to reasons that are acceptable to other rational beings. This is a kind of principled autonomy. The Kantian notion that we should respect the autonomy of others is really saying we should respect the principled autonomy (rational decisions) of others.

The principles that comprise principled autonomy are constrained by the idea they should be universalisable, and not self-defeating. They are best formed as obligations e.g. obligation not to deceive or coerce; obligation to support and assist others who are vulnerable even were it exposes people to risks that they may themselves not elected. This latter obligation is the groundwork for O’Neill’s views on public health ethics:

“Although [the rejection of indifference] cannot require any individual to render all needed assistance to all others in all predicaments (an impossibility), it demands more than the sporadic meeting of others’ needs, for example, by the episodic charitable donations or emergency aid... [In most circumstances] it is best expressed by supporting social and political institutions and practices that reliably reduce and limit vulnerability by providing a reliable degree of security and subsistence for all.”

These ideas have major implications for the governance of research:

An individual’s consent is not absolutely essential to justify research - although consent can be a way to respect another person’s autonomy, Kantians are not wedded to the idea of respecting an individual’s mere sheer choice. An irrational, unprincipled granting or withholding of consent is not held in high regard. Autonomy is an obligation which should be met over the course of a life, and not at every instant. Especially re those who are unable to consent e.g. incapacitated adults or mentally retarded children, it might be said they have no rationality to respect and so there is no need to respect their autonomy. This is not to say we should disrespect them, because others will be expected to support their capacity for rational action as far as possible.

Rational beings are morally obliged to support research activities that work towards safe, effective health care, if the risks are not serious - a...